NCBI Conserved Domain Search

PDZ domain 2 of the canonical isoform 1 of PDZ domain containing 7 (PDZD7), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of the long isoform 1 of PDZD7, and related domains. PDZD7 is critical for the organization of Usher syndrome type 2 (USH2) complex. Usher syndrome is the leading cause of hereditary sensory deaf-blindness in humans; USH2 is the most common sub-type. Formation of the USH2 complex is based upon heterodimerization between PDZD7 and whirlin (another PDZ domain-containing protein) and a subsequent dynamic interplay between USH2 proteins via their multiple PDZ domains. The PDZD7 PDZ2 domain binds GPR98 (also known as VLGR1) and usherin (USH2A). PDZD7 and whirlin form heterodimers through their multiple PDZ domains; whirlin and PDZD7 interact with usherin and GPR98 to form an interdependent ankle link complex. PDZD7 also interacts with myosin VIIa. PDZD7 also forms homodimers through its PDZ2 domain. Various isoforms of PDZD7 produced by alternative splicing have been identified; this subgroup includes the second PDZ domain of the canonical isoform of PDZD7- isoform 1. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PDZD7-like family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467270 [Multi-domain] Cd Length: 85 Bit Score: 183.36 E-value: 1.87e-54

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569006111  208 RRIVHLYTTSDDFCLGFNIRGGKEFGLGIYVSKVDHGGLAEENGIKVGDQVLAANGVRFDDISHSQAVEVLKGQTHIMLT 287
Cdd:cd10834     1 RRIVHLYTTSDDYCLGFNIRGGSEYGLGIYVSKVDPGGLAEQNGIKVGDQILAVNGVSFEDITHSKAVEVLKSQTHLMLT 80


                  ....*
gi 569006111  288 IKETG 292
Cdd:cd10834    81 IKEVG 85

PDZ domain 3 of the canonical isoform 1 of PDZ domain containing 7 (PDZD7), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of the long isoform 1 of PDZD7, and related domains. PDZD7 is critical for the organization of the Usher syndrome type 2 (USH2) complex. Usher syndrome is the leading cause of hereditary sensory deaf-blindness in humans; USH2 is the most common sub-type. Formation of the USH2 complex is based upon heterodimerization between PDZD7 and whirlin (another PDZ domain-containing protein) and a subsequent dynamic interplay between USH2 proteins via their multiple PDZ domains. The PDZD7 PDZ2 domain binds GPR98 (also known as VLGR1) and usherin (USH2A). PDZD7 and whirlin form heterodimers through their multiple PDZ domains; whirlin and PDZD7 interact with usherin and GPR98 to form an interdependent ankle link complex. PDZD7 also interacts with myosin VIIa and can also form homodimers through its PDZ2 domain. Various isoforms of PDZD7 produced by alternative splicing have been identified; this subgroup includes the third PDZ domain of the canonical isoform of PDZD7- isoform 1. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PDZD7-like family PDZ3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467233 [Multi-domain] Cd Length: 89 Bit Score: 180.71 E-value: 2.29e-53

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569006111  856 LRTITLSKMKQSLGISISGGIESKVQPMVKIEKIFPGGAAFLCGDLQAGFELVAVDGESLEQVTHQRAVDTIRRAYRNKA 935
Cdd:cd06751     1 LLTVELSKMKQSLGISISGGIESKVQPVVKIEKIFPGGAAALSGNLKAGYELVSVDGESLQQVTHQQAVDIIRRAYSNKS 80


                  ....*....
gi 569006111  936 REPMELVVR 944
Cdd:cd06751    81 KEPMEIVVK 89

PDZ domain 1 of the canonical isoform 1 of PDZ domain containing 7 (PDZD7), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of the long isoform 1 of PDZD7, and related domains. PDZD7 is critical for the organization of Usher syndrome type 2 (USH2) complex. Usher syndrome is the leading cause of hereditary sensory deaf-blindness in humans; USH2 is the most common sub-type. Formation of the USH2 complex is based upon heterodimerization between PDZD7 and whirlin (another PDZ domain-containing protein) and a subsequent dynamic interplay between USH2 proteins via their multiple PDZ domains. The PDZD7 PDZ2 domain binds GPR98 (also known as VLGR1) and usherin (USH2A). PDZD7 and whirlin form heterodimers through their multiple PDZ domains; whirlin and PDZD7 interact with usherin and GPR98 to form an interdependent ankle link complex. PDZD7 also interacts with myosin VIIa. PDZD7 also forms homodimers through its PDZ2 domain. Various isoforms of PDZD7 produced by alternative splicing have been identified; this subgroup includes the first PDZ domain of the canonical isoform of PDZD7- isoform 1. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PDZD7-like family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467269 [Multi-domain] Cd Length: 84 Bit Score: 158.37 E-value: 1.46e-45

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569006111   84 IHAVRVEKSPSGRLGFSVRGGSEHGLGIFVSKVEEGSSAERAGLCVGDKITEVNGLSLESTTMGSAVRLLTSSSCLHMMV 163
Cdd:cd10833     1 IHTVTVEKSPDGSLGFSVRGGSEHGLGIFVSKVEEGSAAERAGLCVGDKITEVNGVSLENITMSSAVKVLTGSNRLRMVV 80


                  ....
gi 569006111  164 RRMG 167
Cdd:cd10833    81 RRMG 84

harmonin_N_like domain, a protein-binding module of PDZ domain-containing protein 7 and related proteins; Human PDZD7 is a scaffolding protein which associates with the Usher Syndrome protein network, and localizes to the stereocilia Ankle-link. Usher syndrome is the leading cause of genetic deaf-blindness. PDZD7 has a role as in Usher syndrome type 2 (and not in USH1) in humans. Whirlin, Usherin and GRP98 are other USH2 proteins. The latter two form the ankle links and whirlin is thought to be a scaffold for protein interactions at these links. PDZD7, whirlin, and harmonin (an USH1 protein) have a similar domain composition. The domain represented here is a putative protein-binding module based on its sequence similarity to the N-terminal domain of harmonin. Cooperative effects of mutations in PDZD7 and Usherin, and in PDZD7 and GPR98, result in a digenic USH2 phenotype.

Pssm-ID: 259824 Cd Length: 78 Bit Score: 135.58 E-value: 1.01e-37

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gi 569006111  554 WESRRPLIQDLARRLLTDDEVLAVTRHCSRYVHEGGVEDLVRPLLAILDRPTKLLLLRDIRSVVAPTDLGRFDSMVMP 631
Cdd:cd07358     1 SSDSLTRLEEMASRLLTSDEVSAILRHCRRYVEERDVEDLVRPLLAILDTPEKLLLLREIRSLIPPSDLGRFDSMVSP 78

PDZ domain 2 of the full-length isoform of whirlin and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of the full-length isoform of whirlin and related domains. Whirlin is an essential protein for developmental pathways in photoreceptor cells of the retina and hair cells of the inner ear. The full-length whirlin isoform has two harmonin N-like domains, three PDZ domains, a proline-rich region, and a PDZ-binding motif. Whirlin isoforms may form different complexes at the periciliary membrane complex (PMC) in photoreceptors, and the stereociliary tip and base in inner ear hair cells. It interacts with ADGRV1 and usherin at the PMC; with SANS and RpgrORF15 at the connecting cilium in photoreceptors; with EPS8, MYO15A, p55, and CASK proteins at the stereociliary tip of inner ear hair cells; and with ADGRV1, usherin, and PDZD7 at the stereociliary base in inner ear hair cells. Mutations in the gene encoding whirlin (WHRN; also known as USH2D and DFNB31), have been found to cause either USH2 subtype (USH2D) or autosomal recessive non-syndromic deafness type 31 (DFNB31). Whirlin is the key protein in the USH2 complex (whirlin, usherin and GPR98) which recruits other USH2 causative proteins at the periciliary membrane in photoreceptors and the ankle link of the stereocilia in hair cells. Whirlin's interaction with espin, another stereociliary protein, may be important for the architecture of the USH2 complex. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This whirlin family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467223 [Multi-domain] Cd Length: 84 Bit Score: 101.96 E-value: 6.61e-26

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 569006111  222 LGFNIRGGKEFGLGIYVSKVDHGGLAEENGIKVGDQVLAANGVRFDDISHSQAVEVLKGQTHIMLTIKETG 292
Cdd:cd06741    14 LGLMIRGGAEYGLGIYVTGVDPGSVAENAGLKVGDQILEVNGRSFLDITHDEAVKILKSSKHLIMTVKDVG 84

PDZ domain of PDZ domain-containing protein 11, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of PDZD11, and related domains. PDZD11 (also known as ATPase-interacting PDZ protein, plasma membrane calcium ATPase-interacting single-PDZ protein, PMCA-interacting single-PDZ protein, PISP) is involved in the dynamic assembly of apical junctions (AJs). It is recruited by PLEKHA7 to AJs to promote the efficient junctional recruitment and stabilization of nectins, and the efficient early phases of assembly of AJs in epithelial cells. The PDZD11 PDZ domain binds nectin-1 and nectin-3. PDZD11 also binds to a PDZ binding motif located in the C-terminal tail of the human sodium-dependent multivitamin transporter, to the cytoplasmic tail of the Menkes copper ATPase ATP7A, and to the cytoplasmic tail of all plasma membrane Ca2+-ATPase b-splice variants. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PDZD11-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467234 [Multi-domain] Cd Length: 83 Bit Score: 95.84 E-value: 8.67e-24

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 569006111  222 LGFNIRGGKEFGLGIYVSKVDHGGLAEENGIKVGDQVLAANGVRFDDISHSQAVEVLKGQTHIMLTIK 289
Cdd:cd06752    13 LGFNIRGGKASGLGIFISKVIPDSDAHRLGLKEGDQILSVNGVDFEDIEHSEAVKVLKTAREIQMRVR 80

PDZ domain 1 of the full-length isoform of whirlin and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of the full-length isoform of whirlin and related domains. Whirlin is an essential protein for developmental pathways in photoreceptor cells of the retina and hair cells of the inner ear. The full-length whirlin isoform has two harmonin N-like domains, three PDZ domains, a proline-rich region, and a PDZ-binding motif. Whirlin isoforms may form different complexes at the periciliary membrane complex (PMC) in photoreceptors, and the stereociliary tip and base in inner ear hair cells. It interacts with ADGRV1 and usherin at the PMC; with SANS and RpgrORF15 at the connecting cilium in photoreceptors; with EPS8, MYO15A, p55, and CASK proteins at the stereociliary tip of inner ear hair cells; and with ADGRV1, usherin, and PDZD7 at the stereociliary base in inner ear hair cells. Mutations in the gene encoding whirlin (WHRN; also known as USH2D and DFNB31), have been found to cause either USH2 subtype (USH2D) or autosomal recessive non-syndromic deafness type 31 (DFNB31). Whirlin is the key protein in the USH2 complex (whirlin, usherin and GPR98) which recruits other USH2 causative proteins at the periciliary membrane in photoreceptors and the ankle link of the stereocilia in hair cells. Whirlin's interaction with espin, another stereociliary protein, may be important for the architecture of the USH2 complex. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This whirlin family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467222 [Multi-domain] Cd Length: 82 Bit Score: 94.74 E-value: 2.03e-23

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gi 569006111   84 IHAVRVEKSPSGR-LGFSVRGGSEHGLGIFVSKVEEGSSAERAGLCVGDKITEVNGLSLESTTMGSAVRLLTSSSCLHMM 162
Cdd:cd06740     1 VRQVTLKRSKSHEgLGFSIRGGAEHGVGIYVSLVEPGSLAEKEGLRVGDQILRVNDVSFEKVTHAEAVKILRVSKKLVLS 80


                  ..
gi 569006111  163 VR 164
Cdd:cd06740    81 VR 82

PDZ domain of Rap guanine nucleotide exchange factor 2 and Rap guanine nucleotide exchange factor 6, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of Rap guanine nucleotide exchange factor 2 (RapGEF2, also named RA-GEF-1, PDZ-GEF1, CNrasGEF and nRapGEP) and Rap guanine nucleotide exchange factor 6 (RapGEF6, also named RA-GEF-2 and PDZ-GEF2). RapGEF2 and RapGEF6 constitute a subfamily of guanine nucleotide exchange factors (GEFs) for RAP small GTPases that is characterized by the possession of the PDZ and Ras/Rap-associating domains. They activate Rap small GTPases, by catalyzing the release of GDP from the inactive GDP-bound forms, thereby accelerating GTP loading to yield the active GTP-bound forms. The PDZ domain of RapGEF6 (also known as PDZ-GEF2) binds junctional adhesion molecule A (JAM-A). PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This RapGEF2 and RapGEF6 family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467237 [Multi-domain] Cd Length: 83 Bit Score: 94.64 E-value: 2.62e-23

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gi 569006111  209 RIVHLYTTSDDFCLGFNIRGGKEFGLGIYVSKVDHGGLAEENGIKVGDQVLAANGVRFDDISHSQAVEVLKGQTHIMLTI 288
Cdd:cd06755     1 RTVTLTRPSRESPLHFSLLGGSEKGFGIFVSKVEKGSKAAEAGLKRGDQILEVNGQNFENITLKKALEILRNNTHLSITV 80


                  .
gi 569006111  289 K 289
Cdd:cd06755    81 K 81

N-terminal protein-binding module of harmonin and similar domains, also known as HHD (harmonin homology domain); This domain is found in harmonin, and similar proteins such as delphilin, and whirlin. These are postsynaptic density-95/discs-large/ZO-1 (PDZ) domain-containing scaffold proteins. Harmonin and whirlin are organizers of the Usher protein network of the inner ear and the retina, delphilin is found at the cerebellar parallel fiber-Purkinje cell synapses. This domain is also found in CCM2 (also called malcavernin; C7orf22/chromosome 7 open reading frame 22; OSM). CCM2 along with CCM1 and CCM3 constitutes a set of proteins which when mutated are responsible for cerebral cavernous malformations, an autosomal dominant neurovascular disease characterized by cerebral hemorrhages and vascular malformations in the central nervous system. CCM2 plays many functional roles. CCM2 functions as a scaffold involved in small GTPase Rac-dependent p38 mitogen-activated protein kinase (MAPK) activation when the cell is under hyperosmotic stress. It associates with CCM1 in the signaling cascades that regulate vascular integrity and participates in HEG1 (the transmembrane receptor heart of glass 1) mediated endothelial cell junctions. CCM proteins also inhibit the activation of small GTPase RhoA and its downstream effector Rho kinase (ROCK) to limit vascular permeability. CCM2 mediates TrkA-dependent cell death via its N-terminal PTB domain in pediatric neuroblastic tumours; the C-terminal domain of malcavernin represented here has also been refered to as the Karet domain. Harmonin contains a single copy of this domain at its N-terminus which binds specifically to a short internal peptide fragment of the cadherin 23 cytoplasmic domain (a component of the Usher protein network). Whirlin contains two copies of this domain; the first of these has been assayed for interaction with the cytoplasmic domain of cadherin 23 and no interaction could be detected.

Pssm-ID: 259818 Cd Length: 78 Bit Score: 91.49 E-value: 2.72e-22

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gi 569006111  554 WESRRPLIQDLARRLLTDDEVLAVTRHCSRYVHEGGVEDLVRPLLAILDRPTKLLLLRDIRSVVAPTDLGRFDSMVM 630
Cdd:cd07347     1 RRELARLFSEQADQLLTDQERAYVTQALSEYRKGRSVEALVADLFPVLDTPAKLSLLQGLRSLIPPKDQQRFDELVA 77

canonical PDZ domain; Canonical PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain. PDZ domains usually bind to short specific peptide sequences located at the C-terminal end of their partner proteins known as PDZ binding motifs. These domains can also interact with internal peptide motifs and certain lipids, and can take part in a head-to-tail oligomerization with other PDZ domains. The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. The canonical PDZ domain contains six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467153 [Multi-domain] Cd Length: 81 Bit Score: 91.45 E-value: 3.68e-22

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gi 569006111   87 VRVEKSPSGRLGFSVRGGSEHGLGIFVSKVEEGSSAERAG-LCVGDKITEVNGLSLESTTMGSAVRLLTSSS 157
Cdd:cd00136     2 VTLEKDPGGGLGFSIRGGKDGGGGIFVSRVEPGGPAARDGrLRVGDRILEVNGVSLEGLTHEEAVELLKSAG 73

PDZ domain 2 of the full-length isoform of whirlin and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of the full-length isoform of whirlin and related domains. Whirlin is an essential protein for developmental pathways in photoreceptor cells of the retina and hair cells of the inner ear. The full-length whirlin isoform has two harmonin N-like domains, three PDZ domains, a proline-rich region, and a PDZ-binding motif. Whirlin isoforms may form different complexes at the periciliary membrane complex (PMC) in photoreceptors, and the stereociliary tip and base in inner ear hair cells. It interacts with ADGRV1 and usherin at the PMC; with SANS and RpgrORF15 at the connecting cilium in photoreceptors; with EPS8, MYO15A, p55, and CASK proteins at the stereociliary tip of inner ear hair cells; and with ADGRV1, usherin, and PDZD7 at the stereociliary base in inner ear hair cells. Mutations in the gene encoding whirlin (WHRN; also known as USH2D and DFNB31), have been found to cause either USH2 subtype (USH2D) or autosomal recessive non-syndromic deafness type 31 (DFNB31). Whirlin is the key protein in the USH2 complex (whirlin, usherin and GPR98) which recruits other USH2 causative proteins at the periciliary membrane in photoreceptors and the ankle link of the stereocilia in hair cells. Whirlin's interaction with espin, another stereociliary protein, may be important for the architecture of the USH2 complex. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This whirlin family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467223 [Multi-domain] Cd Length: 84 Bit Score: 89.63 E-value: 1.59e-21

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gi 569006111   84 IHAVRVEKSPSGRLGFSVRGGSEHGLGIFVSKVEEGSSAERAGLCVGDKITEVNGLSLESTTMGSAVRLLTSSSCLHMMV 163
Cdd:cd06741     1 ERKVNLVVEDGQSLGLMIRGGAEYGLGIYVTGVDPGSVAENAGLKVGDQILEVNGRSFLDITHDEAVKILKSSKHLIMTV 80


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gi 569006111  164 RRMG 167
Cdd:cd06741    81 KDVG 84

PDZ domain 1 of the full-length isoform of whirlin and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of the full-length isoform of whirlin and related domains. Whirlin is an essential protein for developmental pathways in photoreceptor cells of the retina and hair cells of the inner ear. The full-length whirlin isoform has two harmonin N-like domains, three PDZ domains, a proline-rich region, and a PDZ-binding motif. Whirlin isoforms may form different complexes at the periciliary membrane complex (PMC) in photoreceptors, and the stereociliary tip and base in inner ear hair cells. It interacts with ADGRV1 and usherin at the PMC; with SANS and RpgrORF15 at the connecting cilium in photoreceptors; with EPS8, MYO15A, p55, and CASK proteins at the stereociliary tip of inner ear hair cells; and with ADGRV1, usherin, and PDZD7 at the stereociliary base in inner ear hair cells. Mutations in the gene encoding whirlin (WHRN; also known as USH2D and DFNB31), have been found to cause either USH2 subtype (USH2D) or autosomal recessive non-syndromic deafness type 31 (DFNB31). Whirlin is the key protein in the USH2 complex (whirlin, usherin and GPR98) which recruits other USH2 causative proteins at the periciliary membrane in photoreceptors and the ankle link of the stereocilia in hair cells. Whirlin's interaction with espin, another stereociliary protein, may be important for the architecture of the USH2 complex. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This whirlin family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467222 [Multi-domain] Cd Length: 82 Bit Score: 89.35 E-value: 1.77e-21

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gi 569006111  208 RRIVHLYTTSDDFCLGFNIRGGKEFGLGIYVSKVDHGGLAEENGIKVGDQVLAANGVRFDDISHSQAVEVLKGQTHIMLT 287
Cdd:cd06740     1 VRQVTLKRSKSHEGLGFSIRGGAEHGVGIYVSLVEPGSLAEKEGLRVGDQILRVNDVSFEKVTHAEAVKILRVSKKLVLS 80


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gi 569006111  288 IK 289
Cdd:cd06740    81 VR 82

PDZ domain 1 of the canonical isoform 1 of PDZ domain containing 7 (PDZD7), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of the long isoform 1 of PDZD7, and related domains. PDZD7 is critical for the organization of Usher syndrome type 2 (USH2) complex. Usher syndrome is the leading cause of hereditary sensory deaf-blindness in humans; USH2 is the most common sub-type. Formation of the USH2 complex is based upon heterodimerization between PDZD7 and whirlin (another PDZ domain-containing protein) and a subsequent dynamic interplay between USH2 proteins via their multiple PDZ domains. The PDZD7 PDZ2 domain binds GPR98 (also known as VLGR1) and usherin (USH2A). PDZD7 and whirlin form heterodimers through their multiple PDZ domains; whirlin and PDZD7 interact with usherin and GPR98 to form an interdependent ankle link complex. PDZD7 also interacts with myosin VIIa. PDZD7 also forms homodimers through its PDZ2 domain. Various isoforms of PDZD7 produced by alternative splicing have been identified; this subgroup includes the first PDZ domain of the canonical isoform of PDZD7- isoform 1. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PDZD7-like family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467269 [Multi-domain] Cd Length: 84 Bit Score: 89.03 E-value: 2.30e-21

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 569006111  217 SDDFCLGFNIRGGKEFGLGIYVSKVDHGGLAEENGIKVGDQVLAANGVRFDDISHSQAVEVLKGQTHIMLTIKETG 292
Cdd:cd10833     9 SPDGSLGFSVRGGSEHGLGIFVSKVEEGSAAERAGLCVGDKITEVNGVSLENITMSSAVKVLTGSNRLRMVVRRMG 84

canonical PDZ domain; Canonical PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain. PDZ domains usually bind to short specific peptide sequences located at the C-terminal end of their partner proteins known as PDZ binding motifs. These domains can also interact with internal peptide motifs and certain lipids, and can take part in a head-to-tail oligomerization with other PDZ domains. The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. The canonical PDZ domain contains six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467153 [Multi-domain] Cd Length: 81 Bit Score: 85.29 E-value: 4.37e-20

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569006111  222 LGFNIRGGKEFGLGIYVSKVDHGGLAEENG-IKVGDQVLAANGVRFDDISHSQAVEVLKG-QTHIMLTIK 289
Cdd:cd00136    12 LGFSIRGGKDGGGGIFVSRVEPGGPAARDGrLRVGDRILEVNGVSLEGLTHEEAVELLKSaGGEVTLTVR 81

PDZ domain of PDZ domain-containing protein 11, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of PDZD11, and related domains. PDZD11 (also known as ATPase-interacting PDZ protein, plasma membrane calcium ATPase-interacting single-PDZ protein, PMCA-interacting single-PDZ protein, PISP) is involved in the dynamic assembly of apical junctions (AJs). It is recruited by PLEKHA7 to AJs to promote the efficient junctional recruitment and stabilization of nectins, and the efficient early phases of assembly of AJs in epithelial cells. The PDZD11 PDZ domain binds nectin-1 and nectin-3. PDZD11 also binds to a PDZ binding motif located in the C-terminal tail of the human sodium-dependent multivitamin transporter, to the cytoplasmic tail of the Menkes copper ATPase ATP7A, and to the cytoplasmic tail of all plasma membrane Ca2+-ATPase b-splice variants. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PDZD11-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467234 [Multi-domain] Cd Length: 83 Bit Score: 83.90 E-value: 1.58e-19

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 569006111   86 AVRVEKSPSGRLGFSVRGGSEHGLGIFVSKVEEGSSAERAGLCVGDKITEVNGLSLESTTMGSAVRLLTSSSCLHMMVR 164
Cdd:cd06752     2 TVVLKRPPGEQLGFNIRGGKASGLGIFISKVIPDSDAHRLGLKEGDQILSVNGVDFEDIEHSEAVKVLKTAREIQMRVR 80

Domain present in PSD-95, Dlg, and ZO-1/2; Also called DHR (Dlg homologous region) or GLGF (relatively well conserved tetrapeptide in these domains). Some PDZs have been shown to bind C-terminal polypeptides; others appear to bind internal (non-C-terminal) polypeptides. Different PDZs possess different binding specificities.

Pssm-ID: 214570 [Multi-domain] Cd Length: 85 Bit Score: 80.12 E-value: 3.85e-18

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569006111     83 IIHAVRVEKSPSGrLGFSVRGGSEHGLGIFVSKVEEGSSAERAGLCVGDKITEVNGLSLESTTMGSAVRLLTSSS-CLHM 161
Cdd:smart00228    1 EPRLVELEKGGGG-LGFSLVGGKDEGGGVVVSSVVPGSPAAKAGLRVGDVILEVNGTSVEGLTHLEAVDLLKKAGgKVTL 79


                    ....
gi 569006111    162 MVRR 165
Cdd:smart00228   80 TVLR 83

PDZ domain 1 of harmonin isoforms a, b, and c, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of harmonin isoforms a, b, and c, and related domains. Harmonin (also known as Usher Type 1C, PDZ-73 and AIE-75) is a key organizer of the Usher (USH) protein interactome. USH syndrome is the leading cause of hereditary sensory deaf-blindness in humans; three clinically distinct types of USH have been identified, type 1 to 3. The gene encoding harmonin (USH1C) is the causative gene for the USH type 1C phenotype. There are at least 10 alternatively spliced isoforms of harmonin, which are divided into three subclasses (a, b, and c). All isoforms contain the first two PDZ domains and the first coiled-coil domain. The a and b isoforms all have a third PDZ domain. The different PDZ domains are responsible for interactions with all known Usher syndrome type 1 proteins, and most Usher syndrome type 2 proteins. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This harmonin family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467219 [Multi-domain] Cd Length: 85 Bit Score: 79.61 E-value: 5.19e-18

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569006111   87 VRVEKSPSGRLGFSVRGGSEHGLGIFVSKVEEGSSAERAGLCVGDKITEVNGLSLESTTMGSAVRLLTSSSCLHMMVRRM 166
Cdd:cd06737     5 VRLDRRGPESLGFSVRGGLEHGCGLFVSHVSPGSQADNKGLRVGDEIVRINGYSISQCTHEEVINLIKTKKTVSLKVRHV 84


                  .
gi 569006111  167 G 167
Cdd:cd06737    85 G 85

PDZ domain 3 of the full-length isoform of whirlin, PDZ domain 1 of the short isoform of whirlin, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of the full-length isoform of whirlin, PDZ domain 1 of the short isoform of whirlin, and related domains. Whirlin is an essential protein for developmental pathways in photoreceptor cells of the retina and hair cells of the inner ear. The full-length whirlin isoform has two harmonin N-like domains, three PDZ domains, a proline-rich region, and a PDZ-binding motif. Whirlin isoforms may form different complexes at the periciliary membrane complex (PMC) in photoreceptors, and the stereociliary tip and base in inner ear hair cells. It interacts with ADGRV1 and usherin at the PMC; with SANS and RpgrORF15 at the connecting cilium in photoreceptors; with EPS8, MYO15A, p55, and CASK proteins at the stereociliary tip of inner ear hair cells; and with ADGRV1, usherin, and PDZD7 at the stereociliary base in inner ear hair cells. Mutations in the gene encoding whirlin (WHRN; also known as USH2D and DFNB31), have been found to cause either USH2 subtype (USH2D) or autosomal recessive non-syndromic deafness type 31 (DFNB31). Whirlin is the key protein in the USH2 complex (whirlin, usherin and GPR98) which recruits other USH2 causative proteins at the periciliary membrane in photoreceptors and the ankle link of the stereocilia in hair cells. Whirlin's interaction with espin, another stereociliary protein, may be important for the architecture of the USH2 complex. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This whirlin family PDZ3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F

Pssm-ID: 467224 [Multi-domain] Cd Length: 91 Bit Score: 79.71 E-value: 6.40e-18

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569006111  856 LRTITLSKMKQSLGISISGGIESKvQPMVKIEKIFPGGAAFLCGDLQAGFELVAVDGESLEQVTHQRAVDTIRRAYRNKA 935
Cdd:cd06742     1 TLLVRIKKTKPTLGIAIEGGANTK-QPLPRVINIQRGGSAHNCGGLKVGHVILEVNGTSLRGLEHREAARLIAEAFKNKS 79


                  ....*...
gi 569006111  936 REPMELVV 943
Cdd:cd06742    80 RDYIEFLV 87

PDZ domain of Rap guanine nucleotide exchange factor 2 and Rap guanine nucleotide exchange factor 6, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of Rap guanine nucleotide exchange factor 2 (RapGEF2, also named RA-GEF-1, PDZ-GEF1, CNrasGEF and nRapGEP) and Rap guanine nucleotide exchange factor 6 (RapGEF6, also named RA-GEF-2 and PDZ-GEF2). RapGEF2 and RapGEF6 constitute a subfamily of guanine nucleotide exchange factors (GEFs) for RAP small GTPases that is characterized by the possession of the PDZ and Ras/Rap-associating domains. They activate Rap small GTPases, by catalyzing the release of GDP from the inactive GDP-bound forms, thereby accelerating GTP loading to yield the active GTP-bound forms. The PDZ domain of RapGEF6 (also known as PDZ-GEF2) binds junctional adhesion molecule A (JAM-A). PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This RapGEF2 and RapGEF6 family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467237 [Multi-domain] Cd Length: 83 Bit Score: 77.30 E-value: 3.39e-17

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 569006111   97 LGFSVRGGSEHGLGIFVSKVEEGSSAERAGLCVGDKITEVNGLSLESTTMGSAVRLLTSSSCLHMMVR 164
Cdd:cd06755    14 LHFSLLGGSEKGFGIFVSKVEKGSKAAEAGLKRGDQILEVNGQNFENITLKKALEILRNNTHLSITVK 81

canonical PDZ domain; Canonical PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain. PDZ domains usually bind to short specific peptide sequences located at the C-terminal end of their partner proteins known as PDZ binding motifs. These domains can also interact with internal peptide motifs and certain lipids, and can take part in a head-to-tail oligomerization with other PDZ domains. The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. The canonical PDZ domain contains six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467153 [Multi-domain] Cd Length: 81 Bit Score: 74.89 E-value: 2.13e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569006111  858 TITLSKMK-QSLGISISGGIESKvqPMVKIEKIFPGGAAFLCGDLQAGFELVAVDGESLEQVTHQRAVDTIRrayrnKAR 936
Cdd:cd00136     1 TVTLEKDPgGGLGFSIRGGKDGG--GGIFVSRVEPGGPAARDGRLRVGDRILEVNGVSLEGLTHEEAVELLK-----SAG 73


                  ....*...
gi 569006111  937 EPMELVVR 944
Cdd:cd00136    74 GEVTLTVR 81

PDZ domain 1 of harmonin isoforms a, b, and c, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of harmonin isoforms a, b, and c, and related domains. Harmonin (also known as Usher Type 1C, PDZ-73 and AIE-75) is a key organizer of the Usher (USH) protein interactome. USH syndrome is the leading cause of hereditary sensory deaf-blindness in humans; three clinically distinct types of USH have been identified, type 1 to 3. The gene encoding harmonin (USH1C) is the causative gene for the USH type 1C phenotype. There are at least 10 alternatively spliced isoforms of harmonin, which are divided into three subclasses (a, b, and c). All isoforms contain the first two PDZ domains and the first coiled-coil domain. The a and b isoforms all have a third PDZ domain. The different PDZ domains are responsible for interactions with all known Usher syndrome type 1 proteins, and most Usher syndrome type 2 proteins. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This harmonin family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467219 [Multi-domain] Cd Length: 85 Bit Score: 74.60 E-value: 2.60e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569006111  208 RRIVHLYTTSDDfCLGFNIRGGKEFGLGIYVSKVDHGGLAEENGIKVGDQVLAANGVRFDDISHSQAVEVLKGQTHIMLT 287
Cdd:cd06737     2 LRLVRLDRRGPE-SLGFSVRGGLEHGCGLFVSHVSPGSQADNKGLRVGDEIVRINGYSISQCTHEEVINLIKTKKTVSLK 80


                  ....*
gi 569006111  288 IKETG 292
Cdd:cd06737    81 VRHVG 85

PDZ domain 2 of harmonin isoforms a, b, and c, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of harmonin isoforms a, b, and c, and related domains. Harmonin (also known as Usher Type 1C, PDZ-73 and AIE-75) is a key organizer of the Usher (USH) protein interactome. USH syndrome is the leading cause of hereditary sensory deaf-blindness in humans; three clinically distinct types of USH have been identified, type 1 to 3. The gene encoding harmonin (USH1C) is the causative gene for the USH type 1C phenotype. There are at least 10 alternatively spliced isoforms of harmonin, which are divided into three subclasses (a, b, and c). All isoforms contain the first two PDZ domains and the first coiled-coil domain. The a and b isoforms all have a third PDZ domain. The different PDZ domains are responsible for interactions with all known Usher syndrome type 1 proteins, and most Usher syndrome type 2 proteins. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This harmonin family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467220 [Multi-domain] Cd Length: 82 Bit Score: 73.89 E-value: 4.27e-16

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 569006111  222 LGFNIRGGKEFGLGIYVSKVDHGGLAEENGIKVGDQVLAANGVRFDDISHSQAVEVLKGQTHIMLTIK 289
Cdd:cd06738    15 LGCSISSGPTQKPGIFISNVKPGSLAEEVGLEVGDQIVEVNGTSFTNVDHKEAVMALKSSRHLTITVR 82

PDZ domain; PDZ domains are found in diverse signaling proteins.

Pssm-ID: 395476 [Multi-domain] Cd Length: 81 Bit Score: 73.47 E-value: 7.15e-16

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 569006111    87 VRVEKSPSGRLGFSVRGGSEHGL-GIFVSKVEEGSSAERAGLCVGDKITEVNGLSLESTTMGSAVRLLTSSS 157
Cdd:pfam00595    2 VTLEKDGRGGLGFSLKGGSDQGDpGIFVSEVLPGGAAEAGGLKVGDRILSINGQDVENMTHEEAVLALKGSG 73

PDZ domain of syntrophins, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of syntrophins (including alpha-1-syntrophin, beta-1-syntrophin, beta-2-syntrophin, gamma-1-syntrophin, and gamma-2-syntrophin), and related domains. Syntrophins play a role in recruiting various signaling molecules into signaling complexes and help provide appropriate spatiotemporal regulation of signaling pathways. They function in cytoskeletal organization and maintenance; as components of the dystrophin-glycoprotein complex (DGC), they help maintain structural integrity of skeletal muscle fibers. They link voltage-gated sodium channels to the actin cytoskeleton and the extracellular matrix, and control the localization and activity of the actin reorganizing proteins such as PI3K, PI(3,4)P2 and TAPP1. Through association with various cytoskeletal proteins within the cells, they are involved in processes such as regulation of focal adhesions, myogenesis, calcium homeostasis, and cell migration. They also have roles in synapse formation and in the organization of utrophin, acetylcholine receptor, and acetylcholinesterase at the neuromuscular synapse. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This syntrophin-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467262 [Multi-domain] Cd Length: 83 Bit Score: 73.38 E-value: 7.32e-16

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 569006111   87 VRVEKSPSGRLGFSVRGGSEHGLGIFVSKVEEGSSAERAG-LCVGDKITEVNGLSLESTTMGSAVRLL 153
Cdd:cd06801     3 VRVVKQDVGGLGISIKGGAEHKMPILISKIFKGQAADQTGqLFVGDAILSVNGENLEDATHDEAVQAL 70

PDZ domain 2 of tyrosine kinase PTPN13, FERM and PDZ domain-containing protein 2 (FRMPD2), and similar domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of human PTPN13, and related domains. PTPN13, also known as Fas-associated protein-tyrosine phosphatase 1 (FAP-1), protein-tyrosine phosphatase 1E (PTP-E1), and protein-tyrosine phosphatase (PTPL1), negatively regulates FAS-mediated apoptosis and NGFR-mediated pro-apoptotic signaling, and may also regulate phosphoinositide 3-kinase (PI3K) signaling. It contains 5 PDZ domains; interaction partners of its second PDZ domain (PDZ2) include the Fas receptor (TNFRSF6) and thyroid receptor-interacting protein 6 (TRIP6). The second PDZ (PDZ2) domain, but not PDZ1 or PDZ3, of FRMPD2 binds to GluN2A and GluN2B, two subunits of N-methyl-d-aspartic acid (NMDA) receptors. Other binding partners of the FRMPDZ2 PDZ2 domain include NOD2, and catenin family members, delta catenin (CTNND2), armadillo repeat gene deleted in velo-cardio-facial syndrome (ARVCF) and p0071 (also known as plakophilin 4; PKP4). PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PTPN13-like family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467254 [Multi-domain] Cd Length: 87 Bit Score: 72.63 E-value: 1.35e-15

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 569006111  858 TITLSKMKQSLGISISGGIESKVQ-PMVKIEKIFPGGAAFLCGDLQAGFELVAVDGESLEQVTHQRAVDTIRRA 930
Cdd:cd06792     4 EVELSKKDGSLGISVTGGINTSVRhGGIYVKSLVPGGAAEQDGRIQKGDRLLEVNGVSLEGVTHKQAVECLKNA 77

Domain present in PSD-95, Dlg, and ZO-1/2; Also called DHR (Dlg homologous region) or GLGF (relatively well conserved tetrapeptide in these domains). Some PDZs have been shown to bind C-terminal polypeptides; others appear to bind internal (non-C-terminal) polypeptides. Different PDZs possess different binding specificities.

Pssm-ID: 214570 [Multi-domain] Cd Length: 85 Bit Score: 72.03 E-value: 2.60e-15

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                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 569006111    222 LGFNIRGGKEFGLGIYVSKVDHGGLAEENGIKVGDQVLAANGVRFDDISHSQAVEVLKG-QTHIMLTIK 289
Cdd:smart00228   14 LGFSLVGGKDEGGGVVVSSVVPGSPAAKAGLRVGDVILEVNGTSVEGLTHLEAVDLLKKaGGKVTLTVL 82

PDZ domain 1 of Drosophila Scribble, human Scribble homolog, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of Drosophila Scribble (also known as LAP4), human Scribble homolog (also known as hScrib, LAP4, CriB1, ScrB1 and Vartul), and related domains. They belong to the LAP family, which describes proteins that contain either one or four PDZ domains and 16 LRRs (leucine-rich repeats) and function in controlling cell shape, size and subcellular protein localization. In Drosophila, the Scribble complex, comprising Scribble, discs large, and lethal giant larvae, plays a role in apico-basal cell polarity, in other forms of polarity, including regulation of the actin cytoskeleton, cell signaling and vesicular trafficking, and in tumor development. Mammalian Scribble is important in many aspects of cancer development. Scribble and its homologs can be downregulated or overexpressed in cancer; they have a role in cancer beyond their function in loss of cell polarity. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Scribble-like family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467188 [Multi-domain] Cd Length: 87 Bit Score: 70.00 E-value: 1.35e-14

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569006111   87 VRVEKSPSGrLGFSVRGG------SEHGLGIFVSKVEEGSSAERAGLCVGDKITEVNGLSLESTTMGSAVRLL-TSSSCL 159
Cdd:cd06704     3 ITIERQTGG-LGISIAGGkgstpyKGDDEGIFISRVTEGGPAAKAGVRVGDKLLEVNGVDLVDADHHEAVEALkNSGNTV 81


                  ....*.
gi 569006111  160 HMMVRR 165
Cdd:cd06704    82 TMVVLR 87

PDZ domain of syntrophins, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of syntrophins (including alpha-1-syntrophin, beta-1-syntrophin, beta-2-syntrophin, gamma-1-syntrophin, and gamma-2-syntrophin), and related domains. Syntrophins play a role in recruiting various signaling molecules into signaling complexes and help provide appropriate spatiotemporal regulation of signaling pathways. They function in cytoskeletal organization and maintenance; as components of the dystrophin-glycoprotein complex (DGC), they help maintain structural integrity of skeletal muscle fibers. They link voltage-gated sodium channels to the actin cytoskeleton and the extracellular matrix, and control the localization and activity of the actin reorganizing proteins such as PI3K, PI(3,4)P2 and TAPP1. Through association with various cytoskeletal proteins within the cells, they are involved in processes such as regulation of focal adhesions, myogenesis, calcium homeostasis, and cell migration. They also have roles in synapse formation and in the organization of utrophin, acetylcholine receptor, and acetylcholinesterase at the neuromuscular synapse. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This syntrophin-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467262 [Multi-domain] Cd Length: 83 Bit Score: 67.98 E-value: 5.13e-14

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gi 569006111  857 RTITLSKMKQS-LGISISGGIESKVqPMVkIEKIFPGGAAFLCGDLQAGFELVAVDGESLEQVTHQRAVDTIRRA 930
Cdd:cd06801     1 RTVRVVKQDVGgLGISIKGGAEHKM-PIL-ISKIFKGQAADQTGQLFVGDAILSVNGENLEDATHDEAVQALKNA 73

PDZ domain; PDZ domains are found in diverse signaling proteins.

Pssm-ID: 395476 [Multi-domain] Cd Length: 81 Bit Score: 67.69 E-value: 6.40e-14

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569006111   222 LGFNIRGGKEFGL-GIYVSKVDHGGLAEENGIKVGDQVLAANGVRFDDISHSQAVEVLKGQT-HIMLTIK 289
Cdd:pfam00595   12 LGFSLKGGSDQGDpGIFVSEVLPGGAAEAGGLKVGDRILSINGQDVENMTHEEAVLALKGSGgKVTLTIL 81

PDZ domain of tax1-binding protein 3 (TAX1BP3), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of TAX1BP3, and related domains. TAX1BP3 (also known as glutaminase-interacting protein 3, tax interaction protein 1, TIP-1, tax-interacting protein 1) may regulate a number of protein-protein interactions by competing for PDZ domain binding sites. TAX1BP3 binds beta-catenin and may act as an inhibitor of the Wnt signaling pathway. It competes with LIN7A (also known as Lin-7A or LIN-7A) for inward rectifier potassium channel 4 (KCNJ4) binding, and thereby promotes KCNJ4 internalization. It may play a role in the Rho signaling pathway, and in the activation of CDC42 by the viral protein HPV16 E6. Binding partners of the TAX1BP3 PDZ domain include beta-catenin, KCNJ4, glutaminase liver isoform (GLS2), rho guanine nucleotide exchange factor 16 (ARHGEF16), rhotekin, and CDK5 regulatory subunit-associated protein 3 (also known as LAPZ). PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This TAX1BP3-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467265 [Multi-domain] Cd Length: 94 Bit Score: 67.75 E-value: 9.74e-14

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569006111   96 RLGFSVRGG----------SEHGLGIFVSKVEEGSSAERAGLCVGDKITEVNGLSLESTTMGSAVRLLT-SSSCLHMMVR 164
Cdd:cd10822    14 ILGFSIGGGidqdpsknpfSYTDKGIYVTRVSEGGPAEKAGLQVGDKILQVNGWDMTMVTHKQAVKRLTkKKPVLRMLVT 93


                  .
gi 569006111  165 R 165
Cdd:cd10822    94 R 94

PDZ domain of protein Lin-7 and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of Lin-7 (also known as LIN-7 or LIN7), and related domains. Lin-7 targets and organize protein complexes to epithelial and synaptic plasma membranes. There are three mammalian Lin-7 homologs: Lin-7A (protein lin-7 homolog A, also known as mammalian lin-seven protein 1 (MALS-1), vertebrate lin-7 homolog 1 (Veli-1), tax interaction protein 33); Lin-7B (also known as MALS-2, Veli-2); and Lin-7C (also known as MALS-3, Veli-3). Lin-7 is involved in localization of the Let-23 growth factor receptor to the basolateral membrane of epithelial cells, in tight junction localization of insulin receptor substrate p53 (IRSp53), in retaining gamma-aminobutyric (GABA) transporter (BGT-1) at the basolateral surface of epithelial cells, and in regulating recruitment of neurotransmitter receptors to the postsynaptic density (PSD). The Lin7 PDZ domain binds Let-23, BGT and beta-catenin, and NMDA (N-methyl-D-aspartate) receptor NR2B. Lin-7 also binds to the PDZ binding motif located in the C-terminal tail of Rhotekin, an effector protein for small GTPase Rho. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Lin-7-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467258 [Multi-domain] Cd Length: 86 Bit Score: 67.46 E-value: 1.18e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569006111  209 RIVHLYTTSDDfcLGFNIRGGKEFGLGIYVSKVDHGGLAEENG-IKVGDQVLAANGVRFDDISHSQAVEVLK-GQTHIML 286
Cdd:cd06796     3 RVVELPKTEEG--LGFNVMGGKEQNSPIYISRIIPGGVADRHGgLKRGDQLLSVNGVSVEGEHHEKAVELLKaAQGSVKL 80


                  ....*
gi 569006111  287 TIKET 291
Cdd:cd06796    81 VVRYT 85

PDZ domain 2 of harmonin isoforms a, b, and c, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of harmonin isoforms a, b, and c, and related domains. Harmonin (also known as Usher Type 1C, PDZ-73 and AIE-75) is a key organizer of the Usher (USH) protein interactome. USH syndrome is the leading cause of hereditary sensory deaf-blindness in humans; three clinically distinct types of USH have been identified, type 1 to 3. The gene encoding harmonin (USH1C) is the causative gene for the USH type 1C phenotype. There are at least 10 alternatively spliced isoforms of harmonin, which are divided into three subclasses (a, b, and c). All isoforms contain the first two PDZ domains and the first coiled-coil domain. The a and b isoforms all have a third PDZ domain. The different PDZ domains are responsible for interactions with all known Usher syndrome type 1 proteins, and most Usher syndrome type 2 proteins. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This harmonin family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467220 [Multi-domain] Cd Length: 82 Bit Score: 66.96 E-value: 1.24e-13

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 569006111   97 LGFSVRGGSEHGLGIFVSKVEEGSSAERAGLCVGDKITEVNGLSLESTTMGSAVRLLTSSSCLHMMVR 164
Cdd:cd06738    15 LGCSISSGPTQKPGIFISNVKPGSLAEEVGLEVGDQIVEVNGTSFTNVDHKEAVMALKSSRHLTITVR 82

PDZ domain 3 of PDZ domain containing 2 (PDZD2), PDZ domain 1 of human pro-interleukin-16 (isoform 1, 1332 AA), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of PDZD2, also known as KIAA0300, PIN-1, activated in prostate cancer (AIPC) and PDZ domain-containing protein 3 (PDZK3). PDZD2 has seven PDZ domains. PDZD2 is expressed at exceptionally high levels in the pancreas and certain cancer tissues, such as prostate cancer. It promotes the proliferation of insulinoma cells and is upregulated during prostate tumorigenesis. In osteosarcoma (OS), the microRNA miR-363 acts as a tumor suppressor by inhibiting PDZD2. This family also includes the first PDZ domain (PDZ1) of human pro-interleukin-16 (isoform 1, also known as nPro-Il-16; 1332 amino-acid protein). Precursor IL-16 is cleaved to produce pro-IL-16 and mature IL-16 (derived from the C-terminal 121 AA). Pro-IL-16 functions as a regulator of T cell growth; mature IL-16 is a CD4 ligand that induces chemotaxis and CD25 expression in CD4+ T cells. IL-16 bioactivity has been closely associated with the progression of several different cancers. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PDZD2-like family PDZ3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467240 [Multi-domain] Cd Length: 87 Bit Score: 66.53 E-value: 1.94e-13

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 569006111  857 RTITLSK--MKQSLGISISGGIESKVQPM-VKIEKIFPGGAAFLCGDLQAGFELVAVDGESLEQVTHQRAVDTIRR 929
Cdd:cd06759     1 STIVLMKgaGGKGLGFSIVGGRDSPRGPMgIYVKTIFPGGAAAEDGRLKEGDEILEVNGESLQGLTHQEAIQKFKQ 76

PDZ domain 3 of Drosophila Scribble, human Scribble homolog, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of Drosophila Scribble (also known as LAP4), human Scribble homolog (also known as hScrib, LAP4, CriB1, ScrB1 and Vartul), and related domains. They belong to the LAP family, which describes proteins that contain either one or four PDZ domains and 16 LRRs (leucine-rich repeats) and function in controlling cell shape, size and subcellular protein localization. In Drosophila, the Scribble complex, comprising Scribble, discs large, and lethal giant larvae, plays a role in apico-basal cell polarity, in other forms of polarity, including regulation of the actin cytoskeleton, cell signaling and vesicular trafficking, and in tumor development. Mammalian Scribble is important in many aspects of cancer development. Scribble and its homologs can be downregulated or overexpressed in cancer; they have a role in cancer beyond their function in loss of cell polarity. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Scribble-like family PDZ3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467186 [Multi-domain] Cd Length: 89 Bit Score: 66.51 E-value: 2.72e-13

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569006111   87 VRVEKSpSGRLGFSVRGGSEHGL--------GIFVSKVEEGSSAERAGLCVGDKITEVNGLSLESTTMGSAVR-LLTSSS 157
Cdd:cd06702     3 IHLVKA-GGPLGLSIVGGSDHSShpfgvdepGIFISKVIPDGAAAKSGLRIGDRILSVNGKDLRHATHQEAVSaLLSPGQ 81


                  ....*...
gi 569006111  158 CLHMMVRR 165
Cdd:cd06702    82 EIKLLVRH 89

PDZ domain 3 of Discs Large 5 (Dlg5) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of Drosophila and mammalian Dlg5, and related domains. Dlg5 is a scaffold protein with multiple conserved functions that are independent of each other in regulating growth, cell polarity, and cell adhesion. It has a coiled-coil domain, 4 PDZ domains and a MAGUK domain (an SH3 domain next to a non-catalytically active guanylate kinase domain). Deregulation of Dlg5 has been implicated in the malignancy of several cancer types. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Dlg5-like family PDZ3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467248 [Multi-domain] Cd Length: 82 Bit Score: 64.65 E-value: 8.13e-13

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 569006111   87 VRVEKSpSGRLGFSVRGGsEHGlGIFVSKVEEGSSAERAGLCVGDKITEVNGLSLESTTMGSAVRLLT 154
Cdd:cd06767     6 VSIEKG-SEPLGISIVSG-ENG-GIFVSSVTEGSLAHQAGLEYGDQLLEVNGINLRNATEQQAALILR 70

PDZ domain of Golgi-associated PDZ and coiled-coil motif-containing protein (GOPC), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of GOPC and related domains. GOPC, also known as PIST (PDZ domain protein interacting specifically with TC10), FIG (fused in glioblastoma), and CAL (CFTR-associated ligand), regulates the trafficking of a wide array of proteins, including small GTPases, receptors, and cell surface molecules such as cadherin 23 and CFTR. It may regulate CFTR chloride currents and acid-sensing ASIC3 currents by modulating cell surface expression of both channels, and may play a role in autophagy. Interaction partners of the GOPC PDZ domains include: FZD5, FZD8, ASIC3, CFTR, MUC3, ARFRP1, Ggamma13, neuroligin, and Stargazin. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This GOPC-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467261 [Multi-domain] Cd Length: 83 Bit Score: 64.31 E-value: 1.34e-12

