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Conserved domains on  [gi|8923763|ref|NP_060874|]
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arf-GAP with dual PH domain-containing protein 2 isoform 2 [Homo sapiens]

Protein Classification

ADAP family PH domain-containing protein( domain architecture ID 12962796)

ADAP family PH (pleckstrin homology) domain-containing protein similar to PH region of Arf-GAP with dual PH domain-containing protein 1 (ADAP1) and 2 (ADAP2), which are GTPase-activating proteins for the ADP ribosylation factor family

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
ArfGap_ADAP2 cd08844
ADAP2 GTPase activating protein for Arf, with dual PH domains; The ADAP subfamily, ArfGAPs ...
 4-117 1.97e-76

ADAP2 GTPase activating protein for Arf, with dual PH domains; The ADAP subfamily, ArfGAPs with dual pleckstrin homology (PH) domains, includes two members: ADAP1 and ADAP2. Both ADAP1 (also known as centaurin-alpha1, p42(IP4), or PIP3BP) and ADAP2 (centaurin-alpha2) display a GTPase-activating protein (GAP) activity toward Arf6 (ADP-ribosylation factor 6), which is involved in protein trafficking that regulates endocytic recycling, cytoskeleton remodeling, and neuronal differentiation. ADAP2 has high sequence similarity to the ADAP1 and they both contain a ArfGAP domain at the N-terminus, followed by two PH domains. However, ADAP1, unlike ADAP2, contains a putative N-terminal nuclear localization signal. The PH domains of ADAP1bind to the two second messenger molecules phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3) and inositol 1,3,4,5-tetrakisphosphate (I(1,3,4,5)P4) with identical high affinity, whereas those of ADAP2 specifically binds phosphatidylinositol 3,4-bisphosphate (PI(3,4)P2) and PI(3,4,5)P3, which are produced by activated phosphatidylinositol 3-kinase. ADAP1 is predominantly expressed in the brain neurons, while ADAP2 is broadly expressed, including the adipocytes, heart, and skeletal muscle but not in the brain. The limited distribution and high expression of ADAP1 in the brain indicates that ADAP1 is important for neuronal functions. ADAP1 has been shown to highly expressed in the neurons and plagues of Alzheimer's disease patients. In other hand, ADAP2 gene deletion has been shown to cause circulatory deficiencies and heart shape defects in zebrafish, indicating that ADAP2 has a vital role in heart development. Taken together, the hemizygous deletion of ADAP2 gene may be contributing to the cardiovascular malformation in patients with neurofibromatosis type 1 (NF1) microdeletions.


:

Pssm-ID: 350070 [Multi-domain]  Cd Length: 112  Bit Score: 231.58  E-value: 1.97e-76
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763    4 RERNKKRLLELLRAPdtGNAHCADCGAADPDWASYKLGIFICLNCCGVHRNFPDISRVKSVRLDFWDDSIVEFMIHNGNL 83
Cdd:cd08844   1 RDRNKKRLLELLKLP--GNSVCADCGAPDPDWASYTLGIFICLNCSGVHRNLPDISRVKSIRLDFWEDELVEFMKENGNL 78

                        90       100       110
                ....*....|....*....|....*....|....
gi 8923763   84 RVKAKFEARVPAFYYIPQANDCLVLKEQWIRAKY 117
Cdd:cd08844  79 KAKAKFEAFVPPFYYRPQANDCDVLKEQWIRAKY 112
PH1_ADAP cd13252
ArfGAP with dual PH domains Pleckstrin homology (PH) domain, repeat 1; ADAP (also called ...
 133-241 5.96e-69

ArfGAP with dual PH domains Pleckstrin homology (PH) domain, repeat 1; ADAP (also called centaurin alpha) is a phophatidlyinositide binding protein consisting of an N-terminal ArfGAP domain and two PH domains. In response to growth factor activation, PI3K phosphorylates phosphatidylinositol 4,5-bisphosphate to phosphatidylinositol 3,4,5-trisphosphate. Centaurin alpha 1 is recruited to the plasma membrane following growth factor stimulation by specific binding of its PH domain to phosphatidylinositol 3,4,5-trisphosphate. Centaurin alpha 2 is constitutively bound to the plasma membrane since it binds phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate with equal affinity. This cd contains the first PH domain 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: 270072  Cd Length: 109  Bit Score: 212.12  E-value: 5.96e-69
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763  133 GNREGFLWKRGRDNSQFLRRKFVLLAREGLLKYFTKEQGKSPKAVISIKDLNATFQTEKIGHPHGLQITYRRDGHTRNLF 212
Cdd:cd13252   1 GSKEGFLWKRGKDNNQFKQRKFVLSEREGTLKYFVKEDAKEPKAVISIEELNATFQPEKIGHPNGLQITYLKDGSTRNIF 80

                        90       100
                ....*....|....*....|....*....
gi 8923763  213 VYHESGKEIVDWFNALRAARLQYLKMAFP 241
Cdd:cd13252  81 VYHEDGKEIVDWYNAIRAARLHYLQVAFP 109
PH2_ADAP cd01251
ArfGAP with dual PH domains Pleckstrin homology (PH) domain, repeat 2; ADAP (also called ...
 255-362 7.33e-54

ArfGAP with dual PH domains Pleckstrin homology (PH) domain, repeat 2; ADAP (also called centaurin alpha) is a phophatidlyinositide binding protein consisting of an N-terminal ArfGAP domain and two PH domains. In response to growth factor activation, PI3K phosphorylates phosphatidylinositol 4,5-bisphosphate to phosphatidylinositol 3,4,5-trisphosphate. Centaurin alpha 1 is recruited to the plasma membrane following growth factor stimulation by specific binding of its PH domain to phosphatidylinositol 3,4,5-trisphosphate. Centaurin alpha 2 is constitutively bound to the plasma membrane since it binds phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate with equal affinity. This cd contains the second PH domain 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: 241282  Cd Length: 105  Bit Score: 173.16  E-value: 7.33e-54
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763  255 NYLKQGFMEKTGPKQKEPFKKRWFALDCheRRLLYYKNPLDAFEQGQVFLGNKEQGYEAYEDLPKGIRGnRWKAGLTIVT 334
Cdd:cd01251   1 DFLKEGYLEKTGPKQTDGFRKRWFTLDD--RRLMYFKDPLDAFPKGEIFIGSKEEGYSVREGLPPGIKG-HWGFGFTLVT 77

                        90       100
                ....*....|....*....|....*...
gi 8923763  335 PERRFVLTCPSEKEQQEWLESLRGVLSS 362
Cdd:cd01251  78 PDRTFLLSAETEEERREWITAIQKVLER 105
 
Name Accession Description Interval E-value
ArfGap_ADAP2 cd08844
ADAP2 GTPase activating protein for Arf, with dual PH domains; The ADAP subfamily, ArfGAPs ...
 4-117 1.97e-76

ADAP2 GTPase activating protein for Arf, with dual PH domains; The ADAP subfamily, ArfGAPs with dual pleckstrin homology (PH) domains, includes two members: ADAP1 and ADAP2. Both ADAP1 (also known as centaurin-alpha1, p42(IP4), or PIP3BP) and ADAP2 (centaurin-alpha2) display a GTPase-activating protein (GAP) activity toward Arf6 (ADP-ribosylation factor 6), which is involved in protein trafficking that regulates endocytic recycling, cytoskeleton remodeling, and neuronal differentiation. ADAP2 has high sequence similarity to the ADAP1 and they both contain a ArfGAP domain at the N-terminus, followed by two PH domains. However, ADAP1, unlike ADAP2, contains a putative N-terminal nuclear localization signal. The PH domains of ADAP1bind to the two second messenger molecules phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3) and inositol 1,3,4,5-tetrakisphosphate (I(1,3,4,5)P4) with identical high affinity, whereas those of ADAP2 specifically binds phosphatidylinositol 3,4-bisphosphate (PI(3,4)P2) and PI(3,4,5)P3, which are produced by activated phosphatidylinositol 3-kinase. ADAP1 is predominantly expressed in the brain neurons, while ADAP2 is broadly expressed, including the adipocytes, heart, and skeletal muscle but not in the brain. The limited distribution and high expression of ADAP1 in the brain indicates that ADAP1 is important for neuronal functions. ADAP1 has been shown to highly expressed in the neurons and plagues of Alzheimer's disease patients. In other hand, ADAP2 gene deletion has been shown to cause circulatory deficiencies and heart shape defects in zebrafish, indicating that ADAP2 has a vital role in heart development. Taken together, the hemizygous deletion of ADAP2 gene may be contributing to the cardiovascular malformation in patients with neurofibromatosis type 1 (NF1) microdeletions.


Pssm-ID: 350070 [Multi-domain]  Cd Length: 112  Bit Score: 231.58  E-value: 1.97e-76
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763    4 RERNKKRLLELLRAPdtGNAHCADCGAADPDWASYKLGIFICLNCCGVHRNFPDISRVKSVRLDFWDDSIVEFMIHNGNL 83
Cdd:cd08844   1 RDRNKKRLLELLKLP--GNSVCADCGAPDPDWASYTLGIFICLNCSGVHRNLPDISRVKSIRLDFWEDELVEFMKENGNL 78

                        90       100       110
                ....*....|....*....|....*....|....
gi 8923763   84 RVKAKFEARVPAFYYIPQANDCLVLKEQWIRAKY 117
Cdd:cd08844  79 KAKAKFEAFVPPFYYRPQANDCDVLKEQWIRAKY 112
PH1_ADAP cd13252
ArfGAP with dual PH domains Pleckstrin homology (PH) domain, repeat 1; ADAP (also called ...
 133-241 5.96e-69

ArfGAP with dual PH domains Pleckstrin homology (PH) domain, repeat 1; ADAP (also called centaurin alpha) is a phophatidlyinositide binding protein consisting of an N-terminal ArfGAP domain and two PH domains. In response to growth factor activation, PI3K phosphorylates phosphatidylinositol 4,5-bisphosphate to phosphatidylinositol 3,4,5-trisphosphate. Centaurin alpha 1 is recruited to the plasma membrane following growth factor stimulation by specific binding of its PH domain to phosphatidylinositol 3,4,5-trisphosphate. Centaurin alpha 2 is constitutively bound to the plasma membrane since it binds phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate with equal affinity. This cd contains the first PH domain 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: 270072  Cd Length: 109  Bit Score: 212.12  E-value: 5.96e-69
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763  133 GNREGFLWKRGRDNSQFLRRKFVLLAREGLLKYFTKEQGKSPKAVISIKDLNATFQTEKIGHPHGLQITYRRDGHTRNLF 212
Cdd:cd13252   1 GSKEGFLWKRGKDNNQFKQRKFVLSEREGTLKYFVKEDAKEPKAVISIEELNATFQPEKIGHPNGLQITYLKDGSTRNIF 80

                        90       100
                ....*....|....*....|....*....
gi 8923763  213 VYHESGKEIVDWFNALRAARLQYLKMAFP 241
Cdd:cd13252  81 VYHEDGKEIVDWYNAIRAARLHYLQVAFP 109
PH2_ADAP cd01251
ArfGAP with dual PH domains Pleckstrin homology (PH) domain, repeat 2; ADAP (also called ...
 255-362 7.33e-54

ArfGAP with dual PH domains Pleckstrin homology (PH) domain, repeat 2; ADAP (also called centaurin alpha) is a phophatidlyinositide binding protein consisting of an N-terminal ArfGAP domain and two PH domains. In response to growth factor activation, PI3K phosphorylates phosphatidylinositol 4,5-bisphosphate to phosphatidylinositol 3,4,5-trisphosphate. Centaurin alpha 1 is recruited to the plasma membrane following growth factor stimulation by specific binding of its PH domain to phosphatidylinositol 3,4,5-trisphosphate. Centaurin alpha 2 is constitutively bound to the plasma membrane since it binds phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate with equal affinity. This cd contains the second PH domain 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: 241282  Cd Length: 105  Bit Score: 173.16  E-value: 7.33e-54
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763  255 NYLKQGFMEKTGPKQKEPFKKRWFALDCheRRLLYYKNPLDAFEQGQVFLGNKEQGYEAYEDLPKGIRGnRWKAGLTIVT 334
Cdd:cd01251   1 DFLKEGYLEKTGPKQTDGFRKRWFTLDD--RRLMYFKDPLDAFPKGEIFIGSKEEGYSVREGLPPGIKG-HWGFGFTLVT 77

                        90       100
                ....*....|....*....|....*...
gi 8923763  335 PERRFVLTCPSEKEQQEWLESLRGVLSS 362
Cdd:cd01251  78 PDRTFLLSAETEEERREWITAIQKVLER 105
ArfGap pfam01412
Putative GTPase activating protein for Arf; Putative zinc fingers with GTPase activating ...
 8-126 8.19e-48

Putative GTPase activating protein for Arf; Putative zinc fingers with GTPase activating proteins (GAPs) towards the small GTPase, Arf. The GAP of ARD1 stimulates GTPase hydrolysis for ARD1 but not ARFs.


Pssm-ID: 460200 [Multi-domain]  Cd Length: 117  Bit Score: 158.16  E-value: 8.19e-48
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763      8 KKRLLELLRAPdtGNAHCADCGAADPDWASYKLGIFICLNCCGVHRNF-PDISRVKSVRLDFWDDSIVEFMIHNGNLRVK 86
Cdd:pfam01412   1 KRVLRELLKLP--GNKVCADCGAPNPTWASVNLGIFICIDCSGVHRSLgVHISKVRSLTLDTWTDEQLELMKAGGNDRAN 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 8923763     87 AKFEARVPAFYYIPQaNDCLVLKEQWIRAKYERREFMADG 126
Cdd:pfam01412  79 EFWEANLPPSYKPPP-SSDREKRESFIRAKYVEKKFAKPG 117
ArfGap smart00105
Putative GTP-ase activating proteins for the small GTPase, ARF; Putative zinc fingers with ...
 12-122 2.15e-39

Putative GTP-ase activating proteins for the small GTPase, ARF; Putative zinc fingers with GTPase activating proteins (GAPs) towards the small GTPase, Arf. The GAP of ARD1 stimulates GTPase hydrolysis for ARD1 but not ARFs.


Pssm-ID: 214518 [Multi-domain]  Cd Length: 119  Bit Score: 136.32  E-value: 2.15e-39
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763      12 LELLRApDTGNAHCADCGAADPDWASYKLGIFICLNCCGVHRN-FPDISRVKSVRLDFWDDSIVEFMIHNGNLRVKAKFE 90
Cdd:smart00105   1 LKLLRS-IPGNKKCFDCGAPNPTWASVNLGVFLCIECSGIHRSlGVHISKVRSLTLDTWTEEELRLLQKGGNENANSIWE 79

                           90       100       110
                   ....*....|....*....|....*....|..
gi 8923763      91 ARVPAFYYIPQANDCLVLKEQWIRAKYERREF 122
Cdd:smart00105  80 SNLDDFSLKPPDDDDQQKYESFIAAKYEEKLF 111
COG5347 COG5347
GTPase-activating protein that regulates ARFs (ADP-ribosylation factors), involved in ...
 1-122 2.11e-26

GTPase-activating protein that regulates ARFs (ADP-ribosylation factors), involved in ARF-mediated vesicular transport [Intracellular trafficking and secretion];


Pssm-ID: 227651 [Multi-domain]  Cd Length: 319  Bit Score: 107.56  E-value: 2.11e-26
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763    1 MGDRERNKKRLLELLRAPdtGNAHCADCGAADPDWASYKLGIFICLNCCGVHRN-FPDISRVKSVRLDFWDDSIVEFMIH 79
Cdd:COG5347   1 MSTKSEDRKLLKLLKSDS--SNKKCADCGAPNPTWASVNLGVFLCIDCAGVHRSlGVHISKVKSLTLDNWTEEELRRMEV 78

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*
gi 8923763   80 NGNLRVKAKFEA--RVPAFYYIPQANDCLVlKEQWIRAKYERREF 122
Cdd:COG5347  79 GGNSNANRFYEKnlLDQLLLPIKAKYDSSV-AKKYIRKKYELKKF 122
PLN03114 PLN03114
ADP-ribosylation factor GTPase-activating protein AGD10; Provisional
 7-90 1.25e-12

ADP-ribosylation factor GTPase-activating protein AGD10; Provisional


Pssm-ID: 178661 [Multi-domain]  Cd Length: 395  Bit Score: 68.73  E-value: 1.25e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763     7 NKKRLLELLRApDTGNAHCADCGAADPDWASYKLGIFICLNCCGVHRNFP-DISRVKSVRLDFWDDSIVEFMIHNGNLRV 85
Cdd:PLN03114   8 DKISVFKKLKA-KSDNKICFDCNAKNPTWASVTYGIFLCIDCSAVHRSLGvHISFVRSTNLDSWSSEQLKMMIYGGNNRA 86


                 ....*
gi 8923763    86 KAKFE 90
Cdd:PLN03114  87 QVFFK 91
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 257-361 1.95e-11

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: 60.25  E-value: 1.95e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763     257 LKQGFMEKTGPKQKEPFKKRWFALdcHERRLLYYKNP---LDAFEQGQVFLgnkeQGYEAYEDLPKGIRGNRWkaGLTIV 333
Cdd:smart00233   2 IKEGWLYKKSGGGKKSWKKRYFVL--FNSTLLYYKSKkdkKSYKPKGSIDL----SGCTVREAPDPDSSKKPH--CFEIK 73

                           90       100
                   ....*....|....*....|....*....
gi 8923763     334 TPERR-FVLTCPSEKEQQEWLESLRGVLS 361
Cdd:smart00233  74 TSDRKtLLLQAESEEEREKWVEALRKAIA 102
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 258-361 1.57e-09

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 54.88  E-value: 1.57e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763    258 KQGFMEKTGPKQKEPFKKRWFALdcHERRLLYYKNPL---DAFEQGQVFLgnkeQGYEAYEDLPKGIRGNRWKAGLTIV- 333
Cdd:pfam00169   3 KEGWLLKKGGGKKKSWKKRYFVL--FDGSLLYYKDDKsgkSKEPKGSISL----SGCEVVEVVASDSPKRKFCFELRTGe 76

                          90       100
                  ....*....|....*....|....*....
gi 8923763    334 -TPERRFVLTCPSEKEQQEWLESLRGVLS 361
Cdd:pfam00169  77 rTGKRTYLLQAESEEERKDWIKAIQSAIR 105
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 135-231 1.46e-06

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 46.40  E-value: 1.46e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763    135 REGFLWKRGRDNSQFLRRKFVLLAREGLLkYFTKE---QGKSPKAVISIKDL--NATFQTEKIGHPHGLQITYRRDGHTR 209
Cdd:pfam00169   3 KEGWLLKKGGGKKKSWKKRYFVLFDGSLL-YYKDDksgKSKEPKGSISLSGCevVEVVASDSPKRKFCFELRTGERTGKR 81

