Full text data of VPS4B
VPS4B
(SKD1, VPS42)
[Confidence: low (only semi-automatic identification from reviews)]
Vacuolar protein sorting-associated protein 4B; 3.6.4.6 (Cell migration-inducing gene 1 protein; Suppressor of K(+) transport growth defect 1; Protein SKD1)
Vacuolar protein sorting-associated protein 4B; 3.6.4.6 (Cell migration-inducing gene 1 protein; Suppressor of K(+) transport growth defect 1; Protein SKD1)
UniProt
O75351
ID VPS4B_HUMAN Reviewed; 444 AA.
AC O75351; Q69HW4; Q9GZS7;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
read moreDT 16-JAN-2004, sequence version 2.
DT 22-JAN-2014, entry version 133.
DE RecName: Full=Vacuolar protein sorting-associated protein 4B;
DE EC=3.6.4.6;
DE AltName: Full=Cell migration-inducing gene 1 protein;
DE AltName: Full=Suppressor of K(+) transport growth defect 1;
DE Short=Protein SKD1;
GN Name=VPS4B; Synonyms=SKD1, VPS42; ORFNames=MIG1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH VPS4A,
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND MUTAGENESIS OF GLU-235.
RX PubMed=11563910; DOI=10.1006/jmbi.2001.4917;
RA Scheuring S., Roehricht R.A., Schoening-Burkhardt B., Beyer A.,
RA Mueller S., Abts H.F., Koehrer K.;
RT "Mammalian cells express two VPS4 proteins both of which are involved
RT in intracellular protein trafficking.";
RL J. Mol. Biol. 312:469-480(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Skin;
RX PubMed=12594041; DOI=10.1016/S0378-1119(02)01205-2;
RA Beyer A., Scheuring S., Mueller S., Mincheva A., Lichter P.,
RA Koehrer K.;
RT "Comparative sequence and expression analyses of four mammalian VPS4
RT genes.";
RL Gene 305:47-59(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Umbilical cord blood;
RX PubMed=9653160; DOI=10.1073/pnas.95.14.8175;
RA Mao M., Fu G., Wu J.-S., Zhang Q.-H., Zhou J., Kan L.-X., Huang Q.-H.,
RA He K.-L., Gu B.-W., Han Z.-G., Shen Y., Gu J., Yu Y.-P., Xu S.-H.,
RA Wang Y.-X., Chen S.-J., Chen Z.;
RT "Identification of genes expressed in human CD34(+) hematopoietic
RT stem/progenitor cells by expressed sequence tags and efficient full-
RT length cDNA cloning.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:8175-8180(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kim J.W.;
RT "Identification of a human cell migration gene 1.";
RL Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP INTERACTION WITH CHMP2A.
RX PubMed=11559748;
RA Howard T.L., Stauffer D.R., Degnin C.R., Hollenberg S.M.;
RT "CHMP1 functions as a member of a newly defined family of vesicle
RT trafficking proteins.";
RL J. Cell Sci. 114:2395-2404(2001).
RN [8]
RP FUNCTION IN HIV-1 BUDDING, INTERACTION WITH CHMP1A; CHMP1B CHMP2A;
RP CHMP4B AND CHMP6, AND SUBCELLULAR LOCATION.
RX PubMed=14505570; DOI=10.1016/S0092-8674(03)00714-1;
RA von Schwedler U.K., Stuchell M., Mueller B., Ward D.M., Chung H.-Y.,
RA Morita E., Wang H.E., Davis T., He G.P., Cimbora D.M., Scott A.,
RA Kraeusslich H.-G., Kaplan J., Morham S.G., Sundquist W.I.;
RT "The protein network of HIV budding.";
RL Cell 114:701-713(2003).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-102, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III,
RA Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N.,
RA Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [11]
RP MUTAGENESIS OF ALA-15 AND LEU-66.
RX PubMed=18606141; DOI=10.1016/j.devcel.2008.05.014;
RA Kieffer C., Skalicky J.J., Morita E., De Domenico I., Ward D.M.,
RA Kaplan J., Sundquist W.I.;
RT "Two distinct modes of ESCRT-III recognition are required for VPS4
RT functions in lysosomal protein targeting and HIV-1 budding.";
RL Dev. Cell 15:62-73(2008).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-102, AND MASS
RP SPECTROMETRY.
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [13]
RP INTERACTION WITH VTA1, AND MUTAGENESIS OF 390-GLY--TRP-396.
RX PubMed=18385515; DOI=10.1091/mbc.E07-12-1263;
RA Shim S., Merrill S.A., Hanson P.I.;
RT "Novel interactions of ESCRT-III with LIP5 and VPS4 and their
RT implications for ESCRT-III disassembly.";
RL Mol. Biol. Cell 19:2661-2672(2008).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-102, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-102, AND MASS
RP SPECTROMETRY.
RC TISSUE=Liver;
RX PubMed=18318008; DOI=10.1002/pmic.200700884;
RA Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D.,
RA Zou H., Gu J.;
RT "Large-scale phosphoproteome analysis of human liver tissue by
RT enrichment and fractionation of phosphopeptides with strong anion
RT exchange chromatography.";
RL Proteomics 8:1346-1361(2008).
RN [16]
RP FUNCTION, ASSOCIATION WITH THE CHMP2A-CHMP3 POLYMER, AND ELECTRON
RP MICROSCOPY.
RX PubMed=18687924; DOI=10.1126/science.1161070;
RA Lata S., Schoehn G., Jain A., Pires R., Piehler J., Goettlinger H.G.,
RA Weissenhorn W.;
RT "Helical structures of ESCRT-III are disassembled by VPS4.";
RL Science 321:1354-1357(2008).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [18]
RP INTERACTION WITH IST1.
RX PubMed=19129479; DOI=10.1091/mbc.E08-05-0475;
RA Bajorek M., Morita E., Skalicky J.J., Morham S.G., Babst M.,
RA Sundquist W.I.;
RT "Biochemical analyses of human IST1 and its function in cytokinesis.";
RL Mol. Biol. Cell 20:1360-1373(2009).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-93; SER-102 AND SER-108,
RP AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [21]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-102, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [23]
RP STRUCTURE BY NMR OF 1-77, DOMAIN, AND VARIANT MET-58.
RX PubMed=16018968; DOI=10.1016/j.bbrc.2005.06.110;
RA Takasu H., Jee J.G., Ohno A., Goda N., Fujiwara K., Tochio H.,
RA Shirakawa M., Hiroaki H.;
RT "Structural characterization of the MIT domain from human Vps4b.";
RL Biochem. Biophys. Res. Commun. 334:460-465(2005).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 123-444, SUBUNIT, INTERACTION
RP WITH VTA1, AND MUTAGENESIS OF 208-TRP-LEU-209 AND GLY-210.
RX PubMed=16193069; DOI=10.1038/sj.emboj.7600818;
RA Scott A., Chung H.Y., Gonciarz-Swiatek M., Hill G.C., Whitby F.G.,
RA Gaspar J., Holton J.M., Viswanathan R., Ghaffarian S., Hill C.P.,
RA Sundquist W.I.;
RT "Structural and mechanistic studies of VPS4 proteins.";
RL EMBO J. 24:3658-3669(2005).
