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UniProtKB - Q96QK1 (VPS35_HUMAN)

Entry version 198 (23 Feb 2022)
Sequence version 2 (25 Nov 2002)
Previous versions | rss
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Protein

Vacuolar protein sorting-associated protein 35

Gene

VPS35

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>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 endosome-to-TGN transport of WLS distinct from the SNX-BAR retromer pathway (PubMed:30213940).

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) (PubMed:15078903, PubMed:15247922, PubMed:20164305).

Required for endosomal localization of WASHC2C (PubMed:22070227, PubMed:28892079).

Mediates the association of the CSC with the WASH complex via WASHC2 (PubMed:22070227, PubMed:24980502, PubMed:24819384).

Required for the endosomal localization of TBC1D5 (PubMed:20923837).

4 Publications10 Publications

(Microbial infection) The heterotrimeric retromer cargo-selective complex (CSC) mediates the exit of human papillomavirus from the early endosome and the delivery to the Golgi apparatus.

2 Publications

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

Complete GO annotation on QuickGO ...

GO - Biological processi

Complete GO annotation on QuickGO ...

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Biological processHost-virus interaction, Protein transport, Transport

Enzyme and pathway databases

Pathway Commons web resource for biological pathway data

More...PathwayCommonsi		Q96QK1

Reactome - a knowledgebase of biological pathways and processes

More...Reactomei		R-HSA-3238698, WNT ligand biogenesis and trafficking

SignaLink: a signaling pathway resource with multi-layered regulatory networks

More...SignaLinki		Q96QK1

SIGNOR Signaling Network Open Resource

More...SIGNORi		Q96QK1

Protein family/group databases

Transport Classification Database

More...TCDBi		9.A.3.1.1, the sorting nexin27 (snx27)-retromer assembly apparatus (retromeraa) family

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Vacuolar protein sorting-associated protein 35
Short name:
hVPS35
Alternative name(s):
Maternal-embryonic 3
Vesicle protein sorting 35
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: 'Name', 'Synonyms', 'Ordered locus names' and 'ORF names'.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:VPS351 PublicationImported
Synonyms:MEM3
ORF Names:TCCCTA00141
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the 'taxonomic identifier' or 'taxid'.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes%5Fmanual">proteome</a> can consist of several components.<br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 16

Organism-specific databases

Human Gene Nomenclature Database

More...HGNCi		HGNC:13487, VPS35

Online Mendelian Inheritance in Man (OMIM)

More...MIMi		601501, gene

neXtProt; the human protein knowledge platform

More...neXtProti		NX_Q96QK1

Eukaryotic Pathogen, Vector and Host Database Resources

More...VEuPathDBi		HostDB:ENSG00000069329

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Keywords - Cellular componenti

Cytoplasm, Endosome, Membrane

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the 'Pathology and Biotech' section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei

Parkinson disease 17 (PARK17)6 Publications
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionAn autosomal dominant, adult-onset form of Parkinson disease. Parkinson disease is a complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability, as well as by a clinically significant response to treatment with levodopa. The pathology involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_066659620D → N in PARK17; decreases interaction with WASHC2C, FKBP15 and the WASH complex; impairs recruitment of the WASH complex to endosomes; shows reduced retrograde transport of selective cargo between lysosomes and the Golgi apparatus; shows a progressive reduction in neurite length and branching. 6 PublicationsCorresponds to variant dbSNP:rs188286943EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology%5Fand%5Fbiotech%5Fsection">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi108L → P: Disrupts interaction with VPS26; no effect on interaction with VPS29. 1 Publication1
Mutagenesisi675H → R: Disrupts interaction with VPS29. Does not effect interaction with VPS26. 1 Publication1

Keywords - Diseasei

Neurodegeneration, Parkinson disease, Parkinsonism

Organism-specific databases

DisGeNET

More...DisGeNETi		55737

GeneReviews a resource of expert-authored, peer-reviewed disease descriptions.

