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Protein

Growth factor receptor-bound protein 2

Gene

GRB2

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

Functioni

Adapter protein that provides a critical link between cell surface growth factor receptors and the Ras signaling pathway.
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.

GO - Molecular functioni

  • 1-phosphatidylinositol-3-kinase activity Source: Reactome
  • ephrin receptor binding Source: UniProtKB
  • epidermal growth factor receptor binding Source: UniProtKB
  • identical protein binding Source: IntAct
  • insulin receptor substrate binding Source: UniProtKB
  • neurotrophin TRKA receptor binding Source: UniProtKB
  • non-membrane spanning protein tyrosine kinase activity Source: GO_Central
  • phosphatidylinositol-4,5-bisphosphate 3-kinase activity Source: Reactome
  • phosphotyrosine residue binding Source: CAFA
  • protein kinase binding Source: BHF-UCL
  • protein phosphatase binding Source: Ensembl
  • Ras guanyl-nucleotide exchange factor activity Source: Reactome
  • RNA binding Source: UniProtKB
  • SH3/SH2 adaptor activity Source: UniProtKB
  • SH3 domain binding Source: UniProtKB

GO - Biological processi

Keywordsi

Biological processHost-virus interaction

Enzyme and pathway databases

ReactomeiR-HSA-109704 PI3K Cascade
R-HSA-112412 SOS-mediated signalling
R-HSA-1236382 Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants
R-HSA-1250196 SHC1 events in ERBB2 signaling
R-HSA-1250347 SHC1 events in ERBB4 signaling
R-HSA-1257604 PIP3 activates AKT signaling
R-HSA-1295596 Spry regulation of FGF signaling
R-HSA-1433557 Signaling by SCF-KIT
R-HSA-1433559 Regulation of KIT signaling
R-HSA-167044 Signalling to RAS
R-HSA-179812 GRB2 events in EGFR signaling
R-HSA-180292 GAB1 signalosome
R-HSA-180336 SHC1 events in EGFR signaling
R-HSA-182971 EGFR downregulation
R-HSA-1839117 Signaling by cytosolic FGFR1 fusion mutants
R-HSA-186763 Downstream signal transduction
R-HSA-1963640 GRB2 events in ERBB2 signaling
R-HSA-1963642 PI3K events in ERBB2 signaling
R-HSA-2029482 Regulation of actin dynamics for phagocytic cup formation
R-HSA-210993 Tie2 Signaling
R-HSA-2179392 EGFR Transactivation by Gastrin
R-HSA-2219530 Constitutive Signaling by Aberrant PI3K in Cancer
R-HSA-2424491 DAP12 signaling
R-HSA-2428933 SHC-related events triggered by IGF1R
R-HSA-2730905 Role of LAT2/NTAL/LAB on calcium mobilization
R-HSA-2871796 FCERI mediated MAPK activation
R-HSA-2871809 FCERI mediated Ca+2 mobilization
R-HSA-354194 GRB2:SOS provides linkage to MAPK signaling for Integrins
R-HSA-375165 NCAM signaling for neurite out-growth
R-HSA-388841 Costimulation by the CD28 family
R-HSA-389359 CD28 dependent Vav1 pathway
R-HSA-391160 Signal regulatory protein family interactions
R-HSA-392451 G beta:gamma signalling through PI3Kgamma
R-HSA-512988 Interleukin-3, 5 and GM-CSF signaling
R-HSA-5637810 Constitutive Signaling by EGFRvIII
R-HSA-5654688 SHC-mediated cascade:FGFR1
R-HSA-5654689 PI-3K cascade:FGFR1
R-HSA-5654693 FRS-mediated FGFR1 signaling
R-HSA-5654695 PI-3K cascade:FGFR2
R-HSA-5654699 SHC-mediated cascade:FGFR2
R-HSA-5654700 FRS-mediated FGFR2 signaling
R-HSA-5654704 SHC-mediated cascade:FGFR3
R-HSA-5654706 FRS-mediated FGFR3 signaling
R-HSA-5654710 PI-3K cascade:FGFR3
R-HSA-5654712 FRS-mediated FGFR4 signaling
R-HSA-5654719 SHC-mediated cascade:FGFR4
R-HSA-5654720 PI-3K cascade:FGFR4
R-HSA-5654726 Negative regulation of FGFR1 signaling
R-HSA-5654727 Negative regulation of FGFR2 signaling
R-HSA-5654732 Negative regulation of FGFR3 signaling
R-HSA-5654733 Negative regulation of FGFR4 signaling
R-HSA-5655253 Signaling by FGFR2 in disease
R-HSA-5655291 Signaling by FGFR4 in disease
R-HSA-5655302 Signaling by FGFR1 in disease
R-HSA-5663213 RHO GTPases Activate WASPs and WAVEs
R-HSA-5673001 RAF/MAP kinase cascade
R-HSA-6807004 Negative regulation of MET activity
R-HSA-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-HSA-74749 Signal attenuation
R-HSA-74751 Insulin receptor signalling cascade
R-HSA-8851805 MET activates RAS signaling
R-HSA-8851907 MET activates PI3K/AKT signaling
R-HSA-8853334 Signaling by FGFR3 fusions in cancer
R-HSA-8853338 Signaling by FGFR3 point mutants in cancer
R-HSA-8853659 RET signaling
R-HSA-8856825 Cargo recognition for clathrin-mediated endocytosis
R-HSA-8856828 Clathrin-mediated endocytosis
R-HSA-8865999 MET activates PTPN11
R-HSA-8875360 InlB-mediated entry of Listeria monocytogenes into host cell
R-HSA-8875555 MET activates RAP1 and RAC1
R-HSA-8875656 MET receptor recycling
R-HSA-8983432 Interleukin-15 signaling
R-HSA-9026519 Activated NTRK2 signals through RAS
R-HSA-9028335 Activated NTRK2 signals through PI3K
R-HSA-9028731 Activated NTRK2 signals through FRS2 and FRS3
R-HSA-912526 Interleukin receptor SHC signaling
R-HSA-912631 Regulation of signaling by CBL
R-HSA-983695 Antigen activates B Cell Receptor (BCR) leading to generation of second messengers
SignaLinkiP62993
SIGNORiP62993

