Human Gene GRB2 (ENST00000392564.5) Description and Page Index
  Description: Adapter protein that provides a critical link between cell surface growth factor receptors and the Ras signaling pathway. (from UniProt P62993)
Gencode Transcript: ENST00000392564.5
Gencode Gene: ENSG00000177885.15
Transcript (Including UTRs)
   Position: hg38 chr17:75,318,076-75,393,864 Size: 75,789 Total Exon Count: 5 Strand: -
Coding Region
   Position: hg38 chr17:75,320,368-75,393,628 Size: 73,261 Coding Exon Count: 5 

Page IndexSequence and LinksUniProtKB CommentsProtein StructureOther NamesMethods
Data last updated at UCSC: 2021-06-20 19:51:40

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr17:75,318,076-75,393,864)mRNA (may differ from genome)Protein (217 aa)
Gene SorterGenome BrowserOther Species FASTATable SchemaExonPrimerGeneCards
HGNCMGIPubMedUniProtKB

-  Comments and Description Text from UniProtKB
  ID: GRB2_HUMAN
DESCRIPTION: RecName: Full=Growth factor receptor-bound protein 2; AltName: Full=Adapter protein GRB2; AltName: Full=Protein Ash; AltName: Full=SH2/SH3 adapter GRB2;
FUNCTION: Adapter protein that provides a critical link between cell surface growth factor receptors and the Ras signaling pathway.
FUNCTION: Isoform 2 does not bind to phosphorylated epidermal growth factor receptor (EGFR) but inhibits EGF-induced transactivation of a RAS-responsive element. Isoform 2 acts as a dominant negative protein over GRB2 and by suppressing proliferative signals, may trigger active programmed cell death.
SUBUNIT: Associates with activated Tyr-phosphorylated EGF receptor/EGFR and PDGF receptors via its SH2 domain. Also associates to other cellular Tyr-phosphorylated proteins such as SIT1, IRS1, IRS4, SHC and LNK; probably via the concerted action of both its SH2 and SH3 domains. It also seems to interact with RAS in the signaling pathway leading to DNA synthesis. Binds to and translocates the guanine nucleotide exchange factors SOS. Interacts with phosphorylated TOM1L1 and MET. Interacts with the phosphorylated C-terminus of SH2B2. Interacts with phosphorylated SIT1, LAX1, LAT, LAT2 and LIME1 upon TCR and/or BCR activation. Interacts with NISCH, PTPNS1, REPS2 and the syntrophin SNTA1. Interacts with REPS1 and PIK3C2B via its SH3 domains (By similarity). Interacts with HCV NS5A via its SH3 domains. Interacts with CBL and CBLB. Interacts with AJUBA and CLNK (By similarity). Interacts (via SH2 domain) with TEK/TIE2 (tyrosine phosphorylated) (By similarity). Interacts with SHB, INPP5D/SHIP1, SKAP1 and SKAP2. Forms a complex with MUC1 and SOS1, through interaction of the SH3 domains with SOS1 and the SH2 domain with phosphorylated MUC1. Interacts with PTPN11. Interacts with PRNP and THEMIS (By similarity). Interacts with FLT1 (tyrosine phosphorylated) and KDR. Interacts with PDGFRA (tyrosine phosphorylated); the interaction may be indirect (By similarity). Interacts with RALGPS1 and with HCST. Interacts (via SH3 domain) with HEV ORF3 protein. Interacts with GAPT and PTPRE. Interacts (via SH2 domain) with KIF26A. Interacts (via SH3 2) with GAB2. Interacts with ADAM15. Interacts with THEMIS2. Interacts (via SH2 domain) with AXL and KIT (phosphorylated). Interacts with PTPRJ and BCR. Interacts with FLT4 (tyrosine phosphorylated). Interacts with EPHB1 and SHC1; activates the MAPK/ERK cascade to regulate cell migration. Interacts with PTPN23. Part of a complex including TNK2, GRB2 and one receptor tyrosine kinase (RTK) such as AXL, in which GRB2 promotes RTK recruitment by TNK2. Interacts (via SH2 domain) with CSF1R (tyrosine phosphorylated). Interacts with ERBB4. Interacts with NTRK1 (phosphorylated upon ligand-binding). Interacts with PTK2/FAK1 (tyrosine phosphorylated). Interacts with PTK2B/PYK2 (tyrosine phosphorylated). Isoform 1 interacts with SCIMP. Interacts with PLCG1, LAT and THEMIS upon TCR activation in thymocytes (By similarity). Interacts with TESPA1 and DAB2.