More...GeneReviewsi		VPS35

MalaCards human disease database

More...MalaCardsi		VPS35
MIMi614203, phenotype

Open Targets

More...OpenTargetsi		ENSG00000069329

Orphanet; a database dedicated to information on rare diseases and orphan drugs

More...Orphaneti		411602, Hereditary late-onset Parkinson disease

The Pharmacogenetics and Pharmacogenomics Knowledge Base

More...PharmGKBi		PA37783

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

More...Pharosi		Q96QK1, Tbio

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

More...ChEMBLi		CHEMBL2216744

Genetic variation databases

BioMuta curated single-nucleotide variation and disease association database

More...BioMutai		VPS35

Domain mapping of disease mutations (DMDM)

More...DMDMi		25453321

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section describes the extent of a polypeptide chain in the mature protein following processing or proteolytic cleavage.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00000658961 – 796Vacuolar protein sorting-associated protein 35Add BLAST796

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei7PhosphoserineCombined sources1
Modified residuei783PhosphoserineBy similarity1
Modified residuei791PhosphotyrosineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

The CPTAC Assay portal

More...CPTACi		CPTAC-605

Encyclopedia of Proteome Dynamics

More...EPDi		Q96QK1

jPOST - Japan Proteome Standard Repository/Database

More...jPOSTi		Q96QK1

MassIVE - Mass Spectrometry Interactive Virtual Environment

More...MassIVEi		Q96QK1

MaxQB - The MaxQuant DataBase

More...MaxQBi		Q96QK1

PaxDb, a database of protein abundance averages across all three domains of life

More...PaxDbi		Q96QK1

PeptideAtlas

More...PeptideAtlasi		Q96QK1

PRoteomics IDEntifications database

More...PRIDEi		Q96QK1

ProteomicsDB: a multi-organism proteome resource

More...ProteomicsDBi		77884

PTM databases

GlyGen: Computational and Informatics Resources for Glycoscience

More...GlyGeni		Q96QK1, 1 site, 1 O-linked glycan (1 site)

iPTMnet integrated resource for PTMs in systems biology context

More...iPTMneti		Q96QK1

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

More...PhosphoSitePlusi		Q96QK1

SwissPalm database of S-palmitoylation events

More...SwissPalmi		Q96QK1

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the 'Expression' section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified 'at protein level'.<br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

Ubiquitous. Highly expressed in heart, brain, placenta, skeletal muscle, spleen, thymus, testis, ovary, small intestine, kidney and colon.

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...Bgeei		ENSG00000069329, Expressed in intestine and 125 other tissues

ExpressionAtlas, Differential and Baseline Expression

More...ExpressionAtlasi		Q96QK1, baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

More...Genevisiblei		Q96QK1, HS

Organism-specific databases

Human Protein Atlas

More...HPAi		ENSG00000069329, Low tissue specificity

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction%5Fsection">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Component of the heterotrimeric retromer cargo-selective complex (CSC), also decribed as vacuolar protein sorting subcomplex (VPS), formed by VPS26 (VPS26A or VPS26B), VPS29 and VPS35 (PubMed:11102511, PubMed:28892079). The CSC has a highly elongated structure with VPS26 and VPS29 binding independently at opposite distal ends of VPS35 as central platform (By similarity). 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 respective CSC and SNX-BAR subcomplexes associate with low affinity. 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, VPS26B, VPS29, SNX1, SNX2, IGF2R, SNX3, GOLPH3, LRRK2, SLC11A2, WASHC2A, WASHC2C, FKBP15, WASHC1, RAB7A, SNX27, WASHC5, EHD1 (PubMed:11102511, PubMed:15078903, PubMed:17868075PubMed:22070227, PubMed:19553991, PubMed:21725319, PubMed:22070227, PubMed:22513087, PubMed:23331060, PubMed:23563491, PubMed:23395371, PubMed:24344282, PubMed:24980502, PubMed:17891154, PubMed:19531583, PubMed:30213940).

