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Protein

Vam6/Vps39-like protein

Gene

Vps39

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

May play a role in clustering and fusion of late endosomes and lysosomes (By similarity). 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 (By similarity).By similarity
Plays a role in vesicle-mediated protein trafficking to lysosomal compartments including the endocytic membrane transport and autophagic pathways. Believed to act in part 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. Involved in homotypic vesicle fusions between late endosomes and in heterotypic fusions between late endosomes and lysosomes. Required for fusion of endosomes and autophagosomes with lysosomes (By similarity).By similarity

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Autophagy, Protein transport, Transport

Names & Taxonomyi

Protein namesi
Recommended name:
Vam6/Vps39-like protein
Gene namesi
Name:Vps39
Synonyms:Pldn, Vam6
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:2443189. Vps39.

Subcellular locationi

  • Cytoplasm By similarity
  • Lysosome membrane By similarity; Peripheral membrane protein By similarity
  • Late endosome membrane By similarity; Peripheral membrane protein By similarity
  • Late endosome By similarity
  • Lysosome By similarity

  • Note: Colocalizes with TGFBR1 and TGFBR2 in cytoplasmic vesicular structures and most prominently in cortical vesicles.By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Endosome, Lysosome, Membrane

Pathology & Biotechi

Disruption phenotypei

Embryonic lethal, before E6.5.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 886886Vam6/Vps39-like proteinPRO_0000065902Add
BLAST

Proteomic databases

MaxQBiQ8R5L3.
PaxDbiQ8R5L3.
PRIDEiQ8R5L3.

PTM databases

iPTMnetiQ8R5L3.
PhosphoSiteiQ8R5L3.

Expressioni

Gene expression databases

BgeeiENSMUSG00000027291.
CleanExiMM_PLDN.
MM_VPS39.
ExpressionAtlasiQ8R5L3. baseline and differential.
GenevisibleiQ8R5L3. MM.

Interactioni

Subunit structurei

Homooligomer (By similarity). 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 (By similarity). Component of the putative homotypic fusion and vacuole protein sorting (HOPS) complex; the core of which composed of the class C Vps proteins VPS11, VPS16, VPS18 and VPS33A, is associated with VPS39 and VPS41. Interacts with PLEKHM2; involved in VPS39 recruitment to ARL8B-containing lysosomes (By similarity). Associates with adaptor protein complex 3 (AP-3) and clathrin:AP-3 complexes (PubMed:21411634).By similarity1 Publication

Protein-protein interaction databases

BioGridi234638. 3 interactions.
IntActiQ8R5L3. 1 interaction.
STRINGi10090.ENSMUSP00000099559.

Structurei

3D structure databases

ProteinModelPortaliQ8R5L3.
SMRiQ8R5L3. Positions 71-103.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini15 – 294280CNHPROSITE-ProRule annotationAdd
BLAST
Repeati573 – 750178CHCRAdd
BLAST

Sequence similaritiesi

Belongs to the VAM6/VPS39 family.Curated
Contains 1 CHCR (clathrin heavy-chain) repeat.PROSITE-ProRule annotation
Contains 1 CNH domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG2063. Eukaryota.
ENOG410XNSX. LUCA.
GeneTreeiENSGT00530000063596.
HOGENOMiHOG000046531.
HOVERGENiHBG056493.
InParanoidiQ8R5L3.
KOiK20183.
OMAiCLGPIKM.
OrthoDBiEOG091G04D1.
PhylomeDBiQ8R5L3.
TreeFamiTF105803.

Family and domain databases

InterProiIPR000547. Clathrin_H-chain/VPS_repeat.
IPR001180. CNH_dom.
IPR032914. VAM6/VPS39.
IPR019452. VPS39/TGF_beta_rcpt-assoc_1.
IPR019453. VPS39/TGF_beta_rcpt-assoc_2.
[Graphical view]
PANTHERiPTHR12894:SF10. PTHR12894:SF10. 1 hit.
PfamiPF00637. Clathrin. 1 hit.
PF00780. CNH. 1 hit.
PF10366. Vps39_1. 1 hit.
PF10367. Vps39_2. 1 hit.
[Graphical view]
SMARTiSM00036. CNH. 1 hit.
[Graphical view]
PROSITEiPS50236. CHCR. 1 hit.
PS50219. CNH. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8R5L3-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MHDAFEPVPI LEKLPLQIDC LAAWEEWLLV GTKQGHLLLY RIRKDVVPAD
60 70 80 90 100
VASPESGSCN RFEVTLEKSN KNFSKKIQQI HVVSQFKILV SLLENNIYVH
110 120 130 140 150
DLLTFQQITT VSKAKGASLF TCDLQHTETG EEVLRMCVAV RKKLQLYFWK
160 170 180 190 200
DREFHELQGD FSVPDVPKSM AWCENSICVG FKRDYYLIRV DGKGSIKELF
210 220 230 240 250
PTGKQLEPLV APLADGKVAV GQDDLTVVLN EEGICTQKCA LNWTDIPVAM
260 270 280 290 300
EHQPPYIVAV LPRYVEIRTL EPRLLVQSIE LQRPRFITSG GSNIIYVASN
310 320 330 340 350
HFVWRLIPVP MATQIQQLLQ DKQFELALQL AEMKDDSDSE KQQQIHHIKN
360 370 380 390 400
LYAFNLFCQK RFDESMQVFA KLGTDPTHVM GLYPDLLPTD YRKQLQYPNP
410 420 430 440 450
LPTLSGAELE KAHLALIDYL TQKRSQLVKK LNDSDHQSST SPLMEGTPTI
460 470 480 490 500
KSKKKLLQII DTTLLKCYLH TNVALVAPLL RLENNHCHIE ESEHVLKKAH
510 520 530 540 550
KYSELIILYE KKGLHEKALQ VLVDQSKKAN SPLKGHERTV QYLQHLGTEN
560 570 580 590 600
LHLIFSYSVW VLRDFPEDGL KIFTEDLPEV ESLPRDRVLN FLIENFKALA
610 620 630 640 650
IPYLEHIIHV WEETGSQFHN CLIQLYCEKV QSLMKDYLLS LPTGKSPVPA
660 670 680 690 700
GEEGGELGEY RQKLLMFLEI SSHYDPGRLI CDFPFDGLLE ERALLLGRMG
710 720 730 740 750
KHEQALFIYV HVLKDTKMAK EYCHKHYDQN KEGNKDVYLS LLRMYLSPPS
760 770 780 790 800
IHCLGPIKLE LLEPQANLQA ALQVLELHYS KLDTTKAINL LPANTQINDI
810 820 830 840 850
RIFLEKVLEE NAQKKRFNQV LKNLLHAEFL RVQEERILHQ QVKCIITEEK
860 870 880
VCMVCKKKIG NSAFARYPNG VVVHYFCSKE VNSADT
Length:886
Mass (Da):101,693
Last modified:June 1, 2002 - v1
Checksum:iBD46EF52D404C2DA
GO
Isoform 2 (identifier: Q8R5L3-2) [UniParc]FASTAAdd to basket

