ID VPS39_MOUSE Reviewed; 886 AA.
AC Q8R5L3; Q922I3;
DT 25-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 27-MAR-2024, entry version 151.
DE RecName: Full=Vam6/Vps39-like protein;
GN Name=Vps39; Synonyms=Pldn, Vam6;
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] (ISOFORMS 1 AND 2).
RC STRAIN=Swiss Webster / NIH;
RA Falcon-Perez J.M., Dell'Angelica E.C.;
RL Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Mammary tumor;
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 [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Kidney, 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 DISRUPTION PHENOTYPE.
RX PubMed=20961651; DOI=10.1016/j.imbio.2010.07.006;
RA Messler S., Kropp S., Episkopou V., Felici A., Wurthner J., Lemke R.,
RA Jerabek-Willemsen M., Willecke R., Scheu S., Pfeffer K., Wurthner J.U.;
RT "The TGF-beta signaling modulators TRAP1/TGFBRAP1 and VPS39/Vam6/TLP are
RT essential for early embryonic development.";
RL Immunobiology 216:343-350(2011).
RN [5]
RP SUBUNIT.
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).
CC -!- FUNCTION: May play a role in clustering and fusion of late endosomes
CC and lysosomes (By similarity). Regulator of TGF-beta/activin signaling,
CC inhibiting SMAD3- and activating SMAD2-dependent transcription. Acts by
CC interfering with SMAD3/SMAD4 complex formation, this would lead to
CC inhibition of SMAD3-dependent transcription and relieve SMAD3
CC inhibition of SMAD2-dependent promoters, thus increasing SMAD2-
CC dependent transcription (By similarity).
CC {ECO:0000250|UniProtKB:Q96JC1}.
CC -!- FUNCTION: Plays a role in vesicle-mediated protein trafficking to
CC lysosomal compartments including the endocytic membrane transport and
CC autophagic pathways. Acts as a component of the putative HOPS endosomal
CC tethering complex which is proposed to be involved in the Rab5-to-Rab7
CC endosome conversion probably implicating MON1A/B, and via binding
CC SNAREs and SNARE complexes to mediate tethering and docking events
CC during SNARE-mediated membrane fusion. The HOPS complex is proposed to
CC be recruited to Rab7 on the late endosomal membrane and to regulate
CC late endocytic, phagocytic and autophagic traffic towards lysosomes.
CC Involved in homotypic vesicle fusions between late endosomes and in
CC heterotypic fusions between late endosomes and lysosomes. Required for
CC fusion of endosomes and autophagosomes with lysosomes (By similarity).
CC {ECO:0000250|UniProtKB:Q96JC1}.
CC -!- SUBUNIT: Homooligomer (By similarity). Interacts with TGFBR2 and, less
CC efficiently, with TGFBR1; interaction with TGFBR2 is independent of the
CC receptor kinase activity and of the presence of TGF-beta. Also
CC interacts with ACVR2B, but not with BMPR2. Interacts with SMAD4,
CC preferentially following TGF-beta treatment (By similarity). Component
CC of the putative homotypic fusion and vacuole protein sorting (HOPS)
CC complex; the core of which composed of the class C Vps proteins VPS11,
CC VPS16, VPS18 and VPS33A, is associated with VPS39 and VPS41. Interacts
CC with PLEKHM2; involved in VPS39 recruitment to ARL8B-containing
CC lysosomes (By similarity). Associates with adaptor protein complex 3
CC (AP-3) and clathrin:AP-3 complexes (PubMed:21411634). Interacts with
CC STX17; this interaction is increased in the absence of TMEM39A (By
CC similarity). {ECO:0000250|UniProtKB:Q96JC1,
CC ECO:0000269|PubMed:21411634}.
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}. Note=Colocalizes with TGFBR1 and TGFBR2
CC in cytoplasmic vesicular structures and most prominently in cortical
CC vesicles. {ECO:0000250|UniProtKB:Q96JC1}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8R5L3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8R5L3-2; Sequence=VSP_004076;
CC -!- DISRUPTION PHENOTYPE: Embryonic lethal, before E6.5.
CC {ECO:0000269|PubMed:20961651}.
CC -!- SIMILARITY: Belongs to the VAM6/VPS39 family. {ECO:0000305}.
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DR EMBL; AF281050; AAL79766.1; -; mRNA.
DR EMBL; AF281051; AAL79767.1; -; mRNA.
DR EMBL; BC007479; AAH07479.1; -; mRNA.
DR CCDS; CCDS16619.1; -. [Q8R5L3-2]
DR CCDS; CCDS38210.1; -. [Q8R5L3-1]
DR RefSeq; NP_671495.1; NM_147153.3. [Q8R5L3-1]
DR RefSeq; NP_849182.1; NM_178851.3. [Q8R5L3-2]
DR AlphaFoldDB; Q8R5L3; -.
DR SMR; Q8R5L3; -.
DR BioGRID; 234638; 6.
DR IntAct; Q8R5L3; 4.
DR MINT; Q8R5L3; -.
DR STRING; 10090.ENSMUSP00000099559; -.
DR iPTMnet; Q8R5L3; -.
DR PhosphoSitePlus; Q8R5L3; -.
DR EPD; Q8R5L3; -.
DR MaxQB; Q8R5L3; -.
DR PaxDb; 10090-ENSMUSP00000099559; -.
DR ProteomicsDB; 297888; -. [Q8R5L3-1]
DR ProteomicsDB; 297889; -. [Q8R5L3-2]
DR Pumba; Q8R5L3; -.
DR Antibodypedia; 23540; 124 antibodies from 25 providers.
DR DNASU; 269338; -.
