VPS39_CAEEL
ID VPS39_CAEEL Reviewed; 926 AA.
AC Q1ZXS5; A8JJR1; Q9XUQ4;
DT 30-AUG-2017, integrated into UniProtKB/Swiss-Prot.
DT 18-APR-2006, sequence version 1.
DT 03-AUG-2022, entry version 120.
DE RecName: Full=Vacuolar protein sorting-associated protein 39 homolog {ECO:0000305};
GN Name=vps-39 {ECO:0000312|WormBase:T08G5.5b};
GN ORFNames=T08G5.5 {ECO:0000312|WormBase:T08G5.5b};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2]
RP INTERACTION WITH CUTI-1.
RX PubMed=19357781; DOI=10.1371/journal.pone.0005117;
RA Fritz J.A., Behm C.A.;
RT "CUTI-1: A novel tetraspan protein involved in C. elegans CUTicle formation
RT and epithelial integrity.";
RL PLoS ONE 4:e5117-e5117(2009).
RN [3] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=24501423; DOI=10.1091/mbc.e13-09-0521;
RA Delahaye J.L., Foster O.K., Vine A., Saxton D.S., Curtin T.P., Somhegyi H.,
RA Salesky R., Hermann G.J.;
RT "Caenorhabditis elegans HOPS and CCZ-1 mediate trafficking to lysosome-
RT related organelles independently of RAB-7 and SAND-1.";
RL Mol. Biol. Cell 25:1073-1096(2014).
RN [4] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=25273556; DOI=10.1091/mbc.e13-12-0710;
RA Solinger J.A., Spang A.;
RT "Loss of the Sec1/Munc18-family proteins VPS-33.2 and VPS-33.1 bypasses a
RT block in endosome maturation in Caenorhabditis elegans.";
RL Mol. Biol. Cell 25:3909-3925(2014).
RN [5] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=25126728; DOI=10.4161/auto.29745;
RA Jenzer C., Manil-Segalen M., Lefebvre C., Largeau C., Glatigny A.,
RA Legouis R.;
RT "Human GABARAP can restore autophagosome biogenesis in a C. elegans lgg-1
RT mutant.";
RL Autophagy 10:1868-1872(2014).
RN [6] {ECO:0000305}
RP FUNCTION, INTERACTION WITH LGG-2, AND DISRUPTION PHENOTYPE.
RX PubMed=24374177; DOI=10.1016/j.devcel.2013.11.022;
RA Manil-Segalen M., Lefebvre C., Jenzer C., Trichet M., Boulogne C.,
RA Satiat-Jeunemaitre B., Legouis R.;
RT "The C. elegans LC3 acts downstream of GABARAP to degrade autophagosomes by
RT interacting with the HOPS subunit VPS39.";
RL Dev. Cell 28:43-55(2014).
CC -!- FUNCTION: Plays a role in vesicle-mediated protein trafficking to
CC lysosomal compartments including the endocytic membrane transport and
CC autophagic pathways (By similarity). Believed to act in part as a
CC component of the putative HOPS endosomal tethering complex which is
CC proposed to be involved in the rab-5-to-rab-7 endosome conversion
CC probably implicating sand-1, and via binding SNAREs and SNARE complexes
CC to mediate tethering and docking events during SNARE-mediated membrane
CC fusion (PubMed:25273556). The HOPS complex is proposed to be recruited
CC to rab-7 on the late endosomal membrane and to regulate late endocytic,
CC phagocytic and autophagic traffic towards lysosomes (PubMed:24374177).
CC Involved in homotypic vesicle fusions between late endosomes and in
CC heterotypic fusions between late endosomes and lysosomes (By
CC similarity). Required for fusion of endosomes (By similarity). In
CC association with lgg-2 mediates the tethering of autophagosomes with
CC lysosomes to form autolysosomes (PubMed:25126728, PubMed:24374177).
CC Within the HOPS complex, contributes to the normal development of gut
CC granules in embryonic and adult intestinal cells (PubMed:24501423).
CC {ECO:0000250|UniProtKB:Q96JC1, ECO:0000269|PubMed:24374177,
CC ECO:0000269|PubMed:24501423, ECO:0000269|PubMed:25126728,
CC ECO:0000269|PubMed:25273556}.
CC -!- SUBUNIT: Probable core component of the homotypic fusion and vacuole
CC protein sorting (HOPS) complex consisting of the core class C Vps
CC proteins vps-11, vps-16, vps-18, and which further associates with vps-
CC 33.1, vps-39 and vps-41 (By similarity). May interact with lgg-2
CC (PubMed:24374177). Interacts with cuti-1 (PubMed:19357781).
