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Conserved domains on  [gi|1057503096|ref|NP_001317136|]
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growth factor receptor-bound protein 7 isoform c [Homo sapiens]

Protein Classification

GRB/APBB1IP family PH domain-containing protein; pleckstrin homology domain-containing family G protein( domain architecture ID 13006558)

GRB/APBB1IP family PH (pleckstrin homology) domain-containing protein similar to PH region of Homo sapiens amyloid beta A4 precursor protein-binding family B member 1-interacting protein (APBB1IP) and growth factor receptor-bound protein 10 (GRB10); pleckstrin homology (PH) domain-containing family G protein contains PH and RhoGEF domains, may function as a guanine nucleotide exchange factor; similar to Homo sapiens pleckstrin homology domain-containing family G member 1/2/3 (PLEKHG1/2/3) involved in the regulation of Rho protein signal transduction

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
PH_APBB1IP cd01259
Amyloid beta (A4) Precursor protein-Binding, family B, member 1 Interacting Protein pleckstrin ...
225-347 4.26e-63

Amyloid beta (A4) Precursor protein-Binding, family B, member 1 Interacting Protein pleckstrin homology (PH) domain; APBB1IP consists of a Ras-associated (RA) domain, a PH domain, a family-specific BPS region, and a C-terminal SH2 domain. Grb7, Grb10 and Grb14 are paralogs that are also present in this hierarchy. These adapter proteins bind a variety of receptor tyrosine kinases, including the insulin and insulin-like growth factor-1 (IGF1) receptors. Grb10 and Grb14 are important tissue-specific negative regulators of insulin and IGF1 signaling based and may contribute to type 2 (non-insulin-dependent) diabetes in humans. RA-PH function as a single structural unit and is dimerized via a helical extension of the PH domain. The PH domain here are proposed to bind phosphoinositides non-cannonically ahd are unlikely to bind an activated GTPase. The tandem RA-PH domains are present in a second adapter-protein family, MRL proteins, Caenorhabditis elegans protein MIG-1012, the mammalian proteins RIAM and lamellipodin and the Drosophila melanogaster protein Pico12, all of which are Ena/VASP-binding proteins involved in actin-cytoskeleton rearrangement. 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: 269961  Cd Length: 124  Bit Score: 199.77  E-value: 4.26e-63
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503096 225 NAGSFPEIQGFLQLRGSGRKLWKRFFCFLRRSGLYYSTKGTSKDPRHLQYVADVNESNVYVVTQGRKLYGMPTDFGFCVK 304
Cdd:cd01259     1 NSVSCPEIEGFLYLKEDGKKSWKKRYFVLRASGLYYSPKGKSKESRDLQCLAQFDDYNVYTGLNGKKKYKAPTDFGFCLK 80
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1057503096 305 PNKLR-NGHKGLRIFCSEDEQSRTCWLAAFRLFKYGVQLYKNYQ 347
Cdd:cd01259    81 PNKQQeKGSKDIKYLCAEDEQSRTCWLTAIRLAKYGKQLYENYR 124
RA_GRB7 cd16140
Ras-associating (RA) domain found in growth factor receptor-bound (Grb) protein 7; GRB7, also ...
100-187 1.17e-58

Ras-associating (RA) domain found in growth factor receptor-bound (Grb) protein 7; GRB7, also termed B47, or epidermal growth factor receptor GRB-7, or GRB7 adapter protein, is a signal-transducing cytoplasmic adaptor protein that is co-opted by numerous tyrosine kinases involved in various cellular signaling and functions. Grb7 and its related family members Grb10 and Grb14 share a conserved domain architecture that includes an amino-terminal proline-rich region, a central segment termed the GM region (for Grb and Mig) which includes the RA, PIR, and pleckstrin homology (PH) domains, and a carboxyl-terminal SH2 domain. The tandem RA and PH domains of Grb7/10/14 are also found in a second adaptor family, Rap1-interacting adaptor molecule (RIAM) and lamellipodin, which is involved in actin-cytoskeleton rearrangement. Grb7/10/14 family proteins are phosphorylated on serine/threonine as well as tyrosine residues and are mainly localized to the cytoplasm. Grb7 could interact with activated N-Ras in transfected cells.


:

Pssm-ID: 340557  Cd Length: 88  Bit Score: 186.98  E-value: 1.17e-58
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503096 100 RPHVVKVYSEDGACRSVEVAAGATARHVCEMLVQRAHALSDETWGLVECHPHLALERGLEDHESVVEVQAAWPVGGDSRF 179
Cdd:cd16140     1 GPHVVKVYSEDGTCRSLEVTAGATARHVCEMLVQRAHCLDDESWSLVELHPHLALERCLEDHESVVEVQATWPAGGDSRF 80

                  ....*...
gi 1057503096 180 VFRKNFAK 187
Cdd:cd16140    81 VFRKNFAK 88
BPS pfam08947
BPS (Between PH and SH2); The BPS (Between PH and SH2) domain, comprised of 2 beta strands and ...
365-410 2.38e-20

BPS (Between PH and SH2); The BPS (Between PH and SH2) domain, comprised of 2 beta strands and a C-terminal helix, is an approximately 45 residue region found in the adaptor proteins Grb7/10/14 that mediates inhibition of the tyrosine kinase domain of the insulin receptor by binding of the N-terminal portion of the BPS domain to the substrate peptide groove of the kinase, acting as a pseudosubstrate inhibitor.


