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Conserved domains on  [gi|1847688212|ref|NP_001371067|]
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docking protein 3 isoform 4 [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

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List of domain hits

 Name Accession Description Interval E-value
PTB_DOK1_DOK2_DOK3 cd01203
Downstream of tyrosine kinase 1, 2, and 3 proteins phosphotyrosine-binding domain (PTBi); The ...
 156-254 7.51e-58

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: 185.11  E-value: 7.51e-58
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1847688212 156 EVGEFPVVVQRTEAATRCQLKGPALLVLGPDAIQLREAKGTQALYSWPYHFLRKFGSDKGVFSFEAGRRCHSGEGLFAFS 235
Cdd:cd01203     1 EVKEFPVVVQRTEASERCRLKGSYLLRAGQDALELLDPQTKKPLYSWPYRFLRRFGRDKVMFSFEAGRRCDSGEGLFTFE 80

                          90
                  ....*....|....*....
gi 1847688212 236 TPCAPDLCRAVAGAIARQR 254
Cdd:cd01203    81 TPQGNEIFQAVEAAIAAQK 99
PH_DOK1,2,3 cd14676
Pleckstrin homology (PH) domain of Downstream of tyrosine kinase 1, 2, and 3; The Dok family ...
 9-122 5.78e-52

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: 170.28  E-value: 5.78e-52
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1847688212   9 KDGILYQQHVK-FGKCWRKVWALLYAGGPSGVARLESWEVRDGGLGaagdrSAGPGRRGERRVIRLADCVSVLPADGESC 87
Cdd:cd14676     1 KEGQLYLQQQKfFGKKWRKFWAVLYPASPCGVARLEFFEGKGGPSG-----GKPSKRESDRKVIRLSDCVSVAPAGGESS 75

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1847688212  88 -PRDTGAFLLTTTERSHLLAAQ--HRQAWMGPICQLAF 122
Cdd:cd14676    76 pPRDTAAFLLETTEKLYLLAAEaaERADWVQKLCELAF 113
 
Name Accession Description Interval E-value
PTB_DOK1_DOK2_DOK3 cd01203
Downstream of tyrosine kinase 1, 2, and 3 proteins phosphotyrosine-binding domain (PTBi); The ...
 156-254 7.51e-58

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: 185.11  E-value: 7.51e-58
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1847688212 156 EVGEFPVVVQRTEAATRCQLKGPALLVLGPDAIQLREAKGTQALYSWPYHFLRKFGSDKGVFSFEAGRRCHSGEGLFAFS 235
Cdd:cd01203     1 EVKEFPVVVQRTEASERCRLKGSYLLRAGQDALELLDPQTKKPLYSWPYRFLRRFGRDKVMFSFEAGRRCDSGEGLFTFE 80

                          90
                  ....*....|....*....
gi 1847688212 236 TPCAPDLCRAVAGAIARQR 254
Cdd:cd01203    81 TPQGNEIFQAVEAAIAAQK 99
PH_DOK1,2,3 cd14676
Pleckstrin homology (PH) domain of Downstream of tyrosine kinase 1, 2, and 3; The Dok family ...
 9-122 5.78e-52

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: 170.28  E-value: 5.78e-52
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1847688212   9 KDGILYQQHVK-FGKCWRKVWALLYAGGPSGVARLESWEVRDGGLGaagdrSAGPGRRGERRVIRLADCVSVLPADGESC 87
Cdd:cd14676     1 KEGQLYLQQQKfFGKKWRKFWAVLYPASPCGVARLEFFEGKGGPSG-----GKPSKRESDRKVIRLSDCVSVAPAGGESS 75

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1847688212  88 -PRDTGAFLLTTTERSHLLAAQ--HRQAWMGPICQLAF 122
Cdd:cd14676    76 pPRDTAAFLLETTEKLYLLAAEaaERADWVQKLCELAF 113
IRS pfam02174
PTB domain (IRS-1 type);
157-255 1.08e-44

PTB domain (IRS-1 type);


Pssm-ID: 460473  Cd Length: 99  Bit Score: 150.86  E-value: 1.08e-44
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1847688212 157 VGEFPVVVQRTEAATRCQLKGPALLVLGPDAIQLREAKGTQALYSWPYHFLRKFGSDKGVFSFEAGRRCHSGEGLFAFST 236
Cdd:pfam02174   1 VEVFPVTVRRTGASERCGLSGSYRLCLTAEALTLDKLNTRVPLVSWPLTSLRRYGRDKNFFSFEAGRRCVTGEGEFWFQT 80

                          90
                  ....*....|....*....
gi 1847688212 237 PCAPDLCRAVAGAIARQRE 255
Cdd:pfam02174  81 DDAEEIFETVLAAMKAQKE 99
PTBI smart00310
Phosphotyrosine-binding domain (IRS1-like);
159-255 7.91e-18

Phosphotyrosine-binding domain (IRS1-like);


Pssm-ID: 197644  Cd Length: 99  Bit Score: 78.22  E-value: 7.91e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1847688212  159 EFPVVVQRTEAATRCQLKGPALLVLGPDAIQLREAKGTQ-ALYSWPYHFLRKFGSDKGVFSFEAGRRCHSGEGLFAFSTP 237
Cdd:smart00310   2 QFWVTIRKTEGLERCPLSGSYRLRLTSEELVLWRGLNPRvELVVWPLLSLRRYGRDKVFFFFEAGRRCVSGPGEFTFQTV 81

                           90
                   ....*....|....*...
gi 1847688212  238 CAPDLCRAVAGAIARQRE 255
Cdd:smart00310  82 VAQEIFQLVLEAMQAQKN 99
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 7-114 8.65e-05

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 41.39  E-value: 8.65e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1847688212   7 PIKDGILYQQHVKFGKCWRKVWALLYAGgpsgvaRLESWEvrdgglgaagdRSAGPGRRGERRVIRLADCVSVLPADGES 86
Cdd:pfam00169   1 VVKEGWLLKKGGGKKKSWKKRYFVLFDG------SLLYYK-----------DDKSGKSKEPKGSISLSGCEVVEVVASDS 63

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1847688212  87 CPRDTGaFLLTTTE----RSHLLAA---QHRQAWM 114
Cdd:pfam00169  64 PKRKFC-FELRTGErtgkRTYLLQAeseEERKDWI 97
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 7-114 2.44e-04

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: 40.22  E-value: 2.44e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1847688212    7 PIKDGILYQQHVKFGKCWRKVWALLYAGgpsgvaRLESWEVRDGGLGAAgdrsagpgrrgERRVIRLADCVSVLPADGES 86
Cdd:smart00233   1 VIKEGWLYKKSGGGKKSWKKRYFVLFNS------TLLYYKSKKDKKSYK-----------PKGSIDLSGCTVREAPDPDS 63

                           90       100       110
                   ....*....|....*....|....*....|..
gi 1847688212   87 CPRDtGAFLLTTTER-SHLLAA---QHRQAWM 114
Cdd:smart00233  64 SKKP-HCFEIKTSDRkTLLLQAeseEEREKWV 94
 
Name Accession Description Interval E-value
PTB_DOK1_DOK2_DOK3 cd01203
Downstream of tyrosine kinase 1, 2, and 3 proteins phosphotyrosine-binding domain (PTBi); The ...
 156-254 7.51e-58

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: 185.11  E-value: 7.51e-58
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1847688212 156 EVGEFPVVVQRTEAATRCQLKGPALLVLGPDAIQLREAKGTQALYSWPYHFLRKFGSDKGVFSFEAGRRCHSGEGLFAFS 235
Cdd:cd01203     1 EVKEFPVVVQRTEASERCRLKGSYLLRAGQDALELLDPQTKKPLYSWPYRFLRRFGRDKVMFSFEAGRRCDSGEGLFTFE 80

                          90
                  ....*....|....*....
gi 1847688212 236 TPCAPDLCRAVAGAIARQR 254
Cdd:cd01203    81 TPQGNEIFQAVEAAIAAQK 99
PH_DOK1,2,3 cd14676
Pleckstrin homology (PH) domain of Downstream of tyrosine kinase 1, 2, and 3; The Dok family ...
 9-122 5.78e-52

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: 170.28  E-value: 5.78e-52
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1847688212   9 KDGILYQQHVK-FGKCWRKVWALLYAGGPSGVARLESWEVRDGGLGaagdrSAGPGRRGERRVIRLADCVSVLPADGESC 87
Cdd:cd14676     1 KEGQLYLQQQKfFGKKWRKFWAVLYPASPCGVARLEFFEGKGGPSG-----GKPSKRESDRKVIRLSDCVSVAPAGGESS 75

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1847688212  88 -PRDTGAFLLTTTERSHLLAAQ--HRQAWMGPICQLAF 122
Cdd:cd14676    76 pPRDTAAFLLETTEKLYLLAAEaaERADWVQKLCELAF 113
IRS pfam02174
PTB domain (IRS-1 type);
157-255 1.08e-44

PTB domain (IRS-1 type);


Pssm-ID: 460473  Cd Length: 99  Bit Score: 150.86  E-value: 1.08e-44
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1847688212 157 VGEFPVVVQRTEAATRCQLKGPALLVLGPDAIQLREAKGTQALYSWPYHFLRKFGSDKGVFSFEAGRRCHSGEGLFAFST 236
Cdd:pfam02174   1 VEVFPVTVRRTGASERCGLSGSYRLCLTAEALTLDKLNTRVPLVSWPLTSLRRYGRDKNFFSFEAGRRCVTGEGEFWFQT 80

                          90
                  ....*....|....*....
gi 1847688212 237 PCAPDLCRAVAGAIARQRE 255
Cdd:pfam02174  81 DDAEEIFETVLAAMKAQKE 99
PTBI smart00310
Phosphotyrosine-binding domain (IRS1-like);
159-255 7.91e-18

Phosphotyrosine-binding domain (IRS1-like);