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

Show »
Length:875
Mass (Da):100,653
Checksum:i71B8E8E4A2F8345D
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei47 – 5812VPADV…PESGS → G in isoform 2. 2 PublicationsVSP_004076Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF281050 mRNA. Translation: AAL79766.1.
AF281051 mRNA. Translation: AAL79767.1.
BC007479 mRNA. Translation: AAH07479.1.
CCDSiCCDS16619.1. [Q8R5L3-2]
CCDS38210.1. [Q8R5L3-1]
RefSeqiNP_671495.1. NM_147153.3. [Q8R5L3-1]
NP_849182.1. NM_178851.3. [Q8R5L3-2]
UniGeneiMm.246131.

Genome annotation databases

EnsembliENSMUST00000028752; ENSMUSP00000028752; ENSMUSG00000027291. [Q8R5L3-2]
ENSMUST00000102501; ENSMUSP00000099559; ENSMUSG00000027291. [Q8R5L3-1]
GeneIDi269338.
KEGGimmu:269338.
UCSCiuc008lvj.2. mouse. [Q8R5L3-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF281050 mRNA. Translation: AAL79766.1.
AF281051 mRNA. Translation: AAL79767.1.
BC007479 mRNA. Translation: AAH07479.1.
CCDSiCCDS16619.1. [Q8R5L3-2]
CCDS38210.1. [Q8R5L3-1]
RefSeqiNP_671495.1. NM_147153.3. [Q8R5L3-1]
NP_849182.1. NM_178851.3. [Q8R5L3-2]
UniGeneiMm.246131.

3D structure databases

ProteinModelPortaliQ8R5L3.
SMRiQ8R5L3. Positions 71-103.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi234638. 3 interactions.
IntActiQ8R5L3. 1 interaction.
STRINGi10090.ENSMUSP00000099559.

PTM databases

iPTMnetiQ8R5L3.
PhosphoSiteiQ8R5L3.

Proteomic databases

MaxQBiQ8R5L3.
PaxDbiQ8R5L3.
PRIDEiQ8R5L3.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000028752; ENSMUSP00000028752; ENSMUSG00000027291. [Q8R5L3-2]
ENSMUST00000102501; ENSMUSP00000099559; ENSMUSG00000027291. [Q8R5L3-1]
GeneIDi269338.
KEGGimmu:269338.
UCSCiuc008lvj.2. mouse. [Q8R5L3-1]

Organism-specific databases

CTDi23339.
MGIiMGI:2443189. Vps39.

Phylogenomic databases

eggNOGiKOG2063. Eukaryota.
ENOG410XNSX. LUCA.
GeneTreeiENSGT00530000063596.
HOGENOMiHOG000046531.
HOVERGENiHBG056493.
InParanoidiQ8R5L3.
KOiK20183.
OMAiCLGPIKM.
OrthoDBiEOG091G04D1.
PhylomeDBiQ8R5L3.
TreeFamiTF105803.

Miscellaneous databases

PROiQ8R5L3.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000027291.
CleanExiMM_PLDN.
MM_VPS39.
ExpressionAtlasiQ8R5L3. baseline and differential.
GenevisibleiQ8R5L3. MM.

Family and domain databases

InterProiIPR000547. Clathrin_H-chain/VPS_repeat.
IPR001180. CNH_dom.
IPR032914. VAM6/VPS39.
IPR019452. VPS39/TGF_beta_rcpt-assoc_1.
IPR019453. VPS39/TGF_beta_rcpt-assoc_2.
[Graphical view]
PANTHERiPTHR12894:SF10. PTHR12894:SF10. 1 hit.
PfamiPF00637. Clathrin. 1 hit.
PF00780. CNH. 1 hit.
PF10366. Vps39_1. 1 hit.
PF10367. Vps39_2. 1 hit.
[Graphical view]
SMARTiSM00036. CNH. 1 hit.
[Graphical view]
PROSITEiPS50236. CHCR. 1 hit.
PS50219. CNH. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiVPS39_MOUSE
AccessioniPrimary (citable) accession number: Q8R5L3
Secondary accession number(s): Q922I3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 25, 2002
Last sequence update: June 1, 2002
Last modified: September 7, 2016
This is version 110 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.