CPLM-009644

Genbank Nucleotide ID

Growth factor receptor-bound protein 2

Protein Synonyms/Alias

Adapter protein GRB2; Protein Ash; SH2/SH3 adapter GRB2

Homo sapiens (Human)

Position	Peptide	Type	References
6	**MEAIAKYDFKATA	acetylation	[1]
10	AIAKYDFKATADDEL	ubiquitination	[2]
20	ADDELSFKRGDILKV	ubiquitination	[3]
38	ECDQNWYKAELNGKD	acetylation	[1]
44	YKAELNGKDGFIPKN	ubiquitination	[3, 4]
50	GKDGFIPKNYIEMKP	acetylation	[1]
56	PKNYIEMKPHPWFFG	ubiquitination	[3]
69	FGKIPRAKAEEMLSK	ubiquitination	[2, 4]
76	KAEEMLSKQRHDGAF	ubiquitination	[2, 4, 5]
109	GNDVQHFKVLRDGAG	acetylation	[1, 6]
109	GNDVQHFKVLRDGAG	ubiquitination	[2, 3, 4, 5, 6, 7, 8]

[1] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
[2] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
[3] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
[4] Systematic and quantitative assessment of the ubiquitin-modified proteome.
Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
[5] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
[6] Integrated proteomic analysis of post-translational modifications by serial enrichment.
Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
[7] Mass spectrometric analysis of lysine ubiquitylation reveals promiscuity at site level.
Danielsen JM, Sylvestersen KB, Bekker-Jensen S, Szklarczyk D, Poulsen JW, Horn H, Jensen LJ, Mailand N, Nielsen ML.
Mol Cell Proteomics. 2011 Mar;10(3):M110.003590. [PMID: 21139048]
[8] Global identification of modular cullin-RING ligase substrates.
Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]

Functional Description

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

DOMAIN 1 58 SH3 1.
DOMAIN 60 152 SH2.
DOMAIN 156 215 SH3 2.
MOD_RES 1 1 N-acetylmethionine.
MOD_RES 6 6 N6-acetyllysine.
MOD_RES 50 50 N6-acetyllysine.
MOD_RES 109 109 N6-acetyllysine.
MOD_RES 211 211 Phosphothreonine.

3D-structure; Acetylation; Alternative splicing; Complete proteome; Cytoplasm; Direct protein sequencing; Endosome; Golgi apparatus; Host-virus interaction; Nucleus; Phosphoprotein; Reference proteome; Repeat; SH2 domain; SH3 domain.

UniProt (SWISSPROT/TrEMBL); GenBank; EMBL

GO:0005829; C:cytosol; TAS:HGNC.
GO:0005768; C:endosome; IDA:UniProtKB.
GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
GO:0070436; C:Grb2-EGFR complex; IDA:BHF-UCL.
GO:0008180; C:signalosome; IDA:UniProtKB.
GO:0012506; C:vesicle membrane; IEA:Compara.
GO:0017124; F:SH3 domain binding; IDA:UniProtKB.
GO:0005070; F:SH3/SH2 adaptor activity; TAS:UniProtKB.
GO:0007568; P:aging; IEA:Compara.
GO:0048646; P:anatomical structure formation involved in morphogenesis; IEA:Compara.
GO:0007411; P:axon guidance; TAS:Reactome.
GO:0060670; P:branching involved in labyrinthine layer morphogenesis; IEA:Compara.
GO:0007267; P:cell-cell signaling; TAS:UniProtKB.
GO:0071479; P:cellular response to ionizing radiation; IMP:BHF-UCL.
GO:0007173; P:epidermal growth factor receptor signaling pathway; TAS:UniProtKB.
GO:0038096; P:Fc-gamma receptor signaling pathway involved in phagocytosis; TAS:Reactome.
GO:0008543; P:fibroblast growth factor receptor signaling pathway; TAS:Reactome.
GO:0045087; P:innate immune response; TAS:Reactome.
GO:0008286; P:insulin receptor signaling pathway; IPI:UniProtKB.
GO:0050900; P:leukocyte migration; TAS:Reactome.
GO:0042059; P:negative regulation of epidermal growth factor receptor signaling pathway; TAS:Reactome.
GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome.
GO:0048015; P:phosphatidylinositol-mediated signaling; TAS:Reactome.
GO:0030168; P:platelet activation; TAS:Reactome.
GO:0030838; P:positive regulation of actin filament polymerization; IEA:Compara.
GO:2000379; P:positive regulation of reactive oxygen species metabolic process; IMP:BHF-UCL.
GO:0051291; P:protein heterooligomerization; IEA:Compara.
GO:0007265; P:Ras protein signal transduction; TAS:UniProtKB.
GO:0031623; P:receptor internalization; IMP:BHF-UCL.
GO:0043408; P:regulation of MAPK cascade; IEA:Compara.
GO:0042770; P:signal transduction in response to DNA damage; IMP:BHF-UCL.
GO:0031295; P:T cell costimulation; TAS:Reactome.
GO:0019048; P:virus-host interaction; IEA:UniProtKB-KW.

IPR000108; p67phox.
IPR000980; SH2.
IPR001452; SH3_domain.

PF00017; SH2
PF00018; SH3_1

SM00252; SH2
SM00326; SH3

PS50001; SH2
PS50002; SH3

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