NCBI Home Page NCBI Site Search page NCBI Guide that lists and describes the NCBI resources
Conserved domains on  [gi|41406050|ref|NP_003965|]
View 

docking protein 2 isoform a [Homo sapiens]

Protein Classification

docking protein( domain architecture ID 10199820)

docking protein, also known as downstream of tyrosine kinase (DOK) similar to DOK1, DOK2, and DOK3; DOK1/2 act as negative regulators of the Ras-Erk pathway downstream of many immunoreceptor-mediated signaling systems; DOK3 is a negative regulator of the activation of JNK and mobilization of Ca2+ in B-cell receptor-mediated signaling, interacting with SHIP-1 and Grb2

Gene Ontology:  GO:0005515|GO:0007169
PubMed:  15567406|8987385|10610414|15493994|22728242

Graphical summary

 Zoom to residue level

show extra options »

Show site features     Horizontal zoom: ×

List of domain hits

 Name Accession Description Interval E-value
PH_DOK1,2,3 cd14676
Pleckstrin homology (PH) domain of Downstream of tyrosine kinase 1, 2, and 3; The Dok family ...
 7-114 6.82e-56

Pleckstrin homology (PH) domain of Downstream of tyrosine kinase 1, 2, and 3; The Dok family adapters are phosphorylated by different protein tyrosine kinases. Dok proteins are involved in processes such as modulation of cell differentiation and proliferation, as well as in control of the cell spreading and migration The Dok protein contains an N-terminal pleckstrin homology (PH) domain followed by a central phosphotyrosine binding (PTB) domain, which has a PH-like fold, and a proline- and tyrosine-rich C-terminal tail. The PH domain is binds to acidic phospholids and localizes proteins to the plasma membrane. There are 7 mammalian Dok members: Dok-1 to Dok-7. Dok-1 and Dok-2 act as negative regulators of the Ras-Erk pathway downstream of many immunoreceptor-mediated signaling systems, and it is believed that recruitment of p120 rasGAP by Dok-1 and Dok-2 is critical to their negative regulation. Dok-3 is a negative regulator of the activation of JNK and mobilization of Ca2+ in B-cell receptor-mediated signaling, interacting with SHIP-1 and Grb2. In general, PH domains have diverse functions, but are generally 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. 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: 270195  Cd Length: 113  Bit Score: 179.91  E-value: 6.82e-56
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41406050   7 KQGFLYLQQQQTFGKKWRRFGASLYGGSDCALARLELQEG-----PEKPRRCEAARKVIRLSDCLRVAEAGGEASSPRDT 81
Cdd:cd14676   1 KEGQLYLQQQKFFGKKWRKFWAVLYPASPCGVARLEFFEGkggpsGGKPSKRESDRKVIRLSDCVSVAPAGGESSPPRDT 80

                        90       100       110
                ....*....|....*....|....*....|...
gi 41406050  82 SAFFLETKERLYLLAAPAAERGDWVQAICLLAF 114
Cdd:cd14676  81 AAFLLETTEKLYLLAAEAAERADWVQKLCELAF 113
PTB_DOK1_DOK2_DOK3 cd01203
Downstream of tyrosine kinase 1, 2, and 3 proteins phosphotyrosine-binding domain (PTBi); The ...
 147-246 6.90e-56

