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Reviewed, UniProtKB/Swiss-Prot P62993 (GRB2_HUMAN)

Last modified November 3, 2009. Version 85. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Growth factor receptor-bound protein 2
Alternative name(s):
    Adapter protein GRB2
    SH2/SH3 adapter GRB2
    Protein Ash
Gene names
Name: GRB2
Synonyms: ASH
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length217 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

Adapter protein that provides a critical link between cell surface growth factor receptors and the Ras signaling pathway. Ref.1 Ref.3

Isoform GRB3-3 does not bind to phosphorylated epidermal growth factor receptor (EGFR) but inhibits EGF-induced transactivation of a RAS-responsive element. Isoform GRB3-3 acts as a dominant negative protein over GRB2 and by suppressing proliferative signals, may trigger active programmed cell death. Ref.1 Ref.3

Subunit structure

Associates with activated Tyr-phosphorylated EGF receptors 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 JUB and CLNK 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 PRNP and THEMIS By similarity. Interacts with RALGPS1 and with HCST. Interacts (via SH3 domain) with HEV ORF3 protein. Interacts with GAPT.

Subcellular location

Golgi apparatus By similarity.

Domain

The SH3 domains mediate interaction with RALGPS1 and SHB.

Sequence similarities

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

Contains 1 SH2 domain.

