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 24-JAN-2024, entry version 181. 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 DEL. 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; 155. DR ComplexPortal; CPX-6212; HOPS tethering complex. DR ComplexPortal; CPX-6213; CORVET tethering complex. DR CORUM; Q9H269; -. DR IntAct; Q9H269; 51. DR MINT; Q9H269; -. DR STRING; 9606.ENSP00000369810; -. DR GlyCosmos; Q9H269; 1 site, 2 glycans. 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; 9606-ENSP00000369810; -. DR PeptideAtlas; Q9H269; -. DR ProteomicsDB; 80507; -. [Q9H269-1] DR ProteomicsDB; 80508; -. [Q9H269-2] DR Pumba; Q9H269; -. DR Antibodypedia; 23354; 191 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 AGR; HGNC:14584; -. DR CTD; 64601; -. DR DisGeNET; 64601; -. DR GeneCards; VPS16; -. DR HGNC; HGNC:14584; VPS16. DR HPA; ENSG00000215305; Low tissue specificity. DR MalaCards; VPS16; -. 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; HMTIRDH; -. DR OrthoDB; 1110811at2759; -. 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; 317 hits in 1173 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 187 other cell types or tissues. DR ExpressionAtlas; Q9H269; baseline and differential. DR Genevisible; Q9H269; HS. 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; NAS:ComplexPortal. DR GO; GO:0005769; C:early endosome; IDA:UniProtKB. DR GO; GO:0005768; C:endosome; IBA:GO_Central. DR GO; GO:0010008; C:endosome membrane; TAS:Reactome. 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:0055037; C:recycling endosome; IDA:UniProtKB. DR GO; GO:0003779; F:actin binding; IBA:GO_Central. 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; NAS: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; NAS:ComplexPortal. DR GO; GO:0042144; P:vacuole fusion, non-autophagic; IBA:GO_Central. DR Gene3D; 1.10.150.780; Vps16, C-terminal region; 1. DR InterPro; IPR016534; VPS16. DR InterPro; IPR006925; Vps16_C. DR InterPro; IPR038132; Vps16_C_sf. DR InterPro; IPR006926; Vps16_N. DR PANTHER; PTHR12811; VACUOLAR PROTEIN SORTING VPS16; 1. DR PANTHER; PTHR12811:SF0; VACUOLAR PROTEIN SORTING-ASSOCIATED PROTEIN 16 HOMOLOG; 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 //