DR Ensembl; ENSMUST00000028752.8; ENSMUSP00000028752.8; ENSMUSG00000027291.16. [Q8R5L3-2]
DR Ensembl; ENSMUST00000102501.10; ENSMUSP00000099559.4; ENSMUSG00000027291.16. [Q8R5L3-1]
DR GeneID; 269338; -.
DR KEGG; mmu:269338; -.
DR UCSC; uc008lvj.2; mouse. [Q8R5L3-1]
DR AGR; MGI:2443189; -.
DR CTD; 23339; -.
DR MGI; MGI:2443189; Vps39.
DR VEuPathDB; HostDB:ENSMUSG00000027291; -.
DR eggNOG; KOG2063; Eukaryota.
DR GeneTree; ENSGT00530000063596; -.
DR HOGENOM; CLU_004190_1_1_1; -.
DR InParanoid; Q8R5L3; -.
DR OMA; LFRLPNF; -.
DR OrthoDB; 38195at2759; -.
DR PhylomeDB; Q8R5L3; -.
DR TreeFam; TF105803; -.
DR BioGRID-ORCS; 269338; 19 hits in 80 CRISPR screens.
DR ChiTaRS; Bloc1s6; mouse.
DR PRO; PR:Q8R5L3; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q8R5L3; Protein.
DR Bgee; ENSMUSG00000027291; Expressed in embryonic brain and 247 other cell types or tissues.
DR ExpressionAtlas; Q8R5L3; baseline and differential.
DR Genevisible; Q8R5L3; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0030897; C:HOPS complex; ISO:MGI.
DR GO; GO:0005770; C:late endosome; ISS:UniProtKB.
DR GO; GO:0031902; C:late endosome membrane; ISO:MGI.
DR GO; GO:1902501; C:lysosomal HOPS complex; ISS:UniProtKB.
DR GO; GO:0005765; C:lysosomal membrane; ISO:MGI.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0061909; P:autophagosome-lysosome fusion; ISS:UniProtKB.
DR GO; GO:0006914; P:autophagy; ISO:MGI.
DR GO; GO:0032456; P:endocytic recycling; ISO:MGI.
DR GO; GO:0034058; P:endosomal vesicle fusion; ISO:MGI.
DR GO; GO:0008333; P:endosome to lysosome transport; ISO:MGI.
DR GO; GO:0006886; P:intracellular protein transport; IEA:InterPro.
DR GO; GO:1902774; P:late endosome to lysosome transport; ISO:MGI.
DR InterPro; IPR000547; Clathrin_H-chain/VPS_repeat.
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 PANTHER; PTHR12894; CNH DOMAIN CONTAINING; 1.
DR PANTHER; PTHR12894:SF49; VAM6_VPS39-LIKE PROTEIN; 1.
DR Pfam; PF00780; CNH; 1.
DR Pfam; PF10366; Vps39_1; 1.
DR Pfam; PF10367; Vps39_2; 1.
DR SMART; SM00036; CNH; 1.
DR PROSITE; PS50236; CHCR; 1.
DR PROSITE; PS50219; CNH; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Autophagy; Cytoplasm; Endosome; Lysosome; Membrane;
KW Protein transport; Reference proteome; Transport.
FT CHAIN 1..886
FT /note="Vam6/Vps39-like protein"
FT /id="PRO_0000065902"
FT DOMAIN 15..294
FT /note="CNH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00795"
FT REPEAT 573..750
FT /note="CHCR"
FT VAR_SEQ 47..58
FT /note="VPADVASPESGS -> G (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334, ECO:0000303|Ref.1"
FT /id="VSP_004076"
SQ SEQUENCE 886 AA; 101693 MW; BD46EF52D404C2DA CRC64;
MHDAFEPVPI LEKLPLQIDC LAAWEEWLLV GTKQGHLLLY RIRKDVVPAD VASPESGSCN
RFEVTLEKSN KNFSKKIQQI HVVSQFKILV SLLENNIYVH DLLTFQQITT VSKAKGASLF
TCDLQHTETG EEVLRMCVAV RKKLQLYFWK DREFHELQGD FSVPDVPKSM AWCENSICVG
FKRDYYLIRV DGKGSIKELF PTGKQLEPLV APLADGKVAV GQDDLTVVLN EEGICTQKCA
LNWTDIPVAM EHQPPYIVAV LPRYVEIRTL EPRLLVQSIE LQRPRFITSG GSNIIYVASN
HFVWRLIPVP MATQIQQLLQ DKQFELALQL AEMKDDSDSE KQQQIHHIKN LYAFNLFCQK
RFDESMQVFA KLGTDPTHVM GLYPDLLPTD YRKQLQYPNP LPTLSGAELE KAHLALIDYL
TQKRSQLVKK LNDSDHQSST SPLMEGTPTI KSKKKLLQII DTTLLKCYLH TNVALVAPLL
RLENNHCHIE ESEHVLKKAH KYSELIILYE KKGLHEKALQ VLVDQSKKAN SPLKGHERTV
QYLQHLGTEN LHLIFSYSVW VLRDFPEDGL KIFTEDLPEV ESLPRDRVLN FLIENFKALA
IPYLEHIIHV WEETGSQFHN CLIQLYCEKV QSLMKDYLLS LPTGKSPVPA GEEGGELGEY
RQKLLMFLEI SSHYDPGRLI CDFPFDGLLE ERALLLGRMG KHEQALFIYV HVLKDTKMAK
EYCHKHYDQN KEGNKDVYLS LLRMYLSPPS IHCLGPIKLE LLEPQANLQA ALQVLELHYS
KLDTTKAINL LPANTQINDI RIFLEKVLEE NAQKKRFNQV LKNLLHAEFL RVQEERILHQ
QVKCIITEEK VCMVCKKKIG NSAFARYPNG VVVHYFCSKE VNSADT
//