Protein family/group databases

MoonDBiP62993 Predicted

Names & Taxonomyi

Protein namesi
Recommended name:
Growth factor receptor-bound protein 2
Alternative name(s):
Adapter protein GRB2
Protein Ash
SH2/SH3 adapter GRB2
Gene namesi
Name:GRB2
Synonyms:ASH
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000177885.13
HGNCiHGNC:4566 GRB2
MIMi108355 gene
neXtProtiNX_P62993

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Endosome, Golgi apparatus, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi49P → L: Ineffective in DNA synthesis. Abolishes interaction with SHB; when associated with L-206. Abolishes interaction with SOS1. 3 Publications1
Mutagenesisi89E → K: No effect on the interaction with SOS1. 1 Publication1
Mutagenesisi90S → N: No effect on the interaction with SOS1. 1 Publication1
Mutagenesisi203G → R: Ineffective in DNA synthesis. Abolishes interaction with SOS1. 2 Publications1
Mutagenesisi206P → L: Abolishes interaction with SHB; when associated with L-49. 1 Publication1

Organism-specific databases

DisGeNETi2885
OpenTargetsiENSG00000177885
PharmGKBiPA28962

Chemistry databases

ChEMBLiCHEMBL3663
DrugBankiDB00061 Pegademase bovine

Polymorphism and mutation databases

BioMutaiGRB2
DMDMi51702266

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000881981 – 217Growth factor receptor-bound protein 2Add BLAST217

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei6N6-acetyllysineCombined sources1
Modified residuei50N6-acetyllysineCombined sources1
Modified residuei109N6-acetyllysineCombined sources1
Modified residuei211PhosphothreonineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP62993
MaxQBiP62993
PaxDbiP62993
PeptideAtlasiP62993
PRIDEiP62993
ProteomicsDBi57462
57463 [P62993-2]
TopDownProteomicsiP62993-1 [P62993-1]
P62993-2 [P62993-2]

2D gel databases

OGPiP62993
SWISS-2DPAGEiP62993

PTM databases

iPTMnetiP62993
PhosphoSitePlusiP62993

Expressioni

Gene expression databases

BgeeiENSG00000177885
CleanExiHS_GRB2
ExpressionAtlasiP62993 baseline and differential
GenevisibleiP62993 HS