:

Pssm-ID: 462644  Cd Length: 46  Bit Score: 83.79  E-value: 2.38e-20
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1057503096 365 RSASDNTLVAMDFSGHAGRVIENPREALSVALEEAQAWRKKTNHRL 410
Cdd:pfam08947   1 RSVSESSLVAMDFSGAGGRVIENPEEALSEAEEEGAAWRKKTLRRC 46
 
Name Accession Description Interval E-value
PH_APBB1IP cd01259
Amyloid beta (A4) Precursor protein-Binding, family B, member 1 Interacting Protein pleckstrin ...
225-347 4.26e-63

Amyloid beta (A4) Precursor protein-Binding, family B, member 1 Interacting Protein pleckstrin homology (PH) domain; APBB1IP consists of a Ras-associated (RA) domain, a PH domain, a family-specific BPS region, and a C-terminal SH2 domain. Grb7, Grb10 and Grb14 are paralogs that are also present in this hierarchy. These adapter proteins bind a variety of receptor tyrosine kinases, including the insulin and insulin-like growth factor-1 (IGF1) receptors. Grb10 and Grb14 are important tissue-specific negative regulators of insulin and IGF1 signaling based and may contribute to type 2 (non-insulin-dependent) diabetes in humans. RA-PH function as a single structural unit and is dimerized via a helical extension of the PH domain. The PH domain here are proposed to bind phosphoinositides non-cannonically ahd are unlikely to bind an activated GTPase. The tandem RA-PH domains are present in a second adapter-protein family, MRL proteins, Caenorhabditis elegans protein MIG-1012, the mammalian proteins RIAM and lamellipodin and the Drosophila melanogaster protein Pico12, all of which are Ena/VASP-binding proteins involved in actin-cytoskeleton rearrangement. 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: 269961  Cd Length: 124  Bit Score: 199.77  E-value: 4.26e-63
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503096 225 NAGSFPEIQGFLQLRGSGRKLWKRFFCFLRRSGLYYSTKGTSKDPRHLQYVADVNESNVYVVTQGRKLYGMPTDFGFCVK 304
Cdd:cd01259     1 NSVSCPEIEGFLYLKEDGKKSWKKRYFVLRASGLYYSPKGKSKESRDLQCLAQFDDYNVYTGLNGKKKYKAPTDFGFCLK 80
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1057503096 305 PNKLR-NGHKGLRIFCSEDEQSRTCWLAAFRLFKYGVQLYKNYQ 347
Cdd:cd01259    81 PNKQQeKGSKDIKYLCAEDEQSRTCWLTAIRLAKYGKQLYENYR 124
RA_GRB7 cd16140
Ras-associating (RA) domain found in growth factor receptor-bound (Grb) protein 7; GRB7, also ...
100-187 1.17e-58

Ras-associating (RA) domain found in growth factor receptor-bound (Grb) protein 7; GRB7, also termed B47, or epidermal growth factor receptor GRB-7, or GRB7 adapter protein, is a signal-transducing cytoplasmic adaptor protein that is co-opted by numerous tyrosine kinases involved in various cellular signaling and functions. Grb7 and its related family members Grb10 and Grb14 share a conserved domain architecture that includes an amino-terminal proline-rich region, a central segment termed the GM region (for Grb and Mig) which includes the RA, PIR, and pleckstrin homology (PH) domains, and a carboxyl-terminal SH2 domain. The tandem RA and PH domains of Grb7/10/14 are also found in a second adaptor family, Rap1-interacting adaptor molecule (RIAM) and lamellipodin, which is involved in actin-cytoskeleton rearrangement. Grb7/10/14 family proteins are phosphorylated on serine/threonine as well as tyrosine residues and are mainly localized to the cytoplasm. Grb7 could interact with activated N-Ras in transfected cells.


Pssm-ID: 340557  Cd Length: 88  Bit Score: 186.98  E-value: 1.17e-58
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503096 100 RPHVVKVYSEDGACRSVEVAAGATARHVCEMLVQRAHALSDETWGLVECHPHLALERGLEDHESVVEVQAAWPVGGDSRF 179
Cdd:cd16140     1 GPHVVKVYSEDGTCRSLEVTAGATARHVCEMLVQRAHCLDDESWSLVELHPHLALERCLEDHESVVEVQATWPAGGDSRF 80

                  ....*...
gi 1057503096 180 VFRKNFAK 187
Cdd:cd16140    81 VFRKNFAK 88
BPS pfam08947
BPS (Between PH and SH2); The BPS (Between PH and SH2) domain, comprised of 2 beta strands and ...
365-410 2.38e-20

BPS (Between PH and SH2); The BPS (Between PH and SH2) domain, comprised of 2 beta strands and a C-terminal helix, is an approximately 45 residue region found in the adaptor proteins Grb7/10/14 that mediates inhibition of the tyrosine kinase domain of the insulin receptor by binding of the N-terminal portion of the BPS domain to the substrate peptide groove of the kinase, acting as a pseudosubstrate inhibitor.


Pssm-ID: 462644  Cd Length: 46  Bit Score: 83.79  E-value: 2.38e-20
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1057503096 365 RSASDNTLVAMDFSGHAGRVIENPREALSVALEEAQAWRKKTNHRL 410
Cdd:pfam08947   1 RSVSESSLVAMDFSGAGGRVIENPEEALSEAEEEGAAWRKKTLRRC 46
RA smart00314
Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); ...
100-184 6.03e-20

Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); putative RasGTP effectors in other cases. Kalhammer et al. have shown that not all RA domains bind RasGTP. Predicted structure similar to that determined, and that of the RasGTP-binding domain of Raf kinase. Predicted RA domains in PLC210 and nore1 found to bind RasGTP. Included outliers (Grb7, Grb14, adenylyl cyclases etc.)


Pssm-ID: 214612  Cd Length: 90  Bit Score: 83.89  E-value: 6.03e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503096  100 RPHVVKVYSED---GACRSVEVAAGATARHVCEMLVQRAHALSD-ETWGLVECHPHlALERGLEDHESVVEVQAAWPVGG 175
Cdd:smart00314   1 DTFVLRVYVDDlpgGTYKTLRVSSRTTARDVIQQLLEKFHLTDDpEEYVLVEVLPD-GKERVLPDDENPLQLQKLWPRRG 79
                           90
                   ....*....|
gi 1057503096  176 DS-RFVFRKN 184
Cdd:smart00314  80 PNlRFVLRKR 89
RA pfam00788
Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); ...
101-184 2.43e-17

Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); putative RasGTP effectors in other cases. Recent evidence (not yet in MEDLINE) shows that some RA domains do NOT bind RasGTP. Predicted structure similar to that determined, and that of the RasGTP-binding domain of Raf kinase.


