CPLM-011516

Genbank Nucleotide ID

KH domain-containing, RNA-binding, signal transduction-associated protein 1

Protein Synonyms/Alias

GAP-associated tyrosine phosphoprotein p62; Src-associated in mitosis 68 kDa protein; Sam68; p21 Ras GTPase-activating protein-associated p62; p68

Homo sapiens (Human)

Position	Peptide	Type	References
96	PSATASVKMEPENKY	acetylation	[1]
96	PSATASVKMEPENKY	sumoylation	[2]
102	VKMEPENKYLPELMA	sumoylation	[3]
138	KIQKGDSKKDDEENY	ubiquitination	[4, 5]
152	YLDLFSHKNMKLKER	ubiquitination	[5, 6]
155	LFSHKNMKLKERVLI	ubiquitination	[7, 8]
165	ERVLIPVKQYPKFNF	acetylation	[1]
165	ERVLIPVKQYPKFNF	ubiquitination	[5, 6, 7, 8, 9, 10, 11]
169	IPVKQYPKFNFVGKI	acetylation	[8, 12, 13]
169	IPVKQYPKFNFVGKI	ubiquitination	[5, 6, 7, 8, 10, 11]
175	PKFNFVGKILGPQGN	acetylation	[1, 8, 12, 13]
175	PKFNFVGKILGPQGN	ubiquitination	[5, 6, 7, 8, 11]
185	GPQGNTIKRLQEETG	ubiquitination	[5, 6, 7, 8, 11]
194	LQEETGAKISVLGKG	methylation	[14]
194	LQEETGAKISVLGKG	ubiquitination	[7]
200	AKISVLGKGSMRDKA	methylation	[14]
200	AKISVLGKGSMRDKA	ubiquitination	[7, 8]
206	GKGSMRDKAKEEELR	ubiquitination	[7]
432	APPARPVKGAYREHP	ubiquitination	[5, 6, 7, 8, 11]

[1] Proteomic investigations of lysine acetylation identify diverse substrates of mitochondrial deacetylase sirt3.
Sol EM, Wagner SA, Weinert BT, Kumar A, Kim HS, Deng CX, Choudhary C.
PLoS One. 2012;7(12):e50545. [PMID: 23236377]
[2] SUMO modification of Sam68 enhances its ability to repress cyclin D1 expression and inhibits its ability to induce apoptosis.
Babic I, Cherry E, Fujita DJ.
Oncogene. 2006 Aug 17;25(36):4955-64. [PMID: 16568089]
[3] Site-specific identification of SUMO-2 targets in cells reveals an inverted SUMOylation motif and a hydrophobic cluster SUMOylation motif.
Matic I, Schimmel J, Hendriks IA, van Santen MA, van de Rijke F, van Dam H, Gnad F, Mann M, Vertegaal AC.
Mol Cell. 2010 Aug 27;39(4):641-52. [PMID: 20797634]
[4] 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]
[5] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
Chen Z, Zhou Y, Song J, Zhang Z.
Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
[6] 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]
[7] 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]
[8] 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]
[9] 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]
[10] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
[11] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
[12] 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]
[13] Proteomic investigations reveal a role for RNA processing factor THRAP3 in the DNA damage response.
Beli P, Lukashchuk N, Wagner SA, Weinert BT, Olsen JV, Baskcomb L, Mann M, Jackson SP, Choudhary C.
Mol Cell. 2012 Apr 27;46(2):212-25. [PMID: 22424773]
[14] Large-scale global identification of protein lysine methylation in vivo.
Cao XJ, Arnaudo AM, Garcia BA.
Epigenetics. 2013 May 1;8(5):477-85. [PMID: 23644510]

Functional Description

Recruited and tyrosine phosphorylated by several receptor systems, for example the T-cell, leptin and insulin receptors. Once phosphorylated, functions as an adapter protein in signal transduction cascades by binding to SH2 and SH3 domain- containing proteins. Role in G2-M progression in the cell cycle. Represses CBP-dependent transcriptional activation apparently by competing with other nuclear factors for binding to CBP. Also acts as a putative regulator of mRNA stability and/or translation rates and mediates mRNA nuclear export. Positively regulates the association of constitutive transport element (CTE)-containing mRNA with large polyribosomes and translation initiation. According to some authors, is not involved in the nucleocytoplasmic export of unspliced (CTE)-containing RNA species according to (PubMed:22253824).

DOMAIN 171 197 KH.
MOD_RES 20 20 Phosphoserine.
MOD_RES 29 29 Phosphoserine.
MOD_RES 45 45 Asymmetric dimethylarginine; by PRMT1.
MOD_RES 52 52 Asymmetric dimethylarginine; partial; by
MOD_RES 58 58 Phosphoserine.
MOD_RES 113 113 Phosphoserine (By similarity).
MOD_RES 175 175 N6-acetyllysine.
MOD_RES 291 291 Omega-N-methylated arginine; by PRMT1.
MOD_RES 304 304 Asymmetric dimethylarginine; by PRMT1.
MOD_RES 310 310 Omega-N-methylarginine; by PRMT1.
MOD_RES 315 315 Omega-N-methylarginine; by PRMT1.
MOD_RES 320 320 Dimethylated arginine; in A2780 ovarian
MOD_RES 320 320 Omega-N-methylarginine; by PRMT1.
MOD_RES 325 325 Omega-N-methylarginine; by PRMT1.
MOD_RES 331 331 Dimethylated arginine; in A2780 ovarian
MOD_RES 331 331 Omega-N-methylated arginine; by PRMT1.
MOD_RES 340 340 Omega-N-methylarginine; by PRMT1.
MOD_RES 346 346 Omega-N-methylated arginine; by PRMT1.
MOD_RES 435 435 Phosphotyrosine; by PTK6.
MOD_RES 440 440 Phosphotyrosine; by PTK6.
MOD_RES 443 443 Phosphotyrosine; by PTK6.

3D-structure; Acetylation; Alternative splicing; Cell cycle; Complete proteome; Direct protein sequencing; Membrane; Methylation; Nucleus; Phosphoprotein; Reference proteome; RNA-binding; SH3-binding; Transcription; Transcription regulation.

UniProt (SWISSPROT/TrEMBL); GenBank; EMBL

GO:0005737; C:cytoplasm; IEA:Compara.
GO:0070618; C:Grb2-Sos complex; IEA:Compara.
GO:0016020; C:membrane; IDA:UniProtKB.
GO:0005634; C:nucleus; IDA:UniProtKB.
GO:0003677; F:DNA binding; TAS:ProtInc.
GO:0003723; F:RNA binding; IDA:UniProtKB.
GO:0007050; P:cell cycle arrest; TAS:ProtInc.
GO:0008283; P:cell proliferation; TAS:ProtInc.
GO:0007166; P:cell surface receptor signaling pathway; IDA:UniProtKB.
GO:0000086; P:G2/M transition of mitotic cell cycle; ISS:UniProtKB.
GO:0006397; P:mRNA processing; TAS:ProtInc.
GO:0045892; P:negative regulation of transcription, DNA-dependent; ISS:UniProtKB.
GO:0046833; P:positive regulation of RNA export from nucleus; IDA:UniProtKB.
GO:0045948; P:positive regulation of translational initiation; IDA:UniProtKB.
GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.

IPR004087; KH_dom.
IPR004088; KH_dom_type_1.