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Conserved domains on  [gi|71983825|ref|NP_001023039|]
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DH domain-containing protein [Caenorhabditis elegans]

Protein Classification

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
RhoGEF smart00325
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange ...
301-479 8.77e-40

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains. Improved coverage.


:

Pssm-ID: 214619 [Multi-domain]  Cd Length: 180  Bit Score: 145.14  E-value: 8.77e-40
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71983825    301 AAKELVDSEQRYVDKLKLLGDTFRNRLIKEE-LITNDKITRLLANVSSLYQFHnTHFLPQLLESIRDW-HTTKRIANVVR 378
Cdd:smart00325   1 VLKELLQTERNYVRDLKLLVEVFLKPLKKELkLLSPNELETLFGNIEEIYEFH-RDFLDELEERIEEWdDSVERIGDVFL 79
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71983825    379 KQAPFLKMYSEYTNNYDRATKLFEELKKKKKFADVVKEIEKQAECEGLPLGHHLICPVQRVMRYQLLLQEYKKHLQPSDV 458
Cdd:smart00325  80 KLEEFFKIYSEYCSNHPDALELLKKLKKNPRFQKFLKEIESSPQCRRLTLESLLLKPVQRLTKYPLLLKELLKHTPEDHE 159
                          170       180
                   ....*....|....*....|.
gi 71983825    459 DFDDTTVALELVLQAAAHANE 479
Cdd:smart00325 160 DREDLKKALKAIKELANQVNE 180
PH1_FGD1-4_like cd13388
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 1-4 and similar proteins, ...
510-608 1.13e-39

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 1-4 and similar proteins, N-terminal Pleckstrin homology (PH) domain; In general, FGDs have a RhoGEF (DH) domain, followed by an N-terminal PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activates the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the N-terminal PH domain is involved in intracellular targeting of the DH domain. Mutations in the FGD1 gene are responsible for the X-linked disorder known as faciogenital dysplasia (FGDY). Both FGD1 and FGD3 are targeted by the ubiquitin ligase SCF(FWD1/beta-TrCP) upon phosphorylation of two serine residues in its DSGIDS motif and subsequently degraded by the proteasome. They play different roles to regulate cellular functions, even though their intracellular levels are tightly controlled by the same destruction pathway. FGD4 is one of the genes associated with Charcot-Marie-Tooth neuropathy type 4 (CMT4), a group of progressive motor and sensory axonal and demyelinating neuropathies that are distinguished from other forms of CMT by autosomal recessive inheritance. Those affected have distal muscle weakness and atrophy associated with sensory loss and, frequently, pes cavus foot deformity. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


:

Pssm-ID: 275423  Cd Length: 94  Bit Score: 141.31  E-value: 1.13e-39
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71983825 510 LLKSGSVQKISSTTEKTEERFIFLFNDLVILASERKMIGVSKYKLRAVFSASHMQVCEGDNLEREHSFYLRGSdgtgpKR 589
Cdd:cd13388   1 LIKEGKILKISARNGDTQERYLFLFNDMLLYCSPRLRLIGQKYKVRARFDVDGMQVLEGDNLETPHTFYVRGK-----QR 75
                        90
                ....*....|....*....
gi 71983825 590 CVELFTPTQKEKNDWVDSI 608
Cdd:cd13388  76 SLELQASTQEEKAEWVDAI 94
FYVE smart00064
Protein present in Fab1, YOTB, Vac1, and EEA1; The FYVE zinc finger is named after four ...
641-692 3.90e-14

Protein present in Fab1, YOTB, Vac1, and EEA1; The FYVE zinc finger is named after four proteins where it was first found: Fab1, YOTB/ZK632.12, Vac1, and EEA1. The FYVE finger has been shown to bind two Zn2+ ions. The FYVE finger has eight potential zinc coordinating cysteine positions. The FYVE finger is structurally related to the PHD finger and the RING finger. Many members of this family also include two histidines in a motif R+HHC+XCG, where + represents a charged residue and X any residue. The FYVE finger functions in the membrane recruitment of cytosolic proteins by binding to phosphatidylinositol 3-phosphate (PI3P), which is prominent on endosomes. The R+HHC+XCG motif is critical for PI3P binding.


:

Pssm-ID: 214499 [Multi-domain]  Cd Length: 68  Bit Score: 67.84  E-value: 3.90e-14
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 71983825    641 KHCADCDIEFGFLSRGSKCVKCSRRLCKKCFGRRRN-----ESKKHRICDTCTKNMD 692
Cdd:smart00064  11 SNCMGCGKEFNLTKRRHHCRNCGRIFCSKCSSKKAPlpklgIERPVRVCDDCYENLN 67
PH-like super family cl17171
Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like ...
738-810 1.03e-06

Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like and IRS-like PTB domains, the ran-binding domain, the EVH1 domain, a domain in neurobeachin and the third domain of FERM. All of these domains have a PH fold, but lack significant sequence similarity. They are generally involved in targeting to protein to the appropriate cellular location or interacting with a binding partner. This domain family possesses multiple functions including the ability to bind inositol phosphates and to other proteins.


The actual alignment was detected with superfamily member cd13248:

Pssm-ID: 473070  Cd Length: 104  Bit Score: 47.65  E-value: 1.03e-06
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 71983825 738 RFMVVRDdFCMYTYSSEEDICALAMLPLPGCEVKMC------GEKFTFSVRVGARRMYTMTAEDEQTQMKWLAILDLAA 810
Cdd:cd13248  27 RWFVLKD-NCLYYYKDPEEEKALGSILLPSYTISPAppsdeiSRKFAFKAEHANMRTYYFAADTAEEMEQWMNAMSLAA 104
 
Name Accession Description Interval E-value
RhoGEF smart00325
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange ...
301-479 8.77e-40

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains. Improved coverage.


Pssm-ID: 214619 [Multi-domain]  Cd Length: 180  Bit Score: 145.14  E-value: 8.77e-40
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71983825    301 AAKELVDSEQRYVDKLKLLGDTFRNRLIKEE-LITNDKITRLLANVSSLYQFHnTHFLPQLLESIRDW-HTTKRIANVVR 378
Cdd:smart00325   1 VLKELLQTERNYVRDLKLLVEVFLKPLKKELkLLSPNELETLFGNIEEIYEFH-RDFLDELEERIEEWdDSVERIGDVFL 79
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71983825    379 KQAPFLKMYSEYTNNYDRATKLFEELKKKKKFADVVKEIEKQAECEGLPLGHHLICPVQRVMRYQLLLQEYKKHLQPSDV 458
Cdd:smart00325  80 KLEEFFKIYSEYCSNHPDALELLKKLKKNPRFQKFLKEIESSPQCRRLTLESLLLKPVQRLTKYPLLLKELLKHTPEDHE 159
                          170       180
                   ....*....|....*....|.
gi 71983825    459 DFDDTTVALELVLQAAAHANE 479
Cdd:smart00325 160 DREDLKKALKAIKELANQVNE 180
PH1_FGD1-4_like cd13388
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 1-4 and similar proteins, ...
510-608 1.13e-39

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 1-4 and similar proteins, N-terminal Pleckstrin homology (PH) domain; In general, FGDs have a RhoGEF (DH) domain, followed by an N-terminal PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activates the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the N-terminal PH domain is involved in intracellular targeting of the DH domain. Mutations in the FGD1 gene are responsible for the X-linked disorder known as faciogenital dysplasia (FGDY). Both FGD1 and FGD3 are targeted by the ubiquitin ligase SCF(FWD1/beta-TrCP) upon phosphorylation of two serine residues in its DSGIDS motif and subsequently degraded by the proteasome. They play different roles to regulate cellular functions, even though their intracellular levels are tightly controlled by the same destruction pathway. FGD4 is one of the genes associated with Charcot-Marie-Tooth neuropathy type 4 (CMT4), a group of progressive motor and sensory axonal and demyelinating neuropathies that are distinguished from other forms of CMT by autosomal recessive inheritance. Those affected have distal muscle weakness and atrophy associated with sensory loss and, frequently, pes cavus foot deformity. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275423  Cd Length: 94  Bit Score: 141.31  E-value: 1.13e-39
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71983825 510 LLKSGSVQKISSTTEKTEERFIFLFNDLVILASERKMIGVSKYKLRAVFSASHMQVCEGDNLEREHSFYLRGSdgtgpKR 589
Cdd:cd13388   1 LIKEGKILKISARNGDTQERYLFLFNDMLLYCSPRLRLIGQKYKVRARFDVDGMQVLEGDNLETPHTFYVRGK-----QR 75
                        90
                ....*....|....*....
gi 71983825 590 CVELFTPTQKEKNDWVDSI 608
Cdd:cd13388  76 SLELQASTQEEKAEWVDAI 94
RhoGEF cd00160
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous ...
299-478 1.98e-38

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains.