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569006111   87 VRVEKSPSGRLGFSVRGGSEHGLGIFVSKVEEGSSAER-AGLCVGDKITEVNGLSLESTTMGSAVRLLTS 155
Cdd:cd06800     3 VLLSKEPHEGLGISITGGKEHGVPILISEIHEGQPADRcGGLYVGDAILSVNGIDLRDAKHKEAVTILSQ 72

PDZ domain 3 of human discs large homolog 1 (Dlg1), Dlg2, and Dlg4, Drosophila disc large (Dlg), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of Drosophila Dlg1, human Dlg1, 2, and 4 and related domains. Dlg1 (also known as synapse-associated protein Dlg197; SAP-97), Dlg2 (also known as channel-associated protein of synapse-110; postsynaptic density protein 93, PSD-93), Dlg4 (also known as postsynaptic density protein 95, PSD-95; synapse-associated protein 90, SAP-90) each have 3 PDZ domains and belong to the membrane-associated guanylate kinase family. Dlg1 regulates antigen receptor signaling and cell polarity in lymphocytes, B-cell proliferation and antibody production, and TGFalpha bioavailability; its PDZ3 domain binds pro-TGFalpha, and its PDZ2 domain binds the TACE metalloprotease responsible for cleaving pro-TGFalpha to a soluble form. Dlg2 is involved in N-methyl-D-aspartate (NMDA) receptor signaling, regulating surface expression of NMDA receptors in dorsal horn neurons of the spinal cord; it interacts with NMDA receptor subunits and with Shaker-type K+ channel subunits to cluster into a channel complex. The Dlg4 PDZ1 domain binds NMDA receptors, and its PDZ2 domain binds neuronal nitric oxide synthase (nNOS), forming a complex in neurons. The Drosophila Scribble complex (Scribble, Dlg, and lethal giant larvae) plays a role in apico-basal cell polarity, and in other forms of polarity, including regulation of the actin cytoskeleton, cell signaling and vesicular trafficking, and in tumor development; postsynaptic targeting of Drosophila DLG requires interactions mediated by the first two PDZ domains. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Dlg-like family PDZ3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467257 [Multi-domain] Cd Length: 91 Bit Score: 64.30 E-value: 1.58e-12

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 569006111  222 LGFNIRGGKEfGLGIYVSKVDHGGLAEENG-IKVGDQVLAANGVRFDDISHSQAVEVLK--GQT 282
Cdd:cd06795    14 LGFNIVGGED-GEGIFISFILAGGPADLSGeLRRGDQILSVNGVDLRNATHEQAAAALKnaGQT 76

PDZ domain 1 of Drosophila Scribble, human Scribble homolog, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of Drosophila Scribble (also known as LAP4), human Scribble homolog (also known as hScrib, LAP4, CriB1, ScrB1 and Vartul), and related domains. They belong to the LAP family, which describes proteins that contain either one or four PDZ domains and 16 LRRs (leucine-rich repeats) and function in controlling cell shape, size and subcellular protein localization. In Drosophila, the Scribble complex, comprising Scribble, discs large, and lethal giant larvae, plays a role in apico-basal cell polarity, in other forms of polarity, including regulation of the actin cytoskeleton, cell signaling and vesicular trafficking, and in tumor development. Mammalian Scribble is important in many aspects of cancer development. Scribble and its homologs can be downregulated or overexpressed in cancer; they have a role in cancer beyond their function in loss of cell polarity. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Scribble-like family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467188 [Multi-domain] Cd Length: 87 Bit Score: 61.91 E-value: 9.08e-12

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 569006111  222 LGFNIRGGK------EFGLGIYVSKVDHGGLAEENGIKVGDQVLAANGVRFDDISHSQAVEVLKG 280
Cdd:cd06704    12 LGISIAGGKgstpykGDDEGIFISRVTEGGPAAKAGVRVGDKLLEVNGVDLVDADHHEAVEALKN 76

PDZ domain 2 of Drosophila Scribble, human Scribble homolog, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of Drosophila Scribble (also known as LAP4), human Scribble homolog (also known as hScrib, LAP4, CriB1, ScrB1 and Vartul), and related domains. They belong to the LAP family, which describes proteins that contain either one or four PDZ domains and 16 LRRs (leucine-rich repeats) and function in controlling cell shape, size and subcellular protein localization. In Drosophila, the Scribble complex, comprising Scribble, discs large, and lethal giant larvae, plays a role in apico-basal cell polarity, in other forms of polarity, including regulation of the actin cytoskeleton, cell signaling and vesicular trafficking, and in tumor development. Mammalian Scribble is important in many aspects of cancer development. Scribble and its homologs can be downregulated or overexpressed in cancer; they have a role in cancer beyond their function in loss of cell polarity. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Scribble-like family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467187 [Multi-domain] Cd Length: 92 Bit Score: 61.89 E-value: 1.12e-11

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 569006111  218 DDFCLGFNIRGGKEFGL------GIYVSKVDHGGLAEENG-IKVGDQVLAANGVRFDDISHSQAVEVLKG-QTHIMLTI 288
Cdd:cd06703    10 DGKGLGFSIAGGKGSTPfrdgdeGIFISRITEGGAADRDGkLQVGDRVLSINGVDVTEARHDQAVALLTSsSPTITLVV 88

PDZ domain 4 of Drosophila Scribble, human Scribble homolog, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 4 of Drosophila Scribble (also known as LAP4), human Scribble homolog (also known as hScrib, LAP4, CriB1, ScrB1 and Vartul), and related domains. They belong to the LAP family, which describes proteins that contain either one or four PDZ domains and 16 LRRs (leucine-rich repeats) and function in controlling cell shape, size and subcellular protein localization. In Drosophila, the Scribble complex, comprising Scribble, discs large, and lethal giant larvae, plays a role in apico-basal cell polarity, in other forms of polarity, including regulation of the actin cytoskeleton, cell signaling and vesicular trafficking, and in tumor development. Mammalian Scribble is important in many aspects of cancer development. Scribble and its homologs can be downregulated or overexpressed in cancer; they have a role in cancer beyond their function in loss of cell polarity. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Scribble-like family PDZ4 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467185 [Multi-domain] Cd Length: 98 Bit Score: 61.86 E-value: 1.40e-11

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569006111   87 VRVEKSPSGRLGFSVRGGS---------EHGLGIFVSKVEEGSSAERAG-LCVGDKITEVNGLSLESTTMGSAVRLL-TS 155
Cdd:cd06701     7 LTIVKEPGEKLGISIRGGAkghagnpldPTDEGIFISKINPDGAAARDGrLKVGQRILEVNGQSLLGATHQEAVRILrSV 86


                  ....*...
gi 569006111  156 SSCLHMMV 163
Cdd:cd06701    87 GDTLTLLV 94

PDZ domain 2 of tyrosine kinase PTPN13, FERM and PDZ domain-containing protein 2 (FRMPD2), and similar domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of human PTPN13, and related domains. PTPN13, also known as Fas-associated protein-tyrosine phosphatase 1 (FAP-1), protein-tyrosine phosphatase 1E (PTP-E1), and protein-tyrosine phosphatase (PTPL1), negatively regulates FAS-mediated apoptosis and NGFR-mediated pro-apoptotic signaling, and may also regulate phosphoinositide 3-kinase (PI3K) signaling. It contains 5 PDZ domains; interaction partners of its second PDZ domain (PDZ2) include the Fas receptor (TNFRSF6) and thyroid receptor-interacting protein 6 (TRIP6). The second PDZ (PDZ2) domain, but not PDZ1 or PDZ3, of FRMPD2 binds to GluN2A and GluN2B, two subunits of N-methyl-d-aspartic acid (NMDA) receptors. Other binding partners of the FRMPDZ2 PDZ2 domain include NOD2, and catenin family members, delta catenin (CTNND2), armadillo repeat gene deleted in velo-cardio-facial syndrome (ARVCF) and p0071 (also known as plakophilin 4; PKP4). PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PTPN13-like family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467254 [Multi-domain] Cd Length: 87 Bit Score: 61.46 E-value: 1.45e-11

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gi 569006111  222 LGFNIRGGKEFGL---GIYVSKVDHGGLAEENG-IKVGDQVLAANGVRFDDISHSQAVEVLKGQTHI 284
Cdd:cd06792    14 LGISVTGGINTSVrhgGIYVKSLVPGGAAEQDGrIQKGDRLLEVNGVSLEGVTHKQAVECLKNAGQV 80

PDZ domain 5 of membrane-associated guanylate kinase inverted 1 (MAGI-1), MAGI-2, and MAGI-3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 5 of MAGI1, 2, 3 (MAGI is also known as Membrane-associated guanylate kinase, WW and PDZ domain-containing protein) and related domains. MAGI proteins have been implicated in the control of cell migration and invasion through altering the activity of phosphatase and tensin homolog (PTEN) and modulating Akt signaling. Four MAGI proteins have been identified (MAGI1-3 and MAGIX). MAGI1-3 have 6 PDZ domains and bind to the C-terminus of PTEN via their PDZ2 domain. MAGIX has a single PDZ domain that is related to MAGI1-3 PDZ domain 5, and belongs to this MAGI1,2,3-like family. Other binding partners for MAGI1 include JAM4, C-terminal tail of high risk HPV-18 E6, megalin, TRAF6, Kir4.1 (basolateral K+ channel subunit), and cadherin 23; for MAGI2, include DASM1, dendrin, axin, beta- and delta-catenin, neuroligin, hyperpolarization-activated cation channels, beta1-adrenergic receptors, NMDA receptor, and TARPs; and for MAGI3 includes LPA2. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MAGI family PDZ5 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467217 [Multi-domain] Cd Length: 84 Bit Score: 60.67 E-value: 2.03e-11

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gi 569006111  223 GFNIRGGKEFG-LGIYVSKVDHGGLAEENG-IKVGDQVLAANGVRFDDISHSQAVEVLK-GQTHIMLTIK 289
Cdd:cd06735    14 GFSIRGGREYNnMPLYVLRLAEDGPAQRDGrLRVGDQILEINGESTQGMTHAQAIELIRsGGSVVRLLLR 83

PDZ1 domain of human syntaxin-binding protein 4 (STXBP4), PDZ2 domain of Gallus gallus uncharacterized STXBP4 isoform X1, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of human syntaxin-binding protein 4 (STXBP4), PDZ2 domain of Gallus gallus uncharacterized STXBP4 isoform X1, and related domains. Human STXBP4 (also known as Synip) includes a single PDZ domain, a coiled-coil domain, and a WW domain (named for its two conserved tryptophans); Gallus gallus STXBP4 isoform X1 contains 2 PDZ domains (PDZ1 and PDZ2). Human STXBP4 plays a role in the translocation of transport vesicles from the cytoplasm to the plasma membrane: insulin induces the dissociation of the STXBP4 and STX4 complex liberating STX4 to interact with Vamp2, and to form the SNARE complex thereby promoting vesicle fusion. It may also play a role in the regulation of insulin release by pancreatic beta cells after stimulation by glucose. Human STXBP4 is also known to physically associate with a prominent isoform of TP63 (deltaNp63alpha 9) whose overexpression promotes squamous cell carcinoma development, and in doing so prevents degradation of this isoform by the Cdc20-APC/C complex, Itch, and RACK1. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This STXBP4-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467184 [Multi-domain] Cd Length: 89 Bit Score: 60.01 E-value: 4.90e-11

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gi 569006111  855 ALRTITLSKmKQSLGISISGGIESKVQPMVKIEKIFPGGAAFLCGDLQAGFELVAVDGESLEQVTHQRAVDTIRRA 930
Cdd:cd06698     1 GIQLITVAK-STGLGLSIVGGINRPEGPMVFIQEVIPGGDCYKDGRLRPGDQLVSINKESLIGVTLEEAKSILTRA 75

PDZ domain 13 of multi-PDZ-domain protein 1 (MUPP1) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 13 of MUPP1. MUPP1 and PATJ serve as scaffolding proteins linking different proteins and protein complexes involved in the organization of tight junctions and epithelial polarity. MUPP1 contains an L27 (Lin-2 and Lin-7 binding) domain and 13 PDZ domains. PATJ (also known as INAD-like) contains an L27 domain and ten PDZ domains. PATJ lacks 3 PDZ domains seen in MUPP1: PDZ6, PDZ9, and PDZ13. This MuPP1-like PDZ13 domain is therefore absent from PATJ. MUPP1 and PATJ share several binding partners, including junctional adhesion molecules (JAM), zonula occludens (ZO)-3, Pals1 (protein associated with Lin-7), Par (partitioning defective)-6 proteins, and nectins (adherence junction adhesion molecules). PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MUPP1-like family PDZ13 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467164 [Multi-domain] Cd Length: 83 Bit Score: 58.89 E-value: 1.03e-10

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gi 569006111  858 TITLSKMKQSLGISISGGIESKVQPM-VKIEKIFPGGAAFLCGDLQAGFELVAVDGESLEQVTHQRAVDTIRRA 930
Cdd:cd06676     1 TITLERGSDGLGFSIVGGFGSPHGDLpIYVKTVFEKGAAAEDGRLKRGDQILAVNGESLEGVTHEEAVNILKKT 74

Domain present in PSD-95, Dlg, and ZO-1/2; Also called DHR (Dlg homologous region) or GLGF (relatively well conserved tetrapeptide in these domains). Some PDZs have been shown to bind C-terminal polypeptides; others appear to bind internal (non-C-terminal) polypeptides. Different PDZs possess different binding specificities.

Pssm-ID: 214570 [Multi-domain] Cd Length: 85 Bit Score: 58.93 E-value: 1.09e-10

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gi 569006111    856 LRTITLSKMKQSLGISISGGIESKVQpmVKIEKIFPGGAAFLCGdLQAGFELVAVDGESLEQVTHQRAVDTIRrayrnKA 935
Cdd:smart00228    2 PRLVELEKGGGGLGFSLVGGKDEGGG--VVVSSVVPGSPAAKAG-LRVGDVILEVNGTSVEGLTHLEAVDLLK-----KA 73

                            90
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gi 569006111    936 REPMELVVRVPG 947
Cdd:smart00228   74 GGKVTLTVLRGG 85

PDZ domain 2 of human discs large homolog 1 (Dlg1), Dlg2, and Dlg4, Drosophila disc large (Dlg), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of Drosophila Dlg1, human Dlg1,2, and 4 and related domains. Dlg1 (also known as synapse-associated protein Dlg197 or SAP-97), Dlg2 (also known as channel-associated protein of synapse-110, postsynaptic density protein 93, or PSD-93), Dlg4 (also known as postsynaptic density protein 95, PSD-95, synapse-associated protein 90, or SAP-90) each have 3 PDZ domains and belong to the membrane-associated guanylate kinase family. Dlg1 regulates antigen receptor signaling and cell polarity in lymphocytes, B-cell proliferation and antibody production, and TGFalpha bioavailability; its PDZ3 domain binds pro-TGFalpha, and its PDZ2 domain binds the TACE metalloprotease responsible for cleaving pro-TGFalpha to a soluble form. Dlg2 is involved in N-methyl-D-aspartate (NMDA) receptor signaling. It regulates surface expression of NMDA receptors in dorsal horn neurons of the spinal cord, and it also interacts with NMDA receptor subunits and with Shaker-type K+ channel subunits to cluster into a channel complex. Dlg4 PDZ1 domain binds NMDA receptors, and its PDZ2 domain binds neuronal nitric oxide synthase (nNOS), forming a complex in neurons. The Drosophila Scribble complex (Scribble, Dlg, and lethal giant larvae) plays a role in apico-basal cell polarity, and in other forms of polarity, including regulation of the actin cytoskeleton, cell signaling and vesicular trafficking, and in tumor development. Postsynaptic targeting of Drosophila DLG requires interactions mediated by the first two PDZ domains. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Dlg-like family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467207 [Multi-domain] Cd Length: 85 Bit Score: 58.82 E-value: 1.12e-10

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gi 569006111   91 KSPSGrLGFSVRGG--SEHGLG---IFVSKVEEGSSAERAG-LCVGDKITEVNGLSLESTTMGSAVRLLTSSS 157
Cdd:cd06724     6 KGPKG-LGFSIAGGvgNQHIPGdngIYVTKIIEGGAAQKDGrLQVGDKLLAVNDVSLEEVTHEEAVAALKNTS 77

PDZ domain of synaptojanin-2-binding protein (SYNJ2BP), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of SYNJ2BP, and related domains. SYNJ2BP (also known as mitochondrial outer membrane protein 25, OMP25) regulates endocytosis of activin type 2 receptor kinases through the Ral/RALBP1-dependent pathway and may be involved in suppression of activin-induced signal transduction. Binding partners of the SYNJ2BP PDZ domain include activin type II receptors (ActR-II), and SYNJ2. SYNJ2BP interacts with the PDZ binding motif of the Notch Delta-like ligand 1 (DLL1) and DLL4, promoting Delta-Notch signaling, and inhibiting sprouting angiogenesis. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This SYNJ2BP-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467193 [Multi-domain] Cd Length: 86 Bit Score: 58.84 E-value: 1.16e-10

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gi 569006111  222 LGFNIRGGKEFGL-----GIYVSKVDHGGLAEENG-IKVGDQVLAANGVRFDDISHSQAVEVLK 279
Cdd:cd06709    12 LGFNIVGGTDQPYipndsGIYVAKIKEDGAAAIDGrLQEGDKILEINGQSLENLTHQDAVELFR 75

PDZ1 domain of Gallus gallus uncharacterized syntaxin-binding protein 4 (STXBP4) isoform X1, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of Gallus gallus uncharacterized syntaxin-binding protein 4 (STXBP4) isoform X1, and related domains. Gallus gallus STXBP4 isoform X1 contains 2 PDZ domains (PDZ1 and PDZ2). PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This STXBP4-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467179 [Multi-domain] Cd Length: 88 Bit Score: 58.77 E-value: 1.31e-10

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gi 569006111  859 ITLSKMKQSLGISISGGIESKVQPM--VKIEKIFPGGAAFLCGDLQAGFELVAVDGESLEQVTHQRAVDTIRRAyrnKAR 936
Cdd:cd06692     1 IEFSDCSKGLGIKIIGGYRENTGEEfgIFIKRILPGGLAATDGRLKEGDLILEVNGESLQGVTNERAVSILRSA---SAS 77


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gi 569006111  937 EPMELVV 943
Cdd:cd06692    78 NHMSLLI 84

PDZ domain 1 of PDZ domain-containing RING finger protein 4 (PDZRN4), PDZRN3-B, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of PDZRN4, PDZRN3-B, and related domains. PDZRN4 (also known as ligand of numb protein X 4, and SEMACAP3-like protein) contains an N-terminal RING domain and two tandem repeat PDZ domains. It is involved in the progression of cancer, including human liver cancer and breast cancer, and may contribute to the tumorigenesis of rectal adenocarcinoma. Danio rerio PDZRN3-B may participate in neurogenesis: the first PDZ domain of Danio rerio Pdzrn3 interacts with Kidins220 (Kinase D-interacting substrate 220 kD, also named Ankyrin Repeat-Rich Membrane Spanning), a crucial mediator of signal transduction in neural tissues. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PDZRN4-like family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467199 [Multi-domain] Cd Length: 92 Bit Score: 58.56 E-value: 1.56e-10

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gi 569006111   94 SGRLGFSVRGG-----SEHGL---GIFVSKV-EEGSSAERAGLCVGDKITEVNGLSLESTTMGSAV 150
Cdd:cd06715    11 NGSLGFNIIGGrpcenNQEGSsseGIYVSKIvENGPAADEGGLQVHDRIIEVNGKDLSKATHEEAV 76

PDZ domain of Golgi-associated PDZ and coiled-coil motif-containing protein (GOPC), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of GOPC and related domains. GOPC, also known as PIST (PDZ domain protein interacting specifically with TC10), FIG (fused in glioblastoma), and CAL (CFTR-associated ligand), regulates the trafficking of a wide array of proteins, including small GTPases, receptors, and cell surface molecules such as cadherin 23 and CFTR. It may regulate CFTR chloride currents and acid-sensing ASIC3 currents by modulating cell surface expression of both channels, and may play a role in autophagy. Interaction partners of the GOPC PDZ domains include: FZD5, FZD8, ASIC3, CFTR, MUC3, ARFRP1, Ggamma13, neuroligin, and Stargazin. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This GOPC-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467261 [Multi-domain] Cd Length: 83 Bit Score: 58.15 E-value: 1.60e-10

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gi 569006111  222 LGFNIRGGKEFGLGIYVSKVDHGGLAEE-NGIKVGDQVLAANGVRFDDISHSQAVEVLKGQT 282
Cdd:cd06800    13 LGISITGGKEHGVPILISEIHEGQPADRcGGLYVGDAILSVNGIDLRDAKHKEAVTILSQQR 74

PDZ domain of protein Lin-7 and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of Lin-7 (also known as LIN-7 or LIN7), and related domains. Lin-7 targets and organize protein complexes to epithelial and synaptic plasma membranes. There are three mammalian Lin-7 homologs: Lin-7A (protein lin-7 homolog A, also known as mammalian lin-seven protein 1 (MALS-1), vertebrate lin-7 homolog 1 (Veli-1), tax interaction protein 33); Lin-7B (also known as MALS-2, Veli-2); and Lin-7C (also known as MALS-3, Veli-3). Lin-7 is involved in localization of the Let-23 growth factor receptor to the basolateral membrane of epithelial cells, in tight junction localization of insulin receptor substrate p53 (IRSp53), in retaining gamma-aminobutyric (GABA) transporter (BGT-1) at the basolateral surface of epithelial cells, and in regulating recruitment of neurotransmitter receptors to the postsynaptic density (PSD). The Lin7 PDZ domain binds Let-23, BGT and beta-catenin, and NMDA (N-methyl-D-aspartate) receptor NR2B. Lin-7 also binds to the PDZ binding motif located in the C-terminal tail of Rhotekin, an effector protein for small GTPase Rho. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Lin-7-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467258 [Multi-domain] Cd Length: 86 Bit Score: 58.22 E-value: 1.73e-10

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gi 569006111  857 RTITLSKMKQSLGISISGGIESKVQpmVKIEKIFPGGAAFLCGDLQAGFELVAVDGESLEQVTHQRAVDTIRRA 930
Cdd:cd06796     3 RVVELPKTEEGLGFNVMGGKEQNSP--IYISRIIPGGVADRHGGLKRGDQLLSVNGVSVEGEHHEKAVELLKAA 74

PDZ domain 4 of human Ligand of Numb protein X 1 (LNX1) and LNX2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 4 of LNX1 (also known as PDZ domain-containing RING finger protein 2, PDZRN2)and LNX2 (also known as PDZ domain-containing RING finger protein 1, PDZRN1), and related domains. LNX1 and LNX2 are Ring (Really Interesting New Gene) finger and PDZ domain-containing E3 ubiquitin ligases that bind to the cell fate determinant protein NUMB and mediate its ubiquitination. LNX1 can ubiquitinate a number of other ligands including PPFIA1, KLHL11, KIF7 and ERC2. LNX1 and LNX2 each have four PDZ domains. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This LNX family PDZ4 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467168 [Multi-domain] Cd Length: 89 Bit Score: 58.51 E-value: 1.76e-10

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gi 569006111   85 HAVRVEKSPSGRLGFSVRGGSE--HG-LGIFVSKVEEGSSAERAG-LCVGDKITEVNGLSLESTTMGSAVRLL 153
Cdd:cd06680     1 KDITLRRSSSGSLGFSIVGGYEesHGnQPFFVKSIVPGTPAYNDGrLKCGDIILAVNGVSTVGMSHAALVPLL 73

PDZ domain of synaptojanin-2-binding protein (SYNJ2BP), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of SYNJ2BP, and related domains. SYNJ2BP (also known as mitochondrial outer membrane protein 25, OMP25) regulates endocytosis of activin type 2 receptor kinases through the Ral/RALBP1-dependent pathway and may be involved in suppression of activin-induced signal transduction. Binding partners of the SYNJ2BP PDZ domain include activin type II receptors (ActR-II), and SYNJ2. SYNJ2BP interacts with the PDZ binding motif of the Notch Delta-like ligand 1 (DLL1) and DLL4, promoting Delta-Notch signaling, and inhibiting sprouting angiogenesis. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This SYNJ2BP-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467193 [Multi-domain] Cd Length: 86 Bit Score: 58.07 E-value: 1.77e-10

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gi 569006111   85 HAVRVEKSPSGrLGFSVRGGSEHGL-----GIFVSKVEEGSSAERAG-LCVGDKITEVNGLSLESTTMGSAVRLLTSS 156
Cdd:cd06709     1 EEITLKRGPSG-LGFNIVGGTDQPYipndsGIYVAKIKEDGAAAIDGrLQEGDKILEINGQSLENLTHQDAVELFRNA 77

PDZ domain 10 of multi-PDZ-domain protein 1 (MUPP1), domain 8 of PATJ (protein-associated tight junction) and similar domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 10 of MUPP1, PDZ domain 8 of PATJ, and related domains. MUPP1 and PATJ serve as scaffolding proteins linking different proteins and protein complexes involved in the organization of tight junctions and epithelial polarity. MUPP1 contains an L27 (Lin-2 and Lin-7 binding) domain and 13 PDZ domains. PATJ (also known as INAD-like) contains an L27 domain and ten PDZ domains. MUPP1 and PATJ share several binding partners, including junctional adhesion molecules (JAM), zonula occludens (ZO)-3, Pals1 (protein associated with Lin-7), Par (partitioning defective)-6 proteins, and nectins (adherence junction adhesion molecules). PATJ lacks 3 PDZ domains seen in MUPP1: PDZ6, 9, and 13; consequently, MUPP1 PDZ7 and 8 align with PATJ PDZ6 and 7; and MUPP1 PDZ domains 10-12 align with PATJ PDZ domains 8-10. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MUPP1-like family PDZ10 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467161 [Multi-domain] Cd Length: 86 Bit Score: 58.07 E-value: 1.88e-10

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gi 569006111  858 TITLSKMKQSLGISISGGIESkVQPMVKIEKIFPGGAAFLCGDLQAGFELVAVDGESLEQVTHQRAVDTIRRA 930
Cdd:cd06673     5 TIEINKGKKGLGLSIVGGSDT-LLGAIIIHEVYEDGAAAKDGRLWAGDQILEVNGEDLRKATHDEAINVLRQT 76

PDZ domain 1 of protein tyrosine phosphatase non-receptor type 13 (PTPN13),FERM and PDZ domain-containing protein 2 (FRMPD2), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of PTPN13 [also known as Fas-associated protein-tyrosine phosphatase 1 (FAP-1), protein-tyrosine phosphatase 1E (PTP-E1), and protein-tyrosine phosphatase (PTPL1)], FRMPD2 (also known as PDZ domain-containing protein 4; PDZ domain-containing protein 5C), and related domains. PTPN13 regulates negative apoptotic signaling and mediates phosphoinositide 3-kinase (PI3K) signaling. PTPN13 has five PDZ domains. Proteins known to interact with PTPN13 PDZ domains include: PLEKHA1 and PLEKHA2 via PTPN13-PDZ domain 1, Fas receptor and thyroid receptor-interacting protein 6 via PTPN13-PDZ domain 2, nerve growth factor receptor and protein kinase N2 via PTPN13-PDZ domain 3, PDZ and LIM domain 4 (PDLIM4) via PTPN13-PDZ domains 2 and 4, and brain calpain-2 via PTPN13-PDZ domains 3, 4 and 5. Calpain-2-mediated PTPN13 fragments may be involved in abnormal tau aggregation and increased risk for Alzheimer's disease. FRMPD2 is localized in the basolateral membranes of polarized epithelial cells and is associated with tight junction formation and immune response; it contains 3 PDZ domains. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PTPN13 family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467180 [Multi-domain] Cd Length: 92 Bit Score: 58.18 E-value: 1.90e-10

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gi 569006111   84 IHAVRVEKSPSGRLGFSVRGGSEHG---LGIFVSKVEEGSSAERAG-LCVGDKITEVNGLSLESTTMGSAVRLLTSS 156
Cdd:cd06694     2 IVIVTLKKDPQKGLGFTIVGGENSGsldLGIFVKSIIPGGPADKDGrIKPGDRIIAINGQSLEGKTHHAAVEIIQNA 78

PDZ domain 3 of Discs Large 5 (Dlg5) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of Drosophila and mammalian Dlg5, and related domains. Dlg5 is a scaffold protein with multiple conserved functions that are independent of each other in regulating growth, cell polarity, and cell adhesion. It has a coiled-coil domain, 4 PDZ domains and a MAGUK domain (an SH3 domain next to a non-catalytically active guanylate kinase domain). Deregulation of Dlg5 has been implicated in the malignancy of several cancer types. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Dlg5-like family PDZ3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467248 [Multi-domain] Cd Length: 82 Bit Score: 58.11 E-value: 1.96e-10

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gi 569006111  222 LGFNIRGGKefGLGIYVSKVDHGGLAEENGIKVGDQVLAANGVRFDDISHSQAVEVLkGQTHIMLTIK 289
Cdd:cd06767    15 LGISIVSGE--NGGIFVSSVTEGSLAHQAGLEYGDQLLEVNGINLRNATEQQAALIL-RQCGDTITML 79

periplasmic serine protease, Do/DeqQ family; This family consists of a set proteins various designated DegP, heat shock protein HtrA, and protease DO. The ortholog in Pseudomonas aeruginosa is designated MucD and is found in an operon that controls mucoid phenotype. This family also includes the DegQ (HhoA) paralog in E. coli which can rescue a DegP mutant, but not the smaller DegS paralog, which cannot. Members of this family are located in the periplasm and have separable functions as both protease and chaperone. Members have a trypsin domain and two copies of a PDZ domain. This protein protects bacteria from thermal and other stresses and may be important for the survival of bacterial pathogens.// The chaperone function is dominant at low temperatures, whereas the proteolytic activity is turned on at elevated temperatures. [Protein fate, Protein folding and stabilization, Protein fate, Degradation of proteins, peptides, and glycopeptides]

Pssm-ID: 273938 [Multi-domain] Cd Length: 428 Bit Score: 64.17 E-value: 2.07e-10

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gi 569006111   104 GSEHGLGIFVSKVEEGSSAERAGLCVGDKITEVNGLSLESttmgsavrlltsSSCLHMMVRRMGrvPGIKFSKekTTWVD 183
Cdd:TIGR02037  252 GLEKQRGALVAQVLPGSPAEKAGLKAGDVITSVNGKPISS------------FADLRRAIGTLK--PGKKVTL--GILRK 315

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gi 569006111   184 VVNRRLVVEKCSSTPSDRSSEDGVRRIVhLYTTSDDFCLGFNIRGGKEfglGIYVSKVDHGGLAEENGIKVGDQVLAANG 263
Cdd:TIGR02037  316 GKEKTITVTLGASPEEQASSSNPFLGLT-VANLSPEIRKELRLKGDVK---GVVVTKVVSGSPAARAGLQPGDVILSVNQ 391

                          170       180       190
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gi 569006111   264 VRFDDISH-SQAVEVLKGQTHIMLTIKETGR 293
Cdd:TIGR02037  392 QPVSSVAElRKVLARAKKGGRVALLILRGGA 422

PDZ domain 13 of multi-PDZ-domain protein 1 (MUPP1) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 13 of MUPP1. MUPP1 and PATJ serve as scaffolding proteins linking different proteins and protein complexes involved in the organization of tight junctions and epithelial polarity. MUPP1 contains an L27 (Lin-2 and Lin-7 binding) domain and 13 PDZ domains. PATJ (also known as INAD-like) contains an L27 domain and ten PDZ domains. PATJ lacks 3 PDZ domains seen in MUPP1: PDZ6, PDZ9, and PDZ13. This MuPP1-like PDZ13 domain is therefore absent from PATJ. MUPP1 and PATJ share several binding partners, including junctional adhesion molecules (JAM), zonula occludens (ZO)-3, Pals1 (protein associated with Lin-7), Par (partitioning defective)-6 proteins, and nectins (adherence junction adhesion molecules). PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MUPP1-like family PDZ13 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467164 [Multi-domain] Cd Length: 83 Bit Score: 58.12 E-value: 2.09e-10

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gi 569006111  222 LGFNIRGGkeFG-----LGIYVSKVDHGGLAEENG-IKVGDQVLAANGVRFDDISHSQAVEVLKGQ-THIMLTI 288
Cdd:cd06676    11 LGFSIVGG--FGsphgdLPIYVKTVFEKGAAAEDGrLKRGDQILAVNGESLEGVTHEEAVNILKKTkGTVTLTV 82

PDZ domain of partitioning defective 6 (Par6), Drosophila Rho GTPase-activating protein 100F (RhoGAP100F), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of Par6 (also known as PAR6 or Par-6), RhoGAP100F, and related domains. Par6 is part of a conserved machinery that directs metazoan cell polarity, a process necessary for the function of diverse cell types. Par6 forms a cell polarity-regulatory complex with atypical protein kinase C (aPKC) and Par3. Par6 can also directly associate with PALS1 (proteins associated with Lin7, also known as Stardust) providing a link between the Par3/aPKC/Par6 complex and the PALS1-PATJ (protein-associated TJ) complex. Binding partners of the Par6-PDZ domain include Par3, PALS1/Stardust; leucine-rich repeat-containing protein netrin-G ligand-2 (NGL-2), human crumbs (CRB3) involve in the morphogenesis of the tight junctions in mammalian epithelial cells, and PAR-6 co-operates with the Par6 semi-CRIB domain to bind CDC42. CDC42 regulates the Par6 PDZ domain through an allosteric CRIB-PDZ transition. Drosophila RhoGAP100F, also known as synapse defective protein 1 homolog (syd-1 homolog), is a GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound form. The RhoGAP100F-PDZ domain binds the neurexin C terminus to control synapse formation at the Drosophila neuromuscular junction. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Par6-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467202 [Multi-domain] Cd Length: 84 Bit Score: 57.96 E-value: 2.33e-10

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gi 569006111   87 VRVEKSPSGRLGFSVRGGS--EHGLGIFVSKVEEGSSAERAGLC-VGDKITEVNGLSLESTTMGSAVRLLTSSSCLHMMV 163
Cdd:cd06718     3 VELIKPPGKPLGFYIRDGNgvERVPGIFISRLVLGSLADSTGLLaVGDEILEVNGVEVTGKSLDDVTDMMVAPTRLIITV 82


                  ..
gi 569006111  164 RR 165
Cdd:cd06718    83 KP 84

PDZ domains of the Na+/H+ exchange regulatory cofactor (NHERF) family (NHERF1-4), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of the Na+/H+ exchange regulatory cofactor (NHERF) family of multi-PDZ-domain-containing scaffolding proteins (NHERF1-4), and related domains. The NHERF family includes NHERF1 (also known as EBP50), NHERF2 (also known as E3KARP; TKA-1; SIP-1), NHERF3 (also known as CAP70; CLAMP; Napi-Cap-1; PDZD1) and NHERF4 (also known as IKEPP; PDZK2; Napi-Cap-2). NHERF1 and NHERF2 have tandem PDZ domains (PDZ1-2); NHERF3 and NHERF4 have four PDZ domains (PDZ1-4). NHERFs are involved in the regulation of multiple receptors or transporters, such as type II sodium-phosphate cotransporter (Npt2a), purinergic P2Y1 receptor P2Y1R, the beta2-adrenergic receptor (beta2-AR), parathyroid hormone receptor type 1 (PTHR), the lysophosphatidic acid receptors (LPARs), sodium-hydrogen exchanger 3 (NHE3), and cystic fibrosis transmembrane conductance regulator (CFTR). NHERF-PDZ1 domain interaction partners include Npt2a, purinergic P2Y1 receptor, beta2-AR, CFTR, PTHR, NH3, G-protein-coupled receptor kinase 6 (GRK6A), platelet-derived growth factor receptor (PDGFR), B1 subunit of the H+ATPase, cholesterol, receptor for activated C-kinase RACK1, aquaporin 9, among others. The NHERF PDZ2 domain interacts with fewer proteins: NHERF1 PDZ2 binds Npt2a, PTHR, beta-catenin, aquaporin 9, and RACK1; NHERF2 PDZ2 binds LPA2, P2Y1R, and NHE3, cGMP-dependent protein kinase type II (cGKII). NHERF4 PDZ1 and PDZ4 bind the epithelial Ca(2+) channels TRPV5 and TRPV6. NHERF2/NHERF3 heterodimerization is mediated by PDZ domains of NHERF2 and the C-terminal PDZ domain recognition motif of NHERF3. NHERF4 regulates several transporters mediating influx of xenobiotics and nutrients in the small intestine. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This NHERF-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467249 [Multi-domain] Cd Length: 80 Bit Score: 57.83 E-value: 2.33e-10

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gi 569006111   87 VRVEKSPSGrLGFSVRggSEHG-LGIFVSKVEEGSSAERAGLCVGDKITEVNGLSLESTTMGSAVRLLTSSS 157
Cdd:cd06768     3 CHLVKGPEG-YGFNLH--AEKGrPGHFIREVDPGSPAERAGLKDGDRLVEVNGENVEGESHEQVVEKIKASG 71

PDZ domain of Golgi-associated PDZ and coiled-coil motif-containing protein (GOPC), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of GOPC and related domains. GOPC, also known as PIST (PDZ domain protein interacting specifically with TC10), FIG (fused in glioblastoma), and CAL (CFTR-associated ligand), regulates the trafficking of a wide array of proteins, including small GTPases, receptors, and cell surface molecules such as cadherin 23 and CFTR. It may regulate CFTR chloride currents and acid-sensing ASIC3 currents by modulating cell surface expression of both channels, and may play a role in autophagy. Interaction partners of the GOPC PDZ domains include: FZD5, FZD8, ASIC3, CFTR, MUC3, ARFRP1, Ggamma13, neuroligin, and Stargazin. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This GOPC-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467261 [Multi-domain] Cd Length: 83 Bit Score: 57.38 E-value: 3.71e-10

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gi 569006111  857 RTITLSKMK-QSLGISISGGIESKVqPMVkIEKIFPGGAAFLCGDLQAGFELVAVDGESLEQVTHQRAVD 925
Cdd:cd06800     1 RKVLLSKEPhEGLGISITGGKEHGV-PIL-ISEIHEGQPADRCGGLYVGDAILSVNGIDLRDAKHKEAVT 68

PDZ domain 2 of human discs large homolog 1 (Dlg1), Dlg2, and Dlg4, Drosophila disc large (Dlg), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of Drosophila Dlg1, human Dlg1,2, and 4 and related domains. Dlg1 (also known as synapse-associated protein Dlg197 or SAP-97), Dlg2 (also known as channel-associated protein of synapse-110, postsynaptic density protein 93, or PSD-93), Dlg4 (also known as postsynaptic density protein 95, PSD-95, synapse-associated protein 90, or SAP-90) each have 3 PDZ domains and belong to the membrane-associated guanylate kinase family. Dlg1 regulates antigen receptor signaling and cell polarity in lymphocytes, B-cell proliferation and antibody production, and TGFalpha bioavailability; its PDZ3 domain binds pro-TGFalpha, and its PDZ2 domain binds the TACE metalloprotease responsible for cleaving pro-TGFalpha to a soluble form. Dlg2 is involved in N-methyl-D-aspartate (NMDA) receptor signaling. It regulates surface expression of NMDA receptors in dorsal horn neurons of the spinal cord, and it also interacts with NMDA receptor subunits and with Shaker-type K+ channel subunits to cluster into a channel complex. Dlg4 PDZ1 domain binds NMDA receptors, and its PDZ2 domain binds neuronal nitric oxide synthase (nNOS), forming a complex in neurons. The Drosophila Scribble complex (Scribble, Dlg, and lethal giant larvae) plays a role in apico-basal cell polarity, and in other forms of polarity, including regulation of the actin cytoskeleton, cell signaling and vesicular trafficking, and in tumor development. Postsynaptic targeting of Drosophila DLG requires interactions mediated by the first two PDZ domains. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Dlg-like family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467207 [Multi-domain] Cd Length: 85 Bit Score: 56.89 E-value: 4.92e-10

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gi 569006111  859 ITLSKMKQSLGISISGGIESKVQP---MVKIEKIFPGGAAFLCGDLQAGFELVAVDGESLEQVTHQRAV 924
Cdd:cd06724     2 IKLVKGPKGLGFSIAGGVGNQHIPgdnGIYVTKIIEGGAAQKDGRLQVGDKLLAVNDVSLEEVTHEEAV 70

PDZ domain 5 of Danio rerio tyrosine-protein phosphatase non-receptor type 13 (Ptpn13) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 5 of Danio rerio Ptpn13, and related domains. Protein-tyrosine phosphatases (PTPs) dephosphorylate phosphotyrosyl residues in proteins that are phosphorylated by protein tyrosine kinases (PTKs). Danio rerio Ptpn13 is a classical non-receptor-like PTP. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PTPN13-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467273 [Multi-domain] Cd Length: 80 Bit Score: 56.20 E-value: 7.23e-10

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gi 569006111   86 AVRVEKSPSGRLGFSVRGGsEHGLGIFVSKVEEGSSAERAG-LCVGDKITEVNGLSLESTTMGSAVRLLTSSS 157
Cdd:cd23060     1 QIELEKPANGGLGFSLVGG-EGGSGIFVKSISPGGVADRDGrLQVGDRLLQVNGESVIGLSHSKAVNILRKAK 72

PDZ domain 1 of inactivation-no-after-potential D (INAD), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of INAD, and related domains. INAD assembles key enzymes of the Drosophila compound eye photo-transduction pathway into a supramolecular complex, supporting efficient and fast light signaling. It contains 5 PDZ domains arranged in tandem (PDZ1-PDZ5) which independently bind various proteins. INAD PDZ2 binds eye-specific protein kinase C, INAD PDZ3 binds transient receptor potential (TRP) channel, and INAD PDZ4,5 tandem binds NORPA (phospholipase Cbeta, PLCbeta). Mutations of the inaD gene that lead to disruption of each of these interactions impair fly photo signal transduction. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This INAD-like family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467276 [Multi-domain] Cd Length: 87 Bit Score: 56.37 E-value: 8.02e-10

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gi 569006111  865 KQSLGISISGGiESKVQPMVKIEKIF-----PGGAAFLCGDLQAGFELVAVDGESLEQVTHQRAVDTIRRA 930
Cdd:cd23063     9 KKSFGICIVRG-EVKVSPNTKTTGIFikgiiPDSPAHKCGRLKVGDRILSVNGNDVRNSTEQAAIDLIKEA 78

PDZ domain of PDZ-LIM family proteins, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of PDZ-LIM family proteins including PDLIM1-7, and related domains. PDZ-LIM family proteins (also known as Zasp PDZ domain proteins) are involved in the rearrangement of the actin cytoskeleton; they mediate association with the cytoskeleton through alpha-actinin as well as with other proteins involved in signal transduction pathways. Members of this family include PDLIM1 (also known as C-terminal LIM domain protein 1, elfin, LIM domain protein CLP-36), PDLIM2 (also known as PDZ-LIM protein mystique), PDLIM3 (also known as actinin-associated LIM protein, alpha-actinin-2-associated LIM protein, ALP), PDLIM4 (also known as LIM protein RIL, Reversion-induced LIM protein), PDLIM5 (also known as enigma homolog, ENH, enigma-like PDZ and LIM domains protein), PDLIM6 (also known as LIM domain-binding protein 3, ZASP, Cypher, Oracle), and PDLIM7 (also known as PDZ and LIM domain protein 7, LIM mineralization protein, LMP; protein enigma). PDLIM1 has been shown to negatively regulate NF-kappaB-mediated signaling in the cytoplasm. PDLIM7 negatively regulates p53 through binding murine double minute 2 (MDM2). The PDZ domains of PDZ-LIM family proteins PDLIM1, 2, 3, 5, 6, 7 have been shown to bind actin. Other PDZ-LIM family PDZ domain binding partners include thyroid receptor interacting protein-6 (PDLIM4-PDZ), the LIM domain of PDLIM4 (PDLIM4-PDZ), tropomyosin (PDLIM7-PDZ), myotilin and calsarcin 1 (PDLIM6-PDZ), and proteins from the myotilin and FATZ (calsarcin/myozenin) families (PDLIM1, 3, 4, 6 PDZ domains). PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PDLIM-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467235 [Multi-domain] Cd Length: 79 Bit Score: 56.00 E-value: 8.52e-10

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gi 569006111  223 GFNIRGGKEFGLGIYVSKVDHGGLAEENGIKVGDQVLAANGVRFDDISHSQAVEVLKGQT-HIMLTIK 289
Cdd:cd06753    11 GFRLQGGKDFNQPLTISRVTPGGKAAQANLRPGDVILAINGESTEGMTHLEAQNKIKAATgSLSLTLE 78

PDZ domain of sorting nexin-27 (SNX27), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of SNX27, and related domains. SNX27 is involved in retrograde transport from endosome to plasma membrane. The PDZ domain of SNX27 links cargo identification to retromer-mediated transport. SNX27 binds to the retromer complex (vacuolar protein sorting 26(VPS26)-VPS29-VPS35), via its PDZ domain binding to VPS26. The SNX27 PDZ domain also binds to cargo including the G-protein-coupled receptors (GPCRs): beta2-adrenergic receptor (beta2AR), beta1AR, parathyroid hormone receptor (PTHR), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs), NMDA receptors, 5-hydroxytryptamine 4a receptors, frizzled receptors, and somatostatin receptor subtype 5 (SSTR5). Additional binding partners of the SNX27 PDZ domain include G protein-gated inwardly rectifying potassium (Kir3) channels, angiotensin-converting enzyme 2 (ACE2), and PTEN (phosphatase and tensin homolog deleted on chromosome 10); PTEN binding to SNX27 prevents SNX27's association with the retromer complex. SNX27 has been reported to be a host factor needed for efficient entry of an engineered SARS-CoV-2 variant, the spike protein of which contains a deletion at the S1/S2 subunit cleavage site; the PDZ domain of SNX27 binds angiotensin-converting enzyme 2 (ACE2), and may be involved in recycling ACE2 to the plasma membrane, thereby promoting viral entry. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This SNX27-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467283 [Multi-domain] Cd Length: 93 Bit Score: 56.65 E-value: 8.58e-10

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gi 569006111   85 HAVRVEKSPSGrLGFSVRGG-SEHGL--GI---------FVSKVEEGSSAERAGLCVGDKITEVNGLSLESTTMGSAVRL 152
Cdd:cd23070     1 RVVTIVKSETG-FGFNVRGQvSEGGQlrSIngelyaplqHVSAVLEGGAADKAGVRKGDRILEVNGVNVEGATHKQVVDL 79

                          90
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gi 569006111  153 LTSSS-CLHMMV 163
Cdd:cd23070    80 IKSGGdELTLTV 91

PDZ domain 1 of PDZ domain-containing RING finger protein 4 (PDZRN4), PDZRN3-B, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of PDZRN4, PDZRN3-B, and related domains. PDZRN4 (also known as ligand of numb protein X 4, and SEMACAP3-like protein) contains an N-terminal RING domain and two tandem repeat PDZ domains. It is involved in the progression of cancer, including human liver cancer and breast cancer, and may contribute to the tumorigenesis of rectal adenocarcinoma. Danio rerio PDZRN3-B may participate in neurogenesis: the first PDZ domain of Danio rerio Pdzrn3 interacts with Kidins220 (Kinase D-interacting substrate 220 kD, also named Ankyrin Repeat-Rich Membrane Spanning), a crucial mediator of signal transduction in neural tissues. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PDZRN4-like family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467199 [Multi-domain] Cd Length: 92 Bit Score: 56.63 E-value: 8.78e-10

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 569006111  213 LYTTSDDFCLGFNIRGGK--------EFGLGIYVSKV-DHGGLAEENGIKVGDQVLAANGVRFDDISHSQAVEVLKG 280
Cdd:cd06715     5 VVLHRENGSLGFNIIGGRpcennqegSSSEGIYVSKIvENGPAADEGGLQVHDRIIEVNGKDLSKATHEEAVEAFRT 81

PDZ domain 2 of human discs large homolog 1 (Dlg1), Dlg2, and Dlg4, Drosophila disc large (Dlg), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of Drosophila Dlg1, human Dlg1,2, and 4 and related domains. Dlg1 (also known as synapse-associated protein Dlg197 or SAP-97), Dlg2 (also known as channel-associated protein of synapse-110, postsynaptic density protein 93, or PSD-93), Dlg4 (also known as postsynaptic density protein 95, PSD-95, synapse-associated protein 90, or SAP-90) each have 3 PDZ domains and belong to the membrane-associated guanylate kinase family. Dlg1 regulates antigen receptor signaling and cell polarity in lymphocytes, B-cell proliferation and antibody production, and TGFalpha bioavailability; its PDZ3 domain binds pro-TGFalpha, and its PDZ2 domain binds the TACE metalloprotease responsible for cleaving pro-TGFalpha to a soluble form. Dlg2 is involved in N-methyl-D-aspartate (NMDA) receptor signaling. It regulates surface expression of NMDA receptors in dorsal horn neurons of the spinal cord, and it also interacts with NMDA receptor subunits and with Shaker-type K+ channel subunits to cluster into a channel complex. Dlg4 PDZ1 domain binds NMDA receptors, and its PDZ2 domain binds neuronal nitric oxide synthase (nNOS), forming a complex in neurons. The Drosophila Scribble complex (Scribble, Dlg, and lethal giant larvae) plays a role in apico-basal cell polarity, and in other forms of polarity, including regulation of the actin cytoskeleton, cell signaling and vesicular trafficking, and in tumor development. Postsynaptic targeting of Drosophila DLG requires interactions mediated by the first two PDZ domains. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Dlg-like family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467207 [Multi-domain] Cd Length: 85 Bit Score: 56.12 E-value: 9.47e-10

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 569006111  222 LGFNIRGGK-----EFGLGIYVSKVDHGGLAEENG-IKVGDQVLAANGVRFDDISHSQAVEVLK 279
Cdd:cd06724    11 LGFSIAGGVgnqhiPGDNGIYVTKIIEGGAAQKDGrLQVGDKLLAVNDVSLEEVTHEEAVAALK 74

PDZ domain 3 of harmonin isoforms a and b, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of harmonin isoforms a and b, and related domains. Harmonin (also known as Usher Type 1C, PDZ-73 and AIE-75) is a key organizer of the Usher (USH) protein interactome. USH syndrome is the leading cause of hereditary sensory deaf-blindness in humans; three clinically distinct types of USH have been identified, type 1 to 3. The gene encoding harmonin (USH1C) is the causative gene for the USH type 1C phenotype. There are at least 10 alternatively spliced isoforms of harmonin, which are divided into three subclasses (a, b, and c). All isoforms contain the first two PDZ domains and the first coiled-coil domain. The a and b isoforms all have a third PDZ domain. The different PDZ domains are responsible for interactions with all known Usher syndrome type 1 proteins, and most Usher syndrome type 2 proteins. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This harmonin family PDZ3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467221 [Multi-domain] Cd Length: 94 Bit Score: 56.16 E-value: 1.18e-09

