VPS16_MOUSE
ID VPS16_MOUSE Reviewed; 839 AA.
AC Q920Q4; A2BI91; Q8R3C3; Q99KZ4;
DT 19-SEP-2002, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 3.
DT 25-MAY-2022, entry version 138.
DE RecName: Full=Vacuolar protein sorting-associated protein 16 homolog;
DE Short=mVPS16;
GN Name=Vps16;
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 [MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RA Akazawa C., Kim B.Y., Helmut K.;
RT "Cloning of mouse Vps16.";
RL Submitted (MAR-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=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 [4]
RP NITRATION [LARGE SCALE ANALYSIS] AT TYR-4, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=16800626; DOI=10.1021/bi060474w;
RA Sacksteder C.A., Qian W.-J., Knyushko T.V., Wang H., Chin M.H., Lacan G.,
RA Melega W.P., Camp D.G. II, Smith R.D., Smith D.J., Squier T.C.,
RA Bigelow D.J.;
RT "Endogenously nitrated proteins in mouse brain: links to neurodegenerative
RT disease.";
RL Biochemistry 45:8009-8022(2006).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Kidney, Liver, Lung, Pancreas, 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).
RN [6]
RP INTERACTION WITH AP-3 COMPLEX AND CLATHRIN, AND SUBCELLULAR LOCATION.
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 INTERACTION WITH RAB5C, AND SUBUNIT.
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).
RN [8]
RP MUTAGENESIS OF ASN-52.
RX PubMed=27174565; DOI=10.1038/srep25834;
RA Cai X., Chen X., Wu S., Liu W., Zhang X., Zhang D., He S., Wang B.,
RA Zhang M., Zhang Y., Li Z., Luo K., Cai Z., Li W.;
RT "Homozygous mutation of VPS16 gene is responsible for an autosomal
RT recessive adolescent-onset primary dystonia.";
RL Sci. Rep. 6:25834-25834(2016).
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. Required for
CC recruitment of VPS33A to the HOPS complex. Required for fusion of
CC endosomes and autophagosomes with lysosomes; the function is dependent
CC on its association with VPS33A but not VPS33B. The function in
CC autophagosome-lysosome fusion implicates STX17 but not UVRAG.
CC {ECO:0000250|UniProtKB:Q9H269}.
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 (PubMed:25266290).
CC Interacts with RAB5C (PubMed:25266290). Interacts with STX17, MON1B (By
CC similarity). Associates with adapter protein complex 3 (AP-3) and
CC clathrin:AP-3 complexes (PubMed:21411634).
CC {ECO:0000250|UniProtKB:Q9H269, ECO:0000269|PubMed:21411634,
CC ECO:0000269|PubMed:25266290, ECO:0000305|PubMed:25266290}.
CC -!- INTERACTION:
CC Q920Q4; Q9H9C1: VIPAS39; Xeno; NbExp=4; IntAct=EBI-775797, EBI-749080;
CC -!- SUBCELLULAR LOCATION: Late endosome membrane
CC {ECO:0000250|UniProtKB:Q9H269}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q9H269}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:Q9H269}. Lysosome membrane
CC {ECO:0000250|UniProtKB:Q9H269}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q9H269}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:Q9H269}. Early endosome
CC {ECO:0000250|UniProtKB:Q9H269, ECO:0000269|PubMed:21411634}.
CC Cytoplasmic vesicle, clathrin-coated vesicle
CC {ECO:0000269|PubMed:21411634}. Cytoplasmic vesicle, autophagosome
CC {ECO:0000250|UniProtKB:Q9H269}. Note=Colocalizes with AP-3, clathrin,
CC Rab5 and Rab7b (PubMed:21411634). Cytoplasmic, peripheral membrane
CC protein associated with early endosomes and late endosomes/lysosomes.
CC {ECO:0000250|UniProtKB:Q9H269, ECO:0000269|PubMed:21411634}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q920Q4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q920Q4-2; Sequence=VSP_004019;
CC -!- SIMILARITY: Belongs to the VPS16 family. {ECO:0000305}.
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DR EMBL; AB056721; BAB64892.1; -; mRNA.
DR EMBL; BX890605; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC003944; AAH03944.1; -; mRNA.
DR EMBL; BC025626; AAH25626.1; -; mRNA.
DR CCDS; CCDS38242.1; -. [Q920Q4-1]
DR AlphaFoldDB; Q920Q4; -.
DR SMR; Q920Q4; -.
DR IntAct; Q920Q4; 5.
DR MINT; Q920Q4; -.
DR STRING; 10090.ENSMUSP00000028900; -.
DR iPTMnet; Q920Q4; -.
DR PhosphoSitePlus; Q920Q4; -.
DR EPD; Q920Q4; -.
DR MaxQB; Q920Q4; -.
DR PaxDb; Q920Q4; -.
DR PeptideAtlas; Q920Q4; -.
DR PRIDE; Q920Q4; -.
DR ProteomicsDB; 297813; -. [Q920Q4-1]
DR ProteomicsDB; 297814; -. [Q920Q4-2]
DR MGI; MGI:2136772; Vps16.
DR eggNOG; KOG2280; Eukaryota.
DR InParanoid; Q920Q4; -.
DR PhylomeDB; Q920Q4; -.
DR ChiTaRS; Vps16; mouse.
DR PRO; PR:Q920Q4; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q920Q4; protein.
DR GO; GO:0005884; C:actin filament; IDA:MGI.
