VP33A_HUMAN
ID VP33A_HUMAN Reviewed; 596 AA.
AC Q96AX1; Q547V4; Q9H5Q0;
DT 19-SEP-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=Vacuolar protein sorting-associated protein 33A;
DE Short=hVPS33A;
GN Name=VPS33A;
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=12538872; DOI=10.1073/pnas.0237292100;
RA Suzuki T., Oiso N., Gautam R., Novak E.K., Panthier J.J., Suprabha P.G.,
RA Vida T., Swank R.T., Spritz R.A.;
RT "The mouse organellar biogenesis mutant buff results from a mutation in
RT Vps33a, a homologue of yeast vps33 and Drosophila carnation.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:1146-1150(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
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].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Colon;
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 [5]
RP INTERACTION WITH UVRAG.
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 [6]
RP INTERACTION WITH VIPAS39.
RX PubMed=19109425; DOI=10.1091/mbc.e08-07-0728;
RA Zhu G.D., Salazar G., Zlatic S.A., Fiza B., Doucette M.M., Heilman C.J.,
RA Levey A.I., Faundez V., L'hernault S.W.;
RT "SPE-39 family proteins interact with the HOPS complex and function in
RT lysosomal delivery.";
RL Mol. Biol. Cell 20:1223-1240(2009).
RN [7]
RP INTERACTION WITH MON1A AND 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 [8]
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 [9]
RP INTERACTION WITH AP-3 COMPLEX AND CLATHRIN.
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 [10]
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 [11]
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 [12]
RP FUNCTION OF THE CORVET COMPLEX, 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 [13]
RP FUNCTION, FUNCTION OF THE HOPS COMPLEX, INTERACTION WITH VPS18 AND VPS16,
RP AND MUTAGENESIS OF LYS-429; TYR-438 AND ILE-441.
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 [14]
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 [15]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS), X-RAY CRYSTALLOGRAPHY (2.6
RP ANGSTROMS) IN COMPLEX WITH VPS16, INTERACTION WITH VPS16, AND MUTAGENESIS
RP OF LYS-429; TYR-438 AND ILE-441.
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 INVOLVEMENT IN MPSPS, VARIANT MPSPS TRP-498, CHARACTERIZATION OF VARIANT
RP MPSPS TRP-498, AND INTERACTION WITH VPS16 AND STX17.
RX PubMed=28013294; DOI=10.1093/hmg/ddw377;
RA Kondo H., Maksimova N., Otomo T., Kato H., Imai A., Asano Y., Kobayashi K.,
RA Nojima S., Nakaya A., Hamada Y., Irahara K., Gurinova E., Sukhomyasova A.,
RA Nogovicina A., Savvina M., Yoshimori T., Ozono K., Sakai N.;
RT "Mutation in VPS33A affects metabolism of glycosaminoglycans: a new type of
RT mucopolysaccharidosis with severe systemic symptoms.";
RL Hum. Mol. Genet. 26:173-183(2017).
RN [17]
RP INVOLVEMENT IN MPSPS, AND VARIANT MPSPS TRP-498.
RX PubMed=27547915; DOI=10.1097/mcd.0000000000000149;
RA Dursun A., Yalnizoglu D., Gerdan O.F., Yucel-Yilmaz D., Sagiroglu M.S.,
RA Yuksel B., Gucer S., Sivri S., Ozgul R.K.;
RT "A probable new syndrome with the storage disease phenotype caused by the
RT VPS33A gene mutation.";
RL Clin. Dysmorphol. 26:1-12(2017).
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:23351085,
CC PubMed:24554770, PubMed:25266290, PubMed:25783203). Required for fusion
CC of endosomes and autophagosomes with lysosomes; the function is
CC dependent on its association with VPS16 but not VIPAS39
CC (PubMed:25783203). The function in autophagosome-lysosome fusion
CC implicates STX17 but not UVRAG (PubMed:24554770).
CC {ECO:0000269|PubMed:24554770, ECO:0000269|PubMed:25783203,
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:23351085,
CC PubMed:25783203, PubMed:25266290, PubMed:23901104, PubMed:28013294).