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569006111  857 RTITLSKMKQ--SLGISISGGIESKVQPMVKIEKIFPGGAAFLCGDLQAGFELVAVDGESLEQVTHQRAVDTIRRAYRNK 934
Cdd:cd06739     1 RQVRLLRIKKngPLDLALEGGIDSPLGGKIVVSAVYEGGAADKHGGIVKGDQIMMVNGKSLTDVTLAEAEAALQRAMNSG 80

                          90
                  ....*....|....
gi 569006111  935 AREpMELVVRVPGP 948
Cdd:cd06739    81 GDW-IDLVIAVAPP 93

PDZ domain of synaptopodin 2 (SYNPO2), synaptopodin 2-like protein (SYNPO2L), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of SYNPO2, SYNPO2L, and related domains. SYNPO2 (also known as genethonin-2, myopodin) is a cytoskeleton adaptor protein. It participates in chaperone-assisted selective autophagy (CASA), a mechanism for the disposal of misfolded and damaged proteins and provides a link between the CASA chaperone complex and a membrane-tethering and fusion machinery that generates autophagosome membranes. The SYNPO2 PPxY motif binds CASA cochaperone BCL2-associated athanogene 3 (BAG3) and the SYNPO2 PDZ domain binds vacuolar protein sorting 18 homolog (VPS18). There are three isoforms of SYNPO2, which possess an amino-terminal PDZ domain (SYNPO2a, b, c); the short isoform SYNPO2d, lacks the PDZ domain. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This SYNPO2-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467264 [Multi-domain] Cd Length: 78 Bit Score: 55.78 E-value: 1.19e-09

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 569006111   98 GFSVRGGSEHGLGIFVSKVEEGSSAERAGLCVGDKITEVNGLSLESTTMGSAVRLLTSSS-CLHMMV 163
Cdd:cd10820    11 GFRLQGGSEQKKPLQVAKIRKKSKAALAGLCEGDELLSINGKPCADLSHSEAMDLIDSSGdTLQLLI 77

PDZ domain 5 of membrane-associated guanylate kinase inverted 1 (MAGI-1), MAGI-2, and MAGI-3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 5 of MAGI1, 2, 3 (MAGI is also known as Membrane-associated guanylate kinase, WW and PDZ domain-containing protein) and related domains. MAGI proteins have been implicated in the control of cell migration and invasion through altering the activity of phosphatase and tensin homolog (PTEN) and modulating Akt signaling. Four MAGI proteins have been identified (MAGI1-3 and MAGIX). MAGI1-3 have 6 PDZ domains and bind to the C-terminus of PTEN via their PDZ2 domain. MAGIX has a single PDZ domain that is related to MAGI1-3 PDZ domain 5, and belongs to this MAGI1,2,3-like family. Other binding partners for MAGI1 include JAM4, C-terminal tail of high risk HPV-18 E6, megalin, TRAF6, Kir4.1 (basolateral K+ channel subunit), and cadherin 23; for MAGI2, include DASM1, dendrin, axin, beta- and delta-catenin, neuroligin, hyperpolarization-activated cation channels, beta1-adrenergic receptors, NMDA receptor, and TARPs; and for MAGI3 includes LPA2. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MAGI family PDZ5 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467217 [Multi-domain] Cd Length: 84 Bit Score: 55.66 E-value: 1.30e-09

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569006111   84 IHAVRVEKSPSGrLGFSVRGGSE-HGLGIFVSKVEEGSSAERAG-LCVGDKITEVNGLSLESTTMGSAVRLLTSS-SCLH 160
Cdd:cd06735     1 YYSVELERGPKG-FGFSIRGGREyNNMPLYVLRLAEDGPAQRDGrLRVGDQILEINGESTQGMTHAQAIELIRSGgSVVR 79


                  ....*
gi 569006111  161 MMVRR 165
Cdd:cd06735    80 LLLRR 84

PDZ domain of Drosophila melanogaster PDZ and LIM domain protein Zasp52 (also known as Zasp), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of Drosophila melanogaster Zasp52 and related domains. Drosophila melanogaster Zasp52 (also known as Z band alternatively spliced PDZ-motif protein or Zasp) colocalizes with integrins at myotendinous junctions and with alpha-actinin at Z-disks and is required for muscle attachment as well as Z-disk assembly and maintenance. The Zasp52 actin-binding site includes the extended PDZ domain and the ZM region. The Zasp52-PDZ domain is required for myofibril assembly. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Zasp52-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467281 [Multi-domain] Cd Length: 82 Bit Score: 55.61 E-value: 1.35e-09

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 569006111  223 GFNIRGGKEFGLGIYVSKVDHGGLAEENGIKVGDQVLAANGVRFDDISHSQAVEVLKGQ-THIMLTIK 289
Cdd:cd23068    14 GFRLQGGADFGQPLSIQKVNPGSPADKAGLRRGDVILRINGTDTSNLTHKQAQDLIKRAgNDLQLTVQ 81

PDZ domain 2 of PDZ domain containing 2 (PDZD2), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of PDZD2, also known as KIAA0300, PIN-1, activated in prostate cancer (AIPC) and PDZ domain-containing protein 3 (PDZK3). PDZD2 has seven PDZ domains, and is expressed at exceptionally high levels in the pancreas and certain cancer tissues such as prostate cancer. It promotes the proliferation of insulinoma cells and is upregulated during prostate tumorigenesis. In osteosarcoma (OS), the microRNA miR-363 acts as a tumor suppressor by inhibiting PDZD2. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PDZD2-like family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467239 [Multi-domain] Cd Length: 88 Bit Score: 55.82 E-value: 1.49e-09

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gi 569006111  859 ITLSKMKQSLGISISGGIESKVQPM-VKIEKIFPGGAAFLCGDLQAGFELVAVDGESLEQVTHQRAVDTIRrayrnKARE 937
Cdd:cd06758     5 MHLLKEKGGLGIQITGGKGSKRGDIgIFVAGVEEGGSADRDGRLKKGDELLMINGQSLIGLSHQEAVAILR-----SSAS 79


                  ....*.
gi 569006111  938 PMELVV 943
Cdd:cd06758    80 PVQLVI 85

PDZ domains of the Na+/H+ exchange regulatory cofactor (NHERF) family (NHERF1-4), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of the Na+/H+ exchange regulatory cofactor (NHERF) family of multi-PDZ-domain-containing scaffolding proteins (NHERF1-4), and related domains. The NHERF family includes NHERF1 (also known as EBP50), NHERF2 (also known as E3KARP; TKA-1; SIP-1), NHERF3 (also known as CAP70; CLAMP; Napi-Cap-1; PDZD1) and NHERF4 (also known as IKEPP; PDZK2; Napi-Cap-2). NHERF1 and NHERF2 have tandem PDZ domains (PDZ1-2); NHERF3 and NHERF4 have four PDZ domains (PDZ1-4). NHERFs are involved in the regulation of multiple receptors or transporters, such as type II sodium-phosphate cotransporter (Npt2a), purinergic P2Y1 receptor P2Y1R, the beta2-adrenergic receptor (beta2-AR), parathyroid hormone receptor type 1 (PTHR), the lysophosphatidic acid receptors (LPARs), sodium-hydrogen exchanger 3 (NHE3), and cystic fibrosis transmembrane conductance regulator (CFTR). NHERF-PDZ1 domain interaction partners include Npt2a, purinergic P2Y1 receptor, beta2-AR, CFTR, PTHR, NH3, G-protein-coupled receptor kinase 6 (GRK6A), platelet-derived growth factor receptor (PDGFR), B1 subunit of the H+ATPase, cholesterol, receptor for activated C-kinase RACK1, aquaporin 9, among others. The NHERF PDZ2 domain interacts with fewer proteins: NHERF1 PDZ2 binds Npt2a, PTHR, beta-catenin, aquaporin 9, and RACK1; NHERF2 PDZ2 binds LPA2, P2Y1R, and NHE3, cGMP-dependent protein kinase type II (cGKII). NHERF4 PDZ1 and PDZ4 bind the epithelial Ca(2+) channels TRPV5 and TRPV6. NHERF2/NHERF3 heterodimerization is mediated by PDZ domains of NHERF2 and the C-terminal PDZ domain recognition motif of NHERF3. NHERF4 regulates several transporters mediating influx of xenobiotics and nutrients in the small intestine. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This NHERF-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467249 [Multi-domain] Cd Length: 80 Bit Score: 55.14 E-value: 1.61e-09

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gi 569006111  209 RIVHLYTTSDDFclGFNIRGGKEfGLGIYVSKVDHGGLAEENGIKVGDQVLAANGVRFDDISHSQAVEVLKGQT-HIMLT 287
Cdd:cd06768     1 RLCHLVKGPEGY--GFNLHAEKG-RPGHFIREVDPGSPAERAGLKDGDRLVEVNGENVEGESHEQVVEKIKASGnQVTLL 77

PDZ domain 1 of multi-PDZ-domain protein 1 (MUPP1) and PATJ (protein-associated tight junction), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of MUPP1 and PATJ, and related domains. MUPP1 and PATJ serve as scaffolding proteins linking different proteins and protein complexes involved in the organization of tight junctions and epithelial polarity. MUPP1 contains an L27 (Lin-2 and Lin-7 binding) domain and 13 PDZ domains. PATJ (also known as INAD-like) contains an L27 domain and ten PDZ domains. MUPP1 and PATJ share several binding partners, including junctional adhesion molecules (JAM), zonula occludens (ZO)-3, Pals1 (protein associated with Lin-7), Par (partitioning defective)-6 proteins, and nectins (adherence junction adhesion molecules). PATJ lacks 3 PDZ domains seen in MUPP1: PDZ6, 9, and 13; consequently, MUPP1 PDZ7 and 8 align with PATJ PDZ6 and 7; and MUPP1 PDZ domains 10-12 align with PATJ PDZ domains 8-10. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MUPP1-like family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467176 [Multi-domain] Cd Length: 102 Bit Score: 55.72 E-value: 1.92e-09

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gi 569006111   84 IHAVRVEKSPSGRLGFSVRG-GSEH--GLGIFVSKVEEGSSAERAG-LCVGDKITEVNGLSLEST-TMGSAVRLLTSSS- 157
Cdd:cd06689    15 VEYIELEKPESGGLGFSVVGlKSENrgELGIFVQEIQPGSVAARDGrLKENDQILAINGQPLDQSiSHQQAIAILQQAKg 94


                  ....*...
gi 569006111  158 CLHMMVRR 165
Cdd:cd06689    95 SVELVVAR 102

PDZ domain of syntrophins, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of syntrophins (including alpha-1-syntrophin, beta-1-syntrophin, beta-2-syntrophin, gamma-1-syntrophin, and gamma-2-syntrophin), and related domains. Syntrophins play a role in recruiting various signaling molecules into signaling complexes and help provide appropriate spatiotemporal regulation of signaling pathways. They function in cytoskeletal organization and maintenance; as components of the dystrophin-glycoprotein complex (DGC), they help maintain structural integrity of skeletal muscle fibers. They link voltage-gated sodium channels to the actin cytoskeleton and the extracellular matrix, and control the localization and activity of the actin reorganizing proteins such as PI3K, PI(3,4)P2 and TAPP1. Through association with various cytoskeletal proteins within the cells, they are involved in processes such as regulation of focal adhesions, myogenesis, calcium homeostasis, and cell migration. They also have roles in synapse formation and in the organization of utrophin, acetylcholine receptor, and acetylcholinesterase at the neuromuscular synapse. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This syntrophin-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467262 [Multi-domain] Cd Length: 83 Bit Score: 54.89 E-value: 2.57e-09

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gi 569006111  222 LGFNIRGGKEFGLGIYVSKVDHGGLAEENG-IKVGDQVLAANGVRFDDISHSQAVEVLKG-QTHIMLTIK 289
Cdd:cd06801    13 LGISIKGGAEHKMPILISKIFKGQAADQTGqLFVGDAILSVNGENLEDATHDEAVQALKNaGDEVTLTVK 82

PDZ domain of sorting nexin-27 (SNX27), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of SNX27, and related domains. SNX27 is involved in retrograde transport from endosome to plasma membrane. The PDZ domain of SNX27 links cargo identification to retromer-mediated transport. SNX27 binds to the retromer complex (vacuolar protein sorting 26(VPS26)-VPS29-VPS35), via its PDZ domain binding to VPS26. The SNX27 PDZ domain also binds to cargo including the G-protein-coupled receptors (GPCRs): beta2-adrenergic receptor (beta2AR), beta1AR, parathyroid hormone receptor (PTHR), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs), NMDA receptors, 5-hydroxytryptamine 4a receptors, frizzled receptors, and somatostatin receptor subtype 5 (SSTR5). Additional binding partners of the SNX27 PDZ domain include G protein-gated inwardly rectifying potassium (Kir3) channels, angiotensin-converting enzyme 2 (ACE2), and PTEN (phosphatase and tensin homolog deleted on chromosome 10); PTEN binding to SNX27 prevents SNX27's association with the retromer complex. SNX27 has been reported to be a host factor needed for efficient entry of an engineered SARS-CoV-2 variant, the spike protein of which contains a deletion at the S1/S2 subunit cleavage site; the PDZ domain of SNX27 binds angiotensin-converting enzyme 2 (ACE2), and may be involved in recycling ACE2 to the plasma membrane, thereby promoting viral entry. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This SNX27-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467283 [Multi-domain] Cd Length: 93 Bit Score: 54.34 E-value: 5.06e-09

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gi 569006111  209 RIVHLYTTSDDFclGFNIRG------------GKEFGLGIYVSKVDHGGLAEENGIKVGDQVLAANGVRFDDISHSQAVE 276
Cdd:cd23070     1 RVVTIVKSETGF--GFNVRGqvseggqlrsinGELYAPLQHVSAVLEGGAADKAGVRKGDRILEVNGVNVEGATHKQVVD 78

                          90
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gi 569006111  277 VLK-GQTHIMLTI 288
Cdd:cd23070    79 LIKsGGDELTLTV 91

PDZ domain 7 of PDZ domain containing 2 (PDZD2), PDZ domain 4 of human pro-interleukin-16 (isoform 1, 1332 AA), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 7 of PDZD2, also known as KIAA0300, PIN-1, PAPIN, activated in prostate cancer (AIPC) and PDZ domain-containing protein 3 (PDZK3). PDZD2 has seven PDZ domains. PDZD2 is expressed at exceptionally high levels in the pancreas and certain cancer tissues, such as prostate cancer. It promotes the proliferation of insulinoma cells and is upregulated during prostate tumorigenesis. In osteosarcoma (OS), the microRNA miR-363 acts as a tumor suppressor by inhibiting PDZD2. This family include the PDZ domain of the secreted mature form of human interleukin-16 (IL-16); this is the fourth PDZ domain (PDZ4) of human pro-interleukin-16 (isoform 1, also known as nPro-Il-16). Precursor IL-16 is cleaved to produce pro-IL-16 and C-terminal mature IL-16. Pro-IL-16 functions as a regulator of T cell growth; mature IL-16 is a CD4 ligand that induces chemotaxis and CD25 expression in CD4+ T cells. IL-16 bioactivity has been closely associated with the progression of several different cancers PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PDZD2-like family PDZ7 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467244 [Multi-domain] Cd Length: 86 Bit Score: 53.77 E-value: 6.71e-09

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gi 569006111  856 LRTITLSKMKQSLGISISGGIESKV--QPMVkIEKIFPGGAAFLCGDLQAGFELVAVDGESLEQVTH 920
Cdd:cd06763     1 AVTVELEKGSAGLGFSLEGGKGSPLgdRPLT-IKRIFKGGAAEQSGVLQVGDEILQINGTSLQGLTR 66

PDZ domain 2 of Drosophila Scribble, human Scribble homolog, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of Drosophila Scribble (also known as LAP4), human Scribble homolog (also known as hScrib, LAP4, CriB1, ScrB1 and Vartul), and related domains. They belong to the LAP family, which describes proteins that contain either one or four PDZ domains and 16 LRRs (leucine-rich repeats) and function in controlling cell shape, size and subcellular protein localization. In Drosophila, the Scribble complex, comprising Scribble, discs large, and lethal giant larvae, plays a role in apico-basal cell polarity, in other forms of polarity, including regulation of the actin cytoskeleton, cell signaling and vesicular trafficking, and in tumor development. Mammalian Scribble is important in many aspects of cancer development. Scribble and its homologs can be downregulated or overexpressed in cancer; they have a role in cancer beyond their function in loss of cell polarity. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Scribble-like family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467187 [Multi-domain] Cd Length: 92 Bit Score: 53.80 E-value: 7.11e-09

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gi 569006111   97 LGFSVRGGSEHGL------GIFVSKVEEGSSAERAG-LCVGDKITEVNGLSLESTTMGSAVRLLTSSS 157
Cdd:cd06703    14 LGFSIAGGKGSTPfrdgdeGIFISRITEGGAADRDGkLQVGDRVLSINGVDVTEARHDQAVALLTSSS 81

PDZ domain 1 of protein tyrosine phosphatase non-receptor type 13 (PTPN13), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of PTPN13 [also known as Fas-associated protein-tyrosine phosphatase 1 (FAP-1), protein-tyrosine phosphatase 1E (PTP-E1), and protein-tyrosine phosphatase (PTPL1)], and related domains. PTPN13 regulates negative apoptotic signaling and mediates phosphoinositide 3-kinase (PI3K) signaling. PTPN13 has five PDZ domains. Proteins known to interact with PTPN13 PDZ domains include: PLEKHA1 and PLEKHA2 via PTPN13-PDZ domain 1, Fas receptor and thyroid receptor-interacting protein 6 via PTPN13-PDZ domain 2, nerve growth factor receptor and protein kinase N2 via PTPN13-PDZ domain 3, PDZ and LIM domain 4 (PDLIM4) via PTPN13-PDZ domains 2 and 4, and brain calpain-2 via PTPN13-PDZ domains 3, 4 and 5. Calpain-2-mediated PTPN13 fragments may be involved in abnormal tau aggregation and increased risk for Alzheimer's disease. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PTPN13 family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467285 [Multi-domain] Cd Length: 92 Bit Score: 53.65 E-value: 7.88e-09

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gi 569006111  220 FCLGFNIRGGKEFG---LGIYVSKVDHGGLAEENG-IKVGDQVLAANGVRFDDISHSQAVEVLKG 280
Cdd:cd23072    13 YGLGFQIVGGEKSGrldLGIFISSITPGGPADLDGrLKPGDRLISVNDVSLEGLSHDAAVEILQN 77

PDZ domain 3 of Zonula Occludens-1 (ZO-1), homologs ZO-2 and ZO-3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of ZO-1, -2, -3 and related domains. Zonula occludens proteins (ZO-1, ZO-2, ZO-3) are multi-PDZ domain proteins involved in the maintenance and biogenesis of multi-protein networks at the cytoplasmic surface of intercellular contacts in epithelial and endothelial cells. They have three N-terminal PDZ domains, PDZ1-3, followed by a Src homology-3 (SH3) domain and a guanylate kinase (GuK)-like domain. Among protein-protein interactions for all ZO proteins is the binding of the first PDZ domain (PDZ1) to the C-termini of claudins , and the homo- and hetero-dimerization of ZO-proteins via their second PDZ domain (PDZ2), which takes place by symmetrical domain swapping of the first two beta-strands of PDZ2. At the cell level, ZO-1 and ZO-2 are involved in polarity maintenance, gene transcription, cell proliferation, and tumor cell metastasis. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This ZO family PDZ3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467211 [Multi-domain] Cd Length: 82 Bit Score: 53.34 E-value: 9.38e-09

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gi 569006111   95 GRLGFSVRGGSEhgLGIFVSKVEEGSSAERAGLCVGDKITEVNGLSLESTTMGSAVRLL 153
Cdd:cd06729    11 GSVGLRLAGGND--VGIFVAGVQEGSPAEKQGLQEGDQILKVNGVDFRNLTREEAVLFL 67

PDZ domain 3 of membrane-associated guanylate kinase inverted 1 (MAGI-1), MAGI-2, and MAGI-3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of MAGI1, 2, 3 (MAGI is also known as Membrane-associated guanylate kinase, WW and PDZ domain-containing protein) and related domains. MAGI proteins have been implicated in the control of cell migration and invasion through altering the activity of phosphatase and tensin homolog (PTEN) and modulating Akt signaling. Four MAGI proteins have been identified (MAGI1-3 and MAGIX). MAGI1-3 have 6 PDZ domains and bind to the C-terminus of PTEN via their PDZ2 domain. MAGIX has a single PDZ domain that is related to MAGI1-3 PDZ domain 5. Other binding partners for MAGI1 include JAM4, C-terminal tail of high risk HPV-18 E6, megalin, TRAF6, Kir4.1 (basolateral K+ channel subunit), and cadherin 23; for MAGI2, include DASM1, dendrin, axin, beta- and delta-catenin, neuroligin, hyperpolarization-activated cation channels, beta1-adrenergic receptors, NMDA receptor, and TARPs; and for MAGI3 includes LPA2. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MAGI family PDZ3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2); arranged as beta-strands A, -B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467215 [Multi-domain] Cd Length: 85 Bit Score: 53.38 E-value: 9.95e-09

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gi 569006111  858 TITLSKMKQSLGISISGGIESKVQpmVKIEKIFPGGAAFLCGDLQAGFELVAVDGESLEQVTHQRAVDTIRRAYRN 933
Cdd:cd06733     3 TVFLRRQETGFGFRILGGTEEGSQ--VSIGAIVPGGAADLDGRLRTGDELLSVDGVNVVGASHHKVVDLMGNAARN 76

PDZ domain 1 of protein tyrosine phosphatase non-receptor type 13 (PTPN13),FERM and PDZ domain-containing protein 2 (FRMPD2), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of PTPN13 [also known as Fas-associated protein-tyrosine phosphatase 1 (FAP-1), protein-tyrosine phosphatase 1E (PTP-E1), and protein-tyrosine phosphatase (PTPL1)], FRMPD2 (also known as PDZ domain-containing protein 4; PDZ domain-containing protein 5C), and related domains. PTPN13 regulates negative apoptotic signaling and mediates phosphoinositide 3-kinase (PI3K) signaling. PTPN13 has five PDZ domains. Proteins known to interact with PTPN13 PDZ domains include: PLEKHA1 and PLEKHA2 via PTPN13-PDZ domain 1, Fas receptor and thyroid receptor-interacting protein 6 via PTPN13-PDZ domain 2, nerve growth factor receptor and protein kinase N2 via PTPN13-PDZ domain 3, PDZ and LIM domain 4 (PDLIM4) via PTPN13-PDZ domains 2 and 4, and brain calpain-2 via PTPN13-PDZ domains 3, 4 and 5. Calpain-2-mediated PTPN13 fragments may be involved in abnormal tau aggregation and increased risk for Alzheimer's disease. FRMPD2 is localized in the basolateral membranes of polarized epithelial cells and is associated with tight junction formation and immune response; it contains 3 PDZ domains. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PTPN13 family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467180 [Multi-domain] Cd Length: 92 Bit Score: 53.17 E-value: 1.39e-08

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gi 569006111  222 LGFNIRGGKEFG---LGIYVSKVDHGGLAEENG-IKVGDQVLAANGVRFDDISHSQAVEVLK 279
Cdd:cd06694    15 LGFTIVGGENSGsldLGIFVKSIIPGGPADKDGrIKPGDRIIAINGQSLEGKTHHAAVEIIQ 76

PDZ domain 4 of human Ligand of Numb protein X 1 (LNX1) and LNX2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 4 of LNX1 (also known as PDZ domain-containing RING finger protein 2, PDZRN2)and LNX2 (also known as PDZ domain-containing RING finger protein 1, PDZRN1), and related domains. LNX1 and LNX2 are Ring (Really Interesting New Gene) finger and PDZ domain-containing E3 ubiquitin ligases that bind to the cell fate determinant protein NUMB and mediate its ubiquitination. LNX1 can ubiquitinate a number of other ligands including PPFIA1, KLHL11, KIF7 and ERC2. LNX1 and LNX2 each have four PDZ domains. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This LNX family PDZ4 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467168 [Multi-domain] Cd Length: 89 Bit Score: 52.73 E-value: 1.49e-08

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gi 569006111  222 LGFNIRGGKEFGLG---IYVSKVDHGGLAEENG-IKVGDQVLAANGVRFDDISHSQAVEVLKGQT-HIMLTI 288
Cdd:cd06680    13 LGFSIVGGYEESHGnqpFFVKSIVPGTPAYNDGrLKCGDIILAVNGVSTVGMSHAALVPLLKEQRgRVTLTV 84

PDZ domain; PDZ domains are found in diverse signaling proteins.

Pssm-ID: 395476 [Multi-domain] Cd Length: 81 Bit Score: 52.28 E-value: 1.72e-08

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gi 569006111   858 TITLSKMKQS-LGISISGGIESKVQPmVKIEKIFPGGAAfLCGDLQAGFELVAVDGESLEQVTHQRAVDTIRRA 930
Cdd:pfam00595    1 QVTLEKDGRGgLGFSLKGGSDQGDPG-IFVSEVLPGGAA-EAGGLKVGDRILSINGQDVENMTHEEAVLALKGS 72

PDZ domain 1 of protein tyrosine phosphatase non-receptor type 13 (PTPN13),FERM and PDZ domain-containing protein 2 (FRMPD2), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of PTPN13 [also known as Fas-associated protein-tyrosine phosphatase 1 (FAP-1), protein-tyrosine phosphatase 1E (PTP-E1), and protein-tyrosine phosphatase (PTPL1)], FRMPD2 (also known as PDZ domain-containing protein 4; PDZ domain-containing protein 5C), and related domains. PTPN13 regulates negative apoptotic signaling and mediates phosphoinositide 3-kinase (PI3K) signaling. PTPN13 has five PDZ domains. Proteins known to interact with PTPN13 PDZ domains include: PLEKHA1 and PLEKHA2 via PTPN13-PDZ domain 1, Fas receptor and thyroid receptor-interacting protein 6 via PTPN13-PDZ domain 2, nerve growth factor receptor and protein kinase N2 via PTPN13-PDZ domain 3, PDZ and LIM domain 4 (PDLIM4) via PTPN13-PDZ domains 2 and 4, and brain calpain-2 via PTPN13-PDZ domains 3, 4 and 5. Calpain-2-mediated PTPN13 fragments may be involved in abnormal tau aggregation and increased risk for Alzheimer's disease. FRMPD2 is localized in the basolateral membranes of polarized epithelial cells and is associated with tight junction formation and immune response; it contains 3 PDZ domains. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PTPN13 family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467180 [Multi-domain] Cd Length: 92 Bit Score: 52.78 E-value: 1.82e-08

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gi 569006111  859 ITLSKMKQ-SLGISISGGIES-KVQPMVKIEKIFPGGAAFLCGDLQAGFELVAVDGESLEQVTHQRAVDTIRRA 930
Cdd:cd06694     5 VTLKKDPQkGLGFTIVGGENSgSLDLGIFVKSIIPGGPADKDGRIKPGDRIIAINGQSLEGKTHHAAVEIIQNA 78

PDZ domain 1 of human discs large homolog 1 (Dlg1), Dlg2, and Dlg4, Drosophila disc large (Dlg), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of Drosophila Dlg1, human Dlg1,2, and 4 and related domains. Dlg1 (also known as synapse-associated protein Dlg197 or SAP-97), Dlg2 (also known as channel-associated protein of synapse-110, postsynaptic density protein 93, or PSD-93), Dlg4 (also known as postsynaptic density protein 95, PSD-95, synapse-associated protein 90, or SAP-90) each have 3 PDZ domains and belong to the membrane-associated guanylate kinase family. Dlg1 regulates antigen receptor signaling and cell polarity in lymphocytes, B-cell proliferation and antibody production, and TGFalpha bioavailability; its PDZ3 domain binds pro-TGFalpha, and its PDZ2 domain binds the TACE metalloprotease responsible for cleaving pro-TGFalpha to a soluble form. Dlg2 is involved in N-methyl-D-aspartate (NMDA) receptor signaling. It regulates surface expression of NMDA receptors in dorsal horn neurons of the spinal cord, and it also interacts with NMDA receptor subunits and with Shaker-type K+ channel subunits to cluster into a channel complex. Dlg4 PDZ1 domain binds NMDA receptors, and its PDZ2 domain binds neuronal nitric oxide synthase (nNOS), forming a complex in neurons. The Drosophila Scribble complex (Scribble, Dlg, and lethal giant larvae) plays a role in apico-basal cell polarity, and in other forms of polarity, including regulation of the actin cytoskeleton, cell signaling and vesicular trafficking, and in tumor development. Postsynaptic targeting of Drosophila DLG requires interactions mediated by the first two PDZ domains. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Dlg-like family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467206 [Multi-domain] Cd Length: 89 Bit Score: 52.70 E-value: 1.98e-08

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gi 569006111  858 TITLSKMKQSLGISISGGIESKV---QPMVKIEKIFPGGAAFLCGDLQAGFELVAVDGESLEQVTHQRAVDTIRRA 930
Cdd:cd06723     3 EITLERGNSGLGFSIAGGTDNPHigdDPSIYITKIIPGGAAAADGRLRVNDIILRVNDVDVRNVTHSVAVEALKEA 78

PDZ domain of shroom2, shroom3, shroom4, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of shroom2, shroom3, shroom4, and related domains. Shroom family proteins shroom2 (also known as apical-like protein; protein APXL), shroom3 (also known as shroom-related protein), and shroom4 (also known as second homolog of apical protein) are essential regulators of cell morphology during animal development; they regulate cell architecture by directing the subcellular distribution and activation of Rho kinase (ROCK), which results in the localized activation of non-muscle myosin. The interaction between shroom and ROCK is mediated by the shroom domain 2 (SD2). PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This shroom2,3,4-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467232 [Multi-domain] Cd Length: 82 Bit Score: 52.34 E-value: 1.99e-08

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gi 569006111   98 GFSVRGGSEHGLGIFVSKVEEGSSAERAG-LCVGDKITEVNGLSLESTTMgSAVRLLTSS-SCLHMMVRR 165
Cdd:cd06750    14 GFTLKGGLEHGEPLVISKIEEGGKAASVGkLQVGDEVVNINGVPLSGSRQ-EAIQLVKGShKTLKLVVRR 82

PDZ domain 3 of protein tyrosine phosphatase non-receptor type 13 (PTPN13), FERM and PDZ domain-containing protein 2 (FRMPD2), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of PTPN13 [also known as Fas-associated protein-tyrosine phosphatase 1 (FAP-1), protein-tyrosine phosphatase 1E (PTP-E1), and protein-tyrosine phosphatase (PTPL1)], FRMPD2 (also known as PDZ domain-containing protein 4; PDZ domain-containing protein 5C), and related domains. PTPN13 regulates negative apoptotic signaling and mediates phosphoinositide 3-kinase (PI3K) signaling. PTPN13 has five PDZ domains. Proteins known to interact with PTPN13 PDZ domains include: PLEKHA1 and PLEKHA2 via PTPN13-PDZ domain 1, Fas receptor and thyroid receptor-interacting protein 6 via PTPN13-PDZ domain 2, nerve growth factor receptor and protein kinase N2 via PTPN13-PDZ domain 3, PDZ and LIM domain 4 (PDLIM4) via PTPN13-PDZ domains 2 and 4, and brain calpain-2 via PTPN13-PDZ domains 3, 4 and 5. Calpain-2-mediated PTPN13 fragments may be involved in abnormal tau aggregation and increased risk for Alzheimer's disease. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). FRMPD2 is localized in the basolateral membranes of polarized epithelial cells and is associated with tight junction formation and immune response; it contains 3 PDZ domains). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PTPN13 family PDZ3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467181 [Multi-domain] Cd Length: 90 Bit Score: 52.65 E-value: 2.07e-08

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gi 569006111  858 TITLSKMKQSLGISISGG----IESKVQPMVKIEKIFPGGAAFLCGDLQAGFELVAVDGESLEQVTHQRAVDTIRRA 930
Cdd:cd06695     3 EVKLTKGSSGLGFSFLGGennsPEDPFSGLVRIKKLFPGQPAAESGLIQEGDVILAVNGEPLKGLSYQEVLSLLRGA 79

PDZ domain of protein Lin-7 and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of Lin-7 (also known as LIN-7 or LIN7), and related domains. Lin-7 targets and organize protein complexes to epithelial and synaptic plasma membranes. There are three mammalian Lin-7 homologs: Lin-7A (protein lin-7 homolog A, also known as mammalian lin-seven protein 1 (MALS-1), vertebrate lin-7 homolog 1 (Veli-1), tax interaction protein 33); Lin-7B (also known as MALS-2, Veli-2); and Lin-7C (also known as MALS-3, Veli-3). Lin-7 is involved in localization of the Let-23 growth factor receptor to the basolateral membrane of epithelial cells, in tight junction localization of insulin receptor substrate p53 (IRSp53), in retaining gamma-aminobutyric (GABA) transporter (BGT-1) at the basolateral surface of epithelial cells, and in regulating recruitment of neurotransmitter receptors to the postsynaptic density (PSD). The Lin7 PDZ domain binds Let-23, BGT and beta-catenin, and NMDA (N-methyl-D-aspartate) receptor NR2B. Lin-7 also binds to the PDZ binding motif located in the C-terminal tail of Rhotekin, an effector protein for small GTPase Rho. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Lin-7-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467258 [Multi-domain] Cd Length: 86 Bit Score: 52.05 E-value: 2.39e-08

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gi 569006111   86 AVRVEKSPSGrLGFSVRGGSEHGLGIFVSKVEEGSSAER-AGLCVGDKITEVNGLSLESTTMGSAVRLLTSS 156
Cdd:cd06796     4 VVELPKTEEG-LGFNVMGGKEQNSPIYISRIIPGGVADRhGGLKRGDQLLSVNGVSVEGEHHEKAVELLKAA 74

PDZ domain of densin, erbin, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of densin, erbin, and related domains. Densin (also known as leucine-rich repeat-containing protein 7, LRRC7, densin-180, protein LAP1) and erbin (also known as densin-180-like protein, Erbb2-interacting protein, protein LAP2) belong to the LAP (leucine-rich repeat and PDZ domain) family of scaffolding proteins that play roles in the maintenance of cell shape and apical-basal polarity. Densin and erbin are components of the excitatory postsynaptic compartment and are regulators of dendritic morphology and postsynaptic structure. The densin PDZ domain binds CaV1.3 alpha1 subunit, delta-catenin, and MAGUIN-1. Binding partners of the erbin PDZ domain include ErbB receptor tyrosine kinase ErbB2, HTLV-1 Tax1, Cav1.3 Ca2+channels, and constituents of the cadherin:catenin cell adhesion complex, in particular delta-catenin, p0071 and ARVCF. The erbin PDZ domain binds Smad3, a transductor of the TGFbeta pathway, possibly by a novel interface of binding. Erbin and two other LAP proteins (scribble and lano) redundantly regulate epithelial polarity and apical adhesion complex. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This densin and erbin-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467231 [Multi-domain] Cd Length: 87 Bit Score: 52.33 E-value: 2.52e-08

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gi 569006111   87 VRVEKSPSgrLGFSVRGG-SEHG-------LGIFVSKVEEGSSAERAgLCVGDKITEVNGLSLESTTMGSAVRLL-TSSS 157
Cdd:cd06749     3 VRIEKNPG--LGFSISGGiGSQGnpfrpddDGIFVTKVQPDGPASKL-LQPGDKILEVNGYDFVNIEHGQAVSLLkSFQN 79


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gi 569006111  158 CLHMMVRR 165
Cdd:cd06749    80 TVDLVVER 87

PDZ domain 2 of tyrosine kinase PTPN13, FERM and PDZ domain-containing protein 2 (FRMPD2), and similar domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of human PTPN13, and related domains. PTPN13, also known as Fas-associated protein-tyrosine phosphatase 1 (FAP-1), protein-tyrosine phosphatase 1E (PTP-E1), and protein-tyrosine phosphatase (PTPL1), negatively regulates FAS-mediated apoptosis and NGFR-mediated pro-apoptotic signaling, and may also regulate phosphoinositide 3-kinase (PI3K) signaling. It contains 5 PDZ domains; interaction partners of its second PDZ domain (PDZ2) include the Fas receptor (TNFRSF6) and thyroid receptor-interacting protein 6 (TRIP6). The second PDZ (PDZ2) domain, but not PDZ1 or PDZ3, of FRMPD2 binds to GluN2A and GluN2B, two subunits of N-methyl-d-aspartic acid (NMDA) receptors. Other binding partners of the FRMPDZ2 PDZ2 domain include NOD2, and catenin family members, delta catenin (CTNND2), armadillo repeat gene deleted in velo-cardio-facial syndrome (ARVCF) and p0071 (also known as plakophilin 4; PKP4). PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PTPN13-like family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467254 [Multi-domain] Cd Length: 87 Bit Score: 52.21 E-value: 2.53e-08

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gi 569006111   94 SGRLGFSVRGGSE----HGlGIFVSKVEEGSSAERAG-LCVGDKITEVNGLSLESTTMGSAVRLL 153
Cdd:cd06792    11 DGSLGISVTGGINtsvrHG-GIYVKSLVPGGAAEQDGrIQKGDRLLEVNGVSLEGVTHKQAVECL 74

PDZ domain 3 of multi-PDZ-domain protein 1 (MUPP1) and PATJ (protein-associated tight junction) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of MUPP1 and PATJ, and related domains. MUPP1 and PATJ serve as scaffolding proteins linking different proteins and protein complexes involved in the organization of tight junctions and epithelial polarity. MUPP1 contains an L27 (Lin-2 and Lin-7 binding) domain and 13 PDZ domains. PATJ (also known as INAD-like) contains an L27 domain and ten PDZ domains. MUPP1 and PATJ share several binding partners, including junctional adhesion molecules (JAM), zonula occludens (ZO)-3, Pals1 (protein associated with Lin-7), Par (partitioning defective)-6 proteins, and nectins (adherence junction adhesion molecules). PATJ lacks 3 PDZ domains seen in MUPP1: PDZ6, 9, and 13; consequently, MUPP1 PDZ7 and 8 align with PATJ PDZ6 and 7; and MUPP1 PDZ domains 10-12 align with PATJ PDZ domains 8-10. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MUPP1-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467253 [Multi-domain] Cd Length: 89 Bit Score: 52.23 E-value: 2.65e-08

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                  ....*....|....*....|....*....|....*....|....*....|.
gi 569006111  235 GIYVSKVDHGGLAEENG-IKVGDQVLAANGVRFDDISHSQAVEVLK--GQT 282
Cdd:cd06791    32 GIFVKSIIPGSAADQDGrIQVNDQIIAVDGVNLQGFTNQEAVEVLRntGQV 82

PDZ domain of synaptojanin-2-binding protein (SYNJ2BP), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of SYNJ2BP, and related domains. SYNJ2BP (also known as mitochondrial outer membrane protein 25, OMP25) regulates endocytosis of activin type 2 receptor kinases through the Ral/RALBP1-dependent pathway and may be involved in suppression of activin-induced signal transduction. Binding partners of the SYNJ2BP PDZ domain include activin type II receptors (ActR-II), and SYNJ2. SYNJ2BP interacts with the PDZ binding motif of the Notch Delta-like ligand 1 (DLL1) and DLL4, promoting Delta-Notch signaling, and inhibiting sprouting angiogenesis. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This SYNJ2BP-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467193 [Multi-domain] Cd Length: 86 Bit Score: 51.91 E-value: 2.75e-08

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gi 569006111  858 TITLSKMKQSLGISISGGIESKVQPM---VKIEKIFPGGAAFLCGDLQAGFELVAVDGESLEQVTHQRAVDTIRRA 930
Cdd:cd06709     2 EITLKRGPSGLGFNIVGGTDQPYIPNdsgIYVAKIKEDGAAAIDGRLQEGDKILEINGQSLENLTHQDAVELFRNA 77

PDZ domain 3 of PDZ domain containing 2 (PDZD2), PDZ domain 1 of human pro-interleukin-16 (isoform 1, 1332 AA), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of PDZD2, also known as KIAA0300, PIN-1, activated in prostate cancer (AIPC) and PDZ domain-containing protein 3 (PDZK3). PDZD2 has seven PDZ domains. PDZD2 is expressed at exceptionally high levels in the pancreas and certain cancer tissues, such as prostate cancer. It promotes the proliferation of insulinoma cells and is upregulated during prostate tumorigenesis. In osteosarcoma (OS), the microRNA miR-363 acts as a tumor suppressor by inhibiting PDZD2. This family also includes the first PDZ domain (PDZ1) of human pro-interleukin-16 (isoform 1, also known as nPro-Il-16; 1332 amino-acid protein). Precursor IL-16 is cleaved to produce pro-IL-16 and mature IL-16 (derived from the C-terminal 121 AA). Pro-IL-16 functions as a regulator of T cell growth; mature IL-16 is a CD4 ligand that induces chemotaxis and CD25 expression in CD4+ T cells. IL-16 bioactivity has been closely associated with the progression of several different cancers. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PDZD2-like family PDZ3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467240 [Multi-domain] Cd Length: 87 Bit Score: 51.89 E-value: 3.24e-08

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gi 569006111  222 LGFNIRGGKE--FG-LGIYVSKVDHGGLAEENG-IKVGDQVLAANGVRFDDISHSQAVEVLK 279
Cdd:cd06759    14 LGFSIVGGRDspRGpMGIYVKTIFPGGAAAEDGrLKEGDEILEVNGESLQGLTHQEAIQKFK 75

PDZ domain 1 of FERM and PDZ domain-containing protein 2 (FRMPD2), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of FRMPD2 (also known as PDZ domain-containing protein 4, and related domains. FRMPD2 is localized in the basolateral membranes of polarized epithelial cells and is associated with tight junction formation and immune response; it contains 3 PDZ domains. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PTPN13 family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467284 [Multi-domain] Cd Length: 92 Bit Score: 51.73 E-value: 4.17e-08

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gi 569006111   84 IHAVRVEKSPSGRLGFSVRGGSEHG---LGIFVSKVEEGSSAERAG-LCVGDKITEVNGLSLESTTMGSAVRLLTSS 156
Cdd:cd23071     2 IVCVTLKRDPKRGFGFVIVGGENTGkldLGIFIASIIPGGPAEKDGrIKPGGRLISLNNISLEGVTFNTAVKILQNS 78

PDZ domain of densin, erbin, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of densin, erbin, and related domains. Densin (also known as leucine-rich repeat-containing protein 7, LRRC7, densin-180, protein LAP1) and erbin (also known as densin-180-like protein, Erbb2-interacting protein, protein LAP2) belong to the LAP (leucine-rich repeat and PDZ domain) family of scaffolding proteins that play roles in the maintenance of cell shape and apical-basal polarity. Densin and erbin are components of the excitatory postsynaptic compartment and are regulators of dendritic morphology and postsynaptic structure. The densin PDZ domain binds CaV1.3 alpha1 subunit, delta-catenin, and MAGUIN-1. Binding partners of the erbin PDZ domain include ErbB receptor tyrosine kinase ErbB2, HTLV-1 Tax1, Cav1.3 Ca2+channels, and constituents of the cadherin:catenin cell adhesion complex, in particular delta-catenin, p0071 and ARVCF. The erbin PDZ domain binds Smad3, a transductor of the TGFbeta pathway, possibly by a novel interface of binding. Erbin and two other LAP proteins (scribble and lano) redundantly regulate epithelial polarity and apical adhesion complex. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This densin and erbin-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467231 [Multi-domain] Cd Length: 87 Bit Score: 51.56 E-value: 4.23e-08

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gi 569006111  222 LGFNIRGG--------KEFGLGIYVSKVDHGGLAEeNGIKVGDQVLAANGVRFDDISHSQAVEVLKG-QTHIMLTI 288
Cdd:cd06749    11 LGFSISGGigsqgnpfRPDDDGIFVTKVQPDGPAS-KLLQPGDKILEVNGYDFVNIEHGQAVSLLKSfQNTVDLVV 85

PDZ domain 3 of harmonin isoforms a and b, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of harmonin isoforms a and b, and related domains. Harmonin (also known as Usher Type 1C, PDZ-73 and AIE-75) is a key organizer of the Usher (USH) protein interactome. USH syndrome is the leading cause of hereditary sensory deaf-blindness in humans; three clinically distinct types of USH have been identified, type 1 to 3. The gene encoding harmonin (USH1C) is the causative gene for the USH type 1C phenotype. There are at least 10 alternatively spliced isoforms of harmonin, which are divided into three subclasses (a, b, and c). All isoforms contain the first two PDZ domains and the first coiled-coil domain. The a and b isoforms all have a third PDZ domain. The different PDZ domains are responsible for interactions with all known Usher syndrome type 1 proteins, and most Usher syndrome type 2 proteins. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This harmonin family PDZ3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467221 [Multi-domain] Cd Length: 94 Bit Score: 51.16 E-value: 6.13e-08

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gi 569006111  209 RIVHLYTTSDDFCLGFNIRGGKEFGLG--IYVSKVDHGGLAEENG-IKVGDQVLAANGVRFDDISHSQAVEVLK-----G 280
Cdd:cd06739     1 RQVRLLRIKKNGPLDLALEGGIDSPLGgkIVVSAVYEGGAADKHGgIVKGDQIMMVNGKSLTDVTLAEAEAALQramnsG 80

                          90
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gi 569006111  281 QTHIMLTIKETG 292
Cdd:cd06739    81 GDWIDLVIAVAP 92

PDZ domain of partitioning defective 6 (Par6), Drosophila Rho GTPase-activating protein 100F (RhoGAP100F), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of Par6 (also known as PAR6 or Par-6), RhoGAP100F, and related domains. Par6 is part of a conserved machinery that directs metazoan cell polarity, a process necessary for the function of diverse cell types. Par6 forms a cell polarity-regulatory complex with atypical protein kinase C (aPKC) and Par3. Par6 can also directly associate with PALS1 (proteins associated with Lin7, also known as Stardust) providing a link between the Par3/aPKC/Par6 complex and the PALS1-PATJ (protein-associated TJ) complex. Binding partners of the Par6-PDZ domain include Par3, PALS1/Stardust; leucine-rich repeat-containing protein netrin-G ligand-2 (NGL-2), human crumbs (CRB3) involve in the morphogenesis of the tight junctions in mammalian epithelial cells, and PAR-6 co-operates with the Par6 semi-CRIB domain to bind CDC42. CDC42 regulates the Par6 PDZ domain through an allosteric CRIB-PDZ transition. Drosophila RhoGAP100F, also known as synapse defective protein 1 homolog (syd-1 homolog), is a GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound form. The RhoGAP100F-PDZ domain binds the neurexin C terminus to control synapse formation at the Drosophila neuromuscular junction. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Par6-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467202 [Multi-domain] Cd Length: 84 Bit Score: 51.03 E-value: 6.14e-08

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gi 569006111  222 LGFNIRGG--KEFGLGIYVSKVDHGGLAEENG-IKVGDQVLAANGVRFDDISHSQAVEVLKGQTHIMLTIK 289
Cdd:cd06718    13 LGFYIRDGngVERVPGIFISRLVLGSLADSTGlLAVGDEILEVNGVEVTGKSLDDVTDMMVAPTRLIITVK 83

PDZ domain 4 of Drosophila Scribble, human Scribble homolog, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 4 of Drosophila Scribble (also known as LAP4), human Scribble homolog (also known as hScrib, LAP4, CriB1, ScrB1 and Vartul), and related domains. They belong to the LAP family, which describes proteins that contain either one or four PDZ domains and 16 LRRs (leucine-rich repeats) and function in controlling cell shape, size and subcellular protein localization. In Drosophila, the Scribble complex, comprising Scribble, discs large, and lethal giant larvae, plays a role in apico-basal cell polarity, in other forms of polarity, including regulation of the actin cytoskeleton, cell signaling and vesicular trafficking, and in tumor development. Mammalian Scribble is important in many aspects of cancer development. Scribble and its homologs can be downregulated or overexpressed in cancer; they have a role in cancer beyond their function in loss of cell polarity. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Scribble-like family PDZ4 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467185 [Multi-domain] Cd Length: 98 Bit Score: 51.46 E-value: 6.28e-08

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gi 569006111  856 LRTITLSKMK-QSLGISISGGIESKVQPMVK-------IEKIFPGGAAFLCGDLQAGFELVAVDGESLEQVTHQRAVDTI 927
Cdd:cd06701     4 LQELTIVKEPgEKLGISIRGGAKGHAGNPLDptdegifISKINPDGAAARDGRLKVGQRILEVNGQSLLGATHQEAVRIL 83


                  ...
gi 569006111  928 RRA 930
Cdd:cd06701    84 RSV 86

PDZ1 domain of Gallus gallus uncharacterized syntaxin-binding protein 4 (STXBP4) isoform X1, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of Gallus gallus uncharacterized syntaxin-binding protein 4 (STXBP4) isoform X1, and related domains. Gallus gallus STXBP4 isoform X1 contains 2 PDZ domains (PDZ1 and PDZ2). PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This STXBP4-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467179 [Multi-domain] Cd Length: 88 Bit Score: 51.07 E-value: 6.52e-08

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gi 569006111  223 GFNIRGGKEFGlgIYVSKVDHGGLAEENG-IKVGDQVLAANGVRFDDISHSQAVEVLK---GQTHIMLTI 288
Cdd:cd06692    17 GYRENTGEEFG--IFIKRILPGGLAATDGrLKEGDLILEVNGESLQGVTNERAVSILRsasASNHMSLLI 84

PDZ domain 1 of protein tyrosine phosphatase non-receptor type 13 (PTPN13), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of PTPN13 [also known as Fas-associated protein-tyrosine phosphatase 1 (FAP-1), protein-tyrosine phosphatase 1E (PTP-E1), and protein-tyrosine phosphatase (PTPL1)], and related domains. PTPN13 regulates negative apoptotic signaling and mediates phosphoinositide 3-kinase (PI3K) signaling. PTPN13 has five PDZ domains. Proteins known to interact with PTPN13 PDZ domains include: PLEKHA1 and PLEKHA2 via PTPN13-PDZ domain 1, Fas receptor and thyroid receptor-interacting protein 6 via PTPN13-PDZ domain 2, nerve growth factor receptor and protein kinase N2 via PTPN13-PDZ domain 3, PDZ and LIM domain 4 (PDLIM4) via PTPN13-PDZ domains 2 and 4, and brain calpain-2 via PTPN13-PDZ domains 3, 4 and 5. Calpain-2-mediated PTPN13 fragments may be involved in abnormal tau aggregation and increased risk for Alzheimer's disease. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PTPN13 family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467285 [Multi-domain] Cd Length: 92 Bit Score: 50.95 E-value: 7.51e-08

