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Protein

Fibroblast growth factor receptor substrate 3

Gene

FRS3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Adapter protein that links FGF and NGF receptors to downstream signaling pathways. Involved in the activation of MAP kinases. Down-regulates ERK2 signaling by interfering with the phosphorylation and nuclear translocation of ERK2.1 Publication

GO - Molecular functioni

  • fibroblast growth factor receptor binding Source: MGI
  • identical protein binding Source: IntAct
  • Ras guanyl-nucleotide exchange factor activity Source: Reactome

GO - Biological processi

  • fibroblast growth factor receptor signaling pathway Source: MGI
  • MAPK cascade Source: Reactome
  • positive regulation of GTPase activity Source: GOC
  • signal transduction Source: ProtInc
Complete GO annotation...

Enzyme and pathway databases

ReactomeiR-HSA-5654693. FRS-mediated FGFR1 signaling.
R-HSA-5654699. SHC-mediated cascade:FGFR2.
R-HSA-5654700. FRS-mediated FGFR2 signaling.
R-HSA-5654706. FRS-mediated FGFR3 signaling.
R-HSA-5654712. FRS-mediated FGFR4 signaling.
R-HSA-5654719. SHC-mediated cascade:FGFR4.
R-HSA-5673001. RAF/MAP kinase cascade.
SignaLinkiO43559.

Names & Taxonomyi

Protein namesi
Recommended name:
Fibroblast growth factor receptor substrate 3
Short name:
FGFR substrate 3
Alternative name(s):
FGFR-signaling adaptor SNT2
Suc1-associated neurotrophic factor target 2
Short name:
SNT-2
Gene namesi
Name:FRS3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

HGNCiHGNC:16970. FRS3.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA134961503.

Polymorphism and mutation databases

BioMutaiFRS3.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedSequence analysis
Chaini2 – 492491Fibroblast growth factor receptor substrate 3PRO_0000087346Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi2 – 21N-myristoyl glycine1 Publication

Post-translational modificationi

Phosphorylated by ULK2 in vitro (By similarity). Phosphorylated on tyrosine residues upon stimulation by BFGF or NGFB.By similarity2 Publications

Keywords - PTMi

Lipoprotein, Myristate, Phosphoprotein

Proteomic databases

MaxQBiO43559.
PaxDbiO43559.
PeptideAtlasiO43559.
PRIDEiO43559.

PTM databases

iPTMnetiO43559.
PhosphoSiteiO43559.

Expressioni

Gene expression databases

BgeeiO43559.
CleanExiHS_FRS3.
ExpressionAtlasiO43559. baseline and differential.
GenevisibleiO43559. HS.

Organism-specific databases

HPAiHPA030162.
HPA030174.

Interactioni

Subunit structurei

Binds NTRK1 (By similarity). Binds FGFR1, NGFR, GRB2, PTPN11 and ERK2.By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
itself2EBI-725515,EBI-725515
Q9WMX23EBI-725515,EBI-6863741From a different organism.
ADAMTSL4Q6UY14-33EBI-725515,EBI-10173507
AESQ081173EBI-725515,EBI-717810
GATA1P159763EBI-725515,EBI-3909284
HCKP08631-22EBI-725515,EBI-9834454
NOTCH2NLQ7Z3S93EBI-725515,EBI-945833
PIK3R3Q925693EBI-725515,EBI-79893
PLSCR1O151623EBI-725515,EBI-740019
RFX6Q8HWS33EBI-725515,EBI-746118
SOCS4Q8WXH52EBI-725515,EBI-3942425
SPERTQ8NA613EBI-725515,EBI-741724
SPRY2O435973EBI-725515,EBI-742487
TCF4P158843EBI-725515,EBI-533224
TRIP6Q156543EBI-725515,EBI-742327

GO - Molecular functioni

  • fibroblast growth factor receptor binding Source: MGI
  • identical protein binding Source: IntAct

Protein-protein interaction databases

BioGridi116030. 29 interactions.
IntActiO43559. 24 interactions.
MINTiMINT-1392767.
STRINGi9606.ENSP00000259748.

