VPS16_HUMAN
ID VPS16_HUMAN Reviewed; 839 AA.
AC Q9H269; Q5JUB1; Q8WU31; Q96EE7; Q96N92; Q9H1Q4; Q9H1Q5;
DT 19-SEP-2002, integrated into UniProtKB/Swiss-Prot.
DT 19-SEP-2002, sequence version 2.
DT 03-AUG-2022, entry version 173.
DE RecName: Full=Vacuolar protein sorting-associated protein 16 homolog;
DE Short=hVPS16;
GN Name=VPS16;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=11250079; DOI=10.1016/s0378-1119(01)00333-x;
RA Huizing M., Didier A., Walenta J., Anikster Y., Gahl W.A., Kraemer H.;
RT "Molecular cloning and characterization of human VPS18, VPS11, VPS16, and
RT VPS33.";
RL Gene 264:241-247(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Kidney;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 146-839 (ISOFORM 1).
RC TISSUE=Fetal brain;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 425-839 (ISOFORM 1).
RC TISSUE=Duodenum, Lung, and Ovary;
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 [6]
RP CHARACTERIZATION, INTERACTION WITH VPS11 AND VPS18, SUBUNIT, AND
RP SUBCELLULAR LOCATION.
RX PubMed=11382755; DOI=10.1074/jbc.m101778200;
RA Kim B.Y., Kraemer H., Yamamoto A., Kominami E., Kohsaka S., Akazawa C.;
RT "Molecular characterization of mammalian homologues of class C Vps proteins
RT that interact with syntaxin-7.";
RL J. Biol. Chem. 276:29393-29402(2001).
RN [7]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RC TISSUE=Placenta;
RX PubMed=17897319; DOI=10.1111/j.1600-0854.2007.00643.x;
RA Schroeder B., Wrocklage C., Pan C., Jaeger R., Koesters B., Schaefer H.,
RA Elsaesser H.-P., Mann M., Hasilik A.;
RT "Integral and associated lysosomal membrane proteins.";
RL Traffic 8:1676-1686(2007).
RN [8]
RP SUBCELLULAR LOCATION.
RX PubMed=18552835; DOI=10.1038/ncb1740;
RA Liang C., Lee J.S., Inn K.S., Gack M.U., Li Q., Roberts E.A., Vergne I.,
RA Deretic V., Feng P., Akazawa C., Jung J.U.;
RT "Beclin1-binding UVRAG targets the class C Vps complex to coordinate
RT autophagosome maturation and endocytic trafficking.";
RL Nat. Cell Biol. 10:776-787(2008).
RN [9]
RP INTERACTION WITH MON1B.
RX PubMed=20434987; DOI=10.1016/j.cell.2010.03.011;
RA Poteryaev D., Datta S., Ackema K., Zerial M., Spang A.;
RT "Identification of the switch in early-to-late endosome transition.";
RL Cell 141:497-508(2010).
RN [10]
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., Buerckstuemmer T.,
RA 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 [11]
RP SUBCELLULAR LOCATION.
RX PubMed=21802320; DOI=10.1016/j.immuni.2011.06.009;
RA Garg S., Sharma M., Ung C., Tuli A., Barral D.C., Hava D.L., Veerapen N.,
RA Besra G.S., Hacohen N., Brenner M.B.;
RT "Lysosomal trafficking, antigen presentation, and microbial killing are
RT controlled by the Arf-like GTPase Arl8b.";
RL Immunity 35:182-193(2011).
RN [12]
RP REVIEW ON THE HOPS AND CORVET COMPLEXES.
RX PubMed=23351085; DOI=10.1111/febs.12151;
RA Solinger J.A., Spang A.;
RT "Tethering complexes in the endocytic pathway: CORVET and HOPS.";
RL FEBS J. 280:2743-2757(2013).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [14]
RP FUNCTION, FUNCTION OF THE HOPS COMPLEX, INTERACTION WITH STX17, AND
RP SUBCELLULAR LOCATION.
RX PubMed=24554770; DOI=10.1091/mbc.e13-08-0447;
RA Jiang P., Nishimura T., Sakamaki Y., Itakura E., Hatta T., Natsume T.,
RA Mizushima N.;
RT "The HOPS complex mediates autophagosome-lysosome fusion through
RT interaction with syntaxin 17.";
RL Mol. Biol. Cell 25:1327-1337(2014).
RN [15]
RP INTERACTION WITH TGFBRAP1, SUBUNIT, AND FUNCTION OF THE CORVET COMPLEX.
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 [16]
RP FUNCTION, INTERACTION WITH VPS33A AND VPS18, AND MUTAGENESIS OF ALA-669 AND
RP ARG-725.
