P62993 (GRB2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Growth factor receptor-bound protein 2

Alternative name(s):
Adapter protein GRB2
Protein Ash
SH2/SH3 adapter GRB2

Gene names

Name:	GRB2
Synonyms:	ASH

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	217 AA.
Sequence status	Complete.
Protein existence	Evidence 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 Ref.54 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. Ref.1 Ref.3 Ref.54
Subunit structure	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. Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ref.22 Ref.23 Ref.24 Ref.25 Ref.26 Ref.27 Ref.28 Ref.29 Ref.30 Ref.31 Ref.32 Ref.33 Ref.34 Ref.35 Ref.36 Ref.37 Ref.38 Ref.39 Ref.40 Ref.41 Ref.42 Ref.43 Ref.44 Ref.46 Ref.49 Ref.50 Ref.51 Ref.53 Ref.54 Ref.55 Ref.56 Ref.59 Ref.60 Ref.62 Ref.63
Subcellular location	Nucleus. Cytoplasm. Endosome. Golgi apparatus By similarity Ref.60.
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.

Ontologies

Keywords
Biological process	Host-virus interaction
Cellular component	Cytoplasm Endosome Golgi apparatus Nucleus
Coding sequence diversity	Alternative splicing
Domain	Repeat SH2 domain SH3 domain
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	Ras protein signal transduction Traceable author statement PubMed 8253073. Source: UniProtKB T cell costimulation Traceable author statement. Source: Reactome aging Inferred from electronic annotation. Source: Compara anatomical structure formation involved in morphogenesis Inferred from electronic annotation. Source: Compara axon guidance Traceable author statement. Source: Reactome branching involved in labyrinthine layer morphogenesis Inferred from electronic annotation. Source: Compara cell-cell signaling Traceable author statement PubMed 8253073. Source: UniProtKB cellular response to ionizing radiation Inferred from mutant phenotype PubMed 20160708. Source: BHF-UCL epidermal growth factor receptor signaling pathway Traceable author statement Ref.1. Source: UniProtKB fibroblast growth factor receptor signaling pathway Traceable author statement. Source: Reactome insulin receptor signaling pathway Inferred from physical interaction Ref.11. Source: UniProtKB leukocyte migration Traceable author statement. Source: Reactome negative regulation of epidermal growth factor receptor signaling pathway Traceable author statement. Source: Reactome nerve growth factor receptor signaling pathway Traceable author statement. Source: Reactome platelet activation Traceable author statement. Source: Reactome positive regulation of actin filament polymerization Inferred from electronic annotation. Source: Compara positive regulation of reactive oxygen species metabolic process Inferred from mutant phenotype PubMed 20160708. Source: BHF-UCL protein heterooligomerization Inferred from electronic annotation. Source: Compara receptor internalization Inferred from mutant phenotype PubMed 14985334. Source: BHF-UCL regulation of MAPK cascade Inferred from electronic annotation. Source: Compara signal transduction in response to DNA damage Inferred from mutant phenotype PubMed 20160708. Source: BHF-UCL virus-host interaction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	Golgi apparatus Inferred from electronic annotation. Source: UniProtKB-SubCell Grb2-EGFR complex Inferred from direct assay PubMed 20086093. Source: BHF-UCL cytosol Traceable author statement PubMed 14722116. Source: HGNC endosome Inferred from direct assay Ref.60. Source: UniProtKB signalosome Inferred from direct assay Ref.63. Source: UniProtKB vesicle membrane Inferred from electronic annotation. Source: Compara