CC {ECO:0000250|UniProtKB:Q96JC1, ECO:0000269|PubMed:19357781,
CC ECO:0000305|PubMed:24374177}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q96JC1}.
CC Lysosome membrane {ECO:0000250|UniProtKB:Q96JC1}; Peripheral membrane
CC protein {ECO:0000250|UniProtKB:Q96JC1}. Late endosome membrane
CC {ECO:0000250|UniProtKB:Q96JC1}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q96JC1}. Late endosome
CC {ECO:0000250|UniProtKB:Q96JC1}. Lysosome
CC {ECO:0000250|UniProtKB:Q96JC1}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=b {ECO:0000312|WormBase:T08G5.5b};
CC IsoId=Q1ZXS5-1; Sequence=Displayed;
CC Name=a {ECO:0000312|WormBase:T08G5.5a};
CC IsoId=Q1ZXS5-2; Sequence=VSP_059059;
CC Name=c {ECO:0000312|WormBase:T08G5.5c};
CC IsoId=Q1ZXS5-3; Sequence=VSP_059058, VSP_059059;
CC -!- DISRUPTION PHENOTYPE: In 1-cell to 20-cell stage embryos, there is
CC defective autophagosome degradation with an accumulation of endosomes,
CC lgg-1- and lgg-2-positive autophagosomes, amphisomes and paternal
CC mitochondria close to the nuclei (PubMed:25126728, PubMed:24374177).
CC Reduced number of gut granules in the adult intestine
CC (PubMed:24501423). RNAi-mediated knockdown results in a reduced number
CC of gut granules in embryonic intestinal cells (PubMed:24501423). RNAi-
CC mediated knockdown results in the formation of large late
CC endosomes/lysosomes, but with simultaneous expression of rab-5- and
CC rab-7-positive vesicles on the basal side of gut cells
CC (PubMed:25273556). {ECO:0000269|PubMed:24374177,
CC ECO:0000269|PubMed:24501423, ECO:0000269|PubMed:25126728,
CC ECO:0000269|PubMed:25273556}.
CC -!- SIMILARITY: Belongs to the VAM6/VPS39 family. {ECO:0000305}.
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DR EMBL; BX284605; CAB04720.1; -; Genomic_DNA.
DR EMBL; BX284605; CAJ85769.1; -; Genomic_DNA.
DR EMBL; BX284605; CAP16526.1; -; Genomic_DNA.
DR PIR; T24712; T24712.
DR RefSeq; NP_001041163.1; NM_001047698.2. [Q1ZXS5-2]
DR RefSeq; NP_001041164.1; NM_001047699.4. [Q1ZXS5-1]
DR RefSeq; NP_001123010.1; NM_001129538.2. [Q1ZXS5-3]
DR AlphaFoldDB; Q1ZXS5; -.
DR ComplexPortal; CPX-1136; HOPS complex.
DR DIP; DIP-24817N; -.
DR IntAct; Q1ZXS5; 29.
DR STRING; 6239.T08G5.5b; -.
DR EPD; Q1ZXS5; -.
DR PaxDb; Q1ZXS5; -.
DR EnsemblMetazoa; T08G5.5a.1; T08G5.5a.1; WBGene00011625. [Q1ZXS5-2]
DR EnsemblMetazoa; T08G5.5b.1; T08G5.5b.1; WBGene00011625. [Q1ZXS5-1]
DR EnsemblMetazoa; T08G5.5c.1; T08G5.5c.1; WBGene00011625. [Q1ZXS5-3]
DR GeneID; 179902; -.
DR KEGG; cel:CELE_T08G5.5; -.
DR UCSC; T08G5.5b; c. elegans.
DR CTD; 179902; -.
DR WormBase; T08G5.5a; CE18946; WBGene00011625; vps-39. [Q1ZXS5-2]
DR WormBase; T08G5.5b; CE40122; WBGene00011625; vps-39. [Q1ZXS5-1]
DR WormBase; T08G5.5c; CE41694; WBGene00011625; vps-39. [Q1ZXS5-3]
DR eggNOG; KOG2063; Eukaryota.
DR GeneTree; ENSGT00530000063596; -.
DR InParanoid; Q1ZXS5; -.
DR OMA; DETEMAR; -.
DR OrthoDB; 291710at2759; -.
DR PhylomeDB; Q1ZXS5; -.