RX PubMed=25783203; DOI=10.1111/tra.12283;
RA Wartosch L., Guenesdogan U., Graham S.C., Luzio J.P.;
RT "Recruitment of VPS33A to HOPS by VPS16 Is Required for Lysosome Fusion
RT with Endosomes and Autophagosomes.";
RL Traffic 16:727-742(2015).
RN [17]
RP INVOLVEMENT IN DYT30, AND VARIANT DYT30 LYS-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).
RN [18]
RP INVOLVEMENT IN DYT30, AND VARIANTS DYT30 187-ARG--LYS-839 DEL;
RP 445-TYR--LYS-839 DEL AND 635-ARG--LYS-839.
RX PubMed=32808683; DOI=10.1002/ana.25879;
RG Genomics England Research Consortium;
RA Steel D., Zech M., Zhao C., Barwick K.E.S., Burke D., Demailly D.,
RA Kumar K.R., Zorzi G., Nardocci N., Kaiyrzhanov R., Wagner M., Iuso A.,
RA Berutti R., Skorvanek M., Necpal J., Davis R., Wiethoff S., Mankad K.,
RA Sudhakar S., Ferrini A., Sharma S., Kamsteeg E.J., Tijssen M.A.,
RA Verschuuren C., van Egmond M.E., Flowers J.M., McEntagart M., Tucci A.,
RA Coubes P., Bustos B.I., Gonzalez-Latapi P., Tisch S., Darveniza P.,
RA Gorman K.M., Peall K.J., Boetzel K., Koch J.C., Kmiec T., Plecko B.,
RA Boesch S., Haslinger B., Jech R., Garavaglia B., Wood N., Houlden H.,
RA Gissen P., Lubbe S.J., Sue C.M., Cif L., Mencacci N.E., Anderson G.,
RA Kurian M.A., Winkelmann J.;
RT "Loss-of-Function Variants in HOPS Complex Genes VPS16 and VPS41 Cause
RT Early Onset Dystonia Associated with Lysosomal Abnormalities.";
RL Ann. Neurol. 88:867-877(2020).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 642-736 IN COMPLEX WITH VPS33A,
RP FUNCTION, INTERACTION WITH VPS33A, AND MUTAGENESIS OF ALA-669 AND ARG-725.
RX PubMed=23901104; DOI=10.1073/pnas.1307074110;
RA Graham S.C., Wartosch L., Gray S.R., Scourfield E.J., Deane J.E.,
RA Luzio J.P., Owen D.J.;
RT "Structural basis of Vps33A recruitment to the human HOPS complex by
RT Vps16.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:13345-13350(2013).
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 (PubMed:11382755,
CC PubMed:23351085, PubMed:24554770, PubMed:25266290, PubMed:25783203).
CC Required for recruitment of VPS33A to the HOPS complex
CC (PubMed:23901104). Required for fusion of endosomes and autophagosomes
CC with lysosomes; the function is dependent on its association with
CC VPS33A but not VPS33B (PubMed:25783203). The function in autophagosome-
CC lysosome fusion implicates STX17 but not UVRAG (PubMed:24554770).
CC {ECO:0000269|PubMed:23901104, ECO:0000269|PubMed:24554770,
CC ECO:0000269|PubMed:25783203, ECO:0000305|PubMed:11382755,
CC ECO:0000305|PubMed:23351085, ECO:0000305|PubMed:25266290,
CC ECO:0000305|PubMed:25783203}.
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:11382755,
CC PubMed:25783203, PubMed:23901104, PubMed:25266290). Interacts with
CC RAB5C (By similarity). Interacts with STX17, MON1B (PubMed:20434987,
CC PubMed:24554770). Associates with adapter protein complex 3 (AP-3) and
CC clathrin:AP-3 complexes (By similarity). {ECO:0000250|UniProtKB:Q920Q4,
CC ECO:0000269|PubMed:11382755, ECO:0000269|PubMed:20434987,
CC ECO:0000269|PubMed:24554770, ECO:0000269|PubMed:25266290,
CC ECO:0000305|PubMed:11382755, ECO:0000305|PubMed:25266290}.
