VPS18_MOUSE
ID VPS18_MOUSE Reviewed; 973 AA.
AC Q8R307; Q8BGV6; Q8BZX6; Q8C126;
DT 19-SEP-2002, integrated into UniProtKB/Swiss-Prot.
DT 07-JUN-2004, sequence version 2.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=Vacuolar protein sorting-associated protein 18 homolog;
GN Name=Vps18;
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]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Skin, Testis, and Vagina;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Kidney, and Mammary tumor;
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 [3]
RP FUNCTION.
RX PubMed=14517315; DOI=10.1091/mbc.e03-01-0040;
RA Poupon V., Stewart A., Gray S.R., Piper R.C., Luzio J.P.;
RT "The role of mVps18p in clustering, fusion, and intracellular localization
RT of late endocytic organelles.";
RL Mol. Biol. Cell 14:4015-4027(2003).
RN [4]
RP INTERACTION WITH HOOK1.
RX PubMed=14668490; DOI=10.1091/mbc.e03-06-0358;
RA Richardson S.C.W., Winistorfer S.C., Poupon V., Luzio J.P., Piper R.C.;
RT "Mammalian late vacuole protein sorting orthologues participate in early
RT endosomal fusion and interact with the cytoskeleton.";
RL Mol. Biol. Cell 15:1197-1210(2004).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Spleen, and
RC 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).
RN [6]
RP SUBUNIT.
RX PubMed=21411634; DOI=10.1091/mbc.e10-10-0799;
RA Zlatic S.A., Tornieri K., L'Hernault S.W., Faundez V.;
RT "Clathrin-dependent mechanisms modulate the subcellular distribution of
RT class C Vps/HOPS tether subunits in polarized and nonpolarized cells.";
RL Mol. Biol. Cell 22:1699-1715(2011).
RN [7]
RP FUNCTION.
RX PubMed=22699122; DOI=10.1016/j.bbrc.2012.06.021;
RA Peng C., Yan S., Ye J., Shen L., Xu T., Tao W.;
RT "Vps18 deficiency inhibits dendritogenesis in Purkinje cells by blocking
RT the lysosomal degradation of Lysyl Oxidase.";
RL Biochem. Biophys. Res. Commun. 423:715-720(2012).
RN [8]
RP FUNCTION.
RX PubMed=22854957; DOI=10.1074/jbc.m112.384305;
RA Peng C., Ye J., Yan S., Kong S., Shen Y., Li C., Li Q., Zheng Y., Deng K.,
RA Xu T., Tao W.;
RT "Ablation of vacuole protein sorting 18 (Vps18) gene leads to
RT neurodegeneration and impaired neuronal migration by disrupting multiple
RT vesicle transport pathways to lysosomes.";
RL J. Biol. Chem. 287:32861-32873(2012).
RN [9]
RP SUBUNIT, AND INTERACTION WITH RAB5C.
RX PubMed=25266290; DOI=10.1111/tra.12232;
RA Perini E.D., Schaefer R., Stoeter M., Kalaidzidis Y., Zerial M.;
RT "Mammalian CORVET is required for fusion and conversion of distinct early
RT endosome subpopulations.";
RL Traffic 15:1366-1389(2014).
CC -!- FUNCTION: Plays a role in vesicle-mediated protein trafficking to
CC lysosomal compartments including the endocytic membrane transport and
CC autophagic pathways. Believed to act as a core component of the
CC putative HOPS and CORVET endosomal tethering complexes which are
CC proposed to be involved in the Rab5-to-Rab7 endosome conversion
CC probably implicating MON1A/B, and via binding SNAREs and SNARE
CC complexes to mediate tethering and docking events during SNARE-mediated
CC membrane fusion. The HOPS complex is proposed to be recruited to Rab7
CC on the late endosomal membrane and to regulate late endocytic,
CC phagocytic and autophagic traffic towards lysosomes. The CORVET complex
CC is proposed to function as a Rab5 effector to mediate early endosome
CC fusion probably in specific endosome subpopulations (By similarity).
CC Required for fusion of endosomes and autophagosomes with lysosomes
CC (PubMed:14517315, PubMed:22854957). Involved in dendrite development of
CC Pukinje cells (PubMed:22699122). {ECO:0000250|UniProtKB:Q9P253,
CC ECO:0000269|PubMed:14517315, ECO:0000269|PubMed:22699122,
CC ECO:0000269|PubMed:22854957}.
CC -!- SUBUNIT: Core component of at least two putative endosomal tethering
CC complexes, the homotypic fusion and vacuole protein sorting (HOPS)
CC complex and the class C core vacuole/endosome tethering (CORVET)
CC complex. Their common core is composed of the class C Vps proteins
CC VPS11, VPS16, VPS18 and VPS33A, which in HOPS further associates with
CC VPS39 and VPS41 and in CORVET with VPS8 and TGFBRAP1. Interacts with
CC RAB5C (PubMed:25266290). Interacts with HOOK1 (PubMed:14668490).