                          90       100
                  ....*....|....*....|..
gi 8923763    210 NLFVYHESGKEIVDWFNALRAA 231
Cdd:pfam00169  82 TYLLQAESEEERKDWIKAIQSA 103
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 135-231 1.83e-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: 46.00  E-value: 1.83e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763     135 REGFLWKRGRD-NSQFLRRKFVLlaREGLLKYFTKEQ---GKSPKAVISIKDLNATFQTE--KIGHPHGLQITYrrdGHT 208
Cdd:smart00233   3 KEGWLYKKSGGgKKSWKKRYFVL--FNSTLLYYKSKKdkkSYKPKGSIDLSGCTVREAPDpdSSKKPHCFEIKT---SDR 77

                           90       100
                   ....*....|....*....|...
gi 8923763     209 RNLFVYHESGKEIVDWFNALRAA 231
Cdd:smart00233  78 KTLLLQAESEEEREKWVEALRKA 100
 
Name Accession Description Interval E-value
ArfGap_ADAP2 cd08844
ADAP2 GTPase activating protein for Arf, with dual PH domains; The ADAP subfamily, ArfGAPs ...
 4-117 1.97e-76

ADAP2 GTPase activating protein for Arf, with dual PH domains; The ADAP subfamily, ArfGAPs with dual pleckstrin homology (PH) domains, includes two members: ADAP1 and ADAP2. Both ADAP1 (also known as centaurin-alpha1, p42(IP4), or PIP3BP) and ADAP2 (centaurin-alpha2) display a GTPase-activating protein (GAP) activity toward Arf6 (ADP-ribosylation factor 6), which is involved in protein trafficking that regulates endocytic recycling, cytoskeleton remodeling, and neuronal differentiation. ADAP2 has high sequence similarity to the ADAP1 and they both contain a ArfGAP domain at the N-terminus, followed by two PH domains. However, ADAP1, unlike ADAP2, contains a putative N-terminal nuclear localization signal. The PH domains of ADAP1bind to the two second messenger molecules phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3) and inositol 1,3,4,5-tetrakisphosphate (I(1,3,4,5)P4) with identical high affinity, whereas those of ADAP2 specifically binds phosphatidylinositol 3,4-bisphosphate (PI(3,4)P2) and PI(3,4,5)P3, which are produced by activated phosphatidylinositol 3-kinase. ADAP1 is predominantly expressed in the brain neurons, while ADAP2 is broadly expressed, including the adipocytes, heart, and skeletal muscle but not in the brain. The limited distribution and high expression of ADAP1 in the brain indicates that ADAP1 is important for neuronal functions. ADAP1 has been shown to highly expressed in the neurons and plagues of Alzheimer's disease patients. In other hand, ADAP2 gene deletion has been shown to cause circulatory deficiencies and heart shape defects in zebrafish, indicating that ADAP2 has a vital role in heart development. Taken together, the hemizygous deletion of ADAP2 gene may be contributing to the cardiovascular malformation in patients with neurofibromatosis type 1 (NF1) microdeletions.


Pssm-ID: 350070 [Multi-domain]  Cd Length: 112  Bit Score: 231.58  E-value: 1.97e-76
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763    4 RERNKKRLLELLRAPdtGNAHCADCGAADPDWASYKLGIFICLNCCGVHRNFPDISRVKSVRLDFWDDSIVEFMIHNGNL 83
Cdd:cd08844   1 RDRNKKRLLELLKLP--GNSVCADCGAPDPDWASYTLGIFICLNCSGVHRNLPDISRVKSIRLDFWEDELVEFMKENGNL 78

                        90       100       110
                ....*....|....*....|....*....|....
gi 8923763   84 RVKAKFEARVPAFYYIPQANDCLVLKEQWIRAKY 117
Cdd:cd08844  79 KAKAKFEAFVPPFYYRPQANDCDVLKEQWIRAKY 112
ArfGap_ADAP cd08832
ArfGap with dual PH domains; The ADAP subfamily, ArfGAPs with dual pleckstrin homology (PH) ...
 5-117 8.64e-72

ArfGap with dual PH domains; The ADAP subfamily, ArfGAPs with dual pleckstrin homology (PH) domains, includes two members: ADAP1 and ADAP2. Both ADAP1 (also known as centaurin-alpha1, p42(IP4), or PIP3BP) and ADAP2 (centaurin-alpha2) display a GTPase-activating protein (GAP) activity toward Arf6 (ADP-ribosylation factor 6), which is involved in protein trafficking that regulates endocytic recycling, cytoskeleton remodeling, and neuronal differentiation. ADAP2 has high sequence similarity to the ADAP1 and they both contain a ArfGAP domain at the N-terminus, followed by two PH domains. However, ADAP1, unlike ADAP2, contains a putative N-terminal nuclear localization signal. The PH domains of ADAP1bind to the two second messenger molecules phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3) and inositol 1,3,4,5-tetrakisphosphate (I(1,3,4,5)P4) with identical high affinity, whereas those of ADAP2 specifically binds phosphatidylinositol 3,4-bisphosphate (PI(3,4)P2) and PI(3,4,5)P3, which are produced by activated phosphatidylinositol 3-kinase. ADAP1 is predominantly expressed in the brain neurons, while ADAP2 is broadly expressed, including the adipocytes, heart, and skeletal muscle but not in the brain. The limited distribution and high expression of ADAP1 in the brain indicates that ADAP1 is important for neuronal functions. ADAP1 has been shown to highly expressed in the neurons and plagues of Alzheimer's disease patients. In other hand, ADAP2 gene deletion has been shown to cause circulatory deficiencies and heart shape defects in zebrafish, indicating that ADAP2 has a vital role in heart development. Taken together, the hemizygous deletion of ADAP2 gene may be contributing to the cardiovascular malformation in patients with neurofibromatosis type 1 (NF1) microdeletions.


Pssm-ID: 350061 [Multi-domain]  Cd Length: 113  Bit Score: 219.82  E-value: 8.64e-72
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763    5 ERNKKRLLELLRAPdtGNAHCADCGAADPDWASYKLGIFICLNCCGVHRNFPD-ISRVKSVRLDFWDDSIVEFMIHNGNL 83
Cdd:cd08832   2 ERNKKRLLELLKLP--GNNTCADCGAPDPEWASYNLGVFICLDCSGIHRSLGThISKVKSLRLDNWDDSQVEFMEENGNE 79

                        90       100       110
                ....*....|....*....|....*....|....
gi 8923763   84 RVKAKFEARVPAFYYIPQANDCLVLKEQWIRAKY 117
Cdd:cd08832  80 KAKAKYEAHVPAFYRRPTPTDPQVLREQWIRAKY 113
PH1_ADAP cd13252
ArfGAP with dual PH domains Pleckstrin homology (PH) domain, repeat 1; ADAP (also called ...
 133-241 5.96e-69

ArfGAP with dual PH domains Pleckstrin homology (PH) domain, repeat 1; ADAP (also called centaurin alpha) is a phophatidlyinositide binding protein consisting of an N-terminal ArfGAP domain and two PH domains. In response to growth factor activation, PI3K phosphorylates phosphatidylinositol 4,5-bisphosphate to phosphatidylinositol 3,4,5-trisphosphate. Centaurin alpha 1 is recruited to the plasma membrane following growth factor stimulation by specific binding of its PH domain to phosphatidylinositol 3,4,5-trisphosphate. Centaurin alpha 2 is constitutively bound to the plasma membrane since it binds phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate with equal affinity. This cd contains the first PH domain 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: 270072  Cd Length: 109  Bit Score: 212.12  E-value: 5.96e-69
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763  133 GNREGFLWKRGRDNSQFLRRKFVLLAREGLLKYFTKEQGKSPKAVISIKDLNATFQTEKIGHPHGLQITYRRDGHTRNLF 212
Cdd:cd13252   1 GSKEGFLWKRGKDNNQFKQRKFVLSEREGTLKYFVKEDAKEPKAVISIEELNATFQPEKIGHPNGLQITYLKDGSTRNIF 80

                        90       100
                ....*....|....*....|....*....
gi 8923763  213 VYHESGKEIVDWFNALRAARLQYLKMAFP 241
Cdd:cd13252  81 VYHEDGKEIVDWYNAIRAARLHYLQVAFP 109
ArfGap_ADAP1 cd08843
ADAP1 GTPase activating protein for Arf, with dual PH domains; The ADAP subfamily, ArfGAPs ...
 4-117 4.38e-60

ADAP1 GTPase activating protein for Arf, with dual PH domains; The ADAP subfamily, ArfGAPs with dual pleckstrin homology (PH) domains, includes two members: ADAP1 and ADAP2. Both ADAP1 (also known as centaurin-alpha1, p42(IP4), or PIP3BP) and ADAP2 (centaurin-alpha2) display a GTPase-activating protein (GAP) activity toward Arf6 (ADP-ribosylation factor 6), which is involved in protein trafficking that regulates endocytic recycling, cytoskeleton remodeling, and neuronal differentiation. ADAP2 has high sequence similarity to the ADAP1 and they both contain a ArfGAP domain at the N-terminus, followed by two PH domains. However, ADAP1, unlike ADAP2, contains a putative N-terminal nuclear localization signal. The PH domains of ADAP1bind to the two second messenger molecules phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3) and inositol 1,3,4,5-tetrakisphosphate (I(1,3,4,5)P4) with identical high affinity, whereas those of ADAP2 specifically binds phosphatidylinositol 3,4-bisphosphate (PI(3,4)P2) and PI(3,4,5)P3, which are produced by activated phosphatidylinositol 3-kinase. ADAP1 is predominantly expressed in the brain neurons, while ADAP2 is broadly expressed, including the adipocytes, heart, and skeletal muscle but not in the brain. The limited distribution and high expression of ADAP1 in the brain indicates that ADAP1 is important for neuronal functions. ADAP1 has been shown to highly expressed in the neurons and plagues of Alzheimer's disease patients. In other hand, ADAP2 gene deletion has been shown to cause circulatory deficiencies and heart shape defects in zebrafish, indicating that ADAP2 has a vital role in heart development. Taken together, the hemizygous deletion of ADAP2 gene may be contributing to the cardiovascular malformation in patients with neurofibromatosis type 1 (NF1) microdeletions.


Pssm-ID: 350069 [Multi-domain]  Cd Length: 112  Bit Score: 189.83  E-value: 4.38e-60
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763    4 RERNKKRLLELLRAPdtGNAHCADCGAADPDWASYKLGIFICLNCCGVHRNFPDISRVKSVRLDFWDDSIVEFMIHNGNL 83
Cdd:cd08843   1 GKERRRAVLELLQRP--GNARCADCGAPDPDWASYTLGVFICLSCSGIHRNIPQVSKVKSVRLDAWEEAQVEFMASHGND 78

                        90       100       110
                ....*....|....*....|....*....|....
gi 8923763   84 RVKAKFEARVPAFYYIPQANDCLVLKEQWIRAKY 117
Cdd:cd08843  79 AARARFESKVPSFYYRPTPSDCQLLREQWIRAKY 112
PH2_ADAP cd01251
ArfGAP with dual PH domains Pleckstrin homology (PH) domain, repeat 2; ADAP (also called ...
 255-362 7.33e-54

ArfGAP with dual PH domains Pleckstrin homology (PH) domain, repeat 2; ADAP (also called centaurin alpha) is a phophatidlyinositide binding protein consisting of an N-terminal ArfGAP domain and two PH domains. In response to growth factor activation, PI3K phosphorylates phosphatidylinositol 4,5-bisphosphate to phosphatidylinositol 3,4,5-trisphosphate. Centaurin alpha 1 is recruited to the plasma membrane following growth factor stimulation by specific binding of its PH domain to phosphatidylinositol 3,4,5-trisphosphate. Centaurin alpha 2 is constitutively bound to the plasma membrane since it binds phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate with equal affinity. This cd contains the second PH domain 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: 241282  Cd Length: 105  Bit Score: 173.16  E-value: 7.33e-54
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763  255 NYLKQGFMEKTGPKQKEPFKKRWFALDCheRRLLYYKNPLDAFEQGQVFLGNKEQGYEAYEDLPKGIRGnRWKAGLTIVT 334
Cdd:cd01251   1 DFLKEGYLEKTGPKQTDGFRKRWFTLDD--RRLMYFKDPLDAFPKGEIFIGSKEEGYSVREGLPPGIKG-HWGFGFTLVT 77

                        90       100
                ....*....|....*....|....*...
gi 8923763  335 PERRFVLTCPSEKEQQEWLESLRGVLSS 362
Cdd:cd01251  78 PDRTFLLSAETEEERREWITAIQKVLER 105
ArfGap cd08204
GTPase-activating protein (GAP) for the ADP ribosylation factors (ARFs); ArfGAPs are a family ...
 11-117 3.93e-51

GTPase-activating protein (GAP) for the ADP ribosylation factors (ARFs); ArfGAPs are a family of proteins containing an ArfGAP catalytic domain that induces the hydrolysis of GTP bound to the small guanine nucleotide-binding protein Arf, a member of the Ras superfamily of GTPases. Like all GTP-binding proteins, Arf proteins function as molecular switches, cycling between GTP (active-membrane bound) and GDP (inactive-cytosolic) form. Conversion to the GTP-bound form requires a guanine nucleotide exchange factor (GEF), whereas conversion to the GDP-bound form is catalyzed by a GTPase activating protein (GAP). In that sense, ArfGAPs were originally proposed to function as terminators of Arf signaling, which is mediated by regulating Arf family GTP-binding proteins. However, recent studies suggest that ArfGAPs can also function as Arf effectors, independently of their GAP enzymatic activity to transduce signals in cells. The ArfGAP domain contains a C4-type zinc finger motif and a conserved arginine that is required for activity, within a specific spacing (CX2CX16CX2CX4R). ArfGAPs, which have multiple functional domains, regulate the membrane trafficking and actin cytoskeleton remodeling via specific interactions with signaling lipids such as phosphoinositides and trafficking proteins, which consequently affect cellular events such as cell growth, migration, and cancer invasion. The ArfGAP family, which includes 31 human ArfGAP-domain containing proteins, is divided into 10 subfamilies based on domain structure and sequence similarity. The ArfGAP nomenclature is mainly based on the protein domain structure. For example, ASAP1 contains ArfGAP, SH3, ANK repeat and PH domains; ARAPs contain ArfGAP, Rho GAP, ANK repeat and PH domains; ACAPs contain ArfGAP, BAR (coiled coil), ANK repeat and PH domains; and AGAPs contain Arf GAP, GTP-binding protein-like, ANK repeat and PH domains. Furthermore, the ArfGAPs can be classified into two major types of subfamilies, according to the overall domain structure: the ArfGAP1 type includes 6 subfamilies (ArfGAP1, ArfGAP2/3, ADAP, SMAP, AGFG, and GIT), which contain the ArfGAP domain at the N-terminus of the protein; and the AZAP type includes 4 subfamilies (ASAP, ACAP, AGAP, and ARAP), which contain an ArfGAP domain between the PH and ANK repeat domains.


Pssm-ID: 350058 [Multi-domain]  Cd Length: 106  Bit Score: 166.14  E-value: 3.93e-51
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763   11 LLELLRAPdtGNAHCADCGAADPDWASYKLGIFICLNCCGVHRNF-PDISRVKSVRLDFWDDSIVEFMIHNGNLRVKAKF 89
Cdd:cd08204   1 LEELLKLP--GNKVCADCGAPDPRWASINLGVFICIRCSGIHRSLgVHISKVRSLTLDSWTPEQVELMKAIGNARANAYY 78

                        90       100
                ....*....|....*....|....*...
gi 8923763   90 EARVPAFYYIPQANDCLVLKEQWIRAKY 117
Cdd:cd08204  79 EANLPPGFKKPTPDSSDEEREQFIRAKY 106
ArfGap pfam01412
Putative GTPase activating protein for Arf; Putative zinc fingers with GTPase activating ...
 8-126 8.19e-48

Putative GTPase activating protein for Arf; Putative zinc fingers with GTPase activating proteins (GAPs) towards the small GTPase, Arf. The GAP of ARD1 stimulates GTPase hydrolysis for ARD1 but not ARFs.


Pssm-ID: 460200 [Multi-domain]  Cd Length: 117  Bit Score: 158.16  E-value: 8.19e-48
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763      8 KKRLLELLRAPdtGNAHCADCGAADPDWASYKLGIFICLNCCGVHRNF-PDISRVKSVRLDFWDDSIVEFMIHNGNLRVK 86
Cdd:pfam01412   1 KRVLRELLKLP--GNKVCADCGAPNPTWASVNLGIFICIDCSGVHRSLgVHISKVRSLTLDTWTDEQLELMKAGGNDRAN 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 8923763     87 AKFEARVPAFYYIPQaNDCLVLKEQWIRAKYERREFMADG 126
Cdd:pfam01412  79 EFWEANLPPSYKPPP-SSDREKRESFIRAKYVEKKFAKPG 117
ArfGap smart00105
Putative GTP-ase activating proteins for the small GTPase, ARF; Putative zinc fingers with ...
 12-122 2.15e-39

Putative GTP-ase activating proteins for the small GTPase, ARF; Putative zinc fingers with GTPase activating proteins (GAPs) towards the small GTPase, Arf. The GAP of ARD1 stimulates GTPase hydrolysis for ARD1 but not ARFs.


Pssm-ID: 214518 [Multi-domain]  Cd Length: 119  Bit Score: 136.32  E-value: 2.15e-39
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763      12 LELLRApDTGNAHCADCGAADPDWASYKLGIFICLNCCGVHRN-FPDISRVKSVRLDFWDDSIVEFMIHNGNLRVKAKFE 90
Cdd:smart00105   1 LKLLRS-IPGNKKCFDCGAPNPTWASVNLGVFLCIECSGIHRSlGVHISKVRSLTLDTWTEEELRLLQKGGNENANSIWE 79

                           90       100       110
                   ....*....|....*....|....*....|..
gi 8923763      91 ARVPAFYYIPQANDCLVLKEQWIRAKYERREF 122
Cdd:smart00105  80 SNLDDFSLKPPDDDDQQKYESFIAAKYEEKLF 111
ArfGap_SMAP cd08839
Stromal membrane-associated proteins; a subfamily of the ArfGAP family; The SMAP subfamily of ...
 11-117 5.49e-33

Stromal membrane-associated proteins; a subfamily of the ArfGAP family; The SMAP subfamily of Arf GTPase-activating proteins consists of the two structurally-related members, SMAP1 and SMAP2. Each SMAP member exhibits common and distinct functions in vesicle trafficking. They both bind to clathrin heavy chain molecules and are involved in the trafficking of clathrin-coated vesicles. SMAP1 preferentially exhibits GAP toward Arf6, while SMAP2 prefers Arf1 as a substrate. SMAP1 is involved in Arf6-dependent vesicle trafficking, but not Arf6-mediated actin cytoskeleton reorganization, and regulates clathrin-dependent endocytosis of the transferrin receptors and E-cadherin. SMAP2 regulates Arf1-dependent retrograde transport of TGN38/46 from the early endosome to the trans-Golgi network (TGN). SMAP2 has the Clathrin Assembly Lymphoid Myeloid (CALM)-binding domain, but SMAP1 does not.


