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Protein

Vacuolar protein sorting-associated protein 35

Gene

Vps35

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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

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

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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 Expressed in 305 organ(s), highest expression level in islet of Langerhans
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

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi211137, 14 interactors
CORUMiQ9EQH3
DIPiDIP-32210N
IntActiQ9EQH3, 37 interactors
MINTiQ9EQH3
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
OMAiHLWWATP
OrthoDBiEOG091G0OHF
PhylomeDBiQ9EQH3
TreeFamiTF105659

Family and domain databases

InterProiView protein in InterPro
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, 1 hit

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

Cross-referencesi

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

3D structure databases

ProteinModelPortaliQ9EQH3
SMRiQ9EQH3
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi211137, 14 interactors
CORUMiQ9EQH3
DIPiDIP-32210N
IntActiQ9EQH3, 37 interactors
MINTiQ9EQH3
STRINGi10090.ENSMUSP00000034131

PTM databases

iPTMnetiQ9EQH3
PhosphoSitePlusiQ9EQH3
SwissPalmiQ9EQH3

Proteomic databases

EPDiQ9EQH3
MaxQBiQ9EQH3
PaxDbiQ9EQH3
PRIDEiQ9EQH3

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi55737
MGIiMGI:1890467 Vps35

Phylogenomic databases

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

Enzyme and pathway databases

ReactomeiR-MMU-3238698 WNT ligand biogenesis and trafficking

Miscellaneous databases

ChiTaRSiVps35 mouse
PROiPR:Q9EQH3
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000031696 Expressed in 305 organ(s), highest expression level in islet of Langerhans
CleanExiMM_VPS35
ExpressionAtlasiQ9EQH3 baseline and differential
GenevisibleiQ9EQH3 MM

Family and domain databases

InterProiView protein in InterPro
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, 1 hit
ProtoNetiSearch...

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: November 7, 2018
This is version 144 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. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
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Main funding by: National Institutes of Health

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