Pssm-ID: 425871  Cd Length: 93  Bit Score: 76.99  E-value: 2.43e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503096 101 PHVVKVYSEDGA----CRSVEVAAGATARHVCEMLVQRAH-ALSDETWGLVECHPHLALERGLEDHESVVEVQAAWPV-G 174
Cdd:pfam00788   2 DGVLKVYTEDGKpgttYKTILVSSSTTAEEVIEALLEKFGlEDDPRDYVLVEVLERGGGERRLPDDECPLQIQLQWPRdA 81
                          90
                  ....*....|
gi 1057503096 175 GDSRFVFRKN 184
Cdd:pfam00788  82 SDSRFLLRKR 91
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
230-334 9.54e-13

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: 64.11  E-value: 9.54e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503096  230 PEIQGFLQLRGS-GRKLWKRFFCFLRRSGLYYSTKGTSKDPRHLQYVADVNESNVYVVTQGRKlygMPTDFGFcvkpnKL 308
Cdd:smart00233   1 VIKEGWLYKKSGgGKKSWKKRYFVLFNSTLLYYKSKKDKKSYKPKGSIDLSGCTVREAPDPDS---SKKPHCF-----EI 72
                           90       100
                   ....*....|....*....|....*.
gi 1057503096  309 RNGHKGLRIFCSEDEQSRTCWLAAFR 334
Cdd:smart00233  73 KTSDRKTLLLQAESEEEREKWVEALR 98
PH pfam00169
PH domain; PH stands for pleckstrin homology.
230-338 2.54e-11

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 60.27  E-value: 2.54e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503096 230 PEIQGFLQLRGSGRKL-WKRFFCFLRRSGLYYSTKgtSKDPRHLQYVADVNESNVYVVTQGRKLYgMPTDFGFCVKPNKL 308
Cdd:pfam00169   1 VVKEGWLLKKGGGKKKsWKKRYFVLFDGSLLYYKD--DKSGKSKEPKGSISLSGCEVVEVVASDS-PKRKFCFELRTGER 77
                          90       100       110
                  ....*....|....*....|....*....|
gi 1057503096 309 RNGHKglRIFCSEDEQSRTCWLAAFRLFKY 338
Cdd:pfam00169  78 TGKRT--YLLQAESEEERKDWIKAIQSAIR 105
 
Name Accession Description Interval E-value
PH_APBB1IP cd01259
Amyloid beta (A4) Precursor protein-Binding, family B, member 1 Interacting Protein pleckstrin ...
225-347 4.26e-63

Amyloid beta (A4) Precursor protein-Binding, family B, member 1 Interacting Protein pleckstrin homology (PH) domain; APBB1IP consists of a Ras-associated (RA) domain, a PH domain, a family-specific BPS region, and a C-terminal SH2 domain. Grb7, Grb10 and Grb14 are paralogs that are also present in this hierarchy. These adapter proteins bind a variety of receptor tyrosine kinases, including the insulin and insulin-like growth factor-1 (IGF1) receptors. Grb10 and Grb14 are important tissue-specific negative regulators of insulin and IGF1 signaling based and may contribute to type 2 (non-insulin-dependent) diabetes in humans. RA-PH function as a single structural unit and is dimerized via a helical extension of the PH domain. The PH domain here are proposed to bind phosphoinositides non-cannonically ahd are unlikely to bind an activated GTPase. The tandem RA-PH domains are present in a second adapter-protein family, MRL proteins, Caenorhabditis elegans protein MIG-1012, the mammalian proteins RIAM and lamellipodin and the Drosophila melanogaster protein Pico12, all of which are Ena/VASP-binding proteins involved in actin-cytoskeleton rearrangement. 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: 269961  Cd Length: 124  Bit Score: 199.77  E-value: 4.26e-63
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503096 225 NAGSFPEIQGFLQLRGSGRKLWKRFFCFLRRSGLYYSTKGTSKDPRHLQYVADVNESNVYVVTQGRKLYGMPTDFGFCVK 304
Cdd:cd01259     1 NSVSCPEIEGFLYLKEDGKKSWKKRYFVLRASGLYYSPKGKSKESRDLQCLAQFDDYNVYTGLNGKKKYKAPTDFGFCLK 80
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1057503096 305 PNKLR-NGHKGLRIFCSEDEQSRTCWLAAFRLFKYGVQLYKNYQ 347
Cdd:cd01259    81 PNKQQeKGSKDIKYLCAEDEQSRTCWLTAIRLAKYGKQLYENYR 124
RA_GRB7 cd16140
Ras-associating (RA) domain found in growth factor receptor-bound (Grb) protein 7; GRB7, also ...
100-187 1.17e-58

Ras-associating (RA) domain found in growth factor receptor-bound (Grb) protein 7; GRB7, also termed B47, or epidermal growth factor receptor GRB-7, or GRB7 adapter protein, is a signal-transducing cytoplasmic adaptor protein that is co-opted by numerous tyrosine kinases involved in various cellular signaling and functions. Grb7 and its related family members Grb10 and Grb14 share a conserved domain architecture that includes an amino-terminal proline-rich region, a central segment termed the GM region (for Grb and Mig) which includes the RA, PIR, and pleckstrin homology (PH) domains, and a carboxyl-terminal SH2 domain. The tandem RA and PH domains of Grb7/10/14 are also found in a second adaptor family, Rap1-interacting adaptor molecule (RIAM) and lamellipodin, which is involved in actin-cytoskeleton rearrangement. Grb7/10/14 family proteins are phosphorylated on serine/threonine as well as tyrosine residues and are mainly localized to the cytoplasm. Grb7 could interact with activated N-Ras in transfected cells.


