1XR0,2YS5,2YT2


Conserved Protein Domain Family
PTB_FRS2

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cd01202: PTB_FRS2 (this model, PSSM-Id:241238 is obsolete and has been replaced by 269913)
Click on image for an interactive view with Cn3D
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.
Statistics
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PSSM-Id: 241238
View PSSM: cd01202
Aligned: 41 rows
Threshold Bit Score: 122.277
Threshold Setting Gi: 341882776
Created: 4-Feb-2003
Updated: 1-Feb-2013
Structure
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Program:
Drawing:
Aligned Rows:
 
phosphopeptide
Conserved site includes 32 residues -Click on image for an interactive view with Cn3D
Feature 1:phosphopeptide binding site [polypeptide binding site]
Evidence:
  • Structure:1XR0; Human SNT-1 PTB domain binds FGFR1 peptide, contacts at 4A
    View structure with Cn3D
  • Comment:The SNT-1 phosphotyrosine binding (PTB) domain recognizes activated TRKs at a canonical NPXpY motif and, atypically, binds to nonphosphorylated FGFRs in a region lacking tyrosine or asparagine.
  • Structure:2YS5; Human Snt-2 PTB binds NPM-ALK peptide, contacts at 4A
    View structure with Cn3D

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                  ####             #  #          # ##       # #  # ########  # ##       
1XR0_B         8 DNHRNKFKVINVDDd---------GNELGSGIMELTDTELILYTRK---RDSVKWHYLCLRRYGYDS-NLFSFESGRRCQ 74  human
NP_493958     31 SGASHSFRVYIHGNr--------kKNELVHAWLRVTRTTITLEISK---KECLVWPLPLIRRYGYTSaGIFFFESGRRCE 99  nematode
AAX27995      52 KKWISCFSASLLNCn---------FKEIRQGLLIVRTYDIKFQYVHndrIVVLLWPLHGLRWYGRNR-SLFLFESGSRCK 121 Schistosoma jap...
XP_001951654  10 TLPPFFFKVINIDDn---------GKEKYHGQMEIATSNLILHKSG---EPSIIWPLSTIRRYGYED-FMFCFEAGRASP 76  pea aphid
XP_003144005  24 GGEVRIGEAFMSDDpeafqvfvkkRNKFIPGTLKVTENEIVFIRSR---CETLNWPLHFLRRYGFTSaGIFFFESGRRCS 100 Loa loa
XP_003243111  14 ETTSTIFKVTNIDYs---------GNEINHGQIEITDSDLIMHYANe--KSTISCPLSTIRRYGYED-FMFCFEAGRLSP 81  pea aphid
XP_003383468  18 GMQTGTFTVTNINDd---------HRLVHKGKMVVTATELIYIDNKt--KQEWEWPFKYLRRYGCEG-NVFSFEAGRKCA 85  Amphimedon quee...
EGT38711      51 HGEQPRKALIKLNN----------ELYGFKAWLRISNTTITLEVSK---NEVVRWPLQLIRRYGYTSaGIFFLESGRRCD 117 Caenorhabditis ...
XP_002632282  31 AETVHSFRVYVHGNr--------kKNEMVHAWLRVTSTTISLEITK---KECLIWPLPLIRRYGYTSaGVFFFESGRRCE 99  Caenorhabditis ...
XP_002575819  52 KRKSMCFSVSLLDHd---------FKEIRQGLITVRVYDIKFQYVHnnqTVVLLWPLHGLRWYGRNK-SLFLFQSGSRCK 121 Schistosoma man...
Feature 1        #  #####        #   #  # 
1XR0_B        75 TGQGIFAFKCARAEELFNMLQEIMQ 99  human
NP_493958    100 SGEGMFTFQSKKADEIFQLIQSLIE 124 nematode
AAX27995     122 LGPGLFVFKCKHPQKLIACLEKRIN 146 Schistosoma japonicum
XP_001951654  77 FGQGIFAFRSKDAKNIFNAVKEKLQ 101 pea aphid
XP_003144005 101 SGEGLHTFQSHQAEAIFQLVQSRIQ 125 Loa loa
XP_003243111  82 YGQGIFAFRSKDADKIFNTIKAHLQ 106 pea aphid
XP_003383468  86 NGEGTYAFICKKANILFNMVARNIT 110 Amphimedon queenslandica
EGT38711     118 SGEGMYSFSSKKAGDIFNLIQRLIE 142 Caenorhabditis brenneri
XP_002632282 100 SGEGMFTFQCKKADEIFTLIQTLIE 124 Caenorhabditis briggsae
XP_002575819 122 LGPALFIFKCKHPKRLVSCIEKRIN 146 Schistosoma mansoni

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