Q96JC1 (VPS39_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Vam6/Vps39-like protein

Alternative name(s):
TRAP1-like protein
Short name=hVam6p

Gene names

Name:	VPS39
Synonyms:	KIAA0770, TLP, VAM6

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	886 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	May play a role in clustering and fusion of late endosomes and lysosomes. 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. Ref.1 Ref.9
Subunit structure	Homooligomer. Interacts with TGFBR2 and, less efficiently, with TGFBR1; interaction with TGFBR2 is independent of the receptor kinase activity and of the presence of TGF-beta. Also interacts with ACVR2B, but not with BMPR2. Interacts with SMAD4, preferentially following TGF-beta treatment. Does not interact with SAMD2 or SMAD3. Ref.1 Ref.9
Subcellular location	Cytoplasm. Lysosome membrane; Peripheral membrane protein. Late endosome membrane; Peripheral membrane protein. Note: Colocalizes with TGFBR1 and TGFBR2 in cytoplasmic vesicular structures and most prominently in cortical vesicles. Ref.1 Ref.10
Tissue specificity	Widely expressed, with highest levels in heart, skeletal muscle, kidney, pancreas, brain, placenta and spleen. Ref.1 Ref.9
Sequence similarities	Belongs to the VAM6/VPS39 family. Contains 1 CNH domain.
Sequence caution	The sequence BAA34490.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Biological process	Protein transport Transport
Cellular component	Cytoplasm Endosome Lysosome Membrane
Coding sequence diversity	Alternative splicing
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	protein transport Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	HOPS complex Inferred from direct assay PubMed 19109425. Source: UniProtKB late endosome membrane Inferred from electronic annotation. Source: UniProtKB-SubCell lysosomal membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	small GTPase regulator activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q96JC1-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q96JC1-2)

The sequence of this isoform differs from the canonical sequence as follows:
     47-58: VPADVASPESGS → G