Pssm-ID: 238091 [Multi-domain]  Cd Length: 181  Bit Score: 141.28  E-value: 1.98e-38
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71983825 299 WYAAKELVDSEQRYVDKLKLLGDTFRNRLIKEEL-ITNDKITRLLANVSSLYQFHNThFLPQLLESIRDWHTTK-RIANV 376
Cdd:cd00160   2 QEVIKELLQTERNYVRDLKLLVEVFLKPLDKELLpLSPEEVELLFGNIEEIYEFHRI-FLKSLEERVEEWDKSGpRIGDV 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71983825 377 VRKQAPFLKMYSEYTNNYDRAtklFEELKKKKKFADVVKEIEKQAE--CEGLPLGHHLICPVQRVMRYQLLLQEYKKHLQ 454
Cdd:cd00160  81 FLKLAPFFKIYSEYCSNHPDA---LELLKKLKKFNKFFQEFLEKAEseCGRLKLESLLLKPVQRLTKYPLLLKELLKHTP 157
                       170       180
                ....*....|....*....|....
gi 71983825 455 PSDVDFDDTTVALELVLQAAAHAN 478
Cdd:cd00160 158 DGHEDREDLKKALEAIKEVASQVN 181
RhoGEF pfam00621
RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called ...
301-478 1.19e-35

RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that pfam00169 domains invariably occur C-terminal to RhoGEF/DH domains.


Pssm-ID: 459876 [Multi-domain]  Cd Length: 176  Bit Score: 133.19  E-value: 1.19e-35
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71983825   301 AAKELVDSEQRYVDKLKLLGDTFRNRLIKEELITNDKITRLLANVSSLYQFHNTHFLPQLLESirdWHTTKRIANVVRKQ 380
Cdd:pfam00621   1 VIKELLQTERSYVRDLEILVEVFLPPNSKPLSESEEEIKTIFSNIEEIYELHRQLLLEELLKE---WISIQRIGDIFLKF 77
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71983825   381 APFLKMYSEYTNNYDRATKL-FEELKKKKKFADVVKEIEKQAECEGLPLGHHLICPVQRVMRYQLLLQEYKKHLQPSDVD 459
Cdd:pfam00621  78 APGFKVYSTYCSNYPKALKLlKKLLKKNPKFRAFLEELEANPECRGLDLNSFLIKPVQRIPRYPLLLKELLKHTPPDHPD 157
                         170
                  ....*....|....*....
gi 71983825   460 FDDTTVALELVLQAAAHAN 478
Cdd:pfam00621 158 YEDLKKALEAIKEVAKQIN 176
FYVE smart00064
Protein present in Fab1, YOTB, Vac1, and EEA1; The FYVE zinc finger is named after four ...
641-692 3.90e-14

Protein present in Fab1, YOTB, Vac1, and EEA1; The FYVE zinc finger is named after four proteins where it was first found: Fab1, YOTB/ZK632.12, Vac1, and EEA1. The FYVE finger has been shown to bind two Zn2+ ions. The FYVE finger has eight potential zinc coordinating cysteine positions. The FYVE finger is structurally related to the PHD finger and the RING finger. Many members of this family also include two histidines in a motif R+HHC+XCG, where + represents a charged residue and X any residue. The FYVE finger functions in the membrane recruitment of cytosolic proteins by binding to phosphatidylinositol 3-phosphate (PI3P), which is prominent on endosomes. The R+HHC+XCG motif is critical for PI3P binding.


Pssm-ID: 214499 [Multi-domain]  Cd Length: 68  Bit Score: 67.84  E-value: 3.90e-14
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 71983825    641 KHCADCDIEFGFLSRGSKCVKCSRRLCKKCFGRRRN-----ESKKHRICDTCTKNMD 692
Cdd:smart00064  11 SNCMGCGKEFNLTKRRHHCRNCGRIFCSKCSSKKAPlpklgIERPVRVCDDCYENLN 67
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
510-613 2.91e-09

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 55.25  E-value: 2.91e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71983825    510 LLKSGSVQKISSTTEKT-EERFIFLFNDLVILASERKMigVSKYKLRAVFSASHMQVCE---GDNLEREHSFYLRGSDGt 585
Cdd:smart00233   1 VIKEGWLYKKSGGGKKSwKKRYFVLFNSTLLYYKSKKD--KKSYKPKGSIDLSGCTVREapdPDSSKKPHCFEIKTSDR- 77
                           90       100
                   ....*....|....*....|....*...
gi 71983825    586 gpkRCVELFTPTQKEKNDWVDSIFSIID 613
Cdd:smart00233  78 ---KTLLLQAESEEEREKWVEALRKAIA 102
FYVE_like_SF cd00065
FYVE domain like superfamily; FYVE domain is a 60-80 residue double zinc finger ...
642-687 2.97e-08

FYVE domain like superfamily; FYVE domain is a 60-80 residue double zinc finger motif-containing module named after the four proteins, Fab1, YOTB, Vac1, and EEA1. The canonical FYVE domains are distinguished from other zinc fingers by three signature sequences: an N-terminal WxxD motif (x for any residue), the central basic R(R/K)HHCRxCG patch, and a C-terminal RVC motif, which form a compact phosphatidylinositol 3-phosphate (PtdIns3P, also termed PI3P)-binding site. They are found in many membrane trafficking regulators, including EEA1, Hrs, Vac1p, Vps27p, and FENS-1, which locate to early endosomes, specifically bind PtdIns3P, and play important roles in vesicular traffic and in signal transduction. Some proteins, such as rabphilin-3A and alpha-Rab3-interacting molecules (RIMs), are also involved in membrane trafficking and bind to members of the Rab subfamily of GTP hydrolases. However, they contain FYVE-related domains that are structurally similar to the canonical FYVE domains but lack the three signature sequences. At this point, they may not bind to phosphoinositides. In addition, this superfamily also contains the third group of proteins, caspase-associated ring proteins CARP1 and CARP2. They do not localize to membranes in the cell and are involved in the negative regulation of apoptosis, specifically targeting two initiator caspases, caspase 8 and caspase 10, which are distinguished from other FYVE-type proteins. Moreover, these proteins have an altered sequence in the basic ligand binding patch and lack the WxxD motif that is conserved only in phosphoinositide binding FYVE domains. Thus they constitute a family of unique FYVE-type domains called FYVE-like domains. The FYVE domain is structurally similar to the RING domain and the PHD finger. This superfamily also includes ADDz zinc finger domain, which is a PHD-like zinc finger motif that contains two parts, a C2-C2 and a PHD-like zinc finger.