Downstream of tyrosine kinase 1, 2, and 3 proteins phosphotyrosine-binding domain (PTBi); The Dok family adapters are phosphorylated by different protein tyrosine kinases. Dok proteins are involved in processes such as modulation of cell differentiation and proliferation, as well as in control of the cell spreading and migration The Dok protein contains an N-terminal pleckstrin homology (PH) domain followed by a central phosphotyrosine binding (PTB) domain, which has a PH-like fold, and a proline- and tyrosine-rich C-terminal tail. The PH domain is binds to acidic phospholids and localizes proteins to the plasma membrane, while the PTB domain mediates protein-protein interactions by binding to phosphotyrosine-containing motifs. The C-terminal part of Dok contains multiple tyrosine phosphorylation sites that serve as potential docking sites for Src homology 2-containing proteins such as ras GTPase-activating protein and Nck, leading to inhibition of ras signaling pathway activation and the c-Jun N-terminal kinase (JNK) and c-Jun activation, respectively. There are 7 mammalian Dok members: Dok-1 to Dok-7. Dok-1 and Dok-2 act as negative regulators of the Ras-Erk pathway downstream of many immunoreceptor-mediated signaling systems, and it is believed that recruitment of p120 rasGAP by Dok-1 and Dok-2 is critical to their negative regulation. Dok-3 is a negative regulator of the activation of JNK and mobilization of Ca2+ in B-cell receptor-mediated signaling, interacting with SHIP-1 and Grb2. Dok-4- 6 play roles in protein tyrosine kinase(PTK)-mediated signaling in neural cells and Dok-7 is the key cytoplasmic activator of MuSK (Muscle-Specific Protein Tyrosine Kinase). 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: 269914  Cd Length: 99  Bit Score: 179.34  E-value: 6.90e-56
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41406050 147 PHKEFAVTMRPTEASERCHLRGSYTLRAGESALELWGGPEPgTQLYDWPYRFLRRFGRDKVTFSFEAGRRCVSGEGNFEF 226
Cdd:cd01203   1 EVKEFPVVVQRTEASERCRLKGSYLLRAGQDALELLDPQTK-KPLYSWPYRFLRRFGRDKVMFSFEAGRRCDSGEGLFTF 79

                        90       100
                ....*....|....*....|
gi 41406050 227 ETRQGNEIFLALEEAISAQK 246
Cdd:cd01203  80 ETPQGNEIFQAVEAAIAAQK 99
 
Name Accession Description Interval E-value
PH_DOK1,2,3 cd14676
Pleckstrin homology (PH) domain of Downstream of tyrosine kinase 1, 2, and 3; The Dok family ...
 7-114 6.82e-56

Pleckstrin homology (PH) domain of Downstream of tyrosine kinase 1, 2, and 3; The Dok family adapters are phosphorylated by different protein tyrosine kinases. Dok proteins are involved in processes such as modulation of cell differentiation and proliferation, as well as in control of the cell spreading and migration The Dok protein contains an N-terminal pleckstrin homology (PH) domain followed by a central phosphotyrosine binding (PTB) domain, which has a PH-like fold, and a proline- and tyrosine-rich C-terminal tail. The PH domain is binds to acidic phospholids and localizes proteins to the plasma membrane. There are 7 mammalian Dok members: Dok-1 to Dok-7. Dok-1 and Dok-2 act as negative regulators of the Ras-Erk pathway downstream of many immunoreceptor-mediated signaling systems, and it is believed that recruitment of p120 rasGAP by Dok-1 and Dok-2 is critical to their negative regulation. Dok-3 is a negative regulator of the activation of JNK and mobilization of Ca2+ in B-cell receptor-mediated signaling, interacting with SHIP-1 and Grb2. In general, PH domains have diverse functions, but are generally 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. 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: 270195  Cd Length: 113  Bit Score: 179.91  E-value: 6.82e-56
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41406050   7 KQGFLYLQQQQTFGKKWRRFGASLYGGSDCALARLELQEG-----PEKPRRCEAARKVIRLSDCLRVAEAGGEASSPRDT 81
Cdd:cd14676   1 KEGQLYLQQQKFFGKKWRKFWAVLYPASPCGVARLEFFEGkggpsGGKPSKRESDRKVIRLSDCVSVAPAGGESSPPRDT 80

                        90       100       110
                ....*....|....*....|....*....|...
gi 41406050  82 SAFFLETKERLYLLAAPAAERGDWVQAICLLAF 114
Cdd:cd14676  81 AAFLLETTEKLYLLAAEAAERADWVQKLCELAF 113
PTB_DOK1_DOK2_DOK3 cd01203
Downstream of tyrosine kinase 1, 2, and 3 proteins phosphotyrosine-binding domain (PTBi); The ...
 147-246 6.90e-56

