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Conserved domains on  [gi|712429007|gb|AIW65595|]
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insulin receptor substrate [Tigriopus japonicus]

Protein Classification

PH domain-containing protein( domain architecture ID 106840)

Pleckstrin homology (PH) domain-containing protein may be involved in targeting a protein to the appropriate cellular location or interacting with a binding partner

CATH:  2.30.29.30
Gene Ontology:  GO:0005515
PubMed:  22728242|17233582|15493994

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
PH-like super family cl17171
Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like ...
 74-171 3.58e-22

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


The actual alignment was detected with superfamily member cd01257:

Pssm-ID: 473070  Cd Length: 106  Bit Score: 92.35  E-value: 3.58e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 712429007   74 LRKLKKLQKRWFVLYSASEDGshPAHLEYHENEKNWRDHKPPRNEYILDECLNICQREsrDQKFKYVIDVVSLHEFLSIV 153
Cdd:cd01257     9 LKKLKTMRKRYFVLRAESHGG--PARLEYYENEKKFRRNAEPKRVIPLSSCFNINKRA--DAKHKHLIALYTKDECFGLV 84

                          90
                  ....*....|....*...
gi 712429007  154 FEEEQELKIWLDHLLSLQ 171
Cdd:cd01257    85 AESEEEQDEWYQALLELQ 102
PH-like super family cl17171
Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like ...
 185-289 3.68e-10

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


The actual alignment was detected with superfamily member cd01204:

Pssm-ID: 473070  Cd Length: 106  Bit Score: 58.03  E-value: 3.68e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 712429007  185 YDQVFPVQVKyfkPEDSSNTYLMSGPHRLCVTTEDLRFF---PQGQLKPVIFRLESVRSHMCSDRMFHFQTGRSSPSGAG 261
Cdd:cd01204     1 FEHVWQVTVK---KKGLGQSKNLTGIYRLCLTSKTLSLVklnSEKNPPSVEIQLMNIRRCGHSENFFFIEVGRSAVTGPG 77

                          90       100
                  ....*....|....*....|....*...
gi 712429007  262 TLTLQCDDKDNAVTLNNAANHAMRNAKD 289
Cdd:cd01204    78 ELWMQVDDSVVAQNMHETILEAMKALSE 105
 
Name Accession Description Interval E-value
PH_IRS cd01257
Insulin receptor substrate (IRS) pleckstrin homology (PH) domain; Insulin receptor substrate ...
 74-171 3.58e-22

Insulin receptor substrate (IRS) pleckstrin homology (PH) domain; Insulin receptor substrate (IRS) molecules are mediators in insulin signaling and play a role in maintaining basic cellular functions such as growth and metabolism. They act as docking proteins between the insulin receptor and a complex network of intracellular signaling molecules containing Src homology 2 (SH2) domains. Four members (IRS-1, IRS-2, IRS-3, IRS-4) of this family have been identified that differ as to tissue distribution, subcellular localization, developmental expression, binding to the insulin receptor, and interaction with SH2 domain-containing proteins. IRS molecules have an N-terminal PH domain, followed by an IRS-like PTB domain which has a PH-like fold. 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.cytoskeletal associated molecules, and in lipid associated enzymes.


Pssm-ID: 269959  Cd Length: 106  Bit Score: 92.35  E-value: 3.58e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 712429007   74 LRKLKKLQKRWFVLYSASEDGshPAHLEYHENEKNWRDHKPPRNEYILDECLNICQREsrDQKFKYVIDVVSLHEFLSIV 153
Cdd:cd01257     9 LKKLKTMRKRYFVLRAESHGG--PARLEYYENEKKFRRNAEPKRVIPLSSCFNINKRA--DAKHKHLIALYTKDECFGLV 84

                          90
                  ....*....|....*...
gi 712429007  154 FEEEQELKIWLDHLLSLQ 171
Cdd:cd01257    85 AESEEEQDEWYQALLELQ 102
PTB_IRS cd01204
Insulin receptor substrate phosphotyrosine-binding domain (PTBi); Insulin receptor substrate ...
 185-289 3.68e-10

Insulin receptor substrate phosphotyrosine-binding domain (PTBi); Insulin receptor substrate (IRS) molecules are mediators in insulin signaling and play a role in maintaining basic cellular functions such as growth and metabolism. They act as docking proteins between the insulin receptor and a complex network of intracellular signaling molecules containing Src homology 2 (SH2) domains. Four members (IRS-1, IRS-2, IRS-3, IRS-4) of this family have been identified that differ as to tissue distribution, subcellular localization, developmental expression, binding to the insulin receptor, and interaction with SH2 domain-containing proteins. IRS molecules have an N-terminal PH domain, followed by an IRS-like PTB domain which has a PH-like fold. PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains. This cd is part of the IRS-like subgroup.