Pssm-ID: 340557  Cd Length: 88  Bit Score: 186.98  E-value: 1.17e-58
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503096 100 RPHVVKVYSEDGACRSVEVAAGATARHVCEMLVQRAHALSDETWGLVECHPHLALERGLEDHESVVEVQAAWPVGGDSRF 179
Cdd:cd16140     1 GPHVVKVYSEDGTCRSLEVTAGATARHVCEMLVQRAHCLDDESWSLVELHPHLALERCLEDHESVVEVQATWPAGGDSRF 80

                  ....*...
gi 1057503096 180 VFRKNFAK 187
Cdd:cd16140    81 VFRKNFAK 88
RA_GRB7_10_14 cd16124
Ras-associating (RA) domain found in growth factor receptor-bound (Grb) protein 7/10/14; The ...
101-185 1.09e-52

Ras-associating (RA) domain found in growth factor receptor-bound (Grb) protein 7/10/14; The RA domain is highly conserved among the members of the Grb proteins family which includes Grb7, Grb10 and Grb14. Grb7/10/14 are multi-domain cytoplasmic adaptor proteins that are recruited to activated receptor tyrosine kinases. RA domain has the beta-grasp ubiquitin-like fold with low sequence similarity to ubiquitin (Ub). Ub is a protein modifier in eukaryotes that is involved in various cellular processes including transcriptional regulation, cell cycle control, and DNA repair in eukaryotes. Grb7 and its related family members Grb10 and Grb14 share a conserved domain architecture that includes an amino-terminal proline-rich region, a central segment termed the GM region (for Grb and Mig) which includes the RA, PIR, and pleckstrin homology (PH) domains, and a carboxyl-terminal SH2 domain. The tandem RA and PH domains of Grb7/10/14 are also found in a second adaptor family, Rap1-interacting adaptor molecule (RIAM) and lamellipodin, which is involved in actin-cytoskeleton rearrangement. Grb7/10/14 family proteins are phosphorylated on serine/threonine as well as tyrosine residues and are mainly localized to the cytoplasm.


Pssm-ID: 340541  Cd Length: 85  Bit Score: 171.65  E-value: 1.09e-52
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503096 101 PHVVKVYSEDGACRSVEVAAGATARHVCEMLVQRAHALSDETWGLVECHPHLALERGLEDHESVVEVQAAWPVGGDSRFV 180
Cdd:cd16124     1 KQVVKVYSEDGTSRSVEVAADATARDVCQLLVQKAHALDDESWTLVEHHPHLGLERGLEDHELVVEVQSAWPVGGESKFV 80

                  ....*
gi 1057503096 181 FRKNF 185
Cdd:cd16124    81 FRKNY 85
RA_GRB10 cd16141
Ras-associating (RA) domain found in growth factor receptor-bound (Grb) protein 10; GRB10, ...
102-193 6.51e-35

Ras-associating (RA) domain found in growth factor receptor-bound (Grb) protein 10; GRB10, also termed insulin receptor-binding protein Grb-IR, is a multi-domain cytoplasmic adaptor protein that binds to the insulin-like growth factor 1 receptor (IGF-1R) and inhibits insulin signaling. Grb10 and its related family members Grb7 and Grb14 share a conserved domain architecture that includes an amino-terminal proline-rich region, a central segment termed the GM region (for Grb and Mig) which includes the RA, PIR, and pleckstrin homology (PH) domains, and a carboxyl-terminal SH2 domain. The tandem RA and PH domains of Grb7/10/14 are also found in a second adaptor family, Rap1-interacting adaptor molecule (RIAM) and lamellipodin, which is involved in actin-cytoskeleton rearrangement. Grb7/10/14 family proteins are phosphorylated on serine/threonine as well as tyrosine residues and are mainly localized to the cytoplasm. Grb14 binds to both GTPase-defective mutant Rab5 as well as CNGA1, whereas Grb10 binds only to GTP-bound form of active Rab5.


Pssm-ID: 340558  Cd Length: 92  Bit Score: 124.98  E-value: 6.51e-35
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503096 102 HVVKVYSEDGACRSVEVAAGATARHVCEMLVQRAHALSDETWGLVECHPHLALERGLEDHESVVEVQAAWPvgGDSRFVF 181
Cdd:cd16141     3 HIVKVFSEDGTSKVVEILADMTARDLCQLLVYKSHCVDDNSWTLVEHHPHLGLERCLEDHELVVQVQSTMG--SESKFLF 80
                          90
                  ....*....|..
gi 1057503096 182 RKNFAKYELFKS 193
Cdd:cd16141    81 RKNYAKYEFFKN 92
RA_MRL_like cd17112
Ras-associating (RA) domain found in Mig10/RIAM/Lpd (MRL) family and growth factor ...
103-183 2.23e-29

Ras-associating (RA) domain found in Mig10/RIAM/Lpd (MRL) family and growth factor receptor-bound (Grb) protein 7/10/14; MRL proteins share a common structural architecture, including a central structural unit consisting of a Ras-associating (RA) domain and a pleckstrin homology (PH) domain, an upstream coiled-coil region, and a number of polyproline motifs. RA domain-containing proteins function by interacting with Ras proteins directly or indirectly and are involved in several different functions ranging from tumor suppression to being oncoproteins. Ras proteins are small GTPases that are involved in cellular signal transduction. RA domain has the beta-grasp ubiquitin-like (Ubl) fold with low sequence similarity to ubiquitin (Ub). Ub is a protein modifier in eukaryotes that is involved in various cellular processes including transcriptional regulation, cell cycle control, and DNA repair in eukaryotes. RA and PH form a tandem domain pair (RA-PH), and serve tightly coordinated functions in both Ras GTPase signaling via the RA domain and membrane translocalization via the PH domain. MRL proteins have distinct functions in cell migration and adhesion, signaling, and in cell growth. Grb7/10/14 are multi-domain cytoplasmic adaptor proteins that are recruited to activated receptor tyrosine kinases. Grb7 and its related family members Grb10 and Grb14 share a conserved domain architecture that includes an amino-terminal proline-rich region, a central segment termed the GM region (for Grb and Mig) which includes the RA, PIR, and pleckstrin homology (PH) domains, and a carboxyl-terminal SH2 domain. The tandem RA and PH domains of Grb7/10/14 are also found in a second adaptor family, Rap1-interacting adaptor molecule (RIAM) and lamellipodin, which is involved in actin-cytoskeleton rearrangement. Grb7/10/14 family proteins are phosphorylated on serine/threonine as well as tyrosine residues and are mainly localized to the cytoplasm.