Pssm-ID: 197644  Cd Length: 99  Bit Score: 78.22  E-value: 7.91e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1847688212  159 EFPVVVQRTEAATRCQLKGPALLVLGPDAIQLREAKGTQ-ALYSWPYHFLRKFGSDKGVFSFEAGRRCHSGEGLFAFSTP 237
Cdd:smart00310   2 QFWVTIRKTEGLERCPLSGSYRLRLTSEELVLWRGLNPRvELVVWPLLSLRRYGRDKVFFFFEAGRRCVSGPGEFTFQTV 81

                           90
                   ....*....|....*...
gi 1847688212  238 CAPDLCRAVAGAIARQRE 255
Cdd:smart00310  82 VAQEIFQLVLEAMQAQKN 99
PTB_FRS2 cd01202
Fibroblast growth factor receptor substrate 2 phosphotyrosine-binding domain; FRS2 (also ...
 177-242 3.30e-15

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: 70.69  E-value: 3.30e-15
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1847688212 177 GPALLVLGPDAIQLrEAKGTQALySWPYHFLRKFGSDKGVFSFEAGRRCHSGEGLFAFSTPCAPDL 242
Cdd:cd01202    20 GSGILEVTETELIL-YQRGKEPV-RWPLLCLRRYGYDSNLFSFESGRRCATGEGIYAFKCKRAEEL 83
PTB_DOK4_DOK5_DOK6 cd13164
Downstream of tyrosine kinase 4, 5, and 6 proteins phosphotyrosine-binding domain (PTBi); The ...
 199-255 1.31e-10

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: 58.21  E-value: 1.31e-10
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1847688212 199 LYSWPYHFLRKFGSDKGVFSFEAGRRCHSGEGLFAFSTPCAPDLCRAV---AGAIARQRE 255
Cdd:cd13164    44 LVSWPLCSLRRYGRDSTWFTFEAGRMCDTGEGLFTFQTREGEQIYQRVhsaTLAIAEQHK 103
PTB cd00934
Phosphotyrosine-binding (PTB) PH-like fold; PTB domains have a common PH-like fold and are ...
 156-249 4.00e-06

Phosphotyrosine-binding (PTB) 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 bind 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.


Pssm-ID: 269911  Cd Length: 120  Bit Score: 45.58  E-value: 4.00e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1847688212 156 EVGEFPVVVQRTEAATRCQLKGPALLVLGPDAIQLREAKGTQALYSWPYHFLRKFGSDKG---VFSFEAGRRCHSGEGLF 232
Cdd:cd00934    20 DVVEEALKALAAALKSSKRKPGPVLLEVSSKGVKLLDLDTKELLLRHPLHRISYCGRDPDnpnVFAFIAGEEGGSGFRCH 99

                          90       100
                  ....*....|....*....|
gi 1847688212 233 AFSTP---CAPDLCRAVAGA 249
Cdd:cd00934   100 VFQCEdeeEAEEILQAIGQA 119
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 7-114 8.65e-05

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 41.39  E-value: 8.65e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1847688212   7 PIKDGILYQQHVKFGKCWRKVWALLYAGgpsgvaRLESWEvrdgglgaagdRSAGPGRRGERRVIRLADCVSVLPADGES 86
Cdd:pfam00169   1 VVKEGWLLKKGGGKKKSWKKRYFVLFDG------SLLYYK-----------DDKSGKSKEPKGSISLSGCEVVEVVASDS 63

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1847688212  87 CPRDTGaFLLTTTE----RSHLLAA---QHRQAWM 114
Cdd:pfam00169  64 PKRKFC-FELRTGErtgkRTYLLQAeseEERKDWI 97
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 7-114 2.44e-04

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: 40.22  E-value: 2.44e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1847688212    7 PIKDGILYQQHVKFGKCWRKVWALLYAGgpsgvaRLESWEVRDGGLGAAgdrsagpgrrgERRVIRLADCVSVLPADGES 86
Cdd:smart00233   1 VIKEGWLYKKSGGGKKSWKKRYFVLFNS------TLLYYKSKKDKKSYK-----------PKGSIDLSGCTVREAPDPDS 63

                           90       100       110
                   ....*....|....*....|....*....|..
gi 1847688212   87 CPRDtGAFLLTTTER-SHLLAA---QHRQAWM 114
Cdd:smart00233  64 SKKP-HCFEIKTSDRkTLLLQAeseEEREKWV 94
PTB_DOK7 cd13165
Downstream of tyrosine kinase 7 phosphotyrosine-binding domain (PTBi); The Dok family adapters ...
 156-236 6.16e-04

Downstream of tyrosine kinase 7 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: 269986  Cd Length: 101  Bit Score: 39.03  E-value: 6.16e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1847688212 156 EVGEFPVVVQrteAATRCQlKGPALLVLGPDAIQLREAKGTQALYSWPYHFLRKFGSDKGVFSFEAGRRCHSGEGLFAFS 235
Cdd:cd13165     3 EVHRFPVVVA---PGTKLE-SGPATLHFCNDILVLARDVPPAVLGQWKLSDLRRYGAVPGGFIFEGGTRCGKWAGVFFLS 78


                  .
gi 1847688212 236 T 236
Cdd:cd13165    79 T 79
 
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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