Pssm-ID: 277249 [Multi-domain]  Cd Length: 52  Bit Score: 50.61  E-value: 2.97e-08
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 71983825 642 HCADCDIEFGFLSRGSKCVKCSRRLCKKCFGRRR-----NESKKHRICDTC 687
Cdd:cd00065   1 RCMLCGKKFSLFRRRHHCRRCGRVFCSKCSSKKLplpsfGSGKPVRVCDSC 51
PH pfam00169
PH domain; PH stands for pleckstrin homology.
510-612 5.02e-08

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 51.79  E-value: 5.02e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71983825   510 LLKSGSVQKISSTTEKT-EERFIFLFNDLVILASERKmiGVSKYKLRAVFSASHMQVCE---GDNLEREHSFYLRGSDGT 585
Cdd:pfam00169   1 VVKEGWLLKKGGGKKKSwKKRYFVLFDGSLLYYKDDK--SGKSKEPKGSISLSGCEVVEvvaSDSPKRKFCFELRTGERT 78
                          90       100
                  ....*....|....*....|....*..
gi 71983825   586 GpKRCVELFTPTQKEKNDWVDSIFSII 612
Cdd:pfam00169  79 G-KRTYLLQAESEEERKDWIKAIQSAI 104
PH_PEPP1_2_3 cd13248
Phosphoinositol 3-phosphate binding proteins 1, 2, and 3 pleckstrin homology (PH) domain; ...
738-810 1.03e-06

Phosphoinositol 3-phosphate binding proteins 1, 2, and 3 pleckstrin homology (PH) domain; PEPP1 (also called PLEKHA4/PH domain-containing family A member 4 and RHOXF1/Rhox homeobox family member 1), and related homologs PEPP2 (also called PLEKHA5/PH domain-containing family A member 5) and PEPP3 (also called PLEKHA6/PH domain-containing family A member 6), have PH domains that interact specifically with PtdIns(3,4)P3. Other proteins that bind PtdIns(3,4)P3 specifically are: TAPP1 (tandem PH-domain-containing protein-1) and TAPP2], PtdIns3P AtPH1, and Ptd- Ins(3,5)P2 (centaurin-beta2). All of these proteins contain at least 5 of the 6 conserved amino acids that make up the putative phosphatidylinositol 3,4,5- trisphosphate-binding motif (PPBM) located at their N-terminus. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270068  Cd Length: 104  Bit Score: 47.65  E-value: 1.03e-06
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 71983825 738 RFMVVRDdFCMYTYSSEEDICALAMLPLPGCEVKMC------GEKFTFSVRVGARRMYTMTAEDEQTQMKWLAILDLAA 810
Cdd:cd13248  27 RWFVLKD-NCLYYYKDPEEEKALGSILLPSYTISPAppsdeiSRKFAFKAEHANMRTYYFAADTAEEMEQWMNAMSLAA 104
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
718-811 5.72e-06

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 45.62  E-value: 5.72e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71983825    718 SGVLHssqIRFRGSLGKLLDRFMVVRDDfCMYTYSSEEDICALA---MLPLPGCEV------KMCGEKFTFSVRVGARRM 788
Cdd:smart00233   4 EGWLY---KKSGGGKKSWKKRYFVLFNS-TLLYYKSKKDKKSYKpkgSIDLSGCTVreapdpDSSKKPHCFEIKTSDRKT 79
                           90       100
                   ....*....|....*....|...
gi 71983825    789 YTMTAEDEQTQMKWLAILDLAAN 811
Cdd:smart00233  80 LLLQAESEEEREKWVEALRKAIA 102
 
Name Accession Description Interval E-value
RhoGEF smart00325
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange ...
301-479 8.77e-40

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains. Improved coverage.


Pssm-ID: 214619 [Multi-domain]  Cd Length: 180  Bit Score: 145.14  E-value: 8.77e-40
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71983825    301 AAKELVDSEQRYVDKLKLLGDTFRNRLIKEE-LITNDKITRLLANVSSLYQFHnTHFLPQLLESIRDW-HTTKRIANVVR 378
Cdd:smart00325   1 VLKELLQTERNYVRDLKLLVEVFLKPLKKELkLLSPNELETLFGNIEEIYEFH-RDFLDELEERIEEWdDSVERIGDVFL 79
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71983825    379 KQAPFLKMYSEYTNNYDRATKLFEELKKKKKFADVVKEIEKQAECEGLPLGHHLICPVQRVMRYQLLLQEYKKHLQPSDV 458
Cdd:smart00325  80 KLEEFFKIYSEYCSNHPDALELLKKLKKNPRFQKFLKEIESSPQCRRLTLESLLLKPVQRLTKYPLLLKELLKHTPEDHE 159
                          170       180
                   ....*....|....*....|.
gi 71983825    459 DFDDTTVALELVLQAAAHANE 479
Cdd:smart00325 160 DREDLKKALKAIKELANQVNE 180
PH1_FGD1-4_like cd13388
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 1-4 and similar proteins, ...
510-608 1.13e-39

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 1-4 and similar proteins, N-terminal Pleckstrin homology (PH) domain; In general, FGDs have a RhoGEF (DH) domain, followed by an N-terminal PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activates the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the N-terminal PH domain is involved in intracellular targeting of the DH domain. Mutations in the FGD1 gene are responsible for the X-linked disorder known as faciogenital dysplasia (FGDY). Both FGD1 and FGD3 are targeted by the ubiquitin ligase SCF(FWD1/beta-TrCP) upon phosphorylation of two serine residues in its DSGIDS motif and subsequently degraded by the proteasome. They play different roles to regulate cellular functions, even though their intracellular levels are tightly controlled by the same destruction pathway. FGD4 is one of the genes associated with Charcot-Marie-Tooth neuropathy type 4 (CMT4), a group of progressive motor and sensory axonal and demyelinating neuropathies that are distinguished from other forms of CMT by autosomal recessive inheritance. Those affected have distal muscle weakness and atrophy associated with sensory loss and, frequently, pes cavus foot deformity. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275423  Cd Length: 94  Bit Score: 141.31  E-value: 1.13e-39
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71983825 510 LLKSGSVQKISSTTEKTEERFIFLFNDLVILASERKMIGVSKYKLRAVFSASHMQVCEGDNLEREHSFYLRGSdgtgpKR 589
Cdd:cd13388   1 LIKEGKILKISARNGDTQERYLFLFNDMLLYCSPRLRLIGQKYKVRARFDVDGMQVLEGDNLETPHTFYVRGK-----QR 75
                        90
                ....*....|....*....
gi 71983825 590 CVELFTPTQKEKNDWVDSI 608
Cdd:cd13388  76 SLELQASTQEEKAEWVDAI 94
RhoGEF cd00160
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous ...
299-478 1.98e-38

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains.


Pssm-ID: 238091 [Multi-domain]  Cd Length: 181  Bit Score: 141.28  E-value: 1.98e-38
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71983825 299 WYAAKELVDSEQRYVDKLKLLGDTFRNRLIKEEL-ITNDKITRLLANVSSLYQFHNThFLPQLLESIRDWHTTK-RIANV 376
Cdd:cd00160   2 QEVIKELLQTERNYVRDLKLLVEVFLKPLDKELLpLSPEEVELLFGNIEEIYEFHRI-FLKSLEERVEEWDKSGpRIGDV 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71983825 377 VRKQAPFLKMYSEYTNNYDRAtklFEELKKKKKFADVVKEIEKQAE--CEGLPLGHHLICPVQRVMRYQLLLQEYKKHLQ 454
Cdd:cd00160  81 FLKLAPFFKIYSEYCSNHPDA---LELLKKLKKFNKFFQEFLEKAEseCGRLKLESLLLKPVQRLTKYPLLLKELLKHTP 157
                       170       180
                ....*....|....*....|....
gi 71983825 455 PSDVDFDDTTVALELVLQAAAHAN 478
Cdd:cd00160 158 DGHEDREDLKKALEAIKEVASQVN 181
RhoGEF pfam00621
RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called ...
301-478 1.19e-35

RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that pfam00169 domains invariably occur C-terminal to RhoGEF/DH domains.