RN [25]
RP STRUCTURE BY NMR OF 1-108.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of MIT domain from human SKD1.";
RL Submitted (NOV-2005) to the PDB data bank.
RN [26]
RP STRUCTURE BY NMR OF 1-86 IN COMPLEX WITH CHMP2B, AND INTERACTION WITH
RP CHMP1B.
RX PubMed=17928862; DOI=10.1038/nature06172;
RA Stuchell-Brereton M.D., Skalicky J.J., Kieffer C., Karren M.A.,
RA Ghaffarian S., Sundquist W.I.;
RT "ESCRT-III recognition by VPS4 ATPases.";
RL Nature 449:740-744(2007).
CC -!- FUNCTION: Involved in late steps of the endosomal multivesicular
CC bodies (MVB) pathway. Recognizes membrane-associated ESCRT-III
CC assemblies and catalyzes their disassembly, possibly in
CC combination with membrane fission. Redistributes the ESCRT-III
CC components to the cytoplasm for further rounds of MVB sorting.
CC MVBs contain intraluminal vesicles (ILVs) that are generated by
CC invagination and scission from the limiting membrane of the
CC endosome and mostly are delivered to lysosomes enabling
CC degradation of membrane proteins, such as stimulated growth factor
CC receptors, lysosomal enzymes and lipids. In conjunction with the
CC ESCRT machinery also appears to function in topologically
CC equivalent membrane fission events, such as the terminal stages of
CC cytokinesis and enveloped virus budding (HIV-1 and other
CC lentiviruses).
CC -!- CATALYTIC ACTIVITY: ATP + H(2)O = ADP + phosphate.
CC -!- SUBUNIT: Proposed to be monomeric or homodimeric in nucleotide-
CC free form and to oligomerize upon binding to ATP to form two
CC stacked hexameric or heptameric rings with a central pore through
CC which ESCRT-III substrates are translocated in an ATP-dependent
CC manner. In vitro, associates on the inside of a helical tubular
CC structure formed by a CHMP2A-CHMP3 polymer. Interacts with CHMP1A,
CC CHMP1B, CHMP2A, CHMP4B and CHMP6. Interacts with VPS4A; the
CC interaction suggests a heteromeric assembly with VPS4A. Interacts
CC with VTA1.
CC -!- SUBCELLULAR LOCATION: Prevacuolar compartment membrane; Peripheral
CC membrane protein. Late endosome membrane; Peripheral membrane
CC protein (Probable). Note=Membrane-associated in the prevacuolar
CC endosomal compartment. Localized in HIV-1 particles purified from
CC acutely infected cells.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed.
CC -!- DOMAIN: The MIT domain serves as an adapter for ESCRT-III
CC proteins. It forms an asymmetric three-helix bundle that binds
CC amphipathic MIM (MIT interacting motif) helices along the groove
CC between MIT helices 2 and 3 present in a subset of ESCRT-III
CC proteins thus establishing the canonical MIM-MIT interaction. In
CC an extended conformation along the groove between helices 1 and 3,
CC also binds to a type-2 MIT interacting motif (MIM2).
CC -!- SIMILARITY: Belongs to the AAA ATPase family.
CC -!- SIMILARITY: Contains 1 MIT domain.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; AF195514; AAG33022.1; -; mRNA.
DR EMBL; AF282904; AAG01471.1; -; Genomic_DNA.
DR EMBL; AF038960; AAC39874.1; -; mRNA.
DR EMBL; AY232629; AAP59551.1; -; mRNA.
DR EMBL; CH471096; EAW63143.1; -; Genomic_DNA.
DR EMBL; BC039574; AAH39574.1; -; mRNA.
DR RefSeq; NP_004860.2; NM_004869.3.
DR UniGene; Hs.126550; -.
DR PDB; 1WR0; NMR; -; A=1-77.
DR PDB; 1XWI; X-ray; 2.80 A; A=123-444.
DR PDB; 2CPT; NMR; -; A=1-104.
DR PDB; 2JQH; NMR; -; A=1-86.
DR PDB; 2JQK; NMR; -; A=1-86.
DR PDBsum; 1WR0; -.
DR PDBsum; 1XWI; -.
DR PDBsum; 2CPT; -.
DR PDBsum; 2JQH; -.
DR PDBsum; 2JQK; -.
DR ProteinModelPortal; O75351; -.
DR SMR; O75351; 1-108, 123-444.
DR DIP; DIP-53790N; -.
DR IntAct; O75351; 1.
DR STRING; 9606.ENSP00000238497; -.
DR ChEMBL; CHEMBL2311229; -.
DR PhosphoSite; O75351; -.
DR PaxDb; O75351; -.
DR PeptideAtlas; O75351; -.
DR PRIDE; O75351; -.
DR DNASU; 9525; -.
DR Ensembl; ENST00000238497; ENSP00000238497; ENSG00000119541.
DR GeneID; 9525; -.
DR KEGG; hsa:9525; -.
DR UCSC; uc002lix.3; human.
DR CTD; 9525; -.
DR GeneCards; GC18M061056; -.
DR HGNC; HGNC:10895; VPS4B.
DR HPA; CAB046445; -.
DR MIM; 609983; gene.
DR neXtProt; NX_O75351; -.
DR PharmGKB; PA35795; -.
DR eggNOG; COG0464; -.
DR HOGENOM; HOG000225146; -.
DR HOVERGEN; HBG057074; -.
DR InParanoid; O75351; -.
DR KO; K12196; -.
DR OMA; RADPNKI; -.
DR OrthoDB; EOG74BJS2; -.
DR PhylomeDB; O75351; -.
DR Reactome; REACT_11123; Membrane Trafficking.
DR Reactome; REACT_116125; Disease.
DR EvolutionaryTrace; O75351; -.
DR GeneWiki; VPS4B; -.
DR GenomeRNAi; 9525; -.
DR NextBio; 35700; -.
DR PRO; PR:O75351; -.
DR ArrayExpress; O75351; -.
DR Bgee; O75351; -.
DR CleanEx; HS_VPS4B; -.
DR Genevestigator; O75351; -.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005769; C:early endosome; IDA:UniProtKB.
DR GO; GO:0010008; C:endosome membrane; IDA:UniProtKB.
DR GO; GO:0005770; C:late endosome; IDA:UniProtKB.
DR GO; GO:0031902; C:late endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005764; C:lysosome; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005774; C:vacuolar membrane; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IMP:UniProtKB.
DR GO; GO:0042623; F:ATPase activity, coupled; NAS:UniProtKB.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0007032; P:endosome organization; IEA:Ensembl.
DR GO; GO:0032510; P:endosome to lysosome transport via multivesicular body sorting pathway; IMP:UniProtKB.
DR GO; GO:0032367; P:intracellular cholesterol transport; IMP:UniProtKB.
DR GO; GO:0006813; P:potassium ion transport; IEA:Ensembl.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0033993; P:response to lipid; IDA:UniProtKB.
DR GO; GO:0016032; P:viral process; TAS:Reactome.
DR InterPro; IPR003593; AAA+_ATPase.
