VP33A_MOUSE
ID VP33A_MOUSE Reviewed; 598 AA.
AC Q9D2N9; Q8BGT3;
DT 19-SEP-2002, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 146.
DE RecName: Full=Vacuolar protein sorting-associated protein 33A;
GN Name=Vps33a; Synonyms=Bf, Buff;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], ROLE IN DISEASE, VARIANT GLU-251, AND
RP CHARACTERIZATION OF VARIANT GLU-251.
RC STRAIN=C57BL/6J;
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 STRAIN=C57BL/6J; TISSUE=Bone marrow, Cerebellum, Embryo, and Placenta;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Lung, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [4]
RP INTERACTION WITH RAB5C, 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 [5]
RP SUBCELLULAR LOCATION.
RX PubMed=27628032; DOI=10.1242/bio.018648;
RA Hubert V., Peschel A., Langer B., Groeger M., Rees A., Kain R.;
RT "LAMP-2 is required for incorporating syntaxin-17 into autophagosomes and
RT for their fusion with lysosomes.";
RL Biol. Open 5:1516-1529(2016).
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. Required for
CC fusion of endosomes and autophagosomes with lysosomes; the function is
CC dependent on its association with VPS16 but not VIPAS39. The function
CC in autophagosome-lysosome fusion implicates STX17 but not UVRAG.
CC {ECO:0000250|UniProtKB:Q96AX1}.
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:25266290).
CC Interacts with RAB5C (PubMed:25266290). Interacts with UVRAG, STX17,
CC MON1A and MON1B (By similarity). Associates with adaptor protein
CC complex 3 (AP-3) and clathrin (By similarity). Interacts with PLEKHM1
CC (By similarity). {ECO:0000250|UniProtKB:Q63615,
CC ECO:0000250|UniProtKB:Q96AX1, ECO:0000269|PubMed:25266290,
CC ECO:0000305|PubMed:25266290}.
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:0000269|PubMed:27628032};
CC Peripheral membrane protein {ECO:0000305}; Cytoplasmic side
CC {ECO:0000305}. Early endosome {ECO:0000305}. Cytoplasmic vesicle,
CC autophagosome {ECO:0000269|PubMed:27628032}. Cytoplasmic vesicle,
CC clathrin-coated vesicle {ECO:0000305}.
CC -!- DISEASE: Note=Defects in Vps33a are the cause of the buff mutant which
CC exhibits hypopigmentation in the coat and eyes, due to reduced size and
CC number of melanosomes in their cells. In addition, mice are prone to
CC prolonged bleeding, due to a platelet-storage pool defect.
CC -!- SIMILARITY: Belongs to the STXBP/unc-18/SEC1 family. {ECO:0000305}.
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DR EMBL; AF439858; AAL33578.1; -; mRNA.
DR EMBL; AK019463; BAB31735.1; -; mRNA.
DR EMBL; AK041982; BAC31121.1; -; mRNA.
DR EMBL; AK140553; BAE24421.1; -; mRNA.
DR EMBL; AK150282; BAE29438.1; -; mRNA.
DR EMBL; AK150550; BAE29652.1; -; mRNA.
DR CCDS; CCDS19666.1; -.
DR RefSeq; NP_084205.3; NM_029929.3.
DR AlphaFoldDB; Q9D2N9; -.
DR SMR; Q9D2N9; -.
DR BioGRID; 218770; 18.
DR IntAct; Q9D2N9; 2.
DR STRING; 10090.ENSMUSP00000031388; -.
DR iPTMnet; Q9D2N9; -.
DR PhosphoSitePlus; Q9D2N9; -.
DR EPD; Q9D2N9; -.
DR MaxQB; Q9D2N9; -.
DR PaxDb; Q9D2N9; -.
DR PeptideAtlas; Q9D2N9; -.
DR PRIDE; Q9D2N9; -.
DR ProteomicsDB; 297812; -.
DR DNASU; 77573; -.
DR Ensembl; ENSMUST00000031388; ENSMUSP00000031388; ENSMUSG00000029434.
DR GeneID; 77573; -.
DR KEGG; mmu:77573; -.
DR UCSC; uc008znz.2; mouse.
DR CTD; 65082; -.
DR MGI; MGI:1924823; Vps33a.
DR VEuPathDB; HostDB:ENSMUSG00000029434; -.
DR eggNOG; KOG1302; Eukaryota.
DR GeneTree; ENSGT00940000155165; -.
DR HOGENOM; CLU_016678_3_0_1; -.
DR InParanoid; Q9D2N9; -.
DR OMA; FHIFFVP; -.
