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Protein

Vacuolar protein sorting-associated protein 26A

Gene

VPS26A

Organism
Homo sapiens (Human)
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 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. The SNX27-retromer is believed to be involved in endosome-to-plasma membrane trafficking and recycling of a broad spectrum of cargo proteins (Probable). 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 (PubMed:15078902, PubMed:15078903). Required to regulate transcytosis of the polymeric immunoglobulin receptor (pIgR-pIgA) (PubMed:15247922). Required for the endosomal localization of FAM21A (indicative for the WASH complex) (PubMed:22070227). Required for the endosomal localization of TBC1D5 (PubMed:20923837). Mediates retromer cargo reognition of SORL1 and is involved in trafficking of SORL1 implicated in sorting and processing of APP (PubMed:22279231). Involved in retromer-independent lysosomal sorting of F2R (PubMed:16407403). Involved in recycling of ADRB2 (PubMed:21602791). Enhances the affinity of SNX27 for PDZ-binding motifs in cargo proteins (By similarity).4 PublicationsBy similarityCurated6 Publications

GO - Molecular functioni

  • protein transporter activity Source: UniProtKB

GO - Biological processi

  • intracellular protein transport Source: GO_Central
  • regulation of macroautophagy Source: ParkinsonsUK-UCL
  • retrograde transport, endosome to Golgi Source: UniProtKB
  • retrograde transport, endosome to plasma membrane Source: UniProtKB
  • Wnt signaling pathway Source: Reactome
Complete GO annotation...

Keywords - Biological processi

Protein transport, Transport

Enzyme and pathway databases

BioCyciZFISH:ENSG00000122958-MONOMER.
ReactomeiR-HSA-3238698. WNT ligand biogenesis and trafficking.

Names & Taxonomyi

Protein namesi
Recommended name:
Vacuolar protein sorting-associated protein 26A
Alternative name(s):
Vesicle protein sorting 26A
Short name:
hVPS26
Gene namesi
Name:VPS26A
Synonyms:VPS26
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

HGNCiHGNC:12711. VPS26A.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: UniProtKB
  • early endosome Source: UniProtKB
  • endosome Source: UniProtKB
  • endosome membrane Source: UniProtKB
  • extracellular exosome Source: UniProtKB
  • intracellular membrane-bounded organelle Source: HPA
  • retromer, cargo-selective complex Source: ParkinsonsUK-UCL
  • retromer complex Source: ParkinsonsUK-UCL
  • tubular endosome Source: UniProtKB
  • vesicle Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Endosome, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi235 – 236IM → DD: Abolishes interaction with VPS35 and endosomal subcellular location. 2

Organism-specific databases

DisGeNETi9559.
OpenTargetsiENSG00000122958.
PharmGKBiPA37326.

Polymorphism and mutation databases

BioMutaiVPS26A.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000730071 – 327Vacuolar protein sorting-associated protein 26AAdd BLAST327

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei315PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiO75436.
MaxQBiO75436.
PaxDbiO75436.
PeptideAtlasiO75436.
PRIDEiO75436.

PTM databases

iPTMnetiO75436.
PhosphoSitePlusiO75436.
SwissPalmiO75436.

Expressioni

Inductioni

Down-regulated in Alzheimer disease. No polymorphism or variant is however associated with Alzheimer disease for VPS26A.2 Publications

Gene expression databases

BgeeiENSG00000122958.
CleanExiHS_VPS26A.
ExpressionAtlasiO75436. baseline and differential.
GenevisibleiO75436. HS.

Organism-specific databases

HPAiCAB011602.
CAB075733.
HPA044581.
HPA057498.

Interactioni

Subunit structurei

Component of the heterotrimeric retromer cargo-selective complex (CSC), also descibed as vacuolar protein sorting subcomplex (VPS), formed by VPS26 (VPS26A or VPS26B), VPS29 and VPS35 (PubMed:11102511). 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 VPS29, VPS35, SNX1, SNX2, SNX5, SNX6, SNX3, SNX27, RAB7A, ECM29, EHD1, KIAA0196, SORL1 (PubMed:11102511, PubMed:16190980, PubMed:19619496, PubMed:17868075, PubMed:19531583, PubMed:20682791, PubMed:20923837, PubMed:21725319, PubMed:22279231, PubMed:24344282, PubMed:16732284).3 PublicationsBy similarity11 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
VPS29Q9UBQ05EBI-1043891,EBI-718596
VPS35Q96QK17EBI-1043891,EBI-1054634

Protein-protein interaction databases

BioGridi114930. 99 interactors.
DIPiDIP-29075N.
IntActiO75436. 41 interactors.
MINTiMINT-5000831.
STRINGi9606.ENSP00000263559.