CC -!- INTERACTION:
CC Q9H269; P56962: STX17; NbExp=3; IntAct=EBI-2655929, EBI-2797775;
CC Q9H269; Q8WUH2: TGFBRAP1; NbExp=3; IntAct=EBI-2655929, EBI-2954829;
CC Q9H269; Q9H270: VPS11; NbExp=6; IntAct=EBI-2655929, EBI-373380;
CC Q9H269; Q9P253: VPS18; NbExp=15; IntAct=EBI-2655929, EBI-1053363;
CC Q9H269; Q96AX1: VPS33A; NbExp=15; IntAct=EBI-2655929, EBI-2527283;
CC -!- SUBCELLULAR LOCATION: Late endosome membrane
CC {ECO:0000269|PubMed:17897319}; Peripheral membrane protein
CC {ECO:0000269|PubMed:17897319}; Cytoplasmic side
CC {ECO:0000269|PubMed:17897319}. Lysosome membrane
CC {ECO:0000269|PubMed:17897319, ECO:0000269|PubMed:21802320}; Peripheral
CC membrane protein {ECO:0000269|PubMed:17897319}; Cytoplasmic side
CC {ECO:0000269|PubMed:17897319}. Early endosome
CC {ECO:0000269|PubMed:18552835}. Cytoplasmic vesicle, clathrin-coated
CC vesicle {ECO:0000250|UniProtKB:Q920Q4}. Cytoplasmic vesicle,
CC autophagosome {ECO:0000269|PubMed:24554770}. Note=Colocalizes with AP-
CC 3, clathrin, Rab5 and Rab7b (By similarity). Cytoplasmic, peripheral
CC membrane protein associated with early endosomes and late
CC endosomes/lysosomes. {ECO:0000250|UniProtKB:Q920Q4, ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9H269-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9H269-2; Sequence=VSP_004018;
CC -!- TISSUE SPECIFICITY: Ubiquitous.
CC -!- DISEASE: Dystonia 30 (DYT30) [MIM:619291]: A form of dystonia, a
CC disorder defined by the presence of sustained involuntary muscle
CC contraction, often leading to abnormal postures. DYT30 is characterized
CC by early onset and predominantly cervical, bulbar, orofacial, and upper
CC limb involvement. Some patients have a more complex phenotype with
CC neurocognitive impairment, including mild intellectual disability or
CC psychiatric manifestations. Loss of ambulation is observed in some
CC cases. DYT30 inheritance is autosomal dominant with incomplete
CC penetrance. {ECO:0000269|PubMed:32808683}. Note=The disease is caused
CC by variants affecting the gene represented in this entry. The
CC transmission pattern of DYT30 in most families is consistent with
CC autosomal dominant inheritance. However, a homozygous VPS16 variant has
CC been found in a multigenerational consanguineous family with autosomal
CC recessive inheritance of DYT30. {ECO:0000269|PubMed:27174565}.
CC -!- SIMILARITY: Belongs to the VPS16 family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF308801; AAG34678.1; -; mRNA.
DR EMBL; AK055787; BAB71013.1; -; mRNA.
DR EMBL; AL161656; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL834401; CAD39063.1; -; mRNA.
DR EMBL; BC012422; AAH12422.1; -; mRNA.
DR EMBL; BC021291; AAH21291.2; -; mRNA.
DR EMBL; BC064406; AAH64406.1; -; mRNA.
DR CCDS; CCDS13036.1; -. [Q9H269-1]
DR CCDS; CCDS13037.1; -. [Q9H269-2]
DR RefSeq; NP_072097.2; NM_022575.3. [Q9H269-1]
DR RefSeq; NP_536338.1; NM_080413.2. [Q9H269-2]
DR PDB; 4BX9; X-ray; 2.60 A; C=642-736.
DR PDBsum; 4BX9; -.
DR AlphaFoldDB; Q9H269; -.
DR SMR; Q9H269; -.
DR BioGRID; 122220; 147.
DR ComplexPortal; CPX-6212; HOPS tethering complex.
DR ComplexPortal; CPX-6213; CORVET tethering complex.
DR CORUM; Q9H269; -.
DR IntAct; Q9H269; 47.
DR MINT; Q9H269; -.
DR STRING; 9606.ENSP00000369810; -.
DR GlyGen; Q9H269; 1 site, 2 O-linked glycans (1 site).
DR iPTMnet; Q9H269; -.
DR MetOSite; Q9H269; -.
DR PhosphoSitePlus; Q9H269; -.
DR BioMuta; VPS16; -.
DR DMDM; 23396927; -.
DR EPD; Q9H269; -.
DR jPOST; Q9H269; -.
DR MassIVE; Q9H269; -.
DR MaxQB; Q9H269; -.
DR PaxDb; Q9H269; -.
DR PeptideAtlas; Q9H269; -.
DR PRIDE; Q9H269; -.
DR ProteomicsDB; 80507; -. [Q9H269-1]
DR ProteomicsDB; 80508; -. [Q9H269-2]
DR Antibodypedia; 23354; 175 antibodies from 32 providers.
