The Bin/Amphiphysin/Rvs (BAR) domain of Protein Interacting with C Kinase 1; The BAR domain of Arfaptin-like proteins, also called the Arfaptin domain, is a dimerization and lipid binding module that can detect and drive membrane curvature. Protein Interacting with C Kinase 1 (PICK1), also called Protein kinase C-alpha-binding protein, is highly expressed in brain and testes. PICK1 plays a key role in the trafficking of AMPA receptors, which are critical for regulating synaptic strength and may be important in cellular processes involved in learning and memory. PICK1 is also critical in the early stages of spermiogenesis. Mice deficient in PICK1 are infertile and show characteristics of the human disease globozoospermia such as round-headed sperm, reduced sperm count, and severely impaired sperm motility. PICK1 may also be involved in the neuropathogenesis of schizophrenia. PICK1 contains an N-terminal PDZ domain and a C-terminal BAR domain. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. The BAR domain of PICK1 is necessary for its membrane localization and activation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1935598122 146 NDGLVKRLEELERTAELYKGMTEHTKNLLRAFYELSQTHRAFGDVFSVIGVREPQPAASEAFVKFADAHRSIEKFGIRLL 225
Cdd:cd07659     1 NDGLVKKLEELEQTAELYKGLVEHTKRLLRAFYALSQTHKEFGDLFANIGVREPQPAASEAFTKFGEAHRSIEKFGIELL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1935598122 226 KTIKPMLTDLNTYLNKAIPDTRLTIKKYLDVKFEYLSYCLKVKEMDDEEYSCIALGEPLYRVSTGNYEYRLILRCRQEAR 305
Cdd:cd07659    81 KTLKPMLSDLGTYLNKAIPDTKLTIKKYADVKFEYLSYCLKVKEMDDEEYSYAALDEPLYRVETGNYEYRLILRCRQEAR 160

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1935598122 306 ARFSQMRKDVLEKMELLDQKHVQDIVFQLQRFVSTMSKYYNDCYAVLRDADVFPI 360
Cdd:cd07659   161 ARFAKLRQDVLEKLELLDQKHVQDIVFQLQRFVSALSEYHSDCHELLKEPDLFPI 215

The Bin/Amphiphysin/Rvs (BAR) domain of Protein Interacting with C Kinase 1; The BAR domain of Arfaptin-like proteins, also called the Arfaptin domain, is a dimerization and lipid binding module that can detect and drive membrane curvature. Protein Interacting with C Kinase 1 (PICK1), also called Protein kinase C-alpha-binding protein, is highly expressed in brain and testes. PICK1 plays a key role in the trafficking of AMPA receptors, which are critical for regulating synaptic strength and may be important in cellular processes involved in learning and memory. PICK1 is also critical in the early stages of spermiogenesis. Mice deficient in PICK1 are infertile and show characteristics of the human disease globozoospermia such as round-headed sperm, reduced sperm count, and severely impaired sperm motility. PICK1 may also be involved in the neuropathogenesis of schizophrenia. PICK1 contains an N-terminal PDZ domain and a C-terminal BAR domain. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. The BAR domain of PICK1 is necessary for its membrane localization and activation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1935598122 146 NDGLVKRLEELERTAELYKGMTEHTKNLLRAFYELSQTHRAFGDVFSVIGVREPQPAASEAFVKFADAHRSIEKFGIRLL 225
Cdd:cd07659     1 NDGLVKKLEELEQTAELYKGLVEHTKRLLRAFYALSQTHKEFGDLFANIGVREPQPAASEAFTKFGEAHRSIEKFGIELL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1935598122 226 KTIKPMLTDLNTYLNKAIPDTRLTIKKYLDVKFEYLSYCLKVKEMDDEEYSCIALGEPLYRVSTGNYEYRLILRCRQEAR 305
Cdd:cd07659    81 KTLKPMLSDLGTYLNKAIPDTKLTIKKYADVKFEYLSYCLKVKEMDDEEYSYAALDEPLYRVETGNYEYRLILRCRQEAR 160