Downstream of tyrosine kinase 1, 2, and 3 proteins phosphotyrosine-binding domain (PTBi); The Dok family adapters are phosphorylated by different protein tyrosine kinases. Dok proteins are involved in processes such as modulation of cell differentiation and proliferation, as well as in control of the cell spreading and migration The Dok protein contains an N-terminal pleckstrin homology (PH) domain followed by a central phosphotyrosine binding (PTB) domain, which has a PH-like fold, and a proline- and tyrosine-rich C-terminal tail. The PH domain is binds to acidic phospholids and localizes proteins to the plasma membrane, while the PTB domain mediates protein-protein interactions by binding to phosphotyrosine-containing motifs. The C-terminal part of Dok contains multiple tyrosine phosphorylation sites that serve as potential docking sites for Src homology 2-containing proteins such as ras GTPase-activating protein and Nck, leading to inhibition of ras signaling pathway activation and the c-Jun N-terminal kinase (JNK) and c-Jun activation, respectively. There are 7 mammalian Dok members: Dok-1 to Dok-7. Dok-1 and Dok-2 act as negative regulators of the Ras-Erk pathway downstream of many immunoreceptor-mediated signaling systems, and it is believed that recruitment of p120 rasGAP by Dok-1 and Dok-2 is critical to their negative regulation. Dok-3 is a negative regulator of the activation of JNK and mobilization of Ca2+ in B-cell receptor-mediated signaling, interacting with SHIP-1 and Grb2. Dok-4- 6 play roles in protein tyrosine kinase(PTK)-mediated signaling in neural cells and Dok-7 is the key cytoplasmic activator of MuSK (Muscle-Specific Protein Tyrosine Kinase). 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: 269914  Cd Length: 99  Bit Score: 179.34  E-value: 6.90e-56
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41406050 147 PHKEFAVTMRPTEASERCHLRGSYTLRAGESALELWGGPEPgTQLYDWPYRFLRRFGRDKVTFSFEAGRRCVSGEGNFEF 226
Cdd:cd01203   1 EVKEFPVVVQRTEASERCRLKGSYLLRAGQDALELLDPQTK-KPLYSWPYRFLRRFGRDKVMFSFEAGRRCDSGEGLFTF 79

                        90       100
                ....*....|....*....|
gi 41406050 227 ETRQGNEIFLALEEAISAQK 246
Cdd:cd01203  80 ETPQGNEIFQAVEAAIAAQK 99
PTBI smart00310
Phosphotyrosine-binding domain (IRS1-like);
149-247 2.28e-45

Phosphotyrosine-binding domain (IRS1-like);


Pssm-ID: 197644  Cd Length: 99  Bit Score: 152.18  E-value: 2.28e-45
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41406050    149 KEFAVTMRPTEASERCHLRGSYTLRAGESALELWGGPEPGTQLYDWPYRFLRRFGRDKVTFSFEAGRRCVSGEGNFEFET 228
Cdd:smart00310   1 KQFWVTIRKTEGLERCPLSGSYRLRLTSEELVLWRGLNPRVELVVWPLLSLRRYGRDKVFFFFEAGRRCVSGPGEFTFQT 80

                           90
                   ....*....|....*....
gi 41406050    229 RQGNEIFLALEEAISAQKN 247
Cdd:smart00310  81 VVAQEIFQLVLEAMQAQKN 99
IRS pfam02174
PTB domain (IRS-1 type);
148-247 7.01e-44

PTB domain (IRS-1 type);


Pssm-ID: 460473  Cd Length: 99  Bit Score: 148.17  E-value: 7.01e-44
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41406050   148 HKEFAVTMRPTEASERCHLRGSYTLRAGESALELwGGPEPGTQLYDWPYRFLRRFGRDKVTFSFEAGRRCVSGEGNFEFE 227
Cdd:pfam02174   1 VEVFPVTVRRTGASERCGLSGSYRLCLTAEALTL-DKLNTRVPLVSWPLTSLRRYGRDKNFFSFEAGRRCVTGEGEFWFQ 79