CC Interacts with RAB5C (By similarity). Interacts with UVRAG, STX17,
CC MON1A and MON1B (PubMed:18552835, PubMed:20434987, PubMed:24554770,
CC PubMed:28013294). Interacts with VIPAS39; however, this interaction is
CC debated (PubMed:19109425, PubMed:23901104). Associates with adaptor
CC protein complex 3 (AP-3) and clathrin (PubMed:21411634). Interacts with
CC PLEKHM1 (PubMed:28325809). {ECO:0000250|UniProtKB:Q9D2N9,
CC ECO:0000269|PubMed:19109425, ECO:0000269|PubMed:20434987,
CC ECO:0000269|PubMed:21411634, ECO:0000269|PubMed:23901104,
CC ECO:0000269|PubMed:24554770, ECO:0000269|PubMed:25783203,
CC ECO:0000269|PubMed:28013294, ECO:0000269|PubMed:28325809,
CC ECO:0000305|PubMed:23351085, ECO:0000305|PubMed:25266290}.
CC -!- INTERACTION:
CC Q96AX1; P01023: A2M; NbExp=3; IntAct=EBI-2527283, EBI-640741;
CC Q96AX1; P05067: APP; NbExp=3; IntAct=EBI-2527283, EBI-77613;
CC Q96AX1; Q14790: CASP8; NbExp=3; IntAct=EBI-2527283, EBI-78060;
CC Q96AX1; Q13561: DCTN2; NbExp=3; IntAct=EBI-2527283, EBI-715074;
CC Q96AX1; Q9HAT0: ROPN1; NbExp=3; IntAct=EBI-2527283, EBI-1378139;
CC Q96AX1; P01011: SERPINA3; NbExp=3; IntAct=EBI-2527283, EBI-296557;
CC Q96AX1; P56962: STX17; NbExp=4; IntAct=EBI-2527283, EBI-2797775;
CC Q96AX1; Q9P2Y5: UVRAG; NbExp=4; IntAct=EBI-2527283, EBI-2952704;
CC Q96AX1; Q9H270: VPS11; NbExp=2; IntAct=EBI-2527283, EBI-373380;
CC Q96AX1; Q9H269: VPS16; NbExp=15; IntAct=EBI-2527283, EBI-2655929;
CC Q96AX1; Q9P253: VPS18; NbExp=6; IntAct=EBI-2527283, EBI-1053363;
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle
CC {ECO:0000250|UniProtKB:Q63615}. Late endosome membrane {ECO:0000305};
CC Peripheral membrane protein {ECO:0000305}; Cytoplasmic side
CC {ECO:0000305}. Lysosome membrane {ECO:0000305}; Peripheral membrane
CC protein {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Early endosome
CC {ECO:0000305}. Cytoplasmic vesicle, autophagosome
CC {ECO:0000269|PubMed:24554770}. Cytoplasmic vesicle, clathrin-coated
CC vesicle {ECO:0000305}.
CC -!- DISEASE: Mucopolysaccharidosis-plus syndrome (MPSPS) [MIM:617303]: A
CC form of mucopolysaccharidosis, a group of lysosomal storage diseases
CC characterized by defective degradation of glycosaminoglycans, resulting
CC in their excessive accumulation and secretion. The diseases are
CC progressive and often display a wide spectrum of clinical severity.
CC MPSPS is an autosomal recessive form characterized by coarse facial
CC features, dysostosis multiplex, hepatosplenomegaly, respiratory
CC difficulties, intellectual disability, developmental delay, pyramidal
CC signs, severe chronic anemia, renal involvement and cardiac defects.
CC Laboratory analyses show proteinuria with glomerular foamy cells,
CC excess secretion of urinary glycosaminoglycans, and extremely high
CC levels of plasma heparan sulphate. Disease onset is in infancy. Most
CC patients die in the first years of life due to cardiorespiratory
CC failure. {ECO:0000269|PubMed:27547915, ECO:0000269|PubMed:28013294}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- SIMILARITY: Belongs to the STXBP/unc-18/SEC1 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB15570.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF439857; AAL33577.1; -; mRNA.
DR EMBL; AK026840; BAB15570.1; ALT_FRAME; mRNA.
DR EMBL; CH471054; EAW98319.1; -; Genomic_DNA.
DR EMBL; BC016617; AAH16617.1; -; mRNA.
DR CCDS; CCDS9231.1; -.
DR RefSeq; NP_075067.2; NM_022916.4.
DR PDB; 4BX8; X-ray; 2.40 A; A/B=1-596.
DR PDB; 4BX9; X-ray; 2.60 A; A/B=1-596.
DR PDBsum; 4BX8; -.
DR PDBsum; 4BX9; -.
DR AlphaFoldDB; Q96AX1; -.
DR SMR; Q96AX1; -.
DR BioGRID; 122390; 254.
DR ComplexPortal; CPX-6212; HOPS tethering complex.
DR ComplexPortal; CPX-6213; CORVET tethering complex.