Molecular_function	SH3 domain binding Inferred from direct assay Ref.56. Source: UniProtKB SH3/SH2 adaptor activity Traceable author statement PubMed 8253073. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		4	EBI-401755,EBI-401755
	O92972	2	EBI-401755,EBI-710506	From a different organism.
	P27958	3	EBI-401755,EBI-706378	From a different organism.
ABL2	P42684	2	EBI-401755,EBI-1102694
AGER	Q15109	2	EBI-401755,EBI-1646426
ANK2	Q01484	2	EBI-401755,EBI-941975
ASAP1	Q9ULH1	7	EBI-401755,EBI-346622
ASAP2	O43150	3	EBI-401755,EBI-310968
BRD4	O60885	2	EBI-401755,EBI-723869
CBL	P22681	4	EBI-401755,EBI-518228
CBLB	Q13191	4	EBI-401755,EBI-744027
CD2AP	Q9Y5K6	3	EBI-401755,EBI-298152
COBRA1	Q8WX92	2	EBI-401755,EBI-347721
DAB2	P98082	2	EBI-401755,EBI-1171238
Dab2	P98078	4	EBI-401755,EBI-1391846	From a different organism.
DARS	P14868	2	EBI-401755,EBI-358730
DLGAP1	O14490	3	EBI-401755,EBI-1753207
DLGAP2	Q9P1A6	2	EBI-401755,EBI-1753397
DLGAP4	Q9Y2H0	2	EBI-401755,EBI-722139
DNM1	Q05193	3	EBI-401755,EBI-713135
DNM2	P50570	3	EBI-401755,EBI-346547
DOCK1	Q14185	2	EBI-401755,EBI-446740
EGFR	P00533	12	EBI-401755,EBI-297353
EPHB1	P54762	2	EBI-401755,EBI-80252
ERRFI1	Q9UJM3	4	EBI-401755,EBI-2941912
FANCA	O15360	2	EBI-401755,EBI-81570
FGFR2	P21802	5	EBI-401755,EBI-1028658
FLNA	P21333	2	EBI-401755,EBI-350432
FLNB	O75369	2	EBI-401755,EBI-352089
FLNC	Q14315	2	EBI-401755,EBI-489954
GAB2	Q9UQC2	4	EBI-401755,EBI-975200
GAREM	Q9H706	3	EBI-401755,EBI-3440103
KHDRBS1	Q07666	8	EBI-401755,EBI-1364
KIT	P10721	2	EBI-401755,EBI-1379503
KRT8	P05787	3	EBI-401755,EBI-297852
LEPR	P48357	3	EBI-401755,EBI-518596
MAP2K5	Q13163	2	EBI-401755,EBI-307294
MAP4K1	Q92918	2	EBI-401755,EBI-881
MAP4K3	Q8IVH8	2	EBI-401755,EBI-1758170
MAP4K5	Q9Y4K4	4	EBI-401755,EBI-1279
MED28	Q9H204	3	EBI-401755,EBI-514199
PIK3C2B	O00750	2	EBI-401755,EBI-641107
PIK3R1	P27986	3	EBI-401755,EBI-79464
PIK3R2	O00459	4	EBI-401755,EBI-346930
PLD2	O14939	4	EBI-401755,EBI-1053996
PPP3CA	Q08209	2	EBI-401755,EBI-352922
PRKAB1	Q9Y478	2	EBI-401755,EBI-719769
PTPN11	Q06124	6	EBI-401755,EBI-297779
PTPN23	Q9H3S7	6	EBI-401755,EBI-724478
SF3B4	Q15427	2	EBI-401755,EBI-348469
SHANK2	Q9UPX8	2	EBI-401755,EBI-1570571
SHANK3	Q9BYB0	2	EBI-401755,EBI-1752330
SHC1	P29353	8	EBI-401755,EBI-78835
SOS1	Q07889	9	EBI-401755,EBI-297487
Sos1	Q62245	2	EBI-401755,EBI-1693	From a different organism.
SOS2	Q07890	6	EBI-401755,EBI-298181
STAMBP	O95630	3	EBI-401755,EBI-396676
SYNJ2	O15056	2	EBI-401755,EBI-310513
TNPO1	Q92973	2	EBI-401755,EBI-286693
TPX2	Q9ULW0	2	EBI-401755,EBI-1037322
UGP2	Q16851	2	EBI-401755,EBI-743729
VAV1	P15498	2	EBI-401755,EBI-625518
VAV3	Q9UKW4	5	EBI-401755,EBI-297568
WASL	O00401	3	EBI-401755,EBI-957615
WIPF1	O43516	3	EBI-401755,EBI-346356
WIPF2	Q8TF74	3	EBI-401755,EBI-2850112

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 2 (identifier: P62993-2)

Also known as: GRB3-3;

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

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 217

217

Growth factor receptor-bound protein 2

PRO_0000088198

Regions

Domain

1 – 58

58

SH3 1

Domain

60 – 152

93

SH2

Domain

156 – 215

60

SH3 2

Amino acid modifications

Modified residue

1

1

N-acetylmethionine Ref.58

Modified residue

6

1

N6-acetyllysine Ref.58

Modified residue

50

1

N6-acetyllysine Ref.58

Modified residue

109

1

N6-acetyllysine Ref.58

Modified residue

211

1

Phosphothreonine Ref.52

Natural variations

Alternative sequence

60 – 100

41

Missing in isoform 2.

VSP_001839

Experimental info

Mutagenesis

49

1

P → L: Ineffective in DNA synthesis. Abolishes interaction with SHB; when associated with L-206. Ref.1 Ref.24

Mutagenesis

203

1

G → R: Ineffective in DNA synthesis. Ref.1

Mutagenesis

206

1

P → L: Abolishes interaction with SHB; when associated with L-49. Ref.24

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

217

Helix Strand Turn

Details...