Interacts with MAGEL2; leading to recruitment of the TRIM27:MAGEL2 E3 ubiquitin ligase complex retromer-containing endosomes (PubMed:23452853).

Interacts with SORCS2 (By similarity).

2 PublicationsBy similarity15 Publications

(Microbial infection) Interacts with human papillomavirus 16 minor capsid protein L2 (via C-terminus); this interaction mediates the transport of the capsid from the early endosome to the Golgi apparatus.

1 Publication

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction%5Fsection">Interaction</a>' section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="https://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated at every <a href="http://www.uniprot.org/help/synchronization">UniProt release</a>.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

Hide details

GO - Molecular functioni

Complete GO annotation on QuickGO ...

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGRID)

More...BioGRIDi		120855, 153 interactors

CORUM comprehensive resource of mammalian protein complexes

More...CORUMi		Q96QK1

Database of interacting proteins

More...DIPi		DIP-29076N

Protein interaction database and analysis system

More...IntActi		Q96QK1, 48 interactors

Molecular INTeraction database

More...MINTi		Q96QK1

STRING: functional protein association networks

More...STRINGi		9606.ENSP00000299138

Chemistry databases

BindingDB database of measured binding affinities

More...BindingDBi		Q96QK1

Miscellaneous databases

RNAct, Protein-RNA interaction predictions for model organisms.

More...RNActi		Q96QK1, protein

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

1796
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

SWISS-MODEL Repository - a database of annotated 3D protein structure models

More...SMRi		Q96QK1

Database of comparative protein structure models

More...ModBasei		Search...

Protein Data Bank in Europe - Knowledge Base

More...PDBe-KBi		Search...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

More...EvolutionaryTracei		Q96QK1

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni25 – 44Interaction with SNX31 PublicationAdd BLAST20
Regioni205 – 215Interaction with SNX31 PublicationAdd BLAST11
Regioni438 – 796Interaction with SLC11A21 PublicationAdd BLAST359
Regioni500 – 693Interaction with IGF2R cytoplasmic domain1 PublicationAdd BLAST194

<p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Belongs to the VPS35 family.Curated

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...eggNOGi		KOG1107, Eukaryota

Ensembl GeneTree

More...GeneTreei		ENSGT00390000007315

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

More...HOGENOMi		CLU_005836_1_0_1

InParanoid: Eukaryotic Ortholog Groups

More...InParanoidi		Q96QK1

Identification of Orthologs from Complete Genome Data

More...OMAi		HLWWATP

Database of Orthologous Groups

More...OrthoDBi		316875at2759

Database for complete collections of gene phylogenies

More...PhylomeDBi		Q96QK1

TreeFam database of animal gene trees

More...TreeFami		TF105659

Family and domain databases

Gene3D Structural and Functional Annotation of Protein Families

More...Gene3Di		1.25.40.660, 1 hit

Integrated resource of protein families, domains and functional sites

More...InterProi		View protein in InterPro
IPR016024, ARM-type_fold
IPR005378, Vps35
IPR042491, Vps35_C

The PANTHER Classification System

More...PANTHERi		PTHR11099, PTHR11099, 1 hit

Pfam protein domain database

More...Pfami		View protein in Pfam
PF03635, Vps35, 1 hit

PIRSF; a whole-protein classification database

More...PIRSFi		PIRSF009375, Retromer_Vps35, 1 hit

Superfamily database of structural and functional annotation

More...SUPFAMi		SSF48371, SSF48371, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequence (1+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

This entry has 1 described isoform and 4 potential isoforms that are computationally mapped.Show allAlign All

Q96QK1-1 [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 DIKLFDIFSQ 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
EDPDQQYLIL NTARKHFGAG GNQRIRFTLP PLVFAAYQLA FRYKENSKVD 
       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 HNTLEHLRLR RESPESEGPI YEGLIL
Length:796
Mass (Da):91,707
Last modified:November 25, 2002 - v2
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:i28D2DD1C6B920A0A
GO