Pssm-ID: 459876 [Multi-domain]  Cd Length: 176  Bit Score: 133.19  E-value: 1.19e-35
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71983825   301 AAKELVDSEQRYVDKLKLLGDTFRNRLIKEELITNDKITRLLANVSSLYQFHNTHFLPQLLESirdWHTTKRIANVVRKQ 380
Cdd:pfam00621   1 VIKELLQTERSYVRDLEILVEVFLPPNSKPLSESEEEIKTIFSNIEEIYELHRQLLLEELLKE---WISIQRIGDIFLKF 77
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71983825   381 APFLKMYSEYTNNYDRATKL-FEELKKKKKFADVVKEIEKQAECEGLPLGHHLICPVQRVMRYQLLLQEYKKHLQPSDVD 459
Cdd:pfam00621  78 APGFKVYSTYCSNYPKALKLlKKLLKKNPKFRAFLEELEANPECRGLDLNSFLIKPVQRIPRYPLLLKELLKHTPPDHPD 157
                         170
                  ....*....|....*....
gi 71983825   460 FDDTTVALELVLQAAAHAN 478
Cdd:pfam00621 158 YEDLKKALEAIKEVAKQIN 176
FYVE smart00064
Protein present in Fab1, YOTB, Vac1, and EEA1; The FYVE zinc finger is named after four ...
641-692 3.90e-14

Protein present in Fab1, YOTB, Vac1, and EEA1; The FYVE zinc finger is named after four proteins where it was first found: Fab1, YOTB/ZK632.12, Vac1, and EEA1. The FYVE finger has been shown to bind two Zn2+ ions. The FYVE finger has eight potential zinc coordinating cysteine positions. The FYVE finger is structurally related to the PHD finger and the RING finger. Many members of this family also include two histidines in a motif R+HHC+XCG, where + represents a charged residue and X any residue. The FYVE finger functions in the membrane recruitment of cytosolic proteins by binding to phosphatidylinositol 3-phosphate (PI3P), which is prominent on endosomes. The R+HHC+XCG motif is critical for PI3P binding.


Pssm-ID: 214499 [Multi-domain]  Cd Length: 68  Bit Score: 67.84  E-value: 3.90e-14
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 71983825    641 KHCADCDIEFGFLSRGSKCVKCSRRLCKKCFGRRRN-----ESKKHRICDTCTKNMD 692
Cdd:smart00064  11 SNCMGCGKEFNLTKRRHHCRNCGRIFCSKCSSKKAPlpklgIERPVRVCDDCYENLN 67
PH1_FDG_family cd13328
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia family proteins, N-terminal ...
512-608 1.18e-12

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia family proteins, N-terminal Pleckstrin homology (PH) domain; In general, FGDs have a RhoGEF (DH) domain, followed by an N-terminal PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activates the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the N-terminal PH domain is involved in intracellular targeting of the DH domain. Mutations in the FGD1 gene are responsible for the X-linked disorder known as faciogenital dysplasia (FGDY). PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275410  Cd Length: 92  Bit Score: 64.43  E-value: 1.18e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71983825 512 KSGSVQKISSTTEKTEERFIFLFNDLVILASERKMIGVSKYKLRAVFSASHMQVCEGDNLEREHSFYLRGSdgtgpKRCV 591
Cdd:cd13328   1 KEGQILKLSAKNGTPQPRYLFLFNDMLLYCVPKLSLVGQKFSVRNRLDVAGMKVREPVNENYPHTFKISGK-----ERSL 75
                        90
                ....*....|....*..
gi 71983825 592 ELFTPTQKEKNDWVDSI 608
Cdd:cd13328  76 ELQASSAEEKDEWIQAI 92
PH1_FGD3 cd13387
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 3, N-terminal Pleckstrin ...
510-622 1.30e-12

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 3, N-terminal Pleckstrin homology (PH) domain; In general, FGDs have a RhoGEF (DH) domain, followed by an N-terminal PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activates the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the N-terminal PH domain is involved in intracellular targeting of the DH domain. Both FGD1 and FGD3 are targeted by the ubiquitin ligase SCF(FWD1/beta-TrCP) upon phosphorylation of two serine residues in its DSGIDS motif and subsequently degraded by the proteasome. However, FGD1 and FGD3 induced significantly different morphological changes in HeLa Tet-Off cells and while FGD1 induced long finger-like protrusions, FGD3 induced broad sheet-like protrusions when the level of GTP-bound Cdc42 was significantly increased by the inducible expression of FGD3. They also reciprocally regulated cell motility in inducibly expressed in HeLa Tet-Off cells, FGD1 stimulated cell migration while FGD3 inhibited it. FGD1 and FGD3 therefore play different roles to regulate cellular functions, even though their intracellular levels are tightly controlled by the same destruction pathway through SCF(FWD1/beta-TrCP). PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275422  Cd Length: 108  Bit Score: 64.99  E-value: 1.30e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71983825 510 LLKSGSVQKISSTTEKTEERFIFLFNDLVILASERKMIGVSKYKLRAVFSASHMQVCEGDNLEREHSFYLrgsdgTGPKR 589
Cdd:cd13387   1 LIKEGHIQKLSAKNGTAQDRYLYLFNSMVLYCVPKLRLMGQKFSVREKIDIAGMQVQEIVKQNVPHTFTI-----TGKKR 75
                        90       100       110
                ....*....|....*....|....*....|...
gi 71983825 590 CVELFTPTQKEKNDWVDSIFSIIDEAKAHSLTF 622
Cdd:cd13387  76 SLELQARTEEEKKEWIQVIQATIEKHKQNSETF 108
PH1_FGD5_FGD6 cd13389
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 5 and 6, N-terminal ...
502-622 2.38e-11

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 5 and 6, N-terminal Pleckstrin Homology (PH) domain; FGD5 regulates promotes angiogenesis of vascular endothelial growth factor (VEGF) in vascular endothelial cells, including network formation, permeability, directional movement, and proliferation. The specific function of FGD6 is unknown. In general, FGDs have a RhoGEF (DH) domain, followed by a PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activate the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the PH domain is involved in intracellular targeting of the DH domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275424  Cd Length: 124  Bit Score: 61.52  E-value: 2.38e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71983825 502 SLVSPGRELLKSGSVQKISSttEKTEERFIFLFNDLVILASERKmiGVSKYKLRAVFSASHMQVCEGDNLEREHSFYLRG 581
Cdd:cd13389   6 NIVKPGRKLIKEGELMKVSR--KEMQPRYFFLFNDCLLYTTPVQ--SSGMLKLNNELPLSGMKVKLPEDEEYSNEFQIIS 81
                        90       100       110       120
                ....*....|....*....|....*....|....*....|.
gi 71983825 582 SdgtgpKRCVELFTPTQKEKNDWVDSIFSIIDEAKAHSLTF 622
Cdd:cd13389  82 T-----KRSFTLIASSEEERDEWVKALSRAIEEHTKKQRTF 117
PH1_FGD2 cd13386
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 2, N-terminal Pleckstrin ...
510-622 5.42e-11

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 2, N-terminal Pleckstrin homology (PH) domain; In general, FGDs have a RhoGEF (DH) domain, followed by an N-terminal PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activates the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the N-terminal PH domain is involved in intracellular targeting of the DH domain. Not much is known about FGD2. FGD1 is the best characterized member of the group with mutations here leading to the X-linked disorder known as faciogenital dysplasia (FGDY). PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275421  Cd Length: 108  Bit Score: 60.31  E-value: 5.42e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71983825 510 LLKSGSVQKISSTTEKTEERFIFLFNDLVILASERKMIGVSKYKLRAVFSASHMQVCEGDNLEREHSFYLrgsdgTGPKR 589
Cdd:cd13386   1 LLKEGPVLKISFRNNNPKERYLFLFNNMLLYCVPKVIQVGAKFQVHMRIDVDGMKVRELNDAEFPHSFLV-----SGKQR 75
                        90       100       110
                ....*....|....*....|....*....|...
gi 71983825 590 CVELFTPTQKEKNDWVDSIFSIIDEAKAHSLTF 622
Cdd:cd13386  76 TLELQARSQEEMEAWIQAFQEAIDQNEKRTETF 108
PH1_FARP1-like cd01220
FERM, RhoGEF and pleckstrin domain-containing protein 1 and related proteins Pleckstrin ...
503-618 1.68e-10