Contains 2 SH3 domains.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

O929722EBI-401755,EBI-710506From a different organism.
P266601EBI-401755,EBI-706322From a different organism.
P279583EBI-401755,EBI-706378From a different organism.
Q929361EBI-401755,EBI-1760181
Q929371EBI-401755,EBI-1760197
Q9WMX21EBI-401755,EBI-710918From a different organism.
ABL1P005191EBI-401755,EBI-375543
ABL2P426841EBI-401755,EBI-1102694
ACAP1Q150271EBI-401755,EBI-751746
AFF2P518161EBI-401755,EBI-1754468
AGERQ151091EBI-401755,EBI-1646426
AIREO439181EBI-401755,EBI-1753081
AKAP2Q9Y2D51EBI-401755,EBI-1754555
AKAP6Q130231EBI-401755,EBI-1056102
ANK2Q014841EBI-401755,EBI-941975
APOL5Q9BWW91EBI-401755,EBI-1753592
ARHGEF11O150851EBI-401755,EBI-311099
ASAP1Q9ULH11EBI-401755,EBI-346622
ASAP2O431501EBI-401755,EBI-310968
ASB16Q96NS51EBI-401755,EBI-1751918
ASXL1Q8IXJ91EBI-401755,EBI-1646500
BADQ929341EBI-401755,EBI-700771
BAT2P486341EBI-401755,EBI-347545
BAZ2AQ9UIF91EBI-401755,EBI-934890
BIN1O004991EBI-401755,EBI-719094
BRCA2P515871EBI-401755,EBI-79792
BRD4O608851EBI-401755,EBI-723869
BRPF3Q9ULD41EBI-401755,EBI-1753470
C6P136711EBI-401755,EBI-1753221
CASTP208101EBI-401755,EBI-1268770
CCKBRP322391EBI-401755,EBI-1753137
CCR10P460921EBI-401755,EBI-348022
CDC27P302601EBI-401755,EBI-994813
CDKL5O760391EBI-401755,EBI-1752465
CELSR3Q9NYQ71EBI-401755,EBI-308417
CHRDQ9H2X01EBI-401755,EBI-947551
CKAP5Q140081EBI-401755,EBI-310585
CNTFRP269921EBI-401755,EBI-743758
CNTNAP1P783571EBI-401755,EBI-1751903
COBRA1Q8WX921EBI-401755,EBI-347721
CRYBB3P269981EBI-401755,EBI-1965681
CUGBP2O953191EBI-401755,EBI-949790
CXCR7P251061EBI-401755,EBI-1965291
CYP4F2P783291EBI-401755,EBI-1752413
CYTH2Q994181EBI-401755,EBI-448974
DAB2P980821EBI-401755,EBI-1171238
DAG1Q141181EBI-401755,EBI-1755945
DARSP148681EBI-401755,EBI-358730
DLG4P783521EBI-401755,EBI-80389
DLGAP1O144901EBI-401755,EBI-1753207
DLGAP2Q9P1A61EBI-401755,EBI-1753397
DLGAP3O958861EBI-401755,EBI-1752541
DLGAP4Q9Y2H01EBI-401755,EBI-722139
DLX4Q929881EBI-401755,EBI-1752755
DNM1Q051932EBI-401755,EBI-713135
DOCK1Q141851EBI-401755,EBI-446740
DOCK3Q8IZD91EBI-401755,EBI-1752361
DUSP15Q9H1R21EBI-401755,EBI-1752795
ECT2Q9H8V31EBI-401755,EBI-1054039
EFSO432811EBI-401755,EBI-718488
EGFRP005332EBI-401755,EBI-297353
EHMT2Q96KQ71EBI-401755,EBI-744366
EIF3DO153711EBI-401755,EBI-353818
ELK3P419701EBI-401755,EBI-1758534
EPHB1P547621EBI-401755,EBI-80252
EPS15P425661EBI-401755,EBI-396684
EXTL1Q929351EBI-401755,EBI-1760167
EXTL3O439091EBI-401755,EBI-1754679
F2RL2O002541EBI-401755,EBI-1751853
FAM110AQ9BQ891EBI-401755,EBI-1752811
FANCAO153601EBI-401755,EBI-81570
FCGR2BP319941EBI-401755,EBI-724784
FCGR2CP319951EBI-401755,EBI-1396036
FLNAP213331EBI-401755,EBI-350432
FLNBO753691EBI-401755,EBI-352089
FLNCQ143151EBI-401755,EBI-489954
FOXH1O755931EBI-401755,EBI-1759806
FOXJ1Q929491EBI-401755,EBI-1760377
FUBP3Q96I241EBI-401755,EBI-954200
GABBR1Q9UBS51EBI-401755,EBI-724156
GAD1Q992591EBI-401755,EBI-743184
GCDHQ929471EBI-401755,EBI-1236978
GHRP109121EBI-401755,EBI-286316
GLTSCR1Q9NZM41EBI-401755,EBI-1754943
GNSP155861EBI-401755,EBI-1752200
GPR45Q9Y5Y31EBI-401755,EBI-1751869
GRB10Q133221EBI-401755,EBI-80275
GRIP2Q9C0E41EBI-401755,EBI-949557
GSTZ1O437081EBI-401755,EBI-748043
HCN2Q9UL511EBI-401755,EBI-1751885
HIBCHQ6NVY11EBI-401755,EBI-1965197
HMGN2P052041EBI-401755,EBI-1758689
HMGN3Q156511EBI-401755,EBI-1758705
HNRNPRO433901EBI-401755,EBI-713419
HOXC8P312731EBI-401755,EBI-1752118
ID4P479281EBI-401755,EBI-1754719
IL2RGP317851EBI-401755,EBI-80475
IL3RAP269511EBI-401755,EBI-1757512
IL5RAQ013441EBI-401755,EBI-1759442
ISG20L2Q9H9L31EBI-401755,EBI-751335
JAK2O606741EBI-401755,EBI-518647
KCNB2Q929531EBI-401755,EBI-1760439
KCNH7Q9NS401EBI-401755,EBI-1759868
KCNN1Q929521EBI-401755,EBI-1748210
KCNQ1P517871EBI-401755,EBI-359667
