Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Vacuolar protein sorting-associated protein 35

Gene

Vps35

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

Functioni

Acts as component of the retromer cargo-selective complex (CSC). The CSC is believed to be the core functional component of retromer or respective retromer complex variants acting to prevent missorting of selected transmembrane cargo proteins into the lysosomal degradation pathway. The recruitment of the CSC to the endosomal membrane involves RAB7A and SNX3. The CSC seems to associate with the cytoplasmic domain of cargo proteins predominantly via VPS35; however, these interactions seem to be of low affinity and retromer SNX proteins may also contribute to cargo selectivity thus questioning the classical function of the CSC. The SNX-BAR retromer mediates retrograde transport of cargo proteins from endosomes to the trans-Golgi network (TGN) and is involved in endosome-to-plasma membrane transport for cargo protein recycling. The SNX3-retromer mediates the retrograde transport of WLS distinct from the SNX-BAR retromer pathway. The SNX27-retromer is believed to be involved in endosome-to-plasma membrane trafficking and recycling of a broad spectrum of cargo proteins. The CSC seems to act as recruitment hub for other proteins, such as the WASH complex and TBC1D5 (Probable). Required for retrograde transport of lysosomal enzyme receptor IGF2R and SLC11A2. Required to regulate transcytosis of the polymeric immunoglobulin receptor (pIgR-pIgA). Required for endosomal localization of WASHC2 and mediates the association of the CSC with the WASH complex (By similarity).By similarity

GO - Molecular functioni

  • D1 dopamine receptor binding Source: ParkinsonsUK-UCL
  • protein transporter activity Source: GO_Central

GO - Biological processi

  • lysosome organization Source: ParkinsonsUK-UCL
  • mitochondrial fragmentation involved in apoptotic process Source: MGI
  • mitochondrion to lysosome transport Source: MGI
  • negative regulation of cellular protein localization Source: ParkinsonsUK-UCL
  • negative regulation of gene expression Source: ParkinsonsUK-UCL
  • negative regulation of late endosome to lysosome transport Source: MGI
  • negative regulation of lysosomal protein catabolic process Source: ParkinsonsUK-UCL
  • negative regulation of neuron death Source: ParkinsonsUK-UCL
  • negative regulation of protein homooligomerization Source: ParkinsonsUK-UCL
  • neurotransmitter receptor transport, endosome to plasma membrane Source: ParkinsonsUK-UCL
  • positive regulation of canonical Wnt signaling pathway Source: ParkinsonsUK-UCL
  • positive regulation of cellular protein catabolic process Source: MGI
  • positive regulation of dopamine biosynthetic process Source: ParkinsonsUK-UCL
  • positive regulation of dopamine receptor signaling pathway Source: MGI
  • positive regulation of gene expression Source: ParkinsonsUK-UCL
  • positive regulation of locomotion involved in locomotory behavior Source: ParkinsonsUK-UCL
  • positive regulation of mitochondrial fission Source: MGI
  • positive regulation of Wnt protein secretion Source: ParkinsonsUK-UCL
  • protein destabilization Source: ParkinsonsUK-UCL
  • protein localization to organelle Source: ParkinsonsUK-UCL
  • regulation of cellular protein metabolic process Source: MGI
  • regulation of dendritic spine maintenance Source: MGI
  • regulation of mitochondrion organization Source: MGI
  • regulation of protein stability Source: MGI
  • regulation of terminal button organization Source: MGI
  • retrograde transport, endosome to Golgi Source: UniProtKB
  • retrograde transport, endosome to plasma membrane Source: UniProtKB
  • transcytosis Source: UniProtKB
  • vacuolar protein processing Source: MGI
  • voluntary musculoskeletal movement Source: ParkinsonsUK-UCL

Keywordsi

Biological processProtein transport, Transport

Enzyme and pathway databases

ReactomeiR-MMU-3238698. WNT ligand biogenesis and trafficking.

