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Protein

Growth factor receptor-bound protein 2

Gene

GRB2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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
  • phosphatidylinositol-4,5-bisphosphate 3-kinase activity Source: Reactome
  • poly(A) RNA binding Source: UniProtKB
  • protein kinase binding Source: BHF-UCL
  • Ras guanyl-nucleotide exchange factor activity Source: Reactome
  • SH3/SH2 adaptor activity Source: UniProtKB
  • SH3 domain binding Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Host-virus interaction

Enzyme and pathway databases

BioCyciZFISH:ENSG00000133200-MONOMER.
ReactomeiR-HSA-109704. PI3K Cascade.
R-HSA-112412. SOS-mediated signalling.
R-HSA-114604. GPVI-mediated activation cascade.
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 (SIRP) 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-8875555. MET activates RAP1 and RAC1.
R-HSA-8875656. MET receptor recycling.
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.

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

HGNCiHGNC:4566. GRB2.

Subcellular locationi

  • Nucleus 1 Publication
  • Cytoplasm 1 Publication
  • Endosome 1 Publication
  • Golgi apparatus By similarity

GO - Cellular componenti

  • cell-cell junction Source: Ensembl
  • COP9 signalosome Source: UniProtKB
  • cytoplasm Source: UniProtKB
  • cytosol Source: HGNC
  • endosome Source: UniProtKB
  • extracellular exosome Source: UniProtKB
  • Golgi apparatus Source: UniProtKB-SubCell
  • Grb2-EGFR complex Source: BHF-UCL
  • nucleolus Source: HPA
  • nucleoplasm Source: HPA
  • nucleus Source: UniProtKB
  • plasma membrane Source: Reactome
  • vesicle membrane Source: Ensembl
Complete GO annotation...

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.
TopDownProteomicsiP62993-1. [P62993-1]
P62993-2. [P62993-2]

2D gel databases

OGPiP62993.
SWISS-2DPAGEP62993.