DR CORUM; Q96AX1; -.
DR IntAct; Q96AX1; 27.
DR MINT; Q96AX1; -.
DR STRING; 9606.ENSP00000267199; -.
DR iPTMnet; Q96AX1; -.
DR PhosphoSitePlus; Q96AX1; -.
DR BioMuta; VPS33A; -.
DR DMDM; 23396917; -.
DR EPD; Q96AX1; -.
DR jPOST; Q96AX1; -.
DR MassIVE; Q96AX1; -.
DR MaxQB; Q96AX1; -.
DR PaxDb; Q96AX1; -.
DR PeptideAtlas; Q96AX1; -.
DR PRIDE; Q96AX1; -.
DR ProteomicsDB; 76004; -.
DR TopDownProteomics; Q96AX1; -.
DR Antibodypedia; 31639; 84 antibodies from 20 providers.
DR DNASU; 65082; -.
DR Ensembl; ENST00000267199.9; ENSP00000267199.3; ENSG00000139719.11.
DR GeneID; 65082; -.
DR KEGG; hsa:65082; -.
DR MANE-Select; ENST00000267199.9; ENSP00000267199.3; NM_022916.6; NP_075067.2.
DR UCSC; uc001ucd.4; human.
DR CTD; 65082; -.
DR DisGeNET; 65082; -.
DR GeneCards; VPS33A; -.
DR HGNC; HGNC:18179; VPS33A.
DR HPA; ENSG00000139719; Low tissue specificity.
DR MalaCards; VPS33A; -.
DR MIM; 610034; gene.
DR MIM; 617303; phenotype.
DR neXtProt; NX_Q96AX1; -.
DR OpenTargets; ENSG00000139719; -.
DR Orphanet; 505248; Mucopolysaccharidosis-like syndrome with congenital heart defects and hematopoietic disorders.
DR PharmGKB; PA38306; -.
DR VEuPathDB; HostDB:ENSG00000139719; -.
DR eggNOG; KOG1302; Eukaryota.
DR GeneTree; ENSGT00940000155165; -.
DR HOGENOM; CLU_016678_3_0_1; -.
DR InParanoid; Q96AX1; -.
DR OMA; FHIFFVP; -.
DR OrthoDB; 406738at2759; -.
DR PhylomeDB; Q96AX1; -.
DR TreeFam; TF315126; -.
DR PathwayCommons; Q96AX1; -.
DR Reactome; R-HSA-9754560; SARS-CoV-2 modulates autophagy.
DR SignaLink; Q96AX1; -.
DR BioGRID-ORCS; 65082; 409 hits in 1081 CRISPR screens.
DR ChiTaRS; VPS33A; human.
DR GeneWiki; VPS33A; -.
DR GenomeRNAi; 65082; -.
DR Pharos; Q96AX1; Tbio.
DR PRO; PR:Q96AX1; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q96AX1; protein.
DR Bgee; ENSG00000139719; Expressed in buccal mucosa cell and 164 other tissues.
DR ExpressionAtlas; Q96AX1; baseline and differential.
DR Genevisible; Q96AX1; HS.
DR GO; GO:0005776; C:autophagosome; ISS:UniProtKB.
DR GO; GO:0030136; C:clathrin-coated vesicle; IEA:UniProtKB-SubCell.
DR GO; GO:0033263; C:CORVET complex; IBA:GO_Central.
DR GO; GO:0005769; C:early 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; IBA:GO_Central.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0005773; C:vacuole; IBA:GO_Central.
DR GO; GO:0097352; P:autophagosome maturation; IMP:UniProtKB.
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; IBA:GO_Central.
DR GO; GO:0032418; P:lysosome localization; IDA:UniProtKB.
DR GO; GO:0032400; P:melanosome localization; IDA:UniProtKB.
DR GO; GO:0030220; P:platelet formation; ISS:UniProtKB.
DR GO; GO:0048070; P:regulation of developmental pigmentation; ISS:UniProtKB.
DR GO; GO:0035751; P:regulation of lysosomal lumen pH; IMP:UniProtKB.
DR GO; GO:0035542; P:regulation of SNARE complex assembly; IC:ComplexPortal.
DR GO; GO:0016192; P:vesicle-mediated transport; IDA:MGI.
DR Gene3D; 1.25.40.850; -; 1.
DR Gene3D; 3.40.50.1910; -; 1.
DR Gene3D; 3.40.50.2060; -; 1.
DR Gene3D; 3.90.830.10; -; 1.
DR InterPro; IPR043154; Sec-1-like_dom1.
