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Conserved domains on  [gi|507834061|ref|NP_001265280|]
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fibroblast growth factor receptor substrate 2 [Homo sapiens]

Protein Classification

fibroblast growth factor receptor substrate( domain architecture ID 10100393)

fibroblast growth factor receptor substrate (FRS), also called SNT (Suc1-associated neurotrophic factor target), is a PTB (phosphotyrosine-binding) domain-containing protein, similar to mammalian FRS2 (SNT1) and FRS3 (SNT2), which are adapter proteins that link FGF and NGF receptors to downstream signaling pathways

Gene Ontology:  GO:0005515|GO:0005104|GO:0005068|GO:0008543|GO:0007169
PubMed:  15567406|8987385|10610414

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
PTB_FRS2 cd01202
Fibroblast growth factor receptor substrate 2 phosphotyrosine-binding domain; FRS2 (also ...
 15-106 2.93e-64

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: 203.20  E-value: 2.93e-64
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 507834061  15 DNHRNKFKVINVDDDGNELGSGIMELTDTELILYTRKRDSVKWHYLCLRRYGYDSNLFSFESGRRCQTGQGIFAFKCARA 94
Cdd:cd01202    1 DLHPNIFKVINVDDDGNELGSGILEVTETELILYQRGKEPVRWPLLCLRRYGYDSNLFSFESGRRCATGEGIYAFKCKRA 80

                         90
                 ....*....|..
gi 507834061  95 EELFNMLQEIMQ 106
Cdd:cd01202   81 EELFNLVQRLIQ 92
 
Name Accession Description Interval E-value
PTB_FRS2 cd01202
Fibroblast growth factor receptor substrate 2 phosphotyrosine-binding domain; FRS2 (also ...
 15-106 2.93e-64

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: 203.20  E-value: 2.93e-64
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 507834061  15 DNHRNKFKVINVDDDGNELGSGIMELTDTELILYTRKRDSVKWHYLCLRRYGYDSNLFSFESGRRCQTGQGIFAFKCARA 94
Cdd:cd01202    1 DLHPNIFKVINVDDDGNELGSGILEVTETELILYQRGKEPVRWPLLCLRRYGYDSNLFSFESGRRCATGEGIYAFKCKRA 80

                         90
                 ....*....|..
gi 507834061  95 EELFNMLQEIMQ 106
Cdd:cd01202   81 EELFNLVQRLIQ 92
PTBI smart00310
Phosphotyrosine-binding domain (IRS1-like);
20-110 6.62e-29

Phosphotyrosine-binding domain (IRS1-like);


Pssm-ID: 197644  Cd Length: 99  Bit Score: 109.81  E-value: 6.62e-29
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 507834061    20 KFKVINVDDDGNEL----GSGIMELTDTELILYTR---KRDSVKWHYLCLRRYGYDSNLFSFESGRRCQTGQGIFAFKCA 92
Cdd:smart00310   2 QFWVTIRKTEGLERcplsGSYRLRLTSEELVLWRGlnpRVELVVWPLLSLRRYGRDKVFFFFEAGRRCVSGPGEFTFQTV 81

                           90
                   ....*....|....*...
gi 507834061    93 RAEELFNMLQEIMQNNSI 110
Cdd:smart00310  82 VAQEIFQLVLEAMQAQKN 99
IRS pfam02174
PTB domain (IRS-1 type);
18-106 1.63e-27

PTB domain (IRS-1 type);


Pssm-ID: 460473  Cd Length: 99  Bit Score: 105.79  E-value: 1.63e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 507834061   18 RNKFKVI----NVDDDGNELGSGIMELTDTELILYTR--KRDSVKWHYLCLRRYGYDSNLFSFESGRRCQTGQGIFAFKC 91
Cdd:pfam02174   1 VEVFPVTvrrtGASERCGLSGSYRLCLTAEALTLDKLntRVPLVSWPLTSLRRYGRDKNFFSFEAGRRCVTGEGEFWFQT 80

                          90
                  ....*....|....*
gi 507834061   92 ARAEELFNMLQEIMQ 106
Cdd:pfam02174  81 DDAEEIFETVLAAMK 95
 
Name Accession Description Interval E-value
PTB_FRS2 cd01202
Fibroblast growth factor receptor substrate 2 phosphotyrosine-binding domain; FRS2 (also ...
 15-106 2.93e-64

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: 203.20  E-value: 2.93e-64
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 507834061  15 DNHRNKFKVINVDDDGNELGSGIMELTDTELILYTRKRDSVKWHYLCLRRYGYDSNLFSFESGRRCQTGQGIFAFKCARA 94
Cdd:cd01202    1 DLHPNIFKVINVDDDGNELGSGILEVTETELILYQRGKEPVRWPLLCLRRYGYDSNLFSFESGRRCATGEGIYAFKCKRA 80