Beta strand

2 – 5

4

Beta strand

13 – 15

3

Beta strand

24 – 26

3

Beta strand

36 – 43

8

Beta strand

45 – 49

5

Helix

50 – 52

3

Beta strand

61 – 64

4

Helix

67 – 75

9

Beta strand

78 – 80

3

Beta strand

82 – 87

6

Beta strand

89 – 91

3

Beta strand

95 – 101

7

Beta strand

104 – 109

6

Beta strand

114 – 116

3

Beta strand

118 – 122

5

Beta strand

124 – 127

4

Helix

128 – 134

7

Turn

135 – 137

3

Beta strand

142 – 144

3

Beta strand

149 – 152

4

Beta strand

155 – 157

3

Beta strand

160 – 165

6

Beta strand

171 – 174

4

Beta strand

182 – 187

6

Beta strand

190 – 198

9

Beta strand

201 – 206

6

Helix

207 – 209

3

Beta strand

210 – 212

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Ash-L) [UniParc]. Last modified August 31, 2004. Version 1. Checksum: 83A4B0BA1B248DC4	FASTA	217	25,206
	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
	Isoform 2 (GRB3-3) [UniParc] [UniParc]. Checksum: 70622BED0FE940DE	FASTA	176	20,557
	10 20 30 40 50 60 MEAIAKYDFK ATADDELSFK RGDILKVLNE ECDQNWYKAE LNGKDGFIPK NYIEMKPHPF 70 80 90 100 110 120 GNDVQHFKVL RDGAGKYFLW VVKFNSLNEL VDYHRSTSVS RNQQIFLRDI EQVPQQPTYV 130 140 150 160 170 QALFDFDPQE DGELGFRRGD FIHVMDNSDP NWWKGACHGQ TGMFPRNYVT PVNRNV

References

	« Hide 'large scale' referencesShow '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] [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]	"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] [Europe PMC] [Abstract] 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, 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]	"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] [Europe PMC] [Abstract] 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]	"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] [Europe PMC] [Abstract] 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]	"TrkA alternative splicing: a regulated tumor-promoting switch in human neuroblastoma." Tacconelli A., Farina A.R., Cappabianca L., Desantis G., Tessitore A., Vetuschi A., Sferra R., Rucci N., Argenti B., Screpanti I., Gulino A., Mackay A.R. Cancer Cell 6:347-360(2004) [PubMed] [Europe PMC] [Abstract] 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]	"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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-211, MASS SPECTROMETRY. 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, MASS SPECTROMETRY.
[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]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[62]	"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.
[63]	"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.
[64]	"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.
[65]	"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.
[66]	"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.
[67]	"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] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS).
[68]	"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.
[69]	"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.
[70]	"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.
[71]	"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.
[72]	"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.
[73]	"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.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.

IPI

IPI00021327.
IPI00218070.

PIR

A43321.

RefSeq

NP_002077.1. NM_002086.4.
NP_987102.1. NM_203506.2.

UniGene

Hs.444356.
Hs.708119.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1AZE	NMR	-	A	1-56	[»]
1BM2	X-ray	2.10	A	49-163	[»]
1BMB	X-ray	1.80	A	49-168	[»]
1CJ1	X-ray	3.00	A/B/C/D/E/F/G/H/I/J/K/L	57-152	[»]
1FHS	NMR	-	A	53-163	[»]
1FYR	X-ray	2.40	A/B/C/D	50-161	[»]
1GCQ	X-ray	1.68	A/B	159-217	[»]
1GFC	NMR	-	A	159-215	[»]
1GFD	NMR	-	A	159-215	[»]
1GHU	NMR	-	A	60-158	[»]
1GRI	X-ray	3.10	A/B	1-217	[»]
1IO6	NMR	-	A	159-215	[»]
1JYQ	X-ray	2.00	A/B	60-151	[»]
1JYR	X-ray	1.55	A	60-151	[»]
1JYU	X-ray	2.75	A	60-151	[»]
1QG1	NMR	-	E	58-159	[»]
1TZE	X-ray	2.10	E	55-152	[»]
1X0N	NMR	-	A	58-159	[»]
1ZFP	X-ray	1.80	E	56-153	[»]
2AOA	X-ray	1.99	A/B	55-153	[»]
2AOB	X-ray	1.80	A/B/C/D	55-153	[»]
2H46	X-ray	1.90	E	53-162	[»]
2H5K	X-ray	3.25	A/B	53-162	[»]
2HUW	X-ray	1.90	A/B	53-162	[»]
2VVK	X-ray	1.60	A	161-214	[»]
2VWF	X-ray	1.58	A	159-214	[»]
2W0Z	X-ray	1.70	A	159-214	[»]
3C7I	X-ray	1.70	A	53-162	[»]
3IMD	X-ray	2.00	A/B	53-163	[»]
3IMJ	X-ray	2.02	A/B	53-163	[»]
3IN7	X-ray	2.00	A/C	53-163	[»]
3IN8	X-ray	1.70	A	53-163	[»]
3KFJ	X-ray	2.02	A	53-163	[»]
3MXC	X-ray	2.00	A	55-152	[»]
3MXY	X-ray	2.30	A	55-152	[»]
3N7Y	X-ray	2.02	A/B/C	55-152	[»]
3N84	X-ray	2.00	A/B/C/D/E/F	53-163	[»]
3N8M	X-ray	2.00	A	53-163	[»]
3OV1	X-ray	1.60	A	53-163	[»]
3OVE	X-ray	1.82	A	53-163	[»]
3S8L	X-ray	1.71	A	53-163	[»]
3S8N	X-ray	1.71	A	53-163	[»]
3S8O	X-ray	1.85	A	53-163	[»]