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H3BRJ7H3BRJ7_HUMAN
Vacuolar protein sorting-associated...
VPS35
48Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
I3L4S0I3L4S0_HUMAN
Vacuolar protein sorting-associated...
VPS35
41Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
A0A1W2PP10A0A1W2PP10_HUMAN
Vacuolar protein sorting-associated...
VPS35
46Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
A0A3B3ITD4A0A3B3ITD4_HUMAN
Vacuolar protein sorting-associated...
VPS35
47Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

<p>This subsection of the 'Sequence' section reports difference(s) between the protein sequence shown in the UniProtKB entry and other available protein sequences derived from the same gene.<p><a href='/help/sequence_caution' target='_top'>More...</a></p>Sequence cautioni

The sequence AAG01989 differs from that shown. Reason: Erroneous initiation. Truncated N-terminus.Curated
The sequence BAA91137 differs from that shown. Reason: Erroneous initiation. Truncated N-terminus.Curated
The sequence BAB14626 differs from that shown. Reason: Erroneous initiation. Extended N-terminus.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>Sequence conflicti42A → S in CAB66822 (PubMed:11230166).Curated1
Sequence conflicti160I → T in BAB14626 (PubMed:14702039).Curated1
Sequence conflicti168T → P in AAF89953 (PubMed:11102511).Curated1
Sequence conflicti453S → F in AAH10362 (PubMed:15489334).Curated1
Sequence conflicti526R → G in BAA91790 (PubMed:14702039).Curated1
Sequence conflicti694K → E in BAA91790 (PubMed:14702039).Curated1
Sequence conflicti796L → H in BAA91137 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06665351G → S1 PublicationCorresponds to variant dbSNP:rs193077277EnsemblClinVar.1
Natural variantiVAR_06665457M → I1 PublicationCorresponds to variant dbSNP:rs183554824EnsemblClinVar.1
Natural variantiVAR_06665582T → R1 PublicationCorresponds to variant dbSNP:rs188245364Ensembl.1
Natural variantiVAR_066656241I → M Found in a patient with Parkinson disease. 1 PublicationCorresponds to variant dbSNP:rs192783364EnsemblClinVar.1
Natural variantiVAR_066657316P → S Found in a patient with Parkinson disease. 1 PublicationCorresponds to variant dbSNP:rs770029606EnsemblClinVar.1
Natural variantiVAR_080769469Q → P Found in a consanguineous family with intellectual disability; unknown pathological significance. 1 Publication1
Natural variantiVAR_066658524R → W Found in a patient with Parkinson disease. 1 PublicationCorresponds to variant dbSNP:rs184277092EnsemblClinVar.1
Natural variantiVAR_054046602V → D. Corresponds to variant dbSNP:rs34687100Ensembl.1
Natural variantiVAR_066659620D → N in PARK17; decreases interaction with WASHC2C, FKBP15 and the WASH complex; impairs recruitment of the WASH complex to endosomes; shows reduced retrograde transport of selective cargo between lysosomes and the Golgi apparatus; shows a progressive reduction in neurite length and branching. 6 PublicationsCorresponds to variant dbSNP:rs188286943EnsemblClinVar.1
Natural variantiVAR_066660737A → V1 PublicationCorresponds to variant dbSNP:rs749516404EnsemblClinVar.1
Natural variantiVAR_066661774L → M1 PublicationCorresponds to variant dbSNP:rs192419029EnsemblClinVar.1

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...EMBLi

GenBank nucleotide sequence database

More...GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...DDBJi
Links Updated
AF191298 mRNA Translation: AAF02778.2
AF186382 mRNA Translation: AAG40619.1
AF175265 mRNA Translation: AAF89953.1
AF183418 mRNA Translation: AAG09687.1
AK001614 mRNA Translation: BAA91790.1
AK023650 mRNA Translation: BAB14626.1 Different initiation.
AK000395 mRNA Translation: BAA91137.1 Different initiation.
AL136888 mRNA Translation: CAB66822.1
AL512769 mRNA Translation: CAC21686.1
BC002414 mRNA Translation: AAH02414.1
BC010362 mRNA Translation: AAH10362.1
BC093036 mRNA Translation: AAH93036.1
AY007112 mRNA Translation: AAG01989.1 Different initiation.

