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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034577653  15 DNHRNKFKVINVDDDGNELGSGIMELTDTELILYTRKRDSVKWHYLCLRRYGYDSNLFSFESGRRCQTGQGIFAFKCARA 94
Cdd:cd01202     1 DLHPNIFKVINVDDDGNELGSGILEVTETELILYQRGKEPVRWPLLCLRRYGYDSNLFSFESGRRCATGEGIYAFKCKRA 80

                          90
                  ....*....|..
gi 1034577653  95 EELFNMLQEIMQ 106
Cdd:cd01202    81 EELFNLVQRLIQ 92

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034577653  15 DNHRNKFKVINVDDDGNELGSGIMELTDTELILYTRKRDSVKWHYLCLRRYGYDSNLFSFESGRRCQTGQGIFAFKCARA 94
Cdd:cd01202     1 DLHPNIFKVINVDDDGNELGSGILEVTETELILYQRGKEPVRWPLLCLRRYGYDSNLFSFESGRRCATGEGIYAFKCKRA 80

                          90
                  ....*....|..
gi 1034577653  95 EELFNMLQEIMQ 106
Cdd:cd01202    81 EELFNLVQRLIQ 92

PTB domain (IRS-1 type);

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034577653  18 RNKFKVI----NVDDDGNELGSGIMELTDTELILYTR--KRDSVKWHYLCLRRYGYDSNLFSFESGRRCQTGQGIFAFKC 91
Cdd:pfam02174   1 VEVFPVTvrrtGASERCGLSGSYRLCLTAEALTLDKLntRVPLVSWPLTSLRRYGRDKNFFSFEAGRRCVTGEGEFWFQT 80

                          90
                  ....*....|....*
gi 1034577653  92 ARAEELFNMLQEIMQ 106
Cdd:pfam02174  81 DDAEEIFETVLAAMK 95

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034577653  15 DNHRNKFKVINVDDDGNELGSGIMELTDTELILYTRKRDSVKWHYLCLRRYGYDSNLFSFESGRRCQTGQGIFAFKCARA 94
Cdd:cd01202     1 DLHPNIFKVINVDDDGNELGSGILEVTETELILYQRGKEPVRWPLLCLRRYGYDSNLFSFESGRRCATGEGIYAFKCKRA 80

                          90
                  ....*....|..
gi 1034577653  95 EELFNMLQEIMQ 106
Cdd:cd01202    81 EELFNLVQRLIQ 92

PTB domain (IRS-1 type);

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034577653  18 RNKFKVI----NVDDDGNELGSGIMELTDTELILYTR--KRDSVKWHYLCLRRYGYDSNLFSFESGRRCQTGQGIFAFKC 91
Cdd:pfam02174   1 VEVFPVTvrrtGASERCGLSGSYRLCLTAEALTLDKLntRVPLVSWPLTSLRRYGRDKNFFSFEAGRRCVTGEGEFWFQT 80

                          90
                  ....*....|....*
gi 1034577653  92 ARAEELFNMLQEIMQ 106
Cdd:pfam02174  81 DDAEEIFETVLAAMK 95

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034577653  18 RNKFKVINVDDDGNELGSGIMELTDTELILYTRKRDSV--KWHYLCLRRYGYDS---NLFSFESGRRCQTGQGIFAFKCA 92
Cdd:cd00934    25 ALKALAAALKSSKRKPGPVLLEVSSKGVKLLDLDTKELllRHPLHRISYCGRDPdnpNVFAFIAGEEGGSGFRCHVFQCE 104

                          90
                  ....*....|....*
gi 1034577653  93 RAEELFNMLQEIMQN 107
Cdd:cd00934   105 DEEEAEEILQAIGQA 119

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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 1034577653  57 WHYLCLRRYGYDSNLFSFESGRRCQTGQGIFAFKCARAEEL 97
Cdd:cd13165    45 WKLSDLRRYGAVPGGFIFEGGTRCGKWAGVFFLSTEEGEQI 85