DR InterPro; IPR003959; ATPase_AAA_core.
DR InterPro; IPR003960; ATPase_AAA_CS.
DR InterPro; IPR007330; MIT.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR015415; Vps4_C.
DR Pfam; PF00004; AAA; 1.
DR Pfam; PF04212; MIT; 1.
DR Pfam; PF09336; Vps4_C; 1.
DR SMART; SM00382; AAA; 1.
DR SMART; SM00745; MIT; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS00674; AAA; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Cell cycle; Cell division; Coiled coil;
KW Complete proteome; Endosome; Hydrolase; Membrane; Nucleotide-binding;
KW Phosphoprotein; Polymorphism; Protein transport; Reference proteome;
KW Transport.
FT CHAIN 1 444 Vacuolar protein sorting-associated
FT protein 4B.
FT /FTId=PRO_0000084767.
FT DOMAIN 4 82 MIT.
FT NP_BIND 174 181 ATP (Potential).
FT COILED 19 82 Potential.
FT MOD_RES 93 93 Phosphoserine.
FT MOD_RES 102 102 Phosphoserine.
FT MOD_RES 108 108 Phosphoserine.
FT VARIANT 58 58 I -> M (common polymorphism; induces
FT thermal instability; dbSNP:rs17688948).
FT /FTId=VAR_023385.
FT MUTAGEN 15 15 A->D: Reduces HIV-1 release 10-fold; when
FT associated with D-66.
FT MUTAGEN 15 15 A->D: Reduces HIV-1 release 2-fold.
FT MUTAGEN 66 66 L->D: Reduces HIV-1 release 10-fold; when
FT associated with D-15.
FT MUTAGEN 66 66 L->D: Reduces HIV-1 release 3-fold.
FT MUTAGEN 208 209 WL->AA: Strongly impairs HIV-1 release.
FT MUTAGEN 210 210 G->A: Impairs HIV-1 release.
FT MUTAGEN 235 235 E->Q: Defective in vacuolar protein
FT sorting.
FT MUTAGEN 390 396 Missing: Abolishes interaction with VTA1.
FT CONFLICT 114 114 K -> R (in Ref. 3; AAC39874).
FT CONFLICT 127 127 E -> D (in Ref. 3; AAC39874).
FT CONFLICT 342 342 S -> G (in Ref. 3; AAC39874).
FT TURN 1 3
FT HELIX 6 23
FT HELIX 30 47
FT HELIX 52 55
FT HELIX 56 72
FT TURN 73 75
FT STRAND 87 89
FT STRAND 125 127
FT HELIX 133 135
FT HELIX 140 155
FT HELIX 157 159
FT STRAND 168 178
FT HELIX 180 190
FT STRAND 195 200
FT HELIX 213 225
FT STRAND 227 234
FT TURN 235 237
FT HELIX 238 240
FT STRAND 243 245
FT HELIX 250 263
FT STRAND 265 267
FT STRAND 272 279
FT TURN 281 283
FT HELIX 286 290
FT STRAND 294 297
FT HELIX 303 314
FT HELIX 323 331
FT HELIX 338 349
FT HELIX 351 358
FT STRAND 360 368
FT STRAND 375 383
FT STRAND 386 388
FT STRAND 391 393
FT HELIX 396 398
FT HELIX 401 403
FT HELIX 411 419
FT HELIX 427 438
SQ SEQUENCE 444 AA; 49302 MW; 9D565E4B20AF73FB CRC64;
MSSTSPNLQK AIDLASKAAQ EDKAGNYEEA LQLYQHAVQY FLHVVKYEAQ GDKAKQSIRA
KCTEYLDRAE KLKEYLKNKE KKAQKPVKEG QPSPADEKGN DSDGEGESDD PEKKKLQNQL
QGAIVIERPN VKWSDVAGLE GAKEALKEAV ILPIKFPHLF TGKRTPWRGI LLFGPPGTGK
SYLAKAVATE ANNSTFFSIS SSDLVSKWLG ESEKLVKNLF QLARENKPSI IFIDEIDSLC
GSRSENESEA ARRIKTEFLV QMQGVGVDND GILVLGATNI PWVLDSAIRR RFEKRIYIPL
PEPHARAAMF KLHLGTTQNS LTEADFRELG RKTDGYSGAD ISIIVRDALM QPVRKVQSAT
HFKKVRGPSR ADPNHLVDDL LTPCSPGDPG AIEMTWMDVP GDKLLEPVVS MSDMLRSLSN
TKPTVNEHDL LKLKKFTEDF GQEG
//
ID VPS4B_HUMAN Reviewed; 444 AA.
AC O75351; Q69HW4; Q9GZS7;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
read moreDT 16-JAN-2004, sequence version 2.
DT 22-JAN-2014, entry version 133.
DE RecName: Full=Vacuolar protein sorting-associated protein 4B;
DE EC=3.6.4.6;
DE AltName: Full=Cell migration-inducing gene 1 protein;
DE AltName: Full=Suppressor of K(+) transport growth defect 1;
DE Short=Protein SKD1;
GN Name=VPS4B; Synonyms=SKD1, VPS42; ORFNames=MIG1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH VPS4A,
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND MUTAGENESIS OF GLU-235.
RX PubMed=11563910; DOI=10.1006/jmbi.2001.4917;
RA Scheuring S., Roehricht R.A., Schoening-Burkhardt B., Beyer A.,
RA Mueller S., Abts H.F., Koehrer K.;
RT "Mammalian cells express two VPS4 proteins both of which are involved
RT in intracellular protein trafficking.";
RL J. Mol. Biol. 312:469-480(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Skin;
RX PubMed=12594041; DOI=10.1016/S0378-1119(02)01205-2;
RA Beyer A., Scheuring S., Mueller S., Mincheva A., Lichter P.,
RA Koehrer K.;
RT "Comparative sequence and expression analyses of four mammalian VPS4
RT genes.";
RL Gene 305:47-59(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Umbilical cord blood;
RX PubMed=9653160; DOI=10.1073/pnas.95.14.8175;
RA Mao M., Fu G., Wu J.-S., Zhang Q.-H., Zhou J., Kan L.-X., Huang Q.-H.,
RA He K.-L., Gu B.-W., Han Z.-G., Shen Y., Gu J., Yu Y.-P., Xu S.-H.,
RA Wang Y.-X., Chen S.-J., Chen Z.;
RT "Identification of genes expressed in human CD34(+) hematopoietic
RT stem/progenitor cells by expressed sequence tags and efficient full-
RT length cDNA cloning.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:8175-8180(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kim J.W.;
RT "Identification of a human cell migration gene 1.";
RL Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP INTERACTION WITH CHMP2A.
RX PubMed=11559748;
RA Howard T.L., Stauffer D.R., Degnin C.R., Hollenberg S.M.;
RT "CHMP1 functions as a member of a newly defined family of vesicle
RT trafficking proteins.";
RL J. Cell Sci. 114:2395-2404(2001).
RN [8]
RP FUNCTION IN HIV-1 BUDDING, INTERACTION WITH CHMP1A; CHMP1B CHMP2A;
RP CHMP4B AND CHMP6, AND SUBCELLULAR LOCATION.