CC Interacts with STX7, MON1B (By similarity). Associates with adaptor
CC protein complex 3 (AP-3) and clathrin:AP-3 complexes (PubMed:21411634).
CC Interacts with SYNPO2 (By similarity). Interacts with PLEKHM1 (By
CC similarity). {ECO:0000250|UniProtKB:Q9P253,
CC ECO:0000269|PubMed:14668490, ECO:0000269|PubMed:21411634,
CC ECO:0000269|PubMed:25266290}.
CC -!- INTERACTION:
CC Q8R307; Q9H9C1: VIPAS39; Xeno; NbExp=5; IntAct=EBI-2527788, EBI-749080;
CC -!- SUBCELLULAR LOCATION: Late endosome membrane
CC {ECO:0000250|UniProtKB:Q9P253}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q9P253}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:Q9P253}. Lysosome membrane
CC {ECO:0000250|UniProtKB:Q9P253}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q9P253}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:Q9P253}. Early endosome
CC {ECO:0000250|UniProtKB:Q9P253}. Cytoplasmic vesicle, autophagosome
CC {ECO:0000305}. Cytoplasmic vesicle, clathrin-coated vesicle
CC {ECO:0000305}. Note=Cytoplasmic, peripheral membrane protein associated
CC with early endosomes and late endosomes/lysosomes.
CC -!- SIMILARITY: Belongs to the VPS18 family. {ECO:0000305}.
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DR EMBL; AK029109; BAC26302.1; -; mRNA.
DR EMBL; AK033333; BAC28236.1; -; mRNA.
DR EMBL; AK036915; BAC29637.1; -; mRNA.
DR EMBL; BC026870; AAH26870.1; -; mRNA.
DR EMBL; BC036129; AAH36129.1; -; mRNA.
DR EMBL; BC039176; AAH39176.1; -; mRNA.
DR CCDS; CCDS16599.1; -.
DR RefSeq; NP_758473.3; NM_172269.3.
DR AlphaFoldDB; Q8R307; -.
DR BioGRID; 230740; 19.
DR IntAct; Q8R307; 5.
DR MINT; Q8R307; -.
DR STRING; 10090.ENSMUSP00000036915; -.
DR iPTMnet; Q8R307; -.
DR PhosphoSitePlus; Q8R307; -.
DR EPD; Q8R307; -.
DR MaxQB; Q8R307; -.
DR PaxDb; Q8R307; -.
DR PeptideAtlas; Q8R307; -.
DR PRIDE; Q8R307; -.
DR ProteomicsDB; 297582; -.
DR Antibodypedia; 23197; 160 antibodies from 23 providers.
DR DNASU; 228545; -.
DR Ensembl; ENSMUST00000037280; ENSMUSP00000036915; ENSMUSG00000034216.
DR GeneID; 228545; -.
DR KEGG; mmu:228545; -.
DR UCSC; uc008lto.2; mouse.
DR CTD; 57617; -.
DR MGI; MGI:2443626; Vps18.
DR VEuPathDB; HostDB:ENSMUSG00000034216; -.
DR eggNOG; KOG2034; Eukaryota.
DR GeneTree; ENSGT00940000153635; -.
DR HOGENOM; CLU_003488_1_0_1; -.
DR InParanoid; Q8R307; -.
DR OMA; HVQRESR; -.
DR OrthoDB; 87842at2759; -.
DR PhylomeDB; Q8R307; -.
DR TreeFam; TF105704; -.
DR BioGRID-ORCS; 228545; 23 hits in 75 CRISPR screens.
DR ChiTaRS; Vps18; mouse.
DR PRO; PR:Q8R307; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q8R307; protein.
DR Bgee; ENSMUSG00000034216; Expressed in ankle joint and 175 other tissues.
DR Genevisible; Q8R307; MM.
DR GO; GO:0005884; C:actin filament; IDA:MGI.
DR GO; GO:0005776; C:autophagosome; IEA:UniProtKB-SubCell.
DR GO; GO:0030136; C:clathrin-coated vesicle; IEA:UniProtKB-SubCell.
DR GO; GO:0033263; C:CORVET complex; IDA:UniProtKB.
DR GO; GO:0005769; C:early endosome; IDA:MGI.
DR GO; GO:0005768; C:endosome; IBA:GO_Central.
DR GO; GO:0098978; C:glutamatergic synapse; ISO:MGI.
DR GO; GO:0030897; C:HOPS complex; 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:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005764; C:lysosome; ISO:MGI.
DR GO; GO:0098793; C:presynapse; ISO:MGI.
DR GO; GO:0003779; F:actin binding; IDA:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0030674; F:protein-macromolecule adaptor activity; IBA:GO_Central.
DR GO; GO:0019905; F:syntaxin binding; ISO:MGI.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; ISO:MGI.
DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW.