                          90       100
                  ....*....|....*....|
gi 41406050   228 TRQGNEIFLALEEAISAQKN 247
Cdd:pfam02174  80 TDDAEEIFETVLAAMKAQKE 99
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 6-113 1.13e-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: 44.08  E-value: 1.13e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41406050      6 VKQGFLYlQQQQTFGKKWRRFGASLYGGsdcalaRLELQEgPEKPRRCEAARKVIRLSDClRVAEAGGEASSPRDTSaFF 85
Cdd:smart00233   2 IKEGWLY-KKSGGGKKSWKKRYFVLFNS------TLLYYK-SKKDKKSYKPKGSIDLSGC-TVREAPDPDSSKKPHC-FE 71

                           90       100       110
                   ....*....|....*....|....*....|
gi 41406050     86 LETKER-LYLLAAP-AAERGDWVQAICLLA 113
Cdd:smart00233  72 IKTSDRkTLLLQAEsEEEREKWVEALRKAI 101
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 6-112 2.19e-03

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 37.54  E-value: 2.19e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41406050     6 VKQGFLYlQQQQTFGKKWRRFGASLYGGSdcalarLELQEgPEKPRRCEAARKVIRLSDClRVAEAGGEASSPRDTSaFF 85
Cdd:pfam00169   2 VKEGWLL-KKGGGKKKSWKKRYFVLFDGS------LLYYK-DDKSGKSKEPKGSISLSGC-EVVEVVASDSPKRKFC-FE 71

                          90       100       110
                  ....*....|....*....|....*....|..
gi 41406050    86 LET-----KERLYLLAAPAAERGDWVQAICLL 112
Cdd:pfam00169  72 LRTgertgKRTYLLQAESEEERKDWIKAIQSA 103
 
Name Accession Description Interval E-value
PH_DOK1,2,3 cd14676
Pleckstrin homology (PH) domain of Downstream of tyrosine kinase 1, 2, and 3; The Dok family ...
 7-114 6.82e-56

Pleckstrin homology (PH) domain of Downstream of tyrosine kinase 1, 2, and 3; The Dok family adapters are phosphorylated by different protein tyrosine kinases. Dok proteins are involved in processes such as modulation of cell differentiation and proliferation, as well as in control of the cell spreading and migration The Dok protein contains an N-terminal pleckstrin homology (PH) domain followed by a central phosphotyrosine binding (PTB) domain, which has a PH-like fold, and a proline- and tyrosine-rich C-terminal tail. The PH domain is binds to acidic phospholids and localizes proteins to the plasma membrane. There are 7 mammalian Dok members: Dok-1 to Dok-7. Dok-1 and Dok-2 act as negative regulators of the Ras-Erk pathway downstream of many immunoreceptor-mediated signaling systems, and it is believed that recruitment of p120 rasGAP by Dok-1 and Dok-2 is critical to their negative regulation. Dok-3 is a negative regulator of the activation of JNK and mobilization of Ca2+ in B-cell receptor-mediated signaling, interacting with SHIP-1 and Grb2. In general, PH domains have diverse functions, but are generally 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. 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: 270195  Cd Length: 113  Bit Score: 179.91  E-value: 6.82e-56
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41406050   7 KQGFLYLQQQQTFGKKWRRFGASLYGGSDCALARLELQEG-----PEKPRRCEAARKVIRLSDCLRVAEAGGEASSPRDT 81
Cdd:cd14676   1 KEGQLYLQQQKFFGKKWRKFWAVLYPASPCGVARLEFFEGkggpsGGKPSKRESDRKVIRLSDCVSVAPAGGESSPPRDT 80

                        90       100       110
                ....*....|....*....|....*....|...
gi 41406050  82 SAFFLETKERLYLLAAPAAERGDWVQAICLLAF 114
Cdd:cd14676  81 AAFLLETTEKLYLLAAEAAERADWVQKLCELAF 113
PTB_DOK1_DOK2_DOK3 cd01203
Downstream of tyrosine kinase 1, 2, and 3 proteins phosphotyrosine-binding domain (PTBi); The ...
 147-246 6.90e-56