The Consensus CDS (CCDS) project

More...CCDSi		CCDS10721.1

Protein sequence database of the Protein Information Resource

More...PIRi		JC7516

NCBI Reference Sequences

More...RefSeqi		NP_060676.2, NM_018206.5

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...Ensembli		ENST00000299138; ENSP00000299138; ENSG00000069329

Database of genes from NCBI RefSeq genomes

More...GeneIDi		55737

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...KEGGi		hsa:55737

Matched Annotation from NCBI and EMBL-EBI (MANE) - Phase one

More...MANE-Selecti		ENST00000299138.12; ENSP00000299138.7; NM_018206.6; NP_060676.2

UCSC genome browser

More...UCSCi		uc002eef.5, human

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF191298 mRNA Translation: AAF02778.2
AF186382 mRNA Translation: AAG40619.1
AF175265 mRNA Translation: AAF89953.1
AF183418 mRNA Translation: AAG09687.1
AK001614 mRNA Translation: BAA91790.1
AK023650 mRNA Translation: BAB14626.1 Different initiation.
AK000395 mRNA Translation: BAA91137.1 Different initiation.
AL136888 mRNA Translation: CAB66822.1
AL512769 mRNA Translation: CAC21686.1
BC002414 mRNA Translation: AAH02414.1
BC010362 mRNA Translation: AAH10362.1
BC093036 mRNA Translation: AAH93036.1
AY007112 mRNA Translation: AAG01989.1 Different initiation.
CCDSiCCDS10721.1
PIRiJC7516
RefSeqiNP_060676.2, NM_018206.5

3D structure databases

Select the link destinations:

Protein Data Bank Europe

More...PDBei

Protein Data Bank RCSB

More...RCSB PDBi

Protein Data Bank Japan

More...PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2R17X-ray2.80C/D483-780[»]
5F0JX-ray2.70A14-470[»]
5F0KX-ray3.07A/B/C/D/E14-470[»]
5F0LX-ray3.20A14-470[»]
5F0MX-ray3.10A14-470[»]
5F0PX-ray2.78A14-470[»]
5OSHX-ray4.30B/E/H/K482-780[»]
5OSIX-ray2.52B/E/H/K471-781[»]
7BLNelectron microscopy8.90A/C1-796[»]
7BLOelectron microscopy9.50A/C12-363[»]
SMRiQ96QK1
ModBaseiSearch...
PDBe-KBiSearch...

Protein-protein interaction databases

BioGRIDi120855, 153 interactors
CORUMiQ96QK1
DIPiDIP-29076N
IntActiQ96QK1, 48 interactors
MINTiQ96QK1
STRINGi9606.ENSP00000299138

Chemistry databases

BindingDBiQ96QK1
ChEMBLiCHEMBL2216744

Protein family/group databases

TCDBi9.A.3.1.1, the sorting nexin27 (snx27)-retromer assembly apparatus (retromeraa) family

PTM databases

GlyGeniQ96QK1, 1 site, 1 O-linked glycan (1 site)
iPTMnetiQ96QK1
PhosphoSitePlusiQ96QK1
SwissPalmiQ96QK1

Genetic variation databases

BioMutaiVPS35
DMDMi25453321

Proteomic databases

CPTACiCPTAC-605
EPDiQ96QK1
jPOSTiQ96QK1
MassIVEiQ96QK1
MaxQBiQ96QK1
PaxDbiQ96QK1
PeptideAtlasiQ96QK1
PRIDEiQ96QK1
ProteomicsDBi77884

