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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

  • 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
  • poly(A) RNA binding Source: UniProtKB
  • protein kinase binding Source: BHF-UCL
  • 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

ReactomeiREACT_111040. Signaling by SCF-KIT.
REACT_111080. Spry regulation of FGF signaling.
REACT_111225. Regulation of KIT signaling.
REACT_115852. Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants.
REACT_115854. GRB2 events in ERBB2 signaling.
REACT_115993. SHC1 events in ERBB2 signaling.
REACT_116005. SHC1 events in ERBB4 signaling.
REACT_116008. PI3K events in ERBB2 signaling.
REACT_118700. Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
REACT_12033. Signalling to RAS.
REACT_121096. EGFR Transactivation by Gastrin.
REACT_121141. Signaling by FGFR1 fusion mutants.
REACT_12484. EGFR downregulation.
REACT_12578. GAB1 signalosome.
REACT_12579. SHC1 events in EGFR signaling.
REACT_12606. GRB2 events in EGFR signaling.
REACT_12621. Tie2 Signaling.
REACT_147727. Constitutive Signaling by Aberrant PI3K in Cancer.
REACT_147814. DAP12 signaling.
REACT_15443. GRB2:SOS provides linkage to MAPK signaling for Integrins.
REACT_160086. Regulation of actin dynamics for phagocytic cup formation.
REACT_163701. FCERI mediated MAPK activation.
REACT_163769. Role of LAT2/NTAL/LAB on calcium mobilization.
REACT_163834. FCERI mediated Ca+2 mobilization.
REACT_1695. GPVI-mediated activation cascade.
REACT_17025. Downstream signal transduction.
REACT_18334. NCAM signaling for neurite out-growth.
REACT_19238. CD28 dependent Vav1 pathway.
REACT_19290. G beta:gamma signalling through PI3Kgamma.
REACT_19344. Costimulation by the CD28 family.
REACT_23787. Regulation of signaling by CBL.
REACT_23837. Interleukin-3, 5 and GM-CSF signaling.
REACT_23891. Interleukin receptor SHC signaling.
REACT_23916. Signal regulatory protein (SIRP) family interactions.
REACT_267817. Constitutive Signaling by EGFRvIII.
REACT_355069. FRS-mediated FGFR2 signaling.
REACT_355144. Negative regulation of FGFR3 signaling.
REACT_355159. SHC-mediated cascade:FGFR4.
REACT_355160. PI-3K cascade:FGFR3.
REACT_355194. SHC-mediated cascade:FGFR1.
REACT_355197. SHC-mediated cascade:FGFR3.
REACT_355202. Signaling by FGFR4 mutants.
REACT_355212. FRS-mediated FGFR3 signaling.
REACT_355218. Negative regulation of FGFR1 signaling.
REACT_355221. Signaling by FGFR1 mutants.
REACT_355225. SHC-mediated cascade:FGFR2.
REACT_355227. Negative regulation of FGFR2 signaling.
REACT_355304. PI-3K cascade:FGFR4.
REACT_355313. Signaling by FGFR3 mutants.
REACT_355372. RHO GTPases Activate WASPs and WAVEs.
REACT_355450. PI-3K cascade:FGFR2.
REACT_355511. Signaling by FGFR2 mutants.
REACT_355552. PI-3K cascade:FGFR1.
REACT_355580. FRS2-mediated FGFR4 signaling.
REACT_355584. FRS-mediated FGFR1 signaling.
REACT_355588. Negative regulation of FGFR4 signaling.
REACT_508. Signal attenuation.
REACT_524. SOS-mediated signalling.
REACT_661. SHC-mediated signalling.
REACT_75829. PIP3 activates AKT signaling.
REACT_976. PI3K Cascade.
SignaLinkiP62993.

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
ProteomesiUP000005640 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)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi49 – 491P → L: Ineffective in DNA synthesis. Abolishes interaction with SHB; when associated with L-206. 2 Publications
Mutagenesisi203 – 2031G → R: Ineffective in DNA synthesis. 1 Publication
Mutagenesisi206 – 2061P → L: Abolishes interaction with SHB; when associated with L-49. 1 Publication

Organism-specific databases

PharmGKBiPA28962.

Chemistry

DrugBankiDB00061. Pegademase bovine.

Polymorphism and mutation databases

BioMutaiGRB2.
DMDMi51702266.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 217217Growth factor receptor-bound protein 2PRO_0000088198Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei1 – 11N-acetylmethionine2 Publications
Modified residuei6 – 61N6-acetyllysine1 Publication
Modified residuei50 – 501N6-acetyllysine1 Publication
Modified residuei109 – 1091N6-acetyllysine1 Publication
Modified residuei211 – 2111Phosphothreonine1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiP62993.
PaxDbiP62993.
PRIDEiP62993.

