VPS11_HUMAN
ID VPS11_HUMAN Reviewed; 941 AA.
AC Q9H270; Q8WY89; Q96EP8; Q9H6D9; Q9HCS6;
DT 19-SEP-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 194.
DE RecName: Full=Vacuolar protein sorting-associated protein 11 homolog;
DE Short=hVPS11;
DE AltName: Full=RING finger protein 108;
GN Name=VPS11; Synonyms=RNF108; ORFNames=PP3476;
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].
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 [MRNA], FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION
RP WITH VPS16; VPS18; VPS33A AND STX7.
RC TISSUE=Brain;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye, and Skin;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 144-941.
RX PubMed=15498874; DOI=10.1073/pnas.0404089101;
RA Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H., Qiu X.,
RA Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y., Shu H., Chen X.,
RA Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S., Gu J.;
RT "Large-scale cDNA transfection screening for genes related to cancer
RT development and progression.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 575-941.
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 [6]
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 [7]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH ECPAS.
RX PubMed=20682791; DOI=10.1074/jbc.m110.154120;
RA Gorbea C., Pratt G., Ustrell V., Bell R., Sahasrabudhe S., Hughes R.E.,
RA Rechsteiner M.;
RT "A protein interaction network for Ecm29 links the 26 S proteasome to
RT molecular motors and endosomal components.";
RL J. Biol. Chem. 285:31616-31633(2010).
RN [8]
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 [9]
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 [10]
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 [11]
RP FUNCTION, INTERACTION WITH EZR; RDX AND MSN, AND SUBCELLULAR LOCATION.
RX PubMed=21148287; DOI=10.1091/mbc.e10-09-0796;
RA Chirivino D., Del Maestro L., Formstecher E., Hupe P., Raposo G.,
RA Louvard D., Arpin M.;
RT "The ERM proteins interact with the HOPS complex to regulate the maturation
RT of endosomes.";
RL Mol. Biol. Cell 22:375-385(2011).
RN [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [13]
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 [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-813 AND SER-924, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [15]
RP INTERACTION WITH VPS16; VPS18 AND VPS39.
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).
RN [16]
RP FUNCTION.
RX PubMed=23593995; DOI=10.1111/tra.12077;
RA Kvalvaag A.S., Pust S., Sundet K.I., Engedal N., Simm R., Sandvig K.;
RT "The ERM proteins ezrin and moesin regulate retrograde Shiga toxin
RT transport.";
RL Traffic 14:839-852(2013).
RN [17]
RP FUNCTION OF THE HOPS COMPLEX, AND INTERACTION WITH STX17.
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 [18]
RP FUNCTION OF THE CORVET COMPLEX, SUBUNIT, AND INTERACTION WITH TGFBRAP1.
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 [19]
RP FUNCTION, FUNCTION OF THE HOPS COMPLEX, AND SUBUNIT.
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 [20]
RP INTERACTION WITH PLEKHM1.
RX PubMed=28325809; DOI=10.1083/jcb.201607085;
RA Marwaha R., Arya S.B., Jagga D., Kaur H., Tuli A., Sharma M.;
RT "The Rab7 effector PLEKHM1 binds Arl8b to promote cargo traffic to
RT lysosomes.";
RL J. Cell Biol. 216:1051-1070(2017).
RN [21]
RP INVOLVEMENT IN HLD12, AND VARIANT HLD12 GLY-846.
RX PubMed=26307567; DOI=10.1136/jmedgenet-2015-103239;
RA Edvardson S., Gerhard F., Jalas C., Lachmann J., Golan D., Saada A.,
RA Shaag A., Ungermann C., Elpeleg O.;
RT "Hypomyelination and developmental delay associated with VPS11 mutation in
RT Ashkenazi-Jewish patients.";
RL J. Med. Genet. 52:749-753(2015).
RN [22]
RP VARIANT DYT32 SER-46, AND INVOLVEMENT IN DYT32.
RX PubMed=33452836; DOI=10.1002/ana.26021;
RA Monfrini E., Cogiamanian F., Salani S., Straniero L., Fagiolari G.,
RA Garbellini M., Carsana E., Borellini L., Biella F., Moggio M., Bresolin N.,
RA Corti S., Duga S., Comi G.P., Aureli M., Di Fonzo A.;
RT "A Novel Homozygous VPS11 Variant May Cause Generalized Dystonia.";
RL Ann. Neurol. 89:834-839(2021).