INTERACTION: Self; NbExp=4; IntAct=EBI-401755, EBI-401755; O92972:- (xeno); NbExp=2; IntAct=EBI-401755, EBI-710506; P27958:- (xeno); NbExp=3; IntAct=EBI-401755, EBI-706378; P42684:ABL2; NbExp=2; IntAct=EBI-401755, EBI-1102694; Q15109:AGER; NbExp=2; IntAct=EBI-401755, EBI-1646426; Q01484:ANK2; NbExp=2; IntAct=EBI-401755, EBI-941975; Q9ULH1:ASAP1; NbExp=7; IntAct=EBI-401755, EBI-346622; O43150:ASAP2; NbExp=3; IntAct=EBI-401755, EBI-310968; O60885:BRD4; NbExp=2; IntAct=EBI-401755, EBI-723869; P22681:CBL; NbExp=4; IntAct=EBI-401755, EBI-518228; Q13191:CBLB; NbExp=4; IntAct=EBI-401755, EBI-744027; Q9Y5K6:CD2AP; NbExp=3; IntAct=EBI-401755, EBI-298152; Q8WX92:COBRA1; NbExp=2; IntAct=EBI-401755, EBI-347721; P98082:DAB2; NbExp=2; IntAct=EBI-401755, EBI-1171238; P98078:Dab2 (xeno); NbExp=4; IntAct=EBI-401755, EBI-1391846; P14868:DARS; NbExp=2; IntAct=EBI-401755, EBI-358730; O14490:DLGAP1; NbExp=3; IntAct=EBI-401755, EBI-1753207; Q9P1A6:DLGAP2; NbExp=2; IntAct=EBI-401755, EBI-1753397; Q9Y2H0:DLGAP4; NbExp=2; IntAct=EBI-401755, EBI-722139; Q05193:DNM1; NbExp=3; IntAct=EBI-401755, EBI-713135; Q14185:DOCK1; NbExp=2; IntAct=EBI-401755, EBI-446740; P00533:EGFR; NbExp=12; IntAct=EBI-401755, EBI-297353; P54762:EPHB1; NbExp=2; IntAct=EBI-401755, EBI-80252; Q9UJM3:ERRFI1; NbExp=4; IntAct=EBI-401755, EBI-2941912; Q9H706:FAM59A; NbExp=3; IntAct=EBI-401755, EBI-3440103; O15360:FANCA; NbExp=2; IntAct=EBI-401755, EBI-81570; P21802:FGFR2; NbExp=5; IntAct=EBI-401755, EBI-1028658; P21333:FLNA; NbExp=2; IntAct=EBI-401755, EBI-350432; O75369:FLNB; NbExp=2; IntAct=EBI-401755, EBI-352089; Q14315:FLNC; NbExp=2; IntAct=EBI-401755, EBI-489954; Q9UQC2:GAB2; NbExp=4; IntAct=EBI-401755, EBI-975200; Q07666:KHDRBS1; NbExp=8; IntAct=EBI-401755, EBI-1364; P10721:KIT; NbExp=2; IntAct=EBI-401755, EBI-1379503; P05787:KRT8; NbExp=3; IntAct=EBI-401755, EBI-297852; P48357:LEPR; NbExp=3; IntAct=EBI-401755, EBI-518596; Q13163:MAP2K5; NbExp=2; IntAct=EBI-401755, EBI-307294; Q92918:MAP4K1; NbExp=2; IntAct=EBI-401755, EBI-881; Q8IVH8:MAP4K3; NbExp=2; IntAct=EBI-401755, EBI-1758170; Q9Y4K4:MAP4K5; NbExp=4; IntAct=EBI-401755, EBI-1279; Q9H204:MED28; NbExp=3; IntAct=EBI-401755, EBI-514199; O00750:PIK3C2B; NbExp=2; IntAct=EBI-401755, EBI-641107; P27986:PIK3R1; NbExp=3; IntAct=EBI-401755, EBI-79464; O00459:PIK3R2; NbExp=4; IntAct=EBI-401755, EBI-346930; O14939:PLD2; NbExp=4; IntAct=EBI-401755, EBI-1053996; Q08209:PPP3CA; NbExp=2; IntAct=EBI-401755, EBI-352922; Q9Y478:PRKAB1; NbExp=2; IntAct=EBI-401755, EBI-719769; Q06124:PTPN11; NbExp=6; IntAct=EBI-401755, EBI-297779; Q9H3S7:PTPN23; NbExp=6; IntAct=EBI-401755, EBI-724478; Q8IWN7:RP1L1; NbExp=2; IntAct=EBI-401755, EBI-1757848; Q15427:SF3B4; NbExp=2; IntAct=EBI-401755, EBI-348469; Q9UPX8:SHANK2; NbExp=2; IntAct=EBI-401755, EBI-1570571; Q9BYB0:SHANK3; NbExp=2; IntAct=EBI-401755, EBI-1752330; P29353:SHC1; NbExp=8; IntAct=EBI-401755, EBI-78835; Q07889:SOS1; NbExp=9; IntAct=EBI-401755, EBI-297487; Q62245:Sos1 (xeno); NbExp=2; IntAct=EBI-401755, EBI-1693; Q07890:SOS2; NbExp=6; IntAct=EBI-401755, EBI-298181; O95630:STAMBP; NbExp=3; IntAct=EBI-401755, EBI-396676; O15056:SYNJ2; NbExp=2; IntAct=EBI-401755, EBI-310513; Q92973:TNPO1; NbExp=2; IntAct=EBI-401755, EBI-286693; Q9ULW0:TPX2; NbExp=2; IntAct=EBI-401755, EBI-1037322; Q16851:UGP2; NbExp=2; IntAct=EBI-401755, EBI-743729; P15498:VAV1; NbExp=2; IntAct=EBI-401755, EBI-625518; Q9UKW4:VAV3; NbExp=5; IntAct=EBI-401755, EBI-297568; O00401:WASL; NbExp=3; IntAct=EBI-401755, EBI-957615; O43516:WIPF1; NbExp=3; IntAct=EBI-401755, EBI-346356; Q8TF74:WIPF2; NbExp=3; IntAct=EBI-401755, EBI-2850112;
SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Endosome. Golgi apparatus (By similarity).
DOMAIN: The SH3 domains mediate interaction with RALGPS1 and SHB.
SIMILARITY: Belongs to the GRB2/sem-5/DRK family.
SIMILARITY: Contains 1 SH2 domain.
SIMILARITY: Contains 2 SH3 domains.
WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/GRB2ID386ch17q25.html";

