VPS4A_MOUSE
ID VPS4A_MOUSE Reviewed; 437 AA.
AC Q8VEJ9; Q3TXT2;
DT 12-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 1.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=Vacuolar protein sorting-associated protein 4A {ECO:0000305};
DE EC=3.6.4.6 {ECO:0000250|UniProtKB:O75351};
GN Name=Vps4a {ECO:0000312|MGI:MGI:1890520};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1] {ECO:0000305, ECO:0000312|EMBL:AAM94861.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, MUTAGENESIS OF GLU-228, AND INTERACTION WITH VPS4B.
RC STRAIN=129/SvEvTacfBr {ECO:0000312|EMBL:AAM94861.1};
RC TISSUE=Spleen {ECO:0000312|EMBL:AAM94861.1};
RX PubMed=12594041; DOI=10.1016/s0378-1119(02)01205-2;
RA Beyer A., Scheuring S., Mueller S., Mincheva A., Lichter P., Koehrer K.;
RT "Comparative sequence and expression analyses of four mammalian VPS4
RT genes.";
RL Gene 305:47-59(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Head;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3] {ECO:0000312|EMBL:AAH18368.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N {ECO:0000312|EMBL:AAH18368.1};
RC TISSUE=Mammary gland {ECO:0000312|EMBL:AAH18368.1};
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Heart, Kidney, Lung, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Involved in late steps of the endosomal multivesicular bodies
CC (MVB) pathway. Recognizes membrane-associated ESCRT-III assemblies and
CC catalyzes their disassembly, possibly in combination with membrane
CC fission. Redistributes the ESCRT-III components to the cytoplasm for
CC further rounds of MVB sorting. MVBs contain intraluminal vesicles
CC (ILVs) that are generated by invagination and scission from the
CC limiting membrane of the endosome and mostly are delivered to lysosomes
CC enabling degradation of membrane proteins, such as stimulated growth
CC factor receptors, lysosomal enzymes and lipids. It is required for
CC proper accomplishment of various processes including the regulation of
CC endosome size, primary cilium organization, mitotic spindle
CC organization and chromosome segregation, and nuclear envelope sealing
CC and spindle disassembly during anaphase (By similarity). In conjunction
CC with the ESCRT machinery also appears to function in topologically
CC equivalent membrane fission events, such as the terminal stages of
CC cytokinesis. Involved in cytokinesis: retained at the midbody by
CC ZFYVE19/ANCHR and CHMP4C until abscission checkpoint signaling is
CC terminated at late cytokinesis. It is then released following
CC dephosphorylation of CHMP4C, leading to abscission. VPS4A/B are
CC required for the exosomal release of SDCBP, CD63 and syndecan (By
CC similarity). Critical for normal erythroblast cytokinesis and correct
CC erythropoiesis (By similarity). {ECO:0000250|UniProtKB:Q9UN37}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.6;
CC Evidence={ECO:0000250|UniProtKB:O75351};
CC -!- SUBUNIT: Proposed to be monomeric or homodimeric in nucleotide-free
CC form and to oligomerize upon binding to ATP to form two stacked
CC hexameric or heptameric rings with a central pore through which ESCRT-
CC III substrates are translocated in an ATP-dependent manner (By
CC similarity). Interacts with CHMP1A, CHMP1B, CHMP2A, CHMP2B, CHMP3,
CC CHMP4A, CHMP4B, CHMP4C and CHMP6. Interacts with VPS4B; the interaction
CC suggests a heteromeric assembly with VPS4B. Interacts with SPAST.
CC Interacts with IST1. Interacts with ZFYVE19/ANCHR; leading to retain it
CC at midbody (By similarity). {ECO:0000250,
CC ECO:0000250|UniProtKB:Q9UN37}.
CC -!- SUBCELLULAR LOCATION: Late endosome membrane
CC {ECO:0000269|PubMed:12594041}; Peripheral membrane protein
CC {ECO:0000305|PubMed:12594041}. Midbody {ECO:0000250|UniProtKB:Q9UN37}.
CC Cytoplasm, cytoskeleton, spindle {ECO:0000250|UniProtKB:Q9UN37}.
CC Note=Membrane-associated in the prevacuolar endosomal compartment.
CC Localizes to the midbody of dividing cells, interaction with
CC ZFYVE19/ANCHR mediates retention at midbody. Localized in two distinct
CC rings on either side of the Flemming body (By similarity).
CC {ECO:0000250|UniProtKB:Q9UN37}.
CC -!- TISSUE SPECIFICITY: Highly expressed in testis and moderately in heart
CC and brain. Not detected in spleen, lung, liver, skeletal muscle or
CC kidney. {ECO:0000269|PubMed:12594041}.
CC -!- DOMAIN: The MIT domain serves as an adapter for ESCRT-III proteins. It
CC forms an asymmetric three-helix bundle that binds amphipathic MIM (MIT
CC interacting motif) helices along the groove between MIT helices 2 and 3
CC present in a subset of ESCRT-III proteins thus establishing the
CC canonical MIM-MIT interaction. In an extended conformation along the
CC groove between helices 1 and 3, also binds to a type-2 MIT interacting
CC motif (MIM2) (By similarity). {ECO:0000250|UniProtKB:O75351}.