Downstream of tyrosine kinase 1, 2, and 3 proteins phosphotyrosine-binding domain (PTBi); The Dok family adapters are phosphorylated by different protein tyrosine kinases. Dok proteins are involved in processes such as modulation of cell differentiation and proliferation, as well as in control of the cell spreading and migration The Dok protein contains an N-terminal pleckstrin homology (PH) domain followed by a central phosphotyrosine binding (PTB) domain, which has a PH-like fold, and a proline- and tyrosine-rich C-terminal tail. The PH domain is binds to acidic phospholids and localizes proteins to the plasma membrane, while the PTB domain mediates protein-protein interactions by binding to phosphotyrosine-containing motifs. The C-terminal part of Dok contains multiple tyrosine phosphorylation sites that serve as potential docking sites for Src homology 2-containing proteins such as ras GTPase-activating protein and Nck, leading to inhibition of ras signaling pathway activation and the c-Jun N-terminal kinase (JNK) and c-Jun activation, respectively. There are 7 mammalian Dok members: Dok-1 to Dok-7. Dok-1 and Dok-2 act as negative regulators of the Ras-Erk pathway downstream of many immunoreceptor-mediated signaling systems, and it is believed that recruitment of p120 rasGAP by Dok-1 and Dok-2 is critical to their negative regulation. Dok-3 is a negative regulator of the activation of JNK and mobilization of Ca2+ in B-cell receptor-mediated signaling, interacting with SHIP-1 and Grb2. Dok-4- 6 play roles in protein tyrosine kinase(PTK)-mediated signaling in neural cells and Dok-7 is the key cytoplasmic activator of MuSK (Muscle-Specific Protein Tyrosine Kinase). 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: 269914  Cd Length: 99  Bit Score: 179.34  E-value: 6.90e-56
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41406050 147 PHKEFAVTMRPTEASERCHLRGSYTLRAGESALELWGGPEPgTQLYDWPYRFLRRFGRDKVTFSFEAGRRCVSGEGNFEF 226
Cdd:cd01203   1 EVKEFPVVVQRTEASERCRLKGSYLLRAGQDALELLDPQTK-KPLYSWPYRFLRRFGRDKVMFSFEAGRRCDSGEGLFTF 79

                        90       100
                ....*....|....*....|
gi 41406050 227 ETRQGNEIFLALEEAISAQK 246
Cdd:cd01203  80 ETPQGNEIFQAVEAAIAAQK 99
PTBI smart00310
Phosphotyrosine-binding domain (IRS1-like);
149-247 2.28e-45

Phosphotyrosine-binding domain (IRS1-like);


Pssm-ID: 197644  Cd Length: 99  Bit Score: 152.18  E-value: 2.28e-45
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41406050    149 KEFAVTMRPTEASERCHLRGSYTLRAGESALELWGGPEPGTQLYDWPYRFLRRFGRDKVTFSFEAGRRCVSGEGNFEFET 228
Cdd:smart00310   1 KQFWVTIRKTEGLERCPLSGSYRLRLTSEELVLWRGLNPRVELVVWPLLSLRRYGRDKVFFFFEAGRRCVSGPGEFTFQT 80

                           90
                   ....*....|....*....
gi 41406050    229 RQGNEIFLALEEAISAQKN 247
Cdd:smart00310  81 VVAQEIFQLVLEAMQAQKN 99
IRS pfam02174
PTB domain (IRS-1 type);
148-247 7.01e-44

PTB domain (IRS-1 type);


Pssm-ID: 460473  Cd Length: 99  Bit Score: 148.17  E-value: 7.01e-44
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41406050   148 HKEFAVTMRPTEASERCHLRGSYTLRAGESALELwGGPEPGTQLYDWPYRFLRRFGRDKVTFSFEAGRRCVSGEGNFEFE 227
Cdd:pfam02174   1 VEVFPVTVRRTGASERCGLSGSYRLCLTAEALTL-DKLNTRVPLVSWPLTSLRRYGRDKNFFSFEAGRRCVTGEGEFWFQ 79

                          90       100
                  ....*....|....*....|
gi 41406050   228 TRQGNEIFLALEEAISAQKN 247
Cdd:pfam02174  80 TDDAEEIFETVLAAMKAQKE 99
PTB_DOK4_DOK5_DOK6 cd13164
Downstream of tyrosine kinase 4, 5, and 6 proteins phosphotyrosine-binding domain (PTBi); The ...
 151-244 5.40e-16