Organism-specific databases

HPAiCAB002589
HPA030749
HPA030750

Interactioni

Subunit structurei

Associates (via SH2 domain) with activated EGF and PDGF receptors (tyrosine phosphorylated) (PubMed:10026169, PubMed:19836242). Interacts with PDGFRA (tyrosine phosphorylated); the interaction may be indirect (By similarity). 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 (PubMed:8388384, PubMed:8491186, PubMed:9553137, PubMed:11433379). It also seems to interact with RAS in the signaling pathway leading to DNA synthesis. Interacts with SOS1 (PubMed:8493579, PubMed:7664271). Forms a complex with MUC1 and SOS1, through interaction of the SH3 domains with SOS1 and the SH2 domain with phosphorylated MUC1 (PubMed:7664271). Interacts with phosphorylated MET (PubMed:11063574, PubMed:11827484). Interacts with phosphorylated TOM1L1 (By similarity). Interacts with the phosphorylated C-terminus of SH2B2 (PubMed:9233773). Interacts with phosphorylated SIT1, LAX1, LAT, LAT2 and LIME1 upon TCR and/or BCR activation (By similarity) (PubMed:9489702, PubMed:12359715, PubMed:12486104, PubMed:12514734). Interacts with NISCH, PTPNS1 and REPS2 (PubMed:9062191, PubMed:9422736, PubMed:11912194). Interacts with syntrophin SNTA1 (By similarity). Interacts (via SH3 domains) with REPS1 (By similarity). Interacts (via SH3 domains) with PIK3C2B (PubMed:11533253). Interacts with CBL and CBLB (PubMed:10022120, PubMed:10086340). 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 (PubMed:8723348, PubMed:9108392, PubMed:9484780, PubMed:10942756, PubMed:12171928). Interacts with PTPN11 (By similarity). Interacts with PRNP (By similarity). Interacts with RALGPS1 (PubMed:10747847). Interacts with HCST (PubMed:16582911). Interacts with KDR (By similarity). Interacts with FLT1 (tyrosine-phosphorylated) (By similarity). Interacts with GAPT and PTPRE (PubMed:10980613, PubMed:18559951). Interacts (via SH2 domain) with KIF26A (PubMed:19914172). Interacts (via SH3 2) with GAB2 (PubMed:19523899). Interacts with ADAM15 (PubMed:18296648). Interacts with THEMIS2 (By similarity). Interacts (via SH2 domain) with AXL (phosphorylated) (PubMed:9178760, PubMed:19815557). Interacts (via SH2 domain) with KIT (phosphorylated) (PubMed:15526160, PubMed:16129412). Interacts with PTPRJ and BCR (PubMed:12475979, PubMed:15302586). Interacts with PTPN23 (PubMed:21179510). Interacts with FLT4 (tyrosine phosphorylated) (PubMed:15102829). Interacts with EPHB1 and SHC1; activates the MAPK/ERK cascade to regulate cell migration (PubMed:8798570, PubMed:12925710). Part of a complex including TNK2, GRB2, LTK and one receptor tyrosine kinase (RTK) such as AXL and PDGFRL, in which GRB2 promotes RTK recruitment by TNK2 (PubMed:9178760, PubMed:19815557). Interacts (via SH2 domain) with CSF1R (tyrosine phosphorylated) (PubMed:8262059). Interacts with ERBB4 (PubMed:10867024). Interacts with NTRK1 (phosphorylated upon ligand-binding) (PubMed:15488758). Interacts with PTK2/FAK1 (tyrosine phosphorylated) (PubMed:9148935). Interacts with PTK2B/PYK2 (tyrosine phosphorylated) (PubMed:20521079). Isoform 1 interacts with SCIMP (PubMed:21930792). Interacts (via SH3 domains) with GAREM1 isoform 1 (via