Pssm-ID: 350068 [Multi-domain]  Cd Length: 103  Bit Score: 118.91  E-value: 5.49e-33
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763   11 LLELLRAPDtgNAHCADCGAADPDWASYKLGIFICLNCCGVHRNF-PDISRVKSVRLDFWDDSIVEFMIHNGNLRVKAKF 89
Cdd:cd08839   1 LAKLLREED--NKYCADCGAKGPRWASWNLGVFICIRCAGIHRNLgVHISKVKSVNLDSWTPEQVQSMQEMGNARANAYY 78

                        90       100
                ....*....|....*....|....*...
gi 8923763   90 EARVPAFYYIPQANDCLvlkEQWIRAKY 117
Cdd:cd08839  79 EANLPDGFRRPQTDSAL---ENFIRDKY 103
ArfGap_ACAP cd08835
ArfGAP domain of ACAP (ArfGAP with Coiled-coil, ANK repeat and PH domains) proteins; ArfGAP ...
 10-123 1.83e-28

ArfGAP domain of ACAP (ArfGAP with Coiled-coil, ANK repeat and PH domains) proteins; ArfGAP domain is an essential part of ACAP proteins that play important role in endocytosis, actin remodeling and receptor tyrosine kinase-dependent cell movement. ACAP subfamily of ArfGAPs are composed of coiled coils (BAR, Bin-Amphiphysin-Rvs), PH, ArfGAP and ANK repeats domains. ACAP1 (centaurin beta1) and ACAP2 centaurin beta2) have a GAP (GTPase-activating protein) activity preferentially toward Arf6, which regulates endocytic recycling. Both ACAP1/2 are activated by are activated by the phosphoinositides, PI(4,5)P2 and PI(3,5)P2. ACAP1 binds specifically with recycling cargo proteins such as transferrin receptor (TfR) and cellubrevin. Thus, ACAP1 promotes cargo sorting to enhance TfR recycling from the recycling endosome. In addition, phosphorylation of ACAP by Akt, a serine/threonine protein kinase, regulates the recycling of integrin beta1 to control cell migration. In contrast, ACAP2 does not exhibit a similar interaction with the recycling cargo proteins. It has been shown that ACAP2 functions both as an effector of Ras-related protein Rab35 and as an Arf6-GTPase-activating protein (GAP) during neurite outgrowth of PC12 cells. In addition, ACAP2, together with Rab35, regulates phagocytosis in mammalian macrophages. ACAP3 also positively regulates neurite outgrowth through its GAP activity specific to Arf6 in mouse hippocampal neurons.


Pssm-ID: 350064 [Multi-domain]  Cd Length: 116  Bit Score: 107.34  E-value: 1.83e-28
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763   10 RLLELLRAPdtGNAHCADCGAADPDWASYKLGIFICLNCCGVHRNFP-DISRVKSVRLDFWDDSIVEFMIHNGNLRVKAK 88
Cdd:cd08835   3 ALEQVLSVP--GNAQCCDCGSPDPRWASINLGVTLCIECSGIHRSLGvHVSKVRSLTLDSWEPELLKVMLELGNDVVNRI 80

                        90       100       110
                ....*....|....*....|....*....|....*..
gi 8923763   89 FEARVPAfYYIPQAN-DC-LVLKEQWIRAKYERREFM 123
Cdd:cd08835  81 YEANVPD-DGSVKPTpDSsRQEREAWIRAKYVEKKFV 116
ArfGap_AGAP cd08836
ArfGAP with GTPase domain, ANK repeat and PH domains; The AGAP subfamily of ADP-ribosylation ...
 21-118 6.95e-28

ArfGAP with GTPase domain, ANK repeat and PH domains; The AGAP subfamily of ADP-ribosylation factor GTPase-activating proteins (Arf GAPs) includes three members: AGAP1-3. In addition to the Arf GAP domain, AGAP proteins contain GTP-binding protein-like, ANK repeat and pleckstrin homology (PH) domains. AGAP1 and AGAP2 have phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2)-mediated GTPase-activating protein (GAP) activity preferentially toward Arf1, and function in the endocytic system. AGAP1 and AGAP2 independently regulate AP-3 endosomes and AP-1/Rab4 fast recycling endosomes, respectively. AGAP1, via its PH domain, directly interacts with the adapter protein 3 (AP-3), which is a coat protein involved in trafficking in the endosomal-lysosomal system, and regulates AP-3-dependent trafficking. In other hand, AGAP2 specifically binds the clathrin adaptor protein AP-1 and regulates the AP-1/Rab-4 dependent endosomal trafficking. AGAP2 is overexpressed in different human cancers including prostate carcinoma and glioblastoma, and promotes cancer cell invasion. AGAP3 exists as a component of the NMDA receptor complex that regulates Arf6 and Ras/ERK signaling pathways. Moreover, AGAP3 regulates AMPA receptor trafficking through the ArfGAP domain. Together, AGAP3 is believed to involve in linking NMDA receptor activation to AMPA receptor trafficking.


Pssm-ID: 350065 [Multi-domain]  Cd Length: 108  Bit Score: 105.45  E-value: 6.95e-28
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763   21 GNAHCADCGAADPDWASYKLGIFICLNCCGVHRNF-PDISRVKSVRLDFWDDSIVEFMIHNGNLRVKAKFEARVPAfYYI 99
Cdd:cd08836  11 GNDHCVDCGAPNPDWASLNLGALMCIECSGIHRNLgTHISRVRSLDLDDWPVELLKVMSAIGNDLANSVWEGNTQG-RTK 89

                        90
                ....*....|....*....
gi 8923763  100 PQANDCLVLKEQWIRAKYE 118
Cdd:cd08836  90 PTPDSSREEKERWIRAKYE 108
COG5347 COG5347
GTPase-activating protein that regulates ARFs (ADP-ribosylation factors), involved in ...
 1-122 2.11e-26

GTPase-activating protein that regulates ARFs (ADP-ribosylation factors), involved in ARF-mediated vesicular transport [Intracellular trafficking and secretion];


Pssm-ID: 227651 [Multi-domain]  Cd Length: 319  Bit Score: 107.56  E-value: 2.11e-26
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763    1 MGDRERNKKRLLELLRAPdtGNAHCADCGAADPDWASYKLGIFICLNCCGVHRN-FPDISRVKSVRLDFWDDSIVEFMIH 79
Cdd:COG5347   1 MSTKSEDRKLLKLLKSDS--SNKKCADCGAPNPTWASVNLGVFLCIDCAGVHRSlGVHISKVKSLTLDNWTEEELRRMEV 78

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*
gi 8923763   80 NGNLRVKAKFEA--RVPAFYYIPQANDCLVlKEQWIRAKYERREF 122
Cdd:COG5347  79 GGNSNANRFYEKnlLDQLLLPIKAKYDSSV-AKKYIRKKYELKKF 122
ArfGap_SMAP2 cd08859
Stromal membrane-associated protein 2; a subfamily of the ArfGAP family; The SMAP subfamily of ...
 22-121 5.53e-24

Stromal membrane-associated protein 2; a subfamily of the ArfGAP family; The SMAP subfamily of Arf GTPase-activating proteins consists of the two structurally-related members, SMAP1 and SMAP2. Each SMAP member exhibits common and distinct functions in vesicle trafficking. They both bind to clathrin heavy chain molecules and are involved in the trafficking of clathrin-coated vesicles. SMAP1 preferentially exhibits GAP toward Arf6, while SMAP2 prefers Arf1 as a substrate. SMAP1 is involved in Arf6-dependent vesicle trafficking, but not Arf6-mediated actin cytoskeleton reorganization, and regulates clathrin-dependent endocytosis of the transferrin receptors and E-cadherin. SMAP2 regulates Arf1-dependent retrograde transport of TGN38/46 from the early endosome to the trans-Golgi network (TGN). SMAP2 has the Clathrin Assembly Lymphoid Myeloid (CALM)-binding domain, but SMAP1 does not.


Pssm-ID: 350083 [Multi-domain]  Cd Length: 107  Bit Score: 95.05  E-value: 5.53e-24
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763   22 NAHCADCGAADPDWASYKLGIFICLNCCGVHRNFP-DISRVKSVRLDFWDDSIVEFMIHNGNLRVKAKFEARVPAFYYIP 100
Cdd:cd08859  10 NKFCADCQSKGPRWASWNIGVFICIRCAGIHRNLGvHISRVKSVNLDQWTQEQIQCMQEMGNGKANRLYEAFLPENFRRP 89

                        90       100
                ....*....|....*....|.
gi 8923763  101 QANDCLvlkEQWIRAKYERRE 121
Cdd:cd08859  90 QTDQAV---EGFIRDKYEKKK 107
ArfGap_ArfGap1 cd08830
Arf1 GTPase-activating protein 1; ArfGAP (ADP Ribosylation Factor GTPase Activating Protein) ...
 8-90 7.54e-24

Arf1 GTPase-activating protein 1; ArfGAP (ADP Ribosylation Factor GTPase Activating Protein) domain is a part of ArfGap1-like proteins that play a crucial role in controlling of membrane trafficking, particularly in the formation of COPI (coat protein complex I)-coated vesicles on Golgi membranes. The ArfGAP1 protein subfamily consists of three members: ArfGAP1 (Gcs1p in yeast), ArfGAP2 and ArfGAP3 (both are homologs of yeast Glo3p). ArfGAP2/3 are closely related, but with little similarity to ArfGAP1, except the catalytic ArfGAP domain. They promote hydrolysis of GTP bound to the small G protein ADP-ribosylation factor 1 (Arf1), which leads to the dissociation of coat proteins from Golgi-derived membranes and vesicles. Dissociation of the coat proteins is required for the fusion of these vesicles with target compartments. Thus, the GAP catalytic activity plays a key role in the formation of COPI vesicles from Golgi membrane. In contrast to ArfGAP1, which displays membrane curvature-dependent ArfGAP activity, ArfGAP2 and ArfGAP3 activities are dependent on coatomer (the core COPI complex) which required for efficient recruitment of ArfGAP2 and ArfGAP3 to the Golgi membrane. Accordingly, ArfGAP2/3 has been implicated in coatomer-mediated protein transport between the Golgi complex and the endoplasmic reticulum. Unlike ArfGAP1, which is controlled by membrane curvature through its amphipathic lipid packing sensor (ALPS) motifs, ArfGAP2/3 do not possess ALPS motif.


Pssm-ID: 350059 [Multi-domain]  Cd Length: 115  Bit Score: 94.87  E-value: 7.54e-24
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763    8 KKRLLELLRAPdtGNAHCADCGAADPDWASYKLGIFICLNCCGVHRNFP-DISRVKSVRLDFWDDSIVEFMIHNGNLRVK 86
Cdd:cd08830   2 RAVLRELQKLP--GNNRCFDCGAPNPQWASVSYGIFICLECSGVHRGLGvHISFVRSITMDSWSEKQLKKMELGGNAKLR 79


                ....
gi 8923763   87 AKFE 90
Cdd:cd08830  80 EFFE 83
ArfGap_AGAP3 cd08855
ArfGAP with GTPase domain, ANK repeat and PH domain 3; The AGAP subfamily of ADP-ribosylation ...
 21-118 1.34e-23

ArfGAP with GTPase domain, ANK repeat and PH domain 3; The AGAP subfamily of ADP-ribosylation factor GTPase-activating proteins (Arf GAPs) includes three members: AGAP1-3. In addition to the Arf GAP domain, AGAP proteins contain GTP-binding protein-like, ANK repeat and pleckstrin homology (PH) domains. AGAP3 exists as a component of the NMDA receptor complex that regulates Arf6 and Ras/ERK signaling pathways. Moreover, AGAP3 regulates AMPA receptor trafficking through the ArfGAP domain. Together, AGAP3 is believed to involve in linking NMDA receptor activation to AMPA receptor trafficking. AGAP1 and AGAP2 have phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2)-mediated GTPase-activating protein (GAP) activity preferentially toward Arf1, and function in the endocytic system. AGAP1 and AGAP2 independently regulate AP-3 endosomes and AP-1/Rab4 fast recycling endosomes, respectively. AGAP1, via its PH domain, directly interacts with the adapter protein 3 (AP-3), which is a coat protein involved in trafficking in the endosomal-lysosomal system, and regulates AP-3-dependent trafficking. In other hand, AGAP2 specifically binds the clathrin adaptor protein AP-1 and regulates the AP-1/Rab-4 dependent endosomal trafficking. AGAP2 is overexpressed in different human cancers including prostate carcinoma and glioblastoma, and promotes cancer cell invasion.


Pssm-ID: 350080 [Multi-domain]  Cd Length: 110  Bit Score: 94.35  E-value: 1.34e-23
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763   21 GNAHCADCGAADPDWASYKLGIFICLNCCGVHRNF-PDISRVKSVRLDFWDDSIVEFMIHNGNLRVKAKFEARVPAfYYI 99
Cdd:cd08855  13 GNSFCIDCDAPNPDWASLNLGALMCIECSGIHRNLgTHLSRVRSLDLDDWPVELSMVMTAIGNAMANSVWEGALDG-YSK 91

                        90
                ....*....|....*....
gi 8923763  100 PQANDCLVLKEQWIRAKYE 118
Cdd:cd08855  92 PGPDSTREEKERWIRAKYE 110
ArfGap_ACAP1 cd08852
ArfGAP domain of ACAP1 (ArfGAP with Coiled-coil, ANK repeat and PH domains 1); ACAP1 belongs ...
 13-123 2.02e-23

ArfGAP domain of ACAP1 (ArfGAP with Coiled-coil, ANK repeat and PH domains 1); ACAP1 belongs to the ACAP subfamily of GAPs (GTPase-activating proteins) for the small GTPase Arf (ADP-ribosylation factor). ACAP subfamily of ArfGAPs are composed of Coiled coli (BAR, Bin-Amphiphysin-Rvs), PH, ArfGAP and ANK repeats domains. ACAP1 (centaurin beta1) and ACAP2 centaurin beta2) have a GAP (GTPase-activating protein) activity preferentially toward Arf6, which regulates endocytic recycling. Both ACAP1/2 are activated by are activated by the phosphoinositides, PI(4,5)P2 and PI(3,5)P2. ACAP1 binds specifically with recycling cargo proteins such as transferrin receptor (TfR) and cellubrevin. Thus, ACAP1 promotes cargo sorting to enhance TfR recycling from the recycling endosome. In addition, phosphorylation of ACAP by Akt, a serine/threonine protein kinase, regulates the recycling of integrin beta1 to control cell migration. In contrast, ACAP2 does not exhibit a similar interaction with the recycling cargo proteins. It has been shown that ACAP2 functions both as an effector of Ras-related protein Rab35 and as an Arf6-GTPase-activating protein (GAP) during neurite outgrowth of PC12 cells. Moreover, ACAP2, together with Rab35, regulates phagocytosis in mammalian macrophages. ACAP3 also positively regulates neurite outgrowth through its GAP activity specific to Arf6 in mouse hippocampal neurons.


Pssm-ID: 350077 [Multi-domain]  Cd Length: 120  Bit Score: 93.87  E-value: 2.02e-23
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763   13 ELLRAPdtGNAHCADCGAADPDWASYKLGIFICLNCCGVHRNFP-DISRVKSVRLDFWDDSIVEFMIHNGNLRVKAKFEA 91
Cdd:cd08852   6 QVQSVD--GNAQCCDCREPAPEWASINLGVTLCIQCSGIHRSLGvHFSKVRSLTLDSWEPELVKLMCELGNVIINQIYEA 83

                        90       100       110
                ....*....|....*....|....*....|...
gi 8923763   92 RVPAFYY-IPQANDCLVLKEQWIRAKYERREFM 123
Cdd:cd08852  84 RIEAMAIkKPGPSSSRQEKEAWIRAKYVEKKFI 116
ArfGap_GIT cd08833
The GIT subfamily of ADP-ribosylation factor GTPase-activating proteins; The GIT (G-protein ...
 25-117 4.94e-23

The GIT subfamily of ADP-ribosylation factor GTPase-activating proteins; The GIT (G-protein coupled receptor kinase-interacting protein) subfamily includes GIT1 and GIT2, which have three ANK repeats, a Spa-homology domain (SHD), a coiled-coil domain and a C-terminal paxillin-binding site (PBS). The GIT1/2 proteins are GTPase-activating proteins that function as an inactivator of Arf signaling, and interact with the PIX/Cool family of Rac/Cdc42 guanine nucleotide exchange factors (GEFs). Unlike other ArfGAPs, GIT and PIX (Pak-interacting exchange factor) proteins are tightly associated to form an oligomeric complex that acts as a scaffold and signal integrator that can be recruited for multiple signaling pathways. The GIT/PIX complex functions as a signaling scaffold by binding to specific protein partners. As a result, the complex is transported to specific cellular locations. For instance, the GIT partners paxillin or integrin-alpha4 (to focal adhesions), piccolo and liprin-alpha (to synapses), and the beta-PIX partner Scribble (to epithelial cell-cell contacts and synapses). Moreover, the GIT/PIT complex functions to integrate signals from multiple GTP-binding protein and protein kinase pathways to regulate the actin cytoskeleton and thus cell polarity, adhesion and migration.


Pssm-ID: 350062 [Multi-domain]  Cd Length: 109  Bit Score: 92.36  E-value: 4.94e-23
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763   25 CADCGAADPDWASYKLGIFICLNCCGVHRNF-PDISRVKSVRLDFWDDSIVEFM--IHNGN--------LRVKAKFEARV 93
Cdd:cd08833  11 CADCSAPDPEWASINRGVLICDECCSIHRSLgRHISQVKSLRKDQWPPSLLEMVqtLGNNGansiwehsLLDPSQSGKRK 90

                        90       100
                ....*....|....*....|....
gi 8923763   94 PafyyiPQANDCLVLKEQWIRAKY 117
Cdd:cd08833  91 P-----IPPDPVHPTKEEFIKAKY 109
ArfGap_ACAP2 cd08851
ArfGAP domain of ACAP2 (ArfGAP with Coiled-coil, ANK repeat and PH domains 2); ACAP2 belongs ...
 21-123 1.89e-22

ArfGAP domain of ACAP2 (ArfGAP with Coiled-coil, ANK repeat and PH domains 2); ACAP2 belongs to the ACAP subfamily of GAPs (GTPase-activating proteins) for the small GTPase Arf (ADP-ribosylation factor). ACAP subfamily of ArfGAPs are composed of Coiled coli (BAR, Bin-Amphiphysin-Rvs), PH, ArfGAP and ANK repeats domains. ACAP1 (centaurin beta1) and ACAP2 centaurin beta2) have a GAP (GTPase-activating protein) activity preferentially toward Arf6, which regulates endocytic recycling. Both ACAP1/2 are activated by are activated by the phosphoinositides, PI(4,5)P2 and PI(3,5)P2. ACAP1 binds specifically with recycling cargo proteins such as transferrin receptor (TfR) and cellubrevin. Thus, ACAP1 promotes cargo sorting to enhance TfR recycling from the recycling endosome. In addition, phosphorylation of ACAP by Akt, a serine/threonine protein kinase, regulates the recycling of integrin beta1 to control cell migration. In contrast, ACAP2 does not exhibit a similar interaction with the recycling cargo proteins. It has been shown that ACAP2 functions both as an effector of Ras-related protein Rab35 and as an Arf6-GTPase-activating protein (GAP) during neurite outgrowth of PC12 cells. Moreover, ACAP2, together with Rab35, regulates phagocytosis in mammalian macrophages. ACAP3 also positively regulates neurite outgrowth through its GAP activity specific to Arf6 in mouse hippocampal neurons.