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 SH3 domain) with HEV ORF3 protein (PubMed:11518702). Interacts with HCV NS5A via its SH3 domains (PubMed:10318918). Interacts with herpes simplex virus 1 UL46 (PubMed:23946459). Interacts (via SH2 domain) with PTPRH (phosphorylated form) (By similarity). Interacts with PTPRO (phosphorylated form) (By similarity). Interacts with PTPRB (phosphorylated form) (By similarity).By similarity54 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself5EBI-401755,EBI-401755
O929722EBI-401755,EBI-710506From a different organism.
P266623EBI-401755,EBI-9099462From a different organism.
P279583EBI-401755,EBI-706378From a different organism.
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
BCRP112748EBI-401755,EBI-712838
BLNKQ8WV284EBI-401755,EBI-2623522
BRD4O608852EBI-401755,EBI-723869
C1orf94Q6P1W53EBI-401755,EBI-946029
CBLP2268110EBI-401755,EBI-518228
CBLBQ1319110EBI-401755,EBI-744027
CD2APQ9Y5K63EBI-401755,EBI-298152
DAB2P980822EBI-401755,EBI-1171238
Dab2P980784EBI-401755,EBI-1391846From a different organism.
DARSP148682EBI-401755,EBI-358730
DBN1Q166434EBI-401755,EBI-351394
DDX17Q928413EBI-401755,EBI-746012
DLGAP1O144903EBI-401755,EBI-1753207
DLGAP2Q9P1A62EBI-401755,EBI-1753397
DLGAP4Q9Y2H02EBI-401755,EBI-722139
DNM1Q051933EBI-401755,EBI-713135
DNM2P505706EBI-401755,EBI-346547
DOCK1Q141852EBI-401755,EBI-446740
DPPA4Q7L1903EBI-401755,EBI-710457
EGFRP0053336EBI-401755,EBI-297353
EPHB1P547622EBI-401755,EBI-80252
EPS8Q129293EBI-401755,EBI-375576
ERBB2P046264EBI-401755,EBI-641062
ERBB3P218603EBI-401755,EBI-720706
ERRFI1Q9UJM310EBI-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
GAB1Q134805EBI-401755,EBI-517684
GAB2Q9UQC217EBI-401755,EBI-975200
GAREM1Q9H7068EBI-401755,EBI-3440103
HNRNPKP619785EBI-401755,EBI-304185
HNRPKQ6IBN14EBI-401755,EBI-3440248
HOMEZQ8IX15-33EBI-401755,EBI-10172004
IKZF3Q9UKT95EBI-401755,EBI-747204
INCA1Q0VD863EBI-401755,EBI-6509505
Irs1P355705EBI-401755,EBI-520230From a different organism.
KHDRBS1Q076668EBI-401755,EBI-1364
KITP107216EBI-401755,EBI-1379503
KRT8P057873EBI-401755,EBI-297852
LATO4356112EBI-401755,EBI-1222766
LCP2Q1309412EBI-401755,EBI-346946
LEPRP483573EBI-401755,EBI-518596
LMO2P257913EBI-401755,EBI-739696
LMX1AQ8TE123EBI-401755,EBI-10692065
LNX1Q8TBB13EBI-401755,EBI-739832
LZTS2Q9BRK43EBI-401755,EBI-741037
MAP2K5Q131632EBI-401755,EBI-307294
MAP4K1Q929188EBI-401755,EBI-881
MAP4K3Q8IVH82EBI-401755,EBI-1758170
MAP4K5Q9Y4K44EBI-401755,EBI-1279
MED28Q9H2043EBI-401755,EBI-514199
MYH9P355793EBI-401755,EBI-350338
NELFBQ8WX922EBI-401755,EBI-347721
NIF3L1Q9GZT83EBI-401755,EBI-740897
PAK2Q131772EBI-401755,EBI-1045887
PARD6AQ9NPB6-23EBI-401755,EBI-10693102
PIK3C2BO007502EBI-401755,EBI-641107
PIK3R1P279864EBI-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 a different organism.
PTPN1P180312EBI-401755,EBI-968788
PTPN11Q061246EBI-401755,EBI-297779
Ptpn11P352357EBI-401755,EBI-397236From a different organism.
PTPN22Q9Y2R22EBI-401755,EBI-1211241
PTPN23Q9H3S76EBI-401755,EBI-724478
PTPN6P293503EBI-401755,EBI-78260
PTPRAP184338EBI-401755,EBI-2609645
PTPRTO145222EBI-401755,EBI-728180
RB1P064004EBI-401755,EBI-491274
RELQ048643EBI-401755,EBI-307352
REPS2Q8NFH8-28EBI-401755,EBI-8029141
SF3B4Q154272EBI-401755,EBI-348469
SHANK2Q9UPX82EBI-401755,EBI-1570571
SHANK3Q9BYB02EBI-401755,EBI-1752330
SHC1P2935323EBI-401755,EBI-78835
SHC1P29353-13EBI-401755,EBI-8160716
SOCS4Q8WXH53EBI-401755,EBI-3942425
SOS1Q0788922EBI-401755,EBI-297487
Sos1Q6224511EBI-401755,EBI-1693From a different organism.
SOS2Q078908EBI-401755,EBI-298181
SPRY2O435973EBI-401755,EBI-742487
SRGAP3O432952EBI-401755,EBI-368166
STAMBPO956309EBI-401755,EBI-396676
SYNJ2O150562EBI-401755,EBI-310513
TMEM128Q5BJH2-23EBI-401755,EBI-10694905
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
  • protein kinase binding Source: BHF-UCL
  • SH3/SH2 adaptor activity Source: UniProtKB
  • SH3 domain binding Source: UniProtKB

Protein-protein interaction databases

BioGridi109142. 533 interactors.
DIPiDIP-29229N.
IntActiP62993. 751 interactors.
MINTiMINT-91952.
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