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1935598122 306 ARFSQMRKDVLEKMELLDQKHVQDIVFQLQRFVSTMSKYYNDCYAVLRDADVFPI 360
Cdd:cd07659   161 ARFAKLRQDVLEKLELLDQKHVQDIVFQLQRFVSALSEYHSDCHELLKEPDLFPI 215

Arfaptin-like domain; Arfaptin interacts with ARF1, a small GTPase involved in vesicle budding at the Golgi complex and immature secretory granules. The structure of arfaptin shows that upon binding to a small GTPase, arfaptin forms an elongated, crescent-shaped dimer of three-helix coiled-coils. The N-terminal region of ICA69 is similar to arfaptin.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1935598122  116 IVLKKVKHRLVENMSSGTADAlglsrAILCNDGLVKRLEELERTAELYKGMTEHTKNLLRAFYELSQTHRAFGDVFSVIG 195
Cdd:smart01015   1 KTYKKTKQVLIEKLGKKEDEH-----VVASDAELDAKLELLRSTQRTYEDLLKLIEKYQQRLCNLSQTENELGDFFRDLS 75

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1935598122  196 VREPQPaasEAFVKFADAHRSIEKFGIRLLKTIKPMLTDLNTYLNKAIPDTRLTIKKYLDVKFEYLSYCLKVKE-MDDEE 274
Cdd:smart01015  76 EKDPTL---KAFGMMAETQKALCKSGEQLLAPLNPFISDVNTFVNKAIEDTLLTIKRYEDARTEYRAWMKDVSEeLDPEE 152

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1935598122  275 YSCIalgeplyrvstgnYEYRLILRCRQEARARFSQMRKDVLEKMELLDQKHVQDIVFQLQRFVSTMSKYYNDCYAVL 352
Cdd:smart01015 153 YKQL-------------EKFRKAQRQVQEAKAKFEKLRNDVCQKVDLLEASRVNVLSHQLLLFQNALAAYWEKTAHAL 217

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1935598122   19 VPGKVTLQKDAQNLiGISIGGGAQYCPCLYIVQVFDNTPAALDGtVAAGDEITGVNGRSIKGKTKVEVAKMIQEVKGEVT 98
Cdd:smart00228   1 EPRLVELEKGGGGL-GFSLVGGKDEGGGVVVSSVVPGSPAAKAG-LRVGDVILEVNGTSVEGLTHLEAVDLLKKAGGKVT 78

                   .
gi 1935598122   99 I 99
Cdd:smart00228  79 L 79

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1935598122  33 IGISIGGGAQYcpcLYIVQVFDNTPAALDGtVAAGDEITGVNGRSIKGKTKVEVAKMIQEVKG-EVTIHYNKlqADPKQG 111
Cdd:COG0793    62 LGAELGEEDGK---VVVVSVIPGSPAEKAG-IKPGDIILAIDGKSVAGLTLDDAVKLLRGKAGtKVTLTIKR--PGEGEP 135