2D gel databases

OGPiP62993.
SWISS-2DPAGEP62993.

PTM databases

PhosphoSiteiP62993.

Expressioni

Gene expression databases

BgeeiP62993.
CleanExiHS_GRB2.
ExpressionAtlasiP62993. baseline and differential.
GenevisibleiP62993. HS.

Organism-specific databases

HPAiCAB002589.
HPA030749.
HPA030750.

Interactioni

Subunit structurei

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. Interacts (via SH3 domains) with GAREM isoform 1 (via proline-rich domain and tyrosine phosphorylated); the interaction occurs upon EGF stimulation. Interacts with RAB13; may recruit RAB13 to the leading edge of migrating endothelial cells where it can activate RHOA. Interacts with ASAP3 (phosphorylated form). Interacts with CD28. Interacts with herpes simplex virus 1 UL46.By similarity53 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
CBLBQ131918EBI-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
DNM2P505704EBI-401755,EBI-346547
DOCK1Q141852EBI-401755,EBI-446740
DPPA4Q7L1903EBI-401755,EBI-710457
EGFRP0053332EBI-401755,EBI-297353
EPHB1P547622EBI-401755,EBI-80252
EPS8Q129293EBI-401755,EBI-375576
ERBB2P046264EBI-401755,EBI-641062
ERBB3P218603EBI-401755,EBI-720706
ERRFI1Q9UJM38EBI-401755,EBI-2941912
FAM22FB7ZLH03EBI-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
GAREMQ9H7066EBI-401755,EBI-3440103
HNRNPKP619785EBI-401755,EBI-304185
HNRPKQ6IBN14EBI-401755,EBI-3440248
HOMEZQ8IX15-33EBI-401755,EBI-10172004
IKZF3Q9UKT93EBI-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
LCP2Q1309410EBI-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
STAMBPO956306EBI-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
VAV3Q9UKW45EBI-401755,EBI-297568
VCPP550723EBI-401755,EBI-355164
WASLO004016EBI-401755,EBI-957615
WBP11Q9Y2W24EBI-401755,EBI-714455
WIPF1O435163EBI-401755,EBI-346356
WIPF2Q8TF743EBI-401755,EBI-2850112
ZBTB7BO151563EBI-401755,EBI-740434

Protein-protein interaction databases

BioGridi109142. 480 interactions.
DIPiDIP-29229N.
IntActiP62993. 741 interactions.
MINTiMINT-91952.
STRINGi9606.ENSP00000339007.

Structurei

Secondary structure

1
217
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi2 – 54Combined sources
Beta strandi13 – 153Combined sources
Beta strandi24 – 263Combined sources
Beta strandi36 – 438Combined sources
Beta strandi45 – 495Combined sources
Helixi50 – 523Combined sources
Beta strandi61 – 644Combined sources
Helixi67 – 759Combined sources
Beta strandi78 – 803Combined sources
Beta strandi82 – 876Combined sources
Turni89 – 935Combined sources
Beta strandi95 – 1017Combined sources
Beta strandi104 – 1129Combined sources
Beta strandi114 – 1163Combined sources
Beta strandi118 – 1225Combined sources
Beta strandi124 – 1274Combined sources
Helixi128 – 1347Combined sources
Turni135 – 1373Combined sources
Beta strandi142 – 1443Combined sources
Beta strandi149 – 1524Combined sources
Beta strandi155 – 1573Combined sources
Beta strandi160 – 1656Combined sources
Beta strandi171 – 1744Combined sources
Beta strandi182 – 1876Combined sources
Beta strandi190 – 1989Combined sources
Beta strandi201 – 2066Combined sources
Helixi207 – 2093Combined sources
Beta strandi210 – 2123Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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[»]
DisProtiDP00210.
ProteinModelPortaliP62993.
SMRiP62993. Positions 1-217.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP62993.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini1 – 5858SH3 1PROSITE-ProRule annotationAdd
BLAST
Domaini60 – 15293SH2PROSITE-ProRule annotationAdd
BLAST
Domaini156 – 21560SH3 2PROSITE-ProRule annotationAdd
BLAST

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

eggNOGiNOG298780.
GeneTreeiENSGT00550000074482.
HOGENOMiHOG000251625.
HOVERGENiHBG005404.
InParanoidiP62993.
KOiK04364.
OMAiRFQDSVQ.
OrthoDBiEOG75F4F6.
PhylomeDBiP62993.
TreeFamiTF354288.