Structurei

Secondary structure

1327
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni7 – 11Combined sources5
Beta strandi12 – 18Combined sources7
Helixi21 – 23Combined sources3
Beta strandi26 – 30Combined sources5
Beta strandi36 – 42Combined sources7
Beta strandi48 – 60Combined sources13
Beta strandi63 – 66Combined sources4
Beta strandi68 – 78Combined sources11
Beta strandi85 – 96Combined sources12
Beta strandi98 – 101Combined sources4
Beta strandi105 – 111Combined sources7
Beta strandi124 – 136Combined sources13
Beta strandi139 – 141Combined sources3
Beta strandi143 – 151Combined sources9
Beta strandi164 – 170Combined sources7
Turni171 – 173Combined sources3
Beta strandi174 – 181Combined sources8
Beta strandi183 – 186Combined sources4
Beta strandi190 – 200Combined sources11
Beta strandi204 – 218Combined sources15
Helixi220 – 222Combined sources3
Beta strandi224 – 234Combined sources11
Beta strandi246 – 252Combined sources7
Turni253 – 255Combined sources3
Beta strandi261 – 265Combined sources5
Beta strandi268 – 280Combined sources13
Beta strandi285 – 295Combined sources11

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2FAUX-ray2.10A1-327[»]
ProteinModelPortaliO75436.
SMRiO75436.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO75436.

Family & Domainsi

Sequence similaritiesi

Belongs to the VPS26 family.Curated

Phylogenomic databases

eggNOGiKOG3063. Eukaryota.
ENOG410XSI1. LUCA.
GeneTreeiENSGT00390000002588.
HOGENOMiHOG000191799.
HOVERGENiHBG082914.
InParanoidiO75436.
KOiK18466.
OMAiSDKSNTH.
OrthoDBiEOG091G09TQ.
PhylomeDBiO75436.
TreeFamiTF300907.

Family and domain databases

InterProiIPR028934. Vps26-related.
[Graphical view]
PfamiPF03643. Vps26. 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: O75436-1) [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
MSFLGGFFGP ICEIDIVLND GETRKMAEMK TEDGKVEKHY LFYDGESVSG
60 70 80 90 100
KVNLAFKQPG KRLEHQGIRI EFVGQIELFN DKSNTHEFVN LVKELALPGE
110 120 130 140 150
LTQSRSYDFE FMQVEKPYES YIGANVRLRY FLKVTIVRRL TDLVKEYDLI
160 170 180 190 200
VHQLATYPDV NNSIKMEVGI EDCLHIEFEY NKSKYHLKDV IVGKIYFLLV
210 220 230 240 250
RIKIQHMELQ LIKKEITGIG PSTTTETETI AKYEIMDGAP VKGESIPIRL
260 270 280 290 300
FLAGYDPTPT MRDVNKKFSV RYFLNLVLVD EEDRRYFKQQ EIILWRKAPE
310 320
KLRKQRTNFH QRFESPESQA SAEQPEM
Length:327
Mass (Da):38,170
Last modified:November 25, 2002 - v2
Checksum:iBD3B2EAA6CFCBFA9
GO
Isoform 2 (identifier: O75436-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     243-327: GESIPIRLFL...SQASAEQPEM → GDNFMEKSS

Note: No experimental confirmation available.Curated
Show »
Length:251
Mass (Da):28,938
Checksum:i1140DC4C2D80D257
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti75Q → R in BAB14351 (PubMed:14702039).Curated1
Sequence conflicti242K → Q in BQ048905 (PubMed:15489334).Curated1
Sequence conflicti285 – 286RY → SS in AAF89954 (PubMed:11102511).Curated2
Sequence conflicti285 – 286RY → SS in AAC39912 (PubMed:9653160).Curated2
Isoform 2 (identifier: O75436-2)
Sequence conflicti243G → R in BQ048905 (PubMed:15489334).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_044910243 – 327GESIP…EQPEM → GDNFMEKSS in isoform 2. 1 PublicationAdd BLAST85

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF175266 mRNA. Translation: AAF89954.1.
AF054179 mRNA. Translation: AAC39912.1.
AK022992 mRNA. Translation: BAB14351.1.
AK315496 mRNA. Translation: BAG37880.1.
AL596223, AL442635 Genomic DNA. Translation: CAH71501.1.
AL442635, AL596223 Genomic DNA. Translation: CAH71779.1.
CH471083 Genomic DNA. Translation: EAW54313.1.
BC022505 mRNA. Translation: AAH22505.1.
BQ048905 mRNA. No translation available.
CCDSiCCDS41536.1. [O75436-2]
CCDS7286.1. [O75436-1]
RefSeqiNP_001030337.1. NM_001035260.2. [O75436-2]
NP_001305875.1. NM_001318946.1.
NP_004887.2. NM_004896.4. [O75436-1]
UniGeneiHs.499925.