                          90
                  ....*....|....*.
gi 1935598122 112 MSLDIVLKKVKHRLVE 127
Cdd:COG0793   136 ITVTLTRAEIKLPSVE 151

The Bin/Amphiphysin/Rvs (BAR) domain of Protein Interacting with C Kinase 1; The BAR domain of Arfaptin-like proteins, also called the Arfaptin domain, is a dimerization and lipid binding module that can detect and drive membrane curvature. Protein Interacting with C Kinase 1 (PICK1), also called Protein kinase C-alpha-binding protein, is highly expressed in brain and testes. PICK1 plays a key role in the trafficking of AMPA receptors, which are critical for regulating synaptic strength and may be important in cellular processes involved in learning and memory. PICK1 is also critical in the early stages of spermiogenesis. Mice deficient in PICK1 are infertile and show characteristics of the human disease globozoospermia such as round-headed sperm, reduced sperm count, and severely impaired sperm motility. PICK1 may also be involved in the neuropathogenesis of schizophrenia. PICK1 contains an N-terminal PDZ domain and a C-terminal BAR domain. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. The BAR domain of PICK1 is necessary for its membrane localization and activation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1935598122 146 NDGLVKRLEELERTAELYKGMTEHTKNLLRAFYELSQTHRAFGDVFSVIGVREPQPAASEAFVKFADAHRSIEKFGIRLL 225
Cdd:cd07659     1 NDGLVKKLEELEQTAELYKGLVEHTKRLLRAFYALSQTHKEFGDLFANIGVREPQPAASEAFTKFGEAHRSIEKFGIELL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1935598122 226 KTIKPMLTDLNTYLNKAIPDTRLTIKKYLDVKFEYLSYCLKVKEMDDEEYSCIALGEPLYRVSTGNYEYRLILRCRQEAR 305
Cdd:cd07659    81 KTLKPMLSDLGTYLNKAIPDTKLTIKKYADVKFEYLSYCLKVKEMDDEEYSYAALDEPLYRVETGNYEYRLILRCRQEAR 160

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1935598122 306 ARFSQMRKDVLEKMELLDQKHVQDIVFQLQRFVSTMSKYYNDCYAVLRDADVFPI 360
Cdd:cd07659   161 ARFAKLRQDVLEKLELLDQKHVQDIVFQLQRFVSALSEYHSDCHELLKEPDLFPI 215

Arfaptin-like domain; Arfaptin interacts with ARF1, a small GTPase involved in vesicle budding at the Golgi complex and immature secretory granules. The structure of arfaptin shows that upon binding to a small GTPase, arfaptin forms an elongated, crescent-shaped dimer of three-helix coiled-coils. The N-terminal region of ICA69 is similar to arfaptin.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1935598122 137 LGLSRAILCNDGLVKRLEELERTAELYKGMTEHTKNLLRAFYELSQTHRAFGDVFSVIGVREPQPAASEAFVKFADAHRS 216
Cdd:pfam06456   1 KEDSHAITSDDELDAKLEVLRSIQRTYLGLVKLARNYSKRLYDLSQTQKELGDFFKDLGKHEKQQAAGEAFTAFGETHRF 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1935598122 217 IEKFGIRLLKTIKPMLTDLNTYLNKAIPDTRLTIKKYLDVKFEYLSYCLKVKEMDDEEYSCIALGEPLYRVSTGNYeyrl 296
Cdd:pfam06456  81 LAKQGLALLVPLNRFISSVNTFVNKAIPDTLLTIKRYEDARTEYRAYLLWMKEASDELDPDVAKQMPKFRVAQGNY---- 156

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1935598122 297 ilrcrQEARARFSQMRKDVLEKMELLDQKHVQDIVFQLQRFVSTMSKYYNDCYAVL 352
Cdd:pfam06456 157 -----QEAKAKFDKLRTDVLQKMDLLEANRINVLSHQLTLYQNTLAAYYSKNAKAL 207

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1935598122  21 GKVTLQKDAQNLIGISIGGGAQYCPCLYIVQVFDNTPAALDGTVAAGDEITGVNGRSIKGKTKVEVAKMIQEVKGEVTIH 100
Cdd:cd06722     1 GTVTLKKDAQNLIGISIGGGAPYCPCLYIVQVFDNTPAAKDGTLAAGDEIVGVNGKSVKGKTKVEVAKMIQAVKGEVTIH 80