Pssm-ID: 269915  Cd Length: 106  Bit Score: 58.03  E-value: 3.68e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 712429007  185 YDQVFPVQVKyfkPEDSSNTYLMSGPHRLCVTTEDLRFF---PQGQLKPVIFRLESVRSHMCSDRMFHFQTGRSSPSGAG 261
Cdd:cd01204     1 FEHVWQVTVK---KKGLGQSKNLTGIYRLCLTSKTLSLVklnSEKNPPSVEIQLMNIRRCGHSENFFFIEVGRSAVTGPG 77

                          90       100
                  ....*....|....*....|....*...
gi 712429007  262 TLTLQCDDKDNAVTLNNAANHAMRNAKD 289
Cdd:cd01204    78 ELWMQVDDSVVAQNMHETILEAMKALSE 105
IRS pfam02174
PTB domain (IRS-1 type);
186-272 5.96e-08

PTB domain (IRS-1 type);


Pssm-ID: 460473  Cd Length: 99  Bit Score: 51.48  E-value: 5.96e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 712429007   186 DQVFPVQVKYFKPEDSSNtylMSGPHRLCVTTEDLRF-FPQGQLKPVIFRLESVRSHMCSDRMFHFQTGRSSPSGAGTLT 264
Cdd:pfam02174    1 VEVFPVTVRRTGASERCG---LSGSYRLCLTAEALTLdKLNTRVPLVSWPLTSLRRYGRDKNFFSFEAGRRCVTGEGEFW 77


                   ....*...
gi 712429007   265 LQCDDKDN 272
Cdd:pfam02174   78 FQTDDAEE 85
PTBI smart00310
Phosphotyrosine-binding domain (IRS1-like);
187-267 2.81e-06

Phosphotyrosine-binding domain (IRS1-like);


Pssm-ID: 197644  Cd Length: 99  Bit Score: 47.02  E-value: 2.81e-06
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 712429007    187 QVFPVqvkYFKPEDSSNTYLmSGPHRLCVTTEDLRFFPQGQLKP--VIFRLESVRSHMCSDRMFHFQTGRSSPSGAGTLT 264
Cdd:smart00310    2 QFWVT---IRKTEGLERCPL-SGSYRLRLTSEELVLWRGLNPRVelVVWPLLSLRRYGRDKVFFFFEAGRRCVSGPGEFT 77


                    ...
gi 712429007    265 LQC 267
Cdd:smart00310   78 FQT 80
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 75-172 6.32e-05

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: 43.31  E-value: 6.32e-05
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 712429007     75 RKLKKLQKRWFVLysasedgsHPAHLEYHENEKNWRDHKpPRNEYILDECLNICQRESRDQKFKYVIDVVSLHEF-LSIV 153
Cdd:smart00233   13 GGKKSWKKRYFVL--------FNSTLLYYKSKKDKKSYK-PKGSIDLSGCTVREAPDPDSSKKPHCFEIKTSDRKtLLLQ 83

                            90
                    ....*....|....*....
gi 712429007    154 FEEEQELKIWLDHLLSLQK 172
Cdd:smart00233   84 AESEEEREKWVEALRKAIA 102
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 75-172 1.53e-04

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 42.16  E-value: 1.53e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 712429007    75 RKLKKLQKRWFVLYSASedgshpahLEYHENEKNWRDHKPpRNEYILDECLNICQRESRDQKFKYVIDVVSLH----EFL 150
Cdd:pfam00169   13 GKKKSWKKRYFVLFDGS--------LLYYKDDKSGKSKEP-KGSISLSGCEVVEVVASDSPKRKFCFELRTGErtgkRTY 83

                           90       100
                   ....*....|....*....|..
gi 712429007   151 SIVFEEEQELKIWLDHLLSLQK 172
Cdd:pfam00169   84 LLQAESEEERKDWIKAIQSAIR 105
 
Name Accession Description Interval E-value
PH_IRS cd01257
Insulin receptor substrate (IRS) pleckstrin homology (PH) domain; Insulin receptor substrate ...
 74-171 3.58e-22

Insulin receptor substrate (IRS) pleckstrin homology (PH) domain; Insulin receptor substrate (IRS) molecules are mediators in insulin signaling and play a role in maintaining basic cellular functions such as growth and metabolism. They act as docking proteins between the insulin receptor and a complex network of intracellular signaling molecules containing Src homology 2 (SH2) domains. Four members (IRS-1, IRS-2, IRS-3, IRS-4) of this family have been identified that differ as to tissue distribution, subcellular localization, developmental expression, binding to the insulin receptor, and interaction with SH2 domain-containing proteins. IRS molecules have an N-terminal PH domain, followed by an IRS-like PTB domain which has a PH-like fold. 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.cytoskeletal associated molecules, and in lipid associated enzymes.