Genome annotation databases

EnsembliENST00000263559; ENSP00000263559; ENSG00000122958. [O75436-1]
ENST00000373382; ENSP00000362480; ENSG00000122958. [O75436-1]
ENST00000395098; ENSP00000378532; ENSG00000122958. [O75436-2]
GeneIDi9559.
KEGGihsa:9559.
UCSCiuc001jpb.4. human. [O75436-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF175266 mRNA. Translation: AAF89954.1.
AF054179 mRNA. Translation: AAC39912.1.
AK022992 mRNA. Translation: BAB14351.1.
AK315496 mRNA. Translation: BAG37880.1.
AL596223, AL442635 Genomic DNA. Translation: CAH71501.1.
AL442635, AL596223 Genomic DNA. Translation: CAH71779.1.
CH471083 Genomic DNA. Translation: EAW54313.1.
BC022505 mRNA. Translation: AAH22505.1.
BQ048905 mRNA. No translation available.
CCDSiCCDS41536.1. [O75436-2]
CCDS7286.1. [O75436-1]
RefSeqiNP_001030337.1. NM_001035260.2. [O75436-2]
NP_001305875.1. NM_001318946.1.
NP_004887.2. NM_004896.4. [O75436-1]
UniGeneiHs.499925.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2FAUX-ray2.10A1-327[»]
ProteinModelPortaliO75436.
SMRiO75436.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114930. 99 interactors.
DIPiDIP-29075N.
IntActiO75436. 41 interactors.
MINTiMINT-5000831.
STRINGi9606.ENSP00000263559.

PTM databases

iPTMnetiO75436.
PhosphoSitePlusiO75436.
SwissPalmiO75436.

Polymorphism and mutation databases

BioMutaiVPS26A.

Proteomic databases

EPDiO75436.
MaxQBiO75436.
PaxDbiO75436.
PeptideAtlasiO75436.
PRIDEiO75436.

Protocols and materials databases

DNASUi9559.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000263559; ENSP00000263559; ENSG00000122958. [O75436-1]
ENST00000373382; ENSP00000362480; ENSG00000122958. [O75436-1]
ENST00000395098; ENSP00000378532; ENSG00000122958. [O75436-2]
GeneIDi9559.
KEGGihsa:9559.
UCSCiuc001jpb.4. human. [O75436-1]

Organism-specific databases

CTDi9559.
DisGeNETi9559.
GeneCardsiVPS26A.
HGNCiHGNC:12711. VPS26A.
HPAiCAB011602.
CAB075733.
HPA044581.
HPA057498.
MIMi605506. gene.
neXtProtiNX_O75436.
OpenTargetsiENSG00000122958.
PharmGKBiPA37326.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3063. Eukaryota.
ENOG410XSI1. LUCA.
GeneTreeiENSGT00390000002588.
HOGENOMiHOG000191799.
HOVERGENiHBG082914.
InParanoidiO75436.
KOiK18466.
OMAiSDKSNTH.
OrthoDBiEOG091G09TQ.
PhylomeDBiO75436.
TreeFamiTF300907.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000122958-MONOMER.
ReactomeiR-HSA-3238698. WNT ligand biogenesis and trafficking.

Miscellaneous databases

ChiTaRSiVPS26A. human.
EvolutionaryTraceiO75436.
GeneWikiiVPS26A.
GenomeRNAii9559.
PROiO75436.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000122958.
CleanExiHS_VPS26A.
ExpressionAtlasiO75436. baseline and differential.
GenevisibleiO75436. HS.

Family and domain databases

InterProiIPR028934. Vps26-related.
[Graphical view]
PfamiPF03643. Vps26. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiVP26A_HUMAN
AccessioniPrimary (citable) accession number: O75436
Secondary accession number(s): A8MZ56
, B2RDD3, Q8TBH4, Q9H982
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: November 25, 2002
Last modified: November 2, 2016
This is version 150 of the entry and version 2 of the sequence. [Complete history]
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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. 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.