                  ....
gi 1935598122 101 YNKL 104
Cdd:cd06722    81 YNKL 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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1935598122  22 KVTLQKDAQNLIGISIGGGAQYCPCLYIVQVFDNTPAALDGTVAAGDEITGVNGRSIKGKTKVEVAKMIQEVKGEVTI 99
Cdd:cd00136     1 TVTLEKDPGGGLGFSIRGGKDGGGGIFVSRVEPGGPAARDGRLRVGDRILEVNGVSLEGLTHEEAVELLKSAGGEVTL 78

The Bin/Amphiphysin/Rvs (BAR) domain, a dimerization module that binds membranes and detects membrane curvature; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions including organelle biogenesis, membrane trafficking or remodeling, and cell division and migration. Mutations in BAR containing proteins have been linked to diseases and their inactivation in cells leads to altered membrane dynamics. A BAR domain with an additional N-terminal amphipathic helix (an N-BAR) can drive membrane curvature. These N-BAR domains are found in amphiphysins and endophilins, among others. BAR domains are also frequently found alongside domains that determine lipid specificity, such as the Pleckstrin Homology (PH) and Phox Homology (PX) domains which are present in beta centaurins (ACAPs and ASAPs) and sorting nexins, respectively. A FES-CIP4 Homology (FCH) domain together with a coiled coil region is called the F-BAR domain and is present in Pombe/Cdc15 homology (PCH) family proteins, which include Fes/Fes tyrosine kinases, PACSIN or syndapin, CIP4-like proteins, and srGAPs, among others. The Inverse (I)-BAR or IRSp53/MIM homology Domain (IMD) is found in multi-domain proteins, such as IRSp53 and MIM, that act as scaffolding proteins and transducers of a variety of signaling pathways that link membrane dynamics and the underlying actin cytoskeleton. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. The I-BAR domain induces membrane protrusions in the opposite direction compared to classical BAR and F-BAR domains, which produce membrane invaginations. BAR domains that also serve as protein interaction domains include those of arfaptin and OPHN1-like proteins, among others, which bind to Rac and Rho GAP domains, respectively.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1935598122 154 EELERTAELYKGMTEHTKNLLRAFYELSQTHRAFGDVFSVigvrEPQPAASEAFVKFADAHRSIEKFGIRLLKTIKPMLT 233
Cdd:cd07307     7 KLLKKLIKDTKKLLDSLKELPAAAEKLSEALQELGKELPD----LSNTDLGEALEKFGKIQKELEEFRDQLEQKLENKVI 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1935598122 234 D-LNTYLNKAIPDTRLTIKKY------LDVKFEYLSYCLKVKEMDDEEYSCialgEPLYrvstgnyeyrlilrcrQEARA 306
Cdd:cd07307    83 EpLKEYLKKDLKEIKKRRKKLdkarldYDAAREKLKKLRKKKKDSSKLAEA----EEEL----------------QEAKE 142

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 1935598122 307 RFSQMRKDVLEKMELLDQKHVQDIVFQLQRFVSTMSKYYNDCYAVLRDAD 356
Cdd:cd07307   143 KYEELREELIEDLNKLEEKRKELFLSLLLSFIEAQSEFFKEVLKILEQLL 192

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1935598122  23 VTLQKDAQNLIGISIGGGAQYCPC---LYIVQVFDNTPAALDGTVAAGDEITGVNGRSIKGKTKVEVAKMIQEVKGEVTI 99
Cdd:cd06680     3 ITLRRSSSGSLGFSIVGGYEESHGnqpFFVKSIVPGTPAYNDGRLKCGDIILAVNGVSTVGMSHAALVPLLKEQRGRVTL 82

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1935598122  22 KVTLQKDAQNLIGISI-GGGAQYCPCLYIVQVFDNTPAALDGtVAAGDEITGVNGRSIKGKTKVEVAKMIQEVKGEVTI 99
Cdd:pfam00595   1 QVTLEKDGRGGLGFSLkGGSDQGDPGIFVSEVLPGGAAEAGG-LKVGDRILSINGQDVENMTHEEAVLALKGSGGKVTL 78