KHDRBS1Q076662EBI-401755,EBI-1364
KHSRPQ929451EBI-401755,EBI-1049099
KIF13AQ9H1H91EBI-401755,EBI-1759129
LATO435611EBI-401755,EBI-1222766
LEPRP483571EBI-401755,EBI-518596
LY6DQ142101EBI-401755,EBI-1965225
MAP2K5Q131631EBI-401755,EBI-307294
MAP4K1Q929181EBI-401755,EBI-881
MAP4K3Q8IVH81EBI-401755,EBI-1758170
MAP4K5Q9Y4K42EBI-401755,EBI-1279
MED14O602441EBI-401755,EBI-394489
MED28Q9H2043EBI-401755,EBI-514199
MEPEQ9NQ761EBI-401755,EBI-1753293
MYLKQ157461EBI-401755,EBI-968482
MYRIPQ8NFW91EBI-401755,EBI-1759414
NAP5O145131EBI-401755,EBI-1752508
NEK8Q86SG61EBI-401755,EBI-1752987
NFASCO948561EBI-401755,EBI-1751948
NFS1Q9Y6971EBI-401755,EBI-1751791
NKX2-1P436991EBI-401755,EBI-1391923
NR1H4Q96RI11EBI-401755,EBI-1250177
NR5A1Q132851EBI-401755,EBI-874629
P2RX7Q995721EBI-401755,EBI-1753251
PANX2Q96RD61EBI-401755,EBI-1759592
PAX3P237601EBI-401755,EBI-1167564
PDIA2Q130871EBI-401755,EBI-1752525
PEX13Q929681EBI-401755,EBI-594849
PHACTR2O751671EBI-401755,EBI-1754409
PIK3C2BO007501EBI-401755,EBI-641107
PLCG2P168851EBI-401755,EBI-617403
PLD2O149392EBI-401755,EBI-1053996
PNMA2Q9UL421EBI-401755,EBI-302355
POLD1P283401EBI-401755,EBI-716569
POLR1BQ9H9Y61EBI-401755,EBI-355441
PPP3CAQ082091EBI-401755,EBI-352922
PPP3CBP162981EBI-401755,EBI-1759540
PRG4Q929541EBI-401755,EBI-1760455
PRICKLE3O439001EBI-401755,EBI-1751761
PRKAB1Q9Y4781EBI-401755,EBI-719769
PRSS1P074771EBI-401755,EBI-1222902
PTPN4P290741EBI-401755,EBI-710431
PTPRN2Q929321EBI-401755,EBI-310576
rab1bQ929271EBI-401755,EBI-1760045
RAB1CQ929281EBI-401755,EBI-1760061
rab6bQ929291EBI-401755,EBI-1760079
RAB8BQ929301EBI-401755,EBI-1760095
RGL2Q929421EBI-401755,EBI-1760273
RIMS1Q86UR51EBI-401755,EBI-1043236
RIMS2Q9UQ261EBI-401755,EBI-1756749
RIN3Q8TB241EBI-401755,EBI-1570523
RIT1Q929631EBI-401755,EBI-365845
RIT2Q995781EBI-401755,EBI-365914
RNASENQ9NRR41EBI-401755,EBI-528367
RP1L1Q8IWN71EBI-401755,EBI-1757848
RPL13P263731EBI-401755,EBI-356849
RPP38P783451EBI-401755,EBI-366493
RPUSD2Q8IZ731EBI-401755,EBI-1965305
RRASP103011EBI-401755,EBI-968703
RYR1P218171EBI-401755,EBI-1221290
SCARF2Q96GP61EBI-401755,EBI-1752088
SEMA7AO753261EBI-401755,EBI-1753538
SEPN1Q9NZV51EBI-401755,EBI-1751965
SF3B4Q154271EBI-401755,EBI-348469
SHANK2Q9UPX81EBI-401755,EBI-1570571
SHANK3Q9BYB01EBI-401755,EBI-1752330
SHROOM2Q137961EBI-401755,EBI-1644065
SLC23A1Q9UHI71EBI-401755,EBI-1759386
SLC24A1O607211EBI-401755,EBI-1753504
SLCO2A1Q929591EBI-401755,EBI-1760532
SMAD3P840221EBI-401755,EBI-347161
SMARCC1Q929221EBI-401755,EBI-355653
SMARCC2Q8TAQ21EBI-401755,EBI-357418
SMARCD1Q96GM51EBI-401755,EBI-358489
SMARCD2Q929251EBI-401755,EBI-358441
SMARCD3Q929261EBI-401755,EBI-1760029
SNAPC3Q929661EBI-401755,EBI-1760638
SNX12Q9UMY41EBI-401755,EBI-1752602
SNX17Q150361EBI-401755,EBI-1752620
SNX3O604931EBI-401755,EBI-727209
SNX7Q9UNH61EBI-401755,EBI-751422
SNX8Q9Y5X21EBI-401755,EBI-1752557
SOS1Q078893EBI-401755,EBI-297487
SOS2Q078903EBI-401755,EBI-298181
SP1P080471EBI-401755,EBI-298336
SPENQ96T581EBI-401755,EBI-765739
ST5P785241EBI-401755,EBI-962633
SUV39H2Q9H5I11EBI-401755,EBI-723127
SYNJ2O150561EBI-401755,EBI-310513
TGOLN2O434931EBI-401755,EBI-1752146
TMPOP421671EBI-401755,EBI-455283
TNFRSF14Q929561EBI-401755,EBI-1056653
TNPO1Q929731EBI-401755,EBI-286693
TPX2Q9ULW01EBI-401755,EBI-1037322
TRAIPQ9BWF21EBI-401755,EBI-1756205
TRIM39Q9HCM91EBI-401755,EBI-739510
TSKSQ9UJT21EBI-401755,EBI-852101
TULP1O002941EBI-401755,EBI-1756778
UGP2Q168511EBI-401755,EBI-743729
VAV1P154981EBI-401755,EBI-625518
VPS13AQ96RL71EBI-401755,EBI-1752583
WASLO004011EBI-401755,EBI-957615
WBP7Q9UMN61EBI-401755,EBI-765774
zf30Q929701EBI-401755,EBI-1760698
ZF6Q929671EBI-401755,EBI-1760656
ZKSCAN3Q9BRR01EBI-401755,EBI-1965777
ZNF274Q96GC61EBI-401755,EBI-1965735
ZNF311Q5JNZ31EBI-401755,EBI-1965761
ZNF32P170411EBI-401755,EBI-1965483