Pssm-ID: 350076 [Multi-domain]  Cd Length: 116  Bit Score: 91.20  E-value: 1.89e-22
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763   21 GNAHCADCGAADPDWASYKLGIFICLNCCGVHRNFP-DISRVKSVRLDFWDDSIVEFMIHNGNLRVKAKFEARVPAFYYI 99
Cdd:cd08851  12 GNASCCDCGLADPRWASINLGITLCIECSGIHRSLGvHFSKVRSLTLDTWEPELLKLMCELGNDVINRIYEARVEKMGAK 91

                        90       100
                ....*....|....*....|....*
gi 8923763  100 -PQANDCLVLKEQWIRAKYERREFM 123
Cdd:cd08851  92 kPQPGGQRQEKEAYIRAKYVERKFV 116
ArfGap_AGAP2 cd08853
ArfGAP with GTPase domain, ANK repeat and PH domain 2; The AGAP subfamily of ADP-ribosylation ...
 21-118 1.76e-21

ArfGAP with GTPase domain, ANK repeat and PH domain 2; The AGAP subfamily of ADP-ribosylation factor GTPase-activating proteins (Arf GAPs) includes three members: AGAP1-3. In addition to the Arf GAP domain, AGAP proteins contain GTP-binding protein-like, ANK repeat and pleckstrin homology (PH) domains. AGAP1 and AGAP2 have phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2)-mediated GTPase-activating protein (GAP) activity preferentially toward Arf1, and function in the endocytic system. AGAP1 and AGAP2 independently regulate AP-3 endosomes and AP-1/Rab4 fast recycling endosomes, respectively. AGAP1, via its PH domain, directly interacts with the adapter protein 3 (AP-3), which is a coat protein involved in trafficking in the endosomal-lysosomal system, and regulates AP-3-dependent trafficking. In other hand, AGAP2 specifically binds the clathrin adaptor protein AP-1 and regulates the AP-1/Rab-4 dependent endosomal trafficking. AGAP2 is overexpressed in different human cancers including prostate carcinoma and glioblastoma, and promotes cancer cell invasion. AGAP3 exists as a component of the NMDA receptor complex that regulates Arf6 and Ras/ERK signaling pathways. Moreover, AGAP3 regulates AMPA receptor trafficking through the ArfGAP domain. Together, AGAP3 is believed to involve in linking NMDA receptor activation to AMPA receptor trafficking.


Pssm-ID: 350078 [Multi-domain]  Cd Length: 109  Bit Score: 88.53  E-value: 1.76e-21
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763   21 GNAHCADCGAADPDWASYKLGIFICLNCCGVHRNF-PDISRVKSVRLDFWDDSIVEFMIHNGNLRVKAKFEARVPAfYYI 99
Cdd:cd08853  12 GNSHCVDCETQNPKWASLNLGVLMCIECSGIHRNLgTHLSRVRSLDLDDWPVELRKVMSSIGNELANSIWEGSSQG-QTK 90

                        90
                ....*....|....*....
gi 8923763  100 PQANDCLVLKEQWIRAKYE 118
Cdd:cd08853  91 PSSDSTREEKERWIRAKYE 109
ArfGap_ACAP3 cd08850
ArfGAP domain of ACAP3 (ArfGAP with Coiled-coil, ANK repeat and PH domains 3); ACAP3 belongs ...
 21-123 1.80e-21

ArfGAP domain of ACAP3 (ArfGAP with Coiled-coil, ANK repeat and PH domains 3); ACAP3 belongs to the ACAP subfamily of GAPs (GTPase-activating proteins) for the small GTPase Arf (ADP-ribosylation factor). ACAP subfamily of ArfGAPs are composed of Coiled coli (BAR, Bin-Amphiphysin-Rvs), PH, ArfGAP and ANK repeats domains. It has been shown that ACAP3 positively regulates neurite outgrowth through its GAP activity specific to Arf6 in mouse hippocampal neurons. ACAP1 (centaurin beta1) and ACAP2 centaurin beta2) also have a GAP (GTPase-activating protein) activity preferentially toward Arf6, which regulates endocytic recycling. Both ACAP1/2 are activated by are activated by the phosphoinositides, PI(4,5)P2 and PI(3,5)P2. ACAP1 binds specifically with recycling cargo proteins such as transferrin receptor (TfR) and cellubrevin. Thus, ACAP1 promotes cargo sorting to enhance TfR recycling from the recycling endosome. In addition, phosphorylation of ACAP by Akt, a serine/threonine protein kinase, regulates the recycling of integrin beta1 to control cell migration. In contrast, ACAP2 does not exhibit a similar interaction with the recycling cargo proteins. It has been shown that ACAP2 functions both as an effector of Ras-related protein Rab35 and as an Arf6-GTPase-activating protein (GAP) during neurite outgrowth of PC12 cells. Moreover, ACAP2, together with Rab35, regulates phagocytosis in mammalian macrophages.


Pssm-ID: 350075 [Multi-domain]  Cd Length: 116  Bit Score: 88.46  E-value: 1.80e-21
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763   21 GNAHCADCGAADPDWASYKLGIFICLNCCGVHRNFP-DISRVKSVRLDFWDDSIVEFMIHNGNLRVKAKFEARVP-AFYY 98
Cdd:cd08850  12 GNDQCCDCGQPDPRWASINLGILLCIECSGIHRSLGvHCSKVRSLTLDSWEPELLKLMCELGNSTVNQIYEAQCEeLGLK 91

                        90       100
                ....*....|....*....|....*
gi 8923763   99 IPQANDCLVLKEQWIRAKYERREFM 123
Cdd:cd08850  92 KPTASSSRQDKEAWIKAKYVEKKFL 116
ArfGap_ARAP cd08837
ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing proteins; The ARAP subfamily ...
 21-95 1.96e-20

ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing proteins; The ARAP subfamily includes three members, ARAP1-3, and belongs to the ADP-ribosylation factor GTPase-activating proteins (Arf GAPs) family of proteins that promotes the hydrolysis of GTP bound to Arf, thereby inactivating Arf signaling. The function of Arfs is dependent on GAPs and guanine nucleotide exchange factors (GEFs), which allow Arfs to cycle between the GDP-bound and GTP-bound forms. In addition to the Arf GAP domain, ARAPs contain the SAM (sterile-alpha motif) domain, 5 pleckstrin homology (PH) domains, the Rho-GAP domain, the Ras-association domain, and ANK repeats. ARAPs show phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3)-dependent GAP activity toward Arf6. ARAPs play important roles in endocytic trafficking, cytoskeleton reorganization in response to growth factors stimulation, and focal adhesion dynamics.


Pssm-ID: 350066 [Multi-domain]  Cd Length: 116  Bit Score: 85.89  E-value: 1.96e-20
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 8923763   21 GNAHCADCGAADPDWASYKLGIFICLNCCGVHRNF-PDISRVKSVRLD--FWDDSIVEFMIHNGNLRVKAKFEARVPA 95
Cdd:cd08837  12 ANRFCADCGAPDPDWASINLCVVICKQCAGEHRSLgSNISKVRSLKMDtkVWTEELVELFLKLGNDRANRFWAANLPP 89
ArfGap_ASAP cd08834
ArfGAP domain of ASAP (Arf GAP, SH3, ANK repeat and PH domains) subfamily of ADP-ribosylation ...
 21-122 3.20e-20

ArfGAP domain of ASAP (Arf GAP, SH3, ANK repeat and PH domains) subfamily of ADP-ribosylation factor GTPase-activating proteins; The ArfGAPs are a family of multidomain proteins with a common catalytic domain that promotes the hydrolysis of GTP bound to Arf, thereby inactivating Arf signaling. ASAP-subfamily GAPs include three members: ASAP1, ASAP2, ASAP3. The ASAP subfamily comprises Arf GAP, SH3, ANK repeat and PH domains. From the N-terminus, each member has a BAR, PH, Arf GAP, ANK repeat, and proline rich domains. Unlike ASAP3, ASAP1 and ASAP2 also have an SH3 domain at the C-terminus. ASAP1 and ASAP2 show strong GTPase-activating protein (GAP) activity toward Arf1 and Arf5 and weak activity toward Arf6. ASAP1 is a target of Src and FAK signaling that regulates focal adhesions, circular dorsal ruffles (CDR), invadopodia, and podosomes. ASAP1 GAP activity is synergistically stimulated by phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidic acid. ASAP2 is believed to function as an ArfGAP that controls ARF-mediated vesicle budding when recruited to Golgi membranes. It also functions as a substrate and downstream target for protein tyrosine kinases Pyk2 and Src, a pathway that may be involved in the regulation of vesicular transport. ASAP3 is a focal adhesion-associated ArfGAP that functions in cell migration and invasion. Similar to ASAP1, the GAP activity of ASAP3 is strongly enhanced by PIP2 via PH domain. Like ASAP1, ASAP3 associates with focal adhesions and circular dorsal ruffles. However, unlike ASAP1, ASAP3 does not localize to invadopodia or podosomes. Both ASAP 1 and 3 have been implicated in oncogenesis, as ASAP1 is highly expressed in metastatic breast cancer and ASAP3 in hepatocellular carcinoma.


Pssm-ID: 350063 [Multi-domain]  Cd Length: 117  Bit Score: 84.96  E-value: 3.20e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763   21 GNAHCADCGAADPDWASYKLGIFICLNCCGVHRNFP-DISRVKSVRLDFWDDSIVEFMIHNGNLRVKAKFEARVPAfYYI 99
Cdd:cd08834  14 GNDVCCDCGSPDPTWLSTNLGILTCIECSGVHRELGvHVSRIQSLTLDNLGTSELLLARNLGNEGFNEIMEANLPP-GYK 92

                        90       100
                ....*....|....*....|...
gi 8923763  100 PQANDCLVLKEQWIRAKYERREF 122
Cdd:cd08834  93 PTPNSDMEERKDFIRAKYVEKKF 115
ArfGap_ArfGap2_3_like cd08831
Arf1 GTPase-activating protein 2/3-like; ArfGAP (ADP Ribosylation Factor GTPase Activating ...
 5-90 3.89e-20

Arf1 GTPase-activating protein 2/3-like; ArfGAP (ADP Ribosylation Factor GTPase Activating Protein) domain is a part of ArfGap1-like proteins that play a crucial role in controlling of membrane trafficking, particularly in the formation of COPI (coat protein complex I)-coated vesicles on Golgi membranes. The ArfGAP1 protein subfamily consists of three members: ArfGAP1 (Gcs1p in yeast), ArfGAP2 and ArfGAP3 (both are homologs of yeast Glo3p). ArfGAP2/3 are closely related, but with little similarity to ArfGAP1, except the catalytic ArfGAP domain. They promote hydrolysis of GTP bound to the small G protein ADP-ribosylation factor 1 (Arf1), which leads to the dissociation of coat proteins from Golgi-derived membranes and vesicles. Dissociation of the coat proteins is required for the fusion of these vesicles with target compartments. Thus, the GAP catalytic activity plays a key role in the formation of COPI vesicles from Golgi membrane. In contrast to ArfGAP1, which displays membrane curvature-dependent ArfGAP activity, ArfGAP2 and ArfGAP3 activities are dependent on coatomer (the core COPI complex) which required for efficient recruitment of ArfGAP2 and ArfGAP3 to the Golgi membrane. Accordingly, ArfGAP2/3 has been implicated in coatomer-mediated protein transport between the Golgi complex and the endoplasmic reticulum. Unlike ArfGAP1, which is controlled by membrane curvature through its amphipathic lipid packing sensor (ALPS) motifs, ArfGAP2/3 do not possess ALPS motif.


Pssm-ID: 350060 [Multi-domain]  Cd Length: 116  Bit Score: 84.91  E-value: 3.89e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763    5 ERNKKrLLELLRAPDtgNAHCADCGAADPDWASYKLGIFICLNCCGVHRNF-PDISRVKSVRLDFWDDSIVEFMIHNGNL 83
Cdd:cd08831   1 ERDAI-FKKLRSKPE--NKVCFDCGAKNPTWASVTFGVFLCLDCSGVHRSLgVHISFVRSTNLDSWTPEQLRRMKVGGNA 77


                ....*..
gi 8923763   84 RVKAKFE 90
Cdd:cd08831  78 KAREFFK 84
ArfGap_ASAP3 cd17900
ArfGAP domain of ASAP3 (ArfGAP with ANK repeat and PH domain-containing protein 3); The ...
 7-128 1.38e-19

ArfGAP domain of ASAP3 (ArfGAP with ANK repeat and PH domain-containing protein 3); The ArfGAPs are a family of multidomain proteins with a common catalytic domain that promotes the hydrolysis of GTP bound to Arf, thereby inactivating Arf signaling. ASAP-subfamily GAPs include three members: ASAP1, ASAP2, ASAP3. The ASAP subfamily comprises Arf GAP, SH3, ANK repeat and PH domains. From the N-terminus, each member has a BAR, PH, Arf GAP, ANK repeat, and proline rich domains. Unlike ASAP1 and ASAP2, ASAP3 do not have an SH3 domain at the C-terminus. ASAP1 and ASAP2 show strong GTPase-activating protein (GAP) activity toward Arf1 and Arf5 and weak activity toward Arf6. ASAP1 is a target of Src and FAK signaling that regulates focal adhesions, circular dorsal ruffles (CDR), invadopodia, and podosomes. ASAP1 GAP activity is synergistically stimulated by phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidic acid. ASAP2 is believed to function as an ArfGAP that controls ARF-mediated vesicle budding when recruited to Golgi membranes. It also functions as a substrate and downstream target for protein tyrosine kinases Pyk2 and Src, a pathway that may be involved in the regulation of vesicular transport. ASAP3 is a focal adhesion-associated ArfGAP that functions in cell migration and invasion. Similar to ASAP1, the GAP activity of ASAP3 is strongly enhanced by PIP2 via PH domain. Like ASAP1, ASAP3 associates with focal adhesions and circular dorsal ruffles. However, unlike ASAP1, ASAP3 does not localize to invadopodia or podosomes. ASAP 1 and 3 have been implicated in oncogenesis, as ASAP1 is highly expressed in metastatic breast cancer and ASAP3 in hepatocellular carcinoma.


Pssm-ID: 350087 [Multi-domain]  Cd Length: 124  Bit Score: 83.74  E-value: 1.38e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763    7 NKKRLLELLRAPdtGNAHCADCGAADPDWASYKLGIFICLNCCGVHRNFP-DISRVKSVRLDFWDDSIVEFMIHNGNLRV 85
Cdd:cd17900   2 TKLLIAEVKSRP--GNSQCCDCGAPDPTWLSTNLGILTCIECSGIHRELGvRYSRIQSLTLDLLSTSELLLAVSMGNTRF 79

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....
gi 8923763   86 KAKFEARVPAFYYI-PQANDCLVLKEQWIRAKYERREFMADGET 128
Cdd:cd17900  80 NEVMEATLPAHGGPkPSAESDMGTRKDYIMAKYVEHRFVRKRCT 123
ArfGap_ArfGap1_like cd08959
ARF1 GTPase-activating protein 1-like; ArfGAP (ADP Ribosylation Factor GTPase Activating ...
 8-91 5.60e-19

ARF1 GTPase-activating protein 1-like; ArfGAP (ADP Ribosylation Factor GTPase Activating Protein) domain is a part of ArfGap1-like proteins that play a crucial role in controlling of membrane trafficking, particularly in the formation of COPI (coat protein complex I)-coated vesicles on Golgi membranes. The ArfGAP1 protein subfamily consists of three members: ArfGAP1 (Gcs1p in yeast), ArfGAP2 and ArfGAP3 (both are homologs of yeast Glo3p). ArfGAP2/3 are closely related, but with little similarity to ArfGAP1, except the catalytic ArfGAP domain. They promote hydrolysis of GTP bound to the small G protein ADP-ribosylation factor 1 (Arf1), which leads to the dissociation of coat proteins from Golgi-derived membranes and vesicles. Dissociation of the coat proteins is required for the fusion of these vesicles with target compartments. Thus, the GAP catalytic activity plays a key role in the formation of COPI vesicles from Golgi membrane. In contrast to ArfGAP1, which displays membrane curvature-dependent ArfGAP activity, ArfGAP2 and ArfGAP3 activities are dependent on coatomer (the core COPI complex) which required for efficient recruitment of ArfGAP2 and ArfGAP3 to the Golgi membrane. Accordingly, ArfGAP2/3 has been implicated in coatomer-mediated protein transport between the Golgi complex and the endoplasmic reticulum. Unlike ArfGAP1, which is controlled by membrane curvature through its amphipathic lipid packing sensor (ALPS) motifs, ArfGAP2/3 do not possess ALPS motif.