RX PubMed=14505570; DOI=10.1016/S0092-8674(03)00714-1;
RA von Schwedler U.K., Stuchell M., Mueller B., Ward D.M., Chung H.-Y.,
RA Morita E., Wang H.E., Davis T., He G.P., Cimbora D.M., Scott A.,
RA Kraeusslich H.-G., Kaplan J., Morham S.G., Sundquist W.I.;
RT "The protein network of HIV budding.";
RL Cell 114:701-713(2003).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-102, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III,
RA Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N.,
RA Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [11]
RP MUTAGENESIS OF ALA-15 AND LEU-66.
RX PubMed=18606141; DOI=10.1016/j.devcel.2008.05.014;
RA Kieffer C., Skalicky J.J., Morita E., De Domenico I., Ward D.M.,
RA Kaplan J., Sundquist W.I.;
RT "Two distinct modes of ESCRT-III recognition are required for VPS4
RT functions in lysosomal protein targeting and HIV-1 budding.";
RL Dev. Cell 15:62-73(2008).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-102, AND MASS
RP SPECTROMETRY.
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [13]
RP INTERACTION WITH VTA1, AND MUTAGENESIS OF 390-GLY--TRP-396.
RX PubMed=18385515; DOI=10.1091/mbc.E07-12-1263;
RA Shim S., Merrill S.A., Hanson P.I.;
RT "Novel interactions of ESCRT-III with LIP5 and VPS4 and their
RT implications for ESCRT-III disassembly.";
RL Mol. Biol. Cell 19:2661-2672(2008).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-102, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-102, AND MASS
RP SPECTROMETRY.
RC TISSUE=Liver;
RX PubMed=18318008; DOI=10.1002/pmic.200700884;
RA Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D.,
RA Zou H., Gu J.;
RT "Large-scale phosphoproteome analysis of human liver tissue by
RT enrichment and fractionation of phosphopeptides with strong anion
RT exchange chromatography.";
RL Proteomics 8:1346-1361(2008).
RN [16]
RP FUNCTION, ASSOCIATION WITH THE CHMP2A-CHMP3 POLYMER, AND ELECTRON
RP MICROSCOPY.
RX PubMed=18687924; DOI=10.1126/science.1161070;
RA Lata S., Schoehn G., Jain A., Pires R., Piehler J., Goettlinger H.G.,
RA Weissenhorn W.;
RT "Helical structures of ESCRT-III are disassembled by VPS4.";
RL Science 321:1354-1357(2008).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [18]
RP INTERACTION WITH IST1.
RX PubMed=19129479; DOI=10.1091/mbc.E08-05-0475;
RA Bajorek M., Morita E., Skalicky J.J., Morham S.G., Babst M.,
RA Sundquist W.I.;
RT "Biochemical analyses of human IST1 and its function in cytokinesis.";
RL Mol. Biol. Cell 20:1360-1373(2009).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-93; SER-102 AND SER-108,
RP AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [21]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-102, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [23]
RP STRUCTURE BY NMR OF 1-77, DOMAIN, AND VARIANT MET-58.
RX PubMed=16018968; DOI=10.1016/j.bbrc.2005.06.110;
RA Takasu H., Jee J.G., Ohno A., Goda N., Fujiwara K., Tochio H.,
RA Shirakawa M., Hiroaki H.;
RT "Structural characterization of the MIT domain from human Vps4b.";
RL Biochem. Biophys. Res. Commun. 334:460-465(2005).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 123-444, SUBUNIT, INTERACTION
RP WITH VTA1, AND MUTAGENESIS OF 208-TRP-LEU-209 AND GLY-210.
RX PubMed=16193069; DOI=10.1038/sj.emboj.7600818;
RA Scott A., Chung H.Y., Gonciarz-Swiatek M., Hill G.C., Whitby F.G.,
RA Gaspar J., Holton J.M., Viswanathan R., Ghaffarian S., Hill C.P.,
RA Sundquist W.I.;
RT "Structural and mechanistic studies of VPS4 proteins.";
RL EMBO J. 24:3658-3669(2005).
RN [25]
RP STRUCTURE BY NMR OF 1-108.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of MIT domain from human SKD1.";
RL Submitted (NOV-2005) to the PDB data bank.
RN [26]
RP STRUCTURE BY NMR OF 1-86 IN COMPLEX WITH CHMP2B, AND INTERACTION WITH
RP CHMP1B.
RX PubMed=17928862; DOI=10.1038/nature06172;
RA Stuchell-Brereton M.D., Skalicky J.J., Kieffer C., Karren M.A.,
RA Ghaffarian S., Sundquist W.I.;
RT "ESCRT-III recognition by VPS4 ATPases.";
RL Nature 449:740-744(2007).
CC -!- FUNCTION: Involved in late steps of the endosomal multivesicular
CC bodies (MVB) pathway. Recognizes membrane-associated ESCRT-III
CC assemblies and catalyzes their disassembly, possibly in
CC combination with membrane fission. Redistributes the ESCRT-III
CC components to the cytoplasm for further rounds of MVB sorting.
CC MVBs contain intraluminal vesicles (ILVs) that are generated by
CC invagination and scission from the limiting membrane of the
CC endosome and mostly are delivered to lysosomes enabling
CC degradation of membrane proteins, such as stimulated growth factor
CC receptors, lysosomal enzymes and lipids. In conjunction with the
CC ESCRT machinery also appears to function in topologically
CC equivalent membrane fission events, such as the terminal stages of
CC cytokinesis and enveloped virus budding (HIV-1 and other
CC lentiviruses).
CC -!- CATALYTIC ACTIVITY: ATP + H(2)O = ADP + phosphate.
CC -!- SUBUNIT: Proposed to be monomeric or homodimeric in nucleotide-
CC free form and to oligomerize upon binding to ATP to form two
CC stacked hexameric or heptameric rings with a central pore through
CC which ESCRT-III substrates are translocated in an ATP-dependent
CC manner. In vitro, associates on the inside of a helical tubular
CC structure formed by a CHMP2A-CHMP3 polymer. Interacts with CHMP1A,
CC CHMP1B, CHMP2A, CHMP4B and CHMP6. Interacts with VPS4A; the
CC interaction suggests a heteromeric assembly with VPS4A. Interacts
CC with VTA1.
CC -!- SUBCELLULAR LOCATION: Prevacuolar compartment membrane; Peripheral
CC membrane protein. Late endosome membrane; Peripheral membrane
CC protein (Probable). Note=Membrane-associated in the prevacuolar
CC endosomal compartment. Localized in HIV-1 particles purified from
CC acutely infected cells.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed.
CC -!- DOMAIN: The MIT domain serves as an adapter for ESCRT-III
CC proteins. It forms an asymmetric three-helix bundle that binds
CC amphipathic MIM (MIT interacting motif) helices along the groove
CC between MIT helices 2 and 3 present in a subset of ESCRT-III
CC proteins thus establishing the canonical MIM-MIT interaction. In
CC an extended conformation along the groove between helices 1 and 3,
CC also binds to a type-2 MIT interacting motif (MIM2).
CC -!- SIMILARITY: Belongs to the AAA ATPase family.