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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1935598122  33 IGISIGGGAQyCP----CLYIVQVFDNTPAALDGTVAAGDEITGVNGRSIKGKTKVEVAKMIQEVK-GEVTI 99
Cdd:cd06759    14 LGFSIVGGRD-SPrgpmGIYVKTIFPGGAAAEDGRLKEGDEILEVNGESLQGLTHQEAIQKFKQIKkGLVVL 84

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1935598122  23 VTLQKDAQNLiGISIGGGAQY----CPcLYIVQVFDNTPAALDGTVAAGDEITGVNGRSIKGKTKVEVAKMIQEVKGEVT 98
Cdd:cd06676     2 ITLERGSDGL-GFSIVGGFGSphgdLP-IYVKTVFEKGAAAEDGRLKRGDQILAVNGESLEGVTHEEAVNILKKTKGTVT 79

                  .
gi 1935598122  99 I 99
Cdd:cd06676    80 L 80

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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1935598122  22 KVTLQKDAQNLiGISIGGG--AQYCPC-LYIVQVFDNTPAALDGTVAAGDEITGVNGRSIKGKTKVEVAKMIQEVKGEV 97
Cdd:cd06758     4 KMHLLKEKGGL-GIQITGGkgSKRGDIgIFVAGVEEGGSADRDGRLKKGDELLMINGQSLIGLSHQEAVAILRSSASPV 81

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1935598122  23 VTLQKDAQNLiGISIGGGAQYC--PCLYIVQVFDNTPAALDGTVAAGDEITGVNGRSIKGKTKVEVAKMIQ 91
Cdd:cd06751     4 VELSKMKQSL-GISISGGIESKvqPVVKIEKIFPGGAAALSGNLKAGYELVSVDGESLQQVTHQQAVDIIR 73

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1935598122  26 QKDaqnlIGISIGGGaqycpcLYIVQVFDNTPAALDGTVAAGDEITGVNGRSIKGKTKVEVAKMIQ 91
Cdd:cd06765     7 QKD----SGISLENG------VFISRIVPGSPAAKEGSLTVGDRIIAINGIALDNKSLSECEALLR 62

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1935598122  22 KVTLQKDAQNLiGISIGGG-----AQYCPCLY-IVQVFDNTPAALDGTVAAGDEITGVNGRSIKGKTKVEVAKMIQEVKG 95
Cdd:cd06695     3 EVKLTKGSSGL-GFSFLGGennspEDPFSGLVrIKKLFPGQPAAESGLIQEGDVILAVNGEPLKGLSYQEVLSLLRGAPP 81

                  ....
gi 1935598122  96 EVTI 99
Cdd:cd06695    82 EVTL 85

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1935598122  23 VTLQKDAQNLiGISIGGGAQYC--PcLYIVQVFDNTPAALDGTVAAGDEITGVNGRSIKGKTKVEVAKMIQ 91
Cdd:cd06735     4 VELERGPKGF-GFSIRGGREYNnmP-LYVLRLAEDGPAQRDGRLRVGDQILEINGESTQGMTHAQAIELIR 72

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1935598122  23 VTLQKDAQNLIGISIGGGAQYC--PCLYIVQVFDNTPAALDGTVAAGDEITGVNGRSIKGKTKVEVAKMIQEV 93
Cdd:cd06717     2 VTLNMEKVNFLGISIVGQSNERgdGGIYVGSIMKGGAVAADGRIEPGDMILQVNDISFENMSNDDAVRVLREA 74