proline-rich domain and tyrosine phosphorylated); the interaction occurs upon EGF stimulation (PubMed:19509291). Interacts with DAB2 (By similarity). Interacts with TESPA1 (PubMed:22561606). Interacts with PLCG1, LAT and THEMIS upon TCR activation in thymocytes; the association is weaker in the absence of TESPA1 (By similarity). Interacts with CD28 (PubMed:24098653). Interacts with RAB13; may recruit RAB13 to the leading edge of migrating endothelial cells where it can activate RHOA (By similarity). Interacts with ASAP3 (phosphorylated form) (PubMed:22027826). Interacts (via SH2 domain) with PTPRH (phosphorylated form) (By similarity). Interacts with PTPRO (phosphorylated form) (By similarity). Interacts with PTPRB (phosphorylated form) (By similarity). Interacts (via SH3 domain 2) with PRR14 (via proline-rich region) (PubMed:27041574). Interacts with FCRL6 (tyrosine phosphorylated form) (PubMed:20933011). Interacts with RHEX (via tyrosine-phosphorylated form) (PubMed:25092874).By similarity57 Publications
(Microbial infection) Interacts (via SH3 domain) with hepatitis E virus/HEV ORF3 protein.1 Publication
(Microbial infection) Interacts with hepatitis C virus/HCV protein NS5A via its SH3 domains.1 Publication
(Microbial infection) Interacts with herpes simplex virus 1 protein UL46.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
itself5EBI-401755,EBI-401755
O929722EBI-401755,EBI-710506From Hepatitis C virus genotype 1b (strain HC-J4).
P266623EBI-401755,EBI-9099462From Hepatitis C virus genotype 1b (isolate Japanese).
P279583EBI-401755,EBI-706378From Hepatitis C virus genotype 1a (isolate H).
ABI3Q9P2A43EBI-401755,EBI-742038
ABL2P426842EBI-401755,EBI-1102694
ACAP1Q150273EBI-401755,EBI-751746
ADAM15Q134443EBI-401755,EBI-77818
AESQ081173EBI-401755,EBI-717810
AGERQ151092EBI-401755,EBI-1646426
ANK2Q014842EBI-401755,EBI-941975
ARHGAP9Q9BRR93EBI-401755,EBI-750254
ARHGEF5Q127744EBI-401755,EBI-602199
ARL6IP4Q66PJ3-42EBI-401755,EBI-5280499
ASAP1Q9ULH17EBI-401755,EBI-346622
ASAP2O431503EBI-401755,EBI-310968
AXLP305303EBI-401755,EBI-2850927
BCRP1127410EBI-401755,EBI-712838
BLNKQ8WV285EBI-401755,EBI-2623522
BRD4O608852EBI-401755,EBI-723869
C1orf94Q6P1W53EBI-401755,EBI-946029
CBLP2268115EBI-401755,EBI-518228
CBLBQ1319110EBI-401755,EBI-744027
CD2APQ9Y5K63EBI-401755,EBI-298152
DAB2P980822EBI-401755,EBI-1171238
Dab2P980784EBI-401755,EBI-1391846From Mus musculus.
DARSP148682EBI-401755,EBI-358730
DBN1Q166434EBI-401755,EBI-351394
DDX17Q928413EBI-401755,EBI-746012
DLGAP1O144903EBI-401755,EBI-1753207
DLGAP2Q9P1A62EBI-401755,EBI-1753397
DLGAP4Q9Y2H02EBI-401755,EBI-722139
DNM1Q051935EBI-401755,EBI-713135
DNM2P505707EBI-401755,EBI-346547
DOCK1Q141852EBI-401755,EBI-446740
DPPA4Q7L1903EBI-401755,EBI-710457
EGFRP0053347EBI-401755,EBI-297353
EPHB1P547622EBI-401755,EBI-80252
EPS8Q129293EBI-401755,EBI-375576
ERBB2P046265EBI-401755,EBI-641062
ERBB3P218605EBI-401755,EBI-720706
ERBB4Q153037EBI-401755,EBI-80371
ERRFI1Q9UJM312EBI-401755,EBI-2941912
FAM22FB7ZLH05EBI-401755,EBI-10220102
FANCAO153602EBI-401755,EBI-81570
FGFR2P218025EBI-401755,EBI-1028658
FLNAP213332EBI-401755,EBI-350432
FLNBO753692EBI-401755,EBI-352089
FLNCQ143152EBI-401755,EBI-489954