CC -!- SIMILARITY: Contains 1 MIT domain.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; AF195514; AAG33022.1; -; mRNA.
DR EMBL; AF282904; AAG01471.1; -; Genomic_DNA.
DR EMBL; AF038960; AAC39874.1; -; mRNA.
DR EMBL; AY232629; AAP59551.1; -; mRNA.
DR EMBL; CH471096; EAW63143.1; -; Genomic_DNA.
DR EMBL; BC039574; AAH39574.1; -; mRNA.
DR RefSeq; NP_004860.2; NM_004869.3.
DR UniGene; Hs.126550; -.
DR PDB; 1WR0; NMR; -; A=1-77.
DR PDB; 1XWI; X-ray; 2.80 A; A=123-444.
DR PDB; 2CPT; NMR; -; A=1-104.
DR PDB; 2JQH; NMR; -; A=1-86.
DR PDB; 2JQK; NMR; -; A=1-86.
DR PDBsum; 1WR0; -.
DR PDBsum; 1XWI; -.
DR PDBsum; 2CPT; -.
DR PDBsum; 2JQH; -.
DR PDBsum; 2JQK; -.
DR ProteinModelPortal; O75351; -.
DR SMR; O75351; 1-108, 123-444.
DR DIP; DIP-53790N; -.
DR IntAct; O75351; 1.
DR STRING; 9606.ENSP00000238497; -.
DR ChEMBL; CHEMBL2311229; -.
DR PhosphoSite; O75351; -.
DR PaxDb; O75351; -.
DR PeptideAtlas; O75351; -.
DR PRIDE; O75351; -.
DR DNASU; 9525; -.
DR Ensembl; ENST00000238497; ENSP00000238497; ENSG00000119541.
DR GeneID; 9525; -.
DR KEGG; hsa:9525; -.
DR UCSC; uc002lix.3; human.
DR CTD; 9525; -.
DR GeneCards; GC18M061056; -.
DR HGNC; HGNC:10895; VPS4B.
DR HPA; CAB046445; -.
DR MIM; 609983; gene.
DR neXtProt; NX_O75351; -.
DR PharmGKB; PA35795; -.
DR eggNOG; COG0464; -.
DR HOGENOM; HOG000225146; -.
DR HOVERGEN; HBG057074; -.
DR InParanoid; O75351; -.
DR KO; K12196; -.
DR OMA; RADPNKI; -.
DR OrthoDB; EOG74BJS2; -.
DR PhylomeDB; O75351; -.
DR Reactome; REACT_11123; Membrane Trafficking.
DR Reactome; REACT_116125; Disease.
DR EvolutionaryTrace; O75351; -.
DR GeneWiki; VPS4B; -.
DR GenomeRNAi; 9525; -.
DR NextBio; 35700; -.
DR PRO; PR:O75351; -.
DR ArrayExpress; O75351; -.
DR Bgee; O75351; -.
DR CleanEx; HS_VPS4B; -.
DR Genevestigator; O75351; -.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005769; C:early endosome; IDA:UniProtKB.
DR GO; GO:0010008; C:endosome membrane; IDA:UniProtKB.
DR GO; GO:0005770; C:late endosome; IDA:UniProtKB.
DR GO; GO:0031902; C:late endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005764; C:lysosome; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005774; C:vacuolar membrane; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IMP:UniProtKB.
DR GO; GO:0042623; F:ATPase activity, coupled; NAS:UniProtKB.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0007032; P:endosome organization; IEA:Ensembl.
DR GO; GO:0032510; P:endosome to lysosome transport via multivesicular body sorting pathway; IMP:UniProtKB.
DR GO; GO:0032367; P:intracellular cholesterol transport; IMP:UniProtKB.
DR GO; GO:0006813; P:potassium ion transport; IEA:Ensembl.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0033993; P:response to lipid; IDA:UniProtKB.
DR GO; GO:0016032; P:viral process; TAS:Reactome.
DR InterPro; IPR003593; AAA+_ATPase.
DR InterPro; IPR003959; ATPase_AAA_core.
DR InterPro; IPR003960; ATPase_AAA_CS.
DR InterPro; IPR007330; MIT.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR015415; Vps4_C.
DR Pfam; PF00004; AAA; 1.
DR Pfam; PF04212; MIT; 1.
DR Pfam; PF09336; Vps4_C; 1.
DR SMART; SM00382; AAA; 1.
DR SMART; SM00745; MIT; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS00674; AAA; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Cell cycle; Cell division; Coiled coil;
KW Complete proteome; Endosome; Hydrolase; Membrane; Nucleotide-binding;
KW Phosphoprotein; Polymorphism; Protein transport; Reference proteome;
KW Transport.
FT CHAIN 1 444 Vacuolar protein sorting-associated
FT protein 4B.
FT /FTId=PRO_0000084767.
FT DOMAIN 4 82 MIT.
FT NP_BIND 174 181 ATP (Potential).
FT COILED 19 82 Potential.
FT MOD_RES 93 93 Phosphoserine.
FT MOD_RES 102 102 Phosphoserine.
FT MOD_RES 108 108 Phosphoserine.
FT VARIANT 58 58 I -> M (common polymorphism; induces
FT thermal instability; dbSNP:rs17688948).
FT /FTId=VAR_023385.
FT MUTAGEN 15 15 A->D: Reduces HIV-1 release 10-fold; when
FT associated with D-66.
FT MUTAGEN 15 15 A->D: Reduces HIV-1 release 2-fold.
FT MUTAGEN 66 66 L->D: Reduces HIV-1 release 10-fold; when
FT associated with D-15.
FT MUTAGEN 66 66 L->D: Reduces HIV-1 release 3-fold.
FT MUTAGEN 208 209 WL->AA: Strongly impairs HIV-1 release.
FT MUTAGEN 210 210 G->A: Impairs HIV-1 release.
FT MUTAGEN 235 235 E->Q: Defective in vacuolar protein
FT sorting.
FT MUTAGEN 390 396 Missing: Abolishes interaction with VTA1.
FT CONFLICT 114 114 K -> R (in Ref. 3; AAC39874).
FT CONFLICT 127 127 E -> D (in Ref. 3; AAC39874).
FT CONFLICT 342 342 S -> G (in Ref. 3; AAC39874).