Protocols and materials databases

Antibodypedia a portal for validated antibodies

More...Antibodypediai		28023, 253 antibodies from 41 providers

The DNASU plasmid repository

More...DNASUi		55737

Genome annotation databases

EnsembliENST00000299138; ENSP00000299138; ENSG00000069329
GeneIDi55737
KEGGihsa:55737
MANE-SelectiENST00000299138.12; ENSP00000299138.7; NM_018206.6; NP_060676.2
UCSCiuc002eef.5, human

Organism-specific databases

Comparative Toxicogenomics Database

More...CTDi		55737
DisGeNETi55737

GeneCards: human genes, protein and diseases

More...GeneCardsi		VPS35
GeneReviewsiVPS35
HGNCiHGNC:13487, VPS35
HPAiENSG00000069329, Low tissue specificity
MalaCardsiVPS35
MIMi601501, gene
614203, phenotype
neXtProtiNX_Q96QK1
OpenTargetsiENSG00000069329
Orphaneti411602, Hereditary late-onset Parkinson disease
PharmGKBiPA37783
VEuPathDBiHostDB:ENSG00000069329

GenAtlas: human gene database

More...GenAtlasi		Search...

Phylogenomic databases

eggNOGiKOG1107, Eukaryota
GeneTreeiENSGT00390000007315
HOGENOMiCLU_005836_1_0_1
InParanoidiQ96QK1
OMAiHLWWATP
OrthoDBi316875at2759
PhylomeDBiQ96QK1
TreeFamiTF105659

Enzyme and pathway databases

PathwayCommonsiQ96QK1
ReactomeiR-HSA-3238698, WNT ligand biogenesis and trafficking
SignaLinkiQ96QK1
SIGNORiQ96QK1

Miscellaneous databases

BioGRID ORCS database of CRISPR phenotype screens

More...BioGRID-ORCSi		55737, 380 hits in 1061 CRISPR screens

ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

More...ChiTaRSi		VPS35, human
EvolutionaryTraceiQ96QK1

The Gene Wiki collection of pages on human genes and proteins

More...GeneWikii		VPS35

Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

More...GenomeRNAii		55737
PharosiQ96QK1, Tbio

Protein Ontology

More...PROi		PR:Q96QK1
RNActiQ96QK1, protein

The Stanford Online Universal Resource for Clones and ESTs

More...SOURCEi		Search...

Gene expression databases

BgeeiENSG00000069329, Expressed in intestine and 125 other tissues
ExpressionAtlasiQ96QK1, baseline and differential
GenevisibleiQ96QK1, HS

Family and domain databases

Gene3Di1.25.40.660, 1 hit
InterProiView protein in InterPro
IPR016024, ARM-type_fold
IPR005378, Vps35
IPR042491, Vps35_C
PANTHERiPTHR11099, PTHR11099, 1 hit
PfamiView protein in Pfam
PF03635, Vps35, 1 hit
PIRSFiPIRSF009375, Retromer_Vps35, 1 hit
SUPFAMiSSF48371, SSF48371, 1 hit

MobiDB: a database of protein disorder and mobility annotations

More...MobiDBi		Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the 'Entry information' section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiVPS35_HUMAN
<p>This subsection of the 'Entry information' section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called 'Primary (citable) accession number'.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: Q96QK1
Secondary accession number(s): Q561W2
, Q9H016, Q9H096, Q9H4P3, Q9H8J0, Q9NRS7, Q9NVG2, Q9NX80, Q9NZK2
<p>This subsection of the 'Entry information' section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification ('Last modified'). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 25, 2002
Last sequence update: November 25, 2002
Last modified: February 23, 2022
This is version 198 of the entry and version 2 of the sequence. See complete history.
<p>This subsection of the 'Entry information' section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

<p>This section contains any relevant information that doesn't fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

3D-structure, Reference proteome

Documents

  1. Human chromosome 16
    Human chromosome 16: entries, gene names and cross-references to MIM
  2. Human entries with genetic variants
    List of human entries with genetic variants
  3. Human variants curated from literature reports
    Index of human variants curated from literature reports
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families
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