GAB1Q134809EBI-401755,EBI-517684
GAB2Q9UQC211EBI-401755,EBI-975200
GAB2Q9UQC2-13EBI-15787932,EBI-15787947
GAREM1Q9H7068EBI-401755,EBI-3440103
HNRNPKP619789EBI-401755,EBI-304185
HOMEZQ8IX15-33EBI-401755,EBI-10172004
IKZF3Q9UKT97EBI-401755,EBI-747204
INCA1Q0VD863EBI-401755,EBI-6509505
Irs1P355705EBI-401755,EBI-520230From Rattus norvegicus.
KHDRBS1Q076668EBI-401755,EBI-1364
KITP107216EBI-401755,EBI-1379503
KRT8P057873EBI-401755,EBI-297852
LATO435617EBI-401755,EBI-1222766
LATO43561-23EBI-15787932,EBI-8070286
LCP2Q1309414EBI-401755,EBI-346946
LEPRP483573EBI-401755,EBI-518596
LMO2P257913EBI-401755,EBI-739696
LMX1AQ8TE123EBI-401755,EBI-10692065
LNX1Q8TBB13EBI-401755,EBI-739832
LZTS2Q9BRK43EBI-401755,EBI-741037
MAP2P111377EBI-401755,EBI-2682460
MAP2K5Q131632EBI-401755,EBI-307294
MAP4K1Q929188EBI-401755,EBI-881
MAP4K3Q8IVH82EBI-401755,EBI-1758170
MAP4K5Q9Y4K44EBI-401755,EBI-1279
MED28Q9H2043EBI-401755,EBI-514199
MYH9P355793EBI-401755,EBI-350338
NckipsdQ9ESJ48EBI-401755,EBI-774750From Mus musculus.
NELFBQ8WX922EBI-401755,EBI-347721
NIF3L1Q9GZT83EBI-401755,EBI-740897
PAK2Q131772EBI-401755,EBI-1045887
PARD6AQ9NPB6-23EBI-401755,EBI-10693102
PIK3C2BO007502EBI-401755,EBI-641107
PIK3R1P279866EBI-401755,EBI-79464
PIK3R2O004594EBI-401755,EBI-346930
PLCG1P191742EBI-401755,EBI-79387
PLD2O149394EBI-401755,EBI-1053996
PLEKHS1Q5SXH73EBI-401755,EBI-10691507
PNMA5Q96PV43EBI-401755,EBI-10171633
PPARAQ078693EBI-401755,EBI-78615
PPP3CAQ082093EBI-401755,EBI-352922
PRKAB1Q9Y4782EBI-401755,EBI-719769
Ptk2P341523EBI-401755,EBI-77070From Mus musculus.
PTPN1P180312EBI-401755,EBI-968788
PTPN11Q061246EBI-401755,EBI-297779
Ptpn11P352357EBI-401755,EBI-397236From Mus musculus.
PTPN22Q9Y2R22EBI-401755,EBI-1211241
PTPN23Q9H3S76EBI-401755,EBI-724478
PTPN6P293503EBI-401755,EBI-78260
PTPRAP184339EBI-401755,EBI-2609645
PTPRTO145222EBI-401755,EBI-728180
RAPGEF1Q139053EBI-401755,EBI-976876
RB1P064004EBI-401755,EBI-491274
RELQ048643EBI-401755,EBI-307352
REPS2Q8NFH8-28EBI-401755,EBI-8029141
RHOUQ7L0Q83EBI-401755,EBI-1638043
SF3B4Q154272EBI-401755,EBI-348469
SH2D4AQ9H7883EBI-401755,EBI-747035
SHANK2Q9UPX82EBI-401755,EBI-1570571
SHANK3Q9BYB02EBI-401755,EBI-1752330
SHC1P2935326EBI-401755,EBI-78835
SHC1P29353-13EBI-401755,EBI-8160716
SOCS4Q8WXH53EBI-401755,EBI-3942425
SOS1Q0788923EBI-401755,EBI-297487
Sos1Q622454EBI-401755,EBI-1693From Mus musculus.
SOS2Q078908EBI-401755,EBI-298181
SPRY2O435973EBI-401755,EBI-742487
SRGAP3O432952EBI-401755,EBI-368166
STAMBPO956307EBI-401755,EBI-396676
SYNJ2O150562EBI-401755,EBI-310513
THEMISQ8N1K510EBI-401755,EBI-2873538
THEMISQ8N1K5-110EBI-401755,EBI-15102259
TMEM128Q5BJH2-23EBI-401755,EBI-10694905
TNK2Q079124EBI-401755,EBI-603457
TNPO1Q929732EBI-401755,EBI-286693
TOM1L1O756742EBI-401755,EBI-712991
TP53BP2Q13625-33EBI-401755,EBI-10175039
TPX2Q9ULW02EBI-401755,EBI-1037322
TRIM27P143733EBI-401755,EBI-719493
TSPAN2O606366EBI-401755,EBI-3914288
UGP2Q168512EBI-401755,EBI-743729
VAV1P154982EBI-401755,EBI-625518
VAV3Q9UKW47EBI-401755,EBI-297568
VCPP550723EBI-401755,EBI-355164
WASLO004018EBI-401755,EBI-957615
WBP11Q9Y2W24EBI-401755,EBI-714455
WIPF1O435163EBI-401755,EBI-346356
WIPF2Q8TF743EBI-401755,EBI-2850112
ZBTB7BO151563EBI-401755,EBI-740434