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 fusion of endosomes and autophagosomes with lysosomes
CC (PubMed:25783203). Involved in cargo transport from early to late
CC endosomes and required for the transition from early to late endosomes
CC (PubMed:21148287). Involved in the retrograde Shiga toxin transport
CC (PubMed:23593995). {ECO:0000269|PubMed:21148287,
CC ECO:0000269|PubMed:23593995, ECO:0000269|PubMed:25783203,
CC ECO:0000305|PubMed:11382755, ECO:0000305|PubMed:23351085,
CC ECO:0000305|PubMed:24554770, 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:20434987, PubMed:23351085, PubMed:23901104, PubMed:25266290,
CC PubMed:25783203). Interacts with TGFBRAP1, MON1B, STX7, STX17, EZR,
CC RDX, MSN, ECPAS (PubMed:11382755, PubMed:20682791, PubMed:21148287,
CC PubMed:24554770, PubMed:25266290). Interacts with RAB5C (By
CC similarity). Associates with adaptor protein complex 3 (AP-3) and
CC clathrin:AP-3 complexes (By similarity). Interacts with PLEKHM1
CC (PubMed:28325809). {ECO:0000250|UniProtKB:Q91W86,
CC ECO:0000269|PubMed:11382755, ECO:0000269|PubMed:20434987,
CC ECO:0000269|PubMed:20682791, ECO:0000269|PubMed:23901104,
CC ECO:0000269|PubMed:24554770, ECO:0000269|PubMed:25266290,
CC ECO:0000269|PubMed:25783203, ECO:0000269|PubMed:28325809,
CC ECO:0000305|PubMed:11382755, ECO:0000305|PubMed:23351085,
CC ECO:0000305|PubMed:25266290}.
CC -!- INTERACTION:
CC Q9H270; P05067: APP; NbExp=3; IntAct=EBI-373380, EBI-77613;
CC Q9H270; P35226: BMI1; NbExp=2; IntAct=EBI-373380, EBI-2341576;
CC Q9H270; P28329-3: CHAT; NbExp=3; IntAct=EBI-373380, EBI-25837549;
CC Q9H270; O75190-2: DNAJB6; NbExp=3; IntAct=EBI-373380, EBI-12593112;
CC Q9H270; P22607: FGFR3; NbExp=3; IntAct=EBI-373380, EBI-348399;
CC Q9H270; P06396: GSN; NbExp=3; IntAct=EBI-373380, EBI-351506;
CC Q9H270; P01112: HRAS; NbExp=3; IntAct=EBI-373380, EBI-350145;
CC Q9H270; O14901: KLF11; NbExp=3; IntAct=EBI-373380, EBI-948266;
CC Q9H270; P60410: KRTAP10-8; NbExp=6; IntAct=EBI-373380, EBI-10171774;
CC Q9H270; P16284: PECAM1; NbExp=3; IntAct=EBI-373380, EBI-716404;
CC Q9H270; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-373380, EBI-5235340;
CC Q9H270; O15400: STX7; NbExp=2; IntAct=EBI-373380, EBI-3221827;
CC Q9H270; Q8WUH2: TGFBRAP1; NbExp=3; IntAct=EBI-373380, EBI-2954829;
CC Q9H270; P61086: UBE2K; NbExp=3; IntAct=EBI-373380, EBI-473850;
CC Q9H270; P08670: VIM; NbExp=3; IntAct=EBI-373380, EBI-353844;
CC Q9H270; Q9H269: VPS16; NbExp=6; IntAct=EBI-373380, EBI-2655929;
CC Q9H270; Q9P253: VPS18; NbExp=9; IntAct=EBI-373380, EBI-1053363;
CC Q9H270; Q96AX1: VPS33A; NbExp=2; IntAct=EBI-373380, EBI-2527283;
CC Q9H270; Q96JC1-2: VPS39; NbExp=4; IntAct=EBI-373380, EBI-11962886;
CC Q9H270; Q9Y649; NbExp=3; IntAct=EBI-373380, EBI-25900580;
CC Q9H270; Q63615: Vps33a; Xeno; NbExp=4; IntAct=EBI-373380, EBI-918669;
CC -!- SUBCELLULAR LOCATION: Endosome {ECO:0000269|PubMed:20682791}. Late
CC endosome membrane {ECO:0000269|PubMed:11382755,
CC ECO:0000269|PubMed:21148287}; Peripheral membrane protein
CC {ECO:0000269|PubMed:11382755}; Cytoplasmic side {ECO:0000305}. Lysosome
CC membrane {ECO:0000269|PubMed:11382755, ECO:0000269|PubMed:17897319,
CC ECO:0000269|PubMed:21802320}; Peripheral membrane protein
CC {ECO:0000269|PubMed:11382755}; Cytoplasmic side {ECO:0000305}. Early
CC endosome {ECO:0000269|PubMed:21148287, ECO:0000305}. Cytoplasmic
CC vesicle {ECO:0000305}. Cytoplasmic vesicle, autophagosome
CC {ECO:0000305}. Cytoplasmic vesicle, clathrin-coated vesicle
CC {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Ubiquitous. Expression was highest in heart and low
CC in lung.