FT TURN 1 3
FT HELIX 6 23
FT HELIX 30 47
FT HELIX 52 55
FT HELIX 56 72
FT TURN 73 75
FT STRAND 87 89
FT STRAND 125 127
FT HELIX 133 135
FT HELIX 140 155
FT HELIX 157 159
FT STRAND 168 178
FT HELIX 180 190
FT STRAND 195 200
FT HELIX 213 225
FT STRAND 227 234
FT TURN 235 237
FT HELIX 238 240
FT STRAND 243 245
FT HELIX 250 263
FT STRAND 265 267
FT STRAND 272 279
FT TURN 281 283
FT HELIX 286 290
FT STRAND 294 297
FT HELIX 303 314
FT HELIX 323 331
FT HELIX 338 349
FT HELIX 351 358
FT STRAND 360 368
FT STRAND 375 383
FT STRAND 386 388
FT STRAND 391 393
FT HELIX 396 398
FT HELIX 401 403
FT HELIX 411 419
FT HELIX 427 438
SQ SEQUENCE 444 AA; 49302 MW; 9D565E4B20AF73FB CRC64;
MSSTSPNLQK AIDLASKAAQ EDKAGNYEEA LQLYQHAVQY FLHVVKYEAQ GDKAKQSIRA
KCTEYLDRAE KLKEYLKNKE KKAQKPVKEG QPSPADEKGN DSDGEGESDD PEKKKLQNQL
QGAIVIERPN VKWSDVAGLE GAKEALKEAV ILPIKFPHLF TGKRTPWRGI LLFGPPGTGK
SYLAKAVATE ANNSTFFSIS SSDLVSKWLG ESEKLVKNLF QLARENKPSI IFIDEIDSLC
GSRSENESEA ARRIKTEFLV QMQGVGVDND GILVLGATNI PWVLDSAIRR RFEKRIYIPL
PEPHARAAMF KLHLGTTQNS LTEADFRELG RKTDGYSGAD ISIIVRDALM QPVRKVQSAT
HFKKVRGPSR ADPNHLVDDL LTPCSPGDPG AIEMTWMDVP GDKLLEPVVS MSDMLRSLSN
TKPTVNEHDL LKLKKFTEDF GQEG
//
MIM
609983
*RECORD*
*FIELD* NO
609983
*FIELD* TI
*609983 VACUOLAR PROTEIN SORTING 4, S. CEREVISIAE, HOMOLOG OF, B; VPS4B
;;SKD1, MOUSE, HOMOLOG OF; SKD1
read more*FIELD* TX
DESCRIPTION
VPS4B belongs to the AAA (ATPases associated with diverse cellular
activities) protein family and is involved in lysosomal/endosomal
membrane trafficking (Beyer et al., 2003).
CLONING
By sequencing cDNAs obtained from umbilical cord blood CD34
(142230)-positive hematopoietic stem/progenitor cells, Mao et al. (1998)
identified VPS4B, a human homolog of mouse Skd1. The deduced protein
contains 444 amino acids.
By searching for ESTs similar to yeast Vps4, followed by screening a
human keratinocyte cell line cDNA library, Scheuring et al. (2001)
cloned VPS4B. The deduced 444-amino acid protein shares 80% amino acid
identity with VPS4A (609982) and 60% identity with yeast Vps4. Northern
blot analysis detected a ubiquitously expressed 3.0-kb transcript.
Using Northern blot analysis, Beyer et al. (2003) found that mouse Vps4a
and Vps4b were variably expressed in all tissues examined. Most tissues
showed a strong bias for one or the other Vps4, but some expressed both
equally.
GENE FUNCTION
Scheuring et al. (2001) found that heterologous expression of human
VPS4B in Vps4-null yeast completely suppressed the temperature-sensitive
growth defect and complemented the vacuolar protein sorting defect.
VPS4B distributed throughout the cytosol of transfected wildtype yeast
and occasionally concentrated in small dots close to vacuoles. An
ATPase-deficient VPS4B with a glu235-to-gln (E235Q) mutation within the
AAA domain induced dominant-negative vacuolar protein sorting defects in
wildtype yeast cells. Two-hybrid experiments suggested that VPS4A and
VPS4B could form heteromeric complexes, and the interaction was stronger
if dominant-negative mutants were involved. Neither protein formed
homomeric complexes.
By yeast 2-hybrid analysis, Fujita et al. (2004) found that mouse Skd1
interacted with mouse Chmp2a (610893). Pull-down assays showed that
Chmp2a interacted with Skd1 in transfected HeLa cells, and the
interaction did not require the N- or C-terminal coiled-coil domains of
Chmp2a. Fujita et al. (2004) noted that expression of an ATPase-negative
Skd1 mutant results in formation of an aberrant membrane compartment
made up of early and late endosomes and lysosomes. They found that
cotransfection of HeLa cells with an N-terminally truncated Chmp2a with
the ATPase-negative Skd1 mutant inhibited formation of the aberrant
membrane compartment, suggesting that the N-terminal coiled-coil portion
of Chmp2a directed membrane association of the mutant Skd1 protein.
Fujita et al. (2004) suggested that CHMP2A may play a role in
associating SKD1 with the ESCRT-III (endosomal sorting complex required
for transport III) complex.
By yeast 2-hybrid analysis and pull-down assays, Fujita et al. (2004)
showed that the C-terminal region of mouse Sbp1 (610902) bound Skd1.
Expression of an ATPase-negative mouse Skd1 mutant in HeLa cells
redirected endogenous SBP1 and SKD1 from the cytosol to an aberrant
endosomal structure derived from early and late endosomes and lysosomes.
In control HeLa cells, SKD1 existed as a monomer and SBP1 formed an
oligomer protein complex. The ATPase-negative Skd1 mutant formed large
heterooligomers with endogenous SBP1 and SKD1 when expressed in HeLa
cells, suggesting that the ATPase activity of SKD1 is required for
disassembly of the SBP1/SKD1 complex.
Lin et al. (2005) found that an ATPase-defective mouse Skd1 mutant bound
to late endosomes and caused ubiquitinated proteins to accumulate when
overexpressed in human embryonic kidney cells. Binding of mutant Skd1 to
membranes was saturable, and Skd1 appeared to associate with the
ESCRT-III proteins SNF7-1 (CHMP4A; 610051) and VPS24 (610052). Mutant
Skd1 also coimmunoprecipitated with SNF7-1 and VPS24.
Stuchell-Brereton et al. (2007) independently showed that the
microtubule interacting and transport (MIT) domains of human VPS4A and
VPS4B bind conserved sequence motifs located at the carboxy termini of
the CHMP1-3 class of ESCRT-III proteins. Structures of VPS4A MIT-CHMP1A
(164010) and VPS4B MIT-CHMP2B (609512) complexes revealed that the
C-terminal CHMP motif forms an amphipathic helix that binds in a groove
between the last 2 helices of the tetratricopeptide-like repeat (TPR) of
the VPS4 MIT domain, but in the opposite orientation to that of a
canonic TPR interaction. Distinct pockets in the MIT domain bound 3
conserved leucine residues of the CHMP motif, and mutations that
inhibited these interactions blocked VPS4 recruitment, impaired
endosomal protein sorting, and relieved dominant-negative VPS4
inhibition of HIV budding. Thus, Stuchell-Brereton et al. (2007)
concluded that their studies revealed how the VPS4 ATPases recognize
their CHMP substrates to facilitate the membrane fission events required
for the release of viruses, endosomal vesicles, and daughter cells.
Feng et al. (2013) showed that hepatitis A virus (HAV) released from
cells is cloaked in host-derived membranes, thereby protecting the
virion from antibody-mediated neutralization. The enveloped viruses
(eHAV) resemble exosomes, small vesicles that are important in
intercellular communications. They are fully infectious, sensitive to
extraction with chloroform, and circulate in the blood of infected
humans. Their biogenesis is dependent on host proteins associated with
endosomal-sorting complexes required for transport, namely VPS4B and
ALIX (608074). Feng et al. (2013) concluded that while the hijacking of
membranes by HAV facilitates escape from neutralizing antibodies and
probably promotes virus spread within the liver, anti-capsid antibodies
restrict replication after infection with eHAV, suggesting a possible
explanation for prophylaxis after exposure.