DR SignaLink; Q1ZXS5; -.
DR PRO; PR:Q1ZXS5; -.
DR Proteomes; UP000001940; Chromosome V.
DR Bgee; WBGene00011625; Expressed in germ line (C elegans) and 4 other tissues.
DR ExpressionAtlas; Q1ZXS5; baseline and differential.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0030897; C:HOPS complex; ISS:WormBase.
DR GO; GO:0031902; C:late endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0006914; P:autophagy; IBA:GO_Central.
DR GO; GO:0034058; P:endosomal vesicle fusion; IBA:GO_Central.
DR GO; GO:0042144; P:vacuole fusion, non-autophagic; IC:ComplexPortal.
DR Gene3D; 2.130.10.10; -; 1.
DR InterPro; IPR001180; CNH_dom.
DR InterPro; IPR032914; Vam6/VPS39/TRAP1.
DR InterPro; IPR019452; VPS39/TGF_beta_rcpt-assoc_1.
DR InterPro; IPR019453; VPS39/TGF_beta_rcpt-assoc_2.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR PANTHER; PTHR12894; PTHR12894; 1.
DR Pfam; PF00780; CNH; 1.
DR Pfam; PF10366; Vps39_1; 1.
DR Pfam; PF10367; Vps39_2; 1.
DR SUPFAM; SSF50978; SSF50978; 1.
DR PROSITE; PS50219; CNH; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Autophagy; Cytoplasm; Endosome; Lysosome; Membrane;
KW Reference proteome.
FT CHAIN 1..926
FT /note="Vacuolar protein sorting-associated protein 39
FT homolog"
FT /evidence="ECO:0000305"
FT /id="PRO_0000441276"
FT DOMAIN 15..306
FT /note="CNH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00795"
FT REPEAT 590..768
FT /note="CHCR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01006"
FT VAR_SEQ 385..387
FT /note="Missing (in isoform c)"
FT /evidence="ECO:0000305"
FT /id="VSP_059058"
FT VAR_SEQ 659..661
FT /note="Missing (in isoform a and isoform c)"
FT /evidence="ECO:0000305"
FT /id="VSP_059059"
SQ SEQUENCE 926 AA; 105256 MW; 180A221D7B4FB49F CRC64;
MYDAYTPCEV ALRLPVEVTC LAFQESNQTL LAGGRAGHLY AYTISANRRG FELTNICKSF
HKKAVMELKV CQREDLLLCV SDGQLMAHKL SDPEYKVETL IHKVKPVQTF ARFSPKTSGD
LYVIVSSRKK LYLFKWGEKD GHKEFIEVAL DYNPVFLDTP TSIRCVGEMV FFSVRNEYFS
MTMQKDKTTT SPSEGSTPEG WNGFVTRLLN FNCQPGIVPM IDRRRVAFVR NEIVVTTDIW
GQRPANVLSD EYKFSEVPMQ IVYDSPYLVG MLSKGRVEVR SIFDGQLVQT MSLPKAMTLC
SGARGQVFVA ALSDIWILDT SQNLRKNVSH LIQERHFELA IQLAENSNLF AEEQKLEIKK
KAALNLFNQK KFDESFALFG EIKTDISEVL SIIRMFPELL PDGFQSMTGV VSDMPANDRM
RALLALGSYL SEIRTEHAKH IELYNRLYSS GAAKKTDEDE KAKLLLTLRV VDTTLLKCYI
KTKPMLVDSL IRLQSNACTF EDAKKILESE GRLRSLFILY ETRKKHEMAL DLFIDQSSRP
DADPFFDDAI QQIVEYLQSL GNSNLPLILK YAKWVLAKNL EAGVQIFTSD ETEMARNLNR
KAVVEFLKSE CPDALIPYLE HVIFKWEEPS SYFHETLLEF YVARVNTLFK DYVHAFPDAF
SDENITRAGD EDGELGLYRK RLLKFLEVSH SYSPQTVLLQ LAPHAFYEER ALILGRLKQH
EQALAIYVNT LKNVPAAEEY CRLYYNAHDE TNSQVYLMLF RTLVHPNQQQ LHSIPYHADS
TPFGSYRDDV SEASTLVNST SSYQPDVNTA IKILAKHADK IDTVGALNML PATTPLRVVF
SAINAVIQTT GRQASTRKME KSVSQCAMSK KLERKNKAQS TKIIVNFSSE CVVCEKKIAV
SAFVRYPDGR LAHLYCHNDS QGGNRN
