CPLM-012201

Genbank Nucleotide ID

Phorbol-12-myristate-13-acetate-induced protein 1

Protein Synonyms/Alias

PMA-induced protein 1; Immediate-early-response protein APR; Protein Noxa

Homo sapiens (Human)

Position	Peptide	Type	References
35	QLRRFGDKLNFRQKL	ubiquitination	[1, 2, 3, 4, 5, 6, 7]
41	DKLNFRQKLLNLISK	ubiquitination	[2, 3, 4, 5, 6, 8]
48	KLLNLISKLFCSGT*	ubiquitination	[3, 8, 9]

[1] 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]
[2] 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]
[3] 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]
[4] 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]
[5] 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]
[6] 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]
[7] 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]
[8] Proteome-wide identification of ubiquitylation sites by conjugation of engineered lysine-less ubiquitin.
Oshikawa K, Matsumoto M, Oyamada K, Nakayama KI.
J Proteome Res. 2012 Feb 3;11(2):796-807. [PMID: 22053931]
[9] Global analysis of lysine ubiquitination by ubiquitin remnant immunoaffinity profiling.
Xu G, Paige JS, Jaffrey SR.
Nat Biotechnol. 2010 Aug;28(8):868-73. [PMID: 20639865]

Functional Description

Promotes activation of caspases and apoptosis. Promotes mitochondrial membrane changes and efflux of apoptogenic proteins from the mitochondria. Contributes to p53/TP53-dependent apoptosis after radiation exposure. Promotes proteasomal degradation of MCL1. Competes with BAK1 for binding to MCL1 and can displace BAK1 from its binding site on MCL1 (By similarity). Competes with BIM/BCL2L11 for binding to MCL1 and can displace BIM/BCL2L11 from its binding site on MCL1.

REGION 41 50 Required for mitochondrial location.
MOTIF 29 37 BH3.

3D-structure; Apoptosis; Complete proteome; Mitochondrion; Reference proteome.

UniProt (SWISSPROT/TrEMBL); GenBank; EMBL

GO:0005829; C:cytosol; IDA:UniProtKB.
GO:0005741; C:mitochondrial outer membrane; TAS:Reactome.
GO:0005634; C:nucleus; IDA:UniProtKB.
GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:HGNC.
GO:0006921; P:cellular component disassembly involved in execution phase of apoptosis; IDA:HGNC.
GO:0042149; P:cellular response to glucose starvation; IMP:UniProtKB.
GO:0071456; P:cellular response to hypoxia; IEP:UniProtKB.
GO:0006917; P:induction of apoptosis; IDA:UniProtKB.
GO:0072332; P:intrinsic apoptotic signaling pathway by p53 class mediator; IMP:UniProtKB.
GO:0048147; P:negative regulation of fibroblast proliferation; IEA:Compara.
GO:0010917; P:negative regulation of mitochondrial membrane potential; ISS:UniProtKB.
GO:0043517; P:positive regulation of DNA damage response, signal transduction by p53 class mediator; IMP:UniProtKB.
GO:0010907; P:positive regulation of glucose metabolic process; IDA:UniProtKB.
GO:2001244; P:positive regulation of intrinsic apoptotic signaling pathway; IDA:UniProtKB.
GO:0043525; P:positive regulation of neuron apoptotic process; IEA:Compara.
GO:1900740; P:positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway; TAS:Reactome.
GO:0032461; P:positive regulation of protein oligomerization; IDA:UniProtKB.
GO:0090200; P:positive regulation of release of cytochrome c from mitochondria; IDA:UniProtKB.
GO:0010498; P:proteasomal protein catabolic process; IDA:UniProtKB.
GO:0072593; P:reactive oxygen species metabolic process; IDA:UniProtKB.
GO:0046902; P:regulation of mitochondrial membrane permeability; IDA:UniProtKB.
GO:0001836; P:release of cytochrome c from mitochondria; IEA:Compara.
GO:0006974; P:response to DNA damage stimulus; IEA:Compara.
GO:0043331; P:response to dsRNA; IDA:HGNC.
GO:0009411; P:response to UV; IEA:Compara.
GO:0010165; P:response to X-ray; IEA:Compara.
GO:0043029; P:T cell homeostasis; ISS:UniProtKB.
GO:0006926; P:virus-infected cell apoptotic process; IDA:HGNC.

IPR024140; PMA-induced_Noxa.