Pssm-ID: 340632  Cd Length: 81  Bit Score: 109.68  E-value: 2.23e-29
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503096 103 VVKVYSEDGACRSVEVAAGATARHVCEMLVQRAHALSDETWGLVECHPHLALERGLEDHESVVEVQAAWPVGGDSRFVFR 182
Cdd:cd17112     1 VVKVYNEDGSSKTVAVDENMTARDVCQILVEKNHVDPDKSWSLVEELPELGLERTLEDHELVVDVYSKWPSDSNNKFLFR 80

                  .
gi 1057503096 183 K 183
Cdd:cd17112    81 K 81
RA_GRB14 cd16139
Ras-associating (RA) domain found in growth factor receptor-bound (Grb) protein 14; Grb14, a ...
103-185 3.44e-27

Ras-associating (RA) domain found in growth factor receptor-bound (Grb) protein 14; Grb14, a member of cytoplasmic adaptor proteins, is a tissue-specific negative regulator of insulin signaling. RA domain has the beta-grasp ubiquitin-like fold with low sequence similarity to ubiquitin (Ub). Ubi is a protein modifier in eukaryotes that is involved in various cellular processes including transcriptional regulation, cell cycle control, and DNA repair in eukaryotes. A novel function of Grb14 RA domain is to interact with the nucleotide binding pocket of a cyclic nucleotide gated channel alpha subunit (CNGA1) and inhibits its activity. Grb7 and its related family members Grb10 and Grb14 share a conserved domain architecture that includes an amino-terminal proline-rich region, a central segment termed the GM region (for Grb and Mig) which includes the RA, PIR, and PH domains, and a carboxyl-terminal SH2 domain. Grb7/10/14 family proteins are phosphorylated on serine/threonine as well as tyrosine residues and are mainly localized to the cytoplasm.


Pssm-ID: 340556  Cd Length: 85  Bit Score: 103.76  E-value: 3.44e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503096 103 VVKVYSEDGACRSVEVAAGATARHVCEMLVQRAHALSDETWGLVECHPHLALERGLEDHESVVEVQAAWPVGGDSRFVFR 182
Cdd:cd16139     3 VIKVYSEDDTSRALEVPNDITARDVCQLFILKNHYIDDHSWTLFEHLPHIGLERIIEDHESVIEVQSNWGMETDSRLYFR 82

                  ...
gi 1057503096 183 KNF 185
Cdd:cd16139    83 KNY 85
BPS pfam08947
BPS (Between PH and SH2); The BPS (Between PH and SH2) domain, comprised of 2 beta strands and ...
365-410 2.38e-20

BPS (Between PH and SH2); The BPS (Between PH and SH2) domain, comprised of 2 beta strands and a C-terminal helix, is an approximately 45 residue region found in the adaptor proteins Grb7/10/14 that mediates inhibition of the tyrosine kinase domain of the insulin receptor by binding of the N-terminal portion of the BPS domain to the substrate peptide groove of the kinase, acting as a pseudosubstrate inhibitor.


Pssm-ID: 462644  Cd Length: 46  Bit Score: 83.79  E-value: 2.38e-20
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1057503096 365 RSASDNTLVAMDFSGHAGRVIENPREALSVALEEAQAWRKKTNHRL 410
Cdd:pfam08947   1 RSVSESSLVAMDFSGAGGRVIENPEEALSEAEEEGAAWRKKTLRRC 46
RA smart00314
Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); ...
100-184 6.03e-20

Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); putative RasGTP effectors in other cases. Kalhammer et al. have shown that not all RA domains bind RasGTP. Predicted structure similar to that determined, and that of the RasGTP-binding domain of Raf kinase. Predicted RA domains in PLC210 and nore1 found to bind RasGTP. Included outliers (Grb7, Grb14, adenylyl cyclases etc.)


Pssm-ID: 214612  Cd Length: 90  Bit Score: 83.89  E-value: 6.03e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503096  100 RPHVVKVYSED---GACRSVEVAAGATARHVCEMLVQRAHALSD-ETWGLVECHPHlALERGLEDHESVVEVQAAWPVGG 175
Cdd:smart00314   1 DTFVLRVYVDDlpgGTYKTLRVSSRTTARDVIQQLLEKFHLTDDpEEYVLVEVLPD-GKERVLPDDENPLQLQKLWPRRG 79
                           90
                   ....*....|
gi 1057503096  176 DS-RFVFRKN 184
Cdd:smart00314  80 PNlRFVLRKR 89
RA pfam00788
Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); ...
101-184 2.43e-17

Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); putative RasGTP effectors in other cases. Recent evidence (not yet in MEDLINE) shows that some RA domains do NOT bind RasGTP. Predicted structure similar to that determined, and that of the RasGTP-binding domain of Raf kinase.


Pssm-ID: 425871  Cd Length: 93  Bit Score: 76.99  E-value: 2.43e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503096 101 PHVVKVYSEDGA----CRSVEVAAGATARHVCEMLVQRAH-ALSDETWGLVECHPHLALERGLEDHESVVEVQAAWPV-G 174
Cdd:pfam00788   2 DGVLKVYTEDGKpgttYKTILVSSSTTAEEVIEALLEKFGlEDDPRDYVLVEVLERGGGERRLPDDECPLQIQLQWPRdA 81
                          90
                  ....*....|
gi 1057503096 175 GDSRFVFRKN 184
Cdd:pfam00788  82 SDSRFLLRKR 91
RA_MRL cd01787
Ras-associating (RA) domain of Mig10/RIAM/Lpd (MRL) family; MRL proteins share a common ...
103-171 1.70e-14

Ras-associating (RA) domain of Mig10/RIAM/Lpd (MRL) family; MRL proteins share a common structural architecture, including a central structural unit consisting of a Ras-associating (RA) domain and a pleckstrin homology (PH) domain, an upstream coiled-coil region, and a number of polyproline motifs. RA domain-containing proteins function by interacting with Ras proteins directly or indirectly and are involved in several different functions ranging from tumor suppression to being oncoproteins. Ras proteins are small GTPases that are involved in cellular signal transduction. RA domain has the beta-grasp ubiquitin-like fold with low sequence similarity to ubiquitin (Ub). Ub is a protein modifier in eukaryotes that is involved in various cellular processes including transcriptional regulation, cell cycle control, and DNA repair in eukaryotes. RA and PH form a tandem domain pair (RA-PH), and serve tightly coordinated functions in both Ras GTPase signaling via the RA domain and membrane translocalization via the PH domain. MRL proteins have distinct functions in cell migration and adhesion, signaling, and in cell growth.