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1AZENMR-A1-56[»]
1BM2X-ray2.10A49-163[»]
1BMBX-ray1.80A49-168[»]
1CJ1X-ray3.00A/B/C/D/E/F/G/H/I/J/K/L57-152[»]
1FHSNMR-A53-163[»]
1FYRX-ray2.40A/B/C/D50-161[»]
1GCQX-ray1.68A/B159-217[»]
1GFCNMR-A159-215[»]
1GFDNMR-A159-215[»]
1GHUNMR-A60-158[»]
1GRIX-ray3.10A/B1-217[»]
1IO6NMR-A159-215[»]
1JYQX-ray2.00A/B60-151[»]
1JYRX-ray1.55A60-151[»]
1JYUX-ray2.75A60-151[»]
1QG1NMR-E58-159[»]
1TZEX-ray2.10E55-152[»]
1X0NNMR-A58-159[»]
1ZFPX-ray1.80E56-153[»]
2AOAX-ray1.99A/B55-153[»]
2AOBX-ray1.80A/B/C/D55-153[»]
2H46X-ray1.90E53-162[»]
2H5KX-ray3.25A/B53-162[»]
2HUWX-ray1.90A/B53-162[»]
2VVKX-ray1.60A161-214[»]
2VWFX-ray1.58A159-214[»]
2W0ZX-ray1.70A159-214[»]
3C7IX-ray1.70A53-162[»]
3IMDX-ray2.00A/B53-163[»]
3IMJX-ray2.02A/B53-163[»]
3IN7X-ray2.00A/C53-163[»]
3IN8X-ray1.70A53-163[»]
3KFJX-ray2.02A53-163[»]
3MXCX-ray2.00A55-152[»]
3MXYX-ray2.30A55-152[»]
3N7YX-ray2.02A/B/C55-152[»]
3N84X-ray2.00A/B/C/D/E/F53-163[»]
3N8MX-ray2.00A53-163[»]
3OV1X-ray1.60A53-163[»]
3OVEX-ray1.82A53-163[»]
3S8LX-ray1.71A53-163[»]
3S8NX-ray1.71A53-163[»]
3S8OX-ray1.85A53-163[»]
3WA4X-ray1.35A60-152[»]
4P9VX-ray1.64A53-163[»]
4P9ZX-ray1.80A53-163[»]
5CDWX-ray2.60A/B/C/E/G/H/K/L/O/P/U/V/Y/Z/c/d54-153[»]
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
Contains 1 SH2 domain.PROSITE-ProRule annotation
Contains 2 SH3 domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, SH2 domain, SH3 domain

Phylogenomic databases

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

Family and domain databases

Gene3Di3.30.505.10. 1 hit.
InterProiIPR000980. SH2.
IPR001452. SH3_domain.
[Graphical view]
PfamiPF00017. SH2. 1 hit.
PF00018. SH3_1. 2 hits.
[Graphical view]
PRINTSiPR00401. SH2DOMAIN.
PR00452. SH3DOMAIN.
SMARTiSM00252. SH2. 1 hit.
SM00326. SH3. 2 hits.
[Graphical view]
SUPFAMiSSF50044. SSF50044. 2 hits.
SSF55550. SSF55550. 2 hits.
PROSITEiPS50001. SH2. 1 hit.
PS50002. SH3. 2 hits.
[Graphical view]