Family and domain databases

Gene3Di3.30.505.10. 1 hit.
InterProiIPR030219. Grb2.
IPR000980. SH2.
IPR001452. SH3_domain.
[Graphical view]
PANTHERiPTHR22820:SF27. PTHR22820:SF27. 1 hit.
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)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei60 – 10041Missing in isoform 2. 1 PublicationVSP_001839Add
BLAST

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.
ENST00000392562; ENSP00000376345; ENSG00000177885.
ENST00000392563; ENSP00000376346; ENSG00000177885. [P62993-2]
ENST00000392564; ENSP00000376347; ENSG00000177885.
GeneIDi2885.
KEGGihsa:2885.
UCSCiuc002jnx.4. human.
uc002jny.4. human. [P62993-2]

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
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[»]
DisProtiDP00210.
ProteinModelPortaliP62993.
SMRiP62993. Positions 1-217.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109142. 480 interactions.
DIPiDIP-29229N.
IntActiP62993. 741 interactions.
MINTiMINT-91952.
STRINGi9606.ENSP00000339007.

Chemistry

BindingDBiP62993.
ChEMBLiCHEMBL3663.
DrugBankiDB00061. Pegademase bovine.

PTM databases

PhosphoSiteiP62993.

Polymorphism and mutation databases

BioMutaiGRB2.
DMDMi51702266.

2D gel databases

OGPiP62993.
SWISS-2DPAGEP62993.

Proteomic databases

MaxQBiP62993.
PaxDbiP62993.
PRIDEiP62993.

Protocols and materials databases

DNASUi2885.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000316615; ENSP00000317360; ENSG00000177885. [P62993-2]
ENST00000316804; ENSP00000339007; ENSG00000177885.
ENST00000392562; ENSP00000376345; ENSG00000177885.
ENST00000392563; ENSP00000376346; ENSG00000177885. [P62993-2]
ENST00000392564; ENSP00000376347; ENSG00000177885.
GeneIDi2885.
KEGGihsa:2885.
UCSCiuc002jnx.4. human.
uc002jny.4. human. [P62993-2]

Organism-specific databases

CTDi2885.
GeneCardsiGC17M073313.
HGNCiHGNC:4566. GRB2.
HPAiCAB002589.
HPA030749.
HPA030750.
MIMi108355. gene.
neXtProtiNX_P62993.
PharmGKBiPA28962.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG298780.
GeneTreeiENSGT00550000074482.
HOGENOMiHOG000251625.
HOVERGENiHBG005404.
InParanoidiP62993.
KOiK04364.
OMAiRFQDSVQ.
OrthoDBiEOG75F4F6.
PhylomeDBiP62993.
TreeFamiTF354288.

Enzyme and pathway databases

ReactomeiREACT_111040. Signaling by SCF-KIT.
REACT_111080. Spry regulation of FGF signaling.
REACT_111225. Regulation of KIT signaling.
REACT_115852. Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants.
REACT_115854. GRB2 events in ERBB2 signaling.
REACT_115993. SHC1 events in ERBB2 signaling.
REACT_116005. SHC1 events in ERBB4 signaling.
REACT_116008. PI3K events in ERBB2 signaling.
REACT_118700. Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
REACT_12033. Signalling to RAS.
REACT_121096. EGFR Transactivation by Gastrin.
REACT_121141. Signaling by FGFR1 fusion mutants.
REACT_12484. EGFR downregulation.
REACT_12578. GAB1 signalosome.
REACT_12579. SHC1 events in EGFR signaling.
REACT_12606. GRB2 events in EGFR signaling.
REACT_12621. Tie2 Signaling.
REACT_147727. Constitutive Signaling by Aberrant PI3K in Cancer.
REACT_147814. DAP12 signaling.
REACT_15443. GRB2:SOS provides linkage to MAPK signaling for Integrins.
REACT_160086. Regulation of actin dynamics for phagocytic cup formation.
REACT_163701. FCERI mediated MAPK activation.
REACT_163769. Role of LAT2/NTAL/LAB on calcium mobilization.
REACT_163834. FCERI mediated Ca+2 mobilization.
REACT_1695. GPVI-mediated activation cascade.
REACT_17025. Downstream signal transduction.
REACT_18334. NCAM signaling for neurite out-growth.
REACT_19238. CD28 dependent Vav1 pathway.
REACT_19290. G beta:gamma signalling through PI3Kgamma.
REACT_19344. Costimulation by the CD28 family.
REACT_23787. Regulation of signaling by CBL.
REACT_23837. Interleukin-3, 5 and GM-CSF signaling.
REACT_23891. Interleukin receptor SHC signaling.
REACT_23916. Signal regulatory protein (SIRP) family interactions.
REACT_267817. Constitutive Signaling by EGFRvIII.
REACT_355069. FRS-mediated FGFR2 signaling.
REACT_355144. Negative regulation of FGFR3 signaling.
REACT_355159. SHC-mediated cascade:FGFR4.
REACT_355160. PI-3K cascade:FGFR3.
REACT_355194. SHC-mediated cascade:FGFR1.
REACT_355197. SHC-mediated cascade:FGFR3.
REACT_355202. Signaling by FGFR4 mutants.
REACT_355212. FRS-mediated FGFR3 signaling.
REACT_355218. Negative regulation of FGFR1 signaling.
REACT_355221. Signaling by FGFR1 mutants.
REACT_355225. SHC-mediated cascade:FGFR2.
REACT_355227. Negative regulation of FGFR2 signaling.
REACT_355304. PI-3K cascade:FGFR4.
REACT_355313. Signaling by FGFR3 mutants.
REACT_355372. RHO GTPases Activate WASPs and WAVEs.
REACT_355450. PI-3K cascade:FGFR2.
REACT_355511. Signaling by FGFR2 mutants.
REACT_355552. PI-3K cascade:FGFR1.
REACT_355580. FRS2-mediated FGFR4 signaling.
REACT_355584. FRS-mediated FGFR1 signaling.
REACT_355588. Negative regulation of FGFR4 signaling.
REACT_508. Signal attenuation.
REACT_524. SOS-mediated signalling.
REACT_661. SHC-mediated signalling.
REACT_75829. PIP3 activates AKT signaling.
REACT_976. PI3K Cascade.
SignaLinkiP62993.