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 886	886	Vam6/Vps39-like protein		PRO_0000065901
Regions
	Domain	15 – 294	280	CNH
Natural variations
	Alternative sequence	47 – 58	12	VPADV…PESGS → G in isoform 2.		VSP_004075
Experimental info
	Sequence conflict	135	1	R → Q in AAK72222. Ref.1
	Sequence conflict	191	1	D → G in CAD97646. Ref.5
	Sequence conflict	846	1	I → T in CAD97646. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 24, 2005. Version 2. Checksum: E5A40A3C787EB112	FASTA	886	101,809
	10 20 30 40 50 60 MHDAFEPVPI LEKLPLQIDC LAAWEEWLLV GTKQGHLLLY RIRKDVVPAD VASPESGSCN 70 80 90 100 110 120 RFEVTLEKSN KNFSKKIQQI HVVSQFKILV SLLENNIYVH DLLTFQQITT VSKAKGASLF 130 140 150 160 170 180 TCDLQHTETG EEVLRMCVAV KKKLQLYFWK DREFHELQGD FSVPDVPKSM AWCENSICVG 190 200 210 220 230 240 FKRDYYLIRV DGKGSIKELF PTGKQLEPLV APLADGKVAV GQDDLTVVLN EEGICTQKCA 250 260 270 280 290 300 LNWTDIPVAM EHQPPYIIAV LPRYVEIRTF EPRLLVQSIE LQRPRFITSG GSNIIYVASN 310 320 330 340 350 360 HFVWRLIPVP MATQIQQLLQ DKQFELALQL AEMKDDSDSE KQQQIHHIKN LYAFNLFCQK 370 380 390 400 410 420 RFDESMQVFA KLGTDPTHVM GLYPDLLPTD YRKQLQYPNP LPVLSGAELE KAHLALIDYL 430 440 450 460 470 480 TQKRSQLVKK LNDSDHQSST SPLMEGTPTI KSKKKLLQII DTTLLKCYLH TNVALVAPLL 490 500 510 520 530 540 RLENNHCHIE ESEHVLKKAH KYSELIILYE KKGLHEKALQ VLVDQSKKAN SPLKGHERTV 550 560 570 580 590 600 QYLQHLGTEN LHLIFSYSVW VLRDFPEDGL KIFTEDLPEV ESLPRDRVLG FLIENFKGLA 610 620 630 640 650 660 IPYLEHIIHV WEETGSRFHN CLIQLYCEKV QGLMKEYLLS FPAGKTPVPA GEEEGELGEY 670 680 690 700 710 720 RQKLLMFLEI SSYYDPGRLI CDFPFDGLLE ERALLLGRMG KHEQALFIYV HILKDTRMAE 730 740 750 760 770 780 EYCHKHYDRN KDGNKDVYLS LLRMYLSPPS IHCLGPIKLE LLEPKANLQA ALQVLELHHS 790 800 810 820 830 840 KLDTTKALNL LPANTQINDI RIFLEKVLEE NAQKKRFNQV LKNLLHAEFL RVQEERILHQ 850 860 870 880 QVKCIITEEK VCMVCKKKIG NSAFARYPNG VVVHYFCSKE VNPADT
	Isoform 2 [UniParc]. Checksum: 295A0D8A0E824795	FASTA	875	100,769
	10 20 30 40 50 60 MHDAFEPVPI LEKLPLQIDC LAAWEEWLLV GTKQGHLLLY RIRKDVGCNR FEVTLEKSNK 70 80 90 100 110 120 NFSKKIQQIH VVSQFKILVS LLENNIYVHD LLTFQQITTV SKAKGASLFT CDLQHTETGE 130 140 150 160 170 180 EVLRMCVAVK KKLQLYFWKD REFHELQGDF SVPDVPKSMA WCENSICVGF KRDYYLIRVD 190 200 210 220 230 240 GKGSIKELFP TGKQLEPLVA PLADGKVAVG QDDLTVVLNE EGICTQKCAL NWTDIPVAME 250 260 270 280 290 300 HQPPYIIAVL PRYVEIRTFE PRLLVQSIEL QRPRFITSGG SNIIYVASNH FVWRLIPVPM 310 320 330 340 350 360 ATQIQQLLQD KQFELALQLA EMKDDSDSEK QQQIHHIKNL YAFNLFCQKR FDESMQVFAK 370 380 390 400 410 420 LGTDPTHVMG LYPDLLPTDY RKQLQYPNPL PVLSGAELEK AHLALIDYLT QKRSQLVKKL 430 440 450 460 470 480 NDSDHQSSTS PLMEGTPTIK SKKKLLQIID TTLLKCYLHT NVALVAPLLR LENNHCHIEE 490 500 510 520 530 540 SEHVLKKAHK YSELIILYEK KGLHEKALQV LVDQSKKANS PLKGHERTVQ YLQHLGTENL 550 560 570 580 590 600 HLIFSYSVWV LRDFPEDGLK IFTEDLPEVE SLPRDRVLGF LIENFKGLAI PYLEHIIHVW 610 620 630 640 650 660 EETGSRFHNC LIQLYCEKVQ GLMKEYLLSF PAGKTPVPAG EEEGELGEYR QKLLMFLEIS 670 680 690 700 710 720 SYYDPGRLIC DFPFDGLLEE RALLLGRMGK HEQALFIYVH ILKDTRMAEE YCHKHYDRNK 730 740 750 760 770 780 DGNKDVYLSL LRMYLSPPSI HCLGPIKLEL LEPKANLQAA LQVLELHHSK LDTTKALNLL 790 800 810 820 830 840 PANTQINDIR IFLEKVLEEN AQKKRFNQVL KNLLHAEFLR VQEERILHQQ VKCIITEEKV 850 860 870 CMVCKKKIGN SAFARYPNGV VVHYFCSKEV NPADT

