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Showing Protein Vam6/Vps39-like protein (HMDBP14485)

IdentificationBiological propertiesGene propertiesProtein propertiesExternal linksReferencesXMLShow 0 metabolites
Identification
HMDB Protein ID HMDBP14485
Secondary Accession Numbers None
Name Vam6/Vps39-like protein
Synonyms
  1. TRAP1-like protein
  2. hVam6p
Gene Name VPS39
Protein Type Unknown
Biological Properties
General Function Not Available
Specific Function Regulator of TGF-beta/activin signaling, inhibiting SMAD3- and activating SMAD2-dependent transcription. Acts by interfering with SMAD3/SMAD4 complex formation, this would lead to inhibition of SMAD3-dependent transcription and relieve SMAD3 inhibition of SMAD2-dependent promoters, thus increasing SMAD2-dependent transcription. Does not affect TGF-beta-induced SMAD2 or SMAD3 phosphorylation, nor SMAD2/SMAD4 complex formation.Plays a role in vesicle-mediated protein trafficking to lysosomal compartments including the endocytic membrane transport and autophagic pathways. Acts as a component of the putative HOPS endosomal tethering complex which is proposed to be involved in the Rab5-to-Rab7 endosome conversion probably implicating MON1A/B, and via binding SNAREs and SNARE complexes to mediate tethering and docking events during SNARE-mediated membrane fusion. The HOPS complex is proposed to be recruited to Rab7 on the late endosomal membrane and to regulate late endocytic, phagocytic and autophagic traffic towards lysosomes (PubMed:23351085). Involved in homotypic vesicle fusions between late endosomes and in heterotypic fusions between late endosomes and lysosomes (PubMed:11448994, PubMed:23351085, PubMed:23167963). Required for fusion of endosomes and autophagosomes with lysosomes (PubMed:25783203).
Pathways
  • Salmonella infection
Reactions Not Available
GO Classification
Biological Process
endosome to lysosome transport
autophagosome-lysosome fusion
endosomal vesicle fusion
late endosome to lysosome transport
intracellular protein transport
endocytic recycling
autophagy
Cellular Component
cytoplasm
AP-3 adaptor complex
HOPS complex
lysosomal HOPS complex
late endosome
membrane
late endosome membrane
lysosomal membrane
Cellular Location Not Available
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs Not Available
Gene Sequence Not Available
Protein Properties
Number of Residues 886
Molecular Weight 101808.245
Theoretical pI 6.993
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID Q96JC1
UniProtKB/Swiss-Prot Entry Name VPS39_HUMAN
PDB IDs
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
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  2. Nakajima D, Okazaki N, Yamakawa H, Kikuno R, Ohara O, Nagase T: Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones. DNA Res. 2002 Jun 30;9(3):99-106. [PubMed:12168954 ]
  3. Bechtel S, Rosenfelder H, Duda A, Schmidt CP, Ernst U, Wellenreuther R, Mehrle A, Schuster C, Bahr A, Blocker H, Heubner D, Hoerlein A, Michel G, Wedler H, Kohrer K, Ottenwalder B, Poustka A, Wiemann S, Schupp I: The full-ORF clone resource of the German cDNA Consortium. BMC Genomics. 2007 Oct 31;8:399. [PubMed:17974005 ]
  4. Schroder B, Wrocklage C, Pan C, Jager R, Kosters B, Schafer H, Elsasser HP, Mann M, Hasilik A: Integral and associated lysosomal membrane proteins. Traffic. 2007 Dec;8(12):1676-86. Epub 2007 Sep 26. [PubMed:17897319 ]
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  6. Nagase T, Ishikawa K, Suyama M, Kikuno R, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O: Prediction of the coding sequences of unidentified human genes. XI. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. DNA Res. 1998 Oct 30;5(5):277-86. [PubMed:9872452 ]
  7. Felici A, Wurthner JU, Parks WT, Giam LR, Reiss M, Karpova TS, McNally JG, Roberts AB: TLP, a novel modulator of TGF-beta signaling, has opposite effects on Smad2- and Smad3-dependent signaling. EMBO J. 2003 Sep 1;22(17):4465-77. doi: 10.1093/emboj/cdg428. [PubMed:12941698 ]
  8. Caplan S, Hartnell LM, Aguilar RC, Naslavsky N, Bonifacino JS: Human Vam6p promotes lysosome clustering and fusion in vivo. J Cell Biol. 2001 Jul 9;154(1):109-22. doi: 10.1083/jcb.200102142. [PubMed:11448994 ]
  9. Solinger JA, Spang A: Tethering complexes in the endocytic pathway: CORVET and HOPS. FEBS J. 2013 Jun;280(12):2743-57. doi: 10.1111/febs.12151. Epub 2013 Feb 21. [PubMed:23351085 ]
  10. Graham SC, Wartosch L, Gray SR, Scourfield EJ, Deane JE, Luzio JP, Owen DJ: Structural basis of Vps33A recruitment to the human HOPS complex by Vps16. Proc Natl Acad Sci U S A. 2013 Aug 13;110(33):13345-50. doi: 10.1073/pnas.1307074110. Epub 2013 Jul 30. [PubMed:23901104 ]
  11. Pols MS, ten Brink C, Gosavi P, Oorschot V, Klumperman J: The HOPS proteins hVps41 and hVps39 are required for homotypic and heterotypic late endosome fusion. Traffic. 2013 Feb;14(2):219-32. doi: 10.1111/tra.12027. Epub 2012 Dec 12. [PubMed:23167963 ]
  12. Khatter D, Raina VB, Dwivedi D, Sindhwani A, Bahl S, Sharma M: The small GTPase Arl8b regulates assembly of the mammalian HOPS complex on lysosomes. J Cell Sci. 2015 May 1;128(9):1746-61. doi: 10.1242/jcs.162651. Epub 2015 Apr 23. [PubMed:25908847 ]
  13. Wartosch L, Gunesdogan U, Graham SC, Luzio JP: Recruitment of VPS33A to HOPS by VPS16 Is Required for Lysosome Fusion with Endosomes and Autophagosomes. Traffic. 2015 Jul;16(7):727-42. doi: 10.1111/tra.12283. Epub 2015 Apr 30. [PubMed:25783203 ]
  14. Miao G, Zhang Y, Chen D, Zhang H: The ER-Localized Transmembrane Protein TMEM39A/SUSR2 Regulates Autophagy by Controlling the Trafficking of the PtdIns(4)P Phosphatase SAC1. Mol Cell. 2020 Feb 6;77(3):618-632.e5. doi: 10.1016/j.molcel.2019.10.035. Epub 2019 Dec 2. [PubMed:31806350 ]
  15. Miao G, Zhao H, Li Y, Ji M, Chen Y, Shi Y, Bi Y, Wang P, Zhang H: ORF3a of the COVID-19 virus SARS-CoV-2 blocks HOPS complex-mediated assembly of the SNARE complex required for autolysosome formation. Dev Cell. 2021 Feb 22;56(4):427-442.e5. doi: 10.1016/j.devcel.2020.12.010. Epub 2020 Dec 16. [PubMed:33422265 ]