Miscellaneous databases

ChiTaRSiGRB2. human.
EvolutionaryTraceiP62993.
GeneWikiiGRB2.
GenomeRNAii2885.
NextBioi11389.
PROiP62993.
SOURCEiSearch...

Gene expression databases

BgeeiP62993.
CleanExiHS_GRB2.
ExpressionAtlasiP62993. baseline and differential.
GenevisibleiP62993. HS.

Family and domain databases

Gene3Di3.30.505.10. 1 hit.
InterProiIPR030219. Grb2.
IPR000980. SH2.
IPR001452. SH3_domain.
[Graphical view]
PANTHERiPTHR22820:SF27. PTHR22820:SF27. 1 hit.
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...

Publicationsi

« Hide 'large scale' publications
  1. "The SH2 and SH3 domain-containing protein GRB2 links receptor tyrosine kinases to ras signaling."
    Lowenstein E.J., Daly R.J., Batzer A.G., Li W., Margolis B., Lammers R., Ullrich A., Skolnik E.Y., Bar-Sagi D., Schlessinger J.
    Cell 70:431-442(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, MUTAGENESIS OF PRO-49 AND GLY-203.
    Tissue: Brain.
  2. "Cloning of ASH, a ubiquitous protein composed of one Src homology region (SH) 2 and two SH3 domains, from human and rat cDNA libraries."
    Matuoka K., Yamakawa A., Shibata M., Takenawa T.
    Proc. Natl. Acad. Sci. U.S.A. 89:9015-9019(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Tissue: Fetal lung.
  3. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION.
    Tissue: Placenta.
  4. "The gene structure of the human growth factor bound protein GRB2."
    Bochmann H., Gehrisch S., Jaross W.
    Genomics 56:203-207(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Tissue: Epidermis.
  5. "cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org)."
    Puhl H.L. III, Ikeda S.R., Aronstam R.S.
    Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Brain.
  6. "Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
    Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., LaBaer J.
    Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
  7. "DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage."
    Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L.
    , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.
    Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  8. "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] (ISOFORM 1).
    Tissue: Lymph.
  9. Lubec G., Afjehi-Sadat L., Chen W.-Q., Sun Y.
    Submitted (DEC-2008) to UniProtKB
    Cited for: PROTEIN SEQUENCE OF 11-20; 27-38; 77-109; 118-136; 143-149 AND 179-195, IDENTIFICATION BY MASS SPECTROMETRY.
    Tissue: Brain, Cajal-Retzius cell and Fetal brain cortex.
  10. "Mutation of Tyr697, a GRB2-binding site, and Tyr721, a PI 3-kinase binding site, abrogates signal transduction by the murine CSF-1 receptor expressed in Rat-2 fibroblasts."
    van der Geer P., Hunter T.
    EMBO J. 12:5161-5172(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH CSF1R.
  11. "Insulin stimulates association of insulin receptor substrate-1 with the protein abundant Src homology/growth factor receptor-bound protein 2."
    Tobe K., Matuoka K., Tamemoto H., Ueki K., Kaburagi Y., Asai S., Noguchi T., Matsuda M., Tanaka S., Hattori S., Fukui Y., Akanuma Y., Yazaki Y., Takenawa T., Kadowaki T.
    J. Biol. Chem. 268:11167-11171(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH IRS1.
  12. "The SH2/SH3 domain-containing protein GRB2 interacts with tyrosine-phosphorylated IRS1 and Shc: implications for insulin control of ras signalling."
    Skolnik E.Y., Lee C.-H., Batzer A.G., Vicentini L.M., Zhou M., Daly R.J., Myers M.J. Jr., Backer J.M., Ullrich A., White M.F., Schlessinger J.
    EMBO J. 12:1929-1936(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH IRS1 AND SHC.
  13. "Association of the DF3/MUC1 breast cancer antigen with Grb2 and the Sos/Ras exchange protein."
    Pandey P., Kharbanda S., Kufe D.
    Cancer Res. 55:4000-4003(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION IN A COMPLEX WITH MUC1 AND SOS1, INTERACTION WITH MUC1 AND SOS1.
  14. "Multiple forms of an inositol polyphosphate 5-phosphatase form signaling complexes with Shc and Grb2."
    Kavanaugh W.M., Pot D.A., Chin S.M., Deuter-Reinhard M., Jefferson A.B., Norris F.A., Masiarz F.R., Cousens L.S., Majerus P.W., Williams L.T.
    Curr. Biol. 6:438-445(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH INPP5D.
  15. "Ligand activation of ELK receptor tyrosine kinase promotes its association with Grb10 and Grb2 in vascular endothelial cells."
