VPS26A

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 WASHC2A (indicative for the WASH complex) (PubMed:22070227). Required for the endosomal localization of TBC1D5 (PubMed:20923837). Mediates retromer cargo recognition 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: GO_Central

View the complete GO annotation on QuickGO ...

GO - Biological processⁱ

intracellular protein transport Source: GO_Central
regulation of macroautophagy
Source: ParkinsonsUK-UCL
Traceable author statementⁱ
- 26172538
retrograde transport, endosome to Golgi
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 15078903
retrograde transport, endosome to plasma membrane
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 21602791
Wnt signaling pathway Source: Reactome

View the complete GO annotation on QuickGO ...

Keywordsⁱ

Biological process	Protein transport, Transport

Biological process

Protein transport, Transport

Enzyme and pathway databases

Reactomeⁱ	R-HSA-3238698 WNT ligand biogenesis and trafficking

Reactomeⁱ

R-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
Organismⁱ	Homo sapiens (Human)
Taxonomic identifierⁱ	9606 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo
Proteomesⁱ	UP000005640 Componentⁱ: Chromosome 10

Organism-specific databases

EuPathDBⁱ	HostDB:ENSG00000122958.14
Human Gene Nomenclature Database More...HGNCⁱ	HGNC:12711 VPS26A
MIMⁱ	605506 gene
neXtProtⁱ	NX_O75436

Keywords - Cellular componentⁱ

Cytoplasm, Endosome, Membrane

Pathology & Biotechⁱ

Mutagenesis

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Mutagenesisⁱ	235 – 236	IM → DD: Abolishes interaction with VPS35 and endosomal subcellular location.		2

Organism-specific databases

DisGeNET More...DisGeNETⁱ	9559
Open Targets More...OpenTargetsⁱ	ENSG00000122958
PharmGKBⁱ	PA37326

Polymorphism and mutation databases

BioMutaⁱ	VPS26A

BioMutaⁱ

VPS26A

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
ChainⁱPRO_0000073007	1 – 327	Vacuolar protein sorting-associated protein 26AAdd BLAST		327

Amino acid modifications

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Modified residueⁱ	315	PhosphoserineCombined sources		1

Keywords - PTMⁱ

Phosphoprotein

Proteomic databases

EPDⁱ	O75436
MaxQB - The MaxQuant DataBase More...MaxQBⁱ	O75436
PaxDbⁱ	O75436
PeptideAtlas More...PeptideAtlasⁱ	O75436
PRIDEⁱ	O75436
ProteomicsDBⁱ	50002

PTM databases

iPTMnetⁱ	O75436
PhosphoSitePlusⁱ	O75436
SwissPalmⁱ	O75436

Expressionⁱ

Inductionⁱ

Gene expression databases

Bgeeⁱ	ENSG00000122958 Expressed in 235 organ(s), highest expression level in visceral pleura
CleanExⁱ	HS_VPS26A
ExpressionAtlasⁱ	O75436 baseline and differential
Genevisibleⁱ	O75436 HS

Organism-specific databases

Human Protein Atlas More...HPAⁱ	CAB011602 CAB075733 HPA057498

HPAⁱ

CAB011602
CAB075733
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, ECPAS, EHD1, WASHC5, 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

With	Entry	#Exp.	IntAct	Notes
VPS29	Q9UBQ0	9	EBI-1043891,EBI-718596
VPS35	Q96QK1	17	EBI-1043891,EBI-1054634

Protein-protein interaction databases

BioGridⁱ	114930, 108 interactors
CORUMⁱ	O75436
Database of interacting proteins More...DIPⁱ	DIP-29075N
IntActⁱ	O75436, 47 interactors
Molecular INTeraction database More...MINTⁱ	O75436
STRINGⁱ	9606.ENSP00000263559

Structureⁱ

Secondary structure

Legend: HelixTurnBeta strandPDB Structure known for this area

Feature key	Position(s)	DescriptionActions	Length
Turnⁱ	7 – 11	Combined sources	5
Beta strandⁱ	12 – 18	Combined sources	7
Helixⁱ	21 – 23	Combined sources	3
Beta strandⁱ	26 – 30	Combined sources	5
Helixⁱ	32 – 34	Combined sources	3
Beta strandⁱ	36 – 42	Combined sources	7
Beta strandⁱ	48 – 60	Combined sources	13
Beta strandⁱ	63 – 66	Combined sources	4
Beta strandⁱ	68 – 78	Combined sources	11
Helixⁱ	82 – 84	Combined sources	3
Beta strandⁱ	85 – 96	Combined sources	12
Beta strandⁱ	98 – 101	Combined sources	4
Beta strandⁱ	105 – 111	Combined sources	7
Beta strandⁱ	124 – 136	Combined sources	13
Beta strandⁱ	139 – 141	Combined sources	3
Beta strandⁱ	143 – 151	Combined sources	9
Beta strandⁱ	164 – 170	Combined sources	7
Turnⁱ	171 – 173	Combined sources	3
Beta strandⁱ	174 – 181	Combined sources	8
Beta strandⁱ	183 – 186	Combined sources	4
Beta strandⁱ	190 – 200	Combined sources	11
Beta strandⁱ	204 – 218	Combined sources	15
Helixⁱ	220 – 222	Combined sources	3
Beta strandⁱ	224 – 234	Combined sources	11
Beta strandⁱ	246 – 252	Combined sources	7
Turnⁱ	253 – 255	Combined sources	3
Beta strandⁱ	261 – 265	Combined sources	5
Beta strandⁱ	268 – 280	Combined sources	13
Beta strandⁱ	285 – 295	Combined sources	11

Show more details

3D structure databases

ProteinModelPortalⁱ	O75436
SMRⁱ	O75436
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Miscellaneous databases