DR DNASU; 64601; -.
DR Ensembl; ENST00000380445.8; ENSP00000369810.3; ENSG00000215305.10. [Q9H269-1]
DR Ensembl; ENST00000380469.7; ENSP00000369836.3; ENSG00000215305.10. [Q9H269-2]
DR GeneID; 64601; -.
DR KEGG; hsa:64601; -.
DR MANE-Select; ENST00000380445.8; ENSP00000369810.3; NM_022575.4; NP_072097.2.
DR UCSC; uc002whe.5; human. [Q9H269-1]
DR CTD; 64601; -.
DR DisGeNET; 64601; -.
DR GeneCards; VPS16; -.
DR HGNC; HGNC:14584; VPS16.
DR HPA; ENSG00000215305; Low tissue specificity.
DR MIM; 608550; gene.
DR MIM; 619291; phenotype.
DR neXtProt; NX_Q9H269; -.
DR PharmGKB; PA37903; -.
DR VEuPathDB; HostDB:ENSG00000215305; -.
DR eggNOG; KOG2280; Eukaryota.
DR GeneTree; ENSGT00390000003896; -.
DR HOGENOM; CLU_008909_0_0_1; -.
DR InParanoid; Q9H269; -.
DR OMA; KIYVHWA; -.
DR OrthoDB; 1258856at2759; -.
DR PhylomeDB; Q9H269; -.
DR TreeFam; TF105673; -.
DR PathwayCommons; Q9H269; -.
DR Reactome; R-HSA-9754560; SARS-CoV-2 modulates autophagy.
DR SignaLink; Q9H269; -.
DR SIGNOR; Q9H269; -.
DR BioGRID-ORCS; 64601; 301 hits in 1095 CRISPR screens.
DR ChiTaRS; VPS16; human.
DR GenomeRNAi; 64601; -.
DR Pharos; Q9H269; Tbio.
DR PRO; PR:Q9H269; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; Q9H269; protein.
DR Bgee; ENSG00000215305; Expressed in granulocyte and 185 other tissues.
DR ExpressionAtlas; Q9H269; baseline and differential.
DR Genevisible; Q9H269; HS.
DR GO; GO:0005776; C:autophagosome; IEA:UniProtKB-SubCell.
DR GO; GO:0030424; C:axon; IEA:Ensembl.
DR GO; GO:0030136; C:clathrin-coated vesicle; IEA:UniProtKB-SubCell.
DR GO; GO:0033263; C:CORVET complex; IC:ComplexPortal.
DR GO; GO:0005769; C:early endosome; IDA:UniProtKB.
DR GO; GO:0005768; C:endosome; IBA:GO_Central.
DR GO; GO:0030897; C:HOPS complex; 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:0005765; C:lysosomal membrane; HDA:UniProtKB.
DR GO; GO:0005764; C:lysosome; IDA:UniProtKB.
DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR GO; GO:0055037; C:recycling endosome; IDA:UniProtKB.
DR GO; GO:0003779; F:actin binding; IBA:GO_Central.
DR GO; GO:0051015; F:actin filament binding; IEA:Ensembl.
DR GO; GO:0097352; P:autophagosome maturation; IMP:UniProtKB.
DR GO; GO:0016197; P:endosomal transport; IBA:GO_Central.
DR GO; GO:0034058; P:endosomal vesicle fusion; IC:ComplexPortal.
DR GO; GO:0008333; P:endosome to lysosome transport; IMP:UniProtKB.
DR GO; GO:0006886; P:intracellular protein transport; IEA:InterPro.
DR GO; GO:0035542; P:regulation of SNARE complex assembly; IC:ComplexPortal.
DR GO; GO:0042144; P:vacuole fusion, non-autophagic; IBA:GO_Central.
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 3D-structure; Alternative splicing; Autophagy; Cytoplasmic vesicle;
KW Disease variant; Dystonia; Endosome; Lysosome; Membrane; Nitration;
KW Protein transport; Reference proteome; Transport.