    Stein E., Cerretti D.P., Daniel T.O.
    J. Biol. Chem. 271:23588-23593(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH EPHB1.
  16. "Purification and molecular cloning of SH2- and SH3-containing inositol polyphosphate-5-phosphatase, which is involved in the signaling pathway of granulocyte-macrophage colony-stimulating factor, erythropoietin, and Bcr-Abl."
    Odai H., Sasaki K., Iwamatsu A., Nakamoto T., Ueno H., Yamagata T., Mitani K., Yazaki Y., Hirai H.
    Blood 89:2745-2756(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH INPP5D.
  17. "Focal adhesion kinase overexpression enhances ras-dependent integrin signaling to ERK2/mitogen-activated protein kinase through interactions with and activation of c-Src."
    Schlaepfer D.D., Hunter T.
    J. Biol. Chem. 272:13189-13195(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH PTK2/FAK1.
  18. "A family of proteins that inhibit signalling through tyrosine kinase receptors."
    Kharitonenkov A., Chen Z., Sures I., Wang H., Schilling J., Ullrich A.
    Nature 386:181-186(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH PTPNS1.
  19. "Intracellular signaling of the Ufo/Axl receptor tyrosine kinase is mediated mainly by a multi-substrate docking-site."
    Braunger J., Schleithoff L., Schulz A.S., Kessler H., Lammers R., Ullrich A., Bartram C.R., Janssen J.W.
    Oncogene 14:2619-2631(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH AXL.
  20. "Cloning and characterization of APS, an adaptor molecule containing PH and SH2 domains that is tyrosine phosphorylated upon B-cell receptor stimulation."
    Yokouchi M., Suzuki R., Masuhara M., Komiya S., Inoue A., Yoshimura A.
    Oncogene 15:7-15(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH SH2B2.
  21. "LAT: the ZAP-70 tyrosine kinase substrate that links T cell receptor to cellular activation."
    Zhang W., Sloan-Lancaster J., Kitchen J., Trible R.P., Samelson L.E.
    Cell 92:83-92(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH LAT.
  22. "Identification and characterization of a novel protein interacting with Ral-binding protein 1, a putative effector protein of Ral."
    Ikeda M., Ishida O., Hinoi T., Kishida S., Kikuchi A.
    J. Biol. Chem. 273:814-821(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH REPS2.
  23. "Characterization of insulin receptor substrate 4 in human embryonic kidney 293 cells."
    Fantin V.R., Sparling J.D., Slot J.W., Keller S.R., Lienhard G.E., Lavan B.E.
    J. Biol. Chem. 273:10726-10732(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH IRS4.
  24. "Stimulation through the T cell receptor leads to interactions between SHB and several signaling proteins."
    Welsh M., Songyang Z., Frantz J.D., Trueb T., Reedquist K.A., Karlsson T., Miyazaki M., Cantley L.C., Band H., Shoelson S.E.
    Oncogene 16:891-901(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH SHB, MUTAGENESIS OF PRO-49 AND PRO-206.
  25. "Identification of Grb4/Nckbeta, a src homology 2 and 3 domain-containing adapter protein having similar binding and biological properties to Nck."
    Braverman L.E., Quilliam L.A.
    J. Biol. Chem. 274:5542-5549(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH EGFR.
  26. "Tyrosine phosphorylation and complex formation of Cbl-b upon T cell receptor stimulation."
    Elly C., Witte S., Zhang Z., Rosnet O., Lipkowitz S., Altman A., Liu Y.-C.
    Oncogene 18:1147-1156(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH CBLB.
  27. Cited for: INTERACTION WITH CBL AND CBLB.
  28. "NS5A, a nonstructural protein of hepatitis C virus, binds growth factor receptor-bound protein 2 adaptor protein in a Src homology 3 domain/ligand-dependent manner and perturbs mitogenic signaling."
    Tan S.-L., Nakao H., He Y., Vijaysri S., Neddermann P., Jacobs B.L., Mayer B.J., Katze M.G.
    Proc. Natl. Acad. Sci. U.S.A. 96:5533-5538(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH HCV NS5A.
  29. "Identification and characterization of a new family of guanine nucleotide exchange factors for the ras-related GTPase Ral."
    Rebhun J.F., Chen H., Quilliam L.A.
    J. Biol. Chem. 275:13406-13410(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH RALGPS1.
  30. "Ligand discrimination in signaling through an ErbB4 receptor homodimer."