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gi 569006111  856 LRTITLSK-MKQSLGISISGGIESKVQPM-VKIEKIFPGGAAFLCGDLQAGFELVAVDGESLEQVTHQRAVDTIRrayrn 933
Cdd:cd23072     2 ITLVNLKKdAKYGLGFQIVGGEKSGRLDLgIFISSITPGGPADLDGRLKPGDRLISVNDVSLEGLSHDAAVEILQ----- 76

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gi 569006111  934 KAREPMELVVRVP 946
Cdd:cd23072    77 NAPEDVTLVVSQP 89

PDZ domain 5 of Danio rerio tyrosine-protein phosphatase non-receptor type 13 (Ptpn13) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 5 of Danio rerio Ptpn13, and related domains. Protein-tyrosine phosphatases (PTPs) dephosphorylate phosphotyrosyl residues in proteins that are phosphorylated by protein tyrosine kinases (PTKs). Danio rerio Ptpn13 is a classical non-receptor-like PTP. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PTPN13-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467273 [Multi-domain] Cd Length: 80 Bit Score: 50.43 E-value: 7.57e-08

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gi 569006111  858 TITLSK-MKQSLGISISGGIESKVqpmVKIEKIFPGGAAFLCGDLQAGFELVAVDGESLEQVTHQRAVDTIRRA 930
Cdd:cd23060     1 QIELEKpANGGLGFSLVGGEGGSG---IFVKSISPGGVADRDGRLQVGDRLLQVNGESVIGLSHSKAVNILRKA 71

PDZ domain 5 of membrane-associated guanylate kinase inverted 1 (MAGI-1), MAGI-2, and MAGI-3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 5 of MAGI1, 2, 3 (MAGI is also known as Membrane-associated guanylate kinase, WW and PDZ domain-containing protein) and related domains. MAGI proteins have been implicated in the control of cell migration and invasion through altering the activity of phosphatase and tensin homolog (PTEN) and modulating Akt signaling. Four MAGI proteins have been identified (MAGI1-3 and MAGIX). MAGI1-3 have 6 PDZ domains and bind to the C-terminus of PTEN via their PDZ2 domain. MAGIX has a single PDZ domain that is related to MAGI1-3 PDZ domain 5, and belongs to this MAGI1,2,3-like family. Other binding partners for MAGI1 include JAM4, C-terminal tail of high risk HPV-18 E6, megalin, TRAF6, Kir4.1 (basolateral K+ channel subunit), and cadherin 23; for MAGI2, include DASM1, dendrin, axin, beta- and delta-catenin, neuroligin, hyperpolarization-activated cation channels, beta1-adrenergic receptors, NMDA receptor, and TARPs; and for MAGI3 includes LPA2. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MAGI family PDZ5 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467217 [Multi-domain] Cd Length: 84 Bit Score: 50.66 E-value: 7.71e-08

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gi 569006111  858 TITLSKMKQSLGISISGGIESKVQPMVkIEKIFPGGAAFLCGDLQAGFELVAVDGESLEQVTHQRAVDTIRR 929
Cdd:cd06735     3 SVELERGPKGFGFSIRGGREYNNMPLY-VLRLAEDGPAQRDGRLRVGDQILEINGESTQGMTHAQAIELIRS 73

PDZ domain 3 of multi-PDZ-domain protein 1 (MUPP1) and PATJ (protein-associated tight junction) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of MUPP1 and PATJ, and related domains. MUPP1 and PATJ serve as scaffolding proteins linking different proteins and protein complexes involved in the organization of tight junctions and epithelial polarity. MUPP1 contains an L27 (Lin-2 and Lin-7 binding) domain and 13 PDZ domains. PATJ (also known as INAD-like) contains an L27 domain and ten PDZ domains. MUPP1 and PATJ share several binding partners, including junctional adhesion molecules (JAM), zonula occludens (ZO)-3, Pals1 (protein associated with Lin-7), Par (partitioning defective)-6 proteins, and nectins (adherence junction adhesion molecules). PATJ lacks 3 PDZ domains seen in MUPP1: PDZ6, 9, and 13; consequently, MUPP1 PDZ7 and 8 align with PATJ PDZ6 and 7; and MUPP1 PDZ domains 10-12 align with PATJ PDZ domains 8-10. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MUPP1-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467253 [Multi-domain] Cd Length: 89 Bit Score: 50.69 E-value: 7.76e-08

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gi 569006111  859 ITLSKMKQSLGISISGGIESKVQ---PMVKIEKIFPGGAAFLCGDLQAGFELVAVDGESLEQVTHQRAVDTIRRA 930
Cdd:cd06791     5 VELVKDEQGLGITIAGYVGEKASgelSGIFVKSIIPGSAADQDGRIQVNDQIIAVDGVNLQGFTNQEAVEVLRNT 79

PDZ domain 5 of Danio rerio tyrosine-protein phosphatase non-receptor type 13 (Ptpn13) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 5 of Danio rerio Ptpn13, and related domains. Protein-tyrosine phosphatases (PTPs) dephosphorylate phosphotyrosyl residues in proteins that are phosphorylated by protein tyrosine kinases (PTKs). Danio rerio Ptpn13 is a classical non-receptor-like PTP. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PTPN13-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467273 [Multi-domain] Cd Length: 80 Bit Score: 50.43 E-value: 8.35e-08

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gi 569006111  222 LGFNIRGGkEFGLGIYVSKVDHGGLAEENG-IKVGDQVLAANGVRFDDISHSQAVEVL-KGQTHIMLTI 288
Cdd:cd23060    12 LGFSLVGG-EGGSGIFVKSISPGGVADRDGrLQVGDRLLQVNGESVIGLSHSKAVNILrKAKGTVQLTV 79

PDZ domain of tyrosine-protein phosphatase non-receptor type 3 (PTPN3), tyrosine-protein phosphatase non-receptor type 4 (PTNP4), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of PTPN3, PTPN4 and related domains. PTPN3 (also known as protein-tyrosine phosphatase H1, PTP-H1) has a tumor-suppressive or a tumor-promoting role in many cancers. It serves as a specific phosphatase for the MAP kinase p38gamma; the two interact via their PDZ domains and cooperate to promote Ras-induced oncogenesis. Interaction partners of the PTPN3 PDZ domain include p38gamma and human papillomavirus E6 oncoprotein. PTPN4 (also known as protein-tyrosine phosphatase MEG1) plays a role in immunity, learning, synaptic plasticity or cell homeostasis. p38gamma is also an interaction partner of the PTPN4 PDZ domain: PTPN4 regulates neuronal cell homeostasis by protecting neurons against apoptosis; binding of the C terminus of p38gamma to the PDZ domain of PTPN4, antagonizes the catalytic autoinhibition of PTPN4, leading to cell apoptosis. Other interaction partners of the PTPN4 PDZ domain include glutamate receptor subunit GluN2A, and RABV strain G protein, among others. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PTPN3-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467190 [Multi-domain] Cd Length: 90 Bit Score: 50.39 E-value: 1.07e-07

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gi 569006111   87 VRVEKSPSGRLGFSVRGGSEHGLGIFVSKVEEGSSAERA--GLCVGDKITEVNGLSLESTTMGSAVRLLTSSSCLH 160
Cdd:cd06706     6 IRMKPDENGRFGFNVKGGVDQKMPVIVSRVAPGTPADLCipRLNEGDQVLLINGRDISEHTHDQVVMFIKASRERH 81

second harmonin_N_like domain (repeat 2) of the long isoform of whirlin, and related domains; This subgroup contains the second of two harmonin_N_like domains found in the long isoform of whirlin, and related domains. Whirlin is a postsynaptic density-95/discs-large/ZO-1 (PDZ) domain-containing scaffold protein which binds various components of the Usher protein network of the inner ear and the retina: erythrocyte protein p55, usherin, VlGR1, and myosin XVa. The long isoform of whirlin contains two harmonin_N_like domains, and three PDZ protein-binding domains, PDZ1-3. The short whirlin isoform, derived from an alternative start ATG, lacks the first harmonin_N_like domain but has in common with the long isoform, this second harmonin_N_like domain (designated repeat 2, included in this subgroup) and PDZ3. This second harmonin_N_like domain is a putative protein-binding module based on its sequence similarity to the N-terminal domain of harmonin.

Pssm-ID: 259823 Cd Length: 81 Bit Score: 49.99 E-value: 1.08e-07

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gi 569006111  554 WESRRPLIQDLARRLLTDDEVLAVTRHCSRYVHEG-GVEDLVRPLLAILDRPTKLLLLRDIRSVVAPTDLGRFDSMV 629
Cdd:cd07357     1 SSQTAALVEEKARSLLNRSERATLSYYLAEYSSGHlTVDAFVLALFELLNTPEKFSLLSEIRELVAPEDLDRFDELV 77

PDZ domain of tax1-binding protein 3 (TAX1BP3), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of TAX1BP3, and related domains. TAX1BP3 (also known as glutaminase-interacting protein 3, tax interaction protein 1, TIP-1, tax-interacting protein 1) may regulate a number of protein-protein interactions by competing for PDZ domain binding sites. TAX1BP3 binds beta-catenin and may act as an inhibitor of the Wnt signaling pathway. It competes with LIN7A (also known as Lin-7A or LIN-7A) for inward rectifier potassium channel 4 (KCNJ4) binding, and thereby promotes KCNJ4 internalization. It may play a role in the Rho signaling pathway, and in the activation of CDC42 by the viral protein HPV16 E6. Binding partners of the TAX1BP3 PDZ domain include beta-catenin, KCNJ4, glutaminase liver isoform (GLS2), rho guanine nucleotide exchange factor 16 (ARHGEF16), rhotekin, and CDK5 regulatory subunit-associated protein 3 (also known as LAPZ). PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This TAX1BP3-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467265 [Multi-domain] Cd Length: 94 Bit Score: 50.41 E-value: 1.23e-07

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gi 569006111  222 LGFNIRGG----------KEFGLGIYVSKVDHGGLAEENGIKVGDQVLAANGVRFDDISHSQAVEVLK 279
Cdd:cd10822    15 LGFSIGGGidqdpsknpfSYTDKGIYVTRVSEGGPAEKAGLQVGDKILQVNGWDMTMVTHKQAVKRLT 82

PDZ domain 3 of Drosophila Scribble, human Scribble homolog, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of Drosophila Scribble (also known as LAP4), human Scribble homolog (also known as hScrib, LAP4, CriB1, ScrB1 and Vartul), and related domains. They belong to the LAP family, which describes proteins that contain either one or four PDZ domains and 16 LRRs (leucine-rich repeats) and function in controlling cell shape, size and subcellular protein localization. In Drosophila, the Scribble complex, comprising Scribble, discs large, and lethal giant larvae, plays a role in apico-basal cell polarity, in other forms of polarity, including regulation of the actin cytoskeleton, cell signaling and vesicular trafficking, and in tumor development. Mammalian Scribble is important in many aspects of cancer development. Scribble and its homologs can be downregulated or overexpressed in cancer; they have a role in cancer beyond their function in loss of cell polarity. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Scribble-like family PDZ3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467186 [Multi-domain] Cd Length: 89 Bit Score: 49.95 E-value: 1.40e-07

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gi 569006111  222 LGFNIRGGKE-----FGL---GIYVSKVDHGGLAEENGIKVGDQVLAANGVRFDDISHSQAVEVL 278
Cdd:cd06702    12 LGLSIVGGSDhsshpFGVdepGIFISKVIPDGAAAKSGLRIGDRILSVNGKDLRHATHQEAVSAL 76

PDZ domain of tamalin, cytohesin-1-interacting protein (CYTIP), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of tamalin, cytohesin-1-interacting protein, and related domains. Tamalin (trafficking regulator and scaffold protein tamalin, also known as general receptor for phosphoinositides 1-associated scaffold protein, GRASP) functions to link receptors, including group 1 metabotropic glutamate receptors (mGluRs), to neuronal proteins. The tamalin PDZ domain binds the C-terminal domains of group I mGluRs; it also binds potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2 (HCN2), neurotrophin-3 (NT3) TrkCT1-truncated receptor, SAP90/PSD-95-associated protein, and tamalin itself. CYTIP (cytohesin-1-interacting protein, also known as Pleckstrin homology Sec7 and coiled-coil domain-binding protein) sequesters cytohesin-1 in the cytoplasm, limiting its interaction with beta2 integrins; cytohesin-1 binds the CYTIP coiled coil domain. The CYTIP PDZ domain can bind the C-terminal peptide of protocadherin alpha-1 (PCDHA1), indicating a possible interaction between the two. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This tamalin-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467197 [Multi-domain] Cd Length: 91 Bit Score: 49.93 E-value: 1.64e-07

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gi 569006111  112 FVSKVEEGSSAERAGLCVGDKITEVNGLSLESTTMGSAVRLLTSSSCLHMMV 163
Cdd:cd06713    38 YVCRVHEDSPAYLAGLTAGDVILSVNGVSVEGASHQEIVELIRSSGNTLRLE 89

PDZ domain 6 of PDZ domain containing 2 (PDZD2), PDZ domain 3 of human pro-interleukin-16 (isoform 1, 1332 AA), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 6 of PDZD2, also known as KIAA0300, PIN-1, activated in prostate cancer (AIPC) and PDZ domain-containing protein 3 (PDZK3). PDZD2 has seven PDZ domains. PDZD2 is expressed at exceptionally high levels in the pancreas and certain cancer tissues, such as prostate cancer. It promotes the proliferation of insulinoma cells and is upregulated during prostate tumorigenesis. In osteosarcoma (OS), the microRNA miR-363 acts as a tumor suppressor by inhibiting PDZD2. This family also includes the third PDZ domain (PDZ3) of human pro-interleukin-16 (isoform 1, also known as nPro-IL-16). Precursor IL-16 is cleaved to produce pro-IL-16 and C-terminal mature IL-16. Pro-IL-16 functions as a regulator of T cell growth; mature IL-16 is a CD4 ligand that induces chemotaxis and CD25 expression in CD4+ T cells. IL-16 bioactivity has been closely associated with the progression of several different cancers. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PDZD2-like family PDZ6 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467243 [Multi-domain] Cd Length: 86 Bit Score: 49.95 E-value: 1.65e-07

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gi 569006111  859 ITLSKMK-QSLGISISGGIESKVQPmVKIEKIFPGGAAFLCGDLQAGFELVAVDGESLEQVTHQRAVDTIRRayrnkARE 937
Cdd:cd06762     4 VVLHKEEgSGLGFSLAGGSDLENKS-ITVHRVFPSGLAAQEGTIQKGDRILSINGKSLKGVTHGDALSVLKQ-----ARL 77


                  ....*.
gi 569006111  938 PMELVV 943
Cdd:cd06762    78 PKVAVV 83

PDZ domain 3 of human discs large homolog 1 (Dlg1), Dlg2, and Dlg4, Drosophila disc large (Dlg), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of Drosophila Dlg1, human Dlg1, 2, and 4 and related domains. Dlg1 (also known as synapse-associated protein Dlg197; SAP-97), Dlg2 (also known as channel-associated protein of synapse-110; postsynaptic density protein 93, PSD-93), Dlg4 (also known as postsynaptic density protein 95, PSD-95; synapse-associated protein 90, SAP-90) each have 3 PDZ domains and belong to the membrane-associated guanylate kinase family. Dlg1 regulates antigen receptor signaling and cell polarity in lymphocytes, B-cell proliferation and antibody production, and TGFalpha bioavailability; its PDZ3 domain binds pro-TGFalpha, and its PDZ2 domain binds the TACE metalloprotease responsible for cleaving pro-TGFalpha to a soluble form. Dlg2 is involved in N-methyl-D-aspartate (NMDA) receptor signaling, regulating surface expression of NMDA receptors in dorsal horn neurons of the spinal cord; it interacts with NMDA receptor subunits and with Shaker-type K+ channel subunits to cluster into a channel complex. The Dlg4 PDZ1 domain binds NMDA receptors, and its PDZ2 domain binds neuronal nitric oxide synthase (nNOS), forming a complex in neurons. The Drosophila Scribble complex (Scribble, Dlg, and lethal giant larvae) plays a role in apico-basal cell polarity, and in other forms of polarity, including regulation of the actin cytoskeleton, cell signaling and vesicular trafficking, and in tumor development; postsynaptic targeting of Drosophila DLG requires interactions mediated by the first two PDZ domains. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Dlg-like family PDZ3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467257 [Multi-domain] Cd Length: 91 Bit Score: 50.05 E-value: 1.69e-07

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gi 569006111  857 RTITLSKMKQSLGISISGGIESKvqpMVKIEKIFPGGAAFLCGDLQAGFELVAVDGESLEQVTHQRAVDTIRRA 930
Cdd:cd06795     3 RKIVLHKGSTGLGFNIVGGEDGE---GIFISFILAGGPADLSGELRRGDQILSVNGVDLRNATHEQAAAALKNA 73

PDZ domain of SH3 and multiple ankyrin repeat domains protein 1 (SHANK1), SHANK2, SHANK3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of SHANK1, SHANK2, SHANK3, and related domains. SHANK family proteins, SHANK1 (also known as somatostatin receptor-interacting protein, SSTR-interacting protein, SSTRIP), SHANK2 (also known as cortactin-binding protein 1, proline-rich synapse-associated protein 1), and SHANK3 (proline-rich synapse-associated protein 2) are synaptic scaffolding proteins which are highly enriched in the post-synaptic densities of excitatory synapses. They have been implicated in synaptic transmission, synapse formation, synaptic plasticity, and cytoskeletal remodeling, and are regulators of Cav1 calcium current and CREB target expression. Many protein ligands have been identified for the Shank PDZ domain, such as GKAP (also known as SAPAP), betaPIX (a guanine nucleotide exchange factor used by Rho GTPase family members Rac1 and Cdc42), alpha-latrotoxin, neuroligin, group I metabotropic glutamate receptors (mGluRs), and L-type calcium channels. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This SHANK-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta- strand F.

Pssm-ID: 467228 [Multi-domain] Cd Length: 101 Bit Score: 50.28 E-value: 1.75e-07

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gi 569006111   79 DESDIIHAVRVEKSPSGrLGFSVRGGSEHGLGI------------FVSKVEEGSSAERAGLCVGDKITEVNGLSLESTTM 146
Cdd:cd06746     1 DSIIDPRTVVLQKGDKG-FGFVLRGAKAVGPILeftptpafpalqYLESVDPGGVADKAGLKKGDFLLEINGEDVVKASH 79

                          90
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gi 569006111  147 GSAVRLLTSSS-CLHMMV 163
Cdd:cd06746    80 EQVVNLIRQSGnTLVLKV 97

PDZ domain 3 of human Ligand of Numb protein X 1 (LNX1) and LNX2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of LNX1 (also known as PDZ domain-containing RING finger protein 2, PDZRN2) and LNX2 (also known as PDZ domain-containing RING finger protein 1, PDZRN1), and related domains. LNX1 and LNX2 are Ring (Really Interesting New Gene) finger and PDZ domain-containing E3 ubiquitin ligases that bind to the cell fate determinant protein NUMB and mediate its ubiquitination. LNX1 can ubiquitinate a number of other ligands including PPFIA1, KLHL11, KIF7 and ERC2. LNX1 and LNX2 each have four PDZ domains. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This LNX family PDZ3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467167 [Multi-domain] Cd Length: 88 Bit Score: 49.94 E-value: 1.76e-07

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gi 569006111  857 RTITLSK-MKQSLGISISGGIESKVQPM-VKIEKIFPGGAAFLCGDLQAGFELVAVDGESLEQVTHQRAVDTIRRA 930
Cdd:cd06679     1 KTVTIKKePSESLGISVAGGRGSRRGDLpIYVTNVQPDGCLGRDGRIKKGDVLLSINGISLTNLSHSEAVAVLKAS 76

PDZ domain 2 of PDZ domain containing 2 (PDZD2), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of PDZD2, also known as KIAA0300, PIN-1, activated in prostate cancer (AIPC) and PDZ domain-containing protein 3 (PDZK3). PDZD2 has seven PDZ domains, and is expressed at exceptionally high levels in the pancreas and certain cancer tissues such as prostate cancer. It promotes the proliferation of insulinoma cells and is upregulated during prostate tumorigenesis. In osteosarcoma (OS), the microRNA miR-363 acts as a tumor suppressor by inhibiting PDZD2. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PDZD2-like family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467239 [Multi-domain] Cd Length: 88 Bit Score: 49.66 E-value: 1.81e-07

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gi 569006111   94 SGRLGFSVRGG--SEHG-LGIFVSKVEEGSSAERAG-LCVGDKITEVNGLSLESTTMGSAVRLLTSSSCLHMMV 163
Cdd:cd06758    11 KGGLGIQITGGkgSKRGdIGIFVAGVEEGGSADRDGrLKKGDELLMINGQSLIGLSHQEAVAILRSSASPVQLV 84

PDZ domain 4 of Discs Large 5 (Dlg5) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 4 of Drosophila and mammalian Dlg5, and related domains. Dlg5 is a scaffold protein with multiple conserved functions that are independent of each other in regulating growth, cell polarity, and cell adhesion. It has a coiled-coil domain, 4 PDZ domains and a MAGUK domain (an SH3 domain next to a non-catalytically active guanylate kinase domain). Deregulation of Dlg5 has been implicated in the malignancy of several cancer types. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Dlg5-like family PDZ4 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467247 [Multi-domain] Cd Length: 81 Bit Score: 49.31 E-value: 2.03e-07

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gi 569006111   86 AVRVEKSPSgRLGFSVRGGSEHGlgIFVSKVEEGSSA-ERAGLCVGDKITEVNGLSLESTT 145
Cdd:cd06766     4 LVFLKKSQV-ELGIQLCGGNLHG--IFVEDVEDDSPAkGPDGLVPGDLILEYNSVDMRNKT 61

PDZ domain 2 of PDZ domain containing 2 (PDZD2), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of PDZD2, also known as KIAA0300, PIN-1, activated in prostate cancer (AIPC) and PDZ domain-containing protein 3 (PDZK3). PDZD2 has seven PDZ domains, and is expressed at exceptionally high levels in the pancreas and certain cancer tissues such as prostate cancer. It promotes the proliferation of insulinoma cells and is upregulated during prostate tumorigenesis. In osteosarcoma (OS), the microRNA miR-363 acts as a tumor suppressor by inhibiting PDZD2. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PDZD2-like family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467239 [Multi-domain] Cd Length: 88 Bit Score: 49.27 E-value: 2.34e-07

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gi 569006111  211 VHLYTTSDDfcLGFNIRGG---KEFGLGIYVSKVDHGGLAEENG-IKVGDQVLAANGVRFDDISHSQAVEVLK 279
Cdd:cd06758     5 MHLLKEKGG--LGIQITGGkgsKRGDIGIFVAGVEEGGSADRDGrLKKGDELLMINGQSLIGLSHQEAVAILR 75

PDZ domain of segment polarity protein dishevelled homolog DVL1, DVL2, DVL3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of DVL1-3, and related domains. The dishevelleds (DVL1, 2 and 3 in humans) act downstream of Frizzled (FZD) receptors in both the canonical and non-canonical WNT signaling pathway; they bind the cytoplasmic C-terminus of frizzled family members and transduce the Wnt signal to down-stream effectors. They bind to several proteins known to modulate Wnt signaling. Binding partners of the DVL1 PDZ domain include nucleoredoxin (NXN), Van Gogh-like (VANGL1), Wnt receptor RYK, Dapper 1 (DACT1), Frizzled7 (FZD7), transmembrane protein 88 (TMEM88), Daple (dishevelled-associating protein with a high frequency of leucines), also known as Ccdc88c), and cysteine-rich protein Idax. The DVL2 PDZ domain has been shown to bind the nuclear export signal sequence of the DVL2 protein. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This DVL-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467201 [Multi-domain] Cd Length: 87 Bit Score: 49.29 E-value: 2.42e-07

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gi 569006111  222 LGFNIRGGKEFGL--GIYVSKVDHGGLAEENG-IKVGDQVLAANGVRFDDISHSQAVEVLKGQTH----IMLTIK 289
Cdd:cd06717    12 LGISIVGQSNERGdgGIYVGSIMKGGAVAADGrIEPGDMILQVNDISFENMSNDDAVRVLREAVHkpgpITLTVA 86

PDZ domain of PDZ-LIM family proteins, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of PDZ-LIM family proteins including PDLIM1-7, and related domains. PDZ-LIM family proteins (also known as Zasp PDZ domain proteins) are involved in the rearrangement of the actin cytoskeleton; they mediate association with the cytoskeleton through alpha-actinin as well as with other proteins involved in signal transduction pathways. Members of this family include PDLIM1 (also known as C-terminal LIM domain protein 1, elfin, LIM domain protein CLP-36), PDLIM2 (also known as PDZ-LIM protein mystique), PDLIM3 (also known as actinin-associated LIM protein, alpha-actinin-2-associated LIM protein, ALP), PDLIM4 (also known as LIM protein RIL, Reversion-induced LIM protein), PDLIM5 (also known as enigma homolog, ENH, enigma-like PDZ and LIM domains protein), PDLIM6 (also known as LIM domain-binding protein 3, ZASP, Cypher, Oracle), and PDLIM7 (also known as PDZ and LIM domain protein 7, LIM mineralization protein, LMP; protein enigma). PDLIM1 has been shown to negatively regulate NF-kappaB-mediated signaling in the cytoplasm. PDLIM7 negatively regulates p53 through binding murine double minute 2 (MDM2). The PDZ domains of PDZ-LIM family proteins PDLIM1, 2, 3, 5, 6, 7 have been shown to bind actin. Other PDZ-LIM family PDZ domain binding partners include thyroid receptor interacting protein-6 (PDLIM4-PDZ), the LIM domain of PDLIM4 (PDLIM4-PDZ), tropomyosin (PDLIM7-PDZ), myotilin and calsarcin 1 (PDLIM6-PDZ), and proteins from the myotilin and FATZ (calsarcin/myozenin) families (PDLIM1, 3, 4, 6 PDZ domains). PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PDLIM-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467235 [Multi-domain] Cd Length: 79 Bit Score: 49.07 E-value: 2.75e-07

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gi 569006111   98 GFSVRGGSEHGLGIFVSKVEEGSSAERAGLCVGDKITEVNGLSLESTTMGSAVRLL-TSSSCLHMMVRR 165
Cdd:cd06753    11 GFRLQGGKDFNQPLTISRVTPGGKAAQANLRPGDVILAINGESTEGMTHLEAQNKIkAATGSLSLTLER 79

PDZ domain 1 of human discs large homolog 1 (Dlg1), Dlg2, and Dlg4, Drosophila disc large (Dlg), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of Drosophila Dlg1, human Dlg1,2, and 4 and related domains. Dlg1 (also known as synapse-associated protein Dlg197 or SAP-97), Dlg2 (also known as channel-associated protein of synapse-110, postsynaptic density protein 93, or PSD-93), Dlg4 (also known as postsynaptic density protein 95, PSD-95, synapse-associated protein 90, or SAP-90) each have 3 PDZ domains and belong to the membrane-associated guanylate kinase family. Dlg1 regulates antigen receptor signaling and cell polarity in lymphocytes, B-cell proliferation and antibody production, and TGFalpha bioavailability; its PDZ3 domain binds pro-TGFalpha, and its PDZ2 domain binds the TACE metalloprotease responsible for cleaving pro-TGFalpha to a soluble form. Dlg2 is involved in N-methyl-D-aspartate (NMDA) receptor signaling. It regulates surface expression of NMDA receptors in dorsal horn neurons of the spinal cord, and it also interacts with NMDA receptor subunits and with Shaker-type K+ channel subunits to cluster into a channel complex. Dlg4 PDZ1 domain binds NMDA receptors, and its PDZ2 domain binds neuronal nitric oxide synthase (nNOS), forming a complex in neurons. The Drosophila Scribble complex (Scribble, Dlg, and lethal giant larvae) plays a role in apico-basal cell polarity, and in other forms of polarity, including regulation of the actin cytoskeleton, cell signaling and vesicular trafficking, and in tumor development. Postsynaptic targeting of Drosophila DLG requires interactions mediated by the first two PDZ domains. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Dlg-like family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467206 [Multi-domain] Cd Length: 89 Bit Score: 49.23 E-value: 2.80e-07

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gi 569006111  222 LGFNIRGGKE---FG--LGIYVSKVDHGGLAEENG-IKVGDQVLAANGVRFDDISHSQAVEVLK 279
Cdd:cd06723    13 LGFSIAGGTDnphIGddPSIYITKIIPGGAAAADGrLRVNDIILRVNDVDVRNVTHSVAVEALK 76

PDZ domain 1 of Drosophila Scribble, human Scribble homolog, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of Drosophila Scribble (also known as LAP4), human Scribble homolog (also known as hScrib, LAP4, CriB1, ScrB1 and Vartul), and related domains. They belong to the LAP family, which describes proteins that contain either one or four PDZ domains and 16 LRRs (leucine-rich repeats) and function in controlling cell shape, size and subcellular protein localization. In Drosophila, the Scribble complex, comprising Scribble, discs large, and lethal giant larvae, plays a role in apico-basal cell polarity, in other forms of polarity, including regulation of the actin cytoskeleton, cell signaling and vesicular trafficking, and in tumor development. Mammalian Scribble is important in many aspects of cancer development. Scribble and its homologs can be downregulated or overexpressed in cancer; they have a role in cancer beyond their function in loss of cell polarity. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Scribble-like family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467188 [Multi-domain] Cd Length: 87 Bit Score: 48.81 E-value: 3.31e-07

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gi 569006111  858 TITLSKMKQSLGISISGGIESK----VQPMVKIEKIFPGGAAFLCGdLQAGFELVAVDGESLEQVTHQRAVDTIRRA 930
Cdd:cd06704     2 TITIERQTGGLGISIAGGKGSTpykgDDEGIFISRVTEGGPAAKAG-VRVGDKLLEVNGVDLVDADHHEAVEALKNS 77

PDZ domain 2 of delphilin (L-delphilin isoform), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of delphilin (also known as glutamate receptor, ionotropic, delta 2-interacting protein 1, L-delphilin). Delphilin, a postsynaptic protein which it is selectively expressed at cerebellar Purkinje cells, links the glutamate receptor delta 2 subunit (GluRdelta2) with the actin cytoskeleton and various signaling molecules. Two alternatively spliced isoforms of delphilin have been characterized: L-delphilin has two PDZ domains, PDZ1 and PDZ2, and S-delphilin has a single PDZ domain (PDZ2). These two isoforms are differently palmitoylated and may be involved in controlling GluRdelta2 signaling in Purkinje cells. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This delphilin-like family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F

Pssm-ID: 467226 [Multi-domain] Cd Length: 75 Bit Score: 48.43 E-value: 3.51e-07

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gi 569006111   87 VRVEKSpSGRLGFSVRGGSEhglgIFVSKVEEGSSAERAGLCVGDKITEVNGLSLESTTMGSAVRLLTSS 156
Cdd:cd06744     2 VRVYRG-NGSFGFTLRGHAP----VYIESVDPGSAAERAGLKPGDRILFLNGLDVRNCSHDKVVSLLQGS 66

PDZ domain 1 of protein tyrosine phosphatase non-receptor type 13 (PTPN13), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of PTPN13 [also known as Fas-associated protein-tyrosine phosphatase 1 (FAP-1), protein-tyrosine phosphatase 1E (PTP-E1), and protein-tyrosine phosphatase (PTPL1)], and related domains. PTPN13 regulates negative apoptotic signaling and mediates phosphoinositide 3-kinase (PI3K) signaling. PTPN13 has five PDZ domains. Proteins known to interact with PTPN13 PDZ domains include: PLEKHA1 and PLEKHA2 via PTPN13-PDZ domain 1, Fas receptor and thyroid receptor-interacting protein 6 via PTPN13-PDZ domain 2, nerve growth factor receptor and protein kinase N2 via PTPN13-PDZ domain 3, PDZ and LIM domain 4 (PDLIM4) via PTPN13-PDZ domains 2 and 4, and brain calpain-2 via PTPN13-PDZ domains 3, 4 and 5. Calpain-2-mediated PTPN13 fragments may be involved in abnormal tau aggregation and increased risk for Alzheimer's disease. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PTPN13 family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467285 [Multi-domain] Cd Length: 92 Bit Score: 49.03 E-value: 3.58e-07

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gi 569006111   84 IHAVRVEKSPSGRLGFSVRGGSEHG---LGIFVSKVEEGSSAERAG-LCVGDKITEVNGLSLESTTMGSAVRLLTSS 156
Cdd:cd23072     2 ITLVNLKKDAKYGLGFQIVGGEKSGrldLGIFISSITPGGPADLDGrLKPGDRLISVNDVSLEGLSHDAAVEILQNA 78

PDZ domain of synaptopodin 2 (SYNPO2), synaptopodin 2-like protein (SYNPO2L), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of SYNPO2, SYNPO2L, and related domains. SYNPO2 (also known as genethonin-2, myopodin) is a cytoskeleton adaptor protein. It participates in chaperone-assisted selective autophagy (CASA), a mechanism for the disposal of misfolded and damaged proteins and provides a link between the CASA chaperone complex and a membrane-tethering and fusion machinery that generates autophagosome membranes. The SYNPO2 PPxY motif binds CASA cochaperone BCL2-associated athanogene 3 (BAG3) and the SYNPO2 PDZ domain binds vacuolar protein sorting 18 homolog (VPS18). There are three isoforms of SYNPO2, which possess an amino-terminal PDZ domain (SYNPO2a, b, c); the short isoform SYNPO2d, lacks the PDZ domain. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This SYNPO2-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467264 [Multi-domain] Cd Length: 78 Bit Score: 48.46 E-value: 4.05e-07

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gi 569006111  223 GFNIRGGKEFGLGIYVSKVDHGGLAEENGIKVGDQVLAANGVRFDDISHSQAVEVL 278
Cdd:cd10820    11 GFRLQGGSEQKKPLQVAKIRKKSKAALAGLCEGDELLSINGKPCADLSHSEAMDLI 66

PDZ domain 1 of Zonula Occludens-1 (ZO-1), homologs ZO-2 and ZO-3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of ZO-1, -2, -3 and related domains. Zonula occludens proteins (ZO-1, ZO-2, ZO-3) are multi-PDZ domain proteins involved in the maintenance and biogenesis of multi-protein networks at the cytoplasmic surface of intercellular contacts in epithelial and endothelial cells. They have three N-terminal PDZ domains, PDZ1-3, followed by a Src homology-3 (SH3) domain and a guanylate kinase (GuK)-like domain. Among protein-protein interactions for all ZO proteins is the binding of the first PDZ domain (PDZ1) to the C-termini of claudins, and the homo- and hetero-dimerization of ZO-proteins via their second PDZ domain (PDZ2), which takes place by symmetrical domain swapping of the first two beta-strands of PDZ2. At the cell level, ZO-1 and ZO-2 are involved in polarity maintenance, gene transcription, cell proliferation, and tumor cell metastasis. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This ZO family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467209 [Multi-domain] Cd Length: 87 Bit Score: 48.42 E-value: 4.62e-07

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gi 569006111  212 HLYTTSDD--FCLGFNIRGGKE---FGLG---IYVSKVDHGGLAEENgIKVGDQVLAANGVRFDDISHSQAVEVLKGQTH 283
Cdd:cd06727     1 HTVTLHRApgFGFGIAVSGGRDnphFQSGdtsIVISDVLKGGPAEGK-LQENDRVVSVNGVSMENVEHSFAVQILRKCGK 79


                  ....*..
gi 569006111  284 I-MLTIK 289
Cdd:cd06727    80 TaNITVK 86

PDZ domain 3 of glutamate receptor-interacting protein 1 (GRIP1) and GRIP2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) binding proteins GRIP1 (ABP/GRIP2) and GRIP2, and related domains. GRIP1 and GRIP2 each have 7 PDZ domains. The interaction of GRIP1 and GRIP2 with GluA2/3 (AMPAR subunit) regulates AMPAR trafficking and synaptic targeting. GRIP1 has an essential role in regulating AMPAR trafficking during synaptic plasticity and learning and memory. GRIP1 and GRIP2 interact with a variety of other proteins associated with protein trafficking and internalization, for example GRIP1 also interacts with KIF5 (also known as kinesin 1), EphB receptors, scaffold protein liprin-alpha, and the rasGEF GRASP-1. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This GRIP family PDZ3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467172 [Multi-domain] Cd Length: 87 Bit Score: 48.40 E-value: 4.88e-07

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gi 569006111   87 VRVEKSPSGRLGFSVRGGSEHG-LGIFVSKVEEGSSAERAG-LCVGDKITEVNGLSLESTTMGSAVRLLTSSS 157
Cdd:cd06684     5 VEIEKTPGSSLGITLSTSTHRNkQVIVIDSIKPASIADRCGaLHVGDHILSIDGTSVEHCSLAEATQLLASNS 77

PDZ domain 3 of partitioning defective 3 (Par3), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of Par3 (or PAR3 or Par-3, also known as Atypical PKC isotype-specific-interacting protein, ASIP, Drosophila Bazooka) and related domains. Par3 is a scaffold protein involved in organizing cell polarity across animals. Par3 binds numerous molecules both for its recruitment to one pole of the cell and for downstream contributions to polarized cell function. It regulates cell polarity by targeting the Par complex proteins Par6 and atypical protein kinase C (aPKC) to specific cortical sites. Physical interactions between Par-3 and the Par complex include Par3 PDZ domain 1 binding to the Par6 PDZ domain, Par3 PDZ domain 1 and PDZ domain 3 binding the Par6's PDZ-binding motif, and an interaction with an undefined region of aPKC that requires both Par3 PDZ2 and PDZ3. The PDZ domains of Par3 have also been implicated as potential phosphoinositide signaling integrators, since its second PDZ domain binds to phosphoinositides, and the third PDZ interacts with phosphoinositide phosphatase PTEN. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Par3 family PDZ3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467272 [Multi-domain] Cd Length: 103 Bit Score: 48.82 E-value: 4.89e-07

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gi 569006111  868 LGISISGGIESKVQPMVK-----IEKIFPGGAAFLCGDLQAGFELVAVDGESLEQVTHQRAVDTIRRA 930
Cdd:cd23059    18 LGVSVKGKTSKEDNGGKAdlgifIKSIIHGGAASKDGRLRVNDQLIAVNGESLLGLTNSEAMETLRRA 85

PDZ domain 13 of multi-PDZ-domain protein 1 (MUPP1) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 13 of MUPP1. MUPP1 and PATJ serve as scaffolding proteins linking different proteins and protein complexes involved in the organization of tight junctions and epithelial polarity. MUPP1 contains an L27 (Lin-2 and Lin-7 binding) domain and 13 PDZ domains. PATJ (also known as INAD-like) contains an L27 domain and ten PDZ domains. PATJ lacks 3 PDZ domains seen in MUPP1: PDZ6, PDZ9, and PDZ13. This MuPP1-like PDZ13 domain is therefore absent from PATJ. MUPP1 and PATJ share several binding partners, including junctional adhesion molecules (JAM), zonula occludens (ZO)-3, Pals1 (protein associated with Lin-7), Par (partitioning defective)-6 proteins, and nectins (adherence junction adhesion molecules). PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MUPP1-like family PDZ13 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467164 [Multi-domain] Cd Length: 83 Bit Score: 48.11 E-value: 5.44e-07

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gi 569006111   87 VRVEKSPSGrLGFSVRGG--SEHG-LGIFVSKVEEGSSAERAG-LCVGDKITEVNGLSLESTTMGSAVRLL 153
Cdd:cd06676     2 ITLERGSDG-LGFSIVGGfgSPHGdLPIYVKTVFEKGAAAEDGrLKRGDQILAVNGESLEGVTHEEAVNIL 71

PDZ domain of neurabin-1 and neurabin-2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of neurabin-1 (also known as protein phosphatase 1 regulatory subunit 9A) and neurabin-2 (also known as spinophilin, and protein phosphatase 1 regulatory subunit 9B), and related domains. Neurabin-1 and neurabin-2 are neuronal scaffolding proteins that play important roles in the regulation of synaptic transmission through their ability to interact with and target protein phosphatase 1 (PP1) to dendritic spines where PP1 dephosphorylates and inactivates glutamate receptors. Neurabin-2 interacts with multiple other synaptic proteins, including synaptic signaling and scaffolding proteins (e.g., GluN1 and SAPAP3) and cytoskeletal proteins (e.g., neurofilament medium polypeptide, NF-M). Neurabin-1 and neurabin-2 also binds F-actin. Other binding partners of neurabin-1 include adenosine A1 receptor (A1R), SAD-1 kinase and 70 kDa ribosomal protein S6 kinase (p70-S6K). This PDZ domain is immediately C-terminal to the PP1 binding domain. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This neurabin-like PDZ domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467252 [Multi-domain] Cd Length: 90 Bit Score: 48.57 E-value: 5.88e-07

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gi 569006111   87 VRVEKSPSGrLGFSVRG---GSEHG---LGIFVSKVEEGSSAERAG-LCVGDKITEVNGLSLESTTMGSAVRLLTSSS 157
Cdd:cd06790     5 VELEKGSEG-LGISIIGmgvGADAGlekLGIFVKTVTEGGAAQRDGrIQVNDQIVEVDGISLVGVTQAFAASVLRNTS 81

PDZ domain 12 of multi-PDZ-domain protein 1 (MUPP1), PDZ domain 10 of protein-associated tight junction (PATJ, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 12 of MUPP1, PDZ domain 10 of PATJ, and related domains. MUPP1 and PATJ serve as scaffolding proteins linking different proteins and protein complexes involved in the organization of tight junctions and epithelial polarity. MUPP1 contains an L27 (Lin-2 and Lin-7 binding) domain and 13 PDZ domains. PATJ (also known as INAD-like) contains an L27 domain and ten PDZ domains. MUPP1 and PATJ share several binding partners, including junctional adhesion molecules (JAM), zonula occludens (ZO)-3, Pals1 (protein associated with Lin-7), Par (partitioning defective)-6 proteins, and nectins (adherence junction adhesion molecules). PATJ lacks 3 PDZ domains seen in MUPP1: PDZ6, 9, and 13; consequently, MUPP1 PDZ7 and 8 align with PATJ PDZ6 and 7; and MUPP1 PDZ domains 10-12 align with PATJ PDZ domains 8-10. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MUPP1-like PDZ12 family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F

Pssm-ID: 467163 [Multi-domain] Cd Length: 86 Bit Score: 48.13 E-value: 7.10e-07

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 569006111  857 RTITLSKMKQ-SLGISISGGIESKVQPM-VKIEKIFPGGAAFLCGDLQAGFELVAVDGESLEQVTHQRAVDTIRRAY 931
Cdd:cd06675     1 RTVEIKRGPQdSLGISIAGGVGSPLGDVpVFIAMIQPNGVAAQTGKLKVGDRIVSINGQSTDGLTHSEAVNLLKNAS 77

PDZ domain 3 of human Ligand of Numb protein X 1 (LNX1) and LNX2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of LNX1 (also known as PDZ domain-containing RING finger protein 2, PDZRN2) and LNX2 (also known as PDZ domain-containing RING finger protein 1, PDZRN1), and related domains. LNX1 and LNX2 are Ring (Really Interesting New Gene) finger and PDZ domain-containing E3 ubiquitin ligases that bind to the cell fate determinant protein NUMB and mediate its ubiquitination. LNX1 can ubiquitinate a number of other ligands including PPFIA1, KLHL11, KIF7 and ERC2. LNX1 and LNX2 each have four PDZ domains. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This LNX family PDZ3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467167 [Multi-domain] Cd Length: 88 Bit Score: 48.02 E-value: 7.19e-07

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 569006111  221 CLGFNIRGGKEFGLG---IYVSKVD-HGGLAEENGIKVGDQVLAANGVRFDDISHSQAVEVLK---GQTHIML 286
Cdd:cd06679    12 SLGISVAGGRGSRRGdlpIYVTNVQpDGCLGRDGRIKKGDVLLSINGISLTNLSHSEAVAVLKasaASSSIVL 84

PDZ domain 1 of multi-PDZ-domain protein 1 (MUPP1) and PATJ (protein-associated tight junction), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of MUPP1 and PATJ, and related domains. MUPP1 and PATJ serve as scaffolding proteins linking different proteins and protein complexes involved in the organization of tight junctions and epithelial polarity. MUPP1 contains an L27 (Lin-2 and Lin-7 binding) domain and 13 PDZ domains. PATJ (also known as INAD-like) contains an L27 domain and ten PDZ domains. MUPP1 and PATJ share several binding partners, including junctional adhesion molecules (JAM), zonula occludens (ZO)-3, Pals1 (protein associated with Lin-7), Par (partitioning defective)-6 proteins, and nectins (adherence junction adhesion molecules). PATJ lacks 3 PDZ domains seen in MUPP1: PDZ6, 9, and 13; consequently, MUPP1 PDZ7 and 8 align with PATJ PDZ6 and 7; and MUPP1 PDZ domains 10-12 align with PATJ PDZ domains 8-10. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MUPP1-like family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467176 [Multi-domain] Cd Length: 102 Bit Score: 48.40 E-value: 7.30e-07

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 569006111  222 LGFNIRGGKEF---GLGIYVSKVDHGGLAEENG-IKVGDQVLAANGVRFD-DISHSQAVEVLK 279
Cdd:cd06689    28 LGFSVVGLKSEnrgELGIFVQEIQPGSVAARDGrLKENDQILAINGQPLDqSISHQQAIAILQ 90

PDZ domain of afadin (AFDN), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of afadin (AFDN, also known as ALL1-fused gene from chromosome 6 protein (AF6) and MLLT4), and related domains. AFDN belongs to the adhesion system, probably together with the E-cadherin-catenin system, that plays a role in the organization of homotypic, interneuronal, and heterotypic cell-cell adherens junctions. The AFDN PDZ domain interaction partners include poliovirus receptor-related protein PRR2/nectin, the junctional adhesion molecule (JAM), the breakpoint-cluster-region protein (BCR), connexin36 (Cx36), and a subset of Eph-related receptor tyrosine kinases; it can also bind low molecular weight ligands, in competition with a natural peptide ligand. Other AFDN-binding proteins have been identified. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This AFDN family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467251 [Multi-domain] Cd Length: 89 Bit Score: 48.05 E-value: 7.49e-07

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 569006111  858 TITLSKMKQSLGISISGGIESKVQPM-VKIEKIFPGGAAFLCGDLQAGFELVAVDGESLEQVTHQRAVD 925
Cdd:cd06789     5 TVTLKKVGNGMGLSIVAAKGAGQDKLgIYIKSVVKGGAADLDGRLQAGDQLLSVDGHSLVGLSQERAAE 73

PDZ domain 3 of human discs large homolog 1 (Dlg1), Dlg2, and Dlg4, Drosophila disc large (Dlg), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of Drosophila Dlg1, human Dlg1, 2, and 4 and related domains. Dlg1 (also known as synapse-associated protein Dlg197; SAP-97), Dlg2 (also known as channel-associated protein of synapse-110; postsynaptic density protein 93, PSD-93), Dlg4 (also known as postsynaptic density protein 95, PSD-95; synapse-associated protein 90, SAP-90) each have 3 PDZ domains and belong to the membrane-associated guanylate kinase family. Dlg1 regulates antigen receptor signaling and cell polarity in lymphocytes, B-cell proliferation and antibody production, and TGFalpha bioavailability; its PDZ3 domain binds pro-TGFalpha, and its PDZ2 domain binds the TACE metalloprotease responsible for cleaving pro-TGFalpha to a soluble form. Dlg2 is involved in N-methyl-D-aspartate (NMDA) receptor signaling, regulating surface expression of NMDA receptors in dorsal horn neurons of the spinal cord; it interacts with NMDA receptor subunits and with Shaker-type K+ channel subunits to cluster into a channel complex. The Dlg4 PDZ1 domain binds NMDA receptors, and its PDZ2 domain binds neuronal nitric oxide synthase (nNOS), forming a complex in neurons. The Drosophila Scribble complex (Scribble, Dlg, and lethal giant larvae) plays a role in apico-basal cell polarity, and in other forms of polarity, including regulation of the actin cytoskeleton, cell signaling and vesicular trafficking, and in tumor development; postsynaptic targeting of Drosophila DLG requires interactions mediated by the first two PDZ domains. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Dlg-like family PDZ3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467257 [Multi-domain] Cd Length: 91 Bit Score: 48.12 E-value: 7.59e-07

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 569006111   87 VRVEKSPSGrLGFSVRGGsEHGLGIFVSKVEEGSSAERAG-LCVGDKITEVNGLSLESTTMGSAVRLLTSS 156
Cdd:cd06795     5 IVLHKGSTG-LGFNIVGG-EDGEGIFISFILAGGPADLSGeLRRGDQILSVNGVDLRNATHEQAAAALKNA 73

PDZ domain; This entry represents the PDZ domain from a wide variety of proteins.