Structurei

Secondary structure

1
492
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi11 – 133Combined sources
Beta strandi18 – 269Combined sources
Beta strandi32 – 409Combined sources
Beta strandi45 – 484Combined sources
Beta strandi50 – 523Combined sources
Beta strandi55 – 573Combined sources
Helixi59 – 613Combined sources
Beta strandi65 – 684Combined sources
Beta strandi71 – 766Combined sources
Beta strandi80 – 823Combined sources
Beta strandi84 – 907Combined sources
Helixi94 – 10512Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2KUPNMR-A8-146[»]
2KUQNMR-A8-120[»]
2YS5NMR-A8-146[»]
2YT2NMR-A8-120[»]
ProteinModelPortaliO43559.
SMRiO43559. Positions 3-146.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO43559.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini13 – 115103IRS-type PTBPROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Contains 1 IRS-type PTB domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG4047. Eukaryota.
ENOG410XS2S. LUCA.
GeneTreeiENSGT00510000046707.
HOGENOMiHOG000290694.
HOVERGENiHBG062705.
InParanoidiO43559.
OMAiRHCLQPL.
OrthoDBiEOG7QG43P.
PhylomeDBiO43559.
TreeFamiTF324994.

Family and domain databases

Gene3Di2.30.29.30. 1 hit.
InterProiIPR002404. IRS_PTB.
IPR011993. PH_dom-like.
[Graphical view]
PfamiPF02174. IRS. 1 hit.
[Graphical view]
SMARTiSM00310. PTBI. 1 hit.
[Graphical view]
SUPFAMiSSF50729. SSF50729. 1 hit.
PROSITEiPS51064. IRS_PTB. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

O43559-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGSCCSCLNR DSVPDNHPTK FKVTNVDDEG VELGSGVMEL TQSELVLHLH
60 70 80 90 100
RREAVRWPYL CLRRYGYDSN LFSFESGRRC QTGQGIFAFK CSRAEEIFNL
110 120 130 140 150
LQDLMQCNSI NVMEEPVIIT RNSHPAELDL PRAPQPPNAL GYTVSSFSNG
160 170 180 190 200
CPGEGPRFSA PRRLSTSSLR HPSLGEESTH ALIAPDEQSH TYVNTPASED
210 220 230 240 250
DHRRGRHCLQ PLPEGQAPFL PQARGPDQRD PQVFLQPGQV KFVLGPTPAR
260 270 280 290 300
RHMVKCQGLC PSLHDPPHHN NNNEAPSECP AQPKCTYENV TGGLWRGAGW
310 320 330 340 350
RLSPEEPGWN GLAHRRAALL HYENLPPLPP VWESQAQQLG GEAGDDGDSR
360 370 380 390 400
DGLTPSSNGF PDGEEDETPL QKPTSTRAAI RSHGSFPVPL TRRRGSPRVF
410 420 430 440 450
NFDFRRPGPE PPRQLNYIQV ELKGWGGDRP KGPQNPSSPQ APMPTTHPAR
460 470 480 490
SSDSYAVIDL KKTVAMSNLQ RALPRDDGTA RKTRHNSTDL PL
Length:492
Mass (Da):54,462
Last modified:January 23, 2007 - v3
Checksum:iF06BFC662B531765
GO

Sequence cautioni

The sequence CAI13184.2 differs from that shown. Reason: Erroneous gene model prediction. Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti221 – 2211P → L.
Corresponds to variant rs3747747 [ dbSNP | Ensembl ].
VAR_033855

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF036718 mRNA. Translation: AAB92555.1.
CR457026 mRNA. Translation: CAG33307.1.
AL365205 Genomic DNA. Translation: CAI13183.1.
AL365205 Genomic DNA. Translation: CAI13184.2. Sequence problems.
BC010611 mRNA. Translation: AAH10611.1.
CCDSiCCDS4860.1.
RefSeqiNP_006644.1. NM_006653.4.
XP_011512556.1. XM_011514254.1.
XP_011512557.1. XM_011514255.1.
UniGeneiHs.194208.

Genome annotation databases

EnsembliENST00000259748; ENSP00000259748; ENSG00000137218.
ENST00000373018; ENSP00000362109; ENSG00000137218.
GeneIDi10817.
KEGGihsa:10817.
UCSCiuc003orc.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF036718 mRNA. Translation: AAB92555.1.
CR457026 mRNA. Translation: CAG33307.1.
AL365205 Genomic DNA. Translation: CAI13183.1.
AL365205 Genomic DNA. Translation: CAI13184.2. Sequence problems.
BC010611 mRNA. Translation: AAH10611.1.
CCDSiCCDS4860.1.
RefSeqiNP_006644.1. NM_006653.4.
XP_011512556.1. XM_011514254.1.
XP_011512557.1. XM_011514255.1.
UniGeneiHs.194208.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2KUPNMR-A8-146[»]
2KUQNMR-A8-120[»]
2YS5NMR-A8-146[»]
2YT2NMR-A8-120[»]
ProteinModelPortaliO43559.
SMRiO43559. Positions 3-146.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116030. 29 interactions.
IntActiO43559. 24 interactions.
MINTiMINT-1392767.
STRINGi9606.ENSP00000259748.