CC -!- SIMILARITY: Belongs to the AAA ATPase family. {ECO:0000255}.
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DR EMBL; AF530161; AAM94861.1; -; Genomic_DNA.
DR EMBL; AK047821; BAC33165.1; -; mRNA.
DR EMBL; AK159117; BAE34833.1; -; mRNA.
DR EMBL; BC018368; AAH18368.1; -; mRNA.
DR CCDS; CCDS40463.1; -.
DR RefSeq; NP_569053.1; NM_126165.1.
DR AlphaFoldDB; Q8VEJ9; -.
DR BMRB; Q8VEJ9; -.
DR SMR; Q8VEJ9; -.
DR BioGRID; 227970; 2.
DR ComplexPortal; CPX-340; VPS4A/B complex.
DR IntAct; Q8VEJ9; 1.
DR MINT; Q8VEJ9; -.
DR STRING; 10090.ENSMUSP00000034388; -.
DR iPTMnet; Q8VEJ9; -.
DR PhosphoSitePlus; Q8VEJ9; -.
DR EPD; Q8VEJ9; -.
DR jPOST; Q8VEJ9; -.
DR MaxQB; Q8VEJ9; -.
DR PaxDb; Q8VEJ9; -.
DR PRIDE; Q8VEJ9; -.
DR ProteomicsDB; 297585; -.
DR DNASU; 116733; -.
DR Ensembl; ENSMUST00000034388; ENSMUSP00000034388; ENSMUSG00000031913.
DR GeneID; 116733; -.
DR KEGG; mmu:116733; -.
DR UCSC; uc009ngv.1; mouse.
DR CTD; 27183; -.
DR MGI; MGI:1890520; Vps4a.
DR VEuPathDB; HostDB:ENSMUSG00000031913; -.
DR eggNOG; KOG0739; Eukaryota.
DR GeneTree; ENSGT00940000157319; -.
DR HOGENOM; CLU_000688_21_2_1; -.
DR InParanoid; Q8VEJ9; -.
DR OMA; MFELNVG; -.
DR OrthoDB; 787710at2759; -.
DR PhylomeDB; Q8VEJ9; -.
DR TreeFam; TF105012; -.
DR Reactome; R-MMU-917729; Endosomal Sorting Complex Required For Transport (ESCRT).
DR Reactome; R-MMU-9668328; Sealing of the nuclear envelope (NE) by ESCRT-III.
DR BioGRID-ORCS; 116733; 1 hit in 74 CRISPR screens.
DR ChiTaRS; Vps4a; mouse.
DR PRO; PR:Q8VEJ9; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; Q8VEJ9; protein.
DR Bgee; ENSMUSG00000031913; Expressed in spermatid and 254 other tissues.
DR Genevisible; Q8VEJ9; MM.
DR GO; GO:1904949; C:ATPase complex; IC:ComplexPortal.
DR GO; GO:0005813; C:centrosome; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005769; C:early endosome; ISO:MGI.
DR GO; GO:0005768; C:endosome; ISO:MGI.
DR GO; GO:0010008; C:endosome membrane; ISO:MGI.
DR GO; GO:0090543; C:Flemming body; ISO:MGI.
DR GO; GO:0005770; C:late endosome; ISO:MGI.
DR GO; GO:0031902; C:late endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005764; C:lysosome; ISO:MGI.
DR GO; GO:0030496; C:midbody; ISS:UniProtKB.
DR GO; GO:0005643; C:nuclear pore; IC:ComplexPortal.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0000922; C:spindle pole; ISO:MGI.
DR GO; GO:0005774; C:vacuolar membrane; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; ISO:MGI.
DR GO; GO:0016887; F:ATP hydrolysis activity; ISO:MGI.
DR GO; GO:0008022; F:protein C-terminus binding; ISO:MGI.
DR GO; GO:0019904; F:protein domain specific binding; ISO:MGI.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0031267; F:small GTPase binding; ISO:MGI.
DR GO; GO:0009838; P:abscission; ISS:UniProtKB.
DR GO; GO:0097352; P:autophagosome maturation; IC:ComplexPortal.
DR GO; GO:0006914; P:autophagy; IC:ComplexPortal.
DR GO; GO:0051301; P:cell division; ISO:MGI.
DR GO; GO:0016197; P:endosomal transport; ISO:MGI.
DR GO; GO:0034058; P:endosomal vesicle fusion; ISO:MGI.
DR GO; GO:0032367; P:intracellular cholesterol transport; ISO:MGI.
DR GO; GO:0061738; P:late endosomal microautophagy; IMP:ParkinsonsUK-UCL.
DR GO; GO:0061764; P:late endosome to lysosome transport via multivesicular body sorting pathway; IC:ComplexPortal.
DR GO; GO:0090148; P:membrane fission; IC:ComplexPortal.
DR GO; GO:0061952; P:midbody abscission; ISO:MGI.
DR GO; GO:0044878; P:mitotic cytokinesis checkpoint signaling; ISS:UniProtKB.