FERM, RhoGEF and pleckstrin domain-containing protein 1 and related proteins Pleckstrin Homology (PH) domain, repeat 1; Members here include FARP1 (also called Chondrocyte-derived ezrin-like protein; PH domain-containing family C member 2), FARP2 (also called FIR/FERM domain including RhoGEF; FGD1-related Cdc42-GEF/FRG), and FARP6 (also called Zinc finger FYVE domain-containing protein 24). They are members of the Dbl family guanine nucleotide exchange factors (GEFs) which are upstream positive regulators of Rho GTPases. Little is known about FARP1 and FARP6, though FARP1 has increased expression in differentiated chondrocytes. FARP2 is thought to regulate neurite remodeling by mediating the signaling pathways from membrane proteins to Rac. It is found in brain, lung, and testis, as well as embryonic hippocampal and cortical neurons. FARP1 and FARP2 are composed of a N-terminal FERM domain, a proline-rich (PR) domain, Dbl-homology (DH), and two C-terminal PH domains. FARP6 is composed of Dbl-homology (DH), and two C-terminal PH domains separated by a FYVE domain. This hierarchy contains the first PH repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269928  Cd Length: 109  Bit Score: 58.87  E-value: 1.68e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71983825 503 LVSPGRELLKSGSVQKISSttEKTEERFIFLFNDLVILASeRKMIGVSKYKLRAVFSASHMQVCEGDN-LEREHSFYLRG 581
Cdd:cd01220   1 LVQPGREFIREGCLQKLSK--KGLQQRMFFLFSDVLLYTS-RSPTPSLQFKVHGQLPLRGLMVEESEPeWGVAHCFTIYG 77
                        90       100       110
                ....*....|....*....|....*....|....*..
gi 71983825 582 SDgtgpkRCVELFTPTQKEKNDWVDSIFSIIDEAKAH 618
Cdd:cd01220  78 GN-----RALTVAASSEEEKERWLEDLQRAIDAAKKS 109
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
510-613 2.91e-09

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 55.25  E-value: 2.91e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71983825    510 LLKSGSVQKISSTTEKT-EERFIFLFNDLVILASERKMigVSKYKLRAVFSASHMQVCE---GDNLEREHSFYLRGSDGt 585
Cdd:smart00233   1 VIKEGWLYKKSGGGKKSwKKRYFVLFNSTLLYYKSKKD--KKSYKPKGSIDLSGCTVREapdPDSSKKPHCFEIKTSDR- 77
                           90       100
                   ....*....|....*....|....*...
gi 71983825    586 gpkRCVELFTPTQKEKNDWVDSIFSIID 613
Cdd:smart00233  78 ---KTLLLQAESEEEREKWVEALRKAIA 102
FYVE_like_SF cd00065
FYVE domain like superfamily; FYVE domain is a 60-80 residue double zinc finger ...
642-687 2.97e-08

FYVE domain like superfamily; FYVE domain is a 60-80 residue double zinc finger motif-containing module named after the four proteins, Fab1, YOTB, Vac1, and EEA1. The canonical FYVE domains are distinguished from other zinc fingers by three signature sequences: an N-terminal WxxD motif (x for any residue), the central basic R(R/K)HHCRxCG patch, and a C-terminal RVC motif, which form a compact phosphatidylinositol 3-phosphate (PtdIns3P, also termed PI3P)-binding site. They are found in many membrane trafficking regulators, including EEA1, Hrs, Vac1p, Vps27p, and FENS-1, which locate to early endosomes, specifically bind PtdIns3P, and play important roles in vesicular traffic and in signal transduction. Some proteins, such as rabphilin-3A and alpha-Rab3-interacting molecules (RIMs), are also involved in membrane trafficking and bind to members of the Rab subfamily of GTP hydrolases. However, they contain FYVE-related domains that are structurally similar to the canonical FYVE domains but lack the three signature sequences. At this point, they may not bind to phosphoinositides. In addition, this superfamily also contains the third group of proteins, caspase-associated ring proteins CARP1 and CARP2. They do not localize to membranes in the cell and are involved in the negative regulation of apoptosis, specifically targeting two initiator caspases, caspase 8 and caspase 10, which are distinguished from other FYVE-type proteins. Moreover, these proteins have an altered sequence in the basic ligand binding patch and lack the WxxD motif that is conserved only in phosphoinositide binding FYVE domains. Thus they constitute a family of unique FYVE-type domains called FYVE-like domains. The FYVE domain is structurally similar to the RING domain and the PHD finger. This superfamily also includes ADDz zinc finger domain, which is a PHD-like zinc finger motif that contains two parts, a C2-C2 and a PHD-like zinc finger.


Pssm-ID: 277249 [Multi-domain]  Cd Length: 52  Bit Score: 50.61  E-value: 2.97e-08
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 71983825 642 HCADCDIEFGFLSRGSKCVKCSRRLCKKCFGRRR-----NESKKHRICDTC 687
Cdd:cd00065   1 RCMLCGKKFSLFRRRHHCRRCGRVFCSKCSSKKLplpsfGSGKPVRVCDSC 51
PH1_FDG4 cd15791
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 4, N-terminal Pleckstrin ...
510-608 4.46e-08

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 4, N-terminal Pleckstrin homology (PH) domain; In general, FGDs have a RhoGEF (DH) domain, followed by an N-terminal PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activates the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the N-terminal PH domain is involved in intracellular targeting of the DH domain. FGD4 is one of the genes associated with Charcot-Marie-Tooth neuropathy type 4 (CMT4), a group of progressive motor and sensory axonal and demyelinating neuropathies that are distinguished from other forms of CMT by autosomal recessive inheritance. Those affected have distal muscle weakness and atrophy associated with sensory loss and, frequently, pes cavus foot deformity. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275434  Cd Length: 94  Bit Score: 51.53  E-value: 4.46e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71983825 510 LLKSGSVQKISSTTEKTEERFIFLFNDLVILASERKMIGVSKYKLRAVFSASHMQVCEGDNLEREHSFYLrgsdgTGPKR 589
Cdd:cd15791   1 LIKEGQILKLAARNTSAQERYLFLFNNMLLYCVPKFSLVGSKYTVRTRIGIDGMKVVETQNEDYPHTFQV-----SGKER 75
                        90
                ....*....|....*....
gi 71983825 590 CVELFTPTQKEKNDWVDSI 608
Cdd:cd15791  76 TLELQASSEQDKEEWIKAL 94
PH pfam00169
PH domain; PH stands for pleckstrin homology.
510-612 5.02e-08

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 51.79  E-value: 5.02e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71983825   510 LLKSGSVQKISSTTEKT-EERFIFLFNDLVILASERKmiGVSKYKLRAVFSASHMQVCE---GDNLEREHSFYLRGSDGT 585
Cdd:pfam00169   1 VVKEGWLLKKGGGKKKSwKKRYFVLFDGSLLYYKDDK--SGKSKEPKGSISLSGCEVVEvvaSDSPKRKFCFELRTGERT 78
                          90       100
                  ....*....|....*....|....*..
gi 71983825   586 GpKRCVELFTPTQKEKNDWVDSIFSII 612
Cdd:pfam00169  79 G-KRTYLLQAESEEERKDWIKAIQSAI 104
PH_Phafin2-like cd01218
Phafin2 (also called EAPF, FLJ13187, ZFYVE18 or PLEKHF2) Pleckstrin Homology (PH) domain; ...
489-608 6.47e-08

Phafin2 (also called EAPF, FLJ13187, ZFYVE18 or PLEKHF2) Pleckstrin Homology (PH) domain; Phafin2 is differentially expressed in the liver cancer cell and regulates the structure and function of the endosomes through Rab5-dependent processes. Phafin2 modulates the cell's response to extracellular stimulation by modulating the receptor density on the cell surface. Phafin2 contains a PH domain and a FYVE domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269927 [Multi-domain]  Cd Length: 123  Bit Score: 51.87  E-value: 6.47e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71983825 489 KVIEVQEQLGNS-ISLVSPGRELLKSGSVQKISSTTEKteERFIFLFNDLVILASErkMIGVSKYKLRAVFSASHMQVCE 567
Cdd:cd01218   8 RIAAVESCFGGSgQPLVKPGRVLVGEGVLTKVCRKKPK--PRQFFLFNDILVYGSI--VINKKKYNKQRIIPLEDVKIED 83
                        90       100       110       120
                ....*....|....*....|....*....|....*....|..
gi 71983825 568 -GDNLEREHSFYLRGsdgtgPKRCVELFTPTQKEKNDWVDSI 608
Cdd:cd01218  84 lEDTGELKNGWQIIS-----PKKSFVVYAATATEKSEWMDHI 120
PH_PEPP1_2_3 cd13248
Phosphoinositol 3-phosphate binding proteins 1, 2, and 3 pleckstrin homology (PH) domain; ...
738-810 1.03e-06

