CPLM-022042

Genbank Nucleotide ID

Diablo homolog, mitochondrial

Protein Synonyms/Alias

Direct IAP-binding protein with low pI; Second mitochondria-derived activator of caspase; Smac

Homo sapiens (Human)

Position	Peptide	Type	References
123	QYTSLLGKMNSEEED	ubiquitination	[1, 2]
146	ARAEMTSKHQEYLKL	ubiquitination	[2, 3]
191	RNHIQLVKLQVEEVH	ubiquitination	[1, 2, 3, 4, 5]
203	EVHQLSRKAETKLAE	ubiquitination	[4, 5]
207	LSRKAETKLAEAQIE	ubiquitination	[3, 4, 5]
219	QIEELRQKTQEEGEE	ubiquitination	[2, 6]

[1] 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]
[2] 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]
[3] 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]
[4] 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]
[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] 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]

Functional Description

Promotes apoptosis by activating caspases in the cytochrome c/Apaf-1/caspase-9 pathway. Acts by opposing the inhibitory activity of inhibitor of apoptosis proteins (IAP). Inhibits the activity of BIRC6/bruce by inhibiting its binding to caspases. Isoform 3 attenuates the stability and apoptosis- inhibiting activity of XIAP/BIRC4 by promoting XIAP/BIRC4 ubiquitination and degradation through the ubiquitin-proteasome pathway. Isoform 3 also disrupts XIAP/BIRC4 interacting with processed caspase-9 and promotes caspase-3 activation. Isoform 1 is defective in the capacity to down-regulate the XIAP/BIRC4 abundance.

MOTIF 56 60 IAP-binding.

3D-structure; Alternative splicing; Apoptosis; Complete proteome; Deafness; Direct protein sequencing; Disease mutation; Mitochondrion; Non-syndromic deafness; Reference proteome; Transit peptide; Ubl conjugation.

UniProt (SWISSPROT/TrEMBL); GenBank; EMBL

GO:0035631; C:CD40 receptor complex; ISS:BHF-UCL.
GO:0005829; C:cytosol; TAS:Reactome.
GO:0009898; C:internal side of plasma membrane; ISS:BHF-UCL.
GO:0005758; C:mitochondrial intermembrane space; TAS:Reactome.
GO:0008635; P:activation of cysteine-type endopeptidase activity involved in apoptotic process by cytochrome c; TAS:ProtInc.
GO:0008625; P:extrinsic apoptotic signaling pathway via death domain receptors; TAS:ProtInc.
GO:0006917; P:induction of apoptosis; TAS:ProtInc.
GO:0097193; P:intrinsic apoptotic signaling pathway; TAS:UniProtKB.
GO:0008631; P:intrinsic apoptotic signaling pathway in response to oxidative stress; IEA:Compara.

IPR015142; Smac_DIABLO.
IPR009062; Smac_DIABLO-like.

PF09057; Smac_DIABLO