    Sweeney C., Lai C., Riese D.J. II, Diamonti A.J., Cantley L.C., Carraway K.L. III
    J. Biol. Chem. 275:19803-19807(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH ERBB4.
  31. "Interaction of linker for activation of T cells with multiple adapter proteins in platelets activated by the glycoprotein VI-selective ligand, convulxin."
    Asazuma N., Wilde J.I., Berlanga O., Leduc M., Leo A., Schweighoffer E., Tybulewicz V., Bon C., Liu S.K., McGlade C.J., Schraven B., Watson S.P.
    J. Biol. Chem. 275:33427-33434(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH SKAP2.
  32. "Generation of novel cytoplasmic forms of protein tyrosine phosphatase epsilon by proteolytic processing and translational control."
    Gil-Henn H., Volohonsky G., Toledano-Katchalski H., Gandre S., Elson A.
    Oncogene 19:4375-4384(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH PTPRE.
  33. "Structural and functional dissection of the cytoplasmic domain of the transmembrane adaptor protein SIT (SHP2-interacting transmembrane adaptor protein)."
    Pfrepper K.-I., Marie-Cardine A., Simeoni L., Kuramitsu Y., Leo A., Spicka J., Hilgert I., Scherer J., Schraven B.
    Eur. J. Immunol. 31:1825-1836(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH SIT1.
  34. "The ORF3 protein of hepatitis E virus binds to Src homology 3 domains and activates MAPK."
    Korkaya H., Jameel S., Gupta D., Tyagi S., Kumar R., Zafrullah M., Mazumdar M., Lal S.K., Xiaofang L., Sehgal D., Das S.R., Sahal D.
    J. Biol. Chem. 276:42389-42400(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH HEV ORF3 PROTEIN.
  35. "Recruitment of the class II phosphoinositide 3-kinase C2beta to the epidermal growth factor receptor: role of Grb2."
    Wheeler M., Domin J.
    Mol. Cell. Biol. 21:6660-6667(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION IN A COMPLEX WITH PIK3C2B AND EGFR, INTERACTION WITH PIK3C2B.
  36. "Insulin receptor substrate 4 associates with the protein IRAS."
    Sano H., Liu S.C.H., Lane W.S., Piletz J.E., Lienhard G.E.
    J. Biol. Chem. 277:19439-19447(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH NISCH.
  37. "SKAP55 recruits to lipid rafts and positively mediates the MAPK pathway upon T cell receptor activation."
    Wu L., Yu Z., Shen S.-H.
    J. Biol. Chem. 277:40420-40427(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH SKAP1.
  38. "Molecular cloning of a novel gene encoding a membrane-associated adaptor protein (LAX) in lymphocyte signaling."
    Zhu M., Janssen E., Leung K., Zhang W.
    J. Biol. Chem. 277:46151-46158(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH LAX1.
  39. Cited for: INTERACTION WITH LAT2.
  40. "Hepatocyte growth factor receptor tyrosine kinase met is a substrate of the receptor protein-tyrosine phosphatase DEP-1."
    Palka H.L., Park M., Tonks N.K.
    J. Biol. Chem. 278:5728-5735(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH PTPRJ.
  41. "EphB1 recruits c-Src and p52Shc to activate MAPK/ERK and promote chemotaxis."
    Vindis C., Cerretti D.P., Daniel T.O., Huynh-Do U.
    J. Cell Biol. 162:661-671(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH EPHB1 AND SHC1.
  42. "LAB: a new membrane-associated adaptor molecule in B cell activation."
    Janssen E., Zhu M., Zhang W., Koonpaew S., Zhang W.
    Nat. Immunol. 4:117-123(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH LAT2.
  43. Cited for: INTERACTION WITH NTRK1.
  44. "Activation of vascular endothelial growth factor receptor-3 and its downstream signaling promote cell survival under oxidative stress."
    Wang J.F., Zhang X., Groopman J.E.
    J. Biol. Chem. 279:27088-27097(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH FLT4.
  45. "Signal transduction via the stem cell factor receptor/c-Kit."
    Ronnstrand L.
    Cell. Mol. Life Sci. 61:2535-2548(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW ON INTERACTION WITH KIT AND ROLE IN KIT SIGNALING.
  46. "The c-Fes tyrosine kinase cooperates with the breakpoint cluster region protein (Bcr) to induce neurite extension in a Rac- and Cdc42-dependent manner."
    Laurent C.E., Smithgall T.E.
    Exp. Cell Res. 299:188-198(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH BCR.
  47. "Signaling by Kit protein-tyrosine kinase--the stem cell factor receptor."
    Roskoski R. Jr.