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1935598122  22 KVTLQKDAQNLIGISIGGGAQyCPCLYIVQVFDNtPAALDGTVAAGDEITGVNGRSIKGKTKVEVAKMIQEVKGEVTI 99
Cdd:cd06696     5 EVTLTKSEKGSLGFTVTKGKD-DNGCYIHDIVQD-PAKSDGRLRPGDRLIMVNGVDVTNMSHTEAVSLLRAAPKEVTL 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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1935598122  23 VTLQKDAQNLIGISIGGgAQYCPCLYIVQVFDNTPAALDGTVAAGDEITGVNGRSIKGKTKVEVAKMIQEVKGEVTIHYN 102
Cdd:cd06674     6 VELQKKPGRGLGLSIVG-KRNDTGVFVSDIVKGGAADADGRLMQGDQILSVNGEDVRNASQEAAAALLKCAQGKVRLEVG 84

                  ..
gi 1935598122 103 KL 104
Cdd:cd06674    85 RL 86

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1935598122  20 PG--KVTLQKDAQNLIGISIGGGAQYCPC---------LYIVQVFDNTPAALDGTVAAGDEITGVNGRSIKGKTKVEVAK 88
Cdd:cd06701     2 PGlqELTIVKEPGEKLGISIRGGAKGHAGnpldptdegIFISKINPDGAAARDGRLKVGQRILEVNGQSLLGATHQEAVR 81

                          90
                  ....*....|.
gi 1935598122  89 MIQEVKGEVTI 99
Cdd:cd06701    82 ILRSVGDTLTL 92

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1935598122  17 PTVPGKVTLQKDAQ------NLIGISIGGGAQYCP---CLYIVQVFDNTPAALDGTVAAGDEITGVNGRSIKGKTKVEVA 87
Cdd:cd06714     1 DFLIGRIILQRDPKdgsvsgNGLGLKVVGGKMTESgrlGAYVTKVKPGSVADTVGHLREGDEVLEWNGISLQGKTFEEVQ 80

                          90
                  ....*....|...
gi 1935598122  88 KMIQEVKGEVTIH 100
Cdd:cd06714    81 DIISQSKGEVELV 93

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.

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gi 1935598122  20 PGKVTLQKDAQNLIGISIGGGAQYCPCL---------YIVQVFDNTPAALDGTVAAGDEITGVNGRSIKGKTKVEVAKMI 90
Cdd:cd06671     2 PRRVELWREPGKSLGISIVGGRVMGSRLsngeeirgiFIKHVLEDSPAGRNGTLKTGDRILEVNGVDLRNATHEEAVEAI 81

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

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1935598122  22 KVTLQKDAQNLiGISIGGGA---QYCPclYIVQVFDNTPAALDGTVAAGDEITGVNGRSIKGKTKVEVAKMIQE 92
Cdd:cd06742     3 LVRIKKTKPTL-GIAIEGGAntkQPLP--RVINIQRGGSAHNCGGLKVGHVILEVNGTSLRGLEHREAARLIAE 73

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.

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gi 1935598122  23 VTLQKDAqNLIGISIGGGA-----QYCPcLYIVQVFDNTPAALDGTVAAGDEITGVNGRSIKGKTKVEVAKMIQEVKGE- 96
Cdd:cd06681     5 VTLEKEG-NSFGFVIRGGAhedrnKSRP-LTVTHVRPGGPADREGTIKPGDRLLSVDGISLHGATHAEAMSILKQCGQEa 82

                  ....*..
gi 1935598122  97 -VTIHYN 102
Cdd:cd06681    83 tLLIEYD 89

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1935598122  23 VTLQKDAQNLIGISIGGG---AQYCPCLYIVQVFDNTPAALDGTVAAGDEITGVNGRSIKGKTKVEVAKMIQEVKGEVTI 99
Cdd:cd23072     5 VNLKKDAKYGLGFQIVGGeksGRLDLGIFISSITPGGPADLDGRLKPGDRLISVNDVSLEGLSHDAAVEILQNAPEDVTL 84

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.

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gi 1935598122  62 GTVAAGDEITGVNGRSIKGKTKVEVAKMIQEVKGEVTI 99
Cdd:cd06726    39 GLLHVGDEILEINGIPVSGKTVDELQKLLSSLSGSVTF 76

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.