Phosphoinositol 3-phosphate binding proteins 1, 2, and 3 pleckstrin homology (PH) domain; PEPP1 (also called PLEKHA4/PH domain-containing family A member 4 and RHOXF1/Rhox homeobox family member 1), and related homologs PEPP2 (also called PLEKHA5/PH domain-containing family A member 5) and PEPP3 (also called PLEKHA6/PH domain-containing family A member 6), have PH domains that interact specifically with PtdIns(3,4)P3. Other proteins that bind PtdIns(3,4)P3 specifically are: TAPP1 (tandem PH-domain-containing protein-1) and TAPP2], PtdIns3P AtPH1, and Ptd- Ins(3,5)P2 (centaurin-beta2). All of these proteins contain at least 5 of the 6 conserved amino acids that make up the putative phosphatidylinositol 3,4,5- trisphosphate-binding motif (PPBM) located at their N-terminus. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270068  Cd Length: 104  Bit Score: 47.65  E-value: 1.03e-06
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 71983825 738 RFMVVRDdFCMYTYSSEEDICALAMLPLPGCEVKMC------GEKFTFSVRVGARRMYTMTAEDEQTQMKWLAILDLAA 810
Cdd:cd13248  27 RWFVLKD-NCLYYYKDPEEEKALGSILLPSYTISPAppsdeiSRKFAFKAEHANMRTYYFAADTAEEMEQWMNAMSLAA 104
PH1_FGD6 cd15793
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 6, N-terminal Pleckstrin ...
503-622 1.54e-06

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 6, N-terminal Pleckstrin Homology (PH) domain; FGD5 regulates promotes angiogenesis of vascular endothelial growth factor (VEGF) in vascular endothelial cells, including network formation, permeability, directional movement, and proliferation. The specific function of FGD6 is unknown. In general, FGDs have a RhoGEF (DH) domain, followed by a PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activate the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the PH domain is involved in intracellular targeting of the DH domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275436  Cd Length: 123  Bit Score: 48.10  E-value: 1.54e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71983825 503 LVSPGRELLKSGSVQKISSTTekTEERFIFLFNDLVILASErkmIGVSKYKLRAVFSASHMQVCEGD--------NLER- 573
Cdd:cd15793   7 IVQPGRVFLKEGTLMKLSRKV--MQPRMFFLFNDALLYTTP---VQSGMYKLNNMLSLAGMKVSKPSqeayqnelNIESv 81
                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*....
gi 71983825 574 EHSFYLRGSDGTgpkrcvelftptqkEKNDWVDSIFSIIDEAKAHSLTF 622
Cdd:cd15793  82 ERSFILSASSAT--------------ERDEWLEAISRAIEEYAKKKITF 116
PH2_Kalirin_Trio_p63RhoGEF cd13241
p63RhoGEF pleckstrin homology (PH) domain, repeat 2; The guanine nucleotide exchange factor ...
519-613 2.65e-06

p63RhoGEF pleckstrin homology (PH) domain, repeat 2; The guanine nucleotide exchange factor p63RhoGEF is an effector of the heterotrimeric G protein, Galphaq and linking Galphaq-coupled receptors (GPCRs) to the activation of RhoA. The Dbl(DH) and PH domains of p63RhoGEF interact with the effector-binding site and the C-terminal region of Galphaq and appear to relieve autoinhibition of the catalytic DH domain by the PH domain. Trio, Duet, and p63RhoGEF are shown to constitute a family of Galphaq effectors that appear to activate RhoA both in vitro and in intact cells. Dbs is a guanine nucleotide exchange factor (GEF), which contains spectrin repeats, a rhoGEF (DH) domain and a PH domain. The Dbs PH domain participates in binding to both the Cdc42 and RhoA GTPases. Trio plays an essential role in regulating the actin cytoskeleton during axonal guidance and branching. Trio is a multidomain signaling protein that contains two RhoGEF(DH)-PH domains in tandem. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270061  Cd Length: 140  Bit Score: 47.64  E-value: 2.65e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71983825 519 ISSTTEKTEERFIFLFNDLVILASE---RKMIGVSKYKLRAVFSASHMQVcEGDNLEREHSFYLRGSDGTGPKRCVELFT 595
Cdd:cd13241  29 SAGLLQKGKERRVFLFEQIIIFSEIlgkKTQFSNPGYIYKNHIKVNKMSL-EENVDGDPLRFALKSRDPNNPSETFILQA 107
                        90
                ....*....|....*...
gi 71983825 596 PTQKEKNDWVDSIFSIID 613
Cdd:cd13241 108 ASPEVRQEWVDTINQILD 125
FYVE_Slp3_4_5 cd15747
FYVE-related domain found in the synaptotagmin-like proteins 3, 4, 5; The synaptotagmin-like ...
641-689 4.06e-06

FYVE-related domain found in the synaptotagmin-like proteins 3, 4, 5; The synaptotagmin-like proteins 1-5 (Slp1-5) family belongs to the carboxyl-terminal-type (C-type) tandem C2 proteins superfamily, which also contains the synaptotagmin and the Doc2 families. Slp proteins are putative membrane trafficking proteins that are characterized by the presence of a unique N-terminal Slp homology domain (SHD), and C-terminal tandem C2 domains (known as the C2A domain and C2B domain). The SHD consists of two conserved regions, designated SHD1 (Slp homology domain 1) and SHD2. The SHD1 and SHD2 of Slp3, Slp4 and Slp5 are separated by a putative FYVE zinc finger. By contrast, Slp1 and Slp2 lack such zinc finger and their SHD1 and SHD2 are linked together. This model corresponds to the FYVE zinc finger. At this point, Slp1 and Slp2 are not included in this model. Moreover, the FYVE domains of Slp3, Slp4 and Slp5 resemble a FYVE-related domain that is structurally similar to the canonical FYVE domains but lacks the three signature sequences: an N-terminal WxxD motif (x for any residue), the central basic R(R/K)HHCRxCG patch, and a C-terminal RVC motif.


Pssm-ID: 277286  Cd Length: 48  Bit Score: 44.21  E-value: 4.06e-06
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 71983825 641 KHCADCDIEFGFLS-RGSKCVKCSRRLCKKCfgRRRNESKKHRICDTCTK 689
Cdd:cd15747   1 RICARCREKLGFIFnRGARCPKCSHKVCKKC--RVLTSNTGKWLCTVCHK 48
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
718-811 5.72e-06

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 45.62  E-value: 5.72e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71983825    718 SGVLHssqIRFRGSLGKLLDRFMVVRDDfCMYTYSSEEDICALA---MLPLPGCEV------KMCGEKFTFSVRVGARRM 788
Cdd:smart00233   4 EGWLY---KKSGGGKKSWKKRYFVLFNS-TLLYYKSKKDKKSYKpkgSIDLSGCTVreapdpDSSKKPHCFEIKTSDRKT 79
                           90       100
                   ....*....|....*....|...
gi 71983825    789 YTMTAEDEQTQMKWLAILDLAAN 811
Cdd:smart00233  80 LLLQAESEEEREKWVEALRKAIA 102
PH2_FGD1-4 cd13236
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins pleckstrin homology (PH) ...
743-810 4.18e-05