DR InterPro; IPR043127; Sec-1-like_dom3a.
DR InterPro; IPR001619; Sec1-like.
DR InterPro; IPR027482; Sec1-like_dom2.
DR InterPro; IPR036045; Sec1-like_sf.
DR InterPro; IPR027121; VPS33.
DR InterPro; IPR043155; VPS33_dom3b.
DR PANTHER; PTHR11679; PTHR11679; 1.
DR PANTHER; PTHR11679:SF1; PTHR11679:SF1; 1.
DR Pfam; PF00995; Sec1; 1.
DR SUPFAM; SSF56815; SSF56815; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Autophagy; Cytoplasmic vesicle; Disease variant; Endosome;
KW Lysosome; Membrane; Mucopolysaccharidosis; Protein transport;
KW Reference proteome; Transport.
FT CHAIN 1..596
FT /note="Vacuolar protein sorting-associated protein 33A"
FT /id="PRO_0000206302"
FT VARIANT 256
FT /note="I -> L (in dbSNP:rs34996966)"
FT /id="VAR_052471"
FT VARIANT 498
FT /note="R -> W (in MPSPS; may induce lysosome
FT hyperacidification; does not affect the interaction with
FT VPS16 and STX17; does not affect intracellular trafficking,
FT lipid trafficking, nor cathepsin D processing;
FT dbSNP:rs767748011)"
FT /evidence="ECO:0000269|PubMed:27547915,
FT ECO:0000269|PubMed:28013294"
FT /id="VAR_078032"
FT MUTAGEN 429
FT /note="K->D: Disrupts interaction with VPS16. Disrupts
FT interaction with VPS18 and impairs endosome-lysosome
FT fusion; when associated with K-438. Disrupts interaction
FT with VPS18 and impairs endosome-lysosome fusion; when
FT associated with K-441."
FT /evidence="ECO:0000269|PubMed:23901104,
FT ECO:0000269|PubMed:25783203"
FT MUTAGEN 438
FT /note="Y->D: Disrupts interaction with VPS16. Disrupts
FT interaction with VPS18 and impairs endosome-lysosome
FT fusion; when associated with D-429. Disrupts interaction
FT with VPS18 and impairs endosome-lysosome fusion; when
FT associated with K-441."
FT /evidence="ECO:0000269|PubMed:23901104,
FT ECO:0000269|PubMed:25783203"
FT MUTAGEN 441
FT /note="I->K: Disrupts interaction with VPS16. Disrupts
FT interaction with VPS18 and impairs endosome-lysosome
FT fusion; when associated with D-429. Disrupts interaction
FT with VPS18 and impairs endosome-lysosome fusion; when
FT associated with D-438."
FT /evidence="ECO:0000269|PubMed:23901104,
FT ECO:0000269|PubMed:25783203"
FT HELIX 3..5
FT /evidence="ECO:0007829|PDB:4BX8"
FT STRAND 7..10
FT /evidence="ECO:0007829|PDB:4BX9"
FT HELIX 13..29
FT /evidence="ECO:0007829|PDB:4BX8"
FT STRAND 34..38
FT /evidence="ECO:0007829|PDB:4BX8"
FT HELIX 40..42
FT /evidence="ECO:0007829|PDB:4BX8"
FT HELIX 43..46
FT /evidence="ECO:0007829|PDB:4BX8"
FT TURN 47..49
FT /evidence="ECO:0007829|PDB:4BX8"
FT HELIX 52..57
FT /evidence="ECO:0007829|PDB:4BX8"
FT STRAND 60..65
FT /evidence="ECO:0007829|PDB:4BX8"
FT STRAND 68..70
FT /evidence="ECO:0007829|PDB:4BX9"
FT STRAND 77..83
FT /evidence="ECO:0007829|PDB:4BX8"
FT HELIX 87..98
FT /evidence="ECO:0007829|PDB:4BX8"
FT STRAND 102..104
FT /evidence="ECO:0007829|PDB:4BX8"