Names & Taxonomyi

Protein namesi
Recommended name:
Vacuolar protein sorting-associated protein 35
Alternative name(s):
Maternal-embryonic 3
Vesicle protein sorting 35
Gene namesi
Name:Vps35
Synonyms:Mem3
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 8

Organism-specific databases

MGIiMGI:1890467. Vps35.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: ParkinsonsUK-UCL
  • cytosol Source: MGI
  • early endosome Source: MGI
  • endosome Source: MGI
  • endosome membrane Source: MGI
  • extracellular exosome Source: MGI
  • integral component of membrane Source: MGI
  • late endosome Source: GO_Central
  • lysosomal membrane Source: MGI
  • lysosome Source: MGI
  • mitochondrion Source: Ensembl
  • mitochondrion-derived vesicle Source: MGI
  • neuronal cell body Source: ParkinsonsUK-UCL
  • neuron projection Source: ParkinsonsUK-UCL
  • perinuclear region of cytoplasm Source: ParkinsonsUK-UCL
  • postsynaptic density Source: MGI
  • retromer, cargo-selective complex Source: MGI
  • retromer complex Source: UniProtKB
  • tubular endosome Source: UniProtKB

Keywords - Cellular componenti

Cytoplasm, Endosome, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000658971 – 796Vacuolar protein sorting-associated protein 35Add BLAST796

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei7PhosphoserineBy similarity1
Modified residuei783PhosphoserineCombined sources1
Modified residuei791PhosphotyrosineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ9EQH3.
MaxQBiQ9EQH3.
PaxDbiQ9EQH3.
PRIDEiQ9EQH3.

PTM databases

iPTMnetiQ9EQH3.
PhosphoSitePlusiQ9EQH3.
SwissPalmiQ9EQH3.

Expressioni

Tissue specificityi

Ubiquitous. Highly expressed in fat tissue, testis, brain, kidney, thymus, liver and pancreas, and at lower levels in heart, intestine and skeletal muscle. Detected in oocytes, pre-implantation embryos and at E6.5-E12.5.

Gene expression databases

BgeeiENSMUSG00000031696.
CleanExiMM_VPS35.
ExpressionAtlasiQ9EQH3. baseline and differential.
GenevisibleiQ9EQH3. MM.

Interactioni

Subunit structurei

Component of the heterotrimeric retromer cargo-selective complex (CSC), also described as vacuolar protein sorting subcomplex (VPS) formed by VPS26 (VPS26A or VPS26B), VPS29 and VPS35. The CSC has a highly elongated structure with VPS26 and VPS29 binding independently at opposite distal ends of VPS35 as central platform (PubMed:21040701, PubMed:20875039, PubMed:21920005). The CSC is believed to associate with variable sorting nexins to form functionally distinct retromer complex variants. The originally described retromer complex (also called SNX-BAR retromer) is a pentamer containing the CSC and a heterodimeric membrane-deforming subcomplex formed between SNX1 or SNX2 and SNX5 or SNX6 (also called SNX-BAR subcomplex); the affinity between the respective CSC and SNX-BAR subcomplexes is low. The CSC associates with SNX3 to form a SNX3-retromer complex. The CSC associates with SNX27, the WASH complex and the SNX-BAR subcomplex to form the SNX27-retromer complex (Probable). Interacts with VPS26A, VPS29, VPS26B and LRRK2 (PubMed:16190980, PubMed:21040701, PubMed:20875039, PubMed:21920005, PubMed:23395371). Interacts with SNX1, SNX2, IGF2R, SNX3, GOLPH3, SLC11A2, WASHC2, FKBP15, WASHC1, EHD1. Interacts with MAGEL2; leading to recruitment of the TRIM27:MAGEL2 E3 ubiquitin ligase complex retromer-containing endosomes (By similarity).By similarity5 Publications

GO - Molecular functioni

  • D1 dopamine receptor binding Source: ParkinsonsUK-UCL

Protein-protein interaction databases

BioGridi211137. 7 interactors.
DIPiDIP-32210N.
IntActiQ9EQH3. 20 interactors.
MINTiMINT-1870050.
STRINGi10090.ENSMUSP00000034131.

Structurei

3D structure databases

ProteinModelPortaliQ9EQH3.
SMRiQ9EQH3.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni25 – 44Interaction with SNX3By similarityAdd BLAST20
Regioni205 – 215Interaction with SNX3By similarityAdd BLAST11
Regioni438 – 796Interaction with SLC11A2By similarityAdd BLAST359
Regioni500 – 693Interaction with IGF2R cytoplasmic domainBy similarityAdd BLAST194

Sequence similaritiesi

Belongs to the VPS35 family.Curated

Phylogenomic databases

eggNOGiKOG1107. Eukaryota.
ENOG410XNXC. LUCA.
GeneTreeiENSGT00390000007315.
HOGENOMiHOG000196946.
HOVERGENiHBG054277.
InParanoidiQ9EQH3.
KOiK18468.
OMAiRVADSCM.
OrthoDBiEOG091G0OHF.
PhylomeDBiQ9EQH3.
TreeFamiTF105659.