DR OrthoDB; 406738at2759; -.
DR PhylomeDB; Q9D2N9; -.
DR TreeFam; TF315126; -.
DR BioGRID-ORCS; 77573; 34 hits in 77 CRISPR screens.
DR ChiTaRS; Vps33a; mouse.
DR PRO; PR:Q9D2N9; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q9D2N9; protein.
DR Bgee; ENSMUSG00000029434; Expressed in geniculate ganglion and 233 other tissues.
DR ExpressionAtlas; Q9D2N9; baseline and differential.
DR Genevisible; Q9D2N9; MM.
DR GO; GO:0030123; C:AP-3 adaptor complex; ISO:MGI.
DR GO; GO:0005776; C:autophagosome; IDA:UniProtKB.
DR GO; GO:0071439; C:clathrin complex; ISO:MGI.
DR GO; GO:0030136; C:clathrin-coated vesicle; IEA:UniProtKB-SubCell.
DR GO; GO:0033263; C:CORVET complex; IDA:UniProtKB.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISO:MGI.
DR GO; GO:0005769; C:early endosome; ISO:MGI.
DR GO; GO:0030897; C:HOPS complex; ISO:MGI.
DR GO; GO:0005770; C:late endosome; ISO:MGI.
DR GO; GO:0031902; C:late endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005764; C:lysosome; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR GO; GO:0005773; C:vacuole; IBA:GO_Central.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0097352; P:autophagosome maturation; ISO:MGI.
DR GO; GO:0008333; P:endosome to lysosome transport; ISO:MGI.
DR GO; GO:0006886; P:intracellular protein transport; IBA:GO_Central.
DR GO; GO:0032418; P:lysosome localization; ISO:MGI.
DR GO; GO:0032400; P:melanosome localization; ISO:MGI.
DR GO; GO:0043473; P:pigmentation; IMP:MGI.
DR GO; GO:0030220; P:platelet formation; IMP:MGI.
DR GO; GO:0048070; P:regulation of developmental pigmentation; IMP:MGI.
DR GO; GO:0035751; P:regulation of lysosomal lumen pH; ISS:UniProtKB.
DR GO; GO:0016192; P:vesicle-mediated transport; ISO:MGI.
DR Gene3D; 1.25.40.850; -; 1.
DR Gene3D; 3.40.50.1910; -; 3.
DR Gene3D; 3.40.50.2060; -; 1.
DR InterPro; IPR043154; Sec-1-like_dom1.
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 Autophagy; Cytoplasmic vesicle; Endosome; Lysosome; Membrane;
KW Protein transport; Reference proteome; Transport.
FT CHAIN 1..598
FT /note="Vacuolar protein sorting-associated protein 33A"
FT /id="PRO_0000206303"
FT VARIANT 251
FT /note="D -> E (detected in mice with the buff mutation;
FT leads to melanocytes with a reduced number of
FT undermelanized melanosomes)"
FT /evidence="ECO:0000269|PubMed:12538872"
FT CONFLICT 128
FT /note="L -> V (in Ref. 2; BAB31735)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 598 AA; 67555 MW; 7311BEA79D6C90FA CRC64;
MAAHLSYGRV NLNVLREAVR RELREFLDKC AGSKAIVWDE YLTGPFGLIA QYSLLKEHEV
EKMFTLKGSR LPAADVKNII FLVRPRLELM DIIAENVLSE DRRGPTRDFH ILFVPRRSLL
CEQRLKDLGV LGSFIHREEY SLDLIPFDGD LLSMESEGAF KECYLEGDQT SLYHAAKGLM
TLQALYGTIP QIFGKGECAR QVANMMVRMK REFTGSQNSV FPVFDNLLLL DRNVDLLTPL
ASQLTYEGLI DEIYGIQNSY VKLPPEKFAP KKQGGGSGGK DLPTEAKKLQ LNSAEELYAE
IRDKNFNAVG SVLSKKAKII SAAFEERHNA KTVGEIKQFV SQLPHMQAAR GSLANHTSIA
ELIKDVTTSE DFFDKLTVEQ EFMSGIDTDK VNSYIEDCIA QKHPLIKVLR LVCLQSVCNS
GLKQKVLDYY RREILQTYGY EHILTLNNLE KAGLLKAQTG GRNNYPTIRK TLRLWMDDVN
EQNPTDISYV YSGYAPLSVR LAQLLSRPGW RSIEEVLRIL PGPHFEERQP LPTGLQKKRQ
PGENRVTLVF FLGGVTFAEI AALRFLSQLE DGGTEYVIAT TKLMNGNSWI EALMEKPF