GO - Molecular functioni

  • ephrin receptor binding Source: UniProtKB
  • epidermal growth factor receptor binding Source: UniProtKB
  • identical protein binding Source: IntAct
  • insulin receptor substrate binding Source: UniProtKB
  • neurotrophin TRKA receptor binding Source: UniProtKB
  • phosphotyrosine residue binding Source: CAFA
  • protein kinase binding Source: BHF-UCL
  • protein phosphatase binding Source: Ensembl
  • Ras guanyl-nucleotide exchange factor activity Source: Reactome
  • SH3/SH2 adaptor activity Source: UniProtKB
  • SH3 domain binding Source: UniProtKB

Protein-protein interaction databases

BioGridi109142, 543 interactors
CORUMiP62993
DIPiDIP-29229N
ELMiP62993
IntActiP62993, 788 interactors
MINTiP62993
STRINGi9606.ENSP00000339007

Chemistry databases

BindingDBiP62993

Structurei

Secondary structure

1217
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi2 – 5Combined sources4
Beta strandi13 – 15Combined sources3
Beta strandi24 – 26Combined sources3
Beta strandi36 – 43Combined sources8
Beta strandi45 – 49Combined sources5
Helixi50 – 52Combined sources3
Beta strandi61 – 64Combined sources4
Helixi67 – 75Combined sources9
Beta strandi78 – 80Combined sources3
Beta strandi82 – 87Combined sources6
Turni89 – 93Combined sources5
Beta strandi95 – 101Combined sources7
Beta strandi104 – 112Combined sources9
Beta strandi114 – 116Combined sources3
Beta strandi118 – 122Combined sources5
Beta strandi124 – 127Combined sources4
Helixi128 – 134Combined sources7
Turni135 – 137Combined sources3
Beta strandi142 – 144Combined sources3
Beta strandi149 – 152Combined sources4
Beta strandi155 – 157Combined sources3
Beta strandi160 – 165Combined sources6
Beta strandi171 – 174Combined sources4
Beta strandi182 – 187Combined sources6
Beta strandi190 – 198Combined sources9
Beta strandi201 – 206Combined sources6
Helixi207 – 209Combined sources3
Beta strandi210 – 212Combined sources3

3D structure databases

DisProtiDP00210
ProteinModelPortaliP62993
SMRiP62993
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP62993

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1 – 58SH3 1PROSITE-ProRule annotationAdd BLAST58
Domaini60 – 152SH2PROSITE-ProRule annotationAdd BLAST93
Domaini156 – 215SH3 2PROSITE-ProRule annotationAdd BLAST60

Domaini

The SH3 domains mediate interaction with RALGPS1 and SHB.