Pssm-ID: 269959  Cd Length: 106  Bit Score: 92.35  E-value: 3.58e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 712429007   74 LRKLKKLQKRWFVLYSASEDGshPAHLEYHENEKNWRDHKPPRNEYILDECLNICQREsrDQKFKYVIDVVSLHEFLSIV 153
Cdd:cd01257     9 LKKLKTMRKRYFVLRAESHGG--PARLEYYENEKKFRRNAEPKRVIPLSSCFNINKRA--DAKHKHLIALYTKDECFGLV 84

                          90
                  ....*....|....*...
gi 712429007  154 FEEEQELKIWLDHLLSLQ 171
Cdd:cd01257    85 AESEEEQDEWYQALLELQ 102
PTB_IRS cd01204
Insulin receptor substrate phosphotyrosine-binding domain (PTBi); Insulin receptor substrate ...
 185-289 3.68e-10

Insulin receptor substrate phosphotyrosine-binding domain (PTBi); Insulin receptor substrate (IRS) molecules are mediators in insulin signaling and play a role in maintaining basic cellular functions such as growth and metabolism. They act as docking proteins between the insulin receptor and a complex network of intracellular signaling molecules containing Src homology 2 (SH2) domains. Four members (IRS-1, IRS-2, IRS-3, IRS-4) of this family have been identified that differ as to tissue distribution, subcellular localization, developmental expression, binding to the insulin receptor, and interaction with SH2 domain-containing proteins. IRS molecules have an N-terminal PH domain, followed by an IRS-like PTB domain which has a PH-like fold. PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains. This cd is part of the IRS-like subgroup.


Pssm-ID: 269915  Cd Length: 106  Bit Score: 58.03  E-value: 3.68e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 712429007  185 YDQVFPVQVKyfkPEDSSNTYLMSGPHRLCVTTEDLRFF---PQGQLKPVIFRLESVRSHMCSDRMFHFQTGRSSPSGAG 261
Cdd:cd01204     1 FEHVWQVTVK---KKGLGQSKNLTGIYRLCLTSKTLSLVklnSEKNPPSVEIQLMNIRRCGHSENFFFIEVGRSAVTGPG 77

                          90       100
                  ....*....|....*....|....*...
gi 712429007  262 TLTLQCDDKDNAVTLNNAANHAMRNAKD 289
Cdd:cd01204    78 ELWMQVDDSVVAQNMHETILEAMKALSE 105
IRS pfam02174
PTB domain (IRS-1 type);
186-272 5.96e-08

PTB domain (IRS-1 type);


Pssm-ID: 460473  Cd Length: 99  Bit Score: 51.48  E-value: 5.96e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 712429007   186 DQVFPVQVKYFKPEDSSNtylMSGPHRLCVTTEDLRF-FPQGQLKPVIFRLESVRSHMCSDRMFHFQTGRSSPSGAGTLT 264
Cdd:pfam02174    1 VEVFPVTVRRTGASERCG---LSGSYRLCLTAEALTLdKLNTRVPLVSWPLTSLRRYGRDKNFFSFEAGRRCVTGEGEFW 77


                   ....*...
gi 712429007   265 LQCDDKDN 272
Cdd:pfam02174   78 FQTDDAEE 85
PTBI smart00310
Phosphotyrosine-binding domain (IRS1-like);
187-267 2.81e-06

Phosphotyrosine-binding domain (IRS1-like);


Pssm-ID: 197644  Cd Length: 99  Bit Score: 47.02  E-value: 2.81e-06
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 712429007    187 QVFPVqvkYFKPEDSSNTYLmSGPHRLCVTTEDLRFFPQGQLKP--VIFRLESVRSHMCSDRMFHFQTGRSSPSGAGTLT 264
Cdd:smart00310    2 QFWVT---IRKTEGLERCPL-SGSYRLRLTSEELVLWRGLNPRVelVVWPLLSLRRYGRDKVFFFFEAGRRCVSGPGEFT 77


                    ...
gi 712429007    265 LQC 267
Cdd:smart00310   78 FQT 80
PH_Gab1_Gab2 cd01266
Grb2-associated binding proteins 1 and 2 pleckstrin homology (PH) domain; The Gab subfamily ...
 66-164 2.17e-05