DR GO; GO:0005776; C:autophagosome; IEA:UniProtKB-SubCell.
DR GO; GO:0030424; C:axon; ISO:MGI.
DR GO; GO:0030136; C:clathrin-coated vesicle; IDA:UniProtKB.
DR GO; GO:0033263; C:CORVET complex; IDA:UniProtKB.
DR GO; GO:0005769; C:early endosome; IDA:MGI.
DR GO; GO:0031901; C:early endosome membrane; IDA:UniProtKB.
DR GO; GO:0005768; C:endosome; 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:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0055037; C:recycling endosome; ISO:MGI.
DR GO; GO:0003779; F:actin binding; IDA:MGI.
DR GO; GO:0051015; F:actin filament binding; ISO:MGI.
DR GO; GO:0097352; P:autophagosome maturation; ISO:MGI.
DR GO; GO:0016197; P:endosomal transport; IBA:GO_Central.
DR GO; GO:0008333; P:endosome to lysosome transport; ISO:MGI.
DR GO; GO:0006886; P:intracellular protein transport; IEA:InterPro.
DR GO; GO:0042144; P:vacuole fusion, non-autophagic; IBA:GO_Central.
DR GO; GO:0046718; P:viral entry into host cell; IMP:MGI.
DR Gene3D; 1.10.150.780; -; 1.
DR InterPro; IPR016534; VPS16.
DR InterPro; IPR006925; Vps16_C.
DR InterPro; IPR038132; Vps16_C_sf.
DR InterPro; IPR006926; Vps16_N.
DR PANTHER; PTHR12811; PTHR12811; 1.
DR Pfam; PF04840; Vps16_C; 1.
DR Pfam; PF04841; Vps16_N; 1.
DR PIRSF; PIRSF007949; VPS16; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Autophagy; Cytoplasmic vesicle; Endosome; Lysosome;
KW Membrane; Nitration; Protein transport; Reference proteome; Transport.
FT CHAIN 1..839
FT /note="Vacuolar protein sorting-associated protein 16
FT homolog"
FT /id="PRO_0000065889"
FT REGION 642..736
FT /note="Interaction with VPS33A"
FT /evidence="ECO:0000250|UniProtKB:Q9H269"
FT MOD_RES 4
FT /note="3'-nitrotyrosine"
FT /evidence="ECO:0007744|PubMed:16800626"
FT VAR_SEQ 1..420
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_004019"
FT MUTAGEN 52
FT /note="N->K: Down-regulation of VPS16 expression in mice;
FT mice exhibited obvious abnormality in the behavior and
FT significantly impaired motor function."
FT /evidence="ECO:0000269|PubMed:27174565"
FT CONFLICT 155
FT /note="L -> Q (in Ref. 1; BAB64892)"
FT /evidence="ECO:0000305"
FT CONFLICT 173
FT /note="L -> M (in Ref. 1; BAB64892 and 3; AAH25626)"
FT /evidence="ECO:0000305"
FT CONFLICT 431
FT /note="I -> V (in Ref. 1; BAB64892)"
FT /evidence="ECO:0000305"
FT CONFLICT 493..499
FT /note="ARAWDMR -> VQQKDVS (in Ref. 1; BAB64892 and 3;
FT AAH03944/AAH25626)"
FT /evidence="ECO:0000305"
FT CONFLICT 653
FT /note="T -> M (in Ref. 3; AAH25626)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 839 AA; 94928 MW; 42C9B3C87E5763C2 CRC64;
MDCYTANWNP LGDSAFYRKY ELYSMDWDLK EELKDCLVAA APYGGPIALL RNCWRKEKAA
SVRPVLEIYS ASGLPLASLL WKSGPVVALG WSAEEELLCV QEDGAVLVYG LHGDFRRHFS
MGNEVLQNRV LDARIFHTEF GSGVAILTGA YRFTLSANVG DLKLRRMPEV PGLQSAPSCW
TTLCHDRVPH ILLAVGPDLY LLDHATCSAV TPAGLAPGVS SFLQMAVSFT YRYLALFTDT
GYIWMGTASL KEKLCEFNCN IRAPPKQMVW CSRPRSKERA VVVAWERRLM VVGNAPESIQ
FVLDEDSYLV PELDGVRIFS RSTHEFLHEV PVASEEIFKI ASMAPGALLL EAQKEYEKES
QKADEYLREI QELGQLIQAV QQCIEAAGHE HQPDMQKSLL RAASFGKCFL DRFPPDSFVH
MCQDLRVLNA IRDYHIGIPL TYTQYKQLTI QVLLDRLVLR RLYPLAIQIC EYLRLPEVQG
VSRILAHWAC YKARAWDMRD EDVARAINQK LGDTPGVSYS DIAARAYGCG RTELAIKLLE
YEPRSGEQVP LLLKMKRSKL ALSKAIESGD TDLVFTVLLH LKNELNRGDF FMTLRNQPMA
LSLYRQFCKH QELDTLKDLY NQDDNHQELG SFHIRASYAA EERIEGRVAA LQTAADAFYK
AKNEFAAKAT EDQMRLLRIQ RRLEDELGGR FLDLSLHDTV TTLILGGHNK RAEQLARDFR
IPDKRLWWLK LAALADLEDW EELEKFSKSK KSPIGYLPFV EICMKQHNKH EAKKYASRVG
PEQKVKALLL VGDVAQAAEV AIEHRNETEL SLVLSHCTGA TDGAIADKIQ RARAQAQKK