Family and domain databases

Gene3Di1.25.10.10. 1 hit.
InterProiView protein in InterPro
IPR011989. ARM-like.
IPR016024. ARM-type_fold.
IPR005378. Vps35.
PANTHERiPTHR11099. PTHR11099. 1 hit.
PfamiView protein in Pfam
PF03635. Vps35. 1 hit.
PIRSFiPIRSF009375. Retromer_Vps35. 1 hit.
SUPFAMiSSF48371. SSF48371. 2 hits.

Sequencei

Sequence statusi: Complete.

Q9EQH3-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPTTQQSPQD EQEKLLDEAI QAVKVQSFQM KRCLDKNKLM DALKHASNML
60 70 80 90 100
GELRTSMLSP KSYYELYMAI SDELHYLEVY LTDEFAKGRK VADLYELVQY
110 120 130 140 150
AGNIIPRLYL LITVGVVYVK SFPQSRKDIL KDLVEMCRGV QHPLRGLFLR
160 170 180 190 200
NYLLQCTRNI LPDEGEPTDE ETTGDISDSM DFVLLNFAEM NKLWVRMQHQ
210 220 230 240 250
GHSRDREKRE RERQELRILV GTNLVRLSQL EGVNVERYKQ IVLTGILEQV
260 270 280 290 300
VNCRDALAQE YLMECIIQVF PDEFHLQTLN PFLRACAELH QNVNVKNIII
310 320 330 340 350
ALIDRLALFA HREDGPGIPA EIKLFDIFSQ QVATVIQSRQ DMPSEDVVSL
360 370 380 390 400
QVSLINLAMK CYPDRVDYVD KVLETTVEIF NKLNLEHIAT SSAVSKELTR
410 420 430 440 450
LLKIPVDTYN NILTVLKLKH FHPLFEYFDY ESRKSMSCYV LSNVLDYNTE
460 470 480 490 500
IVSQDQVDSI MNLVSTLIQD QPDQPVEDPD PEDFADEQSL VGRFIHLLRS
510 520 530 540 550
DDPDQQYLIL NTARKHFGAG GNQRIRFTLP PLVFAAYQLA FRYKENSQMD
560 570 580 590 600
DKWEKKCQKI FSFAHQTISA LIKAELAELP LRLFLQGALA AGEIGFENHE
610 620 630 640 650
TVAYEFMSQA FSLYEDEISD SKAQLAAITL IIGTFERMKC FSEENHEPLR
660 670 680 690 700
TQCALAASKL LKKPDQGRAV STCAHLFWSG RNTDKNGEEL HGGKRVMECL
710 720 730 740 750
KKALKIANQC MDPSLQVQLF IEILNRYIYF YEKENDAVTI QVLNQLIQKI
760 770 780 790
REDLPNLESS EETEQINKHF HNTLEHLRSR RESPESEGPI YEGLIL
Length:796
Mass (Da):91,713
Last modified:March 1, 2001 - v1
Checksum:i2ABD338111D641CC
GO

Sequence cautioni

The sequence AAB18153 differs from that shown. Reason: Frameshift at several positions.Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U47024 mRNA. Translation: AAB18153.1. Frameshift.
AF226323 mRNA. Translation: AAG40621.1.
BC005469 mRNA. Translation: AAH05469.1.
BC006637 mRNA. Translation: AAH06637.1.
CCDSiCCDS40421.1.
RefSeqiNP_075373.1. NM_022997.4.
UniGeneiMm.296520.
Mm.391632.

Genome annotation databases

EnsembliENSMUST00000034131; ENSMUSP00000034131; ENSMUSG00000031696.
GeneIDi65114.
KEGGimmu:65114.
UCSCiuc009mpo.1. mouse.

Similar proteinsi

Entry informationi

Entry nameiVPS35_MOUSE
AccessioniPrimary (citable) accession number: Q9EQH3
Secondary accession number(s): Q61123
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 25, 2002
Last sequence update: March 1, 2001
Last modified: August 30, 2017
This is version 135 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, 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