GENE STRUCTURE
Beyer et al. (2003) determined that the VPS4B gene contains 11 exons and
spans 33.3 kb. The promoter region lacks TATA or CAAT boxes, but it
contains CpG islands.
MAPPING
By radiation hybrid analysis, Mao et al. (1998) mapped the VPS4B gene to
chromosome 18q21.32-q21.33. Using FISH and genomic sequence analysis,
Beyer et al. (2003) mapped the VPS4B gene to chromosome 18q21-q22. They
mapped the mouse Vps4b gene to a region of chromosome 1E3 that shares
homology of synteny with human chromosome 18q21-q22.
*FIELD* RF
1. Beyer, A.; Scheuring, S.; Muller, S.; Mincheva, A.; Lichter, P.;
Kohrer, K.: Comparative sequence and expression analyses of four
mammalian VPS4 genes. Gene 305: 47-59, 2003.
2. Feng, Z.; Hensley, L.; McKnight, K. L.; Hu, F.; Madden, V.; Ping,
L.; Jeong, S.-H.; Walker, C.; Lanford, R. E.; Lemon, S. M.: A pathogenic
picornavirus acquires an envelope by hijacking cellular membranes. Nature 496:
367-371, 2013.
3. Fujita, H.; Umezuki, Y.; Imamura, K.; Ishikawa, D.; Uchimura, S.;
Nara, A.; Yoshimori, T.; Hayashizaki, Y.; Kawai, J.; Ishidoh, K.;
Tanaka, Y.; Himeno, M.: Mammalian class E Vps proteins, SBP1 and
mVps2/CHMP2A, interact with and regulate the function of an AAA-ATPase
SKD1/Vps4B. J. Cell Sci. 117: 2997-3009, 2004.
4. Lin, Y.; Kimpler, L. A.; Naismith, T. V.; Lauer, J. M.; Hanson,
P. I.: Interaction of the mammalian endosomal sorting complex required
for transport (ESCRT) III protein hSnf7-1 with itself, membranes,
and the AAA+ ATPase SKD1. J. Biol. Chem. 280: 12799-12809, 2005.
Note: Erratum: J. Biol. Chem. 281: 38966 only, 2006.
5. Mao, M.; Fu, G.; Wu, J.-S.; Zhang, Q.-H.; Zhou, J.; Kan, L.-X.;
Huang, Q.-H.; He, K.-L.; Gu, B.-W.; Han, Z.-G.; Shen, Y.; Gu, J.;
Yu, Y.-P.; Xu, S.-H.; Wang, Y.-X.; Chen, S.-J.; Chen, Z.: Identification
of genes expressed in human CD34+ hematopoietic stem/progenitor cells
by expressed sequence tags and efficient full-length cDNA cloning. Proc.
Nat. Acad. Sci. 95: 8175-8180, 1998.
6. Scheuring, S.; Rohricht, R. A.; Schoning-Burkhardt, B.; Beyer,
A.; Muller, S.; Abts, H. F.; Kohrer, K.: Mammalian cells express
two VPS4 proteins both of which are involved in intracellular protein
trafficking. J. Molec. Biol. 312: 469-480, 2001.
7. Stuchell-Brereton, M. D.; Skalicky, J. J.; Kieffer, C.; Karren,
M. A.; Ghaffarian, S.; Sundquist, W. I.: ESCRT-III recognition by
VPS4 ATPases. Nature 449: 740-744, 2007.
*FIELD* CN
Ada Hamosh - updated: 5/1/2013
Ada Hamosh - updated: 10/26/2007
Patricia A. Hartz - updated: 3/30/2007
Patricia A. Hartz - updated: 4/10/2006
*FIELD* CD
Patricia A. Hartz: 3/20/2006
*FIELD* ED
alopez: 05/01/2013
alopez: 5/1/2013
terry: 8/22/2012
alopez: 11/2/2007
terry: 10/26/2007
mgross: 3/30/2007
carol: 9/27/2006
mgross: 4/13/2006
terry: 4/10/2006
mgross: 3/20/2006
*RECORD*
*FIELD* NO
609983
*FIELD* TI
*609983 VACUOLAR PROTEIN SORTING 4, S. CEREVISIAE, HOMOLOG OF, B; VPS4B
;;SKD1, MOUSE, HOMOLOG OF; SKD1
read more*FIELD* TX
DESCRIPTION
VPS4B belongs to the AAA (ATPases associated with diverse cellular
activities) protein family and is involved in lysosomal/endosomal
membrane trafficking (Beyer et al., 2003).
CLONING
By sequencing cDNAs obtained from umbilical cord blood CD34
(142230)-positive hematopoietic stem/progenitor cells, Mao et al. (1998)
identified VPS4B, a human homolog of mouse Skd1. The deduced protein
contains 444 amino acids.
By searching for ESTs similar to yeast Vps4, followed by screening a
human keratinocyte cell line cDNA library, Scheuring et al. (2001)
cloned VPS4B. The deduced 444-amino acid protein shares 80% amino acid
identity with VPS4A (609982) and 60% identity with yeast Vps4. Northern
blot analysis detected a ubiquitously expressed 3.0-kb transcript.
Using Northern blot analysis, Beyer et al. (2003) found that mouse Vps4a
and Vps4b were variably expressed in all tissues examined. Most tissues
showed a strong bias for one or the other Vps4, but some expressed both
equally.
GENE FUNCTION
Scheuring et al. (2001) found that heterologous expression of human
VPS4B in Vps4-null yeast completely suppressed the temperature-sensitive
growth defect and complemented the vacuolar protein sorting defect.
VPS4B distributed throughout the cytosol of transfected wildtype yeast
and occasionally concentrated in small dots close to vacuoles. An
ATPase-deficient VPS4B with a glu235-to-gln (E235Q) mutation within the
AAA domain induced dominant-negative vacuolar protein sorting defects in
wildtype yeast cells. Two-hybrid experiments suggested that VPS4A and
VPS4B could form heteromeric complexes, and the interaction was stronger
if dominant-negative mutants were involved. Neither protein formed
homomeric complexes.
By yeast 2-hybrid analysis, Fujita et al. (2004) found that mouse Skd1
interacted with mouse Chmp2a (610893). Pull-down assays showed that
Chmp2a interacted with Skd1 in transfected HeLa cells, and the
interaction did not require the N- or C-terminal coiled-coil domains of
Chmp2a. Fujita et al. (2004) noted that expression of an ATPase-negative
Skd1 mutant results in formation of an aberrant membrane compartment
made up of early and late endosomes and lysosomes. They found that
cotransfection of HeLa cells with an N-terminally truncated Chmp2a with
the ATPase-negative Skd1 mutant inhibited formation of the aberrant
membrane compartment, suggesting that the N-terminal coiled-coil portion
of Chmp2a directed membrane association of the mutant Skd1 protein.
