VPS35
Vacuolar protein sorting-associated protein 35
Also known as: FLJ10752, MEM3, PARK17, VPS35_HUMAN
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- Q96QK1
- Gene
- VPS35
- Ensembl
- ENSG00000069329
- Chromosome
- 16
- Canonical length
- 796 aa
- Protein class
- Disease related genes, Human disease related genes, Plasma proteins, Potential drug targets, Predicted intracellular proteins, Transporters
- Subcellular location
- Endosomes,Lysosomes
OverviewNCBI Gene
This gene belongs to a group of vacuolar protein sorting (VPS) genes. The encoded protein is a component of a large multimeric complex, termed the retromer complex, involved in retrograde transport of proteins from endosomes to the trans-Golgi network. The close structural similarity between the yeast and human proteins that make up this complex suggests a similarity in function. Expression studies in yeast and mammalian cells indicate that this protein interacts directly with VPS35, which serves as the core of the retromer complex. [provided by RefSeq, Jul 2008]
Canonical amino-acid sequenceUniProt
796 residues, UniProt reviewed canonical sequence.
>Q96QK1|VPS35
1 MPTTQQSPQD EQEKLLDEAI QAVKVQSFQM KRCLDKNKLM DALKHASNML GELRTSMLSP
61 KSYYELYMAI SDELHYLEVY LTDEFAKGRK VADLYELVQY AGNIIPRLYL LITVGVVYVK
121 SFPQSRKDIL KDLVEMCRGV QHPLRGLFLR NYLLQCTRNI LPDEGEPTDE ETTGDISDSM
181 DFVLLNFAEM NKLWVRMQHQ GHSRDREKRE RERQELRILV GTNLVRLSQL EGVNVERYKQ
241 IVLTGILEQV VNCRDALAQE YLMECIIQVF PDEFHLQTLN PFLRACAELH QNVNVKNIII
301 ALIDRLALFA HREDGPGIPA DIKLFDIFSQ QVATVIQSRQ DMPSEDVVSL QVSLINLAMK
361 CYPDRVDYVD KVLETTVEIF NKLNLEHIAT SSAVSKELTR LLKIPVDTYN NILTVLKLKH
421 FHPLFEYFDY ESRKSMSCYV LSNVLDYNTE IVSQDQVDSI MNLVSTLIQD QPDQPVEDPD
481 PEDFADEQSL VGRFIHLLRS EDPDQQYLIL NTARKHFGAG GNQRIRFTLP PLVFAAYQLA
541 FRYKENSKVD DKWEKKCQKI FSFAHQTISA LIKAELAELP LRLFLQGALA AGEIGFENHE
601 TVAYEFMSQA FSLYEDEISD SKAQLAAITL IIGTFERMKC FSEENHEPLR TQCALAASKL
661 LKKPDQGRAV STCAHLFWSG RNTDKNGEEL HGGKRVMECL KKALKIANQC MDPSLQVQLF
721 IEILNRYIYF YEKENDAVTI QVLNQLIQKI REDLPNLESS EETEQINKHF HNTLEHLRLR
781 RESPESEGPI YEGLILLocalizationUniProt · AlphaFold · HPA
Whether an antibody against VPS35 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Intracellular
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.25
- Highest tissue expression
- 8.9 nTPM
Expression across tissuesHPA
Tissue
- bone marrow: 8.9 nTPM
- parathyroid gland: 4.9 nTPM
- retina: 3.7 nTPM
- spleen: 3.7 nTPM
- thymus: 3.6 nTPM
- skeletal muscle: 3.5 nTPM
Single-cell type
- early primary spermatocytes: 245 nCPM
- respiratory ciliated cells: 220 nCPM
- fallopian tube ciliated cells: 219 nCPM
- esophageal apical cells: 211 nCPM
- neutrophils: 209 nCPM
- urothelial cells: 176 nCPM
Immune cell
- non-classical monocyte: 2.3 nTPM
- intermediate monocyte: 1.7 nTPM
- basophil: 1.5 nTPM
- myeloid DC: 1.5 nTPM
- classical monocyte: 1.3 nTPM
- eosinophil: 1.3 nTPM
Brain region
- pons: 9.7 nTPM
- white matter: 9.7 nTPM
- cerebral cortex: 9.6 nTPM
- basal ganglia: 9.3 nTPM
- hippocampal formation: 9.2 nTPM
- amygdala: 8.9 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about VPS35.
Disease | AllUniProt
Conditions VPS35 is implicated in, by any mechanism.
- Parkinson disease 17 (PARK17) MIM:614203
Disease | GeneticClinVar
3 pathogenic / likely-pathogenic of 287 ClinVar records.
Conditions with pathogenic or likely-pathogenic variants.
- Parkinson disease 17
- Inborn genetic diseases
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.31
- gnomAD pLI
- 0.97
- gnomAD missense Z
- 3.53
- DepMap mean gene effect
- -0.59
- DepMap dependency class
- common
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 6% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- endocytic recycling
- intracellular protein transport
- lysosome organization
- mitochondrial fragmentation involved in apoptotic process
- mitochondrion to lysosome vesicle-mediated transport
- modulation of chemical synaptic transmission
- negative regulation of gene expression
- negative regulation of inflammatory response
- negative regulation of late endosome to lysosome transport
- negative regulation of lysosomal protein catabolic process
- negative regulation of protein homooligomerization
- negative regulation of protein localization
- neurotransmitter receptor transport, endosome to postsynaptic membrane
- positive regulation of canonical Wnt signaling pathway
- positive regulation of dopamine biosynthetic process
- positive regulation of dopamine receptor signaling pathway
- positive regulation of gene expression
- positive regulation of locomotion involved in locomotory behavior
- positive regulation of mitochondrial fission
- positive regulation of protein catabolic process
- positive regulation of protein localization to cell periphery
- positive regulation of Wnt protein secretion
- protein destabilization
- protein localization to endosome
- regulation of dendritic spine maintenance
- regulation of macroautophagy
- regulation of mitochondrion organization
- regulation of postsynapse assembly
- regulation of presynapse assembly
- regulation of protein metabolic process
- regulation of protein stability
- regulation of synapse maturation
- retrograde transport, endosome to Golgi
- transcytosis
- vesicle-mediated transport in synapse
- voluntary musculoskeletal movement
- Wnt signaling pathway
- neurotransmitter receptor transport, endosome to plasma membrane
- regulation of terminal button organization
Molecular functions
Cellular components
- cytosol
- dopaminergic synapse
- early endosome
- endosome
- endosome membrane
- extracellular exosome
- glutamatergic synapse
- late endosome
- lysosomal membrane
- lysosome
- neuron projection
- neuronal cell body
- perinuclear region of cytoplasm
- postsynaptic density
- presynapse
- retromer complex
- retromer, cargo-selective complex
- tubular endosome
- mitochondrion-derived vesicle
Protein domainsUniProt · Pfam · InterPro
- Armadillo-type fold
- Vacuolar protein sorting-associated protein 35
- Vacuolar protein sorting-associated protein 35, C-terminal
- Vacuolar protein sorting-associated protein 35
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of VPS35 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads VPS35 as an antibody target. Whether an autoantibody or antibody against VPS35 could matter depends on whether native VPS35 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
VPS35 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.
Annotation status
The present source text does not explicitly label VPS35 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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