CC -!- DISEASE: Leukodystrophy, hypomyelinating, 12 (HLD12) [MIM:616683]: An
CC autosomal recessive neurologic disorder characterized by developmental
CC delay, spasticity, truncal hypotonia, acquired microcephaly,
CC intellectual disability with variable seizure disorder, accompanied by
CC thin corpus callosum, paucity of white matter and delayed myelination.
CC {ECO:0000269|PubMed:26307567}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Dystonia 32 (DYT32) [MIM:619637]: A form of dystonia, a
CC disorder defined by the presence of sustained involuntary muscle
CC contraction, often leading to abnormal postures. DYT32 is an autosomal
CC recessive, slowly progressive form with onset in adulthood and
CC generalized involvement of the limbs, trunk, neck, and larynx,
CC resulting in dysarthria and dysphagia. Brain imaging may show
CC abnormalities in the basal ganglia. {ECO:0000269|PubMed:33452836}.
CC Note=The disease may be caused by variants affecting the gene
CC represented in this entry.
CC -!- SIMILARITY: Belongs to the VPS11 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAG23761.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAB15320.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={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; AF308800; AAG34677.1; -; mRNA.
DR EMBL; AB027508; BAA95163.2; -; mRNA.
DR EMBL; BC012051; AAH12051.2; -; mRNA.
DR EMBL; BC065563; AAH65563.1; -; mRNA.
DR EMBL; AF258558; AAG23761.1; ALT_FRAME; mRNA.
DR EMBL; AK026012; BAB15320.1; ALT_INIT; mRNA.
DR CCDS; CCDS73404.1; -.
DR RefSeq; NP_001277114.1; NM_001290185.1.
DR RefSeq; NP_068375.3; NM_021729.5.
DR AlphaFoldDB; Q9H270; -.
DR BioGRID; 120930; 88.
DR ComplexPortal; CPX-6212; HOPS tethering complex.
DR ComplexPortal; CPX-6213; CORVET tethering complex.
DR CORUM; Q9H270; -.
DR IntAct; Q9H270; 56.
DR MINT; Q9H270; -.
DR STRING; 9606.ENSP00000481126; -.
DR iPTMnet; Q9H270; -.
DR PhosphoSitePlus; Q9H270; -.
DR BioMuta; VPS11; -.
DR DMDM; 23396928; -.
DR EPD; Q9H270; -.
DR jPOST; Q9H270; -.
DR MassIVE; Q9H270; -.
DR MaxQB; Q9H270; -.
DR PeptideAtlas; Q9H270; -.
DR PRIDE; Q9H270; -.
DR ProteomicsDB; 80509; -.
DR Antibodypedia; 32587; 227 antibodies from 33 providers.
DR DNASU; 55823; -.
DR GeneID; 55823; -.
DR KEGG; hsa:55823; -.
DR UCSC; uc058ier.1; human.
DR CTD; 55823; -.
DR DisGeNET; 55823; -.
DR GeneCards; VPS11; -.
DR HGNC; HGNC:14583; VPS11.