Pssm-ID: 350084 [Multi-domain]  Cd Length: 115  Bit Score: 81.79  E-value: 5.60e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763    8 KKRLLELLRAPDtgNAHCADCGAADPDWASYKLGIFICLNCCGVHRNFP-DISRVKSVRLDFWDDSIVEFMIHNGNLRVK 86
Cdd:cd08959   2 RAVFKKLRSKPE--NKVCFDCGAKNPQWASVTYGIFICLDCSGVHRGLGvHISFVRSTTMDKWTEEQLRKMKVGGNANAR 79


                ....*
gi 8923763   87 AKFEA 91
Cdd:cd08959  80 EFFKQ 84
ArfGap_AGAP1 cd08854
ArfGAP with GTPase domain, ANK repeat and PH domain 1; The AGAP subfamily of ADP-ribosylation ...
 21-118 1.58e-18

ArfGAP with GTPase domain, ANK repeat and PH domain 1; The AGAP subfamily of ADP-ribosylation factor GTPase-activating proteins (Arf GAPs) includes three members: AGAP1-3. In addition to the Arf GAP domain, AGAP proteins contain GTP-binding protein-like, ANK repeat and pleckstrin homology (PH) domains. AGAP1 and AGAP2 have phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2)-mediated GTPase-activating protein (GAP) activity preferentially toward Arf1, and function in the endocytic system. AGAP1 and AGAP2 independently regulate AP-3 endosomes and AP-1/Rab4 fast recycling endosomes, respectively. AGAP1, via its PH domain, directly interacts with the adapter protein 3 (AP-3), which is a coat protein involved in trafficking in the endosomal-lysosomal system, and regulates AP-3-dependent trafficking. In other hand, AGAP2 specifically binds the clathrin adaptor protein AP-1 and regulates the AP-1/Rab-4 dependent endosomal trafficking. AGAP2 is overexpressed in different human cancers including prostate carcinoma and glioblastoma, and promotes cancer cell invasion. AGAP3 exists as a component of the NMDA receptor complex that regulates Arf6 and Ras/ERK signaling pathways. Moreover, AGAP3 regulates AMPA receptor trafficking through the ArfGAP domain. Together, AGAP3 is believed to involve in linking NMDA receptor activation to AMPA receptor trafficking.


Pssm-ID: 350079 [Multi-domain]  Cd Length: 109  Bit Score: 80.44  E-value: 1.58e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763   21 GNAHCADCGAADPDWASYKLGIFICLNCCGVHRNF-PDISRVKSVRLDFWDDSIVEFMIHNGNLRVKAKFEARVPAfYYI 99
Cdd:cd08854  12 GNSLCVDCGAPNPTWASLNLGALICIECSGIHRNLgTHLSRVRSLDLDDWPRELTLVLTAIGNHMANSIWESCTQG-RTK 90

                        90
                ....*....|....*....
gi 8923763  100 PQANDCLVLKEQWIRAKYE 118
Cdd:cd08854  91 PAPDSSREERESWIRAKYE 109
ArfGap_ARAP3 cd17902
ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing protein 3; The ARAP subfamily ...
 22-95 6.29e-17

ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing protein 3; The ARAP subfamily includes three members, ARAP1-3, and belongs to the ADP-ribosylation factor GTPase-activating proteins (Arf GAPs) family of proteins that promotes the hydrolysis of GTP bound to Arf, thereby inactivating Arf signaling. The function of Arfs is dependent on GAPs and guanine nucleotide exchange factors (GEFs), which allow Arfs to cycle between the GDP-bound and GTP-bound forms. In addition to the Arf GAP domain, ARAPs contain the SAM (sterile-alpha motif) domain, 5 pleckstrin homology (PH) domains, the Rho-GAP domain, the Ras-association domain, and ANK repeats. ARAPs show phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3)-dependent GAP activity toward Arf6. ARAPs play important roles in endocytic trafficking, cytoskeleton reorganization in response to growth factors stimulation, and focal adhesion dynamics. ARAP3 possesses a unique dual-specificity GAP activity for Arf6 and RhoA regulated by PI(3,4,5)P3 and a small GTPase Rap1-GTP. The RhoGAP activity of ARAP3 is enhanced by direct binding of Rap1-GTP to the Ras-association (RA) domain. ARAP3 is involved in regulation of cell shape and adhesion.


Pssm-ID: 350089 [Multi-domain]  Cd Length: 116  Bit Score: 76.10  E-value: 6.29e-17
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 8923763   22 NAHCADCGAADPDWASYKLGIFICLNCCGVHRNF-PDISRVKSVRLD--FWDDSIVEFMIHNGNLRVKAKFEARVPA 95
Cdd:cd17902  13 NRFCADCHASSPDWASINLCVVICKQCAGQHRSLgSGISKVQSLKLDtsVWSNEIVQLFIVLGNDRANRFWAARLPA 89
ArfGap_ARAP2 cd08856
ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing protein 2; The ARAP subfamily ...
 22-122 4.16e-16

ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing protein 2; The ARAP subfamily includes three members, ARAP1-3, and belongs to the ADP-ribosylation factor GTPase-activating proteins (Arf GAPs) family of proteins that promotes the hydrolysis of GTP bound to Arf, thereby inactivating Arf signaling. The function of Arfs is dependent on GAPs and guanine nucleotide exchange factors (GEFs), which allow Arfs to cycle between the GDP-bound and GTP-bound forms. In addition to the Arf GAP domain, ARAPs contain the SAM (sterile-alpha motif) domain, 5 pleckstrin homology (PH) domains, the Rho-GAP domain, the Ras-association domain, and ANK repeats. ARAPs show phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3)-dependent GAP activity toward Arf6. ARAPs play important roles in endocytic trafficking, cytoskeleton reorganization in response to growth factors stimulation, and focal adhesion dynamics. ARAP2 localizes to the cell periphery and on focal adhesions composed of paxillin and vinculin, and functions downstream of RhoA to regulate focal adhesion dynamics. ARAP2 is a PI(3,4,5)P3-dependent Arf6 GAP that binds RhoA-GTP, but it lacks the predicted catalytic arginine in the RhoGAP domain and does not have RhoGAP activity. ARAP2 reduces Rac1oGTP levels by reducing Arf6oGTP levels through GAP activity. AGAP2 also binds to and regulates focal adhesion kinase (FAK). Thus, ARAP2 signals through Arf6 and Rac1 to control focal adhesion morphology.


Pssm-ID: 350081 [Multi-domain]  Cd Length: 121  Bit Score: 73.79  E-value: 4.16e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763   22 NAHCADCGAADPDWASYKLGIFICLNCCGVHRNF-PDISRVKSVRLD--FWDDSIVEFMIHNGNLRVKAKFEARVPAFYY 98
Cdd:cd08856  18 NRSCADCKAPDPDWASINLCVVICKKCAGQHRSLgPKDSKVRSLKMDasIWSNELIELFIVVGNKPANLFWAANLFSEED 97

                        90       100
                ....*....|....*....|....
gi 8923763   99 IPQANDcLVLKEQWIRAKYERREF 122
Cdd:cd08856  98 LHMDSD-VEQRTPFITQKYKEGKF 120
ArfGap_ASAP1 cd08848
ArfGAP domain of ASAP1 (ArfGAP with SH3 domain, ANK repeat and PH domain-containing protein 1); ...
 13-122 5.98e-16

ArfGAP domain of ASAP1 (ArfGAP with SH3 domain, ANK repeat and PH domain-containing protein 1); The ArfGAPs are a family of multidomain proteins with a common catalytic domain that promotes the hydrolysis of GTP bound to Arf, thereby inactivating Arf signaling. ASAP-subfamily GAPs include three members: ASAP1, ASAP2, ASAP3. The ASAP subfamily comprises Arf GAP, SH3, ANK repeat and PH domains. From the N-terminus, each member has a BAR, PH, Arf GAP, ANK repeat, and proline rich domains. Unlike ASAP3, ASAP1 and ASAP2 also have an SH3 domain at the C-terminus. ASAP1 and ASAP2 show strong GTPase-activating protein (GAP) activity toward Arf1 and Arf5 and weak activity toward Arf6. ASAP1 is a target of Src and FAK signaling that regulates focal adhesions, circular dorsal ruffles (CDR), invadopodia, and podosomes. ASAP1 GAP activity is synergistically stimulated by phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidic acid. ASAP2 is believed to function as an ArfGAP that controls ARF-mediated vesicle budding when recruited to Golgi membranes. It also functions as a substrate and downstream target for protein tyrosine kinases Pyk2 and Src, a pathway that may be involved in the regulation of vesicular transport. ASAP3 is a focal adhesion-associated ArfGAP that functions in cell migration and invasion. Similar to ASAP1, the GAP activity of ASAP3 is strongly enhanced by PIP2 via PH domain. Like ASAP1, ASAP3 associates with focal adhesions and circular dorsal ruffles. However, unlike ASAP1, ASAP3 does not localize to invadopodia or podosomes. ASAP 1 and 3 have been implicated in oncogenesis, as ASAP1 is highly expressed in metastatic breast cancer and ASAP3 in hepatocellular carcinoma.


Pssm-ID: 350073 [Multi-domain]  Cd Length: 122  Bit Score: 73.53  E-value: 5.98e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763   13 ELLRAPdtGNAHCADCGAADPDWASYKLGIFICLNCCGVHRNFP-DISRVKSVRLDFWDDSIVEFMIHNGNLRVKAKFEA 91
Cdd:cd08848   8 DVQRLP--GNEVCCDCGSPDPTWLSTNLGILTCIECSGIHREMGvHISRIQSLELDKLGTSELLLAKNVGNNSFNDIMEG 85

                        90       100       110
                ....*....|....*....|....*....|.
gi 8923763   92 RVPAFYYIPQANDCLVLKEQWIRAKYERREF 122
Cdd:cd08848  86 NLPSPSPKPSPSSDMTARKEYITAKYVEHRF 116
ArfGap_AGFG cd08838
ArfGAP domain of the AGFG subfamily (ArfGAP domain and FG repeat-containing proteins); The ...
 9-124 7.00e-16

ArfGAP domain of the AGFG subfamily (ArfGAP domain and FG repeat-containing proteins); The ArfGAP domain and FG repeat-containing proteins (AFGF) subfamily of Arf GTPase-activating proteins consists of the two structurally-related members: AGFG1 and AGFG2. AGFG1 (alias: HIV-1 Rev binding protein, HRB; Rev interacting protein, RIP; Rev/Rex activating domain-binding protein, RAB) and AGFG2 are involved in the maintenance and spread of immunodeficiency virus type 1 (HIV-1) infection. The ArfGAP domain of AGFG is related to nucleoporins, which is a class of proteins that mediate nucleocytoplasmic transport. AGFG plays a role in the Rev export pathway, which mediates the nucleocytoplasmic transfer of proteins and RNAs, possibly together by the nuclear export receptor CRM1. In humans, the presence of the FG repeat motifs (11 in AGFG1 and 7 in AGFG2) are thought to be required for these proteins to act as HIV-1 Rev cofactors. Hence, AGFG promotes movement of Rev-responsive element-containing RNAs from the nuclear periphery to the cytoplasm, which is an essential step for HIV-1 replication.


Pssm-ID: 350067 [Multi-domain]  Cd Length: 113  Bit Score: 73.00  E-value: 7.00e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763    9 KRLLELLRAPDtgNAHCADCGAADPDWASYKLGIFICLNCCGVHRNFPdiSRVKSVRLDFWDDSIVEFMIHNGNLRVKAK 88
Cdd:cd08838   2 KILRELLKLPE--NKRCFDCGQRGPTYVNLTFGTFVCTTCSGIHREFN--HRVKSISMSTFTPEEVEFLQAGGNEVARKI 77

                        90       100       110
                ....*....|....*....|....*....|....*..
gi 8923763   89 FEARV-PAFYYIPQANDCLVLKEqWIRAKYERREFMA 124
Cdd:cd08838  78 WLAKWdPRTDPEPDSGDDQKIRE-FIRLKYVDKRWYD 113
ArfGap_ARAP1 cd17901
ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing protein 1; The ARAP subfamily ...
 21-94 3.65e-14

ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing protein 1; The ARAP subfamily includes three members, ARAP1-3, and belongs to the ADP-ribosylation factor GTPase-activating proteins (Arf GAPs) family of proteins that promotes the hydrolysis of GTP bound to Arf, thereby inactivating Arf signaling. The function of Arfs is dependent on GAPs and guanine nucleotide exchange factors (GEFs), which allow Arfs to cycle between the GDP-bound and GTP-bound forms. In addition to the Arf GAP domain, ARAPs contain the SAM (sterile-alpha motif) domain, 5 pleckstrin homology (PH) domains, the Rho-GAP domain, the Ras-association domain, and ANK repeats. ARAPs show phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3)-dependent GAP activity toward Arf6. ARAPs play important roles in endocytic trafficking, cytoskeleton reorganization in response to growth factors stimulation, and focal adhesion dynamics. ARAP1 localizes to the plasma membrane, the Golgi complex, and endosomal compartments. It displays PI(3,4,5)P3-dependent ArfGAP activity that regulates Arf-, RhoA-, and Cdc42-dependent cellular events. For example, ARAP1 inhibits the trafficking of epidermal growth factor receptor (EGFR) to the early endosome.


Pssm-ID: 350088 [Multi-domain]  Cd Length: 116  Bit Score: 68.30  E-value: 3.65e-14
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 8923763   21 GNAHCADCGAADPDWASYKLGIFICLNCCGVHRNF-PDISRVKSVRLD--FWDDSIVEFMIHNGNLRVKAKFEARVP 94
Cdd:cd17901  12 SNRFCADCGSPKPDWASVNLCVVICKRCAGEHRGLgPSVSKVRSLKMDrkVWTEELIELFLLLGNGKANQFWAANVP 88
ArfGap_ASAP2 cd08849
ArfGAP domain of ASAP2 (ArfGAP2 with SH3 domain, ANK repeat and PH domain-containing protein 2) ...
 20-122 1.55e-13

ArfGAP domain of ASAP2 (ArfGAP2 with SH3 domain, ANK repeat and PH domain-containing protein 2); The Arf GAPs are a family of multidomain proteins with a common catalytic domain that promotes the hydrolysis of GTP bound to Arf , thereby inactivating Arf signaling. ASAP-subfamily GAPs include three members: ASAP1, ASAP2, ASAP3. The ASAP subfamily comprises Arf GAP, SH3, ANK repeat and PH domains. From the N-terminus, each member has a BAR, PH, Arf GAP, ANK repeat, and proline rich domains. Unlike ASAP3, ASAP1 and ASAP2 also have an SH3 domain at the C-terminus. ASAP1 and ASAP2 show strong GTPase-activating protein (GAP) activity toward Arf1 and Arf5 and weak activity toward Arf6. ASAP1 is a target of Src and FAK signaling that regulates focal adhesions, circular dorsal ruffles (CDR), invadopodia, and podosomes. ASAP1 GAP activity is synergistically stimulated by phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidic acid. ASAP2 is believed to function as an ArfGAP that controls ARF-mediated vesicle budding when recruited to Golgi membranes. It also functions as a substrate and downstream target for protein tyrosine kinases Pyk2 and Src, a pathway that may be involved in the regulation of vesicular transport.


Pssm-ID: 350074 [Multi-domain]  Cd Length: 123  Bit Score: 66.92  E-value: 1.55e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763   20 TGNAHCADCGAADPDWASYKLGIFICLNCCGVHRNFP-DISRVKSVRLDFWDDSIVEFMIHNGNLRVKAKFEARVPAFYY 98
Cdd:cd08849  13 TGNDVCCDCGAPDPTWLSTNLGILTCIECSGIHRELGvHYSRMQSLTLDVLGTSELLLAKNIGNAGFNEIMEACLPAEDV 92

                        90       100
                ....*....|....*....|....*
gi 8923763   99 I-PQANDCLVLKEQWIRAKYERREF 122
Cdd:cd08849  93 VkPNPGSDMNARKDYITAKYIERRY 117
PLN03114 PLN03114
ADP-ribosylation factor GTPase-activating protein AGD10; Provisional
 7-90 1.25e-12

ADP-ribosylation factor GTPase-activating protein AGD10; Provisional


Pssm-ID: 178661 [Multi-domain]  Cd Length: 395  Bit Score: 68.73  E-value: 1.25e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763     7 NKKRLLELLRApDTGNAHCADCGAADPDWASYKLGIFICLNCCGVHRNFP-DISRVKSVRLDFWDDSIVEFMIHNGNLRV 85
Cdd:PLN03114   8 DKISVFKKLKA-KSDNKICFDCNAKNPTWASVTYGIFLCIDCSAVHRSLGvHISFVRSTNLDSWSSEQLKMMIYGGNNRA 86


                 ....*
gi 8923763    86 KAKFE 90
Cdd:PLN03114  87 QVFFK 91
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 257-361 1.95e-11

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: 60.25  E-value: 1.95e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763     257 LKQGFMEKTGPKQKEPFKKRWFALdcHERRLLYYKNP---LDAFEQGQVFLgnkeQGYEAYEDLPKGIRGNRWkaGLTIV 333
Cdd:smart00233   2 IKEGWLYKKSGGGKKSWKKRYFVL--FNSTLLYYKSKkdkKSYKPKGSIDL----SGCTVREAPDPDSSKKPH--CFEIK 73

                           90       100
                   ....*....|....*....|....*....
gi 8923763     334 TPERR-FVLTCPSEKEQQEWLESLRGVLS 361
Cdd:smart00233  74 TSDRKtLLLQAESEEEREKWVEALRKAIA 102
ArfGap_GIT2 cd08847
GIT2 GTPase activating protein for Arf; The GIT (G-protein coupled receptor kinase-interacting ...
 15-81 2.58e-11

GIT2 GTPase activating protein for Arf; The GIT (G-protein coupled receptor kinase-interacting protein) subfamily includes GIT1 and GIT2, which have three ANK repeats, a Spa-homology domain (SHD), a coiled-coil domain and a C-terminal paxillin-binding site (PBS). The GIT1/2 proteins are GTPase-activating proteins that function as an inactivator of Arf signaling, and interact with the PIX/Cool family of Rac/Cdc42 guanine nucleotide exchange factors (GEFs). Unlike other ArfGAPs, GIT and PIX (Pak-interacting exchange factor) proteins are tightly associated to form an oligomeric complex that acts as a scaffold and signal integrator that can be recruited for multiple signaling pathways. The GIT/PIX complex functions as a signaling scaffold by binding to specific protein partners. As a result, the complex is transported to specific cellular locations. For instance, the GIT partners paxillin or integrin-alpha4 (to focal adhesions), piccolo and liprin-alpha (to synapses), and the beta-PIX partner Scribble (to epithelial cell-cell contacts and synapses). Moreover, the GIT/PIT complex functions to integrate signals from multiple GTP-binding protein and protein kinase pathways to regulate the actin cytoskeleton and thus cell polarity, adhesion and migration.