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gi 1935598122  22 KVTLQKDAQNLIGISI------GGGAQYCPCLYIVQVFDNTPAALDGTVAAGDEITGVNGRSIKGKTKVEVAKMIQE 92
Cdd:cd23063     1 MVVIEKTEKKSFGICIvrgevkVSPNTKTTGIFIKGIIPDSPAHKCGRLKVGDRILSVNGNDVRNSTEQAAIDLIKE 77

Inverse (I)-BAR, also known as the IRSp53/MIM homology Domain (IMD), a dimerization module that binds and bends membranes; Inverse (I)-BAR (or IMD) is a member of the Bin/Amphiphysin/Rvs (BAR) domain family. It is a dimerization and lipid-binding module that bends membranes and induces membrane protrusions in the opposite direction compared to classical BAR and F-BAR domains, which produce membrane invaginations. IMD domains are found in Insulin Receptor tyrosine kinase Substrate p53 (IRSp53), Missing in Metastasis (MIM), and Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2-like (BAIAP2L) proteins. These are multi-domain proteins that act as scaffolding proteins and transducers of a variety of signaling pathways that link membrane dynamics and the underlying actin cytoskeleton. Most members contain an N-terminal IMD, an SH3 domain, and a WASP homology 2 (WH2) actin-binding motif at the C-terminus, exccept for MIM which does not carry an SH3 domain. Some members contain additional domains and motifs. The IMD domain binds and bundles actin filaments, binds membranes and produces membrane protrusions, and interacts with the small GTPase Rac.

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gi 1935598122 171 KNLLRAFYELSQTHRAFGDVFSVIGVREPQPAAS----EAFVKFADAHRSIEKfgiRLLKTIKPMLTDLNTYLNKAIPDT 246
Cdd:cd07605    30 KKYQKALQALSQAAKVFFDALAKIGELASQSRGSqelgEALKQIVDTHKSIEA---SLEQVAKAFHGELILPLEKKLELD 106

                  ....*.
gi 1935598122 247 RLTIKK 252
Cdd:cd07605   107 QKVINK 112

PDZ domain of membrane palmitoylated protein1 (MPP1), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of MPP1, and related domains. MPP1 (also known as MAGUK p55 subfamily member 1, erythrocyte membrane protein p55, EMP55) is a membrane-associated guanylate kinase (MAGUK)-like protein which forms a complex with protein 4.1 and glycophorin C (GPC) at the cytoplasmic face of the plasma membrane; this complex is essential for cytoskeleton-membrane linkage in erythrocytes and many non-erythroid cells, and participates in the determination of membrane stability and cell shape. MPP1, by interacting with various scaffold proteins and cytoskeletal proteins in the postsynaptic density, also plays an important role in organizing synaptic and non-synaptic structures. MPP1 is also a component of the Crumbs protein complex in the mammalian retina and may link the Usher protein network and the Crumbs protein complex. The MPP1 PDZ domain binding partners include GPC, ABCC4, and CADM1/Necl-2/SynCAM1. 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.

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gi 1935598122  62 GTVAAGDEITGVNGRSIKGKTKVEVAKMIQEVKGEVTI 99
Cdd:cd10830    40 GSLHVGDEILEINGKSVTNHSVDQLQKMLKETKGMVSL 77

PDZ domain 2 of Zonula Occludens-1 (ZO-1), ZO-2 and ZO-3, and related domains; form domain-swapping dimers; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 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 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.

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gi 1935598122  22 KVTLQKDAQNL-IGISIGggaqycpC-LYIVQVFDNTPAALDGTVAAGDEITGVNGRSIKGKTKVEVAKMIQEVKGEVTI 99
Cdd:cd06728     2 KVTLTKSRKNDeYGLRLG-------SrIFVKEITPDSLAAKDGNLQEGDIILKINGTPVENLSLSEAKKLIEKSKDKLQL 74