DisProt

DP00210.

ProteinModelPortal

P62993.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29229N.

IntAct

P62993. 653 interactions.

MINT

MINT-91952.

STRING

9606.ENSP00000339007.

PTM databases

PhosphoSite

P62993.

Polymorphism databases

DMDM

51702266.

2D gel databases

OGP

P62993.

SWISS-2DPAGE

P62993.

Proteomic databases

PaxDb

P62993.

PRIDE

P62993.

Protocols and materials databases

DNASU

2885.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000316615; ENSP00000317360; ENSG00000177885.
ENST00000316804; ENSP00000339007; ENSG00000177885.
ENST00000392562; ENSP00000376345; ENSG00000177885.
ENST00000392563; ENSP00000376346; ENSG00000177885.
ENST00000392564; ENSP00000376347; ENSG00000177885.

GeneID

2885.

KEGG

hsa:2885.

UCSC

uc002jnx.4. human.
uc002jny.4. human.

Organism-specific databases

CTD

2885.

GeneCards

GC17M073313.

HGNC

HGNC:4566. GRB2.

HPA

CAB002589.

MIM

108355. gene.

neXtProt

NX_P62993.

PharmGKB

PA28962.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG298780.

HOGENOM

HOG000251625.

HOVERGEN

HBG005404.

InParanoid

P62993.

KO

K04364.

OMA

VETKFVQ.

OrthoDB

EOG4XSKQS.

PhylomeDB

P62993.

Enzyme and pathway databases

Pathway_Interaction_DB

a6b1_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.

Reactome

REACT_111045. Developmental Biology.
REACT_111102. Signal Transduction.
REACT_111155. Cell-Cell communication.
REACT_116125. Disease.
REACT_604. Hemostasis.
REACT_6900. Immune System.

Gene expression databases

ArrayExpress

P62993.

Bgee

P62993.

CleanEx

HS_GRB2.

Genevestigator

P62993.

GermOnline

ENSG00000177885. Homo sapiens.

Family and domain databases

Gene3D

3.30.505.10. 1 hit.

InterPro

IPR000108. p67phox.
IPR000980. SH2.
IPR001452. SH3_domain.
[Graphical view]

Pfam

PF00017. SH2. 1 hit.
PF00018. SH3_1. 2 hits.
[Graphical view]

PRINTS

PR00499. P67PHOX.
PR00401. SH2DOMAIN.
PR00452. SH3DOMAIN.

SMART

SM00252. SH2. 1 hit.
SM00326. SH3. 2 hits.
[Graphical view]

SUPFAM

SSF50044. SH3. 1 hit.

PROSITE

PS50001. SH2. 1 hit.
PS50002. SH3. 2 hits.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P62993.

ChEMBL

CHEMBL3663.

ChiTaRS

GRB2. human.

DrugBank

DB00061. Pegademase bovine.

EvolutionaryTrace

P62993.

GenomeRNAi

2885.

NextBio

11389.

SOURCE

Search...

Entry information

Entry name

GRB2_HUMAN

Accession

Primary (citable) accession number: P62993
Secondary accession number(s): P29354 , Q14450, Q63057, Q63059

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 31, 2004
Last sequence update:	August 31, 2004
Last modified:	May 1, 2013
This is version 125 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.