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.
Isoform 1 (identifier: P62993-1)

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.
Isoform GRB3-3 (identifier: P62993-2)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 217217Growth factor receptor-bound protein 2
PRO_0000088198

Regions

Domain1 – 5858SH3 1
Domain60 – 15293SH2
Domain156 – 21560SH3 2

Amino acid modifications

Modified residue61N6-acetyllysine Ref.38
Modified residue501N6-acetyllysine Ref.38
Modified residue1091N6-acetyllysine Ref.38
Modified residue1601Phosphotyrosine Ref.34
Modified residue2091Phosphotyrosine Ref.34
Modified residue2111Phosphothreonine Ref.36

Natural variations

Alternative sequence60 – 10041Missing in isoform GRB3-3.
VSP_001839

Experimental info

Mutagenesis491P → L: Ineffective in DNA synthesis. Abolishes interaction with SHB; when associated with L-206. Ref.1 Ref.19
Mutagenesis2031G → R: Ineffective in DNA synthesis. Ref.1
Mutagenesis2061P → L: Abolishes interaction with SHB; when associated with L-49. Ref.19

Secondary structure

..................................... 217
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Ash-L) [UniParc].

Last modified August 31, 2004. Version 1.
Checksum: 83A4B0BA1B248DC4

FASTA21725,206
        10         20         30         40         50         60 
MEAIAKYDFK ATADDELSFK RGDILKVLNE ECDQNWYKAE LNGKDGFIPK NYIEMKPHPW 

        70         80         90        100        110        120 
FFGKIPRAKA EEMLSKQRHD GAFLIRESES APGDFSLSVK FGNDVQHFKV LRDGAGKYFL 

       130        140        150        160        170        180 
WVVKFNSLNE LVDYHRSTSV SRNQQIFLRD IEQVPQQPTY VQALFDFDPQ EDGELGFRRG 

       190        200        210 
DFIHVMDNSD PNWWKGACHG QTGMFPRNYV TPVNRNV 

« Hide

Isoform GRB3-3 [UniParc] [UniParc].

