CPLM-023229

Genbank Nucleotide ID

Vacuolar protein sorting-associated protein 4A

Protein Synonyms/Alias

Protein SKD2; VPS4-1; hVPS4

Homo sapiens (Human)

Position	Peptide	Type	References
8	MTTSTLQKAIDLVTK	acetylation	[1]
59	AKESIRAKCVQYLDR	acetylation	[2]
69	QYLDRAEKLKDYLRS	acetylation	[2]
71	LDRAEKLKDYLRSKE	acetylation	[2]
121	MGAVVMEKPNIRWND	ubiquitination	[3]
140	EGAKEALKEAVILPI	ubiquitination	[3, 4]
148	EAVILPIKFPHLFTG	ubiquitination	[4, 5]
156	FPHLFTGKRTPWRGI	ubiquitination	[4]
210	GESEKLVKNLFELAR	ubiquitination	[3, 5]
425	VNADDLLKVKKFSED	ubiquitination	[3]

[1] 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]
[2] 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]
[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] 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] 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]

Functional Description

Involved in late steps of the endosomal multivesicular bodies (MVB) pathway. Recognizes membrane-associated ESCRT-III assemblies and catalyzes their disassembly, possibly in combination with membrane fission. Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. MVBs contain intraluminal vesicles (ILVs) that are generated by invagination and scission from the limiting membrane of the endosome and mostly are delivered to lysosomes enabling degradation of membrane proteins, such as stimulated growth factor receptors, lysosomal enzymes and lipids. In conjunction with the ESCRT machinery also appears to function in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis and enveloped virus budding (HIV-1 and other lentiviruses). Involved in cytokinesis.

DOMAIN 2 80 MIT.
NP_BIND 167 174 ATP (Potential).
REGION 2 84 Interaction with CHMP1B.
MOD_RES 2 2 N-acetylthreonine.
MOD_RES 8 8 N6-acetyllysine.

3D-structure; Acetylation; ATP-binding; Cell cycle; Cell division; Complete proteome; Endosome; Hydrolase; Membrane; Nucleotide-binding; Protein transport; Reference proteome; Transport.

UniProt (SWISSPROT/TrEMBL); GenBank; EMBL

GO:0005829; C:cytosol; TAS:Reactome.
GO:0031902; C:late endosome membrane; IEA:UniProtKB-SubCell.
GO:0030496; C:midbody; IDA:UniProtKB.
GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
GO:0042623; F:ATPase activity, coupled; NAS:UniProtKB.
GO:0016044; P:cellular membrane organization; TAS:Reactome.
GO:0000910; P:cytokinesis; IDA:UniProtKB.
GO:0016197; P:endosomal transport; IMP:UniProtKB.
GO:0015031; P:protein transport; IEA:UniProtKB-KW.
GO:0016192; P:vesicle-mediated transport; IDA:UniProtKB.

IPR003593; AAA+_ATPase.
IPR003959; ATPase_AAA_core.
IPR003960; ATPase_AAA_CS.
IPR007330; MIT.
IPR027417; P-loop_NTPase.
IPR015415; Vps4_C.

PF00004; AAA
PF04212; MIT
PF09336; Vps4_C

SM00382; AAA
SM00745; MIT