Pssm-ID: 436067 [Multi-domain] Cd Length: 54 Bit Score: 46.75 E-value: 8.60e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 569006111   112 FVSKVEEGSSAERAGLCVGDKITEVNGLSLesTTMGSAVRLLTSS--SCLHMMVRR 165
Cdd:pfam17820    1 VVTAVVPGSPAERAGLRVGDVILAVNGKPV--RSLEDVARLLQGSagESVTLTVRR 54

PDZ1 domain of Gallus gallus uncharacterized syntaxin-binding protein 4 (STXBP4) isoform X1, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of Gallus gallus uncharacterized syntaxin-binding protein 4 (STXBP4) isoform X1, and related domains. Gallus gallus STXBP4 isoform X1 contains 2 PDZ domains (PDZ1 and PDZ2). PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This STXBP4-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467179 [Multi-domain] Cd Length: 88 Bit Score: 47.22 E-value: 1.23e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 569006111   97 LGFSVRGG----SEHGLGIFVSKVEEGSSAERAG-LCVGDKITEVNGLSLESTTMGSAVRLL---TSSSCLHMMVRR 165
Cdd:cd06692    10 LGIKIIGGyrenTGEEFGIFIKRILPGGLAATDGrLKEGDLILEVNGESLQGVTNERAVSILrsaSASNHMSLLIAR 86

PDZ domain 6 of glutamate receptor-interacting protein 1 (GRIP1) and GRIP2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) binding proteins GRIP1 (ABP/GRIP2) and GRIP2, and related domains. GRIP1 and GRIP2 each have 7 PDZ domains. The interaction of GRIP1 and GRIP2 with GluA2/3 (AMPAR subunit) regulates AMPAR trafficking and synaptic targeting. GRIP1 has an essential role in regulating AMPAR trafficking during synaptic plasticity and learning and memory. GRIP1 and GRIP2 interact with a variety of other proteins associated with protein trafficking and internalization, for example GRIP1 also interacts with KIF5 (also known as kinesin 1), EphB receptors, scaffold protein liprin-alpha, and the rasGEF GRASP-1. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This GRIP family PDZ6 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467171 [Multi-domain] Cd Length: 85 Bit Score: 47.30 E-value: 1.29e-06

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 569006111   83 IIHAVRVEKSpSGRLGFSVRGGSEHGLGIFVSKVEEGSSAERAG-LCVGDKITEVNGLSLESTTMGSAVRLLTSSS 157
Cdd:cd06683     2 IIYTVELKRY-GGPLGITISGTEEPFDPIVISGLTEGGLAERTGaIHVGDRILAINGESLRGKPLSEAIHLLQNAG 76

PDZ domain 12 of multi-PDZ-domain protein 1 (MUPP1), PDZ domain 10 of protein-associated tight junction (PATJ, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 12 of MUPP1, PDZ domain 10 of PATJ, and related domains. MUPP1 and PATJ serve as scaffolding proteins linking different proteins and protein complexes involved in the organization of tight junctions and epithelial polarity. MUPP1 contains an L27 (Lin-2 and Lin-7 binding) domain and 13 PDZ domains. PATJ (also known as INAD-like) contains an L27 domain and ten PDZ domains. MUPP1 and PATJ share several binding partners, including junctional adhesion molecules (JAM), zonula occludens (ZO)-3, Pals1 (protein associated with Lin-7), Par (partitioning defective)-6 proteins, and nectins (adherence junction adhesion molecules). PATJ lacks 3 PDZ domains seen in MUPP1: PDZ6, 9, and 13; consequently, MUPP1 PDZ7 and 8 align with PATJ PDZ6 and 7; and MUPP1 PDZ domains 10-12 align with PATJ PDZ domains 8-10. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MUPP1-like PDZ12 family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F

Pssm-ID: 467163 [Multi-domain] Cd Length: 86 Bit Score: 47.36 E-value: 1.41e-06

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 569006111  209 RIVHLYTTSDDfCLGFNIRGGKEFGLG---IYVSKVDHGGLAEENG-IKVGDQVLAANGVRFDDISHSQAVEVLK 279
Cdd:cd06675     1 RTVEIKRGPQD-SLGISIAGGVGSPLGdvpVFIAMIQPNGVAAQTGkLKVGDRIVSINGQSTDGLTHSEAVNLLK 74

Predicted metalloprotease, contains C-terminal PDZ domain [General function prediction only];

Pssm-ID: 443174 [Multi-domain] Cd Length: 591 Bit Score: 52.13 E-value: 1.44e-06

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569006111   88 RVEKSPSGRLGFSVrggSEHGLGIFVSKVEEGSSAERAGLCVGDKITEVNGLSLESTTMGSAVRLLTSSSCLHMMVRRMG 167
Cdd:COG3975   476 EDAPSLKPSLGLRV---SADGGGLVVTSVLWGSPAYKAGLSAGDELLAIDGLRVTADNLDDALAAYKPGDPIELLVFRRD 552


                  ..
gi 569006111  168 RV 169
Cdd:COG3975   553 EL 554

PDZ domain of regulator of G-protein signaling 12 (RGS12), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of RGS12, and related domains. RGS12 downregulates GPCR signal transduction by increasing the GTPase activity of G-protein alpha subunits, thereby driving G-proteins into their inactive GDP-bound form. The RGS12 PDZ domain can bind selectively to C-terminal (A/S)-T-X-(L/V) motifs as found within both the CXCR2 IL-8 receptor, and the alternative 3' exon form of RGS12. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This RGS12-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467194 [Multi-domain] Cd Length: 76 Bit Score: 46.86 E-value: 1.48e-06

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 569006111   87 VRVEKSPSGrLGFSVRGGSEhglgIFVSKVEEGSSAERAGLCVGDKITEVNGLSLESTTMGSAVRLLTSSS-CLHMMV 163
Cdd:cd06710     3 VEIARGRAG-YGFTISGQAP----CVLSCVVRGSPADVAGLKAGDQILAVNGINVSKASHEDVVKLIGKCTgVLRLVI 75

PDZ domain 2 of Discs Large 5 (Dlg5) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of Drosophila and mammalian Dlg5, and related domains. Dlg5 is a scaffold protein with multiple conserved functions that are independent of each other in regulating growth, cell polarity, and cell adhesion. It has a coiled-coil domain, 4 PDZ domains and a MAGUK domain (an SH3 domain next to a non-catalytically active guanylate kinase domain). Deregulation of Dlg5 has been implicated in the malignancy of several cancer types. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Dlg5-like family PSZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467246 [Multi-domain] Cd Length: 77 Bit Score: 46.57 E-value: 1.58e-06

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 569006111  103 GGSEHGL----GIFVSKVEEGSSAERAG-LCVGDKITEVNGLSLESTTMGSAVRLLTSSS 157
Cdd:cd06765     6 GQKDSGIslenGVFISRIVPGSPAAKEGsLTVGDRIIAINGIALDNKSLSECEALLRSCR 65

PDZ domain 7 of PDZ domain containing 2 (PDZD2), PDZ domain 4 of human pro-interleukin-16 (isoform 1, 1332 AA), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 7 of PDZD2, also known as KIAA0300, PIN-1, PAPIN, activated in prostate cancer (AIPC) and PDZ domain-containing protein 3 (PDZK3). PDZD2 has seven PDZ domains. PDZD2 is expressed at exceptionally high levels in the pancreas and certain cancer tissues, such as prostate cancer. It promotes the proliferation of insulinoma cells and is upregulated during prostate tumorigenesis. In osteosarcoma (OS), the microRNA miR-363 acts as a tumor suppressor by inhibiting PDZD2. This family include the PDZ domain of the secreted mature form of human interleukin-16 (IL-16); this is the fourth PDZ domain (PDZ4) of human pro-interleukin-16 (isoform 1, also known as nPro-Il-16). Precursor IL-16 is cleaved to produce pro-IL-16 and C-terminal mature IL-16. Pro-IL-16 functions as a regulator of T cell growth; mature IL-16 is a CD4 ligand that induces chemotaxis and CD25 expression in CD4+ T cells. IL-16 bioactivity has been closely associated with the progression of several different cancers PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PDZD2-like family PDZ7 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467244 [Multi-domain] Cd Length: 86 Bit Score: 46.84 E-value: 1.58e-06

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                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 569006111  222 LGFNIRGGKEFGLG---IYVSKVDHGGLAEENG-IKVGDQVLAANGVRFDDISHSQAVEVLK 279
Cdd:cd06763    13 LGFSLEGGKGSPLGdrpLTIKRIFKGGAAEQSGvLQVGDEILQINGTSLQGLTRFEAWNIIK 74

PDZ domain 7 of multi-PDZ-domain protein 1 (MUPP1), PDZ domain 6 of PATJ (protein-associated tight junction) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 7 of MUPP1 and PDZ domain 6 of PATJ, and related domains. MUPP1 and PATJ serve as scaffolding proteins linking different proteins and protein complexes involved in the organization of tight junctions and epithelial polarity. MUPP1 contains an L27 (Lin-2 and Lin-7 binding) domain and 13 PDZ domains. PATJ (also known as INAD-like) contains an L27 domain and ten PDZ domains. MUPP1 and PATJ share several binding partners, including junctional adhesion molecules (JAM), zonula occludens (ZO)-3, Pals1 (protein associated with Lin-7), Par (partitioning defective)-6 proteins, and nectins (adherence junction adhesion molecules). PATJ lacks 3 PDZ domains seen in MUPP1: PDZ6, 9, and 13; consequently, MUPP1 PDZ7 and 8 align with PATJ PDZ6 and 7; and MUPP1 PDZ domains 10-12 align with PATJ PDZ domains 8-10. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MUPP1-like family PDZ7 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467159 [Multi-domain] Cd Length: 96 Bit Score: 47.32 E-value: 1.68e-06

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 569006111   87 VRVEKSPSGRLGFSVRGGSEHGL---------GIFVSKVEEGSSAERAG-LCVGDKITEVNGLSLESTTMGSAV 150
Cdd:cd06671     5 VELWREPGKSLGISIVGGRVMGSrlsngeeirGIFIKHVLEDSPAGRNGtLKTGDRILEVNGVDLRNATHEEAV 78

PDZ domain 2 of PDZ domain-containing RING finger protein 4 (PDZRN4), PDZRN3-B, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of PDZRN4, PDZRN3-B, and related domains. PDZRN4 (also known as ligand of numb protein X 4, and SEMACAP3-like protein) contains an N-terminal RING domain and two tandem repeat PDZ domains. It is involved in the progression of cancer, including human liver cancer and breast cancer, and may contribute to the tumorigenesis of rectal adenocarcinoma. Danio rerio PDZRN3-B may participate in neurogenesis: the first PDZ domain of Danio rerio Pdzrn3 interacts with Kidins220 (Kinase D-interacting substrate 220 kD, also named Ankyrin Repeat-Rich Membrane Spanning), a crucial mediator of signal transduction in neural tissues. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PDZRN4-like family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467200 [Multi-domain] Cd Length: 88 Bit Score: 46.88 E-value: 1.69e-06

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 569006111   91 KSPSGRLGFSV--RGGSEHGLGIFVSKVEEGSSAERAG-LCVGDKITEVNGlsLESTTMGSAVRLLTSS-SCLHMMVRR 165
Cdd:cd06716    11 SNSQEKLGLTLcyRTDDEEDTGIYVSEVDPNSIAAKDGrIREGDQILQING--VDVQNREEAIALLSEEeKSITLLVAR 87

PDZ domain of shroom2, shroom3, shroom4, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of shroom2, shroom3, shroom4, and related domains. Shroom family proteins shroom2 (also known as apical-like protein; protein APXL), shroom3 (also known as shroom-related protein), and shroom4 (also known as second homolog of apical protein) are essential regulators of cell morphology during animal development; they regulate cell architecture by directing the subcellular distribution and activation of Rho kinase (ROCK), which results in the localized activation of non-muscle myosin. The interaction between shroom and ROCK is mediated by the shroom domain 2 (SD2). PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This shroom2,3,4-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467232 [Multi-domain] Cd Length: 82 Bit Score: 46.95 E-value: 1.77e-06

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 569006111  223 GFNIRGGKEFGLGIYVSKVDHGGLAEENG-IKVGDQVLAANGVRFDDiSHSQAVEVLKGQTHIM-LTIK 289
Cdd:cd06750    14 GFTLKGGLEHGEPLVISKIEEGGKAASVGkLQVGDEVVNINGVPLSG-SRQEAIQLVKGSHKTLkLVVR 81

PDZ domain of shroom2, shroom3, shroom4, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of shroom2, shroom3, shroom4, and related domains. Shroom family proteins shroom2 (also known as apical-like protein; protein APXL), shroom3 (also known as shroom-related protein), and shroom4 (also known as second homolog of apical protein) are essential regulators of cell morphology during animal development; they regulate cell architecture by directing the subcellular distribution and activation of Rho kinase (ROCK), which results in the localized activation of non-muscle myosin. The interaction between shroom and ROCK is mediated by the shroom domain 2 (SD2). PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This shroom2,3,4-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467232 [Multi-domain] Cd Length: 82 Bit Score: 46.56 E-value: 2.24e-06

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gi 569006111  869 GISISGGIESKvQPMVkIEKIFPGGAAFLCGDLQAGFELVAVDGESLEQvTHQRAVDTIRRAYRNkarepMELVVR 944
Cdd:cd06750    14 GFTLKGGLEHG-EPLV-ISKIEEGGKAASVGKLQVGDEVVNINGVPLSG-SRQEAIQLVKGSHKT-----LKLVVR 81

PDZ domain 10 of multi-PDZ-domain protein 1 (MUPP1), domain 8 of PATJ (protein-associated tight junction) and similar domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 10 of MUPP1, PDZ domain 8 of PATJ, and related domains. MUPP1 and PATJ serve as scaffolding proteins linking different proteins and protein complexes involved in the organization of tight junctions and epithelial polarity. MUPP1 contains an L27 (Lin-2 and Lin-7 binding) domain and 13 PDZ domains. PATJ (also known as INAD-like) contains an L27 domain and ten PDZ domains. MUPP1 and PATJ share several binding partners, including junctional adhesion molecules (JAM), zonula occludens (ZO)-3, Pals1 (protein associated with Lin-7), Par (partitioning defective)-6 proteins, and nectins (adherence junction adhesion molecules). PATJ lacks 3 PDZ domains seen in MUPP1: PDZ6, 9, and 13; consequently, MUPP1 PDZ7 and 8 align with PATJ PDZ6 and 7; and MUPP1 PDZ domains 10-12 align with PATJ PDZ domains 8-10. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MUPP1-like family PDZ10 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467161 [Multi-domain] Cd Length: 86 Bit Score: 46.52 E-value: 2.39e-06

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569006111   86 AVRVEKSPSGrLGFSVRGGSEHGLG-IFVSKVEEGSSAERAG-LCVGDKITEVNGLSLESTTMGSAVRLLTSS-SCLHMM 162
Cdd:cd06673     5 TIEINKGKKG-LGLSIVGGSDTLLGaIIIHEVYEDGAAAKDGrLWAGDQILEVNGEDLRKATHDEAINVLRQTpQKVRLL 83


                  ...
gi 569006111  163 VRR 165
Cdd:cd06673    84 VYR 86

PDZ domain 2 of glutamate receptor-interacting protein 1 (GRIP1) and GRIP2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) binding proteins GRIP1 (ABP/GRIP2) and GRIP2, and related domains. GRIP1 and GRIP2 each have 7 PDZ domains. The interaction of GRIP1 and GRIP2 with GluA2/3 (AMPAR subunit) regulates AMPAR trafficking and synaptic targeting. GRIP1 has an essential role in regulating AMPAR trafficking during synaptic plasticity and learning and memory. GRIP1 and GRIP2 interact with a variety of other proteins associated with protein trafficking and internalization, for example GRIP1 also interacts with KIF5 (also known as kinesin 1), EphB receptors, scaffold protein liprin-alpha, and the rasGEF GRASP-1. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This GRIP family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467169 [Multi-domain] Cd Length: 89 Bit Score: 46.46 E-value: 2.44e-06

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 569006111  858 TITLSKMKQSLGISISGGI---ESKVQPMVkIEKIFPGGAAFLCGDLQAGFELVAVDGESLEQVTHQRAVDTIR 928
Cdd:cd06681     4 EVTLEKEGNSFGFVIRGGAhedRNKSRPLT-VTHVRPGGPADREGTIKPGDRLLSVDGISLHGATHAEAMSILK 76

PDZ domain 5 of protein tyrosine phosphatase non-receptor type 13 (PTPN13), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 5 of PTPN13 [also known as Fas-associated protein-tyrosine phosphatase 1 (FAP-1), Protein-tyrosine phosphatase 1E (PTP-E1), and Protein-tyrosine phosphatase (PTPL1)] and related domains. PTPN13 regulates negative apoptotic signaling and mediates phosphoinositide 3-kinase (PI3K) signaling. PTPN13 has five PDZ domains. Proteins known to interact with PTPN13 PDZ domains include: PLEKHA1 and PLEKHA2 via PTPN13-PDZ domain 1, Fas receptor and thyroid receptor-interacting protein 6 via PTPN13-PDZ domain 2, nerve growth factor receptor and protein kinase N2 via PTPN13-PDZ domain 3, PDZ and LIM domain 4 (PDLIM4) via PTPN13-PDZ domains 2 and 4, and brain calpain-2 via PTPN13-PDZ domains 3, 4 and 5. Calpain-2-mediated PTPN13 fragments may be involved in abnormal tau aggregation and increased risk for Alzheimer's disease. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PTPN13 family PDZ5 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467183 [Multi-domain] Cd Length: 87 Bit Score: 46.57 E-value: 2.51e-06

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 569006111  859 ITLSKMKQSLGISISGGIESKVQpMVKIEKIFPGGAAFLCGDLQAGFELVAVDGESLEQVTHQRAVDTIRRAYRN 933
Cdd:cd06697     6 ITLTCHPGQLGLKLTGGSDSKYQ-VIYVLEIVPGSAAAEEGSLQPLDIIHYINGVSTQGMTLEDAVRALEASLPT 79

PDZ domain of SH3 and multiple ankyrin repeat domains protein 1 (SHANK1), SHANK2, SHANK3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of SHANK1, SHANK2, SHANK3, and related domains. SHANK family proteins, SHANK1 (also known as somatostatin receptor-interacting protein, SSTR-interacting protein, SSTRIP), SHANK2 (also known as cortactin-binding protein 1, proline-rich synapse-associated protein 1), and SHANK3 (proline-rich synapse-associated protein 2) are synaptic scaffolding proteins which are highly enriched in the post-synaptic densities of excitatory synapses. They have been implicated in synaptic transmission, synapse formation, synaptic plasticity, and cytoskeletal remodeling, and are regulators of Cav1 calcium current and CREB target expression. Many protein ligands have been identified for the Shank PDZ domain, such as GKAP (also known as SAPAP), betaPIX (a guanine nucleotide exchange factor used by Rho GTPase family members Rac1 and Cdc42), alpha-latrotoxin, neuroligin, group I metabotropic glutamate receptors (mGluRs), and L-type calcium channels. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This SHANK-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta- strand F.

Pssm-ID: 467228 [Multi-domain] Cd Length: 101 Bit Score: 46.82 E-value: 2.52e-06

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gi 569006111  209 RIVHLYTTSDDFclGFNIRGGKEFGLGI------------YVSKVDHGGLAEENGIKVGDQVLAANGVRFDDISHSQAVE 276
Cdd:cd06746     7 RTVVLQKGDKGF--GFVLRGAKAVGPILeftptpafpalqYLESVDPGGVADKAGLKKGDFLLEINGEDVVKASHEQVVN 84

                          90
                  ....*....|...
gi 569006111  277 VLK-GQTHIMLTI 288
Cdd:cd06746    85 LIRqSGNTLVLKV 97

circularly permuted PDZ domain of high-temperature requirement factor A (HtrA) family serine proteases and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of HtrA family serine proteases including human HtrA1, HtrA2 (mitochondrial), HtrA3, and HtrA4, and related domains. These proteases are key enzymes associated with pregnancy. Their diverse biological functions include cell growth proliferation, migration and apoptosis. They are also implicated in disorders including Alzheimer's, Parkinson's, arthritis and cancer. HtrA1 (also known as high-temperature requirement A serine peptidase 1, L56, and serine protease 11) substrates include extracellular matrix proteins, proteoglycans, and insulin-like growth factor (IGF)-binding proteins. HtrA1 also inhibits signaling by members of the transforming growth factor beta (TGF-beta) family. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping of beta-strands. The canonical PDZ domain contains six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2); arranged as A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F. This HtrA-like PDZ domain is a circularly permuted PDZ domain which places beta-strand A on the C-terminus. Another permutation exists in the PDZ superfamily which places both beta-strands A and B on the C-terminus.

Pssm-ID: 467624 [Multi-domain] Cd Length: 98 Bit Score: 46.34 E-value: 3.16e-06

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                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 569006111  110 GIFVSKVEEGSSAERAGLCVGDKITEVNGLSLESTT-MGSAVRlltSSSCLHMMVRR 165
Cdd:cd06785    32 GVYVHKVIPGSPAQRAGLKDGDVIISINGKPVKSSSdVYEAVK---SGSSLLVVVRR 85

PDZ domain of PICK1 (protein interacting with C-kinase 1) and similar domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of PICK1, and related domains. PICK1 (also known as PRKCA-binding protein and protein kinase C-alpha-binding protein) plays a key role in regulating trafficking of binding partners by altering either their subcellular targeting and/or surface expression. PICK1 plays a role in synaptic plasticity by regulating the trafficking and internalization of amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors; the PICK1-PDZ domain binds the AMPA receptor subunits. The PICK1 PDZ domain also binds glutamate transporters, Eph receptors, metabotropic glutamate receptors, and ASICs (acid-sensing ion channels), among others. Clustering and synaptic targeting of PICK1 requires direct interaction between the PDZ domain and lipid membranes. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PICK-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta- strand F.

Pssm-ID: 467205 [Multi-domain] Cd Length: 84 Bit Score: 45.87 E-value: 3.86e-06

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gi 569006111  858 TITLSKMKQSL-GISISGGieSKVQPMVKIEKIFPGGAAFLCGDLQAGFELVAVDGESLEQVT 919
Cdd:cd06722     2 TVTLKKDAQNLiGISIGGG--APYCPCLYIVQVFDNTPAAKDGTLAAGDEIVGVNGKSVKGKT 62

PDZ domain of ARHGAP21 and ARHGAP23, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of ARHGAP21, ARHGAP23, and related domains. This subfamily includes the GAPs (GTPase activating proteins): ARHGAP21 (Rho GTPase-activating protein 21; also known as Rho GTPase-activating protein 10, Rho-type GTPase-activating protein 21) and ARHGAP23 (Rho GTPase-activating protein 23; also known as Rho-type GTPase-activating protein 23). GAPs deactivate Rho GTPases by accelerating GTP hydrolysis. ARHGAP21/23 interact with a planar cell polarity (PCP) protein Pk1 to regulate a lateral signaling pathway in migrating cells. The ARHGAP21 PDZ domain binds claudin-2. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This ARHGAP21-23-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467238 [Multi-domain] Cd Length: 109 Bit Score: 46.68 E-value: 3.97e-06

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gi 569006111  111 IFVSKVEEGSSAERAGLCVGDKITEVNGLSLESTTMGSAVRLLTSSS 157
Cdd:cd06756    55 IFVKQVKEGGPAHQAGLCTGDRIVKVNGESVIGKTYSQVIALIQNSD 101

PDZ domain of afadin (AFDN), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of afadin (AFDN, also known as ALL1-fused gene from chromosome 6 protein (AF6) and MLLT4), and related domains. AFDN belongs to the adhesion system, probably together with the E-cadherin-catenin system, that plays a role in the organization of homotypic, interneuronal, and heterotypic cell-cell adherens junctions. The AFDN PDZ domain interaction partners include poliovirus receptor-related protein PRR2/nectin, the junctional adhesion molecule (JAM), the breakpoint-cluster-region protein (BCR), connexin36 (Cx36), and a subset of Eph-related receptor tyrosine kinases; it can also bind low molecular weight ligands, in competition with a natural peptide ligand. Other AFDN-binding proteins have been identified. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This AFDN family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467251 [Multi-domain] Cd Length: 89 Bit Score: 46.13 E-value: 3.98e-06

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gi 569006111   94 SGRLGFSV---RGGSEHGLGIFVSKVEEGSSAERAG-LCVGDKITEVNGLSLESTTMGSAVRLLT-SSSCLHMMVRR 165
Cdd:cd06789    12 GNGMGLSIvaaKGAGQDKLGIYIKSVVKGGAADLDGrLQAGDQLLSVDGHSLVGLSQERAAELMTkTGSVVTLEVAK 88

PDZ domain 12 of multi-PDZ-domain protein 1 (MUPP1), PDZ domain 10 of protein-associated tight junction (PATJ, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 12 of MUPP1, PDZ domain 10 of PATJ, and related domains. MUPP1 and PATJ serve as scaffolding proteins linking different proteins and protein complexes involved in the organization of tight junctions and epithelial polarity. MUPP1 contains an L27 (Lin-2 and Lin-7 binding) domain and 13 PDZ domains. PATJ (also known as INAD-like) contains an L27 domain and ten PDZ domains. MUPP1 and PATJ share several binding partners, including junctional adhesion molecules (JAM), zonula occludens (ZO)-3, Pals1 (protein associated with Lin-7), Par (partitioning defective)-6 proteins, and nectins (adherence junction adhesion molecules). PATJ lacks 3 PDZ domains seen in MUPP1: PDZ6, 9, and 13; consequently, MUPP1 PDZ7 and 8 align with PATJ PDZ6 and 7; and MUPP1 PDZ domains 10-12 align with PATJ PDZ domains 8-10. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MUPP1-like PDZ12 family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F

Pssm-ID: 467163 [Multi-domain] Cd Length: 86 Bit Score: 45.82 E-value: 4.69e-06

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gi 569006111   86 AVRVEKSPSGRLGFSVRGGSEHGLG---IFVSKVEEGSSAERAG-LCVGDKITEVNGLSLESTTMGSAVRLLTSSS 157
Cdd:cd06675     2 TVEIKRGPQDSLGISIAGGVGSPLGdvpVFIAMIQPNGVAAQTGkLKVGDRIVSINGQSTDGLTHSEAVNLLKNAS 77

C-terminal processing protease CtpA/Prc, contains a PDZ domain [Posttranslational modification, protein turnover, chaperones];

Pssm-ID: 440556 [Multi-domain] Cd Length: 341 Bit Score: 49.87 E-value: 4.83e-06

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gi 569006111   95 GRLGFSVRggSEHGlGIFVSKVEEGSSAERAGLCVGDKITEVNGLSLESTTMGSAVRLL 153
Cdd:COG0793    60 GGLGAELG--EEDG-KVVVVSVIPGSPAEKAGIKPGDIILAIDGKSVAGLTLDDAVKLL 115

PDZ domain 2 of delphilin (L-delphilin isoform), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of delphilin (also known as glutamate receptor, ionotropic, delta 2-interacting protein 1, L-delphilin). Delphilin, a postsynaptic protein which it is selectively expressed at cerebellar Purkinje cells, links the glutamate receptor delta 2 subunit (GluRdelta2) with the actin cytoskeleton and various signaling molecules. Two alternatively spliced isoforms of delphilin have been characterized: L-delphilin has two PDZ domains, PDZ1 and PDZ2, and S-delphilin has a single PDZ domain (PDZ2). These two isoforms are differently palmitoylated and may be involved in controlling GluRdelta2 signaling in Purkinje cells. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This delphilin-like family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F

Pssm-ID: 467226 [Multi-domain] Cd Length: 75 Bit Score: 45.34 E-value: 5.29e-06

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gi 569006111  227 RGGKEFGLGI------YVSKVDHGGLAEENGIKVGDQVLAANGVRFDDISHSQAVEVLKG 280
Cdd:cd06744     6 RGNGSFGFTLrghapvYIESVDPGSAAERAGLKPGDRILFLNGLDVRNCSHDKVVSLLQG 65

PDZ domain 3 of PDZ domain containing 2 (PDZD2), PDZ domain 1 of human pro-interleukin-16 (isoform 1, 1332 AA), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of PDZD2, also known as KIAA0300, PIN-1, activated in prostate cancer (AIPC) and PDZ domain-containing protein 3 (PDZK3). PDZD2 has seven PDZ domains. PDZD2 is expressed at exceptionally high levels in the pancreas and certain cancer tissues, such as prostate cancer. It promotes the proliferation of insulinoma cells and is upregulated during prostate tumorigenesis. In osteosarcoma (OS), the microRNA miR-363 acts as a tumor suppressor by inhibiting PDZD2. This family also includes the first PDZ domain (PDZ1) of human pro-interleukin-16 (isoform 1, also known as nPro-Il-16; 1332 amino-acid protein). Precursor IL-16 is cleaved to produce pro-IL-16 and mature IL-16 (derived from the C-terminal 121 AA). Pro-IL-16 functions as a regulator of T cell growth; mature IL-16 is a CD4 ligand that induces chemotaxis and CD25 expression in CD4+ T cells. IL-16 bioactivity has been closely associated with the progression of several different cancers. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PDZD2-like family PDZ3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467240 [Multi-domain] Cd Length: 87 Bit Score: 45.34 E-value: 5.64e-06

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gi 569006111   85 HAVRVEKSPSGR-LGFSVRGG--SEHG-LGIFVSKV-EEGSSAERAGLCVGDKITEVNGLSLESTTMGSAV 150
Cdd:cd06759     1 STIVLMKGAGGKgLGFSIVGGrdSPRGpMGIYVKTIfPGGAAAEDGRLKEGDEILEVNGESLQGLTHQEAI 71

PDZ domain 10 of multi-PDZ-domain protein 1 (MUPP1), domain 8 of PATJ (protein-associated tight junction) and similar domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 10 of MUPP1, PDZ domain 8 of PATJ, and related domains. MUPP1 and PATJ serve as scaffolding proteins linking different proteins and protein complexes involved in the organization of tight junctions and epithelial polarity. MUPP1 contains an L27 (Lin-2 and Lin-7 binding) domain and 13 PDZ domains. PATJ (also known as INAD-like) contains an L27 domain and ten PDZ domains. MUPP1 and PATJ share several binding partners, including junctional adhesion molecules (JAM), zonula occludens (ZO)-3, Pals1 (protein associated with Lin-7), Par (partitioning defective)-6 proteins, and nectins (adherence junction adhesion molecules). PATJ lacks 3 PDZ domains seen in MUPP1: PDZ6, 9, and 13; consequently, MUPP1 PDZ7 and 8 align with PATJ PDZ6 and 7; and MUPP1 PDZ domains 10-12 align with PATJ PDZ domains 8-10. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MUPP1-like family PDZ10 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467161 [Multi-domain] Cd Length: 86 Bit Score: 45.36 E-value: 6.74e-06

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gi 569006111  222 LGFNIRGGKEFGLG-IYVSKVDHGGLAEENG-IKVGDQVLAANGVRFDDISHSQAVEVLKgQT 282
Cdd:cd06673    15 LGLSIVGGSDTLLGaIIIHEVYEDGAAAKDGrLWAGDQILEVNGEDLRKATHDEAINVLR-QT 76

PDZ domain 3 of Drosophila Scribble, human Scribble homolog, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of Drosophila Scribble (also known as LAP4), human Scribble homolog (also known as hScrib, LAP4, CriB1, ScrB1 and Vartul), and related domains. They belong to the LAP family, which describes proteins that contain either one or four PDZ domains and 16 LRRs (leucine-rich repeats) and function in controlling cell shape, size and subcellular protein localization. In Drosophila, the Scribble complex, comprising Scribble, discs large, and lethal giant larvae, plays a role in apico-basal cell polarity, in other forms of polarity, including regulation of the actin cytoskeleton, cell signaling and vesicular trafficking, and in tumor development. Mammalian Scribble is important in many aspects of cancer development. Scribble and its homologs can be downregulated or overexpressed in cancer; they have a role in cancer beyond their function in loss of cell polarity. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Scribble-like family PDZ3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467186 [Multi-domain] Cd Length: 89 Bit Score: 45.33 E-value: 6.89e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 569006111  859 ITLSKMKQSLGISISGGIESKVQPM------VKIEKIFPGGAAFLCGdLQAGFELVAVDGESLEQVTHQRAV 924
Cdd:cd06702     3 IHLVKAGGPLGLSIVGGSDHSSHPFgvdepgIFISKVIPDGAAAKSG-LRIGDRILSVNGKDLRHATHQEAV 73

C-terminal processing protease CtpA/Prc, contains a PDZ domain [Posttranslational modification, protein turnover, chaperones];

Pssm-ID: 440556 [Multi-domain] Cd Length: 341 Bit Score: 49.10 E-value: 7.37e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 569006111  224 FNIRGGKEF-GLGIYVSKVD---------HGGLAEENGIKVGDQVLAANGVRFDDISHSQAVEVLKGQ--THIMLTIK 289
Cdd:COG0793    51 FQESTSGEFgGLGAELGEEDgkvvvvsviPGSPAEKAGIKPGDIILAIDGKSVAGLTLDDAVKLLRGKagTKVTLTIK 128

PDZ domain 4 of Drosophila Scribble, human Scribble homolog, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 4 of Drosophila Scribble (also known as LAP4), human Scribble homolog (also known as hScrib, LAP4, CriB1, ScrB1 and Vartul), and related domains. They belong to the LAP family, which describes proteins that contain either one or four PDZ domains and 16 LRRs (leucine-rich repeats) and function in controlling cell shape, size and subcellular protein localization. In Drosophila, the Scribble complex, comprising Scribble, discs large, and lethal giant larvae, plays a role in apico-basal cell polarity, in other forms of polarity, including regulation of the actin cytoskeleton, cell signaling and vesicular trafficking, and in tumor development. Mammalian Scribble is important in many aspects of cancer development. Scribble and its homologs can be downregulated or overexpressed in cancer; they have a role in cancer beyond their function in loss of cell polarity. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Scribble-like family PDZ4 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467185 [Multi-domain] Cd Length: 98 Bit Score: 45.29 E-value: 7.59e-06

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 569006111  222 LGFNIRGG---------KEFGLGIYVSKVDHGGLAEENG-IKVGDQVLAANGVRFDDISHSQAVEVLKG 280
Cdd:cd06701    17 LGISIRGGakghagnplDPTDEGIFISKINPDGAAARDGrLKVGQRILEVNGQSLLGATHQEAVRILRS 85

PDZ domain of rhophilin-1, rhophilin-2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of rhophilin-1, rhophilin-2, and related domains. Rhophilin-1 (RHPN1, also known as GTP-Rho-binding protein 1) and rhophilin-2 (RHPN2, also known as GTP-Rho-binding protein 2) are Rho-GTP binding proteins involved in cytoskeletal dynamics. Rhophilin-2 inhibits RhoA's activity to induce F-actin stress fibers. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This rhophilin-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467196 [Multi-domain] Cd Length: 78 Bit Score: 44.88 E-value: 8.25e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 569006111   87 VRVEKSPSGrLGFSVRGGSEhglgIFVSKVEEGSSAERAGLCVGDKITEVNG 138
Cdd:cd06712     4 VHLTKEEGG-FGFTLRGDSP----VQVASVDPGSCAAEAGLKEGDYIVSVGG 50

PDZ domain 3 of partitioning defective 3 (Par3), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of Par3 (or PAR3 or Par-3, also known as Atypical PKC isotype-specific-interacting protein, ASIP, Drosophila Bazooka) and related domains. Par3 is a scaffold protein involved in organizing cell polarity across animals. Par3 binds numerous molecules both for its recruitment to one pole of the cell and for downstream contributions to polarized cell function. It regulates cell polarity by targeting the Par complex proteins Par6 and atypical protein kinase C (aPKC) to specific cortical sites. Physical interactions between Par-3 and the Par complex include Par3 PDZ domain 1 binding to the Par6 PDZ domain, Par3 PDZ domain 1 and PDZ domain 3 binding the Par6's PDZ-binding motif, and an interaction with an undefined region of aPKC that requires both Par3 PDZ2 and PDZ3. The PDZ domains of Par3 have also been implicated as potential phosphoinositide signaling integrators, since its second PDZ domain binds to phosphoinositides, and the third PDZ interacts with phosphoinositide phosphatase PTEN. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Par3 family PDZ3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467272 [Multi-domain] Cd Length: 103 Bit Score: 45.35 E-value: 9.07e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569006111   80 ESDIIHaVRVEKSPSGRLGFSVRG-------GSEHGLGIFVSKVEEGSSAERAG-LCVGDKITEVNGLSLESTTMGSAVR 151
Cdd:cd23059     2 EILTFE-IPLNDTGSAGLGVSVKGktskednGGKADLGIFIKSIIHGGAASKDGrLRVNDQLIAVNGESLLGLTNSEAME 80


                  ..
gi 569006111  152 LL 153
Cdd:cd23059    81 TL 82

Periplasmic serine protease, S1-C subfamily, contain C-terminal PDZ domain [Posttranslational modification, protein turnover, chaperones];

Pssm-ID: 440035 [Multi-domain] Cd Length: 274 Bit Score: 48.61 E-value: 9.52e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569006111   65 GRVILINSPIEANSDES---------DIIHAV--------RVEKspsGRLGFSVRG---------GSEHGLGIFVSKVEE 118
Cdd:COG0265   134 GEVIGINTAIISRSGGSqgigfaipiNLAKRVveqlietgRVRR---GWLGVTIQPvtpelaealGLPEPEGVLVARVEP 210

                          90       100
                  ....*....|....*....|
gi 569006111  119 GSSAERAGLCVGDKITEVNG 138
Cdd:COG0265   211 GSPAAKAGLRPGDVILAVDG 230

circularly permuted first PDZ domain (PDZ1) of Escherichia coli periplasmic serine endoprotease DegP and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of Escherichia coli DegP (also known as heat shock protein DegP and Protease Do) and related domains. DegP belongs to the HtrA family of housekeeping proteases. It acts as a protease, degrading transiently denatured and unfolded or misfolded proteins which accumulate in the periplasm following heat shock or other stress conditions, and as a molecular chaperone at low temperatures. DegP has two PDZ domains in addition to the protease domain; its PDZ1 domain is responsible for identifying the distinct substrate sequences that affect degradation (degron) of the substrate sequence, and its PDZ2 domain is responsible for combining with other DegP monomers to form a stable oligomer structure. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains and as well as those with circular permutations and domain swapping of beta-strands. The canonical PDZ domain contains six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2); arranged as A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F. This DegP family PDZ domain 1 is a circularly permuted PDZ domain which places beta-strand A on the C-terminus. Another permutation exists in the PDZ superfamily which places both beta-strands A and B on the C-terminus.

Pssm-ID: 467630 [Multi-domain] Cd Length: 91 Bit Score: 44.78 E-value: 9.55e-06

                          10        20
                  ....*....|....*....|....*....
gi 569006111  110 GIFVSKVEEGSSAERAGLCVGDKITEVNG 138
Cdd:cd10839    26 GALVAQVLPDSPAAKAGLKAGDVILSLNG 54

PDZ domain of neuronal nitric oxide synthase (nNOS), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of nNOS, and related domains. nNOS produces a key signaling molecule, nitric oxide (NO), which has diverse functions throughout the body and acts as a neurotransmitter and intracellular signaling molecule in the central and peripheral nervous system. nNOS is concentrated at synaptic junctions in the brain and motor endplates in skeletal muscle. The PDZ domain of neuronal nitric oxide synthase (nNOS) interacts with the PDZ domain of alpha1-syntrophin (in muscle cells) and with the second PDZ domain of Disks large homolog 4 (Dlg4, also known as PSD-95), and nitric oxide synthase 1 adaptor protein NOS1AP in neurons. Dlg4 binds NMDA receptors, and nNOS, forming a complex in neurons. NOS1AP competes with Dgl4 for the nNOS PDZ domain and prevents the coupling of nNos activation with NMDA receptor-mediated calcium influx. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This nNOS-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467192 [Multi-domain] Cd Length: 110 Bit Score: 45.45 E-value: 1.01e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 569006111  238 VSKVDHGGLAEENG-IKVGDQVLAANGVRFDDISHSQAVEVLKG---QTHIMLTIK 289
Cdd:cd06708    30 ISDLIRGGAAEQSGlVQVGDIILAVNGRPLVDVSYESALEVLRSipsETPVVLILR 85

circularly permuted PDZ domain of Bacillus subtilis HtrA-type serine proteases HtrA, HtrB, and YyxA and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of Bacillus subtilis HtrA/YkdA, HtrB/YvtA and YyxA/YycK, and related domains. HtrA-type serine proteases participate in folding and degradation of aberrant proteins, and in processing and maturation of native proteins. HtrA, HtrB, and YyxA have a single transmembrane domain at the N-terminus and a PDZ domain at the C-terminus. Expression of htrA and htrB genes is induced both by heat shock and by secretion stress (by a common) mechanism; yyxA is neither heat shock nor secretion stress inducible. HtrA and HtrB may have overlapping cellular functions; YyxA may have a cellular function distinct from the other two proteases or have the same function but under different conditions. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains and as well as those with circular permutations and domain swapping of beta-strands. The canonical PDZ domain contains six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2); arranged as A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F. This BsHtrA-like PDZ domain is a circularly permuted PDZ domain which places beta-strand A on the C-terminus. Another permutation exists in the PDZ superfamily which places both beta-strands A and B on the C-terminus.

Pssm-ID: 467622 [Multi-domain] Cd Length: 98 Bit Score: 44.93 E-value: 1.02e-05

                          10        20        30
                  ....*....|....*....|....*....|....*.
gi 569006111  110 GIFVSKVEEGSSAERAGLCVGDKITEVNGLSLESTT 145
Cdd:cd06781    31 GVYVAQVQSNSPAEKAGLKKGDVITKLDGKKVESSS 66

PDZ domain of ARHGEF11, ARHGEF12, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of ARHGEF11, ARHGEF12, and related domains. This subfamily includes the GEFs (guanine exchange factors) ARHGEF11 (Rho guanine nucleotide exchange factor 11, known as PDZ-RhoGEF) and ARHGEF12 (Rho guanine nucleotide exchange factor 12, also known as leukemia-associated RhoGEF). GEFs activate Rho GTPases by promoting GTP binding. ARHGEF11/12 are regulators of G protein signaling (RGS) domain-containing GEFs; the RGS domain mediates their binding to and activation of Galpha (and Gq also in the case of ARHGEF12), in response to G-protein coupled receptor activation. ARHGEF11 and 12 are involved in serum-signaling, and regulate Yes-Associated Protein (YAP1)-dependent transcription. The ARHGEF12 PDZ domain binds plexin-B1 and the receptor tyrosine kinase insulin-like growth factor receptor (IGF-R1) beta-subunit. ARHGEF12 also interacts with glutamate receptor delta-1(GluD1), a postsynaptic organizer of inhibitory synapses in cortical pyramidal neurons. The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This ARHGEF11-12-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467282 [Multi-domain] Cd Length: 76 Bit Score: 44.31 E-value: 1.10e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 569006111   87 VRVEKSPSGrLGFSVRGGSEhglgIFVSKVEEGSSAERAGLCVGDKITEVNGLSLESTTMGSAVRLLTSSSCLHMMV 163
Cdd:cd23069     4 VVIQRDENG-YGLTVSGDNP----VFVQSVKEGGAAYRAGVQEGDRIIKVNGTLVTHSNHLEVVKLIKSGSYVALTL 75

PDZ domain 6 of PDZ domain containing 2 (PDZD2), PDZ domain 3 of human pro-interleukin-16 (isoform 1, 1332 AA), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 6 of PDZD2, also known as KIAA0300, PIN-1, activated in prostate cancer (AIPC) and PDZ domain-containing protein 3 (PDZK3). PDZD2 has seven PDZ domains. PDZD2 is expressed at exceptionally high levels in the pancreas and certain cancer tissues, such as prostate cancer. It promotes the proliferation of insulinoma cells and is upregulated during prostate tumorigenesis. In osteosarcoma (OS), the microRNA miR-363 acts as a tumor suppressor by inhibiting PDZD2. This family also includes the third PDZ domain (PDZ3) of human pro-interleukin-16 (isoform 1, also known as nPro-IL-16). Precursor IL-16 is cleaved to produce pro-IL-16 and C-terminal mature IL-16. Pro-IL-16 functions as a regulator of T cell growth; mature IL-16 is a CD4 ligand that induces chemotaxis and CD25 expression in CD4+ T cells. IL-16 bioactivity has been closely associated with the progression of several different cancers. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PDZD2-like family PDZ6 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467243 [Multi-domain] Cd Length: 86 Bit Score: 44.56 E-value: 1.13e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 569006111  222 LGFNIRGG-----KEfglgIYVSKVDHGGLAEENG-IKVGDQVLAANGVRFDDISHSQAVEVLK 279
Cdd:cd06762    14 LGFSLAGGsdlenKS----ITVHRVFPSGLAAQEGtIQKGDRILSINGKSLKGVTHGDALSVLK 73

PDZ domain 7 of PDZ domain containing 2 (PDZD2), PDZ domain 4 of human pro-interleukin-16 (isoform 1, 1332 AA), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 7 of PDZD2, also known as KIAA0300, PIN-1, PAPIN, activated in prostate cancer (AIPC) and PDZ domain-containing protein 3 (PDZK3). PDZD2 has seven PDZ domains. PDZD2 is expressed at exceptionally high levels in the pancreas and certain cancer tissues, such as prostate cancer. It promotes the proliferation of insulinoma cells and is upregulated during prostate tumorigenesis. In osteosarcoma (OS), the microRNA miR-363 acts as a tumor suppressor by inhibiting PDZD2. This family include the PDZ domain of the secreted mature form of human interleukin-16 (IL-16); this is the fourth PDZ domain (PDZ4) of human pro-interleukin-16 (isoform 1, also known as nPro-Il-16). Precursor IL-16 is cleaved to produce pro-IL-16 and C-terminal mature IL-16. Pro-IL-16 functions as a regulator of T cell growth; mature IL-16 is a CD4 ligand that induces chemotaxis and CD25 expression in CD4+ T cells. IL-16 bioactivity has been closely associated with the progression of several different cancers PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PDZD2-like family PDZ7 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467244 [Multi-domain] Cd Length: 86 Bit Score: 44.53 E-value: 1.29e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 569006111   87 VRVEKSPSGrLGFSVRGGSEHGLG---IFVSKVEEGSSAERAG-LCVGDKITEVNGLSLESTT 145
Cdd:cd06763     4 VELEKGSAG-LGFSLEGGKGSPLGdrpLTIKRIFKGGAAEQSGvLQVGDEILQINGTSLQGLT 65

PDZ domain 3 of Zonula Occludens-1 (ZO-1), homologs ZO-2 and ZO-3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of ZO-1, -2, -3 and related domains. Zonula occludens proteins (ZO-1, ZO-2, ZO-3) are multi-PDZ domain proteins involved in the maintenance and biogenesis of multi-protein networks at the cytoplasmic surface of intercellular contacts in epithelial and endothelial cells. They have three N-terminal PDZ domains, PDZ1-3, followed by a Src homology-3 (SH3) domain and a guanylate kinase (GuK)-like domain. Among protein-protein interactions for all ZO proteins is the binding of the first PDZ domain (PDZ1) to the C-termini of claudins , and the homo- and hetero-dimerization of ZO-proteins via their second PDZ domain (PDZ2), which takes place by symmetrical domain swapping of the first two beta-strands of PDZ2. At the cell level, ZO-1 and ZO-2 are involved in polarity maintenance, gene transcription, cell proliferation, and tumor cell metastasis. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This ZO family PDZ3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467211 [Multi-domain] Cd Length: 82 Bit Score: 44.10 E-value: 1.34e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 569006111  222 LGFNIRGGKEfgLGIYVSKVDHGGLAEENGIKVGDQVLAANGVRFDDISHSQAVEVL 278
Cdd:cd06729    13 VGLRLAGGND--VGIFVAGVQEGSPAEKQGLQEGDQILKVNGVDFRNLTREEAVLFL 67

PDZ domain 1 of Zonula Occludens-1 (ZO-1), homologs ZO-2 and ZO-3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of ZO-1, -2, -3 and related domains. Zonula occludens proteins (ZO-1, ZO-2, ZO-3) are multi-PDZ domain proteins involved in the maintenance and biogenesis of multi-protein networks at the cytoplasmic surface of intercellular contacts in epithelial and endothelial cells. They have three N-terminal PDZ domains, PDZ1-3, followed by a Src homology-3 (SH3) domain and a guanylate kinase (GuK)-like domain. Among protein-protein interactions for all ZO proteins is the binding of the first PDZ domain (PDZ1) to the C-termini of claudins, and the homo- and hetero-dimerization of ZO-proteins via their second PDZ domain (PDZ2), which takes place by symmetrical domain swapping of the first two beta-strands of PDZ2. At the cell level, ZO-1 and ZO-2 are involved in polarity maintenance, gene transcription, cell proliferation, and tumor cell metastasis. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This ZO family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467209 [Multi-domain] Cd Length: 87 Bit Score: 44.57 E-value: 1.36e-05

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569006111  858 TITLSKM-KQSLGISISGGIESK----VQPMVKIEKIFPGGAAFlcGDLQAGFELVAVDGESLEQVTHQRAVDTIRrayr 932
Cdd:cd06727     2 TVTLHRApGFGFGIAVSGGRDNPhfqsGDTSIVISDVLKGGPAE--GKLQENDRVVSVNGVSMENVEHSFAVQILR---- 75

                          90
                  ....*....|..
gi 569006111  933 nKAREPMELVVR 944
Cdd:cd06727    76 -KCGKTANITVK 86

PDZ domain 1 of human Ligand of Numb protein X 1 (LNX1) and LNX2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of LNX1 (also known as PDZ domain-containing RING finger protein 2, PDZRN2) and LNX2 (also known as PDZ domain-containing RING finger protein 1, PDZRN1), and related domains. LNX1 and LNX2 are Ring (Really Interesting New Gene) finger and PDZ domain-containing E3 ubiquitin ligases that bind to the cell fate determinant protein NUMB and mediate its ubiquitination. LNX1 can ubiquitinate a number of other ligands including PPFIA1, KLHL11, KIF7 and ERC2. LNX1 and LNX2 each have four PDZ domains. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This LNX family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467165 [Multi-domain] Cd Length: 89 Bit Score: 44.54 E-value: 1.46e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 569006111  868 LGISISGGIESKVQPMVkIEKIFPGGAAFLCGDLQAGFELVAVDGESLEQVTHQRAVDTIRRAY 931
Cdd:cd06677    17 LGISIVGGNDTPLINIV-IQEVYRDGVIARDGRLLPGDQILEVNGVDISNVTHSQARSVLRQPC 79

PDZ domain 1 of human Ligand of Numb protein X 1 (LNX1) and LNX2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of LNX1 (also known as PDZ domain-containing RING finger protein 2, PDZRN2) and LNX2 (also known as PDZ domain-containing RING finger protein 1, PDZRN1), and related domains. LNX1 and LNX2 are Ring (Really Interesting New Gene) finger and PDZ domain-containing E3 ubiquitin ligases that bind to the cell fate determinant protein NUMB and mediate its ubiquitination. LNX1 can ubiquitinate a number of other ligands including PPFIA1, KLHL11, KIF7 and ERC2. LNX1 and LNX2 each have four PDZ domains. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This LNX family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467165 [Multi-domain] Cd Length: 89 Bit Score: 44.16 E-value: 1.66e-05

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gi 569006111  206 GVRRIVHLYTTSDDFCLGFNIRGGKEFGLG-IYVSKVDHGGLAEENG-IKVGDQVLAANGVRFDDISHSQAVEVLK 279
Cdd:cd06677     1 GEITTIEIHRSDPYEELGISIVGGNDTPLInIVIQEVYRDGVIARDGrLLPGDQILEVNGVDISNVTHSQARSVLR 76

PDZ domain 3 of membrane-associated guanylate kinase inverted 1 (MAGI-1), MAGI-2, and MAGI-3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of MAGI1, 2, 3 (MAGI is also known as Membrane-associated guanylate kinase, WW and PDZ domain-containing protein) and related domains. MAGI proteins have been implicated in the control of cell migration and invasion through altering the activity of phosphatase and tensin homolog (PTEN) and modulating Akt signaling. Four MAGI proteins have been identified (MAGI1-3 and MAGIX). MAGI1-3 have 6 PDZ domains and bind to the C-terminus of PTEN via their PDZ2 domain. MAGIX has a single PDZ domain that is related to MAGI1-3 PDZ domain 5. Other binding partners for MAGI1 include JAM4, C-terminal tail of high risk HPV-18 E6, megalin, TRAF6, Kir4.1 (basolateral K+ channel subunit), and cadherin 23; for MAGI2, include DASM1, dendrin, axin, beta- and delta-catenin, neuroligin, hyperpolarization-activated cation channels, beta1-adrenergic receptors, NMDA receptor, and TARPs; and for MAGI3 includes LPA2. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MAGI family PDZ3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2); arranged as beta-strands A, -B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467215 [Multi-domain] Cd Length: 85 Bit Score: 44.14 E-value: 1.77e-05

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gi 569006111  223 GFNIRGGKEFGLGIYVSKVDHGGLAEENG-IKVGDQVLAANGVRFDDISHSQAVEVLK---GQTHIMLTIK 289
Cdd:cd06733    14 GFRILGGTEEGSQVSIGAIVPGGAADLDGrLRTGDELLSVDGVNVVGASHHKVVDLMGnaaRNGQVNLTVR 84

PDZ domain of Rab3-interacting molecule 1 (RIM), RIM2, piccolo and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of RIM, RIM2, piccolo and related domains. RIM proteins and Gallus gallus protein piccolo (also called aczonin) are involved in neurotransmitter release at presynaptic active zones, the site of vesicle fusion. A protein complex containing RIM proteins positions synaptic vesicles containing synaptotagmin at the active zone. RIM proteins simultaneously activate docking and priming of synaptic vesicles and recruit Ca2+-channels to active zones, thereby connecting primed synaptic vesicles to Ca2+-channels. RIM binding to vesicular Rab proteins (Rab3 and Rab27 isoforms) mediates vesicle docking; RIM binding to Munc13 activates vesicle priming; RIM binding to the Ca2+-channel, both directly and indirectly via RIM-BP, recruits the Ca2+-channels. The RIM PDZ domain interacts with the C-termini of N- and P/Q-type voltage-gated Ca2+-channels. RIM1, RIM2 and piccolo also participate in regulated exocytosis through binding cAMP-GEFII (cAMP-binding protein-guanidine nucleotide exchange factor II). The piccolo PDZ domain binds cAMP-GEFII. RIM2 also plays a role in dendrite formation by melanocytes. Caenorhabditis elegans RIM (also known as unc-10) may be involved in the regulation of defecation and daumone response. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This RIM-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467198 [Multi-domain] Cd Length: 95 Bit Score: 44.08 E-value: 1.84e-05

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 569006111  222 LGFNIRGGKEFG---LGIYVSKVDHGGLAE-ENGIKVGDQVLAANGV-----RFDD----ISHSQA-VEVL 278
Cdd:cd06714    23 LGLKVVGGKMTEsgrLGAYVTKVKPGSVADtVGHLREGDEVLEWNGIslqgkTFEEvqdiISQSKGeVELV 93

PDZ domain of membrane palmitoylated proteins (MPPs), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of MPP1-7 (also known as MAGUK p55 subfamily members 1-7), and related domains. MPPs comprise a subfamily of a larger group of multidomain proteins, namely, membrane-associated guanylate kinases (MAGUKs). MPPs form diverse protein complexes at the cell membranes, which are involved in a wide range of cellular processes, including establishing proper cell structure, polarity and cell adhesion. MPPs have only one PDZ domain. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MPP1-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467208 [Multi-domain] Cd Length: 80 Bit Score: 43.79 E-value: 2.06e-05

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gi 569006111   87 VRVEKSPSGRLGFSVR--GGSehglgIFVSKVEEGSSAERAGLC-VGDKITEVNGLSLESTTMGSAVRLLTSSS 157
Cdd:cd06726     3 VEFEKARDEPLGATIKmeEDS-----VIVARILHGGMAHRSGLLhVGDEILEINGIPVSGKTVDELQKLLSSLS 71

PDZ domain 6 of multi-PDZ-domain protein 1 (MUPP1) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 6 of multi-PDZ-domain protein 1 (MUPP1). MUPP1 and PATJ serve as scaffolding proteins linking different proteins and protein complexes involved in the organization of tight junctions and epithelial polarity. MUPP1 contains an L27 (Lin-2 and Lin-7 binding) domain and 13 PDZ domains. PATJ (also known as INAD-like) contains an L27 domain and ten PDZ domains. PATJ lacks 3 PDZ domains seen in MUPP1: PDZ6, PDZ9, and PDZ13. This MuPP1-like PDZ6 domain is therefore absent from PATJ. MUPP1 and PATJ share several binding partners, including junctional adhesion molecules (JAM), zonula occludens (ZO)-3, Pals1 (protein associated with Lin-7), Par (partitioning defective)-6 proteins, and nectins (adherence junction adhesion molecules). PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MUPP1-like family PDZ6 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F

Pssm-ID: 467158 [Multi-domain] Cd Length: 87 Bit Score: 43.78 E-value: 2.10e-05

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gi 569006111  857 RTITLSKMKQSLGISISGgiESKVQPMVkIEKIFPGGAAFLCGDLQAGFELVAVDGESLEQVTHQRAVDTIRRA 930
Cdd:cd06670     5 RTITIVKGNSSLGITVSA--DKDGNGCI-VKSIIHGGAVSRDGRISVGDFIVSINNESLRNVTNAQARAILRRA 75

circularly permuted PDZ domain of C-terminal processing peptidase (CPP), a serine protease, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of CPP (also known as tail-specific protease, PRC protein, Protease Re, and Photosystem II D1 protein processing peptidase), and related domains. CPP belongs to the peptidase S41A family. It cleaves a C-terminal 11 residue peptide from the precursor form of penicillin-binding protein 3, and may have a role in protecting bacterium from thermal and osmotic stresses. In the plant chloroplast, the enzyme removes the C-terminal extension of the D1 polypeptide of photosystem II. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains and as well as those with circular permutations and domain swapping of beta-strands. The canonical PDZ domain contains six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2); arranged as A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F. This CPP-like PDZ domain is a circularly permuted PDZ domain which places beta-strand A on the C-terminus. Another permutation exists in the PDZ superfamily which places both beta-strands A and B on the C-terminus.