Checksum: 70622BED0FE940DE
Show »

FASTA17620,557

References

« Hide 'large scale' references
[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: 1322798] [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: 1384039] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Fetal lung.
[3]"Cloning of a Grb2 isoform with apoptotic properties."
Fath I., Schweighoffer F., Rey I., Multon M.-C., Boiziau J., Duchesne M., Tocque B.
Science 264:971-974(1994) [PubMed: 8178156] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM GRB3-3), 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: 10051406] [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]"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: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Lymph.
[8]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, MASS SPECTROMETRY.
Tissue: Brain, Cajal-Retzius cell and Fetal brain cortex.
[9]"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: 8388384] [Abstract]
Cited for: INTERACTION WITH IRS1.
[10]"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: 8491186] [Abstract]
Cited for: INTERACTION WITH IRS1 AND SHC.
[11]"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: 7664271] [Abstract]
Cited for: IDENTIFICATION IN A COMPLEX WITH MUC1 AND SOS1, INTERACTION WITH MUC1 AND SOS1.
[12]"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: 8723348] [Abstract]
Cited for: INTERACTION WITH INPP5D.
[13]"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: 9108392] [Abstract]
Cited for: INTERACTION WITH INPP5D.
[14]"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: 9062191] [Abstract]
Cited for: INTERACTION WITH PTPNS1.
[15]"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: 9233773] [Abstract]
Cited for: INTERACTION WITH SH2B2.
[16]"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: 9489702] [Abstract]
Cited for: INTERACTION WITH LAT.
[17]"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: 9422736] [Abstract]
Cited for: INTERACTION WITH REPS2.
[18]"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: 9553137] [Abstract]
Cited for: INTERACTION WITH IRS4.
[19]"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: 9484780] [Abstract]
Cited for: INTERACTION WITH SHB, MUTAGENESIS OF PRO-49 AND PRO-206.
[20]"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: 10022120] [Abstract]
Cited for: INTERACTION WITH CBLB.
[21]"cbl-b inhibits epidermal growth factor receptor signaling."
Ettenberg S.A., Keane M.M., Nau M.M., Frankel M., Wang L.-M., Pierce J.H., Lipkowitz S.
Oncogene 18:1855-1866(1999) [PubMed: 10086340] [Abstract]
Cited for: INTERACTION WITH CBL AND CBLB.
[22]"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: 10318918] [Abstract]
Cited for: INTERACTION WITH HCV NS5A.
[23]"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: 10747847] [Abstract]
Cited for: INTERACTION WITH RALGPS1.
[24]"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: 10942756] [Abstract]
Cited for: INTERACTION WITH SKAP2.
[25]"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: 11433379] [Abstract]
Cited for: INTERACTION WITH SIT1.
[26]"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: 11518702] [Abstract]
Cited for: INTERACTION WITH HEV ORF3 PROTEIN.
[27]"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: 11533253] [Abstract]
Cited for: IDENTIFICATION IN A COMPLEX WITH PIK3C2B AND EGFR, INTERACTION WITH PIK3C2B.
[28]"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: 11912194] [Abstract]
Cited for: INTERACTION WITH NISCH.
[29]"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: 12171928] [Abstract]
Cited for: INTERACTION WITH SKAP1.
[30]"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: 12359715] [Abstract]
Cited for: INTERACTION WITH LAX1.
[31]"Non-T cell activation linker (NTAL): a transmembrane adaptor protein involved in immunoreceptor signaling."
Brdicka T., Imrich M., Angelisova P., Brdickova N., Horvath O., Spicka J., Hilgert I., Luskova P., Draber P., Novak P., Engels N., Wienands J., Simeoni L., Oesterreicher J., Aguado E., Malissen M., Schraven B., Horejsi V.
J. Exp. Med. 196:1617-1626(2002) [PubMed: 12486104] [Abstract]
Cited for: INTERACTION WITH LAT2.
[32]"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: 12514734] [Abstract]
Cited for: INTERACTION WITH LAT2.
[33]"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: 16582911] [Abstract]
Cited for: INTERACTION WITH HCST.
[34]"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: 17081983] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-160 AND TYR-209, MASS SPECTROMETRY.
Tissue: Epithelium.
[35]"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: 18559951] [Abstract]
Cited for: INTERACTION WITH GAPT.
[36]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-211, MASS SPECTROMETRY.
[37]Colinge J., Superti-Furga G., Bennett K.L.
Submitted (OCT-2008) to UniProtKB
Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[38]"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed: 19608861] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-6; LYS-50 AND LYS-109, MASS SPECTROMETRY.
[39]"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: 8794768] [Abstract]
Cited for: STRUCTURE BY NMR OF 58-164.
[40]"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.
[41]"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: 7881903] [Abstract]
Cited for: STRUCTURE BY NMR OF 157-215.
[42]"Crystal structure of the mammalian Grb2 adaptor."
Maignan S., Guilloteau J.-P., Fromage N., Arnoux B., Becquart J., Ducruix A.
Science 268:291-293(1995) [PubMed: 7716522] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS).
[43]"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: 9642078] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 56-153.
[44]"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: 10090780] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 47-163.
[45]"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: 10395476] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 57-152.
[46]"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: 11063574] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 52-160 IN COMPLEX WITH MET.
[47]"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: 11827484] [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.
+Additional computationally mapped references.

