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Conserved domains on  [gi|255069732|ref|NP_001157158|]
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docking protein 5 isoform 2 [Mus musculus]

Protein Classification

docking protein 4/5/6( domain architecture ID 10199829)

docking protein 4/5/6, also known as downstream of tyrosine kinase (DOK) 4/5/6, play roles in protein tyrosine kinase(PTK)-mediated signaling in neural cells

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_DOK4_DOK5_DOK6 cd13164
Downstream of tyrosine kinase 4, 5, and 6 proteins phosphotyrosine-binding domain (PTBi); The ...
 133-235 2.08e-73

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: 220.76  E-value: 2.08e-73
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255069732 133 REQSERFNVYLMPSPNLDVHGECALQITYEYICLWDVQNPRVKLISWPLSALRRYGRDTTWFTFEAGRMCETGEGLFIFQ 212
Cdd:cd13164    1 REQNERFNVFLLPSPNLDVYGECLLQITHENIYLWDIHNPRVKLVSWPLCSLRRYGRDSTWFTFEAGRMCDTGEGLFTFQ 80

                         90       100
                 ....*....|....*....|...
gi 255069732 213 TRDGEAIYQKVHSAALAIAEQHE 235
Cdd:cd13164   81 TREGEQIYQRVHSATLAIAEQHK 103
PH_DOK4_DOK5_DOK6 cd14678
Pleckstrin homology (PH) domain of Downstream of tyrosine kinase 4, 5, and 6 proteins; The Dok ...
 9-113 1.05e-69

Pleckstrin homology (PH) domain of Downstream of tyrosine kinase 4, 5, and 6 proteins; 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). 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: 270197  Cd Length: 105  Bit Score: 211.53  E-value: 1.05e-69
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255069732   9 VKQGYVRIRSRRLGIYQRCWLVFKKASSKGPKRLEKFSDERAAYFRCYHKVTELNNVKNVARLPKSTKKHAIGIYFNDDT 88
Cdd:cd14678    1 VKQGYVRIRSRKLGIYRRCWLVFRKASSKGPKRLEKYPDERAAYLRACHKVTELSNVKNITRLPKETKRHAVAIIFTDDS 80

                         90       100
                 ....*....|....*....|....*
gi 255069732  89 SKTFACESDLEADEWCKVLQMECVG 113
Cdd:cd14678   81 SKTFACDSELEAEEWCKVLSMECLG 105
 
Name Accession Description Interval E-value
PTB_DOK4_DOK5_DOK6 cd13164
Downstream of tyrosine kinase 4, 5, and 6 proteins phosphotyrosine-binding domain (PTBi); The ...
 133-235 2.08e-73

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: 220.76  E-value: 2.08e-73
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255069732 133 REQSERFNVYLMPSPNLDVHGECALQITYEYICLWDVQNPRVKLISWPLSALRRYGRDTTWFTFEAGRMCETGEGLFIFQ 212
Cdd:cd13164    1 REQNERFNVFLLPSPNLDVYGECLLQITHENIYLWDIHNPRVKLVSWPLCSLRRYGRDSTWFTFEAGRMCDTGEGLFTFQ 80

                         90       100
                 ....*....|....*....|...
gi 255069732 213 TRDGEAIYQKVHSAALAIAEQHE 235
Cdd:cd13164   81 TREGEQIYQRVHSATLAIAEQHK 103
PH_DOK4_DOK5_DOK6 cd14678
Pleckstrin homology (PH) domain of Downstream of tyrosine kinase 4, 5, and 6 proteins; The Dok ...
 9-113 1.05e-69

Pleckstrin homology (PH) domain of Downstream of tyrosine kinase 4, 5, and 6 proteins; 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). 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: 270197  Cd Length: 105  Bit Score: 211.53  E-value: 1.05e-69
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255069732   9 VKQGYVRIRSRRLGIYQRCWLVFKKASSKGPKRLEKFSDERAAYFRCYHKVTELNNVKNVARLPKSTKKHAIGIYFNDDT 88
Cdd:cd14678    1 VKQGYVRIRSRKLGIYRRCWLVFRKASSKGPKRLEKYPDERAAYLRACHKVTELSNVKNITRLPKETKRHAVAIIFTDDS 80

                         90       100
                 ....*....|....*....|....*
gi 255069732  89 SKTFACESDLEADEWCKVLQMECVG 113
Cdd:cd14678   81 SKTFACDSELEAEEWCKVLSMECLG 105
IRS pfam02174
PTB domain (IRS-1 type);
137-232 1.01e-39

PTB domain (IRS-1 type);