    Biochem. Biophys. Res. Commun. 337:1-13(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW ON ROLE IN KIT SIGNALING.
  48. "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
    Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
    Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  49. "NKG2D-mediated signaling requires a DAP10-bound Grb2-Vav1 intermediate and phosphatidylinositol-3-kinase in human natural killer cells."
    Upshaw J.L., Arneson L.N., Schoon R.A., Dick C.J., Billadeau D.D., Leibson P.J.
    Nat. Immunol. 7:524-532(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH HCST.
  50. "Identification of a new transmembrane adaptor protein that constitutively binds Grb2 in B cells."
    Liu Y., Zhang W.
    J. Leukoc. Biol. 84:842-851(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH GAPT.
  51. "Distinct functions of natural ADAM-15 cytoplasmic domain variants in human mammary carcinoma."
    Zhong J.L., Poghosyan Z., Pennington C.J., Scott X., Handsley M.M., Warn A., Gavrilovic J., Honert K., Kruger A., Span P.N., Sweep F.C., Edwards D.R.
    Mol. Cancer Res. 6:383-394(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH ADAM15.
  52. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-211, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  53. "An unbiased screen identifies DEP-1 tumor suppressor as a phosphatase controlling EGFR endocytosis."
    Tarcic G., Boguslavsky S.K., Wakim J., Kiuchi T., Liu A., Reinitz F., Nathanson D., Takahashi T., Mischel P.S., Ng T., Yarden Y.
    Curr. Biol. 19:1788-1798(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH EGFR.
  54. "Cytoplasmic ACK1 interaction with multiple receptor tyrosine kinases is mediated by Grb2: an analysis of ACK1 effects on Axl signaling."
    Pao-Chun L., Chan P.M., Chan W., Manser E.
    J. Biol. Chem. 284:34954-34963(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH AXL; LTK; PDGFRL AND TNK2, FUNCTION.
  55. "KIF26A is an unconventional kinesin and regulates GDNF-Ret signaling in enteric neuronal development."
    Zhou R., Niwa S., Homma N., Takei Y., Hirokawa N.
    Cell 139:802-813(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH KIF26A.
  56. "GAREM, a novel adaptor protein for growth factor receptor-bound protein 2, contributes to cellular transformation through the activation of extracellular signal-regulated kinase signaling."
    Tashiro K., Tsunematsu T., Okubo H., Ohta T., Sano E., Yamauchi E., Taniguchi H., Konishi H.
    J. Biol. Chem. 284:20206-20214(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH GAREM.
  57. "Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
    Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
    Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Leukemic T-cell.
  58. "Lysine acetylation targets protein complexes and co-regulates major cellular functions."
    Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
    Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1; LYS-6; LYS-50 AND LYS-109, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  59. "Recruitment of Pyk2 to SHPS-1 signaling complex is required for IGF-I-dependent mitogenic signaling in vascular smooth muscle cells."
    Shen X., Xi G., Radhakrishnan Y., Clemmons D.R.
    Cell. Mol. Life Sci. 67:3893-3903(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH PTK2B/PYK2.
  60. "Histidine domain-protein tyrosine phosphatase interacts with Grb2 and GrpL."
    Tanase C.A.
    PLoS ONE 5:E14339-E14339(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH PTPN23, SUBCELLULAR LOCATION.
  61. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  62. "ACAP4 protein cooperates with Grb2 protein to orchestrate epidermal growth factor-stimulated integrin beta1 recycling in cell migration."
    Yu X., Wang F., Liu H., Adams G., Aikhionbare F., Liu D., Cao X., Fan L., Hu G., Chen Y., Frost A., Partridge E., Ding X., Yao X.
    J. Biol. Chem. 286:43735-43747(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH ASAP3.
  63. "SCIMP, a transmembrane adapter protein involved in major histocompatibility complex class II signaling."
    Draber P., Vonkova I., Stepanek O., Hrdinka M., Kucova M., Skopcova T., Otahal P., Angelisova P., Horejsi V., Yeung M., Weiss A., Brdicka T.
    Mol. Cell. Biol. 31:4550-4562(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH SCIMP.