Cross-references

Sequence databases

M96995 mRNA. Translation: AAA58448.1.
X62852 mRNA. Translation: CAA44664.1.
L29511 mRNA. Translation: AAC37549.1.
AF063618 expand/collapse EMBL AC list , AF063614, AF063615, AF063616, AF063617 Genomic DNA. Translation: AAC72075.1.
AF498925 mRNA. Translation: AAM21073.1.
CR541942 mRNA. Translation: CAG46740.1.
BC000631 mRNA. Translation: AAH00631.1.
IPIIPI00021327.
IPI00218070.
PIRA43321.
RefSeqNP_002077.1.
NP_987102.1.
UniGeneHs.444356
Hs.708119

3D structure databases

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[»]
DisProtDP00210.
ModBaseSearch...

Protein-protein interaction databases

IntActP62993. 486 interactions.
STRINGP62993.

PTM databases

PhosphoSiteP62993.

2-D gel databases

SWISS-2DPAGEP62993.
OGPP62993.

Proteomic databases

PRIDEP62993.

Genome annotation databases

EnsemblENST00000316615; ENSP00000317360; ENSG00000177885; Homo sapiens. [Genome view]
ENST00000316804; ENSP00000339007; ENSG00000177885; Homo sapiens. [Genome view]
ENST00000392562; ENSP00000376345; ENSG00000177885; Homo sapiens. [Genome view]
ENST00000392563; ENSP00000376346; ENSG00000177885; Homo sapiens. [Genome view]
ENST00000392564; ENSP00000376347; ENSG00000177885; Homo sapiens. [Genome view]
GeneID2885.
KEGGhsa:2885.
UCSCuc002jnx.2. human.
uc002jny.2. human.

Organism-specific databases

CTD2885.
GeneCardsGC17M070825.
H-InvDBHIX0014172.
HGNCHGNC:4566. GRB2.
HPACAB002589.
MIM108355. gene.
PharmGKBPA28962.
GenAtlasSearch...

Phylogenomic databases

HOGENOMP62993.
HOVERGENP62993.
OMAAFLIRIS.