Pssm-ID: 460473  Cd Length: 99  Bit Score: 134.30  E-value: 1.01e-39
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255069732  137 ERFNV---YLMPSPNLDVHGECALQITYEYICLwDVQNPRVKLISWPLSALRRYGRDTTWFTFEAGRMCETGEGLFIFQT 213
Cdd:pfam02174   2 EVFPVtvrRTGASERCGLSGSYRLCLTAEALTL-DKLNTRVPLVSWPLTSLRRYGRDKNFFSFEAGRRCVTGEGEFWFQT 80

                          90
                  ....*....|....*....
gi 255069732  214 RDGEAIYQKVHSAALAIAE 232
Cdd:pfam02174  81 DDAEEIFETVLAAMKAQKE 99
PTBI smart00310
Phosphotyrosine-binding domain (IRS1-like);
131-232 1.67e-29

Phosphotyrosine-binding domain (IRS1-like);


Pssm-ID: 197644  Cd Length: 99  Bit Score: 107.88  E-value: 1.67e-29
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255069732   131 VEREQSERFNVYLMPSPNldvHGECALQITYEYICLWDVQNPRVKLISWPLSALRRYGRDTTWFTFEAGRMCETGEGLFI 210
Cdd:smart00310   1 KQFWVTIRKTEGLERCPL---SGSYRLRLTSEELVLWRGLNPRVELVVWPLLSLRRYGRDKVFFFFEAGRRCVSGPGEFT 77

                           90       100
                   ....*....|....*....|..
gi 255069732   211 FQTRDGEAIYQKVHSAALAIAE 232
Cdd:smart00310  78 FQTVVAQEIFQLVLEAMQAQKN 99
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 8-111 5.03e-07

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: 47.16  E-value: 5.03e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255069732     8 IVKQGYVRIRS-RRLGIYQRCWLVFKkasskgPKRLEKFSDERAAYFRCYHKVTELNN--VKNVARLPKSTKKHAIGIYF 84
Cdd:smart00233   1 VIKEGWLYKKSgGGKKSWKKRYFVLF------NSTLLYYKSKKDKKSYKPKGSIDLSGctVREAPDPDSSKKPHCFEIKT 74

                           90       100
                   ....*....|....*....|....*..
gi 255069732    85 NDDTSKTFACESDLEADEWCKVLQMEC 111
Cdd:smart00233  75 SDRKTLLLQAESEEEREKWVEALRKAI 101
 
Name Accession Description Interval E-value
PTB_DOK4_DOK5_DOK6 cd13164
Downstream of tyrosine kinase 4, 5, and 6 proteins phosphotyrosine-binding domain (PTBi); The ...
 133-235 2.08e-73

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: 220.76  E-value: 2.08e-73
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255069732 133 REQSERFNVYLMPSPNLDVHGECALQITYEYICLWDVQNPRVKLISWPLSALRRYGRDTTWFTFEAGRMCETGEGLFIFQ 212
Cdd:cd13164    1 REQNERFNVFLLPSPNLDVYGECLLQITHENIYLWDIHNPRVKLVSWPLCSLRRYGRDSTWFTFEAGRMCDTGEGLFTFQ 80

                         90       100
                 ....*....|....*....|...
gi 255069732 213 TRDGEAIYQKVHSAALAIAEQHE 235
Cdd:cd13164   81 TREGEQIYQRVHSATLAIAEQHK 103
PH_DOK4_DOK5_DOK6 cd14678
Pleckstrin homology (PH) domain of Downstream of tyrosine kinase 4, 5, and 6 proteins; The Dok ...
 9-113 1.05e-69

Pleckstrin homology (PH) domain of Downstream of tyrosine kinase 4, 5, and 6 proteins; 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). 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: 270197  Cd Length: 105  Bit Score: 211.53  E-value: 1.05e-69
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255069732   9 VKQGYVRIRSRRLGIYQRCWLVFKKASSKGPKRLEKFSDERAAYFRCYHKVTELNNVKNVARLPKSTKKHAIGIYFNDDT 88
Cdd:cd14678    1 VKQGYVRIRSRKLGIYRRCWLVFRKASSKGPKRLEKYPDERAAYLRACHKVTELSNVKNITRLPKETKRHAVAIIFTDDS 80

                         90       100
                 ....*....|....*....|....*
gi 255069732  89 SKTFACESDLEADEWCKVLQMECVG 113
Cdd:cd14678   81 SKTFACDSELEAEEWCKVLSMECLG 105
IRS pfam02174
PTB domain (IRS-1 type);
137-232 1.01e-39

PTB domain (IRS-1 type);