Pssm-ID: 340485  Cd Length: 85  Bit Score: 68.60  E-value: 1.70e-14
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1057503096 103 VVKVYSEDGACRSVEVAAGATARHVCEMLVQRAHALSDETWGLVECHPHLALERGLEDHESVVEVQAAW 171
Cdd:cd01787     3 VVKVHMEDGSSKTLLVDERMTVRQVLKQLIEKNHCDPSVDWCLVEQYPDLYMERVFEDHEKLVENLLNW 71
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
230-334 9.54e-13

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: 64.11  E-value: 9.54e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503096  230 PEIQGFLQLRGS-GRKLWKRFFCFLRRSGLYYSTKGTSKDPRHLQYVADVNESNVYVVTQGRKlygMPTDFGFcvkpnKL 308
Cdd:smart00233   1 VIKEGWLYKKSGgGKKSWKKRYFVLFNSTLLYYKSKKDKKSYKPKGSIDLSGCTVREAPDPDS---SKKPHCF-----EI 72
                           90       100
                   ....*....|....*....|....*.
gi 1057503096  309 RNGHKGLRIFCSEDEQSRTCWLAAFR 334
Cdd:smart00233  73 KTSDRKTLLLQAESEEEREKWVEALR 98
RA_MRL_MIG10 cd16138
Ras-associating (RA) domain found in Caenorhabditis elegans abnormal cell migration protein 10 ...
104-181 2.37e-11

Ras-associating (RA) domain found in Caenorhabditis elegans abnormal cell migration protein 10 (MIG-10) and similar proteins; MIG-10 is lamellipodin (Lpd) found in C. elegans. It stabilizes invading cell adhesion to basement membrane and is a negative transcriptional target of Evi-1 proto-oncogene, EGL-43, in C. elegans. It also shows netrin-independent functions and is a transcriptional target of FOS-1A, a transcription factor that promotes basement membrane breaching, during anchor cell invasion in C. elegans. MIG-10 is a member of MRL (Mig10/RIAM/Lpd) family of proteins that is involved in antero-posterior migration of embryonic neurons CAN (canalassociated neurons), ALM (anterior lateral microtubule cells) and HSN (hermaphrodite-specific neurons). MRL proteins share a common structural architecture, including a central structural unit consisting of an RA domain and a pleckstrin homology (PH) domain, an upstream coiled-coil region, and a number of polyproline motifs. RA domain-containing proteins function by interacting with Ras proteins directly or indirectly and are involved in several different functions ranging from tumor suppression to being oncoproteins. RA domain has the beta-grasp ubiquitin-like fold with low sequence similarity to ubiquitin (Ub). Ub is a protein modifier in eukaryotes that is involved in various cellular processes including transcriptional regulation, cell cycle control, and DNA repair in eukaryotes. RA and PH form a tandem domain pair (RA-PH), and serve tightly coordinated functions in both Ras GTPase signaling via the RA domain and membrane translocalization via the PH domain.


Pssm-ID: 340555  Cd Length: 86  Bit Score: 59.77  E-value: 2.37e-11
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1057503096 104 VKVYSEDGACRSVEVAAGATARHVCEMLVQRAHALSDETWGLVECHPHLALERGLEDHESVVEVQAAWPVGGDSRFVF 181
Cdd:cd16138     5 VKAFTEDGSAKSLLVDERMTVGHVTRLLADKNHVAMMPDWAIVEHIPDLYMERVYEDHEKLVENLMMWTRDSPNRLLF 82
PH pfam00169
PH domain; PH stands for pleckstrin homology.
230-338 2.54e-11

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 60.27  E-value: 2.54e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503096 230 PEIQGFLQLRGSGRKL-WKRFFCFLRRSGLYYSTKgtSKDPRHLQYVADVNESNVYVVTQGRKLYgMPTDFGFCVKPNKL 308
Cdd:pfam00169   1 VVKEGWLLKKGGGKKKsWKKRYFVLFDGSLLYYKD--DKSGKSKEPKGSISLSGCEVVEVVASDS-PKRKFCFELRTGER 77
                          90       100       110
                  ....*....|....*....|....*....|
gi 1057503096 309 RNGHKglRIFCSEDEQSRTCWLAAFRLFKY 338
Cdd:pfam00169  78 TGKRT--YLLQAESEEERKDWIKAIQSAIR 105
RA_MRL_RIAM cd16137
Ras-associating (RA) domain found in Rap1-GTP-interacting adapter molecule (RIAM); RIAM, also ...
103-188 4.43e-11

Ras-associating (RA) domain found in Rap1-GTP-interacting adapter molecule (RIAM); RIAM, also termed amyloid beta A4 precursor protein-binding family B member 1-interacting protein, or APBB1-interacting protein 1, or proline-rich EVH1 ligand 1 (PREL-1), or proline-rich protein 73, or retinoic acid-responsive proline-rich protein 1 (RARP-1), is a member of MRL (Mig10/RIAM/Lpd) family proteins that regulates cell migration and promote lamellipodia protrusion in fibroblast by interacting with Ena/VASP proteins. RIAM regulates cell migration and mediates Rap1-induced cell adhesion. MRL proteins share a common structural architecture, including a central structural unit consisting of an RA domain and a pleckstrin homology (PH) domain, an upstream coiled-coil region, and a number of polyproline motifs. RA domain-containing proteins function by interacting with Ras proteins directly or indirectly and are involved in several different functions ranging from tumor suppression to being oncoproteins. RA domain has the beta-grasp ubiquitin-like fold with low sequence similarity to ubiquitin (Ub). Ub is a protein modifier in eukaryotes that is involved in various cellular processes including transcriptional regulation, cell cycle control, and DNA repair in eukaryotes. RIAM also contains a helical region at the amino terminus for talin binding. RA and PH form a tandem domain pair (RA-PH), and serve tightly coordinated functions in both Ras GTPase signaling via the RA domain and membrane translocalization via the PH domain.