Enzyme and pathway databases

Pathway_Interaction_DBa6b1_a6b4_integrin_pathway. a6b1 and a6b4 Integrin signaling.
angiopoietinreceptor_pathway. Angiopoietin receptor Tie2-mediated signaling.
bcr_5pathway. BCR signaling pathway.
endothelinpathway. Endothelins.
epha2_fwdpathway. EPHA2 forward signaling.
ephbfwdpathway. EPHB forward signaling.
epopathway. EPO signaling pathway.
fcer1pathway. Fc-epsilon receptor I signaling in mast cells.
fgf_pathway. FGF signaling pathway.
igf1_pathway. IGF1 pathway.
il2_pi3kpathway. IL2 signaling events mediated by PI3K.
il2_stat5pathway. IL2 signaling events mediated by STAT5.
il2_1pathway. IL2-mediated signaling events.
il4_2pathway. IL4-mediated signaling events.
il6_7pathway. IL6-mediated signaling events.
insulin_pathway. Insulin Pathway.
trkrpathway. Neurotrophic factor-mediated Trk receptor signaling.
pdgfrapathway. PDGFR-alpha signaling pathway.
pdgfrbpathway. PDGFR-beta signaling pathway.
er_nongenomic_pathway. Plasma membrane estrogen receptor signaling.
met_pathway. Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met).
ptp1bpathway. Signaling events mediated by PTP1B.
kitpathway. Signaling events mediated by Stem cell factor receptor (c-Kit).
vegfr1_2_pathway. Signaling events mediated by VEGFR1 and VEGFR2.
ret_pathway. Signaling events regulated by Ret tyrosine kinase.
tcrpathway. TCR signaling in naive CD4+ T cells.
cd8tcrpathway. TCR signaling in naive CD8+ T cells.
tgfbrpathway. TGF-beta receptor signaling.
pi3kplctrkpathway. Trk receptor signaling mediated by PI3K and PLC-gamma.
lymphangiogenesis_pathway. VEGFR3 signaling in lymphatic endothelium.
ReactomeREACT_11061. Signalling by NGF.
REACT_13552. Integrin cell surface interactions.
REACT_16888. Signaling by PDGF.
REACT_18266. Axon guidance.
REACT_498. Signaling by Insulin receptor.
REACT_508. Signal attenuation.
REACT_604. Hemostasis.
REACT_6900. Signaling in Immune system.
REACT_9417. Signaling by EGFR.

Gene expression databases

ArrayExpressP62993.
BgeeP62993.
CleanExHS_GRB2.
GenevestigatorP62993.
GermOnlineENSG00000177885. Homo sapiens.

Family and domain databases

InterProIPR000108. Neu_cyt_fact_2.
IPR000980. SH2.
IPR001452. SH3_domain.
IPR020473. SH3_region.
[Graphical view]
Gene3DG3DSA:3.30.505.10. SH2. 1 hit.
PfamPF00017. SH2. 1 hit.
PF00018. SH3_1. 2 hits.
[Graphical view]
PRINTSPR00499. P67PHOX.
PR00401. SH2DOMAIN.
PR00452. SH3DOMAIN.
ProDomPD000093. SH2. 1 hit.
PD000066. SH3. 2 hits.
[Graphical view] [Entries sharing at least one domain]
SMARTSM00252. SH2. 1 hit.
SM00326. SH3. 2 hits.
[Graphical view]
PROSITEPS50001. SH2. 1 hit.
PS50002. SH3. 2 hits.
[Graphical view]
ProtoNetSearch...

Other Resources

BindingDBP62993.
DrugBankDB00061. Pegademase bovine.
NextBio11389.
SOURCESearch...

Entry information

Entry nameGRB2_HUMAN
AccessionPrimary (citable) accession number: P62993
Secondary accession number(s): P29354 expand/collapse secondary AC list , Q14450, Q63057, Q63059
Entry history
Integrated into UniProtKB/Swiss-Prot: August 31, 2004
Last sequence update: August 31, 2004
Last modified: November 3, 2009
This is version 85 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)
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.

Relevant documents

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents