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   27-MAR-2024, entry version 173.
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; 265.
DR   ComplexPortal; CPX-6212; HOPS tethering complex.
DR   ComplexPortal; CPX-6213; CORVET tethering complex.
DR   CORUM; Q96AX1; -.
DR   IntAct; Q96AX1; 30.
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; 9606-ENSP00000267199; -.
DR   PeptideAtlas; Q96AX1; -.
DR   ProteomicsDB; 76004; -.
DR   Pumba; Q96AX1; -.
DR   TopDownProteomics; Q96AX1; -.
DR   Antibodypedia; 31639; 92 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   AGR; HGNC:18179; -.
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; 22722at2759; -.
DR   PhylomeDB; Q96AX1; -.
DR   TreeFam; TF315126; -.
DR   PathwayCommons; Q96AX1; -.
DR   Reactome; R-HSA-9754560; SARS-CoV-2 modulates autophagy.
DR   SignaLink; Q96AX1; -.
DR   SIGNOR; Q96AX1; -.
DR   BioGRID-ORCS; 65082; 423 hits in 1169 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 166 other cell types or 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: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; IBA:GO_Central.
DR   GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR   GO; GO:0097352; P:autophagosome maturation; IMP:UniProtKB.
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; 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; NAS: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   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; IPR043155; VPS33_dom3b.
DR   PANTHER; PTHR11679:SF85; VACUOLAR PROTEIN SORTING-ASSOCIATED PROTEIN 33A; 1.
DR   PANTHER; PTHR11679; VESICLE PROTEIN SORTING-ASSOCIATED; 1.
DR   Pfam; PF00995; Sec1; 1.
DR   SUPFAM; SSF56815; Sec1/munc18-like (SM) proteins; 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
//