Downstream of tyrosine kinase 4, 5, and 6 proteins phosphotyrosine-binding domain (PTBi); The Dok family adapters are phosphorylated by different protein tyrosine kinases. Dok proteins are involved in processes such as modulation of cell differentiation and proliferation, as well as in control of the cell spreading and migration The Dok protein contains an N-terminal pleckstrin homology (PH) domain followed by a central phosphotyrosine binding (PTB) domain, which has a PH-like fold, and a proline- and tyrosine-rich C-terminal tail. The PH domain binds to acidic phospholids and localizes proteins to the plasma membrane, while the PTB domain mediates protein-protein interactions by binding to phosphotyrosine-containing motifs. The C-terminal part of Dok contains multiple tyrosine phosphorylation sites that serve as potential docking sites for Src homology 2-containing proteins such as ras GTPase-activating protein and Nck, leading to inhibition of ras signaling pathway activation and the c-Jun N-terminal kinase (JNK) and c-Jun activation, respectively. There are 7 mammalian Dok members: Dok-1 to Dok-7. Dok-1 and Dok-2 act as negative regulators of the Ras-Erk pathway downstream of many immunoreceptor-mediated signaling systems, and it is believed that recruitment of p120 rasGAP by Dok-1 and Dok-2 is critical to their negative regulation. Dok-3 is a negative regulator of the activation of JNK and mobilization of Ca2+ in B-cell receptor-mediated signaling, interacting with SHIP-1 and Grb2. Dok-4- 6 play roles in protein tyrosine kinase(PTK)-mediated signaling in neural cells and Dok-7 is the key cytoplasmic activator of MuSK (Muscle-Specific Protein Tyrosine Kinase). 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: 241318  Cd Length: 103  Bit Score: 73.23  E-value: 5.40e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41406050 151 FAVTMRPTEASERChlrGSYTLRAGESALELWGGPEPGTQLYDWPYRFLRRFGRDKVTFSFEAGRRCVSGEGNFEFETRQ 230
Cdd:cd13164   7 FNVFLLPSPNLDVY---GECLLQITHENIYLWDIHNPRVKLVSWPLCSLRRYGRDSTWFTFEAGRMCDTGEGLFTFQTRE 83

                        90
                ....*....|....
gi 41406050 231 GNEIFLALEEAISA 244
Cdd:cd13164  84 GEQIYQRVHSATLA 97
PTB_FRS2 cd01202
Fibroblast growth factor receptor substrate 2 phosphotyrosine-binding domain; FRS2 (also ...
 194-242 3.41e-14

Fibroblast growth factor receptor substrate 2 phosphotyrosine-binding domain; FRS2 (also called Suc1-associated neurotrophic factor (SNT)-induced tyrosine-phosphorylated target) proteins are membrane-anchored adaptor proteins. They are composed of an N-terminal myristoylation site followed by a phosphotyrosine binding (PTB) domain, which has a PH-like fold, and a C-terminal effector domain containing multiple tyrosine and serine/threonine phosphorylation site. The FRS2/SNT proteins show increased tyrosine phosphorylation by activated receptors, such as fibroblast growth factor receptor (FGFR) and TrkA, recruit SH2 domain containing proteins such as Grb2, and mediate signals from activated receptors to a variety of downstream pathways. The PTB domains of the SNT proteins directly interact with the canonical NPXpY motif of TrkA in a phosphorylationdependent manner, they directly bind to the juxtamembrane region of FGFR in a phosphorylation-independent manner. 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: 269913  Cd Length: 92  Bit Score: 67.61  E-value: 3.41e-14
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*....
gi 41406050 194 WPYRFLRRFGRDKVTFSFEAGRRCVSGEGNFEFETRQGNEIFLALEEAI 242
Cdd:cd01202  43 WPLLCLRRYGYDSNLFSFESGRRCATGEGIYAFKCKRAEELFNLVQRLI 91
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 6-113 1.13e-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: 44.08  E-value: 1.13e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41406050      6 VKQGFLYlQQQQTFGKKWRRFGASLYGGsdcalaRLELQEgPEKPRRCEAARKVIRLSDClRVAEAGGEASSPRDTSaFF 85
Cdd:smart00233   2 IKEGWLY-KKSGGGKKSWKKRYFVLFNS------TLLYYK-SKKDKKSYKPKGSIDLSGC-TVREAPDPDSSKKPHC-FE 71