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins pleckstrin homology (PH) domain, C-terminus; In general, FGDs have a RhoGEF (DH) domain, followed by an N-terminal PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activates the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the N-terminal PH domain is involved in intracellular targeting of the DH domain. Not much is known about FGD2. FGD1 is the best characterized member of the group with mutations here leading to the X-linked disorder known as faciogenital dysplasia (FGDY). Both FGD1 and FGD3 are targeted by the ubiquitin ligase SCF(FWD1/beta-TrCP) upon phosphorylation of two serine residues in its DSGIDS motif and subsequently degraded by the proteasome. However, FGD1 and FGD3 induced significantly different morphological changes in HeLa Tet-Off cells and while FGD1 induced long finger-like protrusions, FGD3 induced broad sheet-like protrusions when the level of GTP-bound Cdc42 was significantly increased by the inducible expression of FGD3. They also reciprocally regulated cell motility in inducibly expressed in HeLa Tet-Off cells, FGD1 stimulated cell migration while FGD3 inhibited it. FGD1 and FGD3 therefore play different roles to regulate cellular functions, even though their intracellular levels are tightly controlled by the same destruction pathway through SCF(FWD1/beta-TrCP). FGD4 is one of the genes associated with Charcot-Marie-Tooth neuropathy type 4 (CMT4), a group of progressive motor and sensory axonal and demyelinating neuropathies that are distinguished from other forms of CMT by autosomal recessive inheritance. Those affected have distal muscle weakness and atrophy associated with sensory loss and, frequently, pes cavus foot deformity. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270056  Cd Length: 105  Bit Score: 43.11  E-value: 4.18e-05
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 71983825 743 RDDFCMYTYSSEEDICALAMLPLPGCEVkmcgEKFTFSVRVGARRM---------YTMTAEDEQTQMKWLAILDLAA 810
Cdd:cd13236  33 TEPLVLYLYGAPQDVRAQRTIPLPGCEV----TVPPPEERLDGRHVfklsqskqsHYFSAESEELQQRWLEALSRAA 105
PH1_FGD5 cd15792
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 5, N-terminal Pleckstrin ...
502-621 2.29e-04

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 5, N-terminal Pleckstrin Homology (PH) domain; FGD5 regulates promotes angiogenesis of vascular endothelial growth factor (VEGF) in vascular endothelial cells, including network formation, permeability, directional movement, and proliferation. In general, FGDs have a RhoGEF (DH) domain, followed by a PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activate the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the PH domain is involved in intracellular targeting of the DH domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275435  Cd Length: 123  Bit Score: 41.75  E-value: 2.29e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71983825 502 SLVSPGRELLKSGSVQKISstTEKTEERFIFLFNDLVILASERKMigvSKYKLRAVFSASHMQVCEGDNLEREHSFYLRG 581
Cdd:cd15792   6 DLLQPGREFVKEGTLMKVS--GKNRHPRHLFLMNDVLLYTYPQKD---GKYRLKNTLAVSGMKVSRPVIEKAQNVLKIEV 80
                        90       100       110       120
                ....*....|....*....|....*....|....*....|.
gi 71983825 582 SDgtgpkRCVELFTPTQKEKNDWVDSIF-SIIDEAKAHSLT 621
Cdd:cd15792  81 SE-----VCLTLSASSCSERDEWYSCLSrTIPDDYKAQNAS 116
PH_RARhoGAP cd13319
RA and RhoGAP domain-containing protein Pleckstrin homology PH domain; RARhoGAP (also called ...
508-604 2.46e-04

RA and RhoGAP domain-containing protein Pleckstrin homology PH domain; RARhoGAP (also called Rho GTPase-activating protein 20 and ARHGAP20 ) is thought to function in rearrangements of the cytoskeleton and cell signaling events that occur during spermatogenesis. RARhoGAP was also shown to be activated by Rap1 and to induce inactivation of Rho, resulting in the neurite outgrowth. Recent findings show that ARHGAP20, even although it is located in the middle of the MDR on 11q22-23, is expressed at higher levels in chronic lymphocytic leukemia patients with 11q22-23 and/or 13q14 deletions and its expression pattern suggests a functional link between cases with 11q22-23 and 13q14 deletions. The mechanism needs to be further studied. RARhoGAP contains a PH domain, a Ras-associating domain, a Rho-GAP domain, and ANXL repeats. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270129  Cd Length: 97  Bit Score: 40.69  E-value: 2.46e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71983825 508 RELLKSGSVQkiSSTTEKTEERFIFLFNDLVILAserKMIGVSKYKLRAVFSASHM-------QVCEGdNLEREHSFYLr 580
Cdd:cd13319   1 RTFLLEGPVQ--LTRGLQTQERHLFLFSDVLVVA---KPKSKNSFKLKHKIRLSELwlascvdEVCEG-SKSADKSFVL- 73
                        90       100
                ....*....|....*....|....
gi 71983825 581 GSDGTgpkRCVELFtPTQKEKNDW 604
Cdd:cd13319  74 GWPTT---NFVATF-SSQEEKDLW 93
FYVE_ANFY1 cd15728
FYVE domain found in ankyrin repeat and FYVE domain-containing protein 1 (ANFY1) and similar ...
643-687 3.78e-04

FYVE domain found in ankyrin repeat and FYVE domain-containing protein 1 (ANFY1) and similar proteins; ANFY1, also termed ankyrin repeats hooked to a zinc finger motif (Ankhzn), is a novel cytoplasmic protein that belongs to a new group of double zinc finger proteins involved in vesicle or protein transport. It is ubiquitously expressed in a spatiotemporal-specific manner and is located on endosomes. ANFY1 contains an N-terminal coiled-coil region and a BTB/POZ domain, ankyrin repeats in the middle, and a C-terminal FYVE domain.


Pssm-ID: 277267 [Multi-domain]  Cd Length: 63  Bit Score: 39.33  E-value: 3.78e-04
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 71983825 643 CADCDIEFGFLSRGSKCVKCSRRLCKKCFGR-----RRNESKKHRICDTC 687
Cdd:cd15728  10 CYECGVKFGITTRKHHCRHCGRLLCSKCSTKevpiiKFDLNKPVRVCDVC 59
PH_ephexin cd01221
Ephexin Pleckstrin homology (PH) domain; Ephexin-1 (also called NGEF/ neuronal guanine ...
498-606 7.98e-04

Ephexin Pleckstrin homology (PH) domain; Ephexin-1 (also called NGEF/ neuronal guanine nucleotide exchange factor) plays a role in the homeostatic modulation of presynaptic neurotransmitter release. Specific functions are still unknown for Ephexin-2 (also called RhoGEF19) and Ephexin-3 (also called Rho guanine nucleotide exchange factor 5/RhoGEF5, Transforming immortalized mammary oncogene/p60 TIM, and NGEF/neuronalGEF). Ephexin-4 (also called RhoGEF16) acts downstream of EphA2 to promote ligand-independent breast cancer cell migration and invasion toward epidermal growth factor through activation of RhoG. This in turn results in the activation of RhoG which recruits ELMO2 and Dock4 to form a complex with EphA2 at the tips of cortactin-rich protrusions in migrating breast cancer cells. Ephexin-5 is the specific GEF for RhoA activation and the regulation of vascular smooth muscle contractility. It interacts with EPHA4 PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. The members of the Ephexin family contains a RhoGEF (DH) followed by a PH domain and an SH3 domain. The ephexin PH domain is believed to act with the DH domain in mediating protein-protein interactions. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269929  Cd Length: 131  Bit Score: 40.32  E-value: 7.98e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71983825 498 GNSISLVSPGRELLKSGSVQKISSTTEKTEERFI--------FLFNDLVILASERKMIG--VSKYKLRAVFsasHMQVCE 567
Cdd:cd01221   2 IKAFPLISSSRWLVKRGELTELVEDGGSLTFRKKfsktpvylFLFNDLLLITKKKSEERylVLDYAPRNLV---QVEEVE 78
                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*
gi 71983825 568 GDNL----EREHSFYLRGSDGTGPKRcVELF--TPTQKEKNDWVD 606
Cdd:cd01221  79 DPLQlpqpLGKNLFLLTLLENHEGKT-VELLlsAESESDRERWLS 122
PH_SOS cd01261
Son of Sevenless (SOS) Pleckstrin homology (PH) domain; SOS is a Ras guanine nucleotide ...
509-604 1.55e-03

Son of Sevenless (SOS) Pleckstrin homology (PH) domain; SOS is a Ras guanine nucleotide exchange factor. SOS is thought to transmit signals from activated receptor tyrosine kinases to the Ras signaling pathway. SOS contains a histone domain, Dbl-homology (DH), a PH domain, Rem domain, Cdc25 domain, and a Grb2 binding domain. The SOS PH domain binds to phosphatidylinositol-4,5-bisphosphate (PIP2) and phosphatidic acid (PA). SOS is dependent on Ras binding to the allosteric site via its histone domain for both a lower level of activity (Ras GDP) and maximal activity (Ras GTP). The DH domain blocks the allosteric Ras binding site in SOS. The PH domain is closely associated with the DH domain and the action of the DH-PH unit gates a reciprocal interaction between Ras and SOS. The C-terminal proline-rich domain of SOS binds to the adapter protein Grb2 which localizes the Sos protein to the plasma membrane and diminishes the negative effect of the C-terminal domain on the guanine nucleotide exchange activity of the CDC25-homology domain of SOS. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269963  Cd Length: 109  Bit Score: 38.88  E-value: 1.55e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71983825 509 ELLKSGSVQKISSTTEKTEeRFIFLFNDLVIL-----ASERKMIGVSKYKLRAVFSASHMQVCE-GDNLEREHSFYLRGS 582
Cdd:cd01261   5 EFIMEGTLGKVGSGKRKTE-RHAFLFDGLLLLcksnrRRTSTGGPKPEYRLKEKFFIRKVEINDlEDTEELKNAFEIVPR 83
                        90       100
                ....*....|....*....|..
gi 71983825 583 DGTGpkrcVELFTPTQKEKNDW 604
Cdd:cd01261  84 DQPS----VILFAKSAEEKNNW 101
FYVE_ZFYV1 cd15734
FYVE domains found in zinc finger FYVE domain-containing protein 1 (ZFYV1) and similar ...
641-687 2.25e-03

FYVE domains found in zinc finger FYVE domain-containing protein 1 (ZFYV1) and similar proteins; ZFYV1, also termed double FYVE-containing protein 1 (DFCP1), or SR3, or tandem FYVE fingers-1, is a novel tandem FYVE domain containing protein that binds phosphatidylinositol 3-phosphate (PtdIns3P or PI3P) with high specificity over other phosphoinositides. The subcellular distribution of exogenously-expressed ZFYV1 to Golgi, endoplasmic reticulum (ER) and vesicular is governed in part by its FYVE domains but unaffected by wortmannin, a PI3-kinase inhibitor. In addition to C-terminal tandem FYVE domain, ZFYV1 contains an N-terminal putative C2H2 type zinc finger and a possible nucleotide binding P-loop.


Pssm-ID: 277273 [Multi-domain]  Cd Length: 61  Bit Score: 36.93  E-value: 2.25e-03
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 71983825 641 KHCADCDIEFGFLSRGSKCVKCSRRLCKKCF-GRRRNES----KKHRICDTC 687
Cdd:cd15734   9 KECSVCKRPFSPRLSKHHCRACGQGVCDDCSkNRRPVPSrgwdHPVRVCDPC 60
PH2_FGD5_FGD6 cd13237
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 5 and 6 pleckstrin ...
738-806 4.19e-03

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 5 and 6 pleckstrin homology (PH) domain, C-terminus; FGD5 regulates promotes angiogenesis of vascular endothelial growth factor (VEGF) in vascular endothelial cells, including network formation, permeability, directional movement, and proliferation. The specific function of FGD6 is unknown. In general, FGDs have a RhoGEF (DH) domain, followed by a PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activate the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the PH domain is involved in intracellular targeting of the DH domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270057  Cd Length: 91  Bit Score: 37.39  E-value: 4.19e-03
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 71983825 738 RFMVVRDDFCMYTYSSEEDICALAMLPLPGCEVKMCGEKFT------FSVRVGARRMYTMTAEDEQTQMKWLAIL 806
Cdd:cd13237  17 RLWFVLKDKVLYTYKASEDVVALESVPLLGFTVVTIDESFEedeslvFQLLHKGQLPIIFRADDAETAQRWIEAL 91
FYVE_Hrs cd15720
FYVE domain found in hepatocyte growth factor (HGF)-regulated tyrosine kinase substrate (Hrs) ...
643-687 5.16e-03

FYVE domain found in hepatocyte growth factor (HGF)-regulated tyrosine kinase substrate (Hrs) and similar proteins; Hrs, also termed protein pp110, is a tyrosine phosphorylated protein that plays an important role in the signaling pathway of HGF. It is localized to early endosomes and an essential component of the endosomal sorting and trafficking machinery. Hrs interacts with hypertonia-associated protein Trak1, a novel regulator of endosome-to-lysosome trafficking. It can also forms an Hrs/actinin-4/BERP/myosin V protein complex that is required for efficient transferrin receptor (TfR) recycling but not for epidermal growth factor receptor (EGFR) degradation. Moreover, Hrs, together with STAM proteins, STAM1 and STAM2, and EPs15, forms a multivalent ubiquitin-binding complex that sorts ubiquitinated proteins into the multivesicular body pathway, and plays a regulatory role in endocytosis/exocytosis. Furthermore, Hrs functions as an interactor of the neurofibromatosis 2 tumor suppressor protein schwannomin/merlin. It is also involved in the inhibition of citron kinase-mediated HIV-1 budding. Hrs contains a single ubiquitin-interacting motif (UIM) that is crucial for its function in receptor sorting, and a FYVE domain that harbors double Zn2+ binding sites.


Pssm-ID: 277260 [Multi-domain]  Cd Length: 61  Bit Score: 36.21  E-value: 5.16e-03
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 71983825 643 CADCDIEFGFLSRGSKCVKCSRRLCKKC---------FGRRrnesKKHRICDTC 687
Cdd:cd15720   8 CHRCRVQFGVFQRKHHCRACGQVFCGKCssksstipkFGIE----KEVRVCDPC 57
FYVE_MTMR4 cd15733
FYVE domain found in myotubularin-related protein 4 (MTMR4) and similar proteins; MTMR4, also ...
642-670 8.48e-03

FYVE domain found in myotubularin-related protein 4 (MTMR4) and similar proteins; MTMR4, also termed FYVE domain-containing dual specificity protein phosphatase 2 (FYVE-DSP2), or zinc finger FYVE domain-containing protein 11, is an dual specificity protein phosphatase that specifically dephosphorylates phosphatidylinositol 3-phosphate (PtdIns3P or PI3P). It is localizes to early endosomes, as well as to Rab11- and Sec15-positive recycling endosomes, and regulates sorting from early endosomes. Moreover, MTMR4 is preferentially associated with and dephosphorylated the activated regulatory Smad proteins (R-Smads) in cytoplasm to keep transforming growth factor (TGF) beta signaling in homeostasis. It also functions as an essential negative modulator for the homeostasis of bone morphogenetic protein (BMP)/decapentaplegic (Dpp) signaling. In addition, MTMR4 acts as a novel interactor of the ubiquitin ligase Nedd4 (neural-precursor-cell-expressed developmentally down-regulated 4) and may play a role in the biological process of muscle breakdown. MTMR4 contains an N-terminal PH-GRAM (PH-G) domain, a MTM phosphatase domain, a coiled-coil region, and a C-terminal FYVE domain.


Pssm-ID: 277272 [Multi-domain]  Cd Length: 60  Bit Score: 35.48  E-value: 8.48e-03
                        10        20
                ....*....|....*....|....*....
gi 71983825 642 HCADCDIEFGFLSRGSKCVKCSRRLCKKC 670
Cdd:cd15733   9 HCFGCDCEFWLAKRKHHCRNCGNVFCADC 37
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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