DR HPA; ENSG00000160695; Low tissue specificity.
DR MalaCards; VPS11; -.
DR MIM; 608549; gene.
DR MIM; 616683; phenotype.
DR MIM; 619637; phenotype.
DR neXtProt; NX_Q9H270; -.
DR Orphanet; 466934; VPS11-related autosomal recessive hypomyelinating leukodystrophy.
DR PharmGKB; PA37902; -.
DR VEuPathDB; HostDB:ENSG00000160695; -.
DR eggNOG; KOG2114; Eukaryota.
DR HOGENOM; CLU_001287_3_1_1; -.
DR InParanoid; Q9H270; -.
DR OrthoDB; 429638at2759; -.
DR PhylomeDB; Q9H270; -.
DR PathwayCommons; Q9H270; -.
DR Reactome; R-HSA-9754560; SARS-CoV-2 modulates autophagy.
DR SignaLink; Q9H270; -.
DR SIGNOR; Q9H270; -.
DR BioGRID-ORCS; 55823; 51 hits in 307 CRISPR screens.
DR ChiTaRS; VPS11; human.
DR GeneWiki; VPS11; -.
DR GenomeRNAi; 55823; -.
DR Pharos; Q9H270; Tbio.
DR PRO; PR:Q9H270; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q9H270; protein.
DR Bgee; ENSG00000160695; Expressed in prefrontal cortex and 96 other tissues.
DR ExpressionAtlas; Q9H270; baseline and differential.
DR Genevisible; Q9H270; 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; IC:ComplexPortal.
DR GO; GO:0005769; C:early endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0030139; C:endocytic vesicle; IDA:UniProtKB.
DR GO; GO:0005768; C:endosome; IDA:UniProtKB.
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:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW.
DR GO; GO:0019904; F:protein domain specific binding; IPI:UniProtKB.
DR GO; GO:0030674; F:protein-macromolecule adaptor activity; IBA:GO_Central.
DR GO; GO:0019905; F:syntaxin binding; IDA:UniProtKB.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IMP:FlyBase.
DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW.
DR GO; GO:0034058; P:endosomal vesicle fusion; IMP:UniProtKB.
DR GO; GO:0007032; P:endosome organization; IBA:GO_Central.
DR GO; GO:0008333; P:endosome to lysosome transport; IMP:UniProtKB.
DR GO; GO:0006886; P:intracellular protein transport; IEA:InterPro.
DR GO; GO:0033147; P:negative regulation of intracellular estrogen receptor signaling pathway; IGI:FlyBase.
DR GO; GO:0048284; P:organelle fusion; IBA:GO_Central.
DR GO; GO:2000643; P:positive regulation of early endosome to late endosome transport; IMP:UniProtKB.
DR GO; GO:0045732; P:positive regulation of protein catabolic process; IMP:UniProtKB.
DR GO; GO:1903955; P:positive regulation of protein targeting to mitochondrion; HMP:ParkinsonsUK-UCL.
DR GO; GO:0016567; P:protein ubiquitination; IMP:FlyBase.
DR GO; GO:1902115; P:regulation of organelle assembly; IMP:UniProtKB.
DR GO; GO:0031647; P:regulation of protein stability; HMP:ParkinsonsUK-UCL.
DR GO; GO:0035542; P:regulation of SNARE complex assembly; IC:ComplexPortal.
DR GO; GO:0007033; P:vacuole organization; IBA:GO_Central.
DR GO; GO:0006904; P:vesicle docking involved in exocytosis; IBA:GO_Central.
DR Gene3D; 1.25.40.10; -; 1.
DR Gene3D; 2.130.10.10; -; 1.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR000547; Clathrin_H-chain/VPS_repeat.
DR InterPro; IPR011990; TPR-like_helical_dom_sf.
DR InterPro; IPR016528; VPS11.
DR InterPro; IPR024763; VPS11_C.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR PANTHER; PTHR23323:SF24; PTHR23323:SF24; 1.
DR Pfam; PF00637; Clathrin; 1.
DR Pfam; PF12451; VPS11_C; 1.
DR PIRSF; PIRSF007860; VPS11; 1.
DR SMART; SM00184; RING; 1.
DR SUPFAM; SSF48371; SSF48371; 1.