                           90       100       110
                   ....*....|....*....|....*....|
gi 41406050     86 LETKER-LYLLAAP-AAERGDWVQAICLLA 113
Cdd:smart00233  72 IKTSDRkTLLLQAEsEEEREKWVEALRKAI 101
PH_IRS cd01257
Insulin receptor substrate (IRS) pleckstrin homology (PH) domain; Insulin receptor substrate ...
 3-109 4.06e-05

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: 42.28  E-value: 4.06e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41406050   3 DGAVKQGflYLQQQQTfGKKwRRFgaSLYGGSDCALARLELQEGPEKPRRCEAARKVIRLSDCLRVAEAGGeaSSPRDTS 82
Cdd:cd01257   1 TDVRKSG--YLKKLKT-MRK-RYF--VLRAESHGGPARLEYYENEKKFRRNAEPKRVIPLSSCFNINKRAD--AKHKHLI 72

                        90       100
                ....*....|....*....|....*...
gi 41406050  83 AFFleTK-ERLYLLAAPAAERGDWVQAI 109
Cdd:cd01257  73 ALY--TKdECFGLVAESEEEQDEWYQAL 98
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
 7-109 5.51e-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: 41.76  E-value: 5.51e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41406050   7 KQGFLYLQQQQTFgKKWRRFGASLYGGsdcalaRLELQEgpEKPRRCEAARKVIRLSDCLRVAEAggeaSSPRDTSAFFL 86
Cdd:cd00821   1 KEGYLLKRGGGGL-KSWKKRWFVLFEG------VLLYYK--SKKDSSYKPKGSIPLSGILEVEEV----SPKERPHCFEL 67

                        90       100
                ....*....|....*....|....*
gi 41406050  87 ET-KERLYLLAAP-AAERGDWVQAI 109
Cdd:cd00821  68 VTpDGRTYYLQADsEEERQEWLKAL 92
PH_AtPH1 cd13276
Arabidopsis thaliana Pleckstrin homolog (PH) 1 (AtPH1) PH domain; AtPH1 is expressed in all ...
 7-109 6.23e-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: 38.84  E-value: 6.23e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41406050   7 KQGflYLQQQQTFGKKWRRFGASLYGGSDCALARlelqegpEKPRRCEAARKVIRLSDCLRVAEAGGEASSPrdtSAFFL 86
Cdd:cd13276   1 KAG--WLEKQGEFIKTWRRRWFVLKQGKLFWFKE-------PDVTPYSKPRGVIDLSKCLTVKSAEDATNKE---NAFEL 68

                        90       100
                ....*....|....*....|....
gi 41406050  87 ET-KERLYLLAAPAAERGDWVQAI 109
Cdd:cd13276  69 STpEETFYFIADNEKEKEEWIGAI 92
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 6-112 2.19e-03

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 37.54  E-value: 2.19e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41406050     6 VKQGFLYlQQQQTFGKKWRRFGASLYGGSdcalarLELQEgPEKPRRCEAARKVIRLSDClRVAEAGGEASSPRDTSaFF 85
Cdd:pfam00169   2 VKEGWLL-KKGGGKKKSWKKRYFVLFDGS------LLYYK-DDKSGKSKEPKGSISLSGC-EVVEVVASDSPKRKFC-FE 71

                          90       100       110
                  ....*....|....*....|....*....|..
gi 41406050    86 LET-----KERLYLLAAPAAERGDWVQAICLL 112
Cdd:pfam00169  72 LRTgertgKRTYLLQAESEEERKDWIKAIQSA 103
 
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.
Help | Disclaimer | Write to the Help Desk
NCBI | NLM | NIH