Sequence similaritiesi

Belongs to the GRB2/sem-5/DRK family.Curated

Keywords - Domaini

Repeat, SH2 domain, SH3 domain

Phylogenomic databases

eggNOGiKOG3601 Eukaryota
ENOG410XR1G LUCA
GeneTreeiENSGT00820000126999
HOGENOMiHOG000251625
HOVERGENiHBG005404
InParanoidiP62993
KOiK04364
OMAiHWWHGEI
OrthoDBiEOG091G0HWS
PhylomeDBiP62993
TreeFamiTF354288

Family and domain databases

CDDicd11949 SH3_GRB2_C, 1 hit
cd11946 SH3_GRB2_N, 1 hit
Gene3Di3.30.505.10, 1 hit
InterProiView protein in InterPro
IPR030219 Grb2
IPR035643 GRB2_C_SH3
IPR035641 GRB2_N_SH3
IPR000980 SH2
IPR036860 SH2_dom_sf
IPR036028 SH3-like_dom_sf
IPR001452 SH3_domain
PANTHERiPTHR24418:SF290 PTHR24418:SF290, 1 hit
PfamiView protein in Pfam
PF00017 SH2, 1 hit
PF00018 SH3_1, 2 hits
PRINTSiPR00401 SH2DOMAIN
PR00452 SH3DOMAIN
SMARTiView protein in SMART
SM00252 SH2, 1 hit
SM00326 SH3, 2 hits
SUPFAMiSSF50044 SSF50044, 2 hits
SSF55550 SSF55550, 2 hits
PROSITEiView protein in PROSITE
PS50001 SH2, 1 hit
PS50002 SH3, 2 hits

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Additional isoforms seem to exist.
Isoform 1 (identifier: P62993-1) [UniParc]FASTAAdd to basket
Also known as: Ash-L

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MEAIAKYDFK ATADDELSFK RGDILKVLNE ECDQNWYKAE LNGKDGFIPK
60 70 80 90 100
NYIEMKPHPW FFGKIPRAKA EEMLSKQRHD GAFLIRESES APGDFSLSVK
110 120 130 140 150
FGNDVQHFKV LRDGAGKYFL WVVKFNSLNE LVDYHRSTSV SRNQQIFLRD
160 170 180 190 200
IEQVPQQPTY VQALFDFDPQ EDGELGFRRG DFIHVMDNSD PNWWKGACHG
210
QTGMFPRNYV TPVNRNV
Length:217
Mass (Da):25,206
Last modified:August 31, 2004 - v1
Checksum:i83A4B0BA1B248DC4
GO
Isoform 2 (identifier: P62993-2) [UniParc] [UniParc]FASTAAdd to basket
Also known as: GRB3-3

The sequence of this isoform differs from the canonical sequence as follows:
     60-100: Missing.

Show »
Length:176
Mass (Da):20,557
Checksum:i70622BED0FE940DE
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_00183960 – 100Missing in isoform 2. 1 PublicationAdd BLAST41

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M96995 mRNA Translation: AAA58448.1
X62852 mRNA Translation: CAA44664.1
L29511 mRNA Translation: AAC37549.1
AF063618
, AF063614, AF063615, AF063616, AF063617 Genomic DNA Translation: AAC72075.1
AF498925 mRNA Translation: AAM21073.1
CR541942 mRNA Translation: CAG46740.1
AC011933 Genomic DNA No translation available.
BC000631 mRNA Translation: AAH00631.1
CCDSiCCDS11721.1
CCDS11722.1 [P62993-2]
PIRiA43321
RefSeqiNP_002077.1, NM_002086.4 [P62993-1]
NP_987102.1, NM_203506.2 [P62993-2]
UniGeneiHs.444356

Genome annotation databases

EnsembliENST00000316615; ENSP00000317360; ENSG00000177885 [P62993-2]
ENST00000316804; ENSP00000339007; ENSG00000177885 [P62993-1]
ENST00000392562; ENSP00000376345; ENSG00000177885 [P62993-1]
ENST00000392563; ENSP00000376346; ENSG00000177885 [P62993-2]
ENST00000392564; ENSP00000376347; ENSG00000177885 [P62993-1]
GeneIDi2885
KEGGihsa:2885
UCSCiuc002jnx.5 human

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiGRB2_HUMAN
AccessioniPrimary (citable) accession number: P62993
Secondary accession number(s): P29354
, Q14450, Q63057, Q63059
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 31, 2004
Last sequence update: August 31, 2004
Last modified: July 18, 2018
This is version 184 of the entry and version 1 of the sequence. See 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, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

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