Pssm-ID: 467623 [Multi-domain] Cd Length: 88 Bit Score: 43.63 E-value: 2.40e-05

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gi 569006111  233 GLGIYVSKVDHGGL----------AEENGIKVGDQVLAANGVRFDDISHSQAVEVLKGQ--THIMLTIK 289
Cdd:cd06782     3 GIGIEIGKDDDGYLvvvspipggpAEKAGIKPGDVIVAVDGESVRGMSLDEVVKLLRGPkgTKVKLTIR 71

PDZ domain 7 of multi-PDZ-domain protein 1 (MUPP1), PDZ domain 6 of PATJ (protein-associated tight junction) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 7 of MUPP1 and PDZ domain 6 of PATJ, and related domains. MUPP1 and PATJ serve as scaffolding proteins linking different proteins and protein complexes involved in the organization of tight junctions and epithelial polarity. MUPP1 contains an L27 (Lin-2 and Lin-7 binding) domain and 13 PDZ domains. PATJ (also known as INAD-like) contains an L27 domain and ten PDZ domains. MUPP1 and PATJ share several binding partners, including junctional adhesion molecules (JAM), zonula occludens (ZO)-3, Pals1 (protein associated with Lin-7), Par (partitioning defective)-6 proteins, and nectins (adherence junction adhesion molecules). PATJ lacks 3 PDZ domains seen in MUPP1: PDZ6, 9, and 13; consequently, MUPP1 PDZ7 and 8 align with PATJ PDZ6 and 7; and MUPP1 PDZ domains 10-12 align with PATJ PDZ domains 8-10. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MUPP1-like family PDZ7 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467159 [Multi-domain] Cd Length: 96 Bit Score: 43.85 E-value: 2.50e-05

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gi 569006111  221 CLGFNIRGGKEFGL---------GIYVSKVDHGGLAEENG-IKVGDQVLAANGVRFDDISHSQAVEVLK 279
Cdd:cd06671    14 SLGISIVGGRVMGSrlsngeeirGIFIKHVLEDSPAGRNGtLKTGDRILEVNGVDLRNATHEEAVEAIR 82

PDZ domain of Drosophila melanogaster PDZ and LIM domain protein Zasp52 (also known as Zasp), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of Drosophila melanogaster Zasp52 and related domains. Drosophila melanogaster Zasp52 (also known as Z band alternatively spliced PDZ-motif protein or Zasp) colocalizes with integrins at myotendinous junctions and with alpha-actinin at Z-disks and is required for muscle attachment as well as Z-disk assembly and maintenance. The Zasp52 actin-binding site includes the extended PDZ domain and the ZM region. The Zasp52-PDZ domain is required for myofibril assembly. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Zasp52-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467281 [Multi-domain] Cd Length: 82 Bit Score: 43.29 E-value: 2.50e-05

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gi 569006111  858 TITLSKM--KQSLGISISGGIESKvQPMVkIEKIFPGGAAFLCGdLQAGFELVAVDGESLEQVTHQRAVDTIRRA 930
Cdd:cd23068     1 NIRLRRDdsNTPWGFRLQGGADFG-QPLS-IQKVNPGSPADKAG-LRRGDVILRINGTDTSNLTHKQAQDLIKRA 72

PDZ domain 4 of human Ligand of Numb protein X 1 (LNX1) and LNX2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 4 of LNX1 (also known as PDZ domain-containing RING finger protein 2, PDZRN2)and LNX2 (also known as PDZ domain-containing RING finger protein 1, PDZRN1), and related domains. LNX1 and LNX2 are Ring (Really Interesting New Gene) finger and PDZ domain-containing E3 ubiquitin ligases that bind to the cell fate determinant protein NUMB and mediate its ubiquitination. LNX1 can ubiquitinate a number of other ligands including PPFIA1, KLHL11, KIF7 and ERC2. LNX1 and LNX2 each have four PDZ domains. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This LNX family PDZ4 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467168 [Multi-domain] Cd Length: 89 Bit Score: 43.49 E-value: 2.61e-05

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gi 569006111  857 RTITLSKMKQ-SLGISISGGIESK--VQPmVKIEKIFPGGAAFLCGDLQAGFELVAVDGESLEQVTHQRAVDTIRR 929
Cdd:cd06680     1 KDITLRRSSSgSLGFSIVGGYEEShgNQP-FFVKSIVPGTPAYNDGRLKCGDIILAVNGVSTVGMSHAALVPLLKE 75

PDZ domain 7 of multi-PDZ-domain protein 1 (MUPP1), PDZ domain 6 of PATJ (protein-associated tight junction) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 7 of MUPP1 and PDZ domain 6 of PATJ, and related domains. MUPP1 and PATJ serve as scaffolding proteins linking different proteins and protein complexes involved in the organization of tight junctions and epithelial polarity. MUPP1 contains an L27 (Lin-2 and Lin-7 binding) domain and 13 PDZ domains. PATJ (also known as INAD-like) contains an L27 domain and ten PDZ domains. MUPP1 and PATJ share several binding partners, including junctional adhesion molecules (JAM), zonula occludens (ZO)-3, Pals1 (protein associated with Lin-7), Par (partitioning defective)-6 proteins, and nectins (adherence junction adhesion molecules). PATJ lacks 3 PDZ domains seen in MUPP1: PDZ6, 9, and 13; consequently, MUPP1 PDZ7 and 8 align with PATJ PDZ6 and 7; and MUPP1 PDZ domains 10-12 align with PATJ PDZ domains 8-10. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MUPP1-like family PDZ7 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467159 [Multi-domain] Cd Length: 96 Bit Score: 43.85 E-value: 2.81e-05

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gi 569006111  857 RTITLSK-MKQSLGISISGG--IESKVQPMVKIEKIF-----PGGAAFLCGDLQAGFELVAVDGESLEQVTHQRAVDTIR 928
Cdd:cd06671     3 RRVELWRePGKSLGISIVGGrvMGSRLSNGEEIRGIFikhvlEDSPAGRNGTLKTGDRILEVNGVDLRNATHEEAVEAIR 82

                          90
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gi 569006111  929 rayrnKAREPMELVV 943
Cdd:cd06671    83 -----NAGNPVVFLV 92

PDZ domain of segment polarity protein dishevelled homolog DVL1, DVL2, DVL3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of DVL1-3, and related domains. The dishevelleds (DVL1, 2 and 3 in humans) act downstream of Frizzled (FZD) receptors in both the canonical and non-canonical WNT signaling pathway; they bind the cytoplasmic C-terminus of frizzled family members and transduce the Wnt signal to down-stream effectors. They bind to several proteins known to modulate Wnt signaling. Binding partners of the DVL1 PDZ domain include nucleoredoxin (NXN), Van Gogh-like (VANGL1), Wnt receptor RYK, Dapper 1 (DACT1), Frizzled7 (FZD7), transmembrane protein 88 (TMEM88), Daple (dishevelled-associating protein with a high frequency of leucines), also known as Ccdc88c), and cysteine-rich protein Idax. The DVL2 PDZ domain has been shown to bind the nuclear export signal sequence of the DVL2 protein. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This DVL-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467201 [Multi-domain] Cd Length: 87 Bit Score: 43.51 E-value: 2.82e-05

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gi 569006111  868 LGISISGGIESKVQPMVKIEKIFPGGAAFLCGDLQAGFELVAVDGESLEQVTHQRAVDTIRRAYrnKAREPMELVV 943
Cdd:cd06717    12 LGISIVGQSNERGDGGIYVGSIMKGGAVAADGRIEPGDMILQVNDISFENMSNDDAVRVLREAV--HKPGPITLTV 85

PDZ domain of densin, erbin, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of densin, erbin, and related domains. Densin (also known as leucine-rich repeat-containing protein 7, LRRC7, densin-180, protein LAP1) and erbin (also known as densin-180-like protein, Erbb2-interacting protein, protein LAP2) belong to the LAP (leucine-rich repeat and PDZ domain) family of scaffolding proteins that play roles in the maintenance of cell shape and apical-basal polarity. Densin and erbin are components of the excitatory postsynaptic compartment and are regulators of dendritic morphology and postsynaptic structure. The densin PDZ domain binds CaV1.3 alpha1 subunit, delta-catenin, and MAGUIN-1. Binding partners of the erbin PDZ domain include ErbB receptor tyrosine kinase ErbB2, HTLV-1 Tax1, Cav1.3 Ca2+channels, and constituents of the cadherin:catenin cell adhesion complex, in particular delta-catenin, p0071 and ARVCF. The erbin PDZ domain binds Smad3, a transductor of the TGFbeta pathway, possibly by a novel interface of binding. Erbin and two other LAP proteins (scribble and lano) redundantly regulate epithelial polarity and apical adhesion complex. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This densin and erbin-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467231 [Multi-domain] Cd Length: 87 Bit Score: 43.47 E-value: 2.84e-05

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gi 569006111  868 LGISISGGIESKVQPM------VKIEKIFPGGAAflCGDLQAGFELVAVDGESLEQVTHQRAVDTIRRAYRnkarePMEL 941
Cdd:cd06749    11 LGFSISGGIGSQGNPFrpdddgIFVTKVQPDGPA--SKLLQPGDKILEVNGYDFVNIEHGQAVSLLKSFQN-----TVDL 83


                  ...
gi 569006111  942 VVR 944
Cdd:cd06749    84 VVE 86

PDZ domain of the microtubule-associated serine-threonine (MAST) protein kinase family; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of MAST family kinases, including MAST1-4. These MAST proteins contain a DUF1908 domain, a serine/threonine kinase domain, a AGC-kinase C-terminal domain, and a PDZ domain; MAST family member MASTL is a shorter protein lacking the PDZ domain. The PDZ domain gives the MAST family the capacity to scaffold its own kinase activity. These kinases are implicated in the inhibition of neurite outgrowth and regeneration in cultured cells. Their binding partners include microtubules, beta2-syntrophin, TNF receptor-associated factor 6 (TRAF6), cAMP-regulated phosphoprotein (ARPP-16), and PTEN. This family also includes Caenorhabditis elegans KIN-4 MAST kinase, a key longevity factor acting through binding PTEN phosphatase, and Drosophila Drop out which regulates dynein-dependent transport during embryonic development. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MAST-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467189 [Multi-domain] Cd Length: 93 Bit Score: 43.77 E-value: 2.98e-05

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gi 569006111   89 VEKSPSGrLGFSVR------GGSE----HGLgifVSKVEEGSSAERAGLCVGDKITEVNGLSLESTTMGSAVRLLTSSS 157
Cdd:cd06705     7 IKKGPRG-FGFTLRairvyiGDSDvytvHHL---VTAVEEGSPAYEAGLRPGDLITHVNGEPVQGLLHTQVVQLILKGG 81

PDZ domain of tamalin, cytohesin-1-interacting protein (CYTIP), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of tamalin, cytohesin-1-interacting protein, and related domains. Tamalin (trafficking regulator and scaffold protein tamalin, also known as general receptor for phosphoinositides 1-associated scaffold protein, GRASP) functions to link receptors, including group 1 metabotropic glutamate receptors (mGluRs), to neuronal proteins. The tamalin PDZ domain binds the C-terminal domains of group I mGluRs; it also binds potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2 (HCN2), neurotrophin-3 (NT3) TrkCT1-truncated receptor, SAP90/PSD-95-associated protein, and tamalin itself. CYTIP (cytohesin-1-interacting protein, also known as Pleckstrin homology Sec7 and coiled-coil domain-binding protein) sequesters cytohesin-1 in the cytoplasm, limiting its interaction with beta2 integrins; cytohesin-1 binds the CYTIP coiled coil domain. The CYTIP PDZ domain can bind the C-terminal peptide of protocadherin alpha-1 (PCDHA1), indicating a possible interaction between the two. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This tamalin-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467197 [Multi-domain] Cd Length: 91 Bit Score: 43.38 E-value: 3.08e-05

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569006111  857 RTITLSKM-KQSLGISI-SGGIESKVQPMVK----IEKIFPGGAAFLCGdLQAGFELVAVDGESLEQVTHQRAVDTIRRA 930
Cdd:cd06713     4 RTIILEKQdNETFGFEIqTYGLHHKNSNEVEmctyVCRVHEDSPAYLAG-LTAGDVILSVNGVSVEGASHQEIVELIRSS 82

PDZ domain 9 of multi-PDZ-domain protein 1 (MUPP1) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 9 of MUPP1. MUPP1 and PATJ serve as scaffolding proteins linking different proteins and protein complexes involved in the organization of tight junctions and epithelial polarity. MUPP1 contains an L27 (Lin-2 and Lin-7 binding) domain and 13 PDZ domains. PATJ (also known as INAD-like) contains an L27 domain and ten PDZ domains. PATJ lacks 3 PDZ domains seen in MUPP1: PDZ6, PDZ9, and PDZ13. This MuPP1-like PDZ9 domain is therefore absent from PATJ. MUPP1 and PATJ share several binding partners, including junctional adhesion molecules (JAM), zonula occludens (ZO)-3, Pals1 (protein associated with Lin-7), Par (partitioning defective)-6 proteins, and nectins (adherence junction adhesion molecules). PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MUPP1-like family PDZ9 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467263 [Multi-domain] Cd Length: 79 Bit Score: 43.11 E-value: 3.31e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 569006111  858 TITLSKMKQSLGISISggiESKVQPMVKIEKIFPGGAAFLCGDLQAGFELVAVDGESLEQVTHQRAVDTIRRA 930
Cdd:cd10817     1 HVELPKDQGGLGIAIS---EEDTENGIVIKSLTEGGPAAKDGRLKVGDQILAVDDESVVGCPYEKAISLLKTA 70

PDZ domain of rhophilin-1, rhophilin-2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of rhophilin-1, rhophilin-2, and related domains. Rhophilin-1 (RHPN1, also known as GTP-Rho-binding protein 1) and rhophilin-2 (RHPN2, also known as GTP-Rho-binding protein 2) are Rho-GTP binding proteins involved in cytoskeletal dynamics. Rhophilin-2 inhibits RhoA's activity to induce F-actin stress fibers. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This rhophilin-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467196 [Multi-domain] Cd Length: 78 Bit Score: 42.96 E-value: 3.48e-05

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 569006111  209 RIVHLYTTSDDFclGFNIRGGKEfglgIYVSKVDHGGLAEENGIKVGDQVLAANGVRFDDISHSQAVEVLKG 280
Cdd:cd06712     2 RTVHLTKEEGGF--GFTLRGDSP----VQVASVDPGSCAAEAGLKEGDYIVSVGGVDCKWSKHSEVVKLLKS 67

circularly permuted PDZ domain of C-terminal processing peptidase (CPP), a serine protease, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of CPP (also known as tail-specific protease, PRC protein, Protease Re, and Photosystem II D1 protein processing peptidase), and related domains. CPP belongs to the peptidase S41A family. It cleaves a C-terminal 11 residue peptide from the precursor form of penicillin-binding protein 3, and may have a role in protecting bacterium from thermal and osmotic stresses. In the plant chloroplast, the enzyme removes the C-terminal extension of the D1 polypeptide of photosystem II. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains and as well as those with circular permutations and domain swapping of beta-strands. The canonical PDZ domain contains six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2); arranged as A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F. This CPP-like PDZ domain is a circularly permuted PDZ domain which places beta-strand A on the C-terminus. Another permutation exists in the PDZ superfamily which places both beta-strands A and B on the C-terminus.

Pssm-ID: 467623 [Multi-domain] Cd Length: 88 Bit Score: 43.24 E-value: 3.69e-05

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 569006111  110 GIFVSKVEEGSSAERAGLCVGDKITEVNGLSLESTTMGSAVRLL 153
Cdd:cd06782    15 YLVVVSPIPGGPAEKAGIKPGDVIVAVDGESVRGMSLDEVVKLL 58

PDZ domain 1 of delphilin (L-delphilin isoform), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of delphilin (also known as glutamate receptor, ionotropic, delta 2-interacting protein 1, L-delphilin). Delphilin, a postsynaptic protein which is selectively expressed at cerebellar Purkinje cells, links the glutamate receptor delta 2 subunit (GluRdelta2) with the actin cytoskeleton and various signaling molecules. Two alternatively spliced isoforms of delphilin have been characterized: L-delphilin has two PDZ domains, PDZ1 and PDZ2, and S-delphilin has a single PDZ domain (PDZ2). These two isoforms are differently palmitoylated and may be involved in controlling GluRdelta2 signaling in Purkinje cells. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This delphilin-like family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467225 [Multi-domain] Cd Length: 76 Bit Score: 42.65 E-value: 3.69e-05

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                  ....*....|....*....|....*....|....*....|....
gi 569006111   95 GRLGFSVRGGSEhglgIFVSKVEEGSSAERAGLCVGDKITEVNG 138
Cdd:cd06743     9 EAFGFSIGGSGP----CYILSVEEGSSAHAAGLQPGDQILELDG 48

PDZ domain of Rap guanine nucleotide exchange factor 2 and Rap guanine nucleotide exchange factor 6, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of Rap guanine nucleotide exchange factor 2 (RapGEF2, also named RA-GEF-1, PDZ-GEF1, CNrasGEF and nRapGEP) and Rap guanine nucleotide exchange factor 6 (RapGEF6, also named RA-GEF-2 and PDZ-GEF2). RapGEF2 and RapGEF6 constitute a subfamily of guanine nucleotide exchange factors (GEFs) for RAP small GTPases that is characterized by the possession of the PDZ and Ras/Rap-associating domains. They activate Rap small GTPases, by catalyzing the release of GDP from the inactive GDP-bound forms, thereby accelerating GTP loading to yield the active GTP-bound forms. The PDZ domain of RapGEF6 (also known as PDZ-GEF2) binds junctional adhesion molecule A (JAM-A). PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This RapGEF2 and RapGEF6 family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467237 [Multi-domain] Cd Length: 83 Bit Score: 43.02 E-value: 4.25e-05

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 569006111  857 RTITLSKMKQ--SLGISISGGIESKVqpMVKIEKIFPGGAAFLCGdLQAGFELVAVDGESLEQVTHQRAVDTIR 928
Cdd:cd06755     1 RTVTLTRPSResPLHFSLLGGSEKGF--GIFVSKVEKGSKAAEAG-LKRGDQILEVNGQNFENITLKKALEILR 71

PDZ domain 2 of human Ligand of Numb protein X 1 (LNX1) and LNX2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of LNX1 (also known as PDZ domain-containing RING finger protein 2, PDZRN2) and LNX2 (also known as PDZ domain-containing RING finger protein 1, PDZRN1), and related domains. LNX1 and LNX2 are Ring (Really Interesting New Gene) finger and PDZ domain-containing E3 ubiquitin ligases that bind to the cell fate determinant protein NUMB and mediate its ubiquitination. LNX1 can ubiquitinate a number of other ligands including PPFIA1, KLHL11, KIF7 and ERC2. LNX1 and LNX2 each have four PDZ domains. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This LNX family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467166 [Multi-domain] Cd Length: 82 Bit Score: 42.62 E-value: 4.90e-05

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569006111   87 VRVEKSPSGRLGFS-VRGGSEHGlgIFVSKVEEGSSAERAG-LCVGDKITEVNGLSLESTTMGSAVRLL-TSSSCLHMMV 163
Cdd:cd06678     3 VTLNKRDGEQLGIKlVRKKDEPG--VFILDLLEGGLAARDGrLKSDDRVLAINGQDLRHGTPEQAAQIIqASGERVHFVV 80


                  ..
gi 569006111  164 RR 165
Cdd:cd06678    81 SR 82

PDZ domain 1 of human Ligand of Numb protein X 1 (LNX1) and LNX2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of LNX1 (also known as PDZ domain-containing RING finger protein 2, PDZRN2) and LNX2 (also known as PDZ domain-containing RING finger protein 1, PDZRN1), and related domains. LNX1 and LNX2 are Ring (Really Interesting New Gene) finger and PDZ domain-containing E3 ubiquitin ligases that bind to the cell fate determinant protein NUMB and mediate its ubiquitination. LNX1 can ubiquitinate a number of other ligands including PPFIA1, KLHL11, KIF7 and ERC2. LNX1 and LNX2 each have four PDZ domains. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This LNX family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467165 [Multi-domain] Cd Length: 89 Bit Score: 42.62 E-value: 5.25e-05

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 569006111   91 KSPSGRLGFSVRGGSEHGLG-IFVSKV-EEGSSAERAGLCVGDKITEVNGLSLESTTMGSAVRLLTS-SSCLHMMVRR 165
Cdd:cd06677    11 SDPYEELGISIVGGNDTPLInIVIQEVyRDGVIARDGRLLPGDQILEVNGVDISNVTHSQARSVLRQpCPVLRLTVLR 88

PDZ domain of Drosophila melanogaster PDZ and LIM domain protein Zasp52 (also known as Zasp), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of Drosophila melanogaster Zasp52 and related domains. Drosophila melanogaster Zasp52 (also known as Z band alternatively spliced PDZ-motif protein or Zasp) colocalizes with integrins at myotendinous junctions and with alpha-actinin at Z-disks and is required for muscle attachment as well as Z-disk assembly and maintenance. The Zasp52 actin-binding site includes the extended PDZ domain and the ZM region. The Zasp52-PDZ domain is required for myofibril assembly. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Zasp52-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467281 [Multi-domain] Cd Length: 82 Bit Score: 42.52 E-value: 5.37e-05

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                  ....*....|....*....|....*....|....*....|.
gi 569006111   98 GFSVRGGSEHGLGIFVSKVEEGSSAERAGLCVGDKITEVNG 138
Cdd:cd23068    14 GFRLQGGADFGQPLSIQKVNPGSPADKAGLRRGDVILRING 54

permuted PDZ domain of Deg/high-temperature requirement factor A (HtrA) family of housekeeping serine proteases and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of Deg/HtrA-type serine proteases that participate in folding and degradation of aberrant proteins, and in processing and maturation of native proteins. Typically, these proteases have an N-terminal serine protease domain and at least one C-terminal PDZ domain that recognizes substrates, and in some cases activates the protease function. An exception is yeast Nma11p which has two protease domains and four PDZ domains; its N-terminal half is comprised of a protease domain, followed by two PDZ domains, and its C-terminal half has a similar domain arrangement. HtrA-type proteases include the human HtrA1-4 and MBTPS2, tricorn protease, DegS, DegP and C-terminal processing peptidase, cyanobacterial serine proteases Hhoa, HhoB, and HtrA, and yeast Nma11p. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-termini of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains and as well as those with circular permutations and domain swapping of beta-strands. The canonical PDZ domain contains six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2); arranged as A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F. This Deg/HtrA family PDZ domain is a circularly permuted PDZ domain which places beta-strand A at the C-terminus. Another permutation exists in the PDZ superfamily which places both beta-strands A and B on the C-terminus.

Pssm-ID: 467621 [Multi-domain] Cd Length: 91 Bit Score: 42.67 E-value: 5.54e-05

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                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 569006111  110 GIFVSKVEEGSSAERAGLCVGDKITEVNGLSLESTT-MGSAVRLLTSSSCLHMMVRRMGR 168
Cdd:cd06779    26 GVLVAEVIPGSPAAKAGLKEGDVILSVNGKPVTSFNdLRAALDTKKPGDSLNLTILRDGK 85

PDZ domain 6 of glutamate receptor-interacting protein 1 (GRIP1) and GRIP2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) binding proteins GRIP1 (ABP/GRIP2) and GRIP2, and related domains. GRIP1 and GRIP2 each have 7 PDZ domains. The interaction of GRIP1 and GRIP2 with GluA2/3 (AMPAR subunit) regulates AMPAR trafficking and synaptic targeting. GRIP1 has an essential role in regulating AMPAR trafficking during synaptic plasticity and learning and memory. GRIP1 and GRIP2 interact with a variety of other proteins associated with protein trafficking and internalization, for example GRIP1 also interacts with KIF5 (also known as kinesin 1), EphB receptors, scaffold protein liprin-alpha, and the rasGEF GRASP-1. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This GRIP family PDZ6 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467171 [Multi-domain] Cd Length: 85 Bit Score: 42.68 E-value: 5.94e-05

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                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 569006111  222 LGFNIRGGKEFGLGIYVSKVDHGGLAEENG-IKVGDQVLAANGVRFDDISHSQAVEVL 278
Cdd:cd06683    15 LGITISGTEEPFDPIVISGLTEGGLAERTGaIHVGDRILAINGESLRGKPLSEAIHLL 72

PDZ domain 2 of partitioning defective 3 (Par3), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of Par3 (or PAR3 or Par-3, also known as Atypical PKC isotype-specific-interacting protein, ASIP, Drosophila Bazooka) and related domains. Par3 is a scaffold protein involved in organizing cell polarity across animals. Par3 binds numerous molecules both for its recruitment to one pole of the cell and for downstream contributions to polarized cell function. It regulates cell polarity by targeting the Par complex proteins Par6 and atypical protein kinase C (aPKC) to specific cortical sites. Physical interactions between Par3 and the Par complex include Par3 PDZ domain 1 binding to the Par6 PDZ domain, Par3 PDZ domain 1 and PDZ domain 3 binding the Par6's PDZ-binding motif, and an interaction with an undefined region of aPKC that requires both Par3 PDZ2 and PDZ3. The PDZ domains of Par3 have also been implicated as potential phosphoinositide signaling integrators, since its second PDZ domain binds to phosphoinositides, and the third PDZ interacts with phosphoinositide phosphatase PTEN. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Par3 family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467271 [Multi-domain] Cd Length: 93 Bit Score: 42.63 E-value: 6.45e-05

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569006111  852 STGALRTITLSKMKQSLGISISggieSKVQPM-----VKIEKIFPGGAAFLCGDLQAGFELVAVDGESLEQVTHQRAVDT 926
Cdd:cd23058     1 KIGKKLHIQLKKGPEGLGFSIT----SRDNPTggsgpIYIKNILPKGAAIQDGRLKAGDRLLEVNGVDVTGKTQEEVVSL 76

                          90
                  ....*....|....*..
gi 569006111  927 IRRAyrnKAREPMELVV 943
Cdd:cd23058    77 LRST---KLGGTVSLVV 90

PDZ domain of Rab3-interacting molecule 1 (RIM), RIM2, piccolo and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of RIM, RIM2, piccolo and related domains. RIM proteins and Gallus gallus protein piccolo (also called aczonin) are involved in neurotransmitter release at presynaptic active zones, the site of vesicle fusion. A protein complex containing RIM proteins positions synaptic vesicles containing synaptotagmin at the active zone. RIM proteins simultaneously activate docking and priming of synaptic vesicles and recruit Ca2+-channels to active zones, thereby connecting primed synaptic vesicles to Ca2+-channels. RIM binding to vesicular Rab proteins (Rab3 and Rab27 isoforms) mediates vesicle docking; RIM binding to Munc13 activates vesicle priming; RIM binding to the Ca2+-channel, both directly and indirectly via RIM-BP, recruits the Ca2+-channels. The RIM PDZ domain interacts with the C-termini of N- and P/Q-type voltage-gated Ca2+-channels. RIM1, RIM2 and piccolo also participate in regulated exocytosis through binding cAMP-GEFII (cAMP-binding protein-guanidine nucleotide exchange factor II). The piccolo PDZ domain binds cAMP-GEFII. RIM2 also plays a role in dendrite formation by melanocytes. Caenorhabditis elegans RIM (also known as unc-10) may be involved in the regulation of defecation and daumone response. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This RIM-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467198 [Multi-domain] Cd Length: 95 Bit Score: 42.54 E-value: 6.53e-05

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gi 569006111   61 SSPMGRVILinspieaNSDESDiihavrveKSPSGR-LGFSVRGG--SEHG-LGIFVSKVEEGSSAERAG-LCVGDKITE 135
Cdd:cd06714     1 DFLIGRIIL-------QRDPKD--------GSVSGNgLGLKVVGGkmTESGrLGAYVTKVKPGSVADTVGhLREGDEVLE 65

                          90
                  ....*....|
gi 569006111  136 VNGLSLESTT 145
Cdd:cd06714    66 WNGISLQGKT 75

PDZ domain 2 of glutamate receptor-interacting protein 1 (GRIP1) and GRIP2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) binding proteins GRIP1 (ABP/GRIP2) and GRIP2, and related domains. GRIP1 and GRIP2 each have 7 PDZ domains. The interaction of GRIP1 and GRIP2 with GluA2/3 (AMPAR subunit) regulates AMPAR trafficking and synaptic targeting. GRIP1 has an essential role in regulating AMPAR trafficking during synaptic plasticity and learning and memory. GRIP1 and GRIP2 interact with a variety of other proteins associated with protein trafficking and internalization, for example GRIP1 also interacts with KIF5 (also known as kinesin 1), EphB receptors, scaffold protein liprin-alpha, and the rasGEF GRASP-1. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This GRIP family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467169 [Multi-domain] Cd Length: 89 Bit Score: 42.61 E-value: 6.56e-05

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 569006111  218 DDFCLGFNIRGG--KEFGLG--IYVSKVDHGGLAEENG-IKVGDQVLAANGVRFDDISHSQAVEVLK 279
Cdd:cd06681    10 EGNSFGFVIRGGahEDRNKSrpLTVTHVRPGGPADREGtIKPGDRLLSVDGISLHGATHAEAMSILK 76

PDZ domain 1 and PDZ domain 3 of Drosophila bazooka (DmPar3), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 and 3 of Drosophila bazooka (DmPar3), and related domains. The Par complex comprises atypical protein kinase C (aPKC) and two scaffolding proteins, Par3 (Bazooka (Baz) in Drosophila) and Par6; bazooka (DmPar3) has three central PDZ domains. Both PDZ1 and PDZ3 domains, but not PDZ2, in bazooka (DmPar3) engage in a canonical interaction with the PDZ domain-binding motif in Par6. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This bazooka-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467154 [Multi-domain] Cd Length: 87 Bit Score: 42.34 E-value: 7.30e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 569006111   97 LGFSVRGGSEHGLGIFVSKVEEGSSAERAGLCVGDKITEVNGLSL----ESTTMGSAVRLLTSS 156
Cdd:cd06665    15 LGLTALPDKEHGGGLLVQHVEPGSRAERGRLRRDDRILEINGIKLigltESQVQEQLRRALESS 78

PDZ domain 3 of human Ligand of Numb protein X 1 (LNX1) and LNX2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of LNX1 (also known as PDZ domain-containing RING finger protein 2, PDZRN2) and LNX2 (also known as PDZ domain-containing RING finger protein 1, PDZRN1), and related domains. LNX1 and LNX2 are Ring (Really Interesting New Gene) finger and PDZ domain-containing E3 ubiquitin ligases that bind to the cell fate determinant protein NUMB and mediate its ubiquitination. LNX1 can ubiquitinate a number of other ligands including PPFIA1, KLHL11, KIF7 and ERC2. LNX1 and LNX2 each have four PDZ domains. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This LNX family PDZ3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467167 [Multi-domain] Cd Length: 88 Bit Score: 42.24 E-value: 7.99e-05

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 569006111   87 VRVEKSPSGRLGFSVRGGSEHGLG---IFVSKVEEGSSAERAG-LCVGDKITEVNGLSLESTTMGSAVRLLTSSS 157
Cdd:cd06679     3 VTIKKEPSESLGISVAGGRGSRRGdlpIYVTNVQPDGCLGRDGrIKKGDVLLSINGISLTNLSHSEAVAVLKASA 77

PDZ domain 3 of membrane-associated guanylate kinase inverted 1 (MAGI-1), MAGI-2, and MAGI-3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of MAGI1, 2, 3 (MAGI is also known as Membrane-associated guanylate kinase, WW and PDZ domain-containing protein) and related domains. MAGI proteins have been implicated in the control of cell migration and invasion through altering the activity of phosphatase and tensin homolog (PTEN) and modulating Akt signaling. Four MAGI proteins have been identified (MAGI1-3 and MAGIX). MAGI1-3 have 6 PDZ domains and bind to the C-terminus of PTEN via their PDZ2 domain. MAGIX has a single PDZ domain that is related to MAGI1-3 PDZ domain 5. Other binding partners for MAGI1 include JAM4, C-terminal tail of high risk HPV-18 E6, megalin, TRAF6, Kir4.1 (basolateral K+ channel subunit), and cadherin 23; for MAGI2, include DASM1, dendrin, axin, beta- and delta-catenin, neuroligin, hyperpolarization-activated cation channels, beta1-adrenergic receptors, NMDA receptor, and TARPs; and for MAGI3 includes LPA2. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MAGI family PDZ3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2); arranged as beta-strands A, -B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467215 [Multi-domain] Cd Length: 85 Bit Score: 42.21 E-value: 8.24e-05

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569006111   87 VRVEKSPSGrLGFSVRGGSEHGLGIFVSKVEEGSSAERAG-LCVGDKITEVNGLSLESTTMGSAVRLLTSSS---CLHMM 162
Cdd:cd06733     4 VFLRRQETG-FGFRILGGTEEGSQVSIGAIVPGGAADLDGrLRTGDELLSVDGVNVVGASHHKVVDLMGNAArngQVNLT 82


                  ...
gi 569006111  163 VRR 165
Cdd:cd06733    83 VRR 85

PDZ domain of afadin (AFDN), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of afadin (AFDN, also known as ALL1-fused gene from chromosome 6 protein (AF6) and MLLT4), and related domains. AFDN belongs to the adhesion system, probably together with the E-cadherin-catenin system, that plays a role in the organization of homotypic, interneuronal, and heterotypic cell-cell adherens junctions. The AFDN PDZ domain interaction partners include poliovirus receptor-related protein PRR2/nectin, the junctional adhesion molecule (JAM), the breakpoint-cluster-region protein (BCR), connexin36 (Cx36), and a subset of Eph-related receptor tyrosine kinases; it can also bind low molecular weight ligands, in competition with a natural peptide ligand. Other AFDN-binding proteins have been identified. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This AFDN family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467251 [Multi-domain] Cd Length: 89 Bit Score: 42.27 E-value: 8.64e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 569006111  222 LGFNI---RGGKEFGLGIYVSKVDHGGLAEENG-IKVGDQVLAANGVRFDDISHSQAVEVLkGQT--HIMLTI 288
Cdd:cd06789    15 MGLSIvaaKGAGQDKLGIYIKSVVKGGAADLDGrLQAGDQLLSVDGHSLVGLSQERAAELM-TKTgsVVTLEV 86

PDZ domain of tax1-binding protein 3 (TAX1BP3), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of TAX1BP3, and related domains. TAX1BP3 (also known as glutaminase-interacting protein 3, tax interaction protein 1, TIP-1, tax-interacting protein 1) may regulate a number of protein-protein interactions by competing for PDZ domain binding sites. TAX1BP3 binds beta-catenin and may act as an inhibitor of the Wnt signaling pathway. It competes with LIN7A (also known as Lin-7A or LIN-7A) for inward rectifier potassium channel 4 (KCNJ4) binding, and thereby promotes KCNJ4 internalization. It may play a role in the Rho signaling pathway, and in the activation of CDC42 by the viral protein HPV16 E6. Binding partners of the TAX1BP3 PDZ domain include beta-catenin, KCNJ4, glutaminase liver isoform (GLS2), rho guanine nucleotide exchange factor 16 (ARHGEF16), rhotekin, and CDK5 regulatory subunit-associated protein 3 (also known as LAPZ). PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This TAX1BP3-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467265 [Multi-domain] Cd Length: 94 Bit Score: 42.32 E-value: 9.98e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569006111  859 ITLSKMKQS----LGISISGGIE--------SKVQPMVKIEKIFPGGAAFLCGdLQAGFELVAVDGESLEQVTHQRAVDT 926
Cdd:cd10822     2 IEIHKLRQGenliLGFSIGGGIDqdpsknpfSYTDKGIYVTRVSEGGPAEKAG-LQVGDKILQVNGWDMTMVTHKQAVKR 80


                  ...
gi 569006111  927 IRR 929
Cdd:cd10822    81 LTK 83

PDZ domain 3 of inactivation-no-after-potential D (INAD), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of INAD, and related domains. INAD assembles key enzymes of the Drosophila compound eye photo-transduction pathway into a supramolecular complex, supporting efficient and fast light signaling. It contains 5 PDZ domains arranged in tandem (PDZ1-PDZ5) which independently bind various proteins. INAD PDZ2 binds eye-specific protein kinase C, INAD PDZ3 binds transient receptor potential (TRP) channel, and INAD PDZ4,5 tandem binds NORPA (phospholipase Cbeta, PLCbeta). Mutations of the inaD gene that lead to disruption of each of these interactions impair fly photo signal transduction. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This INAD-like family PDZ3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467277 [Multi-domain] Cd Length: 80 Bit Score: 41.93 E-value: 1.02e-04

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                  ....*....|....*....|....*....|....*....|....*....|..
gi 569006111  105 SEHGLGIFVSKVEEGSSAERAGLCVGDKITEVNGLSLESTTMGSAVRLLTSS 156
Cdd:cd23064    20 AEVGSGIFISDLREGSNAELAGVKVGDMLLAVNQDVTLESNYDDATGLLKRA 71

PDZ domain 3 of multi-PDZ-domain protein 1 (MUPP1) and PATJ (protein-associated tight junction) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of MUPP1 and PATJ, and related domains. MUPP1 and PATJ serve as scaffolding proteins linking different proteins and protein complexes involved in the organization of tight junctions and epithelial polarity. MUPP1 contains an L27 (Lin-2 and Lin-7 binding) domain and 13 PDZ domains. PATJ (also known as INAD-like) contains an L27 domain and ten PDZ domains. MUPP1 and PATJ share several binding partners, including junctional adhesion molecules (JAM), zonula occludens (ZO)-3, Pals1 (protein associated with Lin-7), Par (partitioning defective)-6 proteins, and nectins (adherence junction adhesion molecules). PATJ lacks 3 PDZ domains seen in MUPP1: PDZ6, 9, and 13; consequently, MUPP1 PDZ7 and 8 align with PATJ PDZ6 and 7; and MUPP1 PDZ domains 10-12 align with PATJ PDZ domains 8-10. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MUPP1-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467253 [Multi-domain] Cd Length: 89 Bit Score: 41.83 E-value: 1.06e-04

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 569006111   84 IHAVRVEKSPSGrLGFSVRG-----GSEHGLGIFVSKVEEGSSAERAG-LCVGDKITEVNGLSLESTTMGSAVRLLTSS 156
Cdd:cd06791     2 TFEVELVKDEQG-LGITIAGyvgekASGELSGIFVKSIIPGSAADQDGrIQVNDQIIAVDGVNLQGFTNQEAVEVLRNT 79

PDZ domain of segment polarity protein dishevelled homolog DVL1, DVL2, DVL3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of DVL1-3, and related domains. The dishevelleds (DVL1, 2 and 3 in humans) act downstream of Frizzled (FZD) receptors in both the canonical and non-canonical WNT signaling pathway; they bind the cytoplasmic C-terminus of frizzled family members and transduce the Wnt signal to down-stream effectors. They bind to several proteins known to modulate Wnt signaling. Binding partners of the DVL1 PDZ domain include nucleoredoxin (NXN), Van Gogh-like (VANGL1), Wnt receptor RYK, Dapper 1 (DACT1), Frizzled7 (FZD7), transmembrane protein 88 (TMEM88), Daple (dishevelled-associating protein with a high frequency of leucines), also known as Ccdc88c), and cysteine-rich protein Idax. The DVL2 PDZ domain has been shown to bind the nuclear export signal sequence of the DVL2 protein. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This DVL-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467201 [Multi-domain] Cd Length: 87 Bit Score: 41.97 E-value: 1.13e-04

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                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 569006111   97 LGFSVRGGSEHGL--GIFVSKVEEGSSAERAG-LCVGDKITEVNGLSLESTTMGSAVRLL 153
Cdd:cd06717    12 LGISIVGQSNERGdgGIYVGSIMKGGAVAADGrIEPGDMILQVNDISFENMSNDDAVRVL 71

PDZ domain of tamalin, cytohesin-1-interacting protein (CYTIP), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of tamalin, cytohesin-1-interacting protein, and related domains. Tamalin (trafficking regulator and scaffold protein tamalin, also known as general receptor for phosphoinositides 1-associated scaffold protein, GRASP) functions to link receptors, including group 1 metabotropic glutamate receptors (mGluRs), to neuronal proteins. The tamalin PDZ domain binds the C-terminal domains of group I mGluRs; it also binds potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2 (HCN2), neurotrophin-3 (NT3) TrkCT1-truncated receptor, SAP90/PSD-95-associated protein, and tamalin itself. CYTIP (cytohesin-1-interacting protein, also known as Pleckstrin homology Sec7 and coiled-coil domain-binding protein) sequesters cytohesin-1 in the cytoplasm, limiting its interaction with beta2 integrins; cytohesin-1 binds the CYTIP coiled coil domain. The CYTIP PDZ domain can bind the C-terminal peptide of protocadherin alpha-1 (PCDHA1), indicating a possible interaction between the two. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This tamalin-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467197 [Multi-domain] Cd Length: 91 Bit Score: 41.84 E-value: 1.17e-04

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gi 569006111  237 YVSKVDHGGLAEENGIKVGDQVLAANGVRFDDISHSQAVEVLK--GQTHIMLTI 288
Cdd:cd06713    38 YVCRVHEDSPAYLAGLTAGDVILSVNGVSVEGASHQEIVELIRssGNTLRLETL 91

PDZ domain of Ras-associating and dilute domain-containing protein (Radil) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of Radil (also known as protein KIAA1849) and related domains. Radil is required for cell adhesion and migration of neural crest precursors during development. Radil is a component of a Rasip1-Radil-ARHGAP29 complex at endothelial cell-cell junctions. Rap1, via its effectors Radil and Rasip1 and their binding partner ArhGAP29, controls the endothelial barrier by decreasing Rho-mediated radial tension on cell-cell junctions. ArhGAP29 binds the Radil PDZ domain. The Radil PDZ domain also binds kinesin family protein 14 (KIF14); KIF14 negatively regulates Rap1-mediated inside-out integrin activation by tethering Radil on microtubules. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Radil-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467177 [Multi-domain] Cd Length: 88 Bit Score: 41.89 E-value: 1.18e-04

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gi 569006111  858 TITLSKMKQSLGISISGGIESKVQ-PMVKIEKIFPGGAAFLCGDLQAGFELVAVDGESLEQVTHQRAVDTIRRA 930
Cdd:cd06690     5 VVELERGPKGLGLGLIDGLHTPLRsPGIYIRTLVPDSPAARDGRLRLGDRILAVNGTSLVGADYQSAMDLIRTS 78

PDZ domain of caspase recruitment domain-containing protein 11 (CARD11), CARD14, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of CARD11, CARD14, and related domains. CARD11 (also known as CARD-containing MAGUK protein 1, CARMA1, Bimp3) and CARD14 (also known as CARD-containing MAGUK protein 2, CARMA2, Bimp2) belong to the CARD-containing membrane-associated guanylate kinase (MAGUK) protein family. They play several crucial biological functions, including regulation of immune response and inflammation. The CARD11-Bcl10-MALT1 (CBM) complex bridges T cell receptor signaling to the canonical IkappaB kinase (IKK)/NF-kappaB pathway. CARD14 can form an analogous biochemical complex to activate NF-kappaB during specialized immunity. The CBM complex of CARD14/CARMA2 may bind with TRAF6 and get involved in IL-17 pathways in keratinocytes. The preponderance of protein interactions occurs through the N-terminal half of CARD11 that includes the CARD, LATCH, and coiled-coil domains; the C-terminal PDZ-SH3-MAGUK region binds the adhesion and degranulation-promoting adapter protein (ADAP) and aryl hydrocarbon receptor interacting protein (AIP). PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This CARD11 and CARD14-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467218 [Multi-domain] Cd Length: 75 Bit Score: 41.48 E-value: 1.20e-04

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                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 569006111  100 SVRGGSEHGlgIFVSKVEEGSSAERAGLCVGDKITEVNG--------LSLESTTMGSAVRLL 153
Cdd:cd06736    14 TIIGGNRTG--IFIHSVQPGSAAEKAGLREGTQLLLLEGcirgerqsVSLEDCTKEEAHWTL 73

circularly permuted second PDZ domain (PDZ2) of Escherichia coli periplasmic serine endoprotease DegP and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of Escherichia coli DegP (also known as heat shock protein DegP and Protease Do), and related domains. DegP belongs to the HtrA family of housekeeping proteases. It acts as a protease, degrading transiently denatured and unfolded or misfolded proteins which accumulate in the periplasm following heat shock or other stress conditions, and as a molecular chaperone at low temperatures. DegP has two PDZ domains in addition to the protease domain; its PDZ1 domain is responsible for the identifying the distinct substrate sequences that affect degradation (degron) of the substrate sequence, and its PDZ2 domain is responsible for the combining with other DegP monomers to form a stable oligomer structure. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains and as well as those with circular permutations and domain swapping of beta-strands. The canonical PDZ domain contains six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2); arranged as A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F. This DegP family PDZ domain 2 is a circularly permuted PDZ domain which places beta-strand A on the C-terminus. Another permutation exists in the PDZ superfamily which places both beta-strands A and B on the C-terminus.