Pssm-ID: 460473  Cd Length: 99  Bit Score: 134.30  E-value: 1.01e-39
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255069732  137 ERFNV---YLMPSPNLDVHGECALQITYEYICLwDVQNPRVKLISWPLSALRRYGRDTTWFTFEAGRMCETGEGLFIFQT 213
Cdd:pfam02174   2 EVFPVtvrRTGASERCGLSGSYRLCLTAEALTL-DKLNTRVPLVSWPLTSLRRYGRDKNFFSFEAGRRCVTGEGEFWFQT 80

                          90
                  ....*....|....*....
gi 255069732  214 RDGEAIYQKVHSAALAIAE 232
Cdd:pfam02174  81 DDAEEIFETVLAAMKAQKE 99
PTBI smart00310
Phosphotyrosine-binding domain (IRS1-like);
131-232 1.67e-29

Phosphotyrosine-binding domain (IRS1-like);


Pssm-ID: 197644  Cd Length: 99  Bit Score: 107.88  E-value: 1.67e-29
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255069732   131 VEREQSERFNVYLMPSPNldvHGECALQITYEYICLWDVQNPRVKLISWPLSALRRYGRDTTWFTFEAGRMCETGEGLFI 210
Cdd:smart00310   1 KQFWVTIRKTEGLERCPL---SGSYRLRLTSEELVLWRGLNPRVELVVWPLLSLRRYGRDKVFFFFEAGRRCVSGPGEFT 77

                           90       100
                   ....*....|....*....|..
gi 255069732   211 FQTRDGEAIYQKVHSAALAIAE 232
Cdd:smart00310  78 FQTVVAQEIFQLVLEAMQAQKN 99
PTB_DOK1_DOK2_DOK3 cd01203
Downstream of tyrosine kinase 1, 2, and 3 proteins phosphotyrosine-binding domain (PTBi); The ...
 149-233 4.90e-23

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: 91.12  E-value: 4.90e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255069732 149 LDVHGECALQITYEYICLWDVQNPRVkLISWPLSALRRYGRDTTWFTFEAGRMCETGEGLFIFQTRDGEAIYQKVHSaal 228
Cdd:cd01203   18 CRLKGSYLLRAGQDALELLDPQTKKP-LYSWPYRFLRRFGRDKVMFSFEAGRRCDSGEGLFTFETPQGNEIFQAVEA--- 93


                 ....*
gi 255069732 229 AIAEQ 233
Cdd:cd01203   94 AIAAQ 98
PTB_FRS2 cd01202
Fibroblast growth factor receptor substrate 2 phosphotyrosine-binding domain; FRS2 (also ...
 177-223 8.37e-16

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: 71.46  E-value: 8.37e-16
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 255069732 177 ISWPLSALRRYGRDTTWFTFEAGRMCETGEGLFIFQTRDGEAIYQKV 223
Cdd:cd01202   41 VRWPLLCLRRYGYDSNLFSFESGRRCATGEGIYAFKCKRAEELFNLV 87
PH1_PH_fungal cd13298
Fungal proteins Pleckstrin homology (PH) domain, repeat 1; The functions of these fungal ...
 5-107 1.29e-07

Fungal proteins Pleckstrin homology (PH) domain, repeat 1; The functions of these fungal proteins are unknown, but they all contain 2 PH domains. This cd represents the first PH repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270110  Cd Length: 106  Bit Score: 49.16  E-value: 1.29e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255069732   5 FNDIVKQGYVRIRSRRLGIYQRCWLVFKkasskgPKRLEKFSDERAAyfrCYHKVTELNNVKNVARLPKSTKKHAIGIYF 84
Cdd:cd13298    3 FDRVLKSGYLLKRSRKTKNWKKRWVVLR------PCQLSYYKDEKEY---KLRRVINLSELLAVAPLKDKKRKNVFGIYT 73

                         90       100
                 ....*....|....*....|...
gi 255069732  85 NDDTSKtFACESDLEADEWCKVL 107
Cdd:cd13298   74 PSKNLH-FRATSEKDANEWVEAL 95
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 8-111 5.03e-07

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: 47.16  E-value: 5.03e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255069732     8 IVKQGYVRIRS-RRLGIYQRCWLVFKkasskgPKRLEKFSDERAAYFRCYHKVTELNN--VKNVARLPKSTKKHAIGIYF 84
Cdd:smart00233   1 VIKEGWLYKKSgGGKKSWKKRYFVLF------NSTLLYYKSKKDKKSYKPKGSIDLSGctVREAPDPDSSKKPHCFEIKT 74