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human Vam6p promotes lysosome clustering and fusion in vivo." Caplan S., Hartnell L.M., Aguilar R.C., Naslavsky N., Bonifacino J.S. J. Cell Biol. 154:109-122(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), FUNCTION, HOMOOLIGOMERIZATION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY. Tissue: Brain.
[2]	"A human homolog of yeast Vps39." Dell'Angelica E.C. Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[3]	"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." Nagase T., Ishikawa K., Suyama M., Kikuno R., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 5:277-286(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Brain.
[4]	"Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones." Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T. DNA Res. 9:99-106(2002) [PubMed] [Europe PMC] [Abstract] Cited for: SEQUENCE REVISION.
[5]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Endometrial tumor.
[6]	"Analysis of the DNA sequence and duplication history of human chromosome 15." Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., Abouelleil A. , Arachchi H.M., Baradarani L., Birditt B., Bloom S., Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C. Nature 440:671-675(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 101-886 (ISOFORMS 1/2). Tissue: Lung and Testis.
[9]	"TLP, a novel modulator of TGF-beta signaling, has opposite effects on Smad2- and Smad3-dependent signaling." Felici A., Wurthner J.U., Parks W.T., Giam L.R., Reiss M., Karpova T.S., McNally J.G., Roberts A.B. EMBO J. 22:4465-4477(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH ACVR2B; SMAD4; TGFBR1 AND TGFBR2, TISSUE SPECIFICITY.
[10]	"Integral and associated lysosomal membrane proteins." Schroeder B., Wrocklage C., Pan C., Jaeger R., Koesters B., Schaefer H., Elsaesser H.-P., Mann M., Hasilik A. Traffic 8:1676-1686(2007) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY. Tissue: Placenta.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF280814 mRNA. Translation: AAK72222.1. AF334400 Genomic DNA. Translation: AAK58862.1. AF281052 mRNA. Translation: AAQ05978.1. AB018313 mRNA. Translation: BAA34490.2. Different initiation. BX537404 mRNA. Translation: CAD97646.1. AC036103 Genomic DNA. No translation available. CH471125 Genomic DNA. Translation: EAW92536.1. BC015817 mRNA. Translation: AAH15817.2. BC068559 mRNA. Translation: AAH68559.1.
IPI	IPI00328236. IPI00332744.
RefSeq	NP_056104.2. NM_015289.2.
UniGene	Hs.88025.
3D structure databases
ProteinModelPortal	Q96JC1.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q96JC1. 1 interaction.
STRING	9606.ENSP00000326534.
PTM databases
PhosphoSite	Q96JC1.
Polymorphism databases
DMDM	66774218.
Proteomic databases
PaxDb	Q96JC1.
PRIDE	Q96JC1.
Protocols and materials databases
DNASU	23339.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000318006; ENSP00000326534; ENSG00000166887. ENST00000348544; ENSP00000335193; ENSG00000166887.
GeneID	23339.
KEGG	hsa:23339.
UCSC	uc001zpc.3. human. uc001zpd.3. human.
Organism-specific databases
CTD	23339.
GeneCards	GC15M042450.
H-InvDB	HIX0038106.
HGNC	HGNC:20593. VPS39.
MIM	612188. gene.
neXtProt	NX_Q96JC1.
PharmGKB	PA134945163.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG241434.
HOGENOM	HOG000046531.
HOVERGEN	HBG056493.
InParanoid	Q96JC1.
OMA	CLGPIKM.
PhylomeDB	Q96JC1.
Gene expression databases
ArrayExpress	Q96JC1.
Bgee	Q96JC1.
CleanEx	HS_VPS39.
Genevestigator	Q96JC1.
GermOnline	ENSG00000166887. Homo sapiens.
Family and domain databases
InterPro	IPR001180. Citron. IPR019452. VPS39/TGF_beta_rcpt-assoc_1. IPR019453. VPS39/TGF_beta_rcpt-assoc_2. [Graphical view]
Pfam	PF00780. CNH. 1 hit. PF10366. Vps39_1. 1 hit. PF10367. Vps39_2. 1 hit. [Graphical view]
PROSITE	PS50219. CNH. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	VPS39. human.
GenomeRNAi	23339.
NextBio	45293.
SOURCE	Search...

Entry information

Entry name

VPS39_HUMAN

Accession

Primary (citable) accession number: Q96JC1
Secondary accession number(s): O94869 , Q71SQ6, Q7Z3V3, Q96B93, Q96RM0

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 25, 2002
Last sequence update:	May 24, 2005
Last modified:	April 3, 2013
This is version 95 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.