Pssm-ID: 350072 [Multi-domain]  Cd Length: 111  Bit Score: 60.03  E-value: 2.58e-11
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 8923763   15 LRAPDTgnahCADCGAADPDWASYKLGIFICLNCCGVHRNF-PDISRVKSVRLDFWDDSI---VEFMIHNG 81
Cdd:cd08847   5 LRSSEV----CADCSTSDPRWASVNRGVLICDECCSVHRSLgRHISQVRHLKHTSWPPTLlqmVQTLYNNG 71
ArfGap_ArfGap2 cd09029
Arf1 GTPase-activating protein 2; ArfGAP (ADP Ribosylation Factor GTPase Activating Protein) ...
 11-67 4.51e-11

Arf1 GTPase-activating protein 2; ArfGAP (ADP Ribosylation Factor GTPase Activating Protein) domain is a part of ArfGap1-like proteins that play a crucial role in controlling of membrane trafficking, particularly in the formation of COPI (coat protein complex I)-coated vesicles on Golgi membranes. The ArfGAP1 protein subfamily consists of three members: ArfGAP1 (Gcs1p in yeast), ArfGAP2 and ArfGAP3 (both are homologs of yeast Glo3p). ArfGAP2/3 are closely related, but with little similarity to ArfGAP1, except the catalytic ArfGAP domain. They promote hydrolysis of GTP bound to the small G protein ADP-ribosylation factor 1 (Arf1), which leads to the dissociation of coat proteins from Golgi-derived membranes and vesicles. Dissociation of the coat proteins is required for the fusion of these vesicles with target compartments. Thus, the GAP catalytic activity plays a key role in the formation of COPI vesicles from Golgi membrane. In contrast to ArfGAP1, which displays membrane curvature-dependent ArfGAP activity, ArfGAP2 and ArfGAP3 activities are dependent on coatomer (the core COPI complex) which required for efficient recruitment of ArfGAP2 and ArfGAP3 to the Golgi membrane. Accordingly, ArfGAP2/3 has been implicated in coatomer-mediated protein transport between the Golgi complex and the endoplasmic reticulum. Unlike ArfGAP1, which is controlled by membrane curvature through its amphipathic lipid packing sensor (ALPS) motifs, ArfGAP2/3 do not possess ALPS motif.


Pssm-ID: 350086 [Multi-domain]  Cd Length: 120  Bit Score: 59.69  E-value: 4.51e-11
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 8923763   11 LLELLRAPDTgNAHCADCGAADPDWASYKLGIFICLNCCGVHRNFP-DISRVKSVRLD 67
Cdd:cd09029   9 LFKRLRAIPT-NKACFDCGAKNPSWASITYGVFLCIDCSGVHRSLGvHLSFIRSTELD 65
ArfGap_GIT1 cd08846
GIT1 GTPase activating protein for Arf; The GIT (G-protein coupled receptor kinase-interacting ...
 25-79 1.75e-10

GIT1 GTPase activating protein for Arf; The GIT (G-protein coupled receptor kinase-interacting protein) subfamily includes GIT1 and GIT2, which have three ANK repeats, a Spa-homology domain (SHD), a coiled-coil domain and a C-terminal paxillin-binding site (PBS). The GIT1/2 proteins are GTPase-activating proteins that function as an inactivator of Arf signaling, and interact with the PIX/Cool family of Rac/Cdc42 guanine nucleotide exchange factors (GEFs). Unlike other ArfGAPs, GIT and PIX (Pak-interacting exchange factor) proteins are tightly associated to form an oligomeric complex that acts as a scaffold and signal integrator that can be recruited for multiple signaling pathways. The GIT/PIX complex functions as a signaling scaffold by binding to specific protein partners. As a result, the complex is transported to specific cellular locations. For instance, the GIT partners paxillin or integrin-alpha4 (to focal adhesions), piccolo and liprin-alpha (to synapses), and the beta-PIX partner Scribble (to epithelial cell-cell contacts and synapses). Moreover, the GIT/PIT complex functions to integrate signals from multiple GTP-binding protein and protein kinase pathways to regulate the actin cytoskeleton and thus cell polarity, adhesion and migration.


Pssm-ID: 350071 [Multi-domain]  Cd Length: 111  Bit Score: 57.80  E-value: 1.75e-10
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 8923763   25 CADCGAADPDWASYKLGIFICLNCCGVHRNF-PDISRVKSVRLDFWDDSIVEfMIH 79
Cdd:cd08846  11 CADCSAPDPGWASINRGVLICDECCSVHRSLgRHISIVKHLRHSAWPPTLLQ-MVH 65
ArfGap_ArfGap3 cd09028
Arf1 GTPase-activating protein 3; ArfGAP (ADP Ribosylation Factor GTPase Activating Protein) ...
 15-89 5.76e-10

Arf1 GTPase-activating protein 3; ArfGAP (ADP Ribosylation Factor GTPase Activating Protein) domain is a part of ArfGap1-like proteins that play a crucial role in controlling of membrane trafficking, particularly in the formation of COPI (coat protein complex I)-coated vesicles on Golgi membranes. The ArfGAP1 protein subfamily consists of three members: ArfGAP1 (Gcs1p in yeast), ArfGAP2 and ArfGAP3 (both are homologs of yeast Glo3p). ArfGAP2/3 are closely related, but with little similarity to ArfGAP1, except the catalytic ArfGAP domain. They promote hydrolysis of GTP bound to the small G protein ADP-ribosylation factor 1 (Arf1), which leads to the dissociation of coat proteins from Golgi-derived membranes and vesicles. Dissociation of the coat proteins is required for the fusion of these vesicles with target compartments. Thus, the GAP catalytic activity plays a key role in the formation of COPI vesicles from Golgi membrane. In contrast to ArfGAP1, which displays membrane curvature-dependent ArfGAP activity, ArfGAP2 and ArfGAP3 activities are dependent on coatomer (the core COPI complex) which required for efficient recruitment of ArfGAP2 and ArfGAP3 to the Golgi membrane. Accordingly, ArfGAP2/3 has been implicated in coatomer-mediated protein transport between the Golgi complex and the endoplasmic reticulum. Unlike ArfGAP1, which is controlled by membrane curvature through its amphipathic lipid packing sensor (ALPS) motifs, ArfGAP2/3 do not possess ALPS motif.


Pssm-ID: 350085 [Multi-domain]  Cd Length: 120  Bit Score: 56.61  E-value: 5.76e-10
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 8923763   15 LRAPDTgNAHCADCGAADPDWASYKLGIFICLNCCGVHRNFP-DISRVKSVRLDF-WDDSIVEFMIHNGNLRVKAKF 89
Cdd:cd09028  13 LRSVPT-NKVCFDCGAKNPSWASITYGVFLCIDCSGIHRSLGvHLSFIRSTELDSnWSWFQLRCMQVGGNANASAFF 88
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
 258-356 7.47e-10

Pleckstrin homology (PH) 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: 275388 [Multi-domain]  Cd Length: 92  Bit Score: 55.24  E-value: 7.47e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763  258 KQGFMEKTGPKQKEPFKKRWFALdcHERRLLYYKNPLDAFEQ--GQVFLgnkeQGYEAYEDLPKGIRGNRWKagltIVTP 335
Cdd:cd00821   1 KEGYLLKRGGGGLKSWKKRWFVL--FEGVLLYYKSKKDSSYKpkGSIPL----SGILEVEEVSPKERPHCFE----LVTP 70

                        90       100
                ....*....|....*....|..
gi 8923763  336 -ERRFVLTCPSEKEQQEWLESL 356
Cdd:cd00821  71 dGRTYYLQADSEEERQEWLKAL 92
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 258-361 1.57e-09

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 54.88  E-value: 1.57e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763    258 KQGFMEKTGPKQKEPFKKRWFALdcHERRLLYYKNPL---DAFEQGQVFLgnkeQGYEAYEDLPKGIRGNRWKAGLTIV- 333
Cdd:pfam00169   3 KEGWLLKKGGGKKKSWKKRYFVL--FDGSLLYYKDDKsgkSKEPKGSISL----SGCEVVEVVASDSPKRKFCFELRTGe 76

                          90       100
                  ....*....|....*....|....*....
gi 8923763    334 -TPERRFVLTCPSEKEQQEWLESLRGVLS 361
Cdd:pfam00169  77 rTGKRTYLLQAESEEERKDWIKAIQSAIR 105
PLN03131 PLN03131
hypothetical protein; Provisional
 1-86 1.73e-09

hypothetical protein; Provisional


Pssm-ID: 178677 [Multi-domain]  Cd Length: 705  Bit Score: 59.41  E-value: 1.73e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763     1 MGDR---ERNKKRLLELLRAPDtgNAHCADCGAADPDWASYKLGIFICLNCCGVHRNFpdISRVKSVRLDFWDDSIVEFM 77
Cdd:PLN03131   1 MGSRkeeERNEKIIRGLMKLPP--NRRCINCNSLGPQFVCTNFWTFICMTCSGIHREF--THRVKSVSMSKFTSQDVEAL 76


                 ....*....
gi 8923763    78 IHNGNLRVK 86
Cdd:PLN03131  77 QNGGNQRAR 85
PH1_PLEKHH1_PLEKHH2 cd13282
Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) members 1 and 2 ...
 258-361 2.75e-09

Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) members 1 and 2 (PLEKHH1) PH domain, repeat 1; PLEKHH1 and PLEKHH2 (also called PLEKHH1L) are thought to function in phospholipid binding and signal transduction. There are 3 Human PLEKHH genes: PLEKHH1, PLEKHH2, and PLEKHH3. There are many isoforms, the longest of which contain a FERM domain, a MyTH4 domain, two PH domains, a peroximal domain, a vacuolar domain, and a coiled coil stretch. The FERM domain has a cloverleaf tripart structure (FERM_N, FERM_M, FERM_C/N, alpha-, and C-lobe/A-lobe, B-lobe, C-lobe/F1, F2, F3). The C-lobe/F3 within the FERM domain is part of the PH domain family. 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: 241436  Cd Length: 96  Bit Score: 53.84  E-value: 2.75e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763  258 KQGFMEKTGPKQKEpFKKRWFALdcHERRLLYYKNPLDafeqgqvfLGNKEQGYEAYEDLPKGIRGNRwKAGLTIVTPER 337
Cdd:cd13282   1 KAGYLTKLGGKVKT-WKRRWFVL--KNGELFYYKSPND--------VIRKPQGQIALDGSCEIARAEG-AQTFEIVTEKR 68

                        90       100
                ....*....|....*....|....
gi 8923763  338 RFVLTCPSEKEQQEWLESLRGVLS 361
Cdd:cd13282  69 TYYLTADSENDLDEWIRVIQNVLR 92
ArfGap_AGFG2 cd17903
ArfGAP domain of AGFG2 (ArfGAP domain and FG repeat-containing protein 2); The ArfGAP domain ...
 9-122 2.60e-08

ArfGAP domain of AGFG2 (ArfGAP domain and FG repeat-containing protein 2); The ArfGAP domain and FG repeat-containing proteins (AFGF) subfamily of Arf GTPase-activating proteins consists of the two structurally-related members: AGFG1 and AGFG2. AGFG2 is a member of the HIV-1 Rev binding protein (HRB) family and contains one Arf-GAP zinc finger domain, several Phe-Gly (FG) motifs, and four Asn-Pro-Phe (NPF) motifs. AGFG2 interacts with Eps15 homology (EH) domains and plays a role in the Rev export pathway, which mediates the nucleocytoplasmic transfer of proteins and RNAs. In humans, the presence of the FG repeat motifs (11 in AGFG1 and 7 in AGFG2) are thought to be required for these proteins to act as HIV-1 Rev cofactors. Hence, AGFG promotes movement of Rev-responsive element-containing RNAs from the nuclear periphery to the cytoplasm, which is an essential step for HIV-1 replication.


Pssm-ID: 350090 [Multi-domain]  Cd Length: 116  Bit Score: 51.53  E-value: 2.60e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763    9 KRLLELLRAPdTGNAHCADCGAADPDWASYKLGIFICLNCCGVHRNFPDISRVKSVRLDFWDDSIVEFMIHNGNLRVK-- 86
Cdd:cd17903   2 RRVRELGGCS-AANRHCFECAQRGVTYVDITVGSFVCTTCSGLLRGLNPPHRVKSISMTTFTEPEVLFLQARGNEVCRki 80

                        90       100       110
                ....*....|....*....|....*....|....*...
gi 8923763   87 --AKFEARVPAfyyIPQANDCLVLKEqWIRAKYERREF 122
Cdd:cd17903  81 wlGLFDARTSL---IPDSRDPQKVKE-FLQEKYEKKRW 114
PH_Ses cd13288
Sesquipedalian family Pleckstrin homology (PH) domain; The sesquipedalian family has 2 ...
 132-243 2.89e-08

Sesquipedalian family Pleckstrin homology (PH) domain; The sesquipedalian family has 2 mammalian members: Ses1 and Ses2, which are also callled 7 kDa inositol polyphosphate phosphatase-interacting protein 1 and 2. They play a role in endocytic trafficking and are required for receptor recycling from endosomes, both to the trans-Golgi network and the plasma membrane. Members of this family form homodimers and heterodimers. Sesquipedalian interacts with inositol polyphosphate 5-phosphatase OCRL-1 (INPP5F) also known as Lowe oculocerebrorenal syndrome protein, a phosphatase enzyme that is involved in actin polymerization and is found in the trans-Golgi network and INPP5B. Sesquipedalian contains a single PH 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: 270105 [Multi-domain]  Cd Length: 120  Bit Score: 51.47  E-value: 2.89e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763  132 PGNREGFLWKRGRDNSQFLRRKFVLlaREGLLKYFTKEQGKSPKAVISIKdlNATFQTEKIGHPHGLQITYRRDGhTRNL 211
Cdd:cd13288   7 PVDKEGYLWKKGERNTSYQKRWFVL--KGNLLFYFEKKGDREPLGVIVLE--GCTVELAEDAEPYAFAIRFDGPG-ARSY 81

                        90       100       110
                ....*....|....*....|....*....|..
gi 8923763  212 FVYHESGKEIVDWFNALRAARLQYLKMAFPEL 243
Cdd:cd13288  82 VLAAENQEDMESWMKALSRASYDYLRLTVEEL 113
PLN03119 PLN03119
putative ADP-ribosylation factor GTPase-activating protein AGD14; Provisional
 3-86 3.96e-08

putative ADP-ribosylation factor GTPase-activating protein AGD14; Provisional


Pssm-ID: 178666  Cd Length: 648  Bit Score: 55.24  E-value: 3.96e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763     3 DRERNKKRLLELLRAPDtgNAHCADCGAADPDWASYKLGIFICLNCCGVHRNFpdISRVKSVRLDFWDDSIVEFMIHNGN 82
Cdd:PLN03119   6 EEERNEKIIRGLMKLPP--NRRCINCNSLGPQYVCTTFWTFVCMACSGIHREF--THRVKSVSMSKFTSKEVEVLQNGGN 81


                 ....
gi 8923763    83 LRVK 86
Cdd:PLN03119  82 QRAR 85
PH_TBC1D2A cd01265
TBC1 domain family member 2A pleckstrin homology (PH) domain; TBC1D2A (also called PARIS-1 ...
 256-356 4.88e-08

TBC1 domain family member 2A pleckstrin homology (PH) domain; TBC1D2A (also called PARIS-1/Prostate antigen recognized and identified by SEREX 1 and ARMUS) contains a PH domain and a TBC-type GTPase catalytic domain. TBC1D2A integrates signaling between Arf6, Rac1, and Rab7 during junction disassembly. Activated Rac1 recruits TBC1D2A to locally inactivate Rab7 via its C-terminal TBC/RabGAP domain and facilitate E-cadherin degradation in lysosomes. The TBC1D2A PH domain mediates localization at cell-cell contacts and coprecipitates with cadherin complexes. 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: 269966  Cd Length: 102  Bit Score: 50.40  E-value: 4.88e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763  256 YLkqGFMEKTGPKQKEpFKKRWFALDchERR--LLYYKNPLDAFEQGQVFLGNKEQGYEAyeDLPKGIrgnrwkagLTIV 333
Cdd:cd01265   5 YL--NKLETRGLGLKG-WKRRWFVLD--ESKcqLYYYRSPQDATPLGSIDLSGAAFSYDP--EAEPGQ--------FEIH 69

                        90       100
                ....*....|....*....|...
gi 8923763  334 TPERRFVLTCPSEKEQQEWLESL 356
Cdd:cd01265  70 TPGRVHILKASTRQAMLYWLQAL 92
PH_3BP2 cd13308
SH3 domain-binding protein 2 Pleckstrin homology (PH) domain; SH3BP2 (the gene that encodes ...
 252-357 2.78e-07

SH3 domain-binding protein 2 Pleckstrin homology (PH) domain; SH3BP2 (the gene that encodes the adaptor protein 3BP2), HD, ITU, IT10C3, and ADD1 are located near the Huntington's Disease Gene on Human Chromosome 4pl6.3. SH3BP2 lies in a region that is often missing in individuals with Wolf-Hirschhorn syndrome (WHS). Gain of function mutations in SH3BP2 causes enhanced B-cell antigen receptor (BCR)-mediated activation of nuclear factor of activated T cells (NFAT), resulting in a rare, genetic disorder called cherubism. This results in an increase in the signaling complex formation with Syk, phospholipase C-gamma2 (PLC-gamma2), and Vav1. It was recently discovered that Tankyrase regulates 3BP2 stability through ADP-ribosylation and ubiquitylation by the E3-ubiquitin ligase. Cherubism mutations uncouple 3BP2 from Tankyrase-mediated protein destruction, which results in its stabilization and subsequent hyperactivation of the Src, Syk, and Vav signaling pathways. SH3BP2 is also a potential negative regulator of the abl oncogene. 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: 270118  Cd Length: 113  Bit Score: 48.56  E-value: 2.78e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763  252 LTRNYLKQGFMEKTG--PKQKEPFKKRWFALdcHERRLLYYKNPLDAFEQGQVFLgnkeQGYEAyedLPKGIRGNRWKAG 329
Cdd:cd13308   5 LPRDVIHSGTLTKKGgsQKTLQNWQLRYVII--HQGCVYYYKNDQSAKPKGVFSL----NGYNR---RAAEERTSKLKFV 75

                        90       100       110
                ....*....|....*....|....*....|.
gi 8923763  330 LTIVTP---ERRFVLTCPSEKEQQEWLESLR 357
Cdd:cd13308  76 FKIIHLspdHRTWYFAAKSEDEMSEWMEYIR 106
ArfGap_AGFG1 cd08857
ArfGAP domain of AGFG1 (ArfGAP domain and FG repeat-containing protein 1); The ArfGAP domain ...
 9-122 3.26e-07

ArfGAP domain of AGFG1 (ArfGAP domain and FG repeat-containing protein 1); The ArfGAP domain and FG repeat-containing proteins (AFGF) subfamily of Arf GTPase-activating proteins consists of the two structurally-related members: AGFG1 and AGFG2. AGFG1 (alias: HIV-1 Rev binding protein, HRB; Rev interacting protein, RIP; Rev/Rex activating domain-binding protein, RAB) and AGFG2 are involved in the maintenance and spread of immunodeficiency virus type 1 (HIV-1) infection. The ArfGAP domain of AGFG1 is related to nucleoporins, which is a class of proteins that mediate nucleocytoplasmic transport. AGFG1 plays a role in the Rev export pathway, which mediates the nucleocytoplasmic transfer of proteins and RNAs, possibly together by the nuclear export receptor CRM1. In humans, the presence of the FG repeat motifs (11 in AGFG1 and 7 in AGFG2) are thought to be required for these proteins to act as HIV-1 Rev cofactors. Hence, AGFG1 promotes movement of Rev-responsive element-containing RNAs from the nuclear periphery to the cytoplasm, which is an essential step for HIV-1 replication.