PTM databases

iPTMnetiO43559.
PhosphoSiteiO43559.

Polymorphism and mutation databases

BioMutaiFRS3.

Proteomic databases

MaxQBiO43559.
PaxDbiO43559.
PeptideAtlasiO43559.
PRIDEiO43559.

Protocols and materials databases

DNASUi10817.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000259748; ENSP00000259748; ENSG00000137218.
ENST00000373018; ENSP00000362109; ENSG00000137218.
GeneIDi10817.
KEGGihsa:10817.
UCSCiuc003orc.3. human.

Organism-specific databases

CTDi10817.
GeneCardsiFRS3.
HGNCiHGNC:16970. FRS3.
HPAiHPA030162.
HPA030174.
MIMi607744. gene.
neXtProtiNX_O43559.
PharmGKBiPA134961503.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4047. Eukaryota.
ENOG410XS2S. LUCA.
GeneTreeiENSGT00510000046707.
HOGENOMiHOG000290694.
HOVERGENiHBG062705.
InParanoidiO43559.
OMAiRHCLQPL.
OrthoDBiEOG7QG43P.
PhylomeDBiO43559.
TreeFamiTF324994.

Enzyme and pathway databases

ReactomeiR-HSA-5654693. FRS-mediated FGFR1 signaling.
R-HSA-5654699. SHC-mediated cascade:FGFR2.
R-HSA-5654700. FRS-mediated FGFR2 signaling.
R-HSA-5654706. FRS-mediated FGFR3 signaling.
R-HSA-5654712. FRS-mediated FGFR4 signaling.
R-HSA-5654719. SHC-mediated cascade:FGFR4.
R-HSA-5673001. RAF/MAP kinase cascade.
SignaLinkiO43559.

Miscellaneous databases

ChiTaRSiFRS3. human.
EvolutionaryTraceiO43559.
GeneWikiiFRS3.
GenomeRNAii10817.
PROiO43559.
SOURCEiSearch...

Gene expression databases

BgeeiO43559.
CleanExiHS_FRS3.
ExpressionAtlasiO43559. baseline and differential.
GenevisibleiO43559. HS.

Family and domain databases

Gene3Di2.30.29.30. 1 hit.
InterProiIPR002404. IRS_PTB.
IPR011993. PH_dom-like.
[Graphical view]
PfamiPF02174. IRS. 1 hit.
[Graphical view]
SMARTiSM00310. PTBI. 1 hit.
[Graphical view]
SUPFAMiSSF50729. SSF50729. 1 hit.
PROSITEiPS51064. IRS_PTB. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Novel recognition motif on fibroblast growth factor receptor mediates direct association and activation of SNT adapter proteins."
    Xu H., Lee K.W., Goldfarb M.P.
    J. Biol. Chem. 273:17987-17990(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], MYRISTOYLATION AT GLY-2, PHOSPHORYLATION AT TYROSINE RESIDUES, INTERACTION WITH FGFR1.
    Tissue: Placenta.
  2. "Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
    Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
    Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
  3. "The DNA sequence and analysis of human chromosome 6."
    Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D.
    , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.
    Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Brain.
  5. "SNT-2 interacts with ERK2 and negatively regulates ERK2 signaling in response to EGF stimulation."
    Huang L., Gotoh N., Zhang S., Shibuya M., Yamamoto T., Tsuchida N.
    Biochem. Biophys. Res. Commun. 324:1011-1017(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH ERK2.
  6. "FRS2 family docking proteins with overlapping roles in activation of MAP kinase have distinct spatial-temporal patterns of expression of their transcripts."
    Gotoh N., Laks S., Nakashima M., Lax I., Schlessinger J.
    FEBS Lett. 564:14-18(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH FGFR1; NGFR; GRB2 AND PTPN11, PHOSPHORYLATION AT TYROSINE RESIDUES.
  7. "Solution structure of the complex of the PTB domain of SNT-2 and 19-residue peptide (aa 1571-1589) of HALK."
    RIKEN structural genomics initiative (RSGI)
    Submitted (FEB-2009) to the PDB data bank
    Cited for: STRUCTURE BY NMR OF 6-146.

Entry informationi

Entry nameiFRS3_HUMAN
AccessioniPrimary (citable) accession number: O43559
Secondary accession number(s): Q5T3D5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 19, 2005
Last sequence update: January 23, 2007
Last modified: June 8, 2016
This is version 126 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.