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Conserved domains on  [gi|221554539|ref|NP_001138347|]
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docking protein 3 isoform 2 [Homo sapiens]

Protein Classification

docking protein( domain architecture ID 10199823)

docking protein, also known as downstream of tyrosine kinase (DOK) 1/2/3, such as DOK 1, 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
PH_DOK1,2,3 cd14676
Pleckstrin homology (PH) domain of Downstream of tyrosine kinase 1, 2, and 3; The Dok family ...
 9-123 8.25e-55

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: 174.52  E-value: 8.25e-55
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221554539   9 KDGILYQQHVKFGKKCWRKVWALLYAGGPSGVARLESWEVRDGGLGaagdrSAGPGRRGERRVIRLADCVSVLPADGESC 88
Cdd:cd14676    1 KEGQLYLQQQKFFGKKWRKFWAVLYPASPCGVARLEFFEGKGGPSG-----GKPSKRESDRKVIRLSDCVSVAPAGGESS 75

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 221554539  89 -PRDTGAFLLTTTERSHLLAAQ--HRQAWMGPICQLAF 123
Cdd:cd14676   76 pPRDTAAFLLETTEKLYLLAAEaaERADWVQKLCELAF 113
PH-like super family cl17171
Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like ...
 157-215 1.11e-29

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 cd01203:

Pssm-ID: 473070  Cd Length: 99  Bit Score: 108.84  E-value: 1.11e-29
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 221554539 157 EVGEFPVVVQRTEAATRCQLKGPALLVLGPDAIQLREAKGTQALYSWPYHFLRKFGSDK 215
Cdd:cd01203    1 EVKEFPVVVQRTEASERCRLKGSYLLRAGQDALELLDPQTKKPLYSWPYRFLRRFGRDK 59
 
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 ...
 9-123 8.25e-55

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: 174.52  E-value: 8.25e-55
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221554539   9 KDGILYQQHVKFGKKCWRKVWALLYAGGPSGVARLESWEVRDGGLGaagdrSAGPGRRGERRVIRLADCVSVLPADGESC 88
Cdd:cd14676    1 KEGQLYLQQQKFFGKKWRKFWAVLYPASPCGVARLEFFEGKGGPSG-----GKPSKRESDRKVIRLSDCVSVAPAGGESS 75

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 221554539  89 -PRDTGAFLLTTTERSHLLAAQ--HRQAWMGPICQLAF 123
Cdd:cd14676   76 pPRDTAAFLLETTEKLYLLAAEaaERADWVQKLCELAF 113
PTB_DOK1_DOK2_DOK3 cd01203
Downstream of tyrosine kinase 1, 2, and 3 proteins phosphotyrosine-binding domain (PTBi); The ...
 157-215 1.11e-29

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: 108.84  E-value: 1.11e-29
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 221554539 157 EVGEFPVVVQRTEAATRCQLKGPALLVLGPDAIQLREAKGTQALYSWPYHFLRKFGSDK 215
Cdd:cd01203    1 EVKEFPVVVQRTEASERCRLKGSYLLRAGQDALELLDPQTKKPLYSWPYRFLRRFGRDK 59
IRS pfam02174
PTB domain (IRS-1 type);
158-215 1.21e-19

PTB domain (IRS-1 type);


Pssm-ID: 460473  Cd Length: 99  Bit Score: 82.30  E-value: 1.21e-19
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 221554539  158 VGEFPVVVQRTEAATRCQLKGPALLVLGPDAIQLREAKGTQALYSWPYHFLRKFGSDK 215
Cdd:pfam02174   1 VEVFPVTVRRTGASERCGLSGSYRLCLTAEALTLDKLNTRVPLVSWPLTSLRRYGRDK 58
PTBI smart00310
Phosphotyrosine-binding domain (IRS1-like);
160-215 4.54e-04

Phosphotyrosine-binding domain (IRS1-like);


Pssm-ID: 197644  Cd Length: 99  Bit Score: 38.93  E-value: 4.54e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 221554539   160 EFPVVVQRTEAATRCQLKGPALLVLGPDAIQLREAKGTQ-ALYSWPYHFLRKFGSDK 215
Cdd:smart00310   2 QFWVTIRKTEGLERCPLSGSYRLRLTSEELVLWRGLNPRvELVVWPLLSLRRYGRDK 58
 
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 ...
 9-123 8.25e-55

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: 174.52  E-value: 8.25e-55
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221554539   9 KDGILYQQHVKFGKKCWRKVWALLYAGGPSGVARLESWEVRDGGLGaagdrSAGPGRRGERRVIRLADCVSVLPADGESC 88
Cdd:cd14676    1 KEGQLYLQQQKFFGKKWRKFWAVLYPASPCGVARLEFFEGKGGPSG-----GKPSKRESDRKVIRLSDCVSVAPAGGESS 75

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 221554539  89 -PRDTGAFLLTTTERSHLLAAQ--HRQAWMGPICQLAF 123
Cdd:cd14676   76 pPRDTAAFLLETTEKLYLLAAEaaERADWVQKLCELAF 113
PTB_DOK1_DOK2_DOK3 cd01203
Downstream of tyrosine kinase 1, 2, and 3 proteins phosphotyrosine-binding domain (PTBi); The ...
 157-215 1.11e-29

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: 108.84  E-value: 1.11e-29
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 221554539 157 EVGEFPVVVQRTEAATRCQLKGPALLVLGPDAIQLREAKGTQALYSWPYHFLRKFGSDK 215
Cdd:cd01203    1 EVKEFPVVVQRTEASERCRLKGSYLLRAGQDALELLDPQTKKPLYSWPYRFLRRFGRDK 59
IRS pfam02174
PTB domain (IRS-1 type);
158-215 1.21e-19

PTB domain (IRS-1 type);


Pssm-ID: 460473  Cd Length: 99  Bit Score: 82.30  E-value: 1.21e-19
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 221554539  158 VGEFPVVVQRTEAATRCQLKGPALLVLGPDAIQLREAKGTQALYSWPYHFLRKFGSDK 215
Cdd:pfam02174   1 VEVFPVTVRRTGASERCGLSGSYRLCLTAEALTLDKLNTRVPLVSWPLTSLRRYGRDK 58
PTBI smart00310
Phosphotyrosine-binding domain (IRS1-like);
160-215 4.54e-04

Phosphotyrosine-binding domain (IRS1-like);


Pssm-ID: 197644  Cd Length: 99  Bit Score: 38.93  E-value: 4.54e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 221554539   160 EFPVVVQRTEAATRCQLKGPALLVLGPDAIQLREAKGTQ-ALYSWPYHFLRKFGSDK 215
Cdd:smart00310   2 QFWVTIRKTEGLERCPLSGSYRLRLTSEELVLWRGLNPRvELVVWPLLSLRRYGRDK 58
 
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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