                           90       100
                   ....*....|....*....|....*..
gi 255069732    85 NDDTSKTFACESDLEADEWCKVLQMEC 111
Cdd:smart00233  75 SDRKTLLLQAESEEEREKWVEALRKAI 101
PTB cd00934
Phosphotyrosine-binding (PTB) PH-like fold; PTB domains have a common PH-like fold and are ...
 128-229 6.11e-07

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: 47.50  E-value: 6.11e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255069732 128 ATGVEREQSERFNVYLMPSPNLDVHGECALQITYEYICLWDVQNPRVkLISWPLSALRRYGRD---TTWFTFEAGRMCET 204
Cdd:cd00934   16 SRGVDVVEEALKALAAALKSSKRKPGPVLLEVSSKGVKLLDLDTKEL-LLRHPLHRISYCGRDpdnPNVFAFIAGEEGGS 94

                         90       100
                 ....*....|....*....|....*
gi 255069732 205 GEGLFIFQTRDGEAIYQKVHSAALA 229
Cdd:cd00934   95 GFRCHVFQCEDEEEAEEILQAIGQA 119
PTB_DOK7 cd13165
Downstream of tyrosine kinase 7 phosphotyrosine-binding domain (PTBi); The Dok family adapters ...
 138-219 1.29e-06

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: 45.97  E-value: 1.29e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255069732 138 RFNVYLMPSPNLDVhGECALQITYEYICLWDVQNPRVkLISWPLSALRRYGRDTTWFTFEAGRMCETGEGLFIFQTRDGE 217
Cdd:cd13165    6 RFPVVVAPGTKLES-GPATLHFCNDILVLARDVPPAV-LGQWKLSDLRRYGAVPGGFIFEGGTRCGKWAGVFFLSTEEGE 83


                 ..
gi 255069732 218 AI 219
Cdd:cd13165   84 QI 85
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
 10-107 1.03e-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: 43.30  E-value: 1.03e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255069732  10 KQGYVRIRSRR-LGIYQRCWLVFKKasskgpKRLEKFSDERAAYFRCYHKVtELNNVKNVARLPKSTKKHAIGIYFNDDT 88
Cdd:cd00821    1 KEGYLLKRGGGgLKSWKKRWFVLFE------GVLLYYKSKKDSSYKPKGSI-PLSGILEVEEVSPKERPHCFELVTPDGR 73

                         90
                 ....*....|....*....
gi 255069732  89 SKTFACESDLEADEWCKVL 107
Cdd:cd00821   74 TYYLQADSEEERQEWLKAL 92
PH_IRS cd01257
Insulin receptor substrate (IRS) pleckstrin homology (PH) domain; Insulin receptor substrate ...
 6-107 2.18e-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: 42.66  E-value: 2.18e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255069732   6 NDIVKQGYVR-IRSRRlgiyqRCWLVFKKASSKGPKRLEKFSDE----RAAYFRcyhKVTELNNVKNVARLPKSTKKHAI 80
Cdd:cd01257    1 TDVRKSGYLKkLKTMR-----KRYFVLRAESHGGPARLEYYENEkkfrRNAEPK---RVIPLSSCFNINKRADAKHKHLI 72

                         90       100
                 ....*....|....*....|....*..
gi 255069732  81 GIYFNDDTSkTFACESDLEADEWCKVL 107
Cdd:cd01257   73 ALYTKDECF-GLVAESEEEQDEWYQAL 98
PH_PLEKHJ1 cd13258
Pleckstrin homology domain containing, family J member 1 Pleckstrin homology (PH) domain; ...
 31-109 6.28e-04

Pleckstrin homology domain containing, family J member 1 Pleckstrin homology (PH) domain; PLEKHJ1 (also called GNRPX2/Guanine nucleotide-releasing protein x ). It contains a single PH domain. Very little information is known about PLEKHJ1. PLEKHJ1 has been shown to interact with IKBKG (inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma) and KRT33B (keratin 33B). 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: 270078  Cd Length: 123  Bit Score: 38.84  E-value: 6.28e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255069732  31 FKKASSKGPKRLEKFSdERaaYFRC------YHKVTELNNVK-----------NVARLPKSTKKHAIGIYFNDDTSKT-- 91
Cdd:cd13258   22 IAERQMGGPKKSEVFK-ER--WFKLkgnllfYFRTNEFGDCSepigaivlencRVQMEEITEKPFAFSIVFNDEPEKKyi 98

                         90
                 ....*....|....*...
gi 255069732  92 FACESDLEADEWCKVLQM 109
Cdd:cd13258   99 FSCRSEEQCEQWIEALRQ 116
 
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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