Pssm-ID: 350082 [Multi-domain]  Cd Length: 116  Bit Score: 48.50  E-value: 3.26e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763    9 KRLLELLRAPDtgNAHCADCGAADPDWASYKLGIFICLNCCGVHRNFPDISRVKSVRLDFWDDSIVEFMIHNGNLRVK-- 86
Cdd:cd08857   3 KMLREMTSLPH--NRKCFDCDQRGPTYANMTVGSFVCTSCSGILRGLNPPHRVKSISMTTFTQQEIEFLQKHGNEVCKqi 80

                        90       100       110
                ....*....|....*....|....*....|....*...
gi 8923763   87 --AKFEARVPAfyyIPQANDCLVLKEqWIRAKYERREF 122
Cdd:cd08857  81 wlGLFDDRSSA---IPDFRDPQKVKE-FLQEKYEKKRW 114
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 135-231 1.46e-06

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 46.40  E-value: 1.46e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763    135 REGFLWKRGRDNSQFLRRKFVLLAREGLLkYFTKE---QGKSPKAVISIKDL--NATFQTEKIGHPHGLQITYRRDGHTR 209
Cdd:pfam00169   3 KEGWLLKKGGGKKKSWKKRYFVLFDGSLL-YYKDDksgKSKEPKGSISLSGCevVEVVASDSPKRKFCFELRTGERTGKR 81

                          90       100
                  ....*....|....*....|..
gi 8923763    210 NLFVYHESGKEIVDWFNALRAA 231
Cdd:pfam00169  82 TYLLQAESEEERKDWIKAIQSA 103
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 135-231 1.83e-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: 46.00  E-value: 1.83e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763     135 REGFLWKRGRD-NSQFLRRKFVLlaREGLLKYFTKEQ---GKSPKAVISIKDLNATFQTE--KIGHPHGLQITYrrdGHT 208
Cdd:smart00233   3 KEGWLYKKSGGgKKSWKKRYFVL--FNSTLLYYKSKKdkkSYKPKGSIDLSGCTVREAPDpdSSKKPHCFEIKT---SDR 77

                           90       100
                   ....*....|....*....|...
gi 8923763     209 RNLFVYHESGKEIVDWFNALRAA 231
Cdd:smart00233  78 KTLLLQAESEEEREKWVEALRKA 100
PH2_MyoX cd13296
Myosin X Pleckstrin homology (PH) domain, repeat 2; MyoX, a MyTH-FERM myosin, is a molecular ...
 258-362 1.59e-05

Myosin X Pleckstrin homology (PH) domain, repeat 2; MyoX, a MyTH-FERM myosin, is a molecular motor that has crucial functions in the transport and/or tethering of integrins in the actin-based extensions known as filopodia, microtubule binding, and in netrin-mediated axon guidance. It functions as a dimer. MyoX walks on bundles of actin, rather than single filaments, unlike the other unconventional myosins. MyoX is present in organisms ranging from humans to choanoflagellates, but not in Drosophila and Caenorhabditis elegans.MyoX consists of a N-terminal motor/head region, a neck made of 3 IQ motifs, and a tail consisting of a coiled-coil domain, a PEST region, 3 PH domains, a myosin tail homology 4 (MyTH4), and a FERM domain at its very C-terminus. The first PH domain in the MyoX tail is a split-PH domain, interupted by the second PH domain such that PH 1a and PH 1b flanks PH 2. The third PH domain (PH 3) follows the PH 1b domain. This cd contains the second 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: 270108  Cd Length: 103  Bit Score: 43.22  E-value: 1.59e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763  258 KQGF-MEKTGPK---QKEPFKKRWFALdcHERRLLYYKNPLDafeqgqvflGNKEQGY----EAYEDLPKGIRGNRwkag 329
Cdd:cd13296   1 KSGWlTKKGGGSstlSRRNWKSRWFVL--RDTVLKYYENDQE---------GEKLLGTidirSAKEIVDNDPKENR---- 65

                        90       100       110
                ....*....|....*....|....*....|...
gi 8923763  330 LTIVTPERRFVLTCPSEKEQQEWLESLRGVLSS 362
Cdd:cd13296  66 LSITTEERTYHLVAESPEDASQWVNVLTRVISA 98
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
 135-228 2.40e-05

Pleckstrin homology (PH) 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: 275388 [Multi-domain]  Cd Length: 92  Bit Score: 42.53  E-value: 2.40e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763  135 REGFLWKRGRD-NSQFLRRKFVLlaREGLLKYF--TKEQGKSPKAVISIKDLNATFQTEKIGHPHGLQITYRRDghtRNL 211
Cdd:cd00821   1 KEGYLLKRGGGgLKSWKKRWFVL--FEGVLLYYksKKDSSYKPKGSIPLSGILEVEEVSPKERPHCFELVTPDG---RTY 75

                        90
                ....*....|....*..
gi 8923763  212 FVYHESGKEIVDWFNAL 228
Cdd:cd00821  76 YLQADSEEERQEWLKAL 92
PH1_PH_fungal cd13298
Fungal proteins Pleckstrin homology (PH) domain, repeat 1; The functions of these fungal ...
 137-230 2.73e-05

Fungal proteins Pleckstrin homology (PH) domain, repeat 1; The functions of these fungal proteins are unknown, but they all contain 2 PH domains. This cd represents 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: 270110  Cd Length: 106  Bit Score: 42.61  E-value: 2.73e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763  137 GFLWKRGRDNSQFLRRKFVLlaREGLLKYFTKEQGKSPKAVISIKDLNATFQTEKIGHPHGLQITyrrdGHTRNLFVYHE 216
Cdd:cd13298  10 GYLLKRSRKTKNWKKRWVVL--RPCQLSYYKDEKEYKLRRVINLSELLAVAPLKDKKRKNVFGIY----TPSKNLHFRAT 83

                        90
                ....*....|....
gi 8923763  217 SGKEIVDWFNALRA 230
Cdd:cd13298  84 SEKDANEWVEALRE 97
PH1_ARAP cd13253
ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, ...
 257-362 3.28e-05

ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, repeat 1; ARAP proteins (also called centaurin delta) are phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating proteins that modulate actin cytoskeleton remodeling by regulating ARF and RHO family members. They bind phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4,5)P2) binding. There are 3 mammalian ARAP proteins: ARAP1, ARAP2, and ARAP3. All ARAP proteins contain a N-terminal SAM (sterile alpha motif) domain, 5 PH domains, an ArfGAP domain, 2 ankyrin domain, A RhoGap domain, and a Ras-associating domain. This hierarchy contains the first PH domain in ARAP. 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: 270073  Cd Length: 94  Bit Score: 42.37  E-value: 3.28e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763  257 LKQGFMEKTGPKQKE-PFKKRWFALDchERRLLYYKNPLDAFEQGQVFLgnkeqgyeAYEDLPKGIRGNRWKagltIVTP 335
Cdd:cd13253   1 IKSGYLDKQGGQGNNkGFQKRWVVFD--GLSLRYFDSEKDAYSKRIIPL--------SAISTVRAVGDNKFE----LVTT 66

                        90       100
                ....*....|....*....|....*..
gi 8923763  336 ERRFVLTCPSEKEQQEWLESLRGVLSS 362
Cdd:cd13253  67 NRTFVFRAESDDERNLWCSTLQAAISE 93
PH_TAAP2-like cd13255
Tandem PH-domain-containing protein 2 Pleckstrin homology (PH) domain; The binding of TAPP2 ...
 257-356 4.37e-05

Tandem PH-domain-containing protein 2 Pleckstrin homology (PH) domain; The binding of TAPP2 (also called PLEKHA2) adaptors to PtdIns(3,4)P(2), but not PI(3,4, 5)P3, function as negative regulators of insulin and PI3K signalling pathways (i.e. TAPP/utrophin/syntrophin complex). TAPP2 contains two sequential PH domains in which the C-terminal PH domain specifically binds PtdIns(3,4)P2 with high affinity. The N-terminal PH domain does not interact with any phosphoinositide tested. They also contain a C-terminal PDZ-binding motif that interacts with several PDZ-binding proteins, including PTPN13 (known previously as PTPL1 or FAP-1) as well as the scaffolding proteins MUPP1 (multiple PDZ-domain-containing protein 1), syntrophin and utrophin. The members here are most sequence similar to TAPP2 proteins, but may not be actual TAPP2 proteins. 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: 270075  Cd Length: 110  Bit Score: 42.40  E-value: 4.37e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763  257 LKQGFMEKTGPKQKEpFKKRWFALdcHERRLLYYKNpldafeqgqvflgNKEqgYEAYEDLPKG-------IRGNRWKAG 329
Cdd:cd13255   7 LKAGYLEKKGERRKT-WKKRWFVL--RPTKLAYYKN-------------DKE--YRLLRLIDLTdihtcteVQLKKHDNT 68

                        90       100
                ....*....|....*....|....*..
gi 8923763  330 LTIVTPERRFVLTCPSEKEQQEWLESL 356
Cdd:cd13255  69 FGIVTPARTFYVQADSKAEMESWISAI 95
PH_SWAP-70 cd13273
Switch-associated protein-70 Pleckstrin homology (PH) domain; SWAP-70 (also called ...
 251-357 8.82e-05

Switch-associated protein-70 Pleckstrin homology (PH) domain; SWAP-70 (also called Differentially expressed in FDCP 6/DEF-6 or IRF4-binding protein) functions in cellular signal transduction pathways (in conjunction with Rac), regulates cell motility through actin rearrangement, and contributes to the transformation and invasion activity of mouse embryo fibroblasts. Metazoan SWAP-70 is found in B lymphocytes, mast cells, and in a variety of organs. Metazoan SWAP-70 contains an N-terminal EF-hand motif, a centrally located PH domain, and a C-terminal coiled-coil domain. The PH domain of Metazoan SWAP-70 contains a phosphoinositide-binding site and a nuclear localization signal (NLS), which localize SWAP-70 to the plasma membrane and nucleus, respectively. The NLS is a sequence of four Lys residues located at the N-terminus of the C-terminal a-helix; this is a unique characteristic of the Metazoan SWAP-70 PH domain. The SWAP-70 PH domain binds PtdIns(3,4,5)P3 and PtdIns(4,5)P2 embedded in lipid bilayer vesicles. There are additional plant SWAP70 proteins, but these are not included in this hierarchy. Rice SWAP70 (OsSWAP70) exhibits GEF activity toward the its Rho GTPase, OsRac1, and regulates chitin-induced production of reactive oxygen species and defense gene expression in rice. Arabidopsis SWAP70 (AtSWAP70) plays a role in both PAMP- and effector-triggered immunity. Plant SWAP70 contains both DH and PH domains, but their arrangement is the reverse of that in typical DH-PH-type Rho GEFs, wherein the DH domain is flanked by a C-terminal PH 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: 270092  Cd Length: 110  Bit Score: 41.51  E-value: 8.82e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763  251 FLTRNYLKQGFMEKTGPKQKEpFKKRWFALDCHErrLLYYKNPLDAFEQGQVFLgnkeQGYEAYEDLPKGIRGNRWkagL 330
Cdd:cd13273   3 ELILDVIKKGYLWKKGHLLPT-WTERWFVLKPNS--LSYYKSEDLKEKKGEIAL----DSNCCVESLPDREGKKCR---F 72

                        90       100
                ....*....|....*....|....*..
gi 8923763  331 TIVTPERRFVLTCPSEKEQQEWLESLR 357
Cdd:cd13273  73 LVKTPDKTYELSASDHKTRQEWIAAIQ 99
PH_RasGRF1_2 cd13261
Ras-specific guanine nucleotide-releasing factors 1 and 2 Pleckstrin homology (PH) domain; ...
 133-231 1.36e-04

Ras-specific guanine nucleotide-releasing factors 1 and 2 Pleckstrin homology (PH) domain; RasGRF1 (also called GRF1; CDC25Mm/Ras-specific nucleotide exchange factor CDC25; GNRP/Guanine nucleotide-releasing protein) and RasGRF2 (also called GRF2; Ras guanine nucleotide exchange factor 2) are a family of guanine nucleotide exchange factors (GEFs). They both promote the exchange of Ras-bound GDP by GTP, thereby regulating the RAS signaling pathway. RasGRF1 and RasGRF2 form homooligomers and heterooligomers. GRF1 has 3 isoforms and GRF2 has 2 isoforms. The longest isoforms of RasGRF1 and RasGRF2 contain the following domains: a Rho-GEF domain sandwiched between 2 PH domains, IQ domains, a REM (Ras exchanger motif) domain, and a Ras-GEF domainwhich gives them the capacity to activate both Ras and Rac GTPases in response to signals from a variety of neurotransmitter receptors. Their IQ domains allow them to act as calcium sensors to mediate the actions of NMDA-type and calcium-permeable AMPA-type glutamate receptors. GRF1 also mediates the action of dopamine receptors that signal through cAMP. GRF1 and GRF2 play strikingly different roles in regulating MAP kinase family members, neuronal synaptic plasticity, specific forms of learning and memory, and behavioral responses to psychoactive drugs. 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: 270081  Cd Length: 136  Bit Score: 41.64  E-value: 1.36e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763  133 GNREGFLWKRGRDNSQFLRRKFVLLarEGLLKYFTKEQGKSPKAVI---------SIKDLNATFQTEKIGHPHGLQITYR 203
Cdd:cd13261   5 GTKRGYLSKKTSDSGKWHERWFALY--QNLLFYFENESSSRPSGLYllegcycerLPTPKGALKGKDHLEKQHYFTISFR 82

                        90       100
                ....*....|....*....|....*...
gi 8923763  204 RDGHtRNLFVYHESGKEIVDWFNALRAA 231
Cdd:cd13261  83 HENQ-RQYELRAETESDCDEWVEAIKQA 109
PH_PHLDB1_2 cd14673
Pleckstrin homology-like domain-containing family B member 2 pleckstrin homology (PH) domain; ...
 259-354 1.56e-04

Pleckstrin homology-like domain-containing family B member 2 pleckstrin homology (PH) domain; PHLDB2 (also called LL5beta) and PHLDB1 (also called LL5alpha) are cytoskeleton- and membrane-associated proteins. PHLDB2 has been identified as a key component of the synaptic podosomes that play an important role in in postsynaptic maturation. Both are large proteins containing an N-terminal pleckstrin (PH) 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: 270192  Cd Length: 105  Bit Score: 40.64  E-value: 1.56e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763  259 QGFMEKTGPKQKEpFKKRWFALDCHERRLLYYKNPLDAFEQGQVFLGNKEQGYeaYEDLPKGIRGNRWKAGLTIVTPERR 338
Cdd:cd14673   6 RGFLTKMGGKIKT-WKKRWFVFDRNKRTLSYYVDKHEKKLKGVIYFQAIEEVY--YDHLRSAAKSPNPALTFCVKTHDRL 82

                        90
                ....*....|....*.
gi 8923763  339 FVLTCPSEKEQQEWLE 354
Cdd:cd14673  83 YYMVAPSPEAMRIWMD 98
PH_alsin cd13269
Alsin Pleckstrin homology (PH) domain; The ALS2 gene encodes alsin, a GEF, that has dual ...
 329-365 1.80e-04

Alsin Pleckstrin homology (PH) domain; The ALS2 gene encodes alsin, a GEF, that has dual specificity for Rac1 and Rab5 GTPases. Alsin mutations in the form of truncated proteins are responsible for motor function disorders including juvenile-onset amyotrophic lateral sclerosis, familial juvenile primary lateral sclerosis, and infantile-onset ascending hereditary spastic paralysis. The alsin protein is widely expressed in the developing CNS including neurons of the cerebral cortex, brain stem, spinal cord, and cerebellum. Alsin contains a regulator of chromosome condensation 1 (RCC1) domain, a Rho guanine nucleotide exchanging factor (RhoGEF) domain, a PH domain, a Membrane Occupation and Recognition Nexus (MORN), a vacuolar protein sorting 9 (Vps9) domain, and a Dbl homology (DH) domain. Alsin interacts with Rab5 through its Vps9 domain and through this interaction modulates early endosome fusion and trafficking. The GEF activity of alsin towards Rab5 is regulated by Rac1 function. The GEF activity of alsin for Rac1 occurs via its DH domain and this interaction plays a role in promoting spinal motor neuron survival via multiple Rac-dependent signaling pathways. 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: 241423  Cd Length: 106  Bit Score: 40.45  E-value: 1.80e-04
                        10        20        30
                ....*....|....*....|....*....|....*..
gi 8923763  329 GLTIVTPERRFVLTCPSEKEQQEWLESLRGVLSSPLT 365
Cdd:cd13269  69 ALKITTPEESFTLVASTPQEKAEWLRAINQAIDQALN 105
PH_AtPH1 cd13276
Arabidopsis thaliana Pleckstrin homolog (PH) 1 (AtPH1) PH domain; AtPH1 is expressed in all ...
 135-228 3.98e-04

Arabidopsis thaliana Pleckstrin homolog (PH) 1 (AtPH1) PH domain; AtPH1 is expressed in all plant tissue and is proposed to be the plant homolog of human pleckstrin. Pleckstrin consists of two PH domains separated by a linker region, while AtPH has a single PH domain with a short N-terminal extension. AtPH1 binds PtdIns3P specifically and is thought to be an adaptor molecule since it has no obvious catalytic functions. 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: 270095  Cd Length: 106  Bit Score: 39.61  E-value: 3.98e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763  135 REGFLWKRGRDNSQFLRRKFVLlaREGLLKYFTKE---QGKSPKAVISIKD-LNATFQTEKIGHPHGLQItyrrDGHTRN 210
Cdd:cd13276   1 KAGWLEKQGEFIKTWRRRWFVL--KQGKLFWFKEPdvtPYSKPRGVIDLSKcLTVKSAEDATNKENAFEL----STPEET 74

                        90
                ....*....|....*...
gi 8923763  211 LFVYHESGKEIVDWFNAL 228
Cdd:cd13276  75 FYFIADNEKEKEEWIGAI 92
PH_RhoGap25-like cd13263
Rho GTPase activating protein 25 and related proteins Pleckstrin homology (PH) domain; ...
 257-364 6.18e-04