Pssm-ID: 340554  Cd Length: 89  Bit Score: 59.11  E-value: 4.43e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503096 103 VVKVYSEDGACRSVEVAAGATARHVCEMLVQRAHALSDETWGLVECHPHLALERGLEDHESVVEVQAAWPVGGDSRFVFR 182
Cdd:cd16137     4 VVKVHMNDSSTKTLMVDERQTVRDVLDNLFEKTHCDCNVDWCLYEVNPELQIERFFEDHENVVEVLSDWTRDSENKVLFL 83

                  ....*.
gi 1057503096 183 KNFAKY 188
Cdd:cd16137    84 EKKEKY 89
RA cd17043
Ras-associating (RA) domain, structurally similar to a beta-grasp ubiquitin-like fold; RA ...
103-183 2.03e-10

Ras-associating (RA) domain, structurally similar to a beta-grasp ubiquitin-like fold; RA domain-containing proteins function by interacting with Ras proteins directly or indirectly and are involved in various functions ranging from tumor suppression to being oncoproteins. Ras proteins are small GTPases that are involved in cellular signal transduction. The RA domain has the beta-grasp ubiquitin-like (Ubl) fold with low sequence similarity to ubiquitin (Ub); Ub is a protein modifier in eukaryotes that is involved in various cellular processes, including transcriptional regulation, cell cycle control, and DNA repair. RA-containing proteins include RalGDS, AF6, RIN, RASSF1, SNX27, CYR1, STE50, and phospholipase C epsilon.


Pssm-ID: 340563  Cd Length: 87  Bit Score: 56.94  E-value: 2.03e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503096 103 VVKVYSED----GACRSVEVAAGATARHVCEMLVQRAH-ALSDETWGLVECHPHLALERGLEDHESVVEVQAAW-PVGGD 176
Cdd:cd17043     1 VLKVYDDDlapgSAYKSILVSSTTTAREVVQLLLEKYGlEEDPEDYSLYEVSEKQETERVLHDDECPLLIQLEWgPQGTE 80

                  ....*..
gi 1057503096 177 SRFVFRK 183
Cdd:cd17043    81 FRFVLKR 87
RA_MRL_Lpd cd16136
Ras-associating (RA) domain found in the adapter protein lamellipodin (Lpd); Lpd, also termed ...
103-187 6.68e-09

Ras-associating (RA) domain found in the adapter protein lamellipodin (Lpd); Lpd, also termed Ras-associated and pleckstrin homology domains-containing protein 1 (RAPH1), or amyotrophic lateral sclerosis 2 chromosomal region candidate gene 18 protein, or amyotrophic lateral sclerosis 2 chromosomal region candidate gene 9 protein, or proline-rich EVH1 ligand 2 (PREL-2), or protein RMO1, is a member of MRL (Mig10/RIAM/Lpd) family proteins that regulates cell migration and promote lamellipodia protrusion in fibroblast by interacting with Ena/VASP proteins. MRL proteins share a common structural architecture, including a central structural unit consisting of an RA domain and a pleckstrin homology (PH) domain, an upstream coiled-coil region, and a number of polyproline motifs. Lpd also contains a helical region at the amino terminus for talin binding. RA domain-containing proteins function by interacting with Ras proteins directly or indirectly and are involved in several different functions ranging from tumor suppression to being oncoproteins. RA domain has the beta-grasp ubiquitin-like fold with low sequence similarity to ubiquitin (Ub). Ub is a protein modifier in eukaryotes that is involved in various cellular processes including transcriptional regulation, cell cycle control, and DNA repair in eukaryotes. RA and PH domain in Lpd form a tandem domain pair (RA-PH), and serve tightly coordinated functions in both Ras GTPase signaling via the RA domain and membrane translocalization via the PH domain. Lpd also exhibits other unique enzymatic functions including its catalytic activity of butyrylcholinesterase, a potent therapeutic treatment targeting cocaine abuse.


Pssm-ID: 340553  Cd Length: 90  Bit Score: 52.78  E-value: 6.68e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503096 103 VVKVYSEDGACRSVEVAAGATARHVCEMLVQRAHALSDETWGLVECHPHLALERGLEDHESVVEVQAAWPVGGDSRFVFR 182
Cdd:cd16136     6 VIRVHMSDDSSKTMMVDERQTVRQVLDNLMDKSHCGYSLDWSLVETISELQMERIFEDHENLVENLLNWTRDSQNKLMFV 85

                  ....*
gi 1057503096 183 KNFAK 187
Cdd:cd16136    86 ERIEK 90
RA_ARAPs cd17113
Ras-associating (RA) domain found in Arf-GAP with Rho-GAP domain, ANK repeat and PH ...
104-184 7.87e-09

Ras-associating (RA) domain found in Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing proteins ARAP1, ARAP2, ARAP3, and similar proteins; ARAPs are phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P(3))-dependent Arf Rap-activated guanosine triphosphatase (GTPase)-activating proteins (GAPs). They contain multiple functional domains, including ArfGAP and RhoGAP domains, as well as a sterile alpha motif (Sam) domain, five PH domains, and a RA domain. The RA domain has the beta-grasp ubiquitin-like fold with low sequence similarity to ubiquitin (Ub); Ub is a protein modifier in eukaryotes that is involved in various cellular processes including transcriptional regulation, cell cycle control, and DNA repair in eukaryotes.


Pssm-ID: 340633  Cd Length: 95  Bit Score: 52.63  E-value: 7.87e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503096 104 VKVYSEDGACRSVEVAAGATARHVCEMLVQRAH-ALSDETWGLVECHPHLALERGLEDHESVVEVQAAWPV--GGDSRFV 180
Cdd:cd17113     8 VYIEEKEGTSVNIKVTPTMTAEEVVEQALNKKNlGGPEGNWALFEVIEDGGLERPLHESEKVLDVVLRWSQwpRKSNYLC 87

                  ....
gi 1057503096 181 FRKN 184
Cdd:cd17113    88 VKKN 91
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
232-333 4.49e-06

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: 44.84  E-value: 4.49e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503096 232 IQGFLQLRGSG-RKLWKRFFCFLRRSGLYYSTKGTSKDPRHLQYVADVNESNVYVVTQGRKlygmptDFGFCVKPNKLRN 310
Cdd:cd00821     1 KEGYLLKRGGGgLKSWKKRWFVLFEGVLLYYKSKKDSSYKPKGSIPLSGILEVEEVSPKER------PHCFELVTPDGRT 74
                          90       100
                  ....*....|....*....|...
gi 1057503096 311 GHkglriFCSEDEQSRTCWLAAF 333
Cdd:cd00821    75 YY-----LQADSEEERQEWLKAL 92
PH_RASA1 cd13260
RAS p21 protein activator (GTPase activating protein) 1 Pleckstrin homology (PH) domain; RASA1 ...
233-336 4.69e-05