Pssm-ID: 467631 [Multi-domain] Cd Length: 83 Bit Score: 41.46 E-value: 1.24e-04

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gi 569006111   94 SGRLGFSVRGGSEHGL--GIFVSKVEEGSSAERAGLCVGDKITEVNGLSLES 143
Cdd:cd23084     1 LALEGATVSNVTDEDGgkGVVVTEVDPGSPAAQSGLKKGDVIIGVNRQPVKS 52

PDZ domain 7 of glutamate receptor-interacting protein 1 (GRIP1) and GRIP2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) binding proteins GRIP1 (ABP/GRIP2) and GRIP2, and related domains. GRIP1 and GRIP2 each have 7 PDZ domains. The interaction of GRIP1 and GRIP2 with GluA2/3 (AMPAR subunit) regulates AMPAR trafficking and synaptic targeting. GRIP1 has an essential role in regulating AMPAR trafficking during synaptic plasticity and learning and memory. GRIP1 and GRIP2 interact with a variety of other proteins associated with protein trafficking and internalization, for example GRIP1 also interacts with KIF5 (also known as kinesin 1), EphB receptors, scaffold protein liprin-alpha, and the rasGEF GRASP-1. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This GRIP family PDZ7 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467173 [Multi-domain] Cd Length: 85 Bit Score: 41.47 E-value: 1.37e-04

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gi 569006111   84 IHAVRVEKSPSGR-LGFSVRGG-SEHGlgIFVSKVEEGSSAERAGLCVGDKITEVNGLSLESTTMGSAVRLLTSS-SCLH 160
Cdd:cd06685     3 LHKVTLYKDSDTEdFGFSVSDGlYEKG--VYVNAIRPGGPADLSGLQPYDRILQVNHVRTRDFDCCLVVPLIAESgDKLE 80


                  ....*
gi 569006111  161 MMVRR 165
Cdd:cd06685    81 LVVSR 85

PDZ domain 1 of FERM and PDZ domain-containing protein 2 (FRMPD2), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of FRMPD2 (also known as PDZ domain-containing protein 4, and related domains. FRMPD2 is localized in the basolateral membranes of polarized epithelial cells and is associated with tight junction formation and immune response; it contains 3 PDZ domains. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PTPN13 family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467284 [Multi-domain] Cd Length: 92 Bit Score: 41.71 E-value: 1.45e-04

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gi 569006111  222 LGFNIRGGKEFG---LGIYVSKVDHGGLAEENG-IKVGDQVLAANGVRFDDISHSQAVEVLK 279
Cdd:cd23071    15 FGFVIVGGENTGkldLGIFIASIIPGGPAEKDGrIKPGGRLISLNNISLEGVTFNTAVKILQ 76

PDZ domain 4 of glutamate receptor-interacting protein 1 (GRIP1) and GRIP2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) binding proteins GRIP1 (ABP/GRIP2) and GRIP2, and related domains. GRIP1 and GRIP2 each have 7 PDZ domains. The interaction of GRIP1 and GRIP2 with GluA2/3 (AMPAR subunit) regulates AMPAR trafficking and synaptic targeting. GRIP1 has an essential role in regulating AMPAR trafficking during synaptic plasticity and learning and memory. GRIP1 and GRIP2 interact with a variety of other proteins associated with protein trafficking and internalization, for example GRIP1 also interacts with KIF5 (also known as kinesin 1), EphB receptors, scaffold protein liprin-alpha, and the rasGEF GRASP-1. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This GRIP family PDZ4 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467174 [Multi-domain] Cd Length: 99 Bit Score: 41.56 E-value: 1.65e-04

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 569006111   92 SPSGRLGFSVRGG--SEHGLGI--FVSKVEEGSSAERAG-LCVGDKITEVNGLSLESTTMGSAVRLLTSSS 157
Cdd:cd06686    15 DPLKGFGIQLQGGvfATETLSSppLISFIEPDSPAERCGvLQVGDRVLSINGIPTEDRTLEEANQLLRDSA 85

PDZ domain 1 of syntenin-1, syntenin-2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of syntenin-1, syntenin-2, and related domains. Syntenins are implicated in various cellular processes such as trafficking, signaling, and cancer metastasis. They bind to signaling and adhesion molecules, such as syndecans, neurexins, ephrin B, and phospholipid PIP2. Through its tandem PDZ domains (PDZ1 and PDZ2), syntenin links syndecans to other cell surface receptors and kinases, such as E-cadherin and ephrin-B, establishing signaling crosstalk. During syndecan binding, syntenin PDZ2 serves as a high-affinity domain, and PDZ1, also necessary for binding, acts as a complementary, low-affinity domain; this is also the case for syntenin binding to proto-oncogene c-Src. The syntenin PDZ domain-PIP2 interaction controls Arf6-mediated syndecan recycling through endosomal compartments; both PDZ1 and PDZ2 interact with PIP2. Different binding partners and downstream regulators of syntenin1 PDZ domains, such as to proto-oncogene c-Src, mitogen-activated protein kinase (MAPK), and focal adhesion kinase (FAK), have been identified that promote the progression and invasion of a variety of cancers, such as melanoma, glioblastoma multiforme and breast cancer. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This syntenin-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta- strand F.

Pssm-ID: 467204 [Multi-domain] Cd Length: 79 Bit Score: 41.07 E-value: 1.66e-04

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 569006111   91 KSPSGRLGFSVRGGSEhglGIFVSKVEEGSSAERAGLCVGDKITEVNGLSLESTTMGSAVRLLTSSS--CLHMMVR 164
Cdd:cd06721     7 KDQDGKIGLRVKSIDK---GVFVQLVQANSPAALAGLRFGDQILQINGENVAGWSSDKAHKVLKKASpeRITLAVR 79

PDZ domain 0 of membrane-associated guanylate kinase inverted 1 (MAGI-1), MAGI-2, and MAGI-3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 0 of MAGI1, 2, 3 (MAGI is also known as Membrane-associated guanylate kinase, WW and PDZ domain-containing protein) and related domains. MAGI proteins have been implicated in the control of cell migration and invasion through altering the activity of phosphatase and tensin homolog (PTEN) and modulating Akt signaling. Four MAGI proteins have been identified (MAGI1-3 and MAGIX). MAGI1-3 have 6 PDZ domains and bind to the C-terminus of PTEN via their PDZ2 domain. MAGIX has a single PDZ domain that is related to MAGI1-3 PDZ domain 5. Other binding partners for MAGI1 include JAM4, C-terminal tail of high risk HPV-18 E6, megalin, TRAF6, Kir4.1 (basolateral K+ channel subunit), and cadherin 23; for MAGI2, include DASM1, dendrin, axin, beta- and delta-catenin, neuroligin, hyperpolarization-activated cation channels, beta1-adrenergic receptors, NMDA receptor, and TARPs; and for MAGI3 includes LPA2. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MAGI family PDZ0 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2); arranged as beta-strands A, -B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467212 [Multi-domain] Cd Length: 85 Bit Score: 41.03 E-value: 1.73e-04

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                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 569006111   84 IHAVRVEKSPSGRLGFSVRGGSEHGLGIFVSKVEEGSSAERAG-LCVGDKITEVNGLSL 141
Cdd:cd06730     2 VHECVVSRGPDGELNLEIRGGAENGQFPYLGEVKEDKVVYKSGkLHPGELLLEVNGTPV 60

PDZ domain 3 of glutamate receptor-interacting protein 1 (GRIP1) and GRIP2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) binding proteins GRIP1 (ABP/GRIP2) and GRIP2, and related domains. GRIP1 and GRIP2 each have 7 PDZ domains. The interaction of GRIP1 and GRIP2 with GluA2/3 (AMPAR subunit) regulates AMPAR trafficking and synaptic targeting. GRIP1 has an essential role in regulating AMPAR trafficking during synaptic plasticity and learning and memory. GRIP1 and GRIP2 interact with a variety of other proteins associated with protein trafficking and internalization, for example GRIP1 also interacts with KIF5 (also known as kinesin 1), EphB receptors, scaffold protein liprin-alpha, and the rasGEF GRASP-1. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This GRIP family PDZ3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467172 [Multi-domain] Cd Length: 87 Bit Score: 41.08 E-value: 1.77e-04

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569006111  867 SLGISISGGIESKvQPMVKIEKIFPGGAAFLCGDLQAGFELVAVDGESLEQVTHQRAVDTIRRAYRNKAR 936
Cdd:cd06684    14 SLGITLSTSTHRN-KQVIVIDSIKPASIADRCGALHVGDHILSIDGTSVEHCSLAEATQLLASNSGDQVK 82

PDZ domain of neurabin-1 and neurabin-2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of neurabin-1 (also known as protein phosphatase 1 regulatory subunit 9A) and neurabin-2 (also known as spinophilin, and protein phosphatase 1 regulatory subunit 9B), and related domains. Neurabin-1 and neurabin-2 are neuronal scaffolding proteins that play important roles in the regulation of synaptic transmission through their ability to interact with and target protein phosphatase 1 (PP1) to dendritic spines where PP1 dephosphorylates and inactivates glutamate receptors. Neurabin-2 interacts with multiple other synaptic proteins, including synaptic signaling and scaffolding proteins (e.g., GluN1 and SAPAP3) and cytoskeletal proteins (e.g., neurofilament medium polypeptide, NF-M). Neurabin-1 and neurabin-2 also binds F-actin. Other binding partners of neurabin-1 include adenosine A1 receptor (A1R), SAD-1 kinase and 70 kDa ribosomal protein S6 kinase (p70-S6K). This PDZ domain is immediately C-terminal to the PP1 binding domain. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This neurabin-like PDZ domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467252 [Multi-domain] Cd Length: 90 Bit Score: 41.25 E-value: 1.85e-04

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 569006111  859 ITLSKMKQSLGISISG---GIESKVQPM-VKIEKIFPGGAAFLCGDLQAGFELVAVDGESLEQVTHQRAVDTIR 928
Cdd:cd06790     5 VELEKGSEGLGISIIGmgvGADAGLEKLgIFVKTVTEGGAAQRDGRIQVNDQIVEVDGISLVGVTQAFAASVLR 78

PDZ domain 1 of Discs Large 5 (Dlg5) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of Drosophila and mammalian Dlg5, and related domains. Dlg5 is a scaffold protein with multiple conserved functions that are independent of each other in regulating growth, cell polarity, and cell adhesion. It has a coiled-coil domain, 4 PDZ domains and a MAGUK domain (an SH3 domain next to a non-catalytically active guanylate kinase domain). Deregulation of Dlg5 has been implicated in the malignancy of several cancer types. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Dlg5-like family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467245 [Multi-domain] Cd Length: 95 Bit Score: 41.23 E-value: 1.88e-04

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 569006111  217 SDDFCLGFNIRGGKE-----FGLGIYVSKVDHGGLAeENGIKVGDQVLAANGVRFDDISHSQAVE-VLKGQTHIMLTIK 289
Cdd:cd06764    16 MDLKALGFDIAGGVNdpqfpGDCSIFVTKVDKGSIA-DGRLRVNDCLLRINDVDLTNKDKKQAIQaVLNGGGVINMVVR 93

PDZ domain 11 of MUPP1 of multi-PDZ-domain protein 1 (MUPP1), domain 9 of PATJ (protein-associated tight junction) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 11 of MUPP1, PDZ domain 9 of PATJ, and related domains. MUPP1 and PATJ serve as scaffolding proteins linking different proteins and protein complexes involved in the organization of tight junctions and epithelial polarity. MUPP1 contains an L27 (Lin-2 and Lin-7 binding) domain and 13 PDZ domains. PATJ (also known as INAD-like) contains an L27 domain and ten PDZ domains. MUPP1 and PATJ share several binding partners, including junctional adhesion molecules (JAM), zonula occludens (ZO)-3, Pals1 (protein associated with Lin-7), Par (partitioning defective)-6 proteins, and nectins (adherence junction adhesion molecules). PATJ lacks 3 PDZ domains seen in MUPP1: PDZ6, 9, and 13; consequently, MUPP1 PDZ7 and 8 align with PATJ PDZ6 and 7; and MUPP1 PDZ domains 10-12 align with PATJ PDZ domains 8-10. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MUPP1-like family PDZ11 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467162 [Multi-domain] Cd Length: 87 Bit Score: 41.11 E-value: 1.91e-04

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 569006111   82 DIIHaVRVEKSPSGRLGFSVRGgSEHGLGIFVSKVEEGSSAERAG-LCVGDKITEVNGLSLESTTMGSAVRLL 153
Cdd:cd06674     2 DIFT-VELQKKPGRGLGLSIVG-KRNDTGVFVSDIVKGGAADADGrLMQGDQILSVNGEDVRNASQEAAAALL 72

PDZ domain of microtubule-associated serine-threonine (MAST) protein kinase 3 (MAST3); PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of MAST3, and related domains. MAST3 belongs to the MAST family kinases, which include MAST1-4. These MAST proteins contain a DUF1908 domain, a serine/threonine kinase domain, a AGC-kinase C-terminal domain, and a PDZ domain. MAST3 plays a critical role in regulating the immune response of inflammatory bowel disease (IBD), and is involved in the process of cytoskeleton organization, intracellular signal transduction and peptidyl-serine phosphorylation. MAST3 also promotes the proliferation and inflammation of fibroblast-like synoviocytes in rheumatoid arthritis. Binding partners of MAST3 include cAMP-regulated phosphoprotein (ARPP-16) and the tumor suppressor PTEN. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MAST3 family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467288 [Multi-domain] Cd Length: 94 Bit Score: 41.17 E-value: 2.11e-04

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569006111   83 IIHavrvekSPSGRLGFSVR------GGSE-HGLGIFVSKVEEGSSAERAGLCVGDKITEVNGLSLESTTMGSAVRLLTS 155
Cdd:cd23075     6 IIH------SSGKKYGFTLRairvymGDSDvYTVHHMVWSVEDGSPAQEAGLRAGDLITHINGESVLGLVHMDVVELLLK 79


                  .
gi 569006111  156 S 156
Cdd:cd23075    80 S 80

PDZ domain 11 of MUPP1 of multi-PDZ-domain protein 1 (MUPP1), domain 9 of PATJ (protein-associated tight junction) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 11 of MUPP1, PDZ domain 9 of PATJ, and related domains. MUPP1 and PATJ serve as scaffolding proteins linking different proteins and protein complexes involved in the organization of tight junctions and epithelial polarity. MUPP1 contains an L27 (Lin-2 and Lin-7 binding) domain and 13 PDZ domains. PATJ (also known as INAD-like) contains an L27 domain and ten PDZ domains. MUPP1 and PATJ share several binding partners, including junctional adhesion molecules (JAM), zonula occludens (ZO)-3, Pals1 (protein associated with Lin-7), Par (partitioning defective)-6 proteins, and nectins (adherence junction adhesion molecules). PATJ lacks 3 PDZ domains seen in MUPP1: PDZ6, 9, and 13; consequently, MUPP1 PDZ7 and 8 align with PATJ PDZ6 and 7; and MUPP1 PDZ domains 10-12 align with PATJ PDZ domains 8-10. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MUPP1-like family PDZ11 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467162 [Multi-domain] Cd Length: 87 Bit Score: 41.11 E-value: 2.13e-04

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                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 569006111  222 LGFNIRGgKEFGLGIYVSKVDHGGLAEENG-IKVGDQVLAANGVRFDDISHSQAVEVLK 279
Cdd:cd06674    16 LGLSIVG-KRNDTGVFVSDIVKGGAADADGrLMQGDQILSVNGEDVRNASQEAAAALLK 73

Membrane-associated protease RseP, regulator of RpoE activity [Posttranslational modification, protein turnover, chaperones, Transcription];

Pssm-ID: 440513 [Multi-domain] Cd Length: 349 Bit Score: 44.69 E-value: 2.18e-04

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                  ....*....|....*....|....*....|.
gi 569006111  113 VSKVEEGSSAERAGLCVGDKITEVNGLSLES 143
Cdd:COG0750   132 VGEVVPGSPAAKAGLQPGDRIVAINGQPVTS 162

PDZ domain of membrane palmitoylated proteins 3 (MPP3), MPP4, and MPP7, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of MPP3, MPP4, and MPP7, and related domains. MPP3 (also known as MAGUK p55 subfamily member 3, erythrocyte membrane protein p55, or EMP55), MPP4 (also known as MAGUK p55 subfamily member 4 or Discs large homolog 6), and MPP7 (also known as MAGUK p55 subfamily member 7) are membrane-associated guanylate kinase (MAGUK)-like proteins. MPP3 is part of a cell adhesion protein complex including tumor suppressor CADM1 and actin-binding protein 4.1B. Participation in the Crumbs cell polarity complex has also been demonstrated for MPP7 in epithelial cells, and for MPP3 and MPP4 in the retina. MPP4 is needed for proper localization of plasma membrane calcium ATPases and maintenance of calcium homeostasis at the rod photoreceptor synaptic terminals. Binding partners of the MPP3 PDZ domain include nectin-3, serotonin 5-hydroxytryptamine, 5-HT(2C) receptor, and a cell adhesion protein, TSLC1 (tumor suppressor in lung cancer 1); fragments of MPP4 having the PDZ domain bind CRB (PDZ-SH3-GUK) and GABA transporter GAT1 (PDZ-SH3). PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MPP1-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467260 [Multi-domain] Cd Length: 81 Bit Score: 40.69 E-value: 2.44e-04

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                  ....*....|....*....|....*....|....*....|....*....|...
gi 569006111  106 EHGLGIFVSKVEEGSSAERAGLC-VGDKITEVNGLSLESTTMGSAVRLLTSSS 157
Cdd:cd06799    20 EKTGAIVVARIMRGGAADRSGLIhVGDELREVNGISVEGKDPEEVIQILANSQ 72

PDZ domain 1 of inactivation-no-after-potential D (INAD), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of INAD, and related domains. INAD assembles key enzymes of the Drosophila compound eye photo-transduction pathway into a supramolecular complex, supporting efficient and fast light signaling. It contains 5 PDZ domains arranged in tandem (PDZ1-PDZ5) which independently bind various proteins. INAD PDZ2 binds eye-specific protein kinase C, INAD PDZ3 binds transient receptor potential (TRP) channel, and INAD PDZ4,5 tandem binds NORPA (phospholipase Cbeta, PLCbeta). Mutations of the inaD gene that lead to disruption of each of these interactions impair fly photo signal transduction. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This INAD-like family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467276 [Multi-domain] Cd Length: 87 Bit Score: 40.96 E-value: 2.53e-04

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gi 569006111   87 VRVEKSPSGRLGFSVRGGSEHG------LGIFVSKVEEGSSAERAG-LCVGDKITEVNGLSLESTTMGSAVRLL 153
Cdd:cd23063     2 VVIEKTEKKSFGICIVRGEVKVspntktTGIFIKGIIPDSPAHKCGrLKVGDRILSVNGNDVRNSTEQAAIDLI 75

PDZ domain 1 of PDZ domain-containing RING finger protein 4 (PDZRN4), PDZRN3-B, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of PDZRN4, PDZRN3-B, and related domains. PDZRN4 (also known as ligand of numb protein X 4, and SEMACAP3-like protein) contains an N-terminal RING domain and two tandem repeat PDZ domains. It is involved in the progression of cancer, including human liver cancer and breast cancer, and may contribute to the tumorigenesis of rectal adenocarcinoma. Danio rerio PDZRN3-B may participate in neurogenesis: the first PDZ domain of Danio rerio Pdzrn3 interacts with Kidins220 (Kinase D-interacting substrate 220 kD, also named Ankyrin Repeat-Rich Membrane Spanning), a crucial mediator of signal transduction in neural tissues. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PDZRN4-like family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467199 [Multi-domain] Cd Length: 92 Bit Score: 40.84 E-value: 2.66e-04

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569006111  858 TITLSKMKQSLGISISGG---IESKVQPM---VKIEKIFPGGAAFLCGDLQAGFELVAVDGESLEQVTHQRAVDtirrAY 931
Cdd:cd06715     4 TVVLHRENGSLGFNIIGGrpcENNQEGSSsegIYVSKIVENGPAADEGGLQVHDRIIEVNGKDLSKATHEEAVE----AF 79

                          90
                  ....*....|....
gi 569006111  932 RNkAREPmeLVVRV 945
Cdd:cd06715    80 RT-AKEP--IVVQV 90

PDZ domain 4 of inactivation-no-after-potential D (INAD), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 4 of INAD, and related domains. INAD assembles key enzymes of the Drosophila compound eye photo-transduction pathway into a supramolecular complex, supporting efficient and fast light signaling. It contains 5 PDZ domains arranged in tandem (PDZ1-PDZ5) which independently bind various proteins. INAD PDZ2 binds eye-specific protein kinase C, INAD PDZ3 binds transient receptor potential (TRP) channel, and INAD PDZ4,5 tandem binds NORPA (phospholipase Cbeta, PLCbeta). Mutations of the inaD gene that lead to disruption of each of these interactions impair fly photo signal transduction. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This INAD-like family PDZ4 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467278 [Multi-domain] Cd Length: 82 Bit Score: 40.19 E-value: 3.38e-04

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 569006111   87 VRVEKSPsgrLGFSVRGGSEHGL-GIFVSKV-EEGSSAERAGLCVGDKITEVNGLSLESTTMGSAVRLL 153
Cdd:cd23065     4 LKTDKSP---LGVSVVGGKNHVTtGCIITHIyPNSIVAADKRLKVFDQILDINGTKVHVMTTLKVHQLF 69

PDZ domain 4 of multi-PDZ-domain protein 1 (MUPP1) and PATJ (protein-associated tight junction) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 4 of MUPP1 and PATJ, and related domains. MUPP1 and PATJ serve as scaffolding proteins linking different proteins and protein complexes involved in the organization of tight junctions and epithelial polarity. MUPP1 contains an L27 (Lin-2 and Lin-7 binding) domain and 13 PDZ domains. PATJ (also known as INAD-like) contains an L27 domain and ten PDZ domains. MUPP1 and PATJ share several binding partners, including junctional adhesion molecules (JAM), zonula occludens (ZO)-3, Pals1 (protein associated with Lin-7), Par (partitioning defective)-6 proteins, and nectins (adherence junction adhesion molecules). PATJ lacks 3 PDZ domains seen in MUPP1: PDZ6, 9, and 13; consequently, MUPP1 PDZ7 and 8 align with PATJ PDZ6 and 7; and MUPP1 PDZ domains 10-12 align with PATJ PDZ domains 8-10. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MUPP1-like family PDZ4 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F

Pssm-ID: 467156 [Multi-domain] Cd Length: 88 Bit Score: 40.36 E-value: 3.52e-04

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569006111  861 LSKMKQS--LGISISGGIESKVQPMVKIEKIFPGGAAFLCGDLQAGFELVAVDGESLEQVTHQRAVDTIR 928
Cdd:cd06668     7 LSKFSESsgLGISLEGTVDVEVRGHHYIRSILPEGPVGRNGKLFSGDELLEVNGIQLLGLSHKEVVSILK 76

PDZ domain 3 of the canonical isoform 1 of PDZ domain containing 7 (PDZD7), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of the long isoform 1 of PDZD7, and related domains. PDZD7 is critical for the organization of the Usher syndrome type 2 (USH2) complex. Usher syndrome is the leading cause of hereditary sensory deaf-blindness in humans; USH2 is the most common sub-type. Formation of the USH2 complex is based upon heterodimerization between PDZD7 and whirlin (another PDZ domain-containing protein) and a subsequent dynamic interplay between USH2 proteins via their multiple PDZ domains. The PDZD7 PDZ2 domain binds GPR98 (also known as VLGR1) and usherin (USH2A). PDZD7 and whirlin form heterodimers through their multiple PDZ domains; whirlin and PDZD7 interact with usherin and GPR98 to form an interdependent ankle link complex. PDZD7 also interacts with myosin VIIa and can also form homodimers through its PDZ2 domain. Various isoforms of PDZD7 produced by alternative splicing have been identified; this subgroup includes the third PDZ domain of the canonical isoform of PDZD7- isoform 1. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PDZD7-like family PDZ3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467233 [Multi-domain] Cd Length: 89 Bit Score: 40.50 E-value: 3.80e-04

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                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 569006111  222 LGFNIRGGKEFGLGIYVS--KVDHGGLAEENGI-KVGDQVLAANGVRFDDISHSQAVEVLK 279
Cdd:cd06751    13 LGISISGGIESKVQPVVKieKIFPGGAAALSGNlKAGYELVSVDGESLQQVTHQQAVDIIR 73

PDZ domain of ARHGEF11, ARHGEF12, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of ARHGEF11, ARHGEF12, and related domains. This subfamily includes the GEFs (guanine exchange factors) ARHGEF11 (Rho guanine nucleotide exchange factor 11, known as PDZ-RhoGEF) and ARHGEF12 (Rho guanine nucleotide exchange factor 12, also known as leukemia-associated RhoGEF). GEFs activate Rho GTPases by promoting GTP binding. ARHGEF11/12 are regulators of G protein signaling (RGS) domain-containing GEFs; the RGS domain mediates their binding to and activation of Galpha (and Gq also in the case of ARHGEF12), in response to G-protein coupled receptor activation. ARHGEF11 and 12 are involved in serum-signaling, and regulate Yes-Associated Protein (YAP1)-dependent transcription. The ARHGEF12 PDZ domain binds plexin-B1 and the receptor tyrosine kinase insulin-like growth factor receptor (IGF-R1) beta-subunit. ARHGEF12 also interacts with glutamate receptor delta-1(GluD1), a postsynaptic organizer of inhibitory synapses in cortical pyramidal neurons. The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This ARHGEF11-12-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467282 [Multi-domain] Cd Length: 76 Bit Score: 39.68 E-value: 4.16e-04

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                  ....*....|....*....|....*....|....*....|....*....|....
gi 569006111  236 IYVSKVDHGGLAEENGIKVGDQVLAANGVRFDDISHSQAVEVLKGQTHIMLTIK 289
Cdd:cd23069    23 VFVQSVKEGGAAYRAGVQEGDRIIKVNGTLVTHSNHLEVVKLIKSGSYVALTLL 76

PDZ domain 2 of amyloid-beta A4 precursor protein-binding family A member 1 (APBA1), APBA2, APBA3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of APBA1, APBA2, APBA3, and related domains. The APBA/X11/Mint protein family includes three members: neuron specific APBA1 (also known as X11alpha and Mint1) and APBA2 (also known as X11beta and Mint2), and the ubiquitously expressed APBA3 (also known as X12gamma and Mint3). They are involved in regulating neuronal signaling, trafficking, and plasticity. They contain two PDZ domains (PDZ1 and PDZ2) which bind a variety of proteins: Arf GTPases (APBA1 and APBA2 PDZ2) and neurexin (APBA1 and APBA2 PDZ1 and 2) which are involved in vesicle docking and exocytosis; alpha1B subunit of N-type Ca2+ channel (APBA1 PDZ1) that is involved in ion channels; KIF17 (APBA1 PDZ1) that is involved in transport and traffic; and Alzheimer's disease related proteins, APP (APBA3 PDZ2), CCS (APBA1 PDZ2), NF-kappa-B/p65 (APBA2 PDZ2), presenilin-1 (APBA1 and APBA2 PDZ1 and PDZ2). PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This APBA1,3-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467255 [Multi-domain] Cd Length: 78 Bit Score: 40.08 E-value: 4.31e-04

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 569006111   97 LGFSVRGGsehglgiFVSKVEEGSSAERAGLCVGDKITEVNGLSLESTTMGSAVRLLTSSSC-LHM 161
Cdd:cd06793    16 LGFSVQNG-------IICSLLRGGIAERGGVRVGHRIIEINGQSVVATPHEKIVQLLSNSVGeIHM 74

PDZ domain 1 of human discs large homolog 1 (Dlg1), Dlg2, and Dlg4, Drosophila disc large (Dlg), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of Drosophila Dlg1, human Dlg1,2, and 4 and related domains. Dlg1 (also known as synapse-associated protein Dlg197 or SAP-97), Dlg2 (also known as channel-associated protein of synapse-110, postsynaptic density protein 93, or PSD-93), Dlg4 (also known as postsynaptic density protein 95, PSD-95, synapse-associated protein 90, or SAP-90) each have 3 PDZ domains and belong to the membrane-associated guanylate kinase family. Dlg1 regulates antigen receptor signaling and cell polarity in lymphocytes, B-cell proliferation and antibody production, and TGFalpha bioavailability; its PDZ3 domain binds pro-TGFalpha, and its PDZ2 domain binds the TACE metalloprotease responsible for cleaving pro-TGFalpha to a soluble form. Dlg2 is involved in N-methyl-D-aspartate (NMDA) receptor signaling. It regulates surface expression of NMDA receptors in dorsal horn neurons of the spinal cord, and it also interacts with NMDA receptor subunits and with Shaker-type K+ channel subunits to cluster into a channel complex. Dlg4 PDZ1 domain binds NMDA receptors, and its PDZ2 domain binds neuronal nitric oxide synthase (nNOS), forming a complex in neurons. The Drosophila Scribble complex (Scribble, Dlg, and lethal giant larvae) plays a role in apico-basal cell polarity, and in other forms of polarity, including regulation of the actin cytoskeleton, cell signaling and vesicular trafficking, and in tumor development. Postsynaptic targeting of Drosophila DLG requires interactions mediated by the first two PDZ domains. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Dlg-like family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467206 [Multi-domain] Cd Length: 89 Bit Score: 39.99 E-value: 4.42e-04

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569006111   90 EKSPSGrLGFSVRGGSEHGL-----GIFVSKVEEGSSAERAG-LCVGDKITEVNGLSLESTTMGSAVRLLTSS-SCLHMM 162
Cdd:cd06723     7 ERGNSG-LGFSIAGGTDNPHigddpSIYITKIIPGGAAAADGrLRVNDIILRVNDVDVRNVTHSVAVEALKEAgSIVRLY 85


                  ...
gi 569006111  163 VRR 165
Cdd:cd06723    86 VKR 88

PDZ domain 3 of protein tyrosine phosphatase non-receptor type 13 (PTPN13), FERM and PDZ domain-containing protein 2 (FRMPD2), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of PTPN13 [also known as Fas-associated protein-tyrosine phosphatase 1 (FAP-1), protein-tyrosine phosphatase 1E (PTP-E1), and protein-tyrosine phosphatase (PTPL1)], FRMPD2 (also known as PDZ domain-containing protein 4; PDZ domain-containing protein 5C), and related domains. PTPN13 regulates negative apoptotic signaling and mediates phosphoinositide 3-kinase (PI3K) signaling. PTPN13 has five PDZ domains. Proteins known to interact with PTPN13 PDZ domains include: PLEKHA1 and PLEKHA2 via PTPN13-PDZ domain 1, Fas receptor and thyroid receptor-interacting protein 6 via PTPN13-PDZ domain 2, nerve growth factor receptor and protein kinase N2 via PTPN13-PDZ domain 3, PDZ and LIM domain 4 (PDLIM4) via PTPN13-PDZ domains 2 and 4, and brain calpain-2 via PTPN13-PDZ domains 3, 4 and 5. Calpain-2-mediated PTPN13 fragments may be involved in abnormal tau aggregation and increased risk for Alzheimer's disease. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). FRMPD2 is localized in the basolateral membranes of polarized epithelial cells and is associated with tight junction formation and immune response; it contains 3 PDZ domains). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PTPN13 family PDZ3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467181 [Multi-domain] Cd Length: 90 Bit Score: 40.32 E-value: 4.61e-04

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gi 569006111  222 LGFNIRGGK------EFGLGIYVSKVDHGGLAEENG-IKVGDQVLAANGVRFDDISHSQAVEVLKG 280
Cdd:cd06695    13 LGFSFLGGEnnspedPFSGLVRIKKLFPGQPAAESGlIQEGDVILAVNGEPLKGLSYQEVLSLLRG 78

PDZ domain 2 of PDZ domain-containing RING finger protein 4 (PDZRN4), PDZRN3-B, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of PDZRN4, PDZRN3-B, and related domains. PDZRN4 (also known as ligand of numb protein X 4, and SEMACAP3-like protein) contains an N-terminal RING domain and two tandem repeat PDZ domains. It is involved in the progression of cancer, including human liver cancer and breast cancer, and may contribute to the tumorigenesis of rectal adenocarcinoma. Danio rerio PDZRN3-B may participate in neurogenesis: the first PDZ domain of Danio rerio Pdzrn3 interacts with Kidins220 (Kinase D-interacting substrate 220 kD, also named Ankyrin Repeat-Rich Membrane Spanning), a crucial mediator of signal transduction in neural tissues. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PDZRN4-like family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467200 [Multi-domain] Cd Length: 88 Bit Score: 39.95 E-value: 4.71e-04

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 569006111  211 VHLYTTSDDFCLGFNI--RGGKEFGLGIYVSKVDHGGLAEENG-IKVGDQVLAANGVrfDDISHSQAVEVLKGQT 282
Cdd:cd06716     6 VTLKRSNSQEKLGLTLcyRTDDEEDTGIYVSEVDPNSIAAKDGrIREGDQILQINGV--DVQNREEAIALLSEEE 78

PDZ domain 2 of the canonical isoform 1 of PDZ domain containing 7 (PDZD7), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of the long isoform 1 of PDZD7, and related domains. PDZD7 is critical for the organization of Usher syndrome type 2 (USH2) complex. Usher syndrome is the leading cause of hereditary sensory deaf-blindness in humans; USH2 is the most common sub-type. Formation of the USH2 complex is based upon heterodimerization between PDZD7 and whirlin (another PDZ domain-containing protein) and a subsequent dynamic interplay between USH2 proteins via their multiple PDZ domains. The PDZD7 PDZ2 domain binds GPR98 (also known as VLGR1) and usherin (USH2A). PDZD7 and whirlin form heterodimers through their multiple PDZ domains; whirlin and PDZD7 interact with usherin and GPR98 to form an interdependent ankle link complex. PDZD7 also interacts with myosin VIIa. PDZD7 also forms homodimers through its PDZ2 domain. Various isoforms of PDZD7 produced by alternative splicing have been identified; this subgroup includes the second PDZ domain of the canonical isoform of PDZD7- isoform 1. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PDZD7-like family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467270 [Multi-domain] Cd Length: 85 Bit Score: 39.68 E-value: 5.38e-04

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 569006111  862 SKMKQSLGISISGGIESKVQpmVKIEKIFPGGAAFLCGdLQAGFELVAVDGESLEQVTHQRAVDTIR 928
Cdd:cd10834     9 TSDDYCLGFNIRGGSEYGLG--IYVSKVDPGGLAEQNG-IKVGDQILAVNGVSFEDITHSKAVEVLK 72

PDZ domain of signal-induced proliferation-associated protein 1 (SIPA1), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of SIPA1, and related domains. The Rap-GTPase activating protein SIPA1 (also known as GTPase-activating protein Spa-1, p130 SPA1) is a metastasis promoter; a polymorphism in a region of the Sipa1 gene encoding the PDZ domain is associated with metastasis. The SIPA1 PDZ domain binds ribosomal RNA processing 1 homolog B (Rrp1b). SIPA1 also forms a complex with water channel aquaporin-2 (AQP2) and plays a role in trafficking of AQP2, targeted positioning of which strictly regulates body water homeostasis; the SIPA1 PDZ domain binds AQP2. Rrp1b or AQP2 binding inhibits the RapGAP activity of SIPA1. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This SIPA1-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta- strand F.

Pssm-ID: 467227 [Multi-domain] Cd Length: 73 Bit Score: 39.57 E-value: 5.50e-04

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gi 569006111   95 GRLGFSVrggSEHGlgiFVSKVEEGSSAERAGLCVGDKITEVNGLSLESTTMGSAVRLLTSSSCLHMMV 163
Cdd:cd06745    10 GQLGFHV---NYEG---FVTEVERFGFAWQAGLRQGSRLVEICKVPVATLTHEQMIDLLRTSVKVKVTV 72

PDZ domain 3 of partitioning defective 3 (Par3), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of Par3 (or PAR3 or Par-3, also known as Atypical PKC isotype-specific-interacting protein, ASIP, Drosophila Bazooka) and related domains. Par3 is a scaffold protein involved in organizing cell polarity across animals. Par3 binds numerous molecules both for its recruitment to one pole of the cell and for downstream contributions to polarized cell function. It regulates cell polarity by targeting the Par complex proteins Par6 and atypical protein kinase C (aPKC) to specific cortical sites. Physical interactions between Par-3 and the Par complex include Par3 PDZ domain 1 binding to the Par6 PDZ domain, Par3 PDZ domain 1 and PDZ domain 3 binding the Par6's PDZ-binding motif, and an interaction with an undefined region of aPKC that requires both Par3 PDZ2 and PDZ3. The PDZ domains of Par3 have also been implicated as potential phosphoinositide signaling integrators, since its second PDZ domain binds to phosphoinositides, and the third PDZ interacts with phosphoinositide phosphatase PTEN. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Par3 family PDZ3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467272 [Multi-domain] Cd Length: 103 Bit Score: 40.34 E-value: 5.51e-04

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                  ....*....|....*....|....*....|....*....|....*..
gi 569006111  234 LGIYVSKVDHGGLAEENG-IKVGDQVLAANGVRFDDISHSQAVEVLK 279
Cdd:cd23059    37 LGIFIKSIIHGGAASKDGrLRVNDQLIAVNGESLLGLTNSEAMETLR 83

PDZ domain; This entry represents the PDZ domain from a wide variety of proteins.

Pssm-ID: 436067 [Multi-domain] Cd Length: 54 Bit Score: 38.66 E-value: 5.52e-04

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                   ....*....|....*....|....*....|....*....|....*....|....*
gi 569006111   237 YVSKVDHGGLAEENGIKVGDQVLAANGVRFDDISHsqAVEVLKGQTH--IMLTIK 289
Cdd:pfam17820    1 VVTAVVPGSPAERAGLRVGDVILAVNGKPVRSLED--VARLLQGSAGesVTLTVR 53

domain similar to the N-terminal protein-binding module of harmonin; uncharacterized subgroup; This domain is a putative protein-binding module based on its sequence similarity to the N-terminal domain of harmonin. Harmonin (not belonging to this group) is a postsynaptic density-95/discs-large/ZO-1 (PDZ) domain-containing scaffold protein, which organizes the Usher protein network of the inner ear and the retina. This domain is also related to domains found in several other scaffold proteins which organize supramolecular complexes.

Pssm-ID: 259827 Cd Length: 78 Bit Score: 39.36 E-value: 6.34e-04

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gi 569006111  562 QDLARRLLTDDEVLAVTRHCSRYVHEGGVEDLVRPLLAILDRPTKLLLLRDIRSVVAPTDLGRFDSM 628
Cdd:cd13933     9 ITNARLLLNEAEREVLCTLLKEYKQSRSVDRLVLCLTHVLDTPAKLDLLKDLRHLIPAELLAKFDRL 75

PDZ domain 3 of harmonin isoforms a and b, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of harmonin isoforms a and b, and related domains. Harmonin (also known as Usher Type 1C, PDZ-73 and AIE-75) is a key organizer of the Usher (USH) protein interactome. USH syndrome is the leading cause of hereditary sensory deaf-blindness in humans; three clinically distinct types of USH have been identified, type 1 to 3. The gene encoding harmonin (USH1C) is the causative gene for the USH type 1C phenotype. There are at least 10 alternatively spliced isoforms of harmonin, which are divided into three subclasses (a, b, and c). All isoforms contain the first two PDZ domains and the first coiled-coil domain. The a and b isoforms all have a third PDZ domain. The different PDZ domains are responsible for interactions with all known Usher syndrome type 1 proteins, and most Usher syndrome type 2 proteins. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This harmonin family PDZ3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467221 [Multi-domain] Cd Length: 94 Bit Score: 39.60 E-value: 7.03e-04

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gi 569006111   94 SGRLGFSVRGGSEHGLG--IFVSKVEEGSSAERAG-LCVGDKITEVNGLSLESTTMGSAVRLL 153
Cdd:cd06739    11 NGPLDLALEGGIDSPLGgkIVVSAVYEGGAADKHGgIVKGDQIMMVNGKSLTDVTLAEAEAAL 73

circularly permuted PDZ domains of Escherichia coli Regulator of sigma-E protease (RseP) and related domains; Permuted PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of ResP (also known as Site-2 protease RseP, and YaeL), and related domains. RseP is involved in the regulation of an extracytoplasmic stress response through the cleavage of membrane-spanning anti-stress-response transcription factor (anti-sigmE) protein RseA; it cleaves the peptide bond between the critical alanine and cysteine in the transmembrane region of RseA, releasing the cytoplasmic domain of RseA with its associated sigmaE. RseP contains two tandem-arranged periplasmic PDZ domains (PDZ-N/PDZ1 and PDZ-C/PDZ2) which act to negatively regulate protease action on intact RseA; they serve as a size-exclusion filter which prevents the access of an intact RseA into the active site of RseP. PDZ domains usually bind in sequence-specific manner to short peptide sequences located at the C-terminal of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains and as well as those with circular permutations and domain swapping of beta-strands. The canonical PDZ domain contains six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2); arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F. This RseP family PDZ domain is a circularly permuted PDZ domain which places both beta-strands A and B at the C-terminus. Another permutation exists in the PDZ superfamily which places beta-strand A at the C-terminus.

Pssm-ID: 467638 [Multi-domain] Cd Length: 83 Bit Score: 39.48 E-value: 7.35e-04

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                  ....*....|....*....|....*....|.
gi 569006111  113 VSKVEEGSSAERAGLCVGDKITEVNGLSLES 143
Cdd:cd23081     3 VGEVVANSPAAEAGLKPGDRILKIDGQKVRT 33

PDZ domain 2 of Drosophila Scribble, human Scribble homolog, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of Drosophila Scribble (also known as LAP4), human Scribble homolog (also known as hScrib, LAP4, CriB1, ScrB1 and Vartul), and related domains. They belong to the LAP family, which describes proteins that contain either one or four PDZ domains and 16 LRRs (leucine-rich repeats) and function in controlling cell shape, size and subcellular protein localization. In Drosophila, the Scribble complex, comprising Scribble, discs large, and lethal giant larvae, plays a role in apico-basal cell polarity, in other forms of polarity, including regulation of the actin cytoskeleton, cell signaling and vesicular trafficking, and in tumor development. Mammalian Scribble is important in many aspects of cancer development. Scribble and its homologs can be downregulated or overexpressed in cancer; they have a role in cancer beyond their function in loss of cell polarity. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Scribble-like family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467187 [Multi-domain] Cd Length: 92 Bit Score: 39.55 E-value: 7.73e-04

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 569006111  858 TITLSKMKQSLGISISGGIESKV----QPMVKIEKIFPGGAAFLCGDLQAGFELVAVDGESLEQVTHQRAV 924
Cdd:cd06703     4 TTTLIRDGKGLGFSIAGGKGSTPfrdgDEGIFISRITEGGAADRDGKLQVGDRVLSINGVDVTEARHDQAV 74

PDZ domain of PDZ-LIM family proteins, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of PDZ-LIM family proteins including PDLIM1-7, and related domains. PDZ-LIM family proteins (also known as Zasp PDZ domain proteins) are involved in the rearrangement of the actin cytoskeleton; they mediate association with the cytoskeleton through alpha-actinin as well as with other proteins involved in signal transduction pathways. Members of this family include PDLIM1 (also known as C-terminal LIM domain protein 1, elfin, LIM domain protein CLP-36), PDLIM2 (also known as PDZ-LIM protein mystique), PDLIM3 (also known as actinin-associated LIM protein, alpha-actinin-2-associated LIM protein, ALP), PDLIM4 (also known as LIM protein RIL, Reversion-induced LIM protein), PDLIM5 (also known as enigma homolog, ENH, enigma-like PDZ and LIM domains protein), PDLIM6 (also known as LIM domain-binding protein 3, ZASP, Cypher, Oracle), and PDLIM7 (also known as PDZ and LIM domain protein 7, LIM mineralization protein, LMP; protein enigma). PDLIM1 has been shown to negatively regulate NF-kappaB-mediated signaling in the cytoplasm. PDLIM7 negatively regulates p53 through binding murine double minute 2 (MDM2). The PDZ domains of PDZ-LIM family proteins PDLIM1, 2, 3, 5, 6, 7 have been shown to bind actin. Other PDZ-LIM family PDZ domain binding partners include thyroid receptor interacting protein-6 (PDLIM4-PDZ), the LIM domain of PDLIM4 (PDLIM4-PDZ), tropomyosin (PDLIM7-PDZ), myotilin and calsarcin 1 (PDLIM6-PDZ), and proteins from the myotilin and FATZ (calsarcin/myozenin) families (PDLIM1, 3, 4, 6 PDZ domains). PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PDLIM-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467235 [Multi-domain] Cd Length: 79 Bit Score: 39.05 E-value: 9.05e-04

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gi 569006111  869 GISISGGIESKvQPMVkIEKIFPGGAAFLCGdLQAGFELVAVDGESLEQVTHQRAVDTIRRA 930
Cdd:cd06753    11 GFRLQGGKDFN-QPLT-ISRVTPGGKAAQAN-LRPGDVILAINGESTEGMTHLEAQNKIKAA 69

PDZ domain 1 of harmonin isoforms a, b, and c, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of harmonin isoforms a, b, and c, and related domains. Harmonin (also known as Usher Type 1C, PDZ-73 and AIE-75) is a key organizer of the Usher (USH) protein interactome. USH syndrome is the leading cause of hereditary sensory deaf-blindness in humans; three clinically distinct types of USH have been identified, type 1 to 3. The gene encoding harmonin (USH1C) is the causative gene for the USH type 1C phenotype. There are at least 10 alternatively spliced isoforms of harmonin, which are divided into three subclasses (a, b, and c). All isoforms contain the first two PDZ domains and the first coiled-coil domain. The a and b isoforms all have a third PDZ domain. The different PDZ domains are responsible for interactions with all known Usher syndrome type 1 proteins, and most Usher syndrome type 2 proteins. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This harmonin family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467219 [Multi-domain] Cd Length: 85 Bit Score: 39.16 E-value: 9.14e-04

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gi 569006111  867 SLGISISGGIESKVQpmVKIEKIFPGGAAFLCGdLQAGFELVAVDGESLEQVTHQRAVDTIrrayrnKAREPMELVVRVP 946
Cdd:cd06737    14 SLGFSVRGGLEHGCG--LFVSHVSPGSQADNKG-LRVGDEIVRINGYSISQCTHEEVINLI------KTKKTVSLKVRHV 84


                  .
gi 569006111  947 G 947
Cdd:cd06737    85 G 85

Periplasmic serine protease, S1-C subfamily, contain C-terminal PDZ domain [Posttranslational modification, protein turnover, chaperones];

Pssm-ID: 440035 [Multi-domain] Cd Length: 274 Bit Score: 42.06 E-value: 1.03e-03

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gi 569006111  230 KEFGL----GIYVSKVDHGGLAEENGIKVGDQVLAANGVRFDDIS 270
Cdd:COG0265   193 EALGLpepeGVLVARVEPGSPAAKAGLRPGDVILAVDGKPVTSAR 237

PDZ domain of regulator of G-protein signaling 3 (RGS3), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of RGS3, and related domains. RGS3 down-regulates GPCR signal transduction by increasing the GTPase activity of G-protein alpha subunits, thereby driving G-proteins into their inactive GDP-bound form. It downregulates G-protein-mediated release of inositol phosphates and activation of MAP kinases. In Eph/ephrin signaling, RGS3 binds via its PDZ domain to the cytoplasmic C terminus of Eph receptor tyrosine kinase EphB. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This RGS3-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467195 [Multi-domain] Cd Length: 77 Bit Score: 38.91 E-value: 1.09e-03

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gi 569006111  227 RGGKEFGLGI------YVSKVDHGGLAEENGIKVGDQVLAANGVrfdDISHSQAVEV 277
Cdd:cd06711     7 RGKDGFGFTIcddspvRVQAVDPGGPAEQAGLQQGDTVLQINGQ---PVERSKCVEL 60

PDZ domain 6 of glutamate receptor-interacting protein 1 (GRIP1) and GRIP2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) binding proteins GRIP1 (ABP/GRIP2) and GRIP2, and related domains. GRIP1 and GRIP2 each have 7 PDZ domains. The interaction of GRIP1 and GRIP2 with GluA2/3 (AMPAR subunit) regulates AMPAR trafficking and synaptic targeting. GRIP1 has an essential role in regulating AMPAR trafficking during synaptic plasticity and learning and memory. GRIP1 and GRIP2 interact with a variety of other proteins associated with protein trafficking and internalization, for example GRIP1 also interacts with KIF5 (also known as kinesin 1), EphB receptors, scaffold protein liprin-alpha, and the rasGEF GRASP-1. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This GRIP family PDZ6 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467171 [Multi-domain] Cd Length: 85 Bit Score: 38.82 E-value: 1.11e-03

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gi 569006111  858 TITLSKMKQSLGISISGGiESKVQPmVKIEKIFPGGAAFLCGDLQAGFELVAVDGESLEQVTHQRAVDTIRRA 930
Cdd:cd06683     5 TVELKRYGGPLGITISGT-EEPFDP-IVISGLTEGGLAERTGAIHVGDRILAINGESLRGKPLSEAIHLLQNA 75

PDZ domain 1 of multi-PDZ-domain protein 1 (MUPP1) and PATJ (protein-associated tight junction), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of MUPP1 and PATJ, and related domains. MUPP1 and PATJ serve as scaffolding proteins linking different proteins and protein complexes involved in the organization of tight junctions and epithelial polarity. MUPP1 contains an L27 (Lin-2 and Lin-7 binding) domain and 13 PDZ domains. PATJ (also known as INAD-like) contains an L27 domain and ten PDZ domains. MUPP1 and PATJ share several binding partners, including junctional adhesion molecules (JAM), zonula occludens (ZO)-3, Pals1 (protein associated with Lin-7), Par (partitioning defective)-6 proteins, and nectins (adherence junction adhesion molecules). PATJ lacks 3 PDZ domains seen in MUPP1: PDZ6, 9, and 13; consequently, MUPP1 PDZ7 and 8 align with PATJ PDZ6 and 7; and MUPP1 PDZ domains 10-12 align with PATJ PDZ domains 8-10. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MUPP1-like family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467176 [Multi-domain] Cd Length: 102 Bit Score: 39.15 E-value: 1.20e-03

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gi 569006111  858 TITLSK-MKQSLGISISG-GIESKVQPMVKIEKIFPGGAAFLCGDLQAGFELVAVDGESLEQ-VTHQRAVdtirrAYRNK 934
Cdd:cd06689    17 YIELEKpESGGLGFSVVGlKSENRGELGIFVQEIQPGSVAARDGRLKENDQILAINGQPLDQsISHQQAI-----AILQQ 91


                  ....*....
gi 569006111  935 AREPMELVV 943
Cdd:cd06689    92 AKGSVELVV 100

PDZ domain 2 of Discs Large 5 (Dlg5) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of Drosophila and mammalian Dlg5, and related domains. Dlg5 is a scaffold protein with multiple conserved functions that are independent of each other in regulating growth, cell polarity, and cell adhesion. It has a coiled-coil domain, 4 PDZ domains and a MAGUK domain (an SH3 domain next to a non-catalytically active guanylate kinase domain). Deregulation of Dlg5 has been implicated in the malignancy of several cancer types. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Dlg5-like family PSZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467246 [Multi-domain] Cd Length: 77 Bit Score: 38.48 E-value: 1.26e-03

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gi 569006111  225 NIRGGKEFGL----GIYVSKVDHGGL-AEENGIKVGDQVLAANGVRFDDISHSQAVEVLKG-QTHIMLTI 288
Cdd:cd06765     3 NLSGQKDSGIslenGVFISRIVPGSPaAKEGSLTVGDRIIAINGIALDNKSLSECEALLRScRDSLSLSL 72

circularly permuted PDZ domain 2 (PDZ-C) of Escherichia coli Regulator of sigma-E protease (RseP) and related domains; Permuted PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of ResP (also known as Site-2 protease RseP, and YaeL) and related domains. RseP is involved in the regulation of an extracytoplasmic stress response through the cleavage of membrane-spanning anti-stress-response transcription factor (anti-sigmaE) protein RseA; it cleaves the peptide bond between the critical alanine and cysteine in the transmembrane region of RseA, releasing the cytoplasmic domain of RseA with it associated sigmaE. RseP contains two tandem-arranged periplasmic PDZ domains (PDZ-N/PDZ1 and PDZ-C/PDZ2) which act to negatively regulate protease action on intact RseA; they serve as a size-exclusion filter which prevents the access of an intact RseA into the active site of RseP. PDZ domains usually bind in sequence-specific manner to short peptide sequences located at the C-terminal of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains and as well as those with circular permutations and domain swapping of beta-strands. The canonical PDZ domain contains six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2); arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F. This RseP family PDZ domain is a circularly permuted PDZ domain which places both beta-strands A and B at the C-terminus. Another permutation exists in the PDZ superfamily which places beta-strand A at the C-terminus.