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR000108 - p67phox
IPR000980 - SH2
IPR001452 - SH3_domain

Pfam Domains:
PF00017 - SH2 domain
PF00018 - SH3 domain

Protein Data Bank (PDB) 3-D Structure
MuPIT help

1AZE
- NMR

1BM2
- X-ray

1BMB
- X-ray
To conserve bandwidth, only the images from the first 3 structures are shown.
1CJ1 - X-ray 1FHS - NMR 1FYR - X-ray
1GCQ - X-ray 1GFC - NMR 1GFD - NMR
1GHU - NMR 1GRI - X-ray 1IO6 - NMR
1JYQ - X-ray 1JYR - X-ray 1JYU - X-ray
1QG1 - NMR 1TZE - X-ray 1X0N - NMR
1ZFP - X-ray 2AOA - X-ray 2AOB - X-ray
2H46 - X-ray 2H5K - X-ray 2HUW - X-ray
2VVK - X-ray 2VWF - X-ray 2W0Z - X-ray
3C7I - X-ray 3IMD - X-ray 3IMJ - X-ray
3IN7 - X-ray 3IN8 - X-ray 3KFJ - X-ray
3MXC - X-ray 3MXY - X-ray 3N7Y - X-ray
3N84 - X-ray 3N8M - X-ray 3OV1 - X-ray
3OVE - X-ray 3S8L - X-ray 3S8N - X-ray
3S8O - X-ray


ModBase Predicted Comparative 3D Structure on P62993
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-  Other Names for This Gene
  UCSC ID: ENST00000392564.5
Representative RNA: AK091010
Protein: P62993 (aka GRB2_HUMAN)

+  Methods, Credits, and Use Restrictions
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