DR GO; GO:0007032; P:endosome organization; IDA:MGI.
DR GO; GO:0008333; P:endosome to lysosome transport; ISO:MGI.
DR GO; GO:0006886; P:intracellular protein transport; IEA:InterPro.
DR GO; GO:0007040; P:lysosome organization; ISO:MGI.
DR GO; GO:0033147; P:negative regulation of intracellular estrogen receptor signaling pathway; ISO:MGI.
DR GO; GO:0048284; P:organelle fusion; IBA:GO_Central.
DR GO; GO:0016567; P:protein ubiquitination; ISO:MGI.
DR GO; GO:2000300; P:regulation of synaptic vesicle exocytosis; ISO:MGI.
DR GO; GO:0007033; P:vacuole organization; IBA:GO_Central.
DR GO; GO:0006904; P:vesicle docking involved in exocytosis; IBA:GO_Central.
DR GO; GO:0046718; P:viral entry into host cell; IMP:MGI.
DR InterPro; IPR000547; Clathrin_H-chain/VPS_repeat.
DR InterPro; IPR007810; Pep3_Vps18.
DR Pfam; PF00637; Clathrin; 1.
DR Pfam; PF05131; Pep3_Vps18; 1.
DR PROSITE; PS50236; CHCR; 1.
PE 1: Evidence at protein level;
KW Acetylation; Autophagy; Coiled coil; Cytoplasmic vesicle; Endosome;
KW Lysosome; Membrane; Metal-binding; Phosphoprotein; Protein transport;
KW Reference proteome; Transport; Zinc; Zinc-finger.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q9P253"
FT CHAIN 2..973
FT /note="Vacuolar protein sorting-associated protein 18
FT homolog"
FT /id="PRO_0000055907"
FT REPEAT 618..772
FT /note="CHCR"
FT ZN_FING 853..947
FT /note="RING-type"
FT COILED 454..481
FT /evidence="ECO:0000255"
FT COILED 802..848
FT /evidence="ECO:0000255"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:Q9P253"
FT MOD_RES 3
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9P253"
FT MOD_RES 11
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9P253"
FT MOD_RES 13
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9P253"
FT MOD_RES 362
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9P253"
FT MOD_RES 689
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9P253"
FT MOD_RES 912
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9P253"
FT CONFLICT 676
FT /note="P -> T (in Ref. 1; BAC28236)"
FT /evidence="ECO:0000305"
FT CONFLICT 943
FT /note="E -> G (in Ref. 1; BAC26302)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 973 AA; 110219 MW; 6B4E90FC39DC897F CRC64;
MASILDEYED SLSRSAVLQT GCPSVGIPHS GYVSAHLEKE VPIFTKQRVD FTPSERITSL
VVSCNQLCMS LGKDTLLRID LGKASEPNRV ELGRKDDAKV HKMFLDHTGS HLLVALSSTE
VLYMNRNGQK ARPLARWKGQ LVESVGWNKA MGNESSTGPI LVGTAQGQIF EAELSASEGG
LFGPAPDLYF RPLYVLNEEG GPAPVCSLEA ERGPDGRGFV IATTRQRLFQ FIGRAVEDTE
AQGFAGLFAA YTDHPPPFRE FPSNLGYSEL AFYTPKLRSA PRAFAWMMGD GVLYGSLDCG
RPDSLLSEER VWEYPAGVGP GANPPLAIVL TQFHFLLLLA DRVEAVCTLT GQVVLRDHFL
EKFGPLRHMV KDSSTGHLWA YTERAVFRYH VQREARDVWR TYLDMNRFDL AKEYCRERPD
CLDTVLAREA DFCFRQHRYL ESARCYALTQ SYFEEIALKF LEARQEEALA EFLQRKLAGL
KPTERTQATL LTTWLTELYL SRLGALQGDP DALTLYRDTR ECFRTFLSSP RHKEWLFASR
ASIHELLASH GDTEHMVYFA VIMQDYERVV AYHCQHEAYE EALAVLARHR DPQLFYKFSP
ILIRHIPRQL VDAWIEMGSR LDARQLIPAL VNYSQGGEAQ QVSQAIRYME FCVNVLGETE
QAIHNYLLSL YARGQPASLL AYLEQAGASP HRVHYDLKYA LRLCAEHGHH RACVHVYKVL
ELYEEAVDLA LQVDVDLAKQ CADLPEEDEE LRKKLWLKIA RHVVQEEEDV QTAMACLASC
PLLKIEDVLP FFPDFVTIDH FKEAICSSLK AYNHHIQELQ REMEEATASA QRIRRDLQEL
RGRYGTVEPQ DKCSTCDFPL LNRPFYLFLC GHMFHADCLL QAVRPGLPAY KQARLEELQR
KLGAAPPPTK GSVKAKEAEA GAAAVGPSRE QLKADLDELV AAECVYCGEL MIRSIDRPFI
DPQRYEEEHL SWL