FT CHAIN 1..839
FT /note="Vacuolar protein sorting-associated protein 16
FT homolog"
FT /id="PRO_0000065888"
FT REGION 642..736
FT /note="Interaction with VPS33A"
FT /evidence="ECO:0000269|PubMed:23901104"
FT MOD_RES 4
FT /note="3'-nitrotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q920Q4"
FT VAR_SEQ 300..443
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_004018"
FT VARIANT 52
FT /note="N -> K (in DYT30; dbSNP:rs367642720)"
FT /evidence="ECO:0000269|PubMed:27174565"
FT /id="VAR_076520"
FT VARIANT 187..839
FT /note="Missing (in DYT30)"
FT /evidence="ECO:0000269|PubMed:32808683"
FT /id="VAR_085701"
FT VARIANT 445..839
FT /note="Missing (in DYT30)"
FT /evidence="ECO:0000269|PubMed:32808683"
FT /id="VAR_085702"
FT VARIANT 635..839
FT /note="Missing (in DYT30)"
FT /evidence="ECO:0000269|PubMed:32808683"
FT /id="VAR_085703"
FT VARIANT 637
FT /note="S -> I (in dbSNP:rs35773586)"
FT /id="VAR_053776"
FT MUTAGEN 669
FT /note="A->D: Disrupts interaction with VPS33A, no effect on
FT interaction with VPS18 and impairs endosome-lysosome
FT fusion; when associated with E-725."
FT /evidence="ECO:0000269|PubMed:23901104,
FT ECO:0000269|PubMed:25783203"
FT MUTAGEN 725
FT /note="R->E: Disrupts interaction with VPS33A, no effect on
FT interaction with VPS18 and impairs endosome-lysosome
FT fusion; when associated with D-669."
FT /evidence="ECO:0000269|PubMed:23901104,
FT ECO:0000269|PubMed:25783203"
FT CONFLICT 87
FT /note="V -> A (in Ref. 2; BAB71013)"
FT /evidence="ECO:0000305"
FT CONFLICT 612
FT /note="E -> G (in Ref. 2; BAB71013)"
FT /evidence="ECO:0000305"
FT CONFLICT 690..691
FT /note="QF -> LQ (in Ref. 5; AAH12422)"
FT /evidence="ECO:0000305"
FT CONFLICT 768
FT /note="N -> T (in Ref. 1; AAG34678)"
FT /evidence="ECO:0000305"
FT CONFLICT 809
FT /note="E -> D (in Ref. 5; AAH12422)"
FT /evidence="ECO:0000305"
FT HELIX 645..660
FT /evidence="ECO:0007829|PDB:4BX9"
FT HELIX 664..687
FT /evidence="ECO:0007829|PDB:4BX9"
FT HELIX 696..705
FT /evidence="ECO:0007829|PDB:4BX9"
FT HELIX 709..718
FT /evidence="ECO:0007829|PDB:4BX9"
FT HELIX 723..734
FT /evidence="ECO:0007829|PDB:4BX9"
SQ SEQUENCE 839 AA; 94694 MW; 9C4292D455C19A60 CRC64;
MDCYTANWNP LGDSAFYRKY ELYSMDWDLK EELRDCLVAA APYGGPIALL RNPWRKEKAA
SVRPVLDIYS ASGMPLASLL WKSGPVVSLG WSAEEELLCV QEDGAVLVYG LHGDFRRHFS
MGNEVLQNRV LDARIFHTEF GSGVAILTGA HRFTLSANVG DLKLRRMPEV PGLQSAPSCW
TVLCQDRVAH ILLAVGPDLY LLDHAACSAV TPPGLAPGVS SFLQMAVSFT YRHLALFTDT
GYIWMGTASL KEKLCEFNCN IRAPPKQMVW CSRPRSKERA VVVAWERRLM VVGDAPESIQ
FVLDEDSYLV PELDGVRIFS RSTHEFLHEV PAASEEIFKI ASMAPGALLL EAQKEYEKES
QKADEYLREI QELGQLTQAV QQCIEAAGHE HQPDMQKSLL RAASFGKCFL DRFPPDSFVH
MCQDLRVLNA VRDYHIGIPL TYSQYKQLTI QVLLDRLVLR RLYPLAIQIC EYLRLPEVQG
VSRILAHWAC YKVQQKDVSD EDVARAINQK LGDTPGVSYS DIAARAYGCG RTELAIKLLE
YEPRSGEQVP LLLKMKRSKL ALSKAIESGD TDLVFTVLLH LKNELNRGDF FMTLRNQPMA
LSLYRQFCKH QELETLKDLY NQDDNHQELG SFHIRASYAA EERIEGRVAA LQTAADAFYK
AKNEFAAKAT EDQMRLLRLQ RRLEDELGGQ FLDLSLHDTV TTLILGGHNK RAEQLARDFR
IPDKRLWWLK LTALADLEDW EELEKFSKSK KSPIGYLPFV EICMKQHNKY EAKKYASRVG
PEQKVKALLL VGDVAQAADV AIEHRNEAEL SLVLSHCTGA TDGATADKIQ RARAQAQKK