Pssm-ID: 467640 [Multi-domain] Cd Length: 85 Bit Score: 38.65 E-value: 1.28e-03

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gi 569006111  113 VSKVEEGSSAERAGLCVGDKITEVNGLSLE 142
Cdd:cd23083     3 LANVQPNSAAEKAGLQAGDRIVKVDGQPLT 32

PDZ domain 2 of glutamate receptor-interacting protein 1 (GRIP1) and GRIP2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) binding proteins GRIP1 (ABP/GRIP2) and GRIP2, and related domains. GRIP1 and GRIP2 each have 7 PDZ domains. The interaction of GRIP1 and GRIP2 with GluA2/3 (AMPAR subunit) regulates AMPAR trafficking and synaptic targeting. GRIP1 has an essential role in regulating AMPAR trafficking during synaptic plasticity and learning and memory. GRIP1 and GRIP2 interact with a variety of other proteins associated with protein trafficking and internalization, for example GRIP1 also interacts with KIF5 (also known as kinesin 1), EphB receptors, scaffold protein liprin-alpha, and the rasGEF GRASP-1. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This GRIP family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467169 [Multi-domain] Cd Length: 89 Bit Score: 38.75 E-value: 1.48e-03

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gi 569006111   84 IHAVRVEKSPSGrLGFSVRGG-SEHGLG---IFVSKVEEGSSAERAG-LCVGDKITEVNGLSLESTTMGSAVRLLTSSS 157
Cdd:cd06681     2 TVEVTLEKEGNS-FGFVIRGGaHEDRNKsrpLTVTHVRPGGPADREGtIKPGDRLLSVDGISLHGATHAEAMSILKQCG 79

PDZ domain of LIM Kinase (LIMK) family, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of the LIMK protein family, and related domains. The LIMK family is composed of LIMK1 and LIMK2, which are common downstream effectors of several signalization pathways and function as signaling nodes that control cytoskeleton dynamics through the phosphorylation of cofilin family proteins. They also control microtubule dynamics. The LIMK1 PDZ domain binds tubulin and nischarin. LIMK1 also binds a carboxy-terminal motif of membrane type 1-matrix metalloproteinase (MT1-MMP, also known as MMP14) having features of a PDZ domain-binding site; MT1-MMP is a major protease involved in dissemination of carcinoma cells during cancer progression. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This LIMK-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467236 [Multi-domain] Cd Length: 92 Bit Score: 38.79 E-value: 1.54e-03

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gi 569006111   87 VRVEKSPSGRLGFSV---RGGSEHGLGIFVSKVEEGS-SAERAGLCVGDKITEVNGLSLESTTMGSAVRLLTSSS 157
Cdd:cd06754     7 VSIPPTPEGKRGFSVsveKGCSEHSHTVRVSELDPMHlSPDLKSLHVGDRILEVNGTPVRDLSLEEIDDLIQSTS 81

PDZ domain of PDZ domain-containing protein 11, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of PDZD11, and related domains. PDZD11 (also known as ATPase-interacting PDZ protein, plasma membrane calcium ATPase-interacting single-PDZ protein, PMCA-interacting single-PDZ protein, PISP) is involved in the dynamic assembly of apical junctions (AJs). It is recruited by PLEKHA7 to AJs to promote the efficient junctional recruitment and stabilization of nectins, and the efficient early phases of assembly of AJs in epithelial cells. The PDZD11 PDZ domain binds nectin-1 and nectin-3. PDZD11 also binds to a PDZ binding motif located in the C-terminal tail of the human sodium-dependent multivitamin transporter, to the cytoplasmic tail of the Menkes copper ATPase ATP7A, and to the cytoplasmic tail of all plasma membrane Ca2+-ATPase b-splice variants. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PDZD11-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467234 [Multi-domain] Cd Length: 83 Bit Score: 38.45 E-value: 1.66e-03

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gi 569006111  857 RTITLSKMK-QSLGISISGGIESkvQPMVKIEKIFPGGAAFLCGdLQAGFELVAVDGESLEQVTHQRAVDTIRRA 930
Cdd:cd06752     1 RTVVLKRPPgEQLGFNIRGGKAS--GLGIFISKVIPDSDAHRLG-LKEGDQILSVNGVDFEDIEHSEAVKVLKTA 72

PDZ domain 5 of protein tyrosine phosphatase non-receptor type 13 (PTPN13), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 5 of PTPN13 [also known as Fas-associated protein-tyrosine phosphatase 1 (FAP-1), Protein-tyrosine phosphatase 1E (PTP-E1), and Protein-tyrosine phosphatase (PTPL1)] and related domains. PTPN13 regulates negative apoptotic signaling and mediates phosphoinositide 3-kinase (PI3K) signaling. PTPN13 has five PDZ domains. Proteins known to interact with PTPN13 PDZ domains include: PLEKHA1 and PLEKHA2 via PTPN13-PDZ domain 1, Fas receptor and thyroid receptor-interacting protein 6 via PTPN13-PDZ domain 2, nerve growth factor receptor and protein kinase N2 via PTPN13-PDZ domain 3, PDZ and LIM domain 4 (PDLIM4) via PTPN13-PDZ domains 2 and 4, and brain calpain-2 via PTPN13-PDZ domains 3, 4 and 5. Calpain-2-mediated PTPN13 fragments may be involved in abnormal tau aggregation and increased risk for Alzheimer's disease. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PTPN13 family PDZ5 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467183 [Multi-domain] Cd Length: 87 Bit Score: 38.48 E-value: 1.67e-03

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gi 569006111   95 GRLGFSVRGGSEHGL-GIFVSKVEEGSSAERAG-LCVGDKITEVNGLSLESTTMGSAVRLLTSS 156
Cdd:cd06697    13 GQLGLKLTGGSDSKYqVIYVLEIVPGSAAAEEGsLQPLDIIHYINGVSTQGMTLEDAVRALEAS 76

PDZ domain of tyrosine-protein phosphatase non-receptor type 3 (PTPN3), tyrosine-protein phosphatase non-receptor type 4 (PTNP4), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of PTPN3, PTPN4 and related domains. PTPN3 (also known as protein-tyrosine phosphatase H1, PTP-H1) has a tumor-suppressive or a tumor-promoting role in many cancers. It serves as a specific phosphatase for the MAP kinase p38gamma; the two interact via their PDZ domains and cooperate to promote Ras-induced oncogenesis. Interaction partners of the PTPN3 PDZ domain include p38gamma and human papillomavirus E6 oncoprotein. PTPN4 (also known as protein-tyrosine phosphatase MEG1) plays a role in immunity, learning, synaptic plasticity or cell homeostasis. p38gamma is also an interaction partner of the PTPN4 PDZ domain: PTPN4 regulates neuronal cell homeostasis by protecting neurons against apoptosis; binding of the C terminus of p38gamma to the PDZ domain of PTPN4, antagonizes the catalytic autoinhibition of PTPN4, leading to cell apoptosis. Other interaction partners of the PTPN4 PDZ domain include glutamate receptor subunit GluN2A, and RABV strain G protein, among others. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PTPN3-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467190 [Multi-domain] Cd Length: 90 Bit Score: 38.45 E-value: 1.72e-03

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gi 569006111  223 GFNIRGGKEFGLGIYVSKVDHGGLAEENGIKV--GDQVLAANGVRFDDISHSQAVEVLKGQTH-----IMLTIK 289
Cdd:cd06706    17 GFNVKGGVDQKMPVIVSRVAPGTPADLCIPRLneGDQVLLINGRDISEHTHDQVVMFIKASRErhsgeLVLLVR 90

PDZ domain 4 of Discs Large 5 (Dlg5) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 4 of Drosophila and mammalian Dlg5, and related domains. Dlg5 is a scaffold protein with multiple conserved functions that are independent of each other in regulating growth, cell polarity, and cell adhesion. It has a coiled-coil domain, 4 PDZ domains and a MAGUK domain (an SH3 domain next to a non-catalytically active guanylate kinase domain). Deregulation of Dlg5 has been implicated in the malignancy of several cancer types. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Dlg5-like family PDZ4 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467247 [Multi-domain] Cd Length: 81 Bit Score: 38.14 E-value: 1.81e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 569006111  209 RIVHLYTTSDDfcLGFNIRGGKEFGlgIYVSKVDHGGLAEE-NGIKVGDQVLAANGVRFDDISHSQA-VEVLK 279
Cdd:cd06766     3 RLVFLKKSQVE--LGIQLCGGNLHG--IFVEDVEDDSPAKGpDGLVPGDLILEYNSVDMRNKTAEEAyLEMLK 71

PDZ domain of microtubule-associated serine-threonine (MAST) protein kinase 1; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of MAST family kinase MAST1, and related domains. MAST1 belongs to the MAST family kinases, which include MAST1-4. These MAST proteins contain a DUF1908 domain, a serine/threonine kinase domain, a AGC-kinase C-terminal domain, and a PDZ domain; MAST family member MASTL is a shorter protein lacking the PDZ domain. MAST1 functions as a scaffold protein to link the dystrophin/utrophin network with microfilaments via syntrophin, and it has been identified as a main driver of cisplatin resistance in human cancers. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MAST1 family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F

Pssm-ID: 467286 [Multi-domain] Cd Length: 95 Bit Score: 38.47 E-value: 2.00e-03

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 569006111  113 VSKVEEGSSAERAGLCVGDKITEVNGLSLESTTMGSAVRLLTSS 156
Cdd:cd23073    37 VWHVEEGGPAQEAGLCAGDLITHVNGEPVHGMVHPEVVELILKS 80

PDZ domain 1 of Discs Large 5 (Dlg5) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of Drosophila and mammalian Dlg5, and related domains. Dlg5 is a scaffold protein with multiple conserved functions that are independent of each other in regulating growth, cell polarity, and cell adhesion. It has a coiled-coil domain, 4 PDZ domains and a MAGUK domain (an SH3 domain next to a non-catalytically active guanylate kinase domain). Deregulation of Dlg5 has been implicated in the malignancy of several cancer types. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Dlg5-like family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467245 [Multi-domain] Cd Length: 95 Bit Score: 38.53 E-value: 2.04e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 569006111   97 LGFSVRGG-SEHGL----GIFVSKVEEGSSAErAGLCVGDKITEVNGLSLESTTMGSAVR-LLTSSSCLHMMVRR 165
Cdd:cd06764    21 LGFDIAGGvNDPQFpgdcSIFVTKVDKGSIAD-GRLRVNDCLLRINDVDLTNKDKKQAIQaVLNGGGVINMVVRR 94

PDZ domain 2 of partitioning defective 3 (Par3), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of Par3 (or PAR3 or Par-3, also known as Atypical PKC isotype-specific-interacting protein, ASIP, Drosophila Bazooka) and related domains. Par3 is a scaffold protein involved in organizing cell polarity across animals. Par3 binds numerous molecules both for its recruitment to one pole of the cell and for downstream contributions to polarized cell function. It regulates cell polarity by targeting the Par complex proteins Par6 and atypical protein kinase C (aPKC) to specific cortical sites. Physical interactions between Par3 and the Par complex include Par3 PDZ domain 1 binding to the Par6 PDZ domain, Par3 PDZ domain 1 and PDZ domain 3 binding the Par6's PDZ-binding motif, and an interaction with an undefined region of aPKC that requires both Par3 PDZ2 and PDZ3. The PDZ domains of Par3 have also been implicated as potential phosphoinositide signaling integrators, since its second PDZ domain binds to phosphoinositides, and the third PDZ interacts with phosphoinositide phosphatase PTEN. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Par3 family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467271 [Multi-domain] Cd Length: 93 Bit Score: 38.39 E-value: 2.32e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569006111   91 KSPSGrLGFSV--RGGSEHGLG-IFVSKVEEGSSAERAG-LCVGDKITEVNGLS------------LESTTMGSAVRLLT 154
Cdd:cd23058    12 KGPEG-LGFSItsRDNPTGGSGpIYIKNILPKGAAIQDGrLKAGDRLLEVNGVDvtgktqeevvslLRSTKLGGTVSLVV 90


                  .
gi 569006111  155 S 155
Cdd:cd23058    91 S 91

PDZ domain of regulator of G-protein signaling 3 (RGS3), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of RGS3, and related domains. RGS3 down-regulates GPCR signal transduction by increasing the GTPase activity of G-protein alpha subunits, thereby driving G-proteins into their inactive GDP-bound form. It downregulates G-protein-mediated release of inositol phosphates and activation of MAP kinases. In Eph/ephrin signaling, RGS3 binds via its PDZ domain to the cytoplasmic C terminus of Eph receptor tyrosine kinase EphB. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This RGS3-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467195 [Multi-domain] Cd Length: 77 Bit Score: 37.37 E-value: 2.90e-03

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 569006111  113 VSKVEEGSSAERAGLCVGDKITEVNGLSLESTTMGSAVRLLTSS 156
Cdd:cd06711    24 VQAVDPGGPAEQAGLQQGDTVLQINGQPVERSKCVELAHAIRNC 67

PDZ domain 8 of multi-PDZ-domain protein 1 (MUPP1), PDZ domain 7 of protein-associated tight junction (PATJ), PDZ domain 2 of Drosophila melanogaster inactivation-no-after-potential D (INAD), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 8 of MUPP1, PDZ domain 7 of PATJ, and PDZ domain 2 of Drosophila melanogaster INAD, and related domains. MUPP1 and PATJ serve as scaffolding proteins linking different proteins and protein complexes involved in the organization of tight junctions and epithelial polarity. MUPP1 contains an L27 (Lin-2 and Lin-7 binding) domain and 13 PDZ domains. PATJ (also known as INAD-like) contains an L27 domain and ten PDZ domains. MUPP1 and PATJ share several binding partners, including junctional adhesion molecules (JAM), zonula occludens (ZO)-3, Pals1 (protein associated with Lin-7), Par (partitioning defective)-6 proteins, and nectins (adherence junction adhesion molecules). PATJ lacks 3 PDZ domains seen in MUPP1: PDZ6, 9, and 13; consequently, MUPP1 PDZ7 and 8 align with PATJ PDZ6 and 7; and MUPP1 PDZ domains 10-12 align with PATJ PDZ domains 8-10. INAD assembles key enzymes of the Drosophila compound eye photo-transduction pathway into a supramolecular complex, supporting efficient and fast light signaling. It contains 5 PDZ domains arranged in tandem (PDZ1-PDZ5) which independently bind various proteins. INAD PDZ2 binds eye-specific protein kinase C. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MUPP1-like family PDZ8 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467160 [Multi-domain] Cd Length: 84 Bit Score: 37.66 E-value: 2.93e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 569006111  856 LRTITLSKMKQSLGISISGGiESKVQPMVKIEKIFPGGAAFLCGDLQAGFELVAVDGESLEQVTHQRAVDTIRRA 930
Cdd:cd06672     1 LHLIELEKGSSGLGLSLAGN-KDRSRMSVFVVGIDPDGAAGKDGRIQVGDELLEINGQVLYGRSHLNASAIIKSA 74

C-terminal processing protease CtpA/Prc, contains a PDZ domain [Posttranslational modification, protein turnover, chaperones];

Pssm-ID: 440556 [Multi-domain] Cd Length: 341 Bit Score: 41.01 E-value: 3.07e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569006111  861 LSKMKQSLGISISG-GIE-SKVQPMVKIEKIFPGGAAFLCGdLQAGFELVAVDGESLEQVTHQRAVDTIRRA-------- 930
Cdd:COG0793    48 YEDFQESTSGEFGGlGAElGEEDGKVVVVSVIPGSPAEKAG-IKPGDIILAIDGKSVAGLTLDDAVKLLRGKagtkvtlt 126

                          90
                  ....*....|....*
gi 569006111  931 -YRNKAREPMELVVR 944
Cdd:COG0793   127 iKRPGEGEPITVTLT 141

PDZ domain 1 of amyloid-beta A4 precursor protein-binding family A member 1 (APBA1), APBA2, APBA3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of APBA1, APBA2, APBA3, and related domains. The APBA/X11/Mint protein family includes three members: neuron specific APBA1 (also known as X11alpha and Mint1) and APBA2 (also known as X11beta and Mint2), and the ubiquitously expressed APBA3 (also known as (X12gamma and Mint3). They are involved in regulating neuronal signaling, trafficking and plasticity. They contain two PDZ domains (PDZ1 and PDZ2) which bind a variety of proteins: Arf GTPases (APBA1 and APBA2 PDZ2) and neurexin (APBA1 and APBA2 PDZ1 and 2), which are involved in vesicle docking and exocytosis; alpha1B subunit of N-type Ca2+ channel (APBA1 PDZ1) that is involved in ion channels; KIF17 (APBA1 PDZ1) that is involved in transport and traffic; and Alzheimer's disease related proteins such as APP (APBA3 PDZ2), CCS (APBA1 PDZ2), NF-kappa-B/p65 (APBA2 PDZ2), presenilin-1 (APBA1 and APBA2 PDZ1 and PDZ2). PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This APBA1,2,3-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta- strand F.

Pssm-ID: 467203 [Multi-domain] Cd Length: 86 Bit Score: 37.62 E-value: 3.12e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 569006111  857 RTITLSKMK-QSLGISIsggIES---KVQPMVKIEKIFPGGAAFLCGDLQAGFELVAVDGESL 915
Cdd:cd06720     1 KEVVVEKQKgEILGVVI---VESgwgSLLPTVVVANMMPGGPAARSGKLNIGDQIMSINGTSL 60

PDZ domain of Ras-associating and dilute domain-containing protein (Radil) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of Radil (also known as protein KIAA1849) and related domains. Radil is required for cell adhesion and migration of neural crest precursors during development. Radil is a component of a Rasip1-Radil-ARHGAP29 complex at endothelial cell-cell junctions. Rap1, via its effectors Radil and Rasip1 and their binding partner ArhGAP29, controls the endothelial barrier by decreasing Rho-mediated radial tension on cell-cell junctions. ArhGAP29 binds the Radil PDZ domain. The Radil PDZ domain also binds kinesin family protein 14 (KIF14); KIF14 negatively regulates Rap1-mediated inside-out integrin activation by tethering Radil on microtubules. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Radil-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467177 [Multi-domain] Cd Length: 88 Bit Score: 37.66 E-value: 3.29e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 569006111   84 IHAVRVEKSPSGrLGFSVRGGSEHGL---GIFVSKVEEGSSAERAG-LCVGDKITEVNGLSLESTTMGSAVRLLTSS 156
Cdd:cd06690     3 VFVVELERGPKG-LGLGLIDGLHTPLrspGIYIRTLVPDSPAARDGrLRLGDRILAVNGTSLVGADYQSAMDLIRTS 78

PDZ domain 3 of inactivation-no-after-potential D (INAD), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of INAD, and related domains. INAD assembles key enzymes of the Drosophila compound eye photo-transduction pathway into a supramolecular complex, supporting efficient and fast light signaling. It contains 5 PDZ domains arranged in tandem (PDZ1-PDZ5) which independently bind various proteins. INAD PDZ2 binds eye-specific protein kinase C, INAD PDZ3 binds transient receptor potential (TRP) channel, and INAD PDZ4,5 tandem binds NORPA (phospholipase Cbeta, PLCbeta). Mutations of the inaD gene that lead to disruption of each of these interactions impair fly photo signal transduction. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This INAD-like family PDZ3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467277 [Multi-domain] Cd Length: 80 Bit Score: 37.31 E-value: 3.32e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569006111  222 LGFNIRGGK--EFGLGIYVSKVDHGGLAEENGIKVGDQVLAANGVRFDDISHSQAVEVLKgQTHIMLTIK 289
Cdd:cd23064    10 LGIMVIYGKhaEVGSGIFISDLREGSNAELAGVKVGDMLLAVNQDVTLESNYDDATGLLK-RAEGVVTMI 78

PDZ domain 1 of Zonula Occludens-1 (ZO-1), homologs ZO-2 and ZO-3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of ZO-1, -2, -3 and related domains. Zonula occludens proteins (ZO-1, ZO-2, ZO-3) are multi-PDZ domain proteins involved in the maintenance and biogenesis of multi-protein networks at the cytoplasmic surface of intercellular contacts in epithelial and endothelial cells. They have three N-terminal PDZ domains, PDZ1-3, followed by a Src homology-3 (SH3) domain and a guanylate kinase (GuK)-like domain. Among protein-protein interactions for all ZO proteins is the binding of the first PDZ domain (PDZ1) to the C-termini of claudins, and the homo- and hetero-dimerization of ZO-proteins via their second PDZ domain (PDZ2), which takes place by symmetrical domain swapping of the first two beta-strands of PDZ2. At the cell level, ZO-1 and ZO-2 are involved in polarity maintenance, gene transcription, cell proliferation, and tumor cell metastasis. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This ZO family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467209 [Multi-domain] Cd Length: 87 Bit Score: 37.64 E-value: 3.59e-03

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569006111   85 HAVRVEKSPSGRLGFSVRGG--SEHGLG----IFVSKVEEGSSAErAGLCVGDKITEVNGLSLESTTMGSAVRLL-TSSS 157
Cdd:cd06727     1 HTVTLHRAPGFGFGIAVSGGrdNPHFQSgdtsIVISDVLKGGPAE-GKLQENDRVVSVNGVSMENVEHSFAVQILrKCGK 79


                  ....*...
gi 569006111  158 CLHMMVRR 165
Cdd:cd06727    80 TANITVKR 87

PDZ domain;

Pssm-ID: 433015 [Multi-domain] Cd Length: 74 Bit Score: 37.25 E-value: 3.85e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 569006111   235 GIYVSKVDHGGLAEENGIKVGDQVLAANGVRFDDISHSQAV 275
Cdd:pfam13180    7 GVVVVSVKSSGPAAKAGLKAGDVILSIDGRKINDLTDLESA 47

PDZ domain of DEP domain-containing mTOR-interacting protein (DEPTOR), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of DEPTOR, and related domains. DEPTOR (also known as DEP domain-containing protein 6, DEP6) is a regulatory protein of mTOR signaling; it is a negative regulator of both the mTORC1 and mTORC2 signaling pathways. DEPTOR's PDZ domain binds to mTOR's FAT domain to suppress mTOR's kinase activity. The DEPTOR PDZ domain also binds lysine-specific demethylase 4A (KDM4A), leucine-rich repeat containing 4 (LRRC4), p38gamma, and major intrinsically disordered Notch2-binding receptor 1 (MINAR1, also known as Ubtor). DEPTOR also interacts with salt-inducible kinase 3 (SIK3). PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This DEPTOR-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467280 [Multi-domain] Cd Length: 75 Bit Score: 37.01 E-value: 3.97e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 569006111  217 SDDFCLGFNIRGGKEfglgIYVSKVDHGGLAEENGIKVGDQVLAANGVRFDDISHSQ-AVEVLKGQTHIMLTI 288
Cdd:cd23067     6 GDAVGWGFVVRGSKP----CHIQAVDPSGPAAAAGMKVCQFIVSVNGLNVLHMDHRTvSNLILTGPRTIVMEV 74

PDZ domain 2 of the full-length isoform of whirlin and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of the full-length isoform of whirlin and related domains. Whirlin is an essential protein for developmental pathways in photoreceptor cells of the retina and hair cells of the inner ear. The full-length whirlin isoform has two harmonin N-like domains, three PDZ domains, a proline-rich region, and a PDZ-binding motif. Whirlin isoforms may form different complexes at the periciliary membrane complex (PMC) in photoreceptors, and the stereociliary tip and base in inner ear hair cells. It interacts with ADGRV1 and usherin at the PMC; with SANS and RpgrORF15 at the connecting cilium in photoreceptors; with EPS8, MYO15A, p55, and CASK proteins at the stereociliary tip of inner ear hair cells; and with ADGRV1, usherin, and PDZD7 at the stereociliary base in inner ear hair cells. Mutations in the gene encoding whirlin (WHRN; also known as USH2D and DFNB31), have been found to cause either USH2 subtype (USH2D) or autosomal recessive non-syndromic deafness type 31 (DFNB31). Whirlin is the key protein in the USH2 complex (whirlin, usherin and GPR98) which recruits other USH2 causative proteins at the periciliary membrane in photoreceptors and the ankle link of the stereocilia in hair cells. Whirlin's interaction with espin, another stereociliary protein, may be important for the architecture of the USH2 complex. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This whirlin family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467223 [Multi-domain] Cd Length: 84 Bit Score: 37.24 E-value: 4.06e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 569006111  866 QSLGISISGGIESKVQpmVKIEKIFPGGAAFLCGdLQAGFELVAVDGESLEQVTHQRAVDTIR 928
Cdd:cd06741    12 QSLGLMIRGGAEYGLG--IYVTGVDPGSVAENAG-LKVGDQILEVNGRSFLDITHDEAVKILK 71

circularly permuted PDZ domain of Arabidopsis thaliana putative protease Do-like 14 (DEGP14) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of Arabidopsis thaliana putative protease DEGP14 and related domains. DEGP14 is a putative protease belonging to the HtrA family of housekeeping proteases. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains and as well as those with circular permutations and domain swapping of beta-strands. The canonical PDZ domain contains six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2); arranged as A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F. This AtDEGP14-like PDZ domain is a circularly permuted PDZ domain which places beta-strand A on the C-terminus. Another permutation exists in the PDZ superfamily which places both beta-strands A and B on the C-terminus.

Pssm-ID: 467632 [Multi-domain] Cd Length: 101 Bit Score: 37.83 E-value: 4.32e-03

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                  ....*....|....*....|....*....|....*.
gi 569006111  110 GIFVSKVEEGSSAERAGLCVGDKITEVNGLSLESTT 145
Cdd:cd23085    32 GVLVPQVIPGSPAERAGLRPGDVIVEFDGKPVDSTK 67

PDZ domain 5 of glutamate receptor-interacting protein 1 (GRIP1) and GRIP2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) binding proteins GRIP1 (ABP/GRIP2) and GRIP2, and related domains. GRIP1 and GRIP2 each have 7 PDZ domains. The interaction of GRIP1 and GRIP2 with GluA2/3 (AMPAR subunit) regulates AMPAR trafficking and synaptic targeting. GRIP1 has an essential role in regulating AMPAR trafficking during synaptic plasticity and learning and memory. GRIP1 and GRIP2 interact with a variety of other proteins associated with protein trafficking and internalization, for example GRIP1 also interacts with KIF5 (also known as kinesin 1), EphB receptors, scaffold protein liprin-alpha, and the rasGEF GRASP-1. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This GRIP family domain PDZ5 is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467170 [Multi-domain] Cd Length: 85 Bit Score: 37.32 E-value: 4.46e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 569006111  867 SLGISISGGIESKVQPMVKIEKIFPGGAAFLCGDLQAGFELVAVDGESLEQVTHQRAVDTIRRA 930
Cdd:cd06682    12 GLGITISAPKNRKPGDPLIISDVKKGSVAHRTGTLEPGDKLLAIDNIRLDNCSMEDAAQILQQA 75

circularly permuted PDZ domain of C-terminal processing peptidase (CPP), a serine protease, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of CPP (also known as tail-specific protease, PRC protein, Protease Re, and Photosystem II D1 protein processing peptidase), and related domains. CPP belongs to the peptidase S41A family. It cleaves a C-terminal 11 residue peptide from the precursor form of penicillin-binding protein 3, and may have a role in protecting bacterium from thermal and osmotic stresses. In the plant chloroplast, the enzyme removes the C-terminal extension of the D1 polypeptide of photosystem II. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains and as well as those with circular permutations and domain swapping of beta-strands. The canonical PDZ domain contains six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2); arranged as A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F. This CPP-like PDZ domain is a circularly permuted PDZ domain which places beta-strand A on the C-terminus. Another permutation exists in the PDZ superfamily which places both beta-strands A and B on the C-terminus.

Pssm-ID: 467623 [Multi-domain] Cd Length: 88 Bit Score: 37.08 E-value: 4.76e-03

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 569006111  884 VKIEKIFPGGAAFLCGdLQAGFELVAVDGESLEQVTHQRAVDTIR 928
Cdd:cd06782    16 LVVVSPIPGGPAEKAG-IKPGDVIVAVDGESVRGMSLDEVVKLLR 59

PDZ domain of neuronal nitric oxide synthase (nNOS), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of nNOS, and related domains. nNOS produces a key signaling molecule, nitric oxide (NO), which has diverse functions throughout the body and acts as a neurotransmitter and intracellular signaling molecule in the central and peripheral nervous system. nNOS is concentrated at synaptic junctions in the brain and motor endplates in skeletal muscle. The PDZ domain of neuronal nitric oxide synthase (nNOS) interacts with the PDZ domain of alpha1-syntrophin (in muscle cells) and with the second PDZ domain of Disks large homolog 4 (Dlg4, also known as PSD-95), and nitric oxide synthase 1 adaptor protein NOS1AP in neurons. Dlg4 binds NMDA receptors, and nNOS, forming a complex in neurons. NOS1AP competes with Dgl4 for the nNOS PDZ domain and prevents the coupling of nNos activation with NMDA receptor-mediated calcium influx. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This nNOS-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467192 [Multi-domain] Cd Length: 110 Bit Score: 37.74 E-value: 4.78e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 569006111   86 AVRVEKSPSGRLGFSVRGGSEHGLGIfVSKVEEGSSAERAGLC-VGDKITEVNGLSLESTTMGSAVRLLTS 155
Cdd:cd06708     4 SVRLFKRKVGGLGFLVKQRVCKPPVI-ISDLIRGGAAEQSGLVqVGDIILAVNGRPLVDVSYESALEVLRS 73

PDZ domain 1 of partitioning defective 3 (Par3), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of Par3 (or PAR3 or Par-3, also known as Atypical PKC isotype-specific-interacting protein, ASIP) and related domains; Drosophila bazooka PDZ1 belongs to a different PDZ family. Par3 is a scaffold protein involved in organizing cell polarity across animals. Par3 binds numerous molecules both for its recruitment to one pole of the cell and for downstream contributions to polarized cell function. It regulates cell polarity by targeting the Par complex proteins Par6 and atypical protein kinase C (aPKC) to specific cortical sites. Physical interactions between Par3 and the Par complex include: Par-3 PDZ domain 1 binding to the Par6 PDZ domain, Par3 PDZ domain 1 and PDZ domain 3 binding the Par6's PDZ-binding motif, and an interaction with an undefined region of aPKC that requires both Par3 PDZ2 and PDZ3. The PDZ domains of Par3 have also been implicated as potential phosphoinositide signaling integrators, since its second PDZ domain binds to phosphoinositides, and the third PDZ interacts with phosphoinositide phosphatase PTEN. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Par3 family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467178 [Multi-domain] Cd Length: 98 Bit Score: 37.59 E-value: 4.89e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 569006111   84 IHAVRVEKSPSGRLgfsvrggsehgLGIFVSKVEEGSSAERAGLC-VGDKITEVNGLSL 141
Cdd:cd06691    19 IHVVPFSSSLSGRT-----------LGLLIRGIEEGSRAERDGRFqENDCIVEINGVDL 66

PDZ domain 2 of delphilin (L-delphilin isoform), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of delphilin (also known as glutamate receptor, ionotropic, delta 2-interacting protein 1, L-delphilin). Delphilin, a postsynaptic protein which it is selectively expressed at cerebellar Purkinje cells, links the glutamate receptor delta 2 subunit (GluRdelta2) with the actin cytoskeleton and various signaling molecules. Two alternatively spliced isoforms of delphilin have been characterized: L-delphilin has two PDZ domains, PDZ1 and PDZ2, and S-delphilin has a single PDZ domain (PDZ2). These two isoforms are differently palmitoylated and may be involved in controlling GluRdelta2 signaling in Purkinje cells. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This delphilin-like family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F

Pssm-ID: 467226 [Multi-domain] Cd Length: 75 Bit Score: 36.87 E-value: 5.08e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 569006111  858 TITLSKMKQSLGISISGGIEskvqpmVKIEKIFPGGAAFLCGdLQAGFELVAVDGESLEQVTHQRAVD 925
Cdd:cd06744     1 TVRVYRGNGSFGFTLRGHAP------VYIESVDPGSAAERAG-LKPGDRILFLNGLDVRNCSHDKVVS 61

Predicted metalloprotease, contains C-terminal PDZ domain [General function prediction only];

Pssm-ID: 443174 [Multi-domain] Cd Length: 591 Bit Score: 40.58 E-value: 5.08e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569006111  855 ALRTITLSKMKQSLGISISggiesKVQPMVKIEKIFPGGAAFLCGdLQAGFELVAVDGeslEQVTHQRAVDTIRRAyrnK 934
Cdd:COG3975   472 KLVYEDAPSLKPSLGLRVS-----ADGGGLVVTSVLWGSPAYKAG-LSAGDELLAIDG---LRVTADNLDDALAAY---K 539


                  ....*....
gi 569006111  935 AREPMELVV 943
Cdd:COG3975   540 PGDPIELLV 548

periplasmic serine protease, Do/DeqQ family; This family consists of a set proteins various designated DegP, heat shock protein HtrA, and protease DO. The ortholog in Pseudomonas aeruginosa is designated MucD and is found in an operon that controls mucoid phenotype. This family also includes the DegQ (HhoA) paralog in E. coli which can rescue a DegP mutant, but not the smaller DegS paralog, which cannot. Members of this family are located in the periplasm and have separable functions as both protease and chaperone. Members have a trypsin domain and two copies of a PDZ domain. This protein protects bacteria from thermal and other stresses and may be important for the survival of bacterial pathogens.// The chaperone function is dominant at low temperatures, whereas the proteolytic activity is turned on at elevated temperatures. [Protein fate, Protein folding and stabilization, Protein fate, Degradation of proteins, peptides, and glycopeptides]

Pssm-ID: 273938 [Multi-domain] Cd Length: 428 Bit Score: 40.67 E-value: 5.12e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569006111    67 VILINSPIEANSDESDIIHAVRVEKSPSGRLGFSVRGGSEhglGIFVSKVEEGSSAERAGLCVGDKITEVNGLSLESTT- 145
Cdd:TIGR02037  323 VTLGASPEEQASSSNPFLGLTVANLSPEIRKELRLKGDVK---GVVVTKVVSGSPAARAGLQPGDVILSVNQQPVSSVAe 399

                           90       100
                   ....*....|....*....|...
gi 569006111   146 MGSAVRLLTSSSCLHMMVRRMGR 168
Cdd:TIGR02037  400 LRKVLARAKKGGRVALLILRGGA 422

Peptidase family M50;

Pssm-ID: 426630 [Multi-domain] Cd Length: 291 Bit Score: 40.17 E-value: 5.13e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 569006111   112 FVSKVEEGSSAERAGLCVGDKITEVNGLSLESTTMGSAVRLLTSSSCLHMMVRRMGRV 169
Cdd:pfam02163   96 VIGGVAPGSPAAKAGLKPGDVILSINGKKITSWQDLVEALAKSPGKPITLTVERGGQT 153

PDZ domain 4 of membrane-associated guanylate kinase inverted 1 (MAGI-1), MAGI-2, and MAGI-3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 4 of MAGI1, 2, 3 (MAGI is also known as Membrane-associated guanylate kinase, WW and PDZ domain-containing protein) and related domains. MAGI proteins have been implicated in the control of cell migration and invasion through altering the activity of phosphatase and tensin homolog (PTEN) and modulating Akt signaling. Four MAGI proteins have been identified (MAGI1-3 and MAGIX). MAGI1-3 have 6 PDZ domains and bind to the C-terminus of PTEN via their PDZ2 domain. MAGIX has a single PDZ domain that is related to MAGI1-3 PDZ domain 5. Other binding partners for MAGI1 include JAM4, C-terminal tail of high risk HPV-18 E6, megalin, TRAF6, Kir4.1 (basolateral K+ channel subunit), and cadherin 23; for MAGI2, include DASM1, dendrin, axin, beta- and delta-catenin, neuroligin, hyperpolarization-activated cation channels, beta1-adrenergic receptors, NMDA receptor, and TARPs; and for MAGI3 includes LPA2. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MAGI family PDZ4 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2); arranged as beta-strands A, -B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467216 [Multi-domain] Cd Length: 84 Bit Score: 36.82 E-value: 6.20e-03

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 569006111  252 IKVGDQVLAANGVRFDDISHSQAVEVLK-GQTHIMLTI 288
Cdd:cd06734    45 LKVGDRILAVNGISILNLSHGDIVNLIKdSGLSVTLTI 82

PDZ domain of neuronal nitric oxide synthase (nNOS), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of nNOS, and related domains. nNOS produces a key signaling molecule, nitric oxide (NO), which has diverse functions throughout the body and acts as a neurotransmitter and intracellular signaling molecule in the central and peripheral nervous system. nNOS is concentrated at synaptic junctions in the brain and motor endplates in skeletal muscle. The PDZ domain of neuronal nitric oxide synthase (nNOS) interacts with the PDZ domain of alpha1-syntrophin (in muscle cells) and with the second PDZ domain of Disks large homolog 4 (Dlg4, also known as PSD-95), and nitric oxide synthase 1 adaptor protein NOS1AP in neurons. Dlg4 binds NMDA receptors, and nNOS, forming a complex in neurons. NOS1AP competes with Dgl4 for the nNOS PDZ domain and prevents the coupling of nNos activation with NMDA receptor-mediated calcium influx. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This nNOS-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467192 [Multi-domain] Cd Length: 110 Bit Score: 37.36 E-value: 6.39e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 569006111  877 ESKVQPMVKIEKIFPGGAAFLCGDLQAGFELVAVDGESLEQVTHQRAVDTIR 928
Cdd:cd06708    21 QRVCKPPVIISDLIRGGAAEQSGLVQVGDIILAVNGRPLVDVSYESALEVLR 72

PDZ domain 9 of multi-PDZ-domain protein 1 (MUPP1) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 9 of MUPP1. MUPP1 and PATJ serve as scaffolding proteins linking different proteins and protein complexes involved in the organization of tight junctions and epithelial polarity. MUPP1 contains an L27 (Lin-2 and Lin-7 binding) domain and 13 PDZ domains. PATJ (also known as INAD-like) contains an L27 domain and ten PDZ domains. PATJ lacks 3 PDZ domains seen in MUPP1: PDZ6, PDZ9, and PDZ13. This MuPP1-like PDZ9 domain is therefore absent from PATJ. MUPP1 and PATJ share several binding partners, including junctional adhesion molecules (JAM), zonula occludens (ZO)-3, Pals1 (protein associated with Lin-7), Par (partitioning defective)-6 proteins, and nectins (adherence junction adhesion molecules). PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MUPP1-like family PDZ9 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467263 [Multi-domain] Cd Length: 79 Bit Score: 36.56 E-value: 6.54e-03

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                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 569006111  235 GIYVSKVDHGGLAEENG-IKVGDQVLAANGVRFDDISHSQAVEVLK-GQTHIMLTI 288
Cdd:cd10817    23 GIVIKSLTEGGPAAKDGrLKVGDQILAVDDESVVGCPYEKAISLLKtAKGTVKLTV 78

PDZ domain 5 of glutamate receptor-interacting protein 1 (GRIP1) and GRIP2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) binding proteins GRIP1 (ABP/GRIP2) and GRIP2, and related domains. GRIP1 and GRIP2 each have 7 PDZ domains. The interaction of GRIP1 and GRIP2 with GluA2/3 (AMPAR subunit) regulates AMPAR trafficking and synaptic targeting. GRIP1 has an essential role in regulating AMPAR trafficking during synaptic plasticity and learning and memory. GRIP1 and GRIP2 interact with a variety of other proteins associated with protein trafficking and internalization, for example GRIP1 also interacts with KIF5 (also known as kinesin 1), EphB receptors, scaffold protein liprin-alpha, and the rasGEF GRASP-1. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This GRIP family domain PDZ5 is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467170 [Multi-domain] Cd Length: 85 Bit Score: 36.55 E-value: 7.06e-03

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 569006111   87 VRVEKSPSGRLGFSVRGGSEHGLG--IFVSKVEEGSSAERAG-LCVGDKITEVNGLSLESTTMGSAVRLLTSS 156
Cdd:cd06682     3 VKLPKRSGVGLGITISAPKNRKPGdpLIISDVKKGSVAHRTGtLEPGDKLLAIDNIRLDNCSMEDAAQILQQA 75

PDZ domain 4 of protein tyrosine phosphatase non-receptor type 13 (PTPN13), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 4 of PTPN13 [also known as Fas-associated protein-tyrosine phosphatase 1 (FAP-1), protein-tyrosine phosphatase 1E (PTP-E1), and protein-tyrosine phosphatase (PTPL1)] and related domains. PTPN13 regulates negative apoptotic signaling and mediates phosphoinositide 3-kinase (PI3K) signaling. PTPN13 has five PDZ domains. Proteins known to interact with PTPN13 PDZ domains include: PLEKHA1 and PLEKHA2 via PTPN13-PDZ domain 1, Fas receptor and thyroid receptor-interacting protein 6 via PTPN13-PDZ domain 2, nerve growth factor receptor and protein kinase N2 via PTPN13-PDZ domain 3, PDZ and LIM domain 4 (PDLIM4) via PTPN13-PDZ domains 2 and 4, and brain calpain-2 via PTPN13-PDZ domains 3, 4 and 5. Calpain-2-mediated PTPN13 fragments may be involved in abnormal tau aggregation and increased risk for Alzheimer's disease. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PTPN13 family PDZ4 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467182 [Multi-domain] Cd Length: 85 Bit Score: 36.52 E-value: 7.11e-03

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 569006111   91 KSPSGRLGFSVRGGSEHGlGIFVSKVEEGSSAERAGLCVGDKITEVNGLSLESTTMGSAVRLLTSSS-CLHMMVRR 165
Cdd:cd06696    10 KSEKGSLGFTVTKGKDDN-GCYIHDIVQDPAKSDGRLRPGDRLIMVNGVDVTNMSHTEAVSLLRAAPkEVTLVLGR 84

first harmonin_N_like domain (repeat 1) of the long isoform of whirlin, and related domains; This subgroup contains the first of two harmonin_N_like domains of the long isoform of whirlin, and related domains. Whirlin is a postsynaptic density-95/discs-large/ZO-1 (PDZ) domain-containing scaffold protein which binds various components of the Usher protein network of the inner ear and the retina: erythrocyte protein p55, usherin, VlGR1, and myosin XVa. The long isoform of whirlin contains two harmonin_N_like domains, and three PDZ protein-binding domains, PDZ1-3. This first harmonin_N_like domain precedes PDZ1, and is a putative protein-binding module based on its sequence similarity to the N-terminal domain of harmonin. This first harmonin_N_like domain has been assayed for interaction with the cytoplasmic domain of cadherin 23 (a component of the Usher network and an interacting partner of the harmonin N-domain), however no interaction could be detected. The short whirlin isoform, derived from an alternative start ATG, lacks this first harmonin_N_like domain. The short isoform has in common with the long isoform, the second harmonin_N_like domain (designated repeat 2, not present in this subgroup), and PDZ3.

Pssm-ID: 259822 Cd Length: 78 Bit Score: 36.31 E-value: 7.27e-03

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 569006111  561 IQDLARRLLTDDEVLAVTRHCSRYVHEGGVEDLVRPLLAILDRPTKLLLLRDIRSVVAPTDLGRFD 626
Cdd:cd07356     8 LHVALTKLLSDAEREEFTHCLNCYHKNRNVYDLVQSLKVVLDSPEKRQLFPLLRLVIPRSDQALFD 73

PDZ domains of the Na+/H+ exchange regulatory cofactor (NHERF) family (NHERF1-4), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of the Na+/H+ exchange regulatory cofactor (NHERF) family of multi-PDZ-domain-containing scaffolding proteins (NHERF1-4), and related domains. The NHERF family includes NHERF1 (also known as EBP50), NHERF2 (also known as E3KARP; TKA-1; SIP-1), NHERF3 (also known as CAP70; CLAMP; Napi-Cap-1; PDZD1) and NHERF4 (also known as IKEPP; PDZK2; Napi-Cap-2). NHERF1 and NHERF2 have tandem PDZ domains (PDZ1-2); NHERF3 and NHERF4 have four PDZ domains (PDZ1-4). NHERFs are involved in the regulation of multiple receptors or transporters, such as type II sodium-phosphate cotransporter (Npt2a), purinergic P2Y1 receptor P2Y1R, the beta2-adrenergic receptor (beta2-AR), parathyroid hormone receptor type 1 (PTHR), the lysophosphatidic acid receptors (LPARs), sodium-hydrogen exchanger 3 (NHE3), and cystic fibrosis transmembrane conductance regulator (CFTR). NHERF-PDZ1 domain interaction partners include Npt2a, purinergic P2Y1 receptor, beta2-AR, CFTR, PTHR, NH3, G-protein-coupled receptor kinase 6 (GRK6A), platelet-derived growth factor receptor (PDGFR), B1 subunit of the H+ATPase, cholesterol, receptor for activated C-kinase RACK1, aquaporin 9, among others. The NHERF PDZ2 domain interacts with fewer proteins: NHERF1 PDZ2 binds Npt2a, PTHR, beta-catenin, aquaporin 9, and RACK1; NHERF2 PDZ2 binds LPA2, P2Y1R, and NHE3, cGMP-dependent protein kinase type II (cGKII). NHERF4 PDZ1 and PDZ4 bind the epithelial Ca(2+) channels TRPV5 and TRPV6. NHERF2/NHERF3 heterodimerization is mediated by PDZ domains of NHERF2 and the C-terminal PDZ domain recognition motif of NHERF3. NHERF4 regulates several transporters mediating influx of xenobiotics and nutrients in the small intestine. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This NHERF-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467249 [Multi-domain] Cd Length: 80 Bit Score: 36.26 E-value: 8.80e-03

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                  ....*....|....*....|....*....|....*....|...
gi 569006111  886 IEKIFPGGAAFLCGdLQAGFELVAVDGESLEQVTHQRAVDTIR 928
Cdd:cd06768    27 IREVDPGSPAERAG-LKDGDRLVEVNGENVEGESHEQVVEKIK 68

PDZ domain of neurabin-1 and neurabin-2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of neurabin-1 (also known as protein phosphatase 1 regulatory subunit 9A) and neurabin-2 (also known as spinophilin, and protein phosphatase 1 regulatory subunit 9B), and related domains. Neurabin-1 and neurabin-2 are neuronal scaffolding proteins that play important roles in the regulation of synaptic transmission through their ability to interact with and target protein phosphatase 1 (PP1) to dendritic spines where PP1 dephosphorylates and inactivates glutamate receptors. Neurabin-2 interacts with multiple other synaptic proteins, including synaptic signaling and scaffolding proteins (e.g., GluN1 and SAPAP3) and cytoskeletal proteins (e.g., neurofilament medium polypeptide, NF-M). Neurabin-1 and neurabin-2 also binds F-actin. Other binding partners of neurabin-1 include adenosine A1 receptor (A1R), SAD-1 kinase and 70 kDa ribosomal protein S6 kinase (p70-S6K). This PDZ domain is immediately C-terminal to the PP1 binding domain. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This neurabin-like PDZ domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467252 [Multi-domain] Cd Length: 90 Bit Score: 36.63 E-value: 8.89e-03

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gi 569006111  222 LGFNIRG---GKEFG---LGIYVSKVDHGGLAEENG-IKVGDQVLAANGVRFDDISHSQAVEVLK 279
Cdd:cd06790    14 LGISIIGmgvGADAGlekLGIFVKTVTEGGAAQRDGrIQVNDQIVEVDGISLVGVTQAFAASVLR 78

first harmonin_N_like domain (repeat 1) of L-delphilin, and related domains; This subgroup contains the first of two harmonin_N_like domains of an alternatively spliced longer variant of mouse delphilin (L-delphilin, isoform 1), and related domains. Delphilin is a scaffold protein which binds the glutamate receptor delta-2 (GRID2) subunit and the monocarboxylate transporter 2 at the cerebellar parallel fiber-Purkinje cell synapses. The N-terminus of L-delphilin contains this harmonin_N_like domain preceded by a postsynaptic density-95/discs-large/ZO-1 (PDZ) protein-binding domain, PDZ1. L-delphilin, in common with the shorter C-terminal isoforms (S-delphilin/delphilin alpha and delphilin beta) has a second harmonin_N_like domain (not belonging to this subgroup) and a second PDZ domain, PDZ2. This first harmonin_N_like domain is a putative protein-binding module based on its sequence similarity to the N-terminal domain of harmonin.

Pssm-ID: 259820 Cd Length: 80 Bit Score: 36.11 E-value: 9.86e-03

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gi 569006111  584 YVHEGGVEDLVRPLLAILDRPTKLLLLRDIRSVVAPTDLGRFDSMV 629
Cdd:cd07354    33 YAADRNVEMLAEALTDILTTEAHRKLLDEIRYFIPNKHRARFDKLV 78