Rho GTPase activating protein 25 and related proteins Pleckstrin homology (PH) domain; RhoGAP25 (also called ArhGap25) like other RhoGaps are involved in cell polarity, cell morphology and cytoskeletal organization. They act as GTPase activators for the Rac-type GTPases by converting them to an inactive GDP-bound state and control actin remodeling by inactivating Rac downstream of Rho leading to suppress leading edge protrusion and promotes cell retraction to achieve cellular polarity and are able to suppress RAC1 and CDC42 activity in vitro. Overexpression of these proteins induces cell rounding with partial or complete disruption of actin stress fibers and formation of membrane ruffles, lamellipodia, and filopodia. This hierarchy contains RhoGAP22, RhoGAP24, and RhoGAP25. Members here contain an N-terminal PH domain followed by a RhoGAP domain and either a BAR or TATA Binding Protein (TBP) Associated Factor 4 (TAF4) 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: 270083  Cd Length: 114  Bit Score: 39.29  E-value: 6.18e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763  257 LKQGFMEKTGPKQKEpFKKRWFALDCHErrLLYYKNPLDAFEQGQVFL-GNK---------EQGYEAYEDLPKGirgnrw 326
Cdd:cd13263   4 IKSGWLKKQGSIVKN-WQQRWFVLRGDQ--LYYYKDEDDTKPQGTIPLpGNKvkevpfnpeEPGKFLFEIIPGG------ 74

                        90       100       110
                ....*....|....*....|....*....|....*....
gi 8923763  327 kaGLTIVTPERR-FVLTCPSEKEQQEWLESLRGVLSSPL 364
Cdd:cd13263  75 --GGDRMTSNHDsYLLMANSQAEMEEWVKVIRRVIGSPF 111
PH_PEPP1_2_3 cd13248
Phosphoinositol 3-phosphate binding proteins 1, 2, and 3 pleckstrin homology (PH) domain; ...
 258-357 8.92e-04

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: 38.41  E-value: 8.92e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763  258 KQGFMEK---TGPKQkepFKKRWFALdcHERRLLYYKNPLDAFEQGQVFLgnkeQGYEAYEDLPKGiRGNRwKAGLTIVT 334
Cdd:cd13248   9 MSGWLHKqggSGLKN---WRKRWFVL--KDNCLYYYKDPEEEKALGSILL----PSYTISPAPPSD-EISR-KFAFKAEH 77

                        90       100
                ....*....|....*....|....
gi 8923763  335 PE-RRFVLTCPSEKEQQEWLESLR 357
Cdd:cd13248  78 ANmRTYYFAADTAEEMEQWMNAMS 101
PH_DAPP1 cd10573
Dual Adaptor for Phosphotyrosine and 3-Phosphoinositides Pleckstrin homology (PH) domain; ...
 133-230 9.12e-04

Dual Adaptor for Phosphotyrosine and 3-Phosphoinositides Pleckstrin homology (PH) domain; DAPP1 (also known as PHISH/3' phosphoinositide-interacting SH2 domain-containing protein or Bam32) plays a role in B-cell activation and has potential roles in T-cell and mast cell function. DAPP1 promotes B cell receptor (BCR) induced activation of Rho GTPases Rac1 and Cdc42, which feed into mitogen-activated protein kinases (MAPK) activation pathways and affect cytoskeletal rearrangement. DAPP1can also regulate BCR-induced activation of extracellular signal-regulated kinase (ERK), and c-jun NH2-terminal kinase (JNK). DAPP1 contains an N-terminal SH2 domain and a C-terminal pleckstrin homology (PH) domain with a single tyrosine phosphorylation site located centrally. DAPP1 binds strongly to both PtdIns(3,4,5)P3 and PtdIns(3,4)P2. The PH domain is essential for plasma membrane recruitment of PI3K upon cell activation. 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: 269977 [Multi-domain]  Cd Length: 96  Bit Score: 38.07  E-value: 9.12e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763  133 GNREGFLWKRGRDNSQFLRRKFVLLAREglLKYFTKEQGKSPKAVISIKDLNATFQTEKIGHPHGLQITYRrdghTRNLF 212
Cdd:cd10573   3 GSKEGYLTKLGGIVKNWKTRWFVLRRNE--LKYFKTRGDTKPIRVLDLRECSSVQRDYSQGKVNCFCLVFP----ERTFY 76

                        90
                ....*....|....*...
gi 8923763  213 VYHESGKEIVDWFNALRA 230
Cdd:cd10573  77 MYANTEEEADEWVKLLKW 94
PH_DGK_type2 cd13274
Type 2 Diacylglycerol kinase Pleckstrin homology (PH) domain; DGK (also called DAGK) catalyzes ...
 331-359 1.62e-03

Type 2 Diacylglycerol kinase Pleckstrin homology (PH) domain; DGK (also called DAGK) catalyzes the conversion of diacylglycerol (DAG) to phosphatidic acid (PA) utilizing ATP as a source of the phosphate. In non-stimulated cells, DGK activity is low and DAG is used for glycerophospholipid biosynthesis. Upon receptor activation of the phosphoinositide pathway, DGK activity increases which drives the conversion of DAG to PA. DGK acts as a switch by terminating the signalling of one lipid while simultaneously activating signalling by another. There are 9 mammalian DGK isoforms all with conserved catalytic domains and two cysteine rich domains. These are further classified into 5 groups according to the presence of additional functional domains and substrate specificity: Type 1 - DGK-alpha, DGK-beta, DGK-gamma - contain EF-hand motifs and a recoverin homology domain; Type 2 - DGK-delta, DGK-eta, and DGK-kappa- contain a pleckstrin homology domain, two cysteine-rich zinc finger-like structures, and a separated catalytic region; Type 3 - DGK-epsilon - has specificity for arachidonate-containing DAG; Type 4 - DGK-zeta, DGK-iota- contain a MARCKS homology domain, ankyrin repeats, a C-terminal nuclear localization signal, and a PDZ-binding motif; Type 5 - DGK-theta - contains a third cysteine-rich domain, a pleckstrin homology domain and a proline rich region. The type 2 DGKs are present as part of this Metazoan DGK hierarchy. They have a N-terminal PH domain, two cysteine rich domains, followed by bipartite catalytic domains, and a C-terminal SAM domain. Their catalytic domains and perhaps other DGK catalytic domains may function as two independent units in a coordinated fashion. They may also require other motifs for maximal activity because several DGK catalytic domains have very little DAG kinase activity when expressed as isolated subunits. 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: 270093  Cd Length: 97  Bit Score: 37.38  E-value: 1.62e-03
                        10        20
                ....*....|....*....|....*....
gi 8923763  331 TIVTPERRFVLTCPSEKEQQEWLESLRGV 359
Cdd:cd13274  62 TVITPFRKLILCAESRKEMEEWISALKTV 90
PH_PLEKHJ1 cd13258
Pleckstrin homology domain containing, family J member 1 Pleckstrin homology (PH) domain; ...
 266-358 2.41e-03

Pleckstrin homology domain containing, family J member 1 Pleckstrin homology (PH) domain; PLEKHJ1 (also called GNRPX2/Guanine nucleotide-releasing protein x ). It contains a single PH domain. Very little information is known about PLEKHJ1. PLEKHJ1 has been shown to interact with IKBKG (inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma) and KRT33B (keratin 33B). 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: 270078  Cd Length: 123  Bit Score: 37.69  E-value: 2.41e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763  266 GPKQKEPFKKRWFALDCHerrLLYYKNpLDAFEQGQ----VFLgnKEQGYEAYEDLPKGirgnrwKAGLTIV---TPERR 338
Cdd:cd13258  29 GPKKSEVFKERWFKLKGN---LLFYFR-TNEFGDCSepigAIV--LENCRVQMEEITEK------PFAFSIVfndEPEKK 96

                        90       100
                ....*....|....*....|
gi 8923763  339 FVLTCPSEKEQQEWLESLRG 358
Cdd:cd13258  97 YIFSCRSEEQCEQWIEALRQ 116
PH2_ARAP cd13254
ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, ...
 329-357 2.87e-03

ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, repeat 2; ARAP proteins (also called centaurin delta) are phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating proteins that modulate actin cytoskeleton remodeling by regulating ARF and RHO family members. They bind phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4,5)P2) binding. There are 3 mammalian ARAP proteins: ARAP1, ARAP2, and ARAP3. All ARAP proteins contain a N-terminal SAM (sterile alpha motif) domain, 5 PH domains, an ArfGAP domain, 2 ankyrin domain, A RhoGap domain, and a Ras-associating domain. This hierarchy contains the second PH domain in ARAP. 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: 270074  Cd Length: 90  Bit Score: 36.62  E-value: 2.87e-03
                        10        20
                ....*....|....*....|....*....
gi 8923763  329 GLTIVTPERRFVLTCPSEKEQQEWLESLR 357
Cdd:cd13254  62 SFDLTTPYRSFSFTAESEHEKQEWIEAVQ 90
PH_GAP1-like cd01244
RAS p21 protein activator (GTPase activating protein) family pleckstrin homology (PH) domain; ...
 135-231 3.28e-03

RAS p21 protein activator (GTPase activating protein) family pleckstrin homology (PH) domain; RASAL1, GAP1(m), GAP1(IP4BP), and CAPRI are all members of the GAP1 family of GTPase-activating proteins. They contain N-terminal SH2-SH3-SH2 domains, followed by two C2 domains, a PH domain, a RasGAP domain, and a BTK domain. With the notable exception of GAP1(m), they all possess an arginine finger-dependent GAP activity on the Ras-related protein Rap1. They act as a suppressor of RAS enhancing the weak intrinsic GTPase activity of RAS proteins resulting in the inactive GDP-bound form of RAS, allowing control of cellular proliferation and differentiation. PH domains share little sequence conservation, but all have a common fold, which is electrostatically polarized. 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: 269950  Cd Length: 107  Bit Score: 36.88  E-value: 3.28e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763  135 REGFLWKR--GRDN----SQFLRRKFVLLAREglLKYFtKEQGKSPKAVISIKDLNATFQTEK--IGHPHGLQITYRRdg 206
Cdd:cd01244   1 KEGYLIKRaqGRKKkfgrKNFKKRYFRLTNEA--LSYS-KSKGKQPLCSIPLEDILAVERVEEesFKMKNMFQIVQPD-- 75

                        90       100
                ....*....|....*....|....*
gi 8923763  207 htRNLFVYHESGKEIVDWFNALRAA 231
Cdd:cd01244  76 --RTLYLQAKNVVELNEWLSALRKV 98
PH_Sbf1_hMTMR5 cd01235
Set binding factor 1 (also called Human MTMR5) Pleckstrin Homology (PH) domain; Sbf1 is a ...
 136-195 3.90e-03

Set binding factor 1 (also called Human MTMR5) Pleckstrin Homology (PH) domain; Sbf1 is a myotubularin-related pseudo-phosphatase. Both Sbf1 and myotubularin interact with the SET domains of Hrx and other epigenetic regulatory proteins, but Sbf1 lacks phosphatase activity due to several amino acid changes in its structurally preserved catalytic pocket. It contains pleckstrin (PH), GEF, and myotubularin homology domains that are thought to be responsible for signaling and growth control. Sbf1 functions as an inhibitor of cellular growth. The N-terminal GEF homology domain serves to inhibit the transforming effects of Sbf1. 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: 269941  Cd Length: 106  Bit Score: 36.54  E-value: 3.90e-03
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 8923763  136 EGFLWKRGRDNSQFLRRKFVLLAREGLLKYFTKEQGKSPKAVISIKDLNA-TFQTEKIGHP 195
Cdd:cd01235   6 EGYLYKRGALLKGWKQRWFVLDSTKHQLRYYESREDTKCKGFIDLAEVESvTPATPIIGAP 66
PH3_MyoX-like cd13297
Myosin X-like Pleckstrin homology (PH) domain, repeat 3; MyoX, a MyTH-FERM myosin, is a ...
 260-362 4.10e-03

Myosin X-like Pleckstrin homology (PH) domain, repeat 3; MyoX, a MyTH-FERM myosin, is a molecular motor that has crucial functions in the transport and/or tethering of integrins in the actin-based extensions known as filopodia, microtubule binding, and in netrin-mediated axon guidance. It functions as a dimer. MyoX walks on bundles of actin, rather than single filaments, unlike the other unconventional myosins. MyoX is present in organisms ranging from humans to choanoflagellates, but not in Drosophila and Caenorhabditis elegans.MyoX consists of a N-terminal motor/head region, a neck made of 3 IQ motifs, and a tail consisting of a coiled-coil domain, a PEST region, 3 PH domains, a myosin tail homology 4 (MyTH4), and a FERM domain at its very C-terminus. The first PH domain in the MyoX tail is a split-PH domain, interupted by the second PH domain such that PH 1a and PH 1b flanks PH 2. The third PH domain (PH 3) follows the PH 1b domain. This cd contains the third MyoX PH repeat. PLEKHH3/Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) member 3 is also part of this CD and like MyoX contains a FERM domain, a MyTH4 domain, and a single PH domain. Not much is known about the function of PLEKHH3. 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: 270109  Cd Length: 126  Bit Score: 37.03  E-value: 4.10e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763  260 GFMEKTGPKQKE----PFKKRWFALDCHErrLLYYKNPL-DAFEQGQVFLGNKEQGYEAYEDLPKgiRGNRWKagLTIVT 334
Cdd:cd13297  17 GWLYKEGGKGGArgnlTKKKRWFVLTGNS--LDYYKSSEkNSLKLGTLVLNSLCSVVPPDEKMAK--ETGYWT--FTVHG 90

                        90       100
                ....*....|....*....|....*...
gi 8923763  335 PERRFVLTCPSEKEQQEWLESLRGVLSS 362
Cdd:cd13297  91 RKHSFRLYTKLQEEAMRWVNAIQDVIDS 118
PH_RASA1 cd13260
RAS p21 protein activator (GTPase activating protein) 1 Pleckstrin homology (PH) domain; RASA1 ...
 132-230 6.59e-03

RAS p21 protein activator (GTPase activating protein) 1 Pleckstrin homology (PH) domain; RASA1 (also called RasGap1 or p120) is a member of the RasGAP family of GTPase-activating proteins. RASA1 contains N-terminal SH2-SH3-SH2 domains, followed by two C2 domains, a PH domain, a RasGAP domain, and a BTK domain. Splice variants lack the N-terminal domains. It is a cytosolic vertebrate protein that acts as a suppressor of RAS via its C-terminal GAP domain function, enhancing the weak intrinsic GTPase activity of RAS proteins resulting in the inactive GDP-bound form of RAS, allowing control of cellular proliferation and differentiation. Additionally, it is involved in mitogenic signal transmission towards downstream interacting partners through its N-terminal SH2-SH3-SH2 domains. RASA1 interacts with a number of proteins including: G3BP1, SOCS3, ANXA6, Huntingtin, KHDRBS1, Src, EPHB3, EPH receptor B2, Insulin-like growth factor 1 receptor, PTK2B, DOK1, PDGFRB, HCK, Caveolin 2, DNAJA3, HRAS, GNB2L1 and NCK1. 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: 270080  Cd Length: 103  Bit Score: 35.78  E-value: 6.59e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763  132 PGNREGFLWKRGRDNSQFLRRKFVLLAREGLLKYFTKEQGKSPKAVIsikDLNATF----QTEKIGHPHGLQITYRRDGH 207
Cdd:cd13260   2 GIDKKGYLLKKGGKNKKWKNLYFVLEGKEQHLYFFDNEKRTKPKGLI---DLSYCSlypvHDSLFGRPNCFQIVVRALNE 78

                        90       100
                ....*....|....*....|...
gi 8923763  208 TRNLFVYHESGKEIVDWFNALRA 230
Cdd:cd13260  79 STITYLCADTAELAQEWMRALRA 101
PH_3BP2 cd13308
SH3 domain-binding protein 2 Pleckstrin homology (PH) domain; SH3BP2 (the gene that encodes ...
 135-229 6.84e-03

SH3 domain-binding protein 2 Pleckstrin homology (PH) domain; SH3BP2 (the gene that encodes the adaptor protein 3BP2), HD, ITU, IT10C3, and ADD1 are located near the Huntington's Disease Gene on Human Chromosome 4pl6.3. SH3BP2 lies in a region that is often missing in individuals with Wolf-Hirschhorn syndrome (WHS). Gain of function mutations in SH3BP2 causes enhanced B-cell antigen receptor (BCR)-mediated activation of nuclear factor of activated T cells (NFAT), resulting in a rare, genetic disorder called cherubism. This results in an increase in the signaling complex formation with Syk, phospholipase C-gamma2 (PLC-gamma2), and Vav1. It was recently discovered that Tankyrase regulates 3BP2 stability through ADP-ribosylation and ubiquitylation by the E3-ubiquitin ligase. Cherubism mutations uncouple 3BP2 from Tankyrase-mediated protein destruction, which results in its stabilization and subsequent hyperactivation of the Src, Syk, and Vav signaling pathways. SH3BP2 is also a potential negative regulator of the abl oncogene. 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: 270118  Cd Length: 113  Bit Score: 36.23  E-value: 6.84e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763  135 REGFLWKRGRDNSQFLR---RKFVLLarEGLLKYFTKEQGKSPKAVISIKDLNATFQTE---------KIGHPHGLQITY 202
Cdd:cd13308  11 HSGTLTKKGGSQKTLQNwqlRYVIIH--QGCVYYYKNDQSAKPKGVFSLNGYNRRAAEErtsklkfvfKIIHLSPDHRTW 88

                        90       100
                ....*....|....*....|....*..
gi 8923763  203 rrdghtrnlFVYHESGKEIVDWFNALR 229
Cdd:cd13308  89 ---------YFAAKSEDEMSEWMEYIR 106
PH_KIFIA_KIFIB cd01233
KIFIA and KIFIB protein pleckstrin homology (PH) domain; The kinesin-3 family motors KIFIA ...
 274-353 9.99e-03

KIFIA and KIFIB protein pleckstrin homology (PH) domain; The kinesin-3 family motors KIFIA (Caenorhabditis elegans homolog unc-104) and KIFIB transport synaptic vesicle precursors that contain synaptic vesicle proteins, such as synaptophysin, synaptotagmin and the small GTPase RAB3A, but they do not transport organelles that contain plasma membrane proteins. They have a N-terminal motor domain, followed by a coiled-coil domain, and a C-terminal PH domain. KIF1A adopts a monomeric form in vitro, but acts as a processive dimer in vivo. KIF1B has alternatively spliced isoforms distinguished by the presence or absence of insertion sequences in the conserved amino-terminal region of the protein; this results in their different motor activities. KIF1A and KIF1B bind to RAB3 proteins through the adaptor protein mitogen-activated protein kinase (MAPK) -activating death domain (MADD; also calledDENN), which was first identified as a RAB3 guanine nucleotide exchange factor (GEF). 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: 269939  Cd Length: 103  Bit Score: 35.26  E-value: 9.99e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923763  274 KKRWFALdcheRR--LLYYKNPLDAFEQGQVFLGNKEQGYEayEDLPKGIrGNRWKagLTIVTPERRFVLTCPSEKEQQE 351
Cdd:cd01233  23 VRRWVVL----RRpyLHIYSSEKDGDERGVINLSTARVEYS--PDQEALL-GRPNV--FAVYTPTNSYLLQARSEKEMQD 93


                ..
gi 8923763  352 WL 353
Cdd:cd01233  94 WL 95
 
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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