  64. "Tespa1 is involved in late thymocyte development through the regulation of TCR-mediated signaling."
    Wang D., Zheng M., Lei L., Ji J., Yao Y., Qiu Y., Ma L., Lou J., Ouyang C., Zhang X., He Y., Chi J., Wang L., Kuang Y., Wang J., Cao X., Lu L.
    Nat. Immunol. 13:560-568(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH TESPA1.
    Tissue: Thymocyte.
  65. Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  66. "Role of herpes simplex virus VP11/12 tyrosine-based motifs in binding and activation of the Src family kinase Lck and recruitment of p85, Grb2, and Shc."
    Strunk U., Saffran H.A., Wu F.W., Smiley J.R.
    J. Virol. 87:11276-11286(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH HERPES SIMPLEX VIRUS 1 UL46.
  67. "Nuclear magnetic resonance solution structure of the growth factor receptor-bound protein 2 Src homology 2 domain."
    Thornton K.H., Mueller W.T., McConnell P., Zhu G., Saltiel A.R., Thanabal V.
    Biochemistry 35:11852-11864(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF 58-164.
  68. "The three-dimensional solution structure of the Src homology domain-2 of the growth factor receptor-bound protein-2."
    Senior M.M., Frederick A.F., Black S., Murgolo N.J., Perkins L.M., Wilson O., Snow M.E., Wang Y.-S.
    J. Biomol. NMR 11:153-164(1998)
    Cited for: STRUCTURE BY NMR OF 52-163.
  69. "Solution structure and ligand-binding site of the carboxy-terminal SH3 domain of GRB2."
    Kohda D., Terasawa H., Ichikawa S., Ogura K., Hatanaka H., Mandiyan V., Ullrich A., Schlessinger J., Inagaki F.
    Structure 2:1029-1040(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF 157-215.
  70. Cited for: X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS).
  71. "Structural basis for the high affinity of amino-aromatic SH2 phosphopeptide ligands."
    Rahuel J., Garcia-Echeverria C., Furet P., Strauss A., Caravatti G., Fretz H., Schoepfer J., Gay B.
    J. Mol. Biol. 279:1013-1022(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 56-153.
  72. "Structural and conformational requirements for high-affinity binding to the SH2 domain of Grb2(1)."
    Ettmayer P., France D., Gounarides J., Jarosinski M., Martin M.-S., Rondeau J.-M., Sabio M., Topiol S., Weidmann B., Zurini M., Bair K.W.
    J. Med. Chem. 42:971-980(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 47-163.
  73. "Structure-based design, synthesis, and X-ray crystallography of a high- affinity antagonist of the Grb2-SH2 domain containing an asparagine mimetic."
    Furet P., Garcia-Echeverria C., Gay B., Schoepfer J., Zeller M., Rahuel J.
    J. Med. Chem. 42:2358-2363(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 57-152.
  74. "Dimer formation through domain swapping in the crystal structure of the Grb2-SH2-Ac-pYVNV complex."
    Schiering N., Casale E., Caccia P., Giordano P., Battistini C.
    Biochemistry 39:13376-13382(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 52-160 IN COMPLEX WITH MET.
  75. "Crystal structures of the SH2 domain of Grb2: highlight on the binding of a new high-affinity inhibitor."
    Nioche P., Liu W.-Q., Broutin I., Charbonnier F., Latreille M.-T., Vidal M., Roques B., Garbay C., Ducruix A.
    J. Mol. Biol. 315:1167-1177(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 56-151 IN COMPLEX WITH THE TYROSINE PHOSPHORYLATED PEPTIDE TYR-VAL-ASN-VAL-GLN-ASN AND IN COMPLEX WITH A PEPTIDE INHIBITOR.
  76. "Distinct binding modes of two epitopes in Gab2 that interact with the SH3C domain of Grb2."
    Harkiolaki M., Tsirka T., Lewitzky M., Simister P.C., Joshi D., Bird L.E., Jones E.Y., O'Reilly N., Feller S.M.
    Structure 17:809-822(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.58 ANGSTROMS) OF 158-211 IN COMPLEX WITH GAB2.
  77. "High resolution crystal structure of the Grb2 SH2 domain with a phosphopeptide derived from CD28."
    Higo K., Ikura T., Oda M., Morii H., Takahashi J., Abe R., Ito N.
    PLoS ONE 8:E74482-E74482(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.35 ANGSTROMS) OF 60-152 IN COMPLEX WITH CD28, INTERACTION WITH CD28.

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: July 22, 2015
This is version 150 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

External Data

Dasty 3

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 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.