CPLM-010825

Genbank Nucleotide ID

Protein Synonyms/Alias

HLA-DR-associated protein II; Inhibitor of granzyme A-activated DNase; IGAAD; PHAPII; Phosphatase 2A inhibitor I2PP2A; I-2PP2A; Template-activating factor I; TAF-I

Homo sapiens (Human)

Position	Peptide	Type	References
7	*MSAPAAKVSKKELN	acetylation	[1, 2]
7	*MSAPAAKVSKKELN	ubiquitination	[2, 3, 4]
10	APAAKVSKKELNSNH	acetylation	[5]
10	APAAKVSKKELNSNH	ubiquitination	[2]
11	PAAKVSKKELNSNHD	acetylation	[1, 2, 6, 7, 8, 9]
55	QASEEILKVEQKYNK	ubiquitination	[10]
59	EILKVEQKYNKLRQP	acetylation	[11]
70	LRQPFFQKRSELIAK	ubiquitination	[4, 10]
119	VTEFEDIKSGYRIDF	ubiquitination	[3, 10]
137	ENPYFENKVLSKEFH	ubiquitination	[3, 4, 10]
141	FENKVLSKEFHLNES	ubiquitination	[4, 10]
154	ESGDPSSKSTEIKWK	ubiquitination	[4, 10]
159	SSKSTEIKWKSGKDL	ubiquitination	[4]

[1] 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]
[2] 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]
[3] 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]
[4] 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]
[5] Substrate and functional diversity of lysine acetylation revealed by a proteomics survey.
Kim SC, Sprung R, Chen Y, Xu Y, Ball H, Pei J, Cheng T, Kho Y, Xiao H, Xiao L, Grishin NV, White M, Yang XJ, Zhao Y.
Mol Cell. 2006 Aug;23(4):607-18. [PMID: 16916647]
[6] 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]
[7] Regulation of cellular metabolism by protein lysine acetylation.
Zhao S, Xu W, Jiang W, Yu W, Lin Y, Zhang T, Yao J, Zhou L, Zeng Y, Li H, Li Y, Shi J, An W, Hancock SM, He F, Qin L, Chin J, Yang P, Chen X, Lei Q, Xiong Y, Guan KL.
Science. 2010 Feb 19;327(5968):1000-4. [PMID: 20167786]
[8] Identification of lysine acetyltransferase p300 substrates using 4-pentynoyl-coenzyme A and bioorthogonal proteomics.
Yang YY, Grammel M, Hang HC.
Bioorg Med Chem Lett. 2011 Sep 1;21(17):4976-9. [PMID: 21669532]
[9] 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]
[10] 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]
[11] Spermidine and resveratrol induce autophagy by distinct pathways converging on the acetylproteome.
Morselli E, Mariño G, Bennetzen MV, Eisenberg T, Megalou E, Schroeder S, Cabrera S, Bénit P, Rustin P, Criollo A, Kepp O, Galluzzi L, Shen S, Malik SA, Maiuri MC, Horio Y, López-Otín C, Andersen JS, Tavernarakis N, Madeo F, Kroemer G.
J Cell Biol. 2011 Feb 21;192(4):615-29. [PMID: 21339330]

Functional Description

Multitasking protein, involved in apoptosis, transcription, nucleosome assembly and histone chaperoning. Isoform 2 anti-apoptotic activity is mediated by inhibition of the GZMA-activated DNase, NME1. In the course of cytotoxic T- lymphocyte (CTL)-induced apoptosis, GZMA cleaves SET, disrupting its binding to NME1 and releasing NME1 inhibition. Isoform 1 and isoform 2 are potent inhibitors of protein phosphatase 2A. Isoform 1 and isoform 2 inhibit EP300/CREBBP and PCAF-mediated acetylation of histones (HAT) and nucleosomes, most probably by masking the accessibility of lysines of histones to the acetylases. The predominant target for inhibition is histone H4. HAT inhibition leads to silencing of HAT-dependent transcription and prevents active demethylation of DNA. Both isoforms stimulate DNA replication of the adenovirus genome complexed with viral core proteins; however, isoform 2 specific activity is higher.

REGION 31 78 Dimerization.
REGION 79 225 Earmuff domain.
MOD_RES 2 2 N,N,N-trimethylalanine (By similarity).
MOD_RES 7 7 Phosphoserine.
MOD_RES 132 132 N6-acetyllysine.
MOD_RES 146 146 Phosphotyrosine (By similarity).
MOD_RES 150 150 N6-acetyllysine.
MOD_RES 172 172 N6-acetyllysine.
CROSSLNK 154 154 Glycyl lysine isopeptide (Lys-Gly)

3D-structure; Acetylation; Alternative splicing; Chaperone; Chromosomal rearrangement; Complete proteome; Cytoplasm; Direct protein sequencing; DNA-binding; Endoplasmic reticulum; Isopeptide bond; Methylation; Nucleus; Phosphoprotein; Polymorphism; Proto-oncogene; Reference proteome; Ubl conjugation.

UniProt (SWISSPROT/TrEMBL); GenBank; EMBL

GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
GO:0005654; C:nucleoplasm; TAS:Reactome.
GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
GO:0043234; C:protein complex; IDA:UniProtKB.
GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
GO:0042393; F:histone binding; TAS:UniProtKB.
GO:0004864; F:protein phosphatase inhibitor activity; TAS:ProtInc.
GO:0008601; F:protein phosphatase type 2A regulator activity; TAS:UniProtKB.
GO:0006260; P:DNA replication; TAS:ProtInc.
GO:0010467; P:gene expression; TAS:Reactome.
GO:0016071; P:mRNA metabolic process; TAS:Reactome.
GO:0035067; P:negative regulation of histone acetylation; TAS:UniProtKB.
GO:0043524; P:negative regulation of neuron apoptotic process; IGI:MGI.
GO:0045892; P:negative regulation of transcription, DNA-dependent; IDA:UniProtKB.
GO:0006913; P:nucleocytoplasmic transport; NAS:UniProtKB.
GO:0006334; P:nucleosome assembly; TAS:ProtInc.
GO:0006337; P:nucleosome disassembly; TAS:UniProtKB.

IPR002164; NAP_family.