                         90
                 ....*....|..
gi 507834061  95 EELFNMLQEIMQ 106
Cdd:cd01202   81 EELFNLVQRLIQ 92
PTBI smart00310
Phosphotyrosine-binding domain (IRS1-like);
20-110 6.62e-29

Phosphotyrosine-binding domain (IRS1-like);


Pssm-ID: 197644  Cd Length: 99  Bit Score: 109.81  E-value: 6.62e-29
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 507834061    20 KFKVINVDDDGNEL----GSGIMELTDTELILYTR---KRDSVKWHYLCLRRYGYDSNLFSFESGRRCQTGQGIFAFKCA 92
Cdd:smart00310   2 QFWVTIRKTEGLERcplsGSYRLRLTSEELVLWRGlnpRVELVVWPLLSLRRYGRDKVFFFFEAGRRCVSGPGEFTFQTV 81

                           90
                   ....*....|....*...
gi 507834061    93 RAEELFNMLQEIMQNNSI 110
Cdd:smart00310  82 VAQEIFQLVLEAMQAQKN 99
IRS pfam02174
PTB domain (IRS-1 type);
18-106 1.63e-27

PTB domain (IRS-1 type);


Pssm-ID: 460473  Cd Length: 99  Bit Score: 105.79  E-value: 1.63e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 507834061   18 RNKFKVI----NVDDDGNELGSGIMELTDTELILYTR--KRDSVKWHYLCLRRYGYDSNLFSFESGRRCQTGQGIFAFKC 91
Cdd:pfam02174   1 VEVFPVTvrrtGASERCGLSGSYRLCLTAEALTLDKLntRVPLVSWPLTSLRRYGRDKNFFSFEAGRRCVTGEGEFWFQT 80

                          90
                  ....*....|....*
gi 507834061   92 ARAEELFNMLQEIMQ 106
Cdd:pfam02174  81 DDAEEIFETVLAAMK 95
PTB_DOK1_DOK2_DOK3 cd01203
Downstream of tyrosine kinase 1, 2, and 3 proteins phosphotyrosine-binding domain (PTBi); The ...
 56-103 1.51e-13

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: 66.47  E-value: 1.51e-13
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 507834061  56 KWHYLCLRRYGYDSNLFSFESGRRCQTGQGIFAFKCARAEELFNMLQE 103
Cdd:cd01203   46 SWPYRFLRRFGRDKVMFSFEAGRRCDSGEGLFTFETPQGNEIFQAVEA 93
PTB cd00934
Phosphotyrosine-binding (PTB) PH-like fold; PTB domains have a common PH-like fold and are ...
 18-107 7.72e-10

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: 56.75  E-value: 7.72e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 507834061  18 RNKFKVINVDDDGNELGSGIMELTDTELILYTRKRDSV--KWHYLCLRRYGYDS---NLFSFESGRRCQTGQGIFAFKCA 92
Cdd:cd00934   25 ALKALAAALKSSKRKPGPVLLEVSSKGVKLLDLDTKELllRHPLHRISYCGRDPdnpNVFAFIAGEEGGSGFRCHVFQCE 104

                         90
                 ....*....|....*
gi 507834061  93 RAEELFNMLQEIMQN 107
Cdd:cd00934  105 DEEEAEEILQAIGQA 119
PTB_DOK4_DOK5_DOK6 cd13164
Downstream of tyrosine kinase 4, 5, and 6 proteins phosphotyrosine-binding domain (PTBi); The ...
 34-98 5.59e-09

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: 53.59  E-value: 5.59e-09
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 507834061  34 GSGIMELTDTELILYTRKRDSVK---WHYLCLRRYGYDSNLFSFESGRRCQTGQGIFAFKCARAEELF 98
Cdd:cd13164   21 GECLLQITHENIYLWDIHNPRVKlvsWPLCSLRRYGRDSTWFTFEAGRMCDTGEGLFTFQTREGEQIY 88
PTB_DOK7 cd13165
Downstream of tyrosine kinase 7 phosphotyrosine-binding domain (PTBi); The Dok family adapters ...
 57-97 8.46e-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: 38.65  E-value: 8.46e-04
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|.
gi 507834061  57 WHYLCLRRYGYDSNLFSFESGRRCQTGQGIFAFKCARAEEL 97
Cdd:cd13165   45 WKLSDLRRYGAVPGGFIFEGGTRCGKWAGVFFLSTEEGEQI 85
 
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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