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

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1AZENMR-A1-56[»]
1BM2X-ray2.10A49-163[»]
1BMBX-ray1.80A49-168[»]
1CJ1X-ray3.00A/B/C/D/E/F/G/H/I/J/K/L57-152[»]
1FHSNMR-A53-163[»]
1FYRX-ray2.40A/B/C/D50-161[»]
1GCQX-ray1.68A/B159-217[»]
1GFCNMR-A159-215[»]
1GFDNMR-A159-215[»]
1GHUNMR-A60-158[»]
1GRIX-ray3.10A/B1-217[»]
1IO6NMR-A159-215[»]
1JYQX-ray2.00A/B60-151[»]
1JYRX-ray1.55A60-151[»]
1JYUX-ray2.75A60-151[»]
1QG1NMR-E58-159[»]
1TZEX-ray2.10E55-152[»]
1X0NNMR-A58-159[»]
1ZFPX-ray1.80E56-153[»]
2AOAX-ray1.99A/B55-153[»]
2AOBX-ray1.80A/B/C/D55-153[»]
2H46X-ray1.90E53-162[»]
2H5KX-ray3.25A/B53-162[»]
2HUWX-ray1.90A/B53-162[»]
2VVKX-ray1.60A161-214[»]
2VWFX-ray1.58A159-214[»]
2W0ZX-ray1.70A159-214[»]
3C7IX-ray1.70A53-162[»]
3IMDX-ray2.00A/B53-163[»]
3IMJX-ray2.02A/B53-163[»]
3IN7X-ray2.00A/C53-163[»]
3IN8X-ray1.70A53-163[»]
3KFJX-ray2.02A53-163[»]
3MXCX-ray2.00A55-152[»]
3MXYX-ray2.30A55-152[»]
3N7YX-ray2.02A/B/C55-152[»]
3N84X-ray2.00A/B/C/D/E/F53-163[»]
3N8MX-ray2.00A53-163[»]
3OV1X-ray1.60A53-163[»]
3OVEX-ray1.82A53-163[»]
3S8LX-ray1.71A53-163[»]
3S8NX-ray1.71A53-163[»]
3S8OX-ray1.85A53-163[»]
3WA4X-ray1.35A60-152[»]
4P9VX-ray1.64A53-163[»]
4P9ZX-ray1.80A53-163[»]
5CDWX-ray2.60A/B/C/E/G/H/K/L/O/P/U/V/Y/Z/c/d54-153[»]
DisProtiDP00210.
ProteinModelPortaliP62993.
SMRiP62993.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109142. 533 interactors.
DIPiDIP-29229N.
IntActiP62993. 751 interactors.
MINTiMINT-91952.
STRINGi9606.ENSP00000339007.

Chemistry databases

BindingDBiP62993.
ChEMBLiCHEMBL3663.
DrugBankiDB00061. Pegademase bovine.

PTM databases

iPTMnetiP62993.
PhosphoSitePlusiP62993.

Polymorphism and mutation databases

BioMutaiGRB2.
DMDMi51702266.

2D gel databases

OGPiP62993.
SWISS-2DPAGEP62993.

Proteomic databases

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

Protocols and materials databases

DNASUi2885.
Structural Biology KnowledgebaseSearch...

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.

Organism-specific databases

CTDi2885.
DisGeNETi2885.
GeneCardsiGRB2.
HGNCiHGNC:4566. GRB2.
HPAiCAB002589.
HPA030749.
HPA030750.
MIMi108355. gene.
neXtProtiNX_P62993.
OpenTargetsiENSG00000177885.
PharmGKBiPA28962.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciZFISH:ENSG00000133200-MONOMER.
ReactomeiR-HSA-109704. PI3K Cascade.
R-HSA-112412. SOS-mediated signalling.
R-HSA-114604. GPVI-mediated activation cascade.
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 (SIRP) 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-8875555. MET activates RAP1 and RAC1.
R-HSA-8875656. MET receptor recycling.
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.

Miscellaneous databases

ChiTaRSiGRB2. human.
EvolutionaryTraceiP62993.
GeneWikiiGRB2.
GenomeRNAii2885.
PROiP62993.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000177885.
CleanExiHS_GRB2.
ExpressionAtlasiP62993. baseline and differential.
GenevisibleiP62993. HS.

Family and domain databases

Gene3Di3.30.505.10. 1 hit.
InterProiIPR000980. SH2.
IPR001452. SH3_domain.
[Graphical view]
PfamiPF00017. SH2. 1 hit.
PF00018. SH3_1. 2 hits.
[Graphical view]
PRINTSiPR00401. SH2DOMAIN.
PR00452. SH3DOMAIN.
SMARTiSM00252. SH2. 1 hit.
SM00326. SH3. 2 hits.
[Graphical view]
SUPFAMiSSF50044. SSF50044. 2 hits.
SSF55550. SSF55550. 2 hits.
PROSITEiPS50001. SH2. 1 hit.
PS50002. SH3. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiGRB2_HUMAN
AccessioniPrimary (citable) accession number: P62993
Secondary accession number(s): P29354
, Q14450, Q63057, Q63059
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 31, 2004
Last sequence update: August 31, 2004
Last modified: November 30, 2016
This is version 165 of the entry and version 1 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, 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

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.