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: 42.33  E-value: 4.69e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503096 233 QGFLQLRGSGRKLWKRFFCFL--RRSGLYYSTKGTSKDPRHLqyvADVNESNVYVVTQgrKLYGMPTDFGFCVKPNKLRN 310
Cdd:cd13260     6 KGYLLKKGGKNKKWKNLYFVLegKEQHLYFFDNEKRTKPKGL---IDLSYCSLYPVHD--SLFGRPNCFQIVVRALNEST 80
                          90       100
                  ....*....|....*....|....*.
gi 1057503096 311 GHkglrIFCSEDEQSRTCWLAAFRLF 336
Cdd:cd13260    81 IT----YLCADTAELAQEWMRALRAF 102
FERM_F1_DdMyo7_like cd17208
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in Dictyostelium ...
99-183 7.37e-05

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in Dictyostelium discoideum Myosin-VIIa (DdMyo7) and similar proteins; DdMyo7, also termed Myosin-I heavy chain, or class VII unconventional myosin, or M7, plays a role in adhesion in Dictyostelium where it is a component of a complex of proteins that serve to link membrane receptors to the underlying actin cytoskeleton. It interacts with talinA, an actin-binding protein with a known role in cell-substrate adhesion. DdMyo7 is required for phagocytosis. It is also essential for the extension of filopodia, plasma membrane protrusions filled with parallel bundles of F-actin. Members in this family contain a myosin motor domain, two MyTH4 domains, two FERM (Band 4.1, ezrin, radixin, moesin) domains, and two Pleckstrin homology (PH) domains. Some family members contain an extra SH3 domain. Each FERM domain is made up of three sub-domains, F1, F2, and F3. This family corresponds to the F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N).


Pssm-ID: 340728  Cd Length: 98  Bit Score: 41.47  E-value: 7.37e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503096  99 SRPHVVKVYSEDGACRSVEVAAGATARHVCEMLVQRAHALSD-ETWGLVECHPhlALERGLEDHESVVEVQAAW------ 171
Cdd:cd17208     1 RRPIVARFYFLDGQFKALEFDSAATAAEVLEQLKQKIGLRSTaDGFALYEVFG--GIERAILPEEKVADVLSKWeklqrt 78
                          90
                  ....*....|....*.
gi 1057503096 172 ---PVG-GDSRFVFRK 183
Cdd:cd17208    79 masCAAqQAVKFVFKK 94
PH_ACAP cd13250
ArfGAP with coiled-coil, ankyrin repeat and PH domains Pleckstrin homology (PH) domain; ACAP ...
232-334 2.89e-04

ArfGAP with coiled-coil, ankyrin repeat and PH domains Pleckstrin homology (PH) domain; ACAP (also called centaurin beta) functions both as a Rab35 effector and as an Arf6-GTPase-activating protein (GAP) by which it controls actin remodeling and membrane trafficking. ACAP contain an NH2-terminal bin/amphiphysin/Rvs (BAR) domain, a phospholipid-binding domain, a PH domain, a GAP domain, and four ankyrin repeats. The AZAPs constitute a family of Arf GAPs that are characterized by an NH2-terminal pleckstrin homology (PH) domain and a central Arf GAP domain followed by two or more ankyrin repeats. On the basis of sequence and domain organization, the AZAP family is further subdivided into four subfamilies: 1) the ACAPs contain an NH2-terminal bin/amphiphysin/Rvs (BAR) domain (a phospholipid-binding domain that is thought to sense membrane curvature), a single PH domain followed by the GAP domain, and four ankyrin repeats; 2) the ASAPs also contain an NH2-terminal BAR domain, the tandem PH domain/GAP domain, three ankyrin repeats, two proline-rich regions, and a COOH-terminal Src homology 3 domain; 3) the AGAPs contain an NH2-terminal GTPase-like domain (GLD), a split PH domain, and the GAP domain followed by four ankyrin repeats; and 4) the ARAPs contain both an Arf GAP domain and a Rho GAP domain, as well as an NH2-terminal sterile-a motif (SAM), a proline-rich region, a GTPase-binding domain, and five PH domains. PMID 18003747 and 19055940 Centaurin can bind to phosphatidlyinositol (3,4,5)P3. 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: 270070  Cd Length: 98  Bit Score: 39.90  E-value: 2.89e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503096 232 IQGFLQLRGS-GRKLWKRFFCFLRRSGLYYSTKGTSKDPRHLqyVADVNESNVYVVTQgrklygmpTDFGFC---VKPNK 307
Cdd:cd13250     1 KEGYLFKRSSnAFKTWKRRWFSLQNGQLYYQKRDKKDEPTVM--VEDLRLCTVKPTED--------SDRRFCfevISPTK 70
                          90       100
                  ....*....|....*....|....*....
gi 1057503096 308 lrnghkglrIFC--SEDEQSRTCWLAAFR 334
Cdd:cd13250    71 ---------SYMlqAESEEDRQAWIQAIQ 90
PH1_PH_fungal cd13298
Fungal proteins Pleckstrin homology (PH) domain, repeat 1; The functions of these fungal ...
232-336 7.41e-03

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: 36.06  E-value: 7.41e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503096 232 IQGFLQLRGSGRKLWKRFFCFLRRSGLYYSTKGTSKDPRHLQYVADVNESNVYVVTQgrklygMPTDFGFcVKPNKlrNG 311
Cdd:cd13298     8 KSGYLLKRSRKTKNWKKRWVVLRPCQLSYYKDEKEYKLRRVINLSELLAVAPLKDKK------RKNVFGI-YTPSK--NL 78
                          90       100
                  ....*....|....*....|....*
gi 1057503096 312 HkglriFCSEDEQSRTCWLAAFRLF 336
Cdd:cd13298    79 H-----FRATSEKDANEWVEALREE 98
 
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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