DR SUPFAM; SSF50978; SSF50978; 1.
DR PROSITE; PS50236; CHCR; 2.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW Acetylation; Autophagy; Coiled coil; Cytoplasmic vesicle; Disease variant;
KW Dystonia; Endosome; Leukodystrophy; Lysosome; Membrane; Metal-binding;
KW Methylation; Nucleotide-binding; Phosphoprotein; Protein transport;
KW Reference proteome; Repeat; Transport; Zinc; Zinc-finger.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:22223895"
FT CHAIN 2..941
FT /note="Vacuolar protein sorting-associated protein 11
FT homolog"
FT /id="PRO_0000055902"
FT REPEAT 411..561
FT /note="CHCR 1"
FT REPEAT 572..736
FT /note="CHCR 2"
FT ZN_FING 822..861
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT COILED 772..813
FT /evidence="ECO:0000255"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:22223895"
FT MOD_RES 813
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 904
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q91W86"
FT MOD_RES 924
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VARIANT 46
FT /note="P -> S (in DYT32; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:33452836"
FT /id="VAR_086501"
FT VARIANT 770
FT /note="V -> I (in dbSNP:rs11558589)"
FT /id="VAR_059813"
FT VARIANT 846
FT /note="C -> G (in HLD12)"
FT /evidence="ECO:0000269|PubMed:26307567"
FT /id="VAR_076393"
FT CONFLICT 635..636
FT /note="AH -> VI (in Ref. 2; BAA95163)"
FT /evidence="ECO:0000305"
FT CONFLICT 871
FT /note="I -> T (in Ref. 5; BAB15320)"
FT /evidence="ECO:0000305"
FT CONFLICT 889
FT /note="R -> K (in Ref. 2; BAA95163 and 4; AAG23761)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 941 AA; 107837 MW; C1F8E538ED1B56DB CRC64;
MAAYLQWRRF VFFDKELVKE PLSNDGAAPG ATPASGSAAS KFLCLPPGIT VCDSGRGSLV
FGDMEGQIWF LPRSLQLTGF QAYKLRVTHL YQLKQHNILA SVGEDEEGIN PLVKIWNLEK
RDGGNPLCTR IFPAIPGTEP TVVSCLTVHE NLNFMAIGFT DGSVTLNKGD ITRDRHSKTQ
ILHKGNYPVT GLAFRQAGKT THLFVVTTEN VQSYIVSGKD YPRVELDTHG CGLRCSALSD
PSQDLQFIVA GDECVYLYQP DERGPCFAFE GHKLIAHWFR GYLIIVSRDR KVSPKSEFTS
RDSQSSDKQI LNIYDLCNKF IAYSTVFEDV VDVLAEWGSL YVLTRDGRVH ALQEKDTQTK
LEMLFKKNLF EMAINLAKSQ HLDSDGLAQI FMQYGDHLYS KGNHDGAVQQ YIRTIGKLEP
SYVIRKFLDA QRIHNLTAYL QTLHRQSLAN ADHTTLLLNC YTKLKDSSKL EEFIKKKSES
EVHFDVETAI KVLRQAGYYS HALYLAENHA HHEWYLKIQL EDIKNYQEAL RYIGKLPFEQ
AESNMKRYGK ILMHHIPEQT TQLLKGLCTD YRPSLEGRSD REAPGCRANS EEFIPIFANN
PRELKAFLEH MSEVQPDSPQ GIYDTLLELR LQNWAHEKDP QVKEKLHAEA ISLLKSGRFC
DVFDKALVLC QMHDFQDGVL YLYEQGKLFQ QIMHYHMQHE QYRQVISVCE RHGEQDPSLW
EQALSYFARK EEDCKEYVAA VLKHIENKNL MPPLLVVQTL AHNSTATLSV IRDYLVQKLQ
KQSQQIAQDE LRVRRYREET TRIRQEIQEL KASPKIFQKT KCSICNSALE LPSVHFLCGH
SFHQHCFESY SESDADCPTC LPENRKVMDM IRAQEQKRDL HDQFQHQLRC SNDSFSVIAD
YFGRGVFNKL TLLTDPPTAR LTSSLEAGLQ RDLLMHSRRG T