Fujita et al. (2004) suggested that CHMP2A may play a role in
associating SKD1 with the ESCRT-III (endosomal sorting complex required
for transport III) complex.
By yeast 2-hybrid analysis and pull-down assays, Fujita et al. (2004)
showed that the C-terminal region of mouse Sbp1 (610902) bound Skd1.
Expression of an ATPase-negative mouse Skd1 mutant in HeLa cells
redirected endogenous SBP1 and SKD1 from the cytosol to an aberrant
endosomal structure derived from early and late endosomes and lysosomes.
In control HeLa cells, SKD1 existed as a monomer and SBP1 formed an
oligomer protein complex. The ATPase-negative Skd1 mutant formed large
heterooligomers with endogenous SBP1 and SKD1 when expressed in HeLa
cells, suggesting that the ATPase activity of SKD1 is required for
disassembly of the SBP1/SKD1 complex.
Lin et al. (2005) found that an ATPase-defective mouse Skd1 mutant bound
to late endosomes and caused ubiquitinated proteins to accumulate when
overexpressed in human embryonic kidney cells. Binding of mutant Skd1 to
membranes was saturable, and Skd1 appeared to associate with the
ESCRT-III proteins SNF7-1 (CHMP4A; 610051) and VPS24 (610052). Mutant
Skd1 also coimmunoprecipitated with SNF7-1 and VPS24.
Stuchell-Brereton et al. (2007) independently showed that the
microtubule interacting and transport (MIT) domains of human VPS4A and
VPS4B bind conserved sequence motifs located at the carboxy termini of
the CHMP1-3 class of ESCRT-III proteins. Structures of VPS4A MIT-CHMP1A
(164010) and VPS4B MIT-CHMP2B (609512) complexes revealed that the
C-terminal CHMP motif forms an amphipathic helix that binds in a groove
between the last 2 helices of the tetratricopeptide-like repeat (TPR) of
the VPS4 MIT domain, but in the opposite orientation to that of a
canonic TPR interaction. Distinct pockets in the MIT domain bound 3
conserved leucine residues of the CHMP motif, and mutations that
inhibited these interactions blocked VPS4 recruitment, impaired
endosomal protein sorting, and relieved dominant-negative VPS4
inhibition of HIV budding. Thus, Stuchell-Brereton et al. (2007)
concluded that their studies revealed how the VPS4 ATPases recognize
their CHMP substrates to facilitate the membrane fission events required
for the release of viruses, endosomal vesicles, and daughter cells.
Feng et al. (2013) showed that hepatitis A virus (HAV) released from
cells is cloaked in host-derived membranes, thereby protecting the
virion from antibody-mediated neutralization. The enveloped viruses
(eHAV) resemble exosomes, small vesicles that are important in
intercellular communications. They are fully infectious, sensitive to
extraction with chloroform, and circulate in the blood of infected
humans. Their biogenesis is dependent on host proteins associated with
endosomal-sorting complexes required for transport, namely VPS4B and
ALIX (608074). Feng et al. (2013) concluded that while the hijacking of
membranes by HAV facilitates escape from neutralizing antibodies and
probably promotes virus spread within the liver, anti-capsid antibodies
restrict replication after infection with eHAV, suggesting a possible
explanation for prophylaxis after exposure.
GENE STRUCTURE
Beyer et al. (2003) determined that the VPS4B gene contains 11 exons and
spans 33.3 kb. The promoter region lacks TATA or CAAT boxes, but it
contains CpG islands.
MAPPING
By radiation hybrid analysis, Mao et al. (1998) mapped the VPS4B gene to
chromosome 18q21.32-q21.33. Using FISH and genomic sequence analysis,
Beyer et al. (2003) mapped the VPS4B gene to chromosome 18q21-q22. They
mapped the mouse Vps4b gene to a region of chromosome 1E3 that shares
homology of synteny with human chromosome 18q21-q22.
*FIELD* RF
1. Beyer, A.; Scheuring, S.; Muller, S.; Mincheva, A.; Lichter, P.;
Kohrer, K.: Comparative sequence and expression analyses of four
mammalian VPS4 genes. Gene 305: 47-59, 2003.
2. Feng, Z.; Hensley, L.; McKnight, K. L.; Hu, F.; Madden, V.; Ping,
L.; Jeong, S.-H.; Walker, C.; Lanford, R. E.; Lemon, S. M.: A pathogenic
picornavirus acquires an envelope by hijacking cellular membranes. Nature 496:
367-371, 2013.
3. Fujita, H.; Umezuki, Y.; Imamura, K.; Ishikawa, D.; Uchimura, S.;
Nara, A.; Yoshimori, T.; Hayashizaki, Y.; Kawai, J.; Ishidoh, K.;
Tanaka, Y.; Himeno, M.: Mammalian class E Vps proteins, SBP1 and
mVps2/CHMP2A, interact with and regulate the function of an AAA-ATPase
SKD1/Vps4B. J. Cell Sci. 117: 2997-3009, 2004.
4. Lin, Y.; Kimpler, L. A.; Naismith, T. V.; Lauer, J. M.; Hanson,
P. I.: Interaction of the mammalian endosomal sorting complex required
for transport (ESCRT) III protein hSnf7-1 with itself, membranes,
and the AAA+ ATPase SKD1. J. Biol. Chem. 280: 12799-12809, 2005.
Note: Erratum: J. Biol. Chem. 281: 38966 only, 2006.
5. Mao, M.; Fu, G.; Wu, J.-S.; Zhang, Q.-H.; Zhou, J.; Kan, L.-X.;
Huang, Q.-H.; He, K.-L.; Gu, B.-W.; Han, Z.-G.; Shen, Y.; Gu, J.;
Yu, Y.-P.; Xu, S.-H.; Wang, Y.-X.; Chen, S.-J.; Chen, Z.: Identification
of genes expressed in human CD34+ hematopoietic stem/progenitor cells
by expressed sequence tags and efficient full-length cDNA cloning. Proc.
Nat. Acad. Sci. 95: 8175-8180, 1998.
6. Scheuring, S.; Rohricht, R. A.; Schoning-Burkhardt, B.; Beyer,
A.; Muller, S.; Abts, H. F.; Kohrer, K.: Mammalian cells express
two VPS4 proteins both of which are involved in intracellular protein
trafficking. J. Molec. Biol. 312: 469-480, 2001.
7. Stuchell-Brereton, M. D.; Skalicky, J. J.; Kieffer, C.; Karren,
M. A.; Ghaffarian, S.; Sundquist, W. I.: ESCRT-III recognition by
VPS4 ATPases. Nature 449: 740-744, 2007.
*FIELD* CN
Ada Hamosh - updated: 5/1/2013
Ada Hamosh - updated: 10/26/2007
Patricia A. Hartz - updated: 3/30/2007
Patricia A. Hartz - updated: 4/10/2006
*FIELD* CD
Patricia A. Hartz: 3/20/2006
*FIELD* ED
alopez: 05/01/2013
alopez: 5/1/2013
terry: 8/22/2012
alopez: 11/2/2007
terry: 10/26/2007
mgross: 3/30/2007
carol: 9/27/2006
mgross: 4/13/2006
terry: 4/10/2006
mgross: 3/20/2006