DR GO; GO:0007080; P:mitotic metaphase plate congression; ISO:MGI.
DR GO; GO:0036258; P:multivesicular body assembly; IMP:ParkinsonsUK-UCL.
DR GO; GO:0071985; P:multivesicular body sorting pathway; IC:ComplexPortal.
DR GO; GO:0060548; P:negative regulation of cell death; IC:ComplexPortal.
DR GO; GO:0032466; P:negative regulation of cytokinesis; ISS:UniProtKB.
DR GO; GO:0031468; P:nuclear membrane reassembly; IC:ComplexPortal.
DR GO; GO:0006997; P:nucleus organization; ISO:MGI.
DR GO; GO:0001778; P:plasma membrane repair; IC:ComplexPortal.
DR GO; GO:1903543; P:positive regulation of exosomal secretion; ISO:MGI.
DR GO; GO:1903774; P:positive regulation of viral budding via host ESCRT complex; ISO:MGI.
DR GO; GO:0006622; P:protein targeting to lysosome; ISO:MGI.
DR GO; GO:0032880; P:regulation of protein localization; ISO:MGI.
DR GO; GO:1903076; P:regulation of protein localization to plasma membrane; ISO:MGI.
DR GO; GO:0043162; P:ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway; ISO:MGI.
DR GO; GO:0090611; P:ubiquitin-independent protein catabolic process via the multivesicular body sorting pathway; ISO:MGI.
DR GO; GO:0007033; P:vacuole organization; IBA:GO_Central.
DR GO; GO:0006900; P:vesicle budding from membrane; ISO:MGI.
DR GO; GO:0072319; P:vesicle uncoating; ISO:MGI.
DR GO; GO:0016192; P:vesicle-mediated transport; ISS:UniProtKB.
DR GO; GO:0046761; P:viral budding from plasma membrane; IMP:UniProtKB.
DR GO; GO:0039702; P:viral budding via host ESCRT complex; ISO:MGI.
DR GO; GO:0019076; P:viral release from host cell; ISO:MGI.
DR CDD; cd02678; MIT_VPS4; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR003593; AAA+_ATPase.
DR InterPro; IPR041569; AAA_lid_3.
DR InterPro; IPR003959; ATPase_AAA_core.
DR InterPro; IPR003960; ATPase_AAA_CS.
DR InterPro; IPR007330; MIT_dom.
DR InterPro; IPR036181; MIT_dom_sf.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR031255; VPS4.
DR InterPro; IPR015415; Vps4_C.
DR InterPro; IPR045253; VPS4_MIT.
DR PANTHER; PTHR23074:SF72; PTHR23074:SF72; 1.
DR Pfam; PF00004; AAA; 1.
DR Pfam; PF17862; AAA_lid_3; 1.
DR Pfam; PF04212; MIT; 1.
DR Pfam; PF09336; Vps4_C; 1.
DR SMART; SM00382; AAA; 1.
DR SMART; SM00745; MIT; 1.
DR SUPFAM; SSF116846; SSF116846; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS00674; AAA; 1.
PE 1: Evidence at protein level;
KW Acetylation; ATP-binding; Cell cycle; Cell division; Coiled coil;
KW Cytoplasm; Cytoskeleton; Endosome; Hydrolase; Membrane; Nucleotide-binding;
KW Phosphoprotein; Protein transport; Reference proteome; Transport.
FT CHAIN 1..437
FT /note="Vacuolar protein sorting-associated protein 4A"
FT /id="PRO_0000084766"
FT DOMAIN 2..80
FT /note="MIT"
FT REGION 75..106
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 15..37
FT /evidence="ECO:0000255"
FT BINDING 167..174
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000305"
FT MOD_RES 8
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9UN37"
FT MOD_RES 95
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q793F9"
FT MOD_RES 97
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q793F9"
FT MUTAGEN 228
FT /note="E->Q: Perinuclear localization."
FT /evidence="ECO:0000269|PubMed:12594041"
SQ SEQUENCE 437 AA; 48907 MW; B67CF13F7AFD9129 CRC64;
MTTSTLQKAI DLVTKATEED KAKNYEEALR LYQHAVEYFL HAIKYEAHSD KAKESIRAKC
MQYLDRAEKL KDYLRNKEKH GKKPVKENQS EGKGSDSDSE GDNPEKKKLQ EQLMGAVVME
KPNIRWNDVA GLEGAKEALK EAVILPIKFP HLFTGKRTPW RGILLFGPPG TGKSYLAKAV
ATEANNSTFF SVSSSDLMSK WLGESEKLVK NLFELARQHK PSIIFIDEVD SLCGSRNENE
SEAARRIKTE FLVQMQGVGN NNDGTLVLGA TNIPWVLDSA IRRRFEKRIY IPLPEEAARA
QMFRLHLGST PHNLTDANIH ELARKTEGYS GADISIIVRD SLMQPVRKVQ SATHFKKVCG
PSRTNPSVMI DDLLTPCSPG DPGAIEMTWM DVPGDKLLEP VVCMSDMLRS LATTRPTVNA
DDLLKVKKFS EDFGQES