FT STRAND 108..115
FT /evidence="ECO:0007829|PDB:4BX8"
FT HELIX 119..128
FT /evidence="ECO:0007829|PDB:4BX8"
FT HELIX 130..133
FT /evidence="ECO:0007829|PDB:4BX8"
FT STRAND 134..139
FT /evidence="ECO:0007829|PDB:4BX8"
FT STRAND 144..148
FT /evidence="ECO:0007829|PDB:4BX8"
FT STRAND 151..153
FT /evidence="ECO:0007829|PDB:4BX8"
FT HELIX 159..165
FT /evidence="ECO:0007829|PDB:4BX8"
FT HELIX 170..186
FT /evidence="ECO:0007829|PDB:4BX8"
FT STRAND 190..196
FT /evidence="ECO:0007829|PDB:4BX8"
FT HELIX 197..211
FT /evidence="ECO:0007829|PDB:4BX8"
FT STRAND 225..231
FT /evidence="ECO:0007829|PDB:4BX8"
FT HELIX 232..234
FT /evidence="ECO:0007829|PDB:4BX8"
FT HELIX 238..240
FT /evidence="ECO:0007829|PDB:4BX8"
FT HELIX 246..253
FT /evidence="ECO:0007829|PDB:4BX8"
FT STRAND 260..263
FT /evidence="ECO:0007829|PDB:4BX8"
FT STRAND 274..276
FT /evidence="ECO:0007829|PDB:4BX8"
FT STRAND 285..288
FT /evidence="ECO:0007829|PDB:4BX8"
FT HELIX 294..299
FT /evidence="ECO:0007829|PDB:4BX8"
FT HELIX 304..306
FT /evidence="ECO:0007829|PDB:4BX8"
FT HELIX 307..326
FT /evidence="ECO:0007829|PDB:4BX8"
FT HELIX 337..365
FT /evidence="ECO:0007829|PDB:4BX8"
FT HELIX 368..381
FT /evidence="ECO:0007829|PDB:4BX8"
FT HELIX 391..398
FT /evidence="ECO:0007829|PDB:4BX8"
FT HELIX 403..417
FT /evidence="ECO:0007829|PDB:4BX8"
FT HELIX 422..436
FT /evidence="ECO:0007829|PDB:4BX8"
FT HELIX 440..449
FT /evidence="ECO:0007829|PDB:4BX8"
FT HELIX 463..469
FT /evidence="ECO:0007829|PDB:4BX8"
FT STRAND 479..481
FT /evidence="ECO:0007829|PDB:4BX8"
FT HELIX 485..489
FT /evidence="ECO:0007829|PDB:4BX8"
FT HELIX 495..504
FT /evidence="ECO:0007829|PDB:4BX8"
FT HELIX 508..511
FT /evidence="ECO:0007829|PDB:4BX8"
FT HELIX 512..516
FT /evidence="ECO:0007829|PDB:4BX8"
FT STRAND 518..520
FT /evidence="ECO:0007829|PDB:4BX8"
FT STRAND 522..526
FT /evidence="ECO:0007829|PDB:4BX8"
FT STRAND 543..551
FT /evidence="ECO:0007829|PDB:4BX8"
FT HELIX 555..565
FT /evidence="ECO:0007829|PDB:4BX8"
FT STRAND 568..570
FT /evidence="ECO:0007829|PDB:4BX8"
FT STRAND 572..579
FT /evidence="ECO:0007829|PDB:4BX8"
FT HELIX 584..589
FT /evidence="ECO:0007829|PDB:4BX8"
SQ SEQUENCE 596 AA; 67611 MW; 12442A1D9A223F56 CRC64;
MAAHLSYGRV NLNVLREAVR RELREFLDKC AGSKAIVWDE YLTGPFGLIA QYSLLKEHEV
EKMFTLKGNR LPAADVKNII FFVRPRLELM DIIAENVLSE DRRGPTRDFH ILFVPRRSLL
CEQRLKDLGV LGSFIHREEY SLDLIPFDGD LLSMESEGAF KECYLEGDQT SLYHAAKGLM
TLQALYGTIP QIFGKGECAR QVANMMIRMK REFTGSQNSI FPVFDNLLLL DRNVDLLTPL
ATQLTYEGLI DEIYGIQNSY VKLPPEKFAP KKQGDGGKDL PTEAKKLQLN SAEELYAEIR
DKNFNAVGSV LSKKAKIISA AFEERHNAKT VGEIKQFVSQ LPHMQAARGS LANHTSIAEL
IKDVTTSEDF FDKLTVEQEF MSGIDTDKVN NYIEDCIAQK HSLIKVLRLV CLQSVCNSGL
KQKVLDYYKR EILQTYGYEH ILTLHNLEKA GLLKPQTGGR NNYPTIRKTL RLWMDDVNEQ
NPTDISYVYS GYAPLSVRLA QLLSRPGWRS IEEVLRILPG PHFEERQPLP TGLQKKRQPG
ENRVTLIFFL GGVTFAEIAA LRFLSQLEDG GTEYVIATTK LMNGTSWIEA LMEKPF