Grb2-associated binding proteins 1 and 2 pleckstrin homology (PH) domain; The Gab subfamily includes several Gab proteins, Drosophila DOS and C. elegans SOC-1. They are scaffolding adaptor proteins, which possess N-terminal PH domains and a C-terminus with proline-rich regions and multiple phosphorylation sites. Following activation of growth factor receptors, Gab proteins are tyrosine phosphorylated and activate PI3K, which generates 3-phosphoinositide lipids. By binding to these lipids via the PH domain, Gab proteins remain in proximity to the receptor, leading to further signaling. While not all Gab proteins depend on the PH domain for recruitment, it is required for Gab activity. The members in this cd include the Gab1 and Gab2 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: 241297  Cd Length: 123  Bit Score: 44.94  E-value: 2.17e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 712429007   66 AQKVISASLRKL---KKL-----QKRWFVLYSASEDGShPAHLEYHENeknwrDH--KPPRneyILDecLNICQR----- 130
Cdd:cd01266     2 GEVVCSGWLRKSppeKKLrryawKKRWFVLRSGRLSGD-PDVLEYYKN-----DHakKPIR---VID--LNLCEQvdagl 70

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 712429007  131 --ESRDQKFKYVIDVVSLHEFLSIVFEEEQELKIWL 164
Cdd:cd01266    71 tfNKKELENSYIFDIKTIDRIFYLVAETEEDMNKWV 106
PH_Gab-like cd13324
Grb2-associated binding protein family Pleckstrin homology (PH) domain; Gab proteins are ...
 75-165 4.46e-05

Grb2-associated binding protein family Pleckstrin homology (PH) domain; Gab proteins are scaffolding adaptor proteins, which possess N-terminal PH domains and a C-terminus with proline-rich regions and multiple phosphorylation sites. Following activation of growth factor receptors, Gab proteins are tyrosine phosphorylated and activate PI3K, which generates 3-phosphoinositide lipids. By binding to these lipids via the PH domain, Gab proteins remain in proximity to the receptor, leading to further signaling. While not all Gab proteins depend on the PH domain for recruitment, it is required for Gab activity. There are 3 families: Gab1, Gab2, and Gab3. 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: 270133  Cd Length: 112  Bit Score: 43.94  E-value: 4.46e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 712429007   75 RKLK--KLQKRWFVLYSASEDGShPAHLEYHENEknwrDHKPPRNEYILDECLNICQR---ESRDQKFKYVIDVVSLHEF 149
Cdd:cd13324    14 KKIWraAWRRRWFVLRSGRLSGG-QDVLEYYTDD----HCKKLKGIIDLDQCEQVDAGltfEKKKFKNQFIFDIRTPKRT 88

                          90
                  ....*....|....*.
gi 712429007  150 LSIVFEEEQELKIWLD 165
Cdd:cd13324    89 YYLVAETEEEMNKWVR 104
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 75-172 6.32e-05

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: 43.31  E-value: 6.32e-05
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 712429007     75 RKLKKLQKRWFVLysasedgsHPAHLEYHENEKNWRDHKpPRNEYILDECLNICQRESRDQKFKYVIDVVSLHEF-LSIV 153
Cdd:smart00233   13 GGKKSWKKRYFVL--------FNSTLLYYKSKKDKKSYK-PKGSIDLSGCTVREAPDPDSSKKPHCFEIKTSDRKtLLLQ 83

                            90
                    ....*....|....*....
gi 712429007    154 FEEEQELKIWLDHLLSLQK 172
Cdd:smart00233   84 AESEEEREKWVEALRKAIA 102
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 75-172 1.53e-04

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 42.16  E-value: 1.53e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 712429007    75 RKLKKLQKRWFVLYSASedgshpahLEYHENEKNWRDHKPpRNEYILDECLNICQRESRDQKFKYVIDVVSLH----EFL 150
Cdd:pfam00169   13 GKKKSWKKRYFVLFDGS--------LLYYKDDKSGKSKEP-KGSISLSGCEVVEVVASDSPKRKFCFELRTGErtgkRTY 83

                           90       100
                   ....*....|....*....|..
gi 712429007   151 SIVFEEEQELKIWLDHLLSLQK 172
Cdd:pfam00169   84 LLQAESEEERKDWIKAIQSAIR 105
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
 75-167 3.07e-04

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: 40.99  E-value: 3.07e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 712429007   75 RKLKKLQKRWFVLysasedgsHPAHLEYHENEKNWrdHKPPRNEYILDECLNICQRESRDQKFKYVIdVVSLHEFLSIVF 154
Cdd:cd00821    11 GGLKSWKKRWFVL--------FEGVLLYYKSKKDS--SYKPKGSIPLSGILEVEEVSPKERPHCFEL-VTPDGRTYYLQA 79

                          90
                  ....*....|...
gi 712429007  155 EEEQELKIWLDHL 167
Cdd:cd00821    80 DSEEERQEWLKAL 92
 
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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