CPLM-018272

Genbank Nucleotide ID

Programmed cell death 6-interacting protein

Protein Synonyms/Alias

PDCD6-interacting protein; ALG-2-interacting protein 1; ALG-2-interacting protein X; Hp95

AIP1; ALIX; KIAA1375

Homo sapiens (Human)

Position	Peptide	Type	References
19	TSEVDLAKPLVKFIQ	ubiquitination	[1, 2, 3, 4, 5]
23	DLAKPLVKFIQQTYP	ubiquitination	[1, 3, 5, 6]
48	RAAEELSKLRRAAVG	acetylation	[7]
48	RAAEELSKLRRAAVG	ubiquitination	[3]
60	AVGRPLDKHEGALET	ubiquitination	[3]
101	TWKDAFDKGSLFGGS	acetylation	[8]
101	TWKDAFDKGSLFGGS	ubiquitination	[1, 3, 9, 10]
215	MKDAIIAKLANQAAD	acetylation	[7]
215	MKDAIIAKLANQAAD	ubiquitination	[2]
229	DYFGDAFKQCQYKDT	ubiquitination	[3]
234	AFKQCQYKDTLPKEV	ubiquitination	[3]
298	YDEYVNVKDFSDKIN	acetylation	[8]
303	NVKDFSDKINRALAA	ubiquitination	[2]
313	RALAAAKKDNDFIYH	ubiquitination	[10]
334	KDLDPIGKATLVKST	ubiquitination	[3]
339	IGKATLVKSTPVNVP	acetylation	[8]
339	IGKATLVKSTPVNVP	ubiquitination	[3]
350	VNVPISQKFTDLFEK	acetylation	[8]
350	VNVPISQKFTDLFEK	ubiquitination	[1, 3, 5, 6, 10]
357	KFTDLFEKMVPVSVQ	ubiquitination	[2, 3, 4]
486	TPSNELYKPLRAEGT	acetylation	[8]
486	TPSNELYKPLRAEGT	ubiquitination	[6]
501	NFRTVLDKAVQADGQ	ubiquitination	[1, 2, 3, 4, 5, 6, 10, 11]
541	IPSANPAKTMQGSEV	ubiquitination	[3]
564	SNLDEVKKEREGLEN	ubiquitination	[3]
638	VSHQEFSKMKQSNNE	ubiquitination	[2, 3, 4, 10, 12]
640	HQEFSKMKQSNNEAN	ubiquitination	[2, 3, 4, 10, 13, 14]
675	ANLKEGTKFYNELTE	ubiquitination	[4]
707	TERDELLKDLQQSIA	ubiquitination	[1, 2, 3, 4, 5, 6, 11, 15, 16]
751	PRTMPPTKPQPPARP	ubiquitination	[1, 5, 6]

[1] 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]
[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] 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]
[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] 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]
[7] 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]
[8] 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]
[9] Proteomic analyses reveal divergent ubiquitylation site patterns in murine tissues.
Wagner SA, Beli P, Weinert BT, Schölz C, Kelstrup CD, Young C, Nielsen ML, Olsen JV, Brakebusch C, Choudhary C.
Mol Cell Proteomics. 2012 Dec;11(12):1578-85. [PMID: 22790023]
[10] 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]
[11] 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]
[12] 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]
[13] Ubiquitin ligase substrate identification through quantitative proteomics at both the protein and peptide levels.
Lee KA, Hammerle LP, Andrews PS, Stokes MP, Mustelin T, Silva JC, Black RA, Doedens JR.
J Biol Chem. 2011 Dec 2;286(48):41530-8. [PMID: 21987572]
[14] 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]
[15] 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]
[16] 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]

Functional Description

Class E VPS protein involved in concentration and sorting of cargo proteins of the multivesicular body (MVB) for incorporation into intralumenal vesicles (ILVs) that are generated by invagination and scission from the limiting membrane of the endosome. Binds to the phospholipid lysobisphosphatidic acid (LBPA) which is abundant in MVBs internal membranes. The MVB pathway appears to require the sequential function of ESCRT-O, -I,-II and -III complexes. The ESCRT machinery also functions in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis and enveloped virus budding (HIV-1 and other lentiviruses). Appears to be an adapter for a subset of ESCRT-III proteins, such as CHMP4, to function at distinct membranes. Required for completion of cytokinesis. Involved in HIV-1 virus budding. Can replace TSG101 it its role of supporting HIV-1 release; this function implies the interaction with CHMP4B. May play a role in the regulation of both apoptosis and cell proliferation.

DOMAIN 3 392 BRO1.
REGION 176 868 Interaction with EIAV p9.
REGION 176 503 Interaction with CHMP4A, CHMP4B and
REGION 503 868 Self-association.
REGION 717 720 Interaction with TSG101.
REGION 797 806 Interaction with CEP55.
REGION 864 868 Essential to promote virus budding.
MOD_RES 2 2 N-acetylalanine.
MOD_RES 215 215 N6-acetyllysine.
MOD_RES 730 730 Phosphoserine.
MOD_RES 738 738 Phosphothreonine.
MOD_RES 741 741 Phosphothreonine.

3D-structure; Acetylation; Alternative splicing; Apoptosis; Cell cycle; Cell division; Complete proteome; Cytoplasm; Cytoskeleton; Direct protein sequencing; Host-virus interaction; Phosphoprotein; Polymorphism; Protein transport; Reference proteome; Transport.

UniProt (SWISSPROT/TrEMBL); GenBank; EMBL

GO:0005737; C:cytoplasm; IDA:HPA.
GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
GO:0005815; C:microtubule organizing center; IEA:UniProtKB-SubCell.
GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
GO:0051301; P:cell division; IEA:UniProtKB-KW.
GO:0015031; P:protein transport; IEA:UniProtKB-KW.
GO:0019048; P:virus-host interaction; IEA:UniProtKB-KW.

IPR025304; ALIX_V_dom.
IPR004328; BRO1_dom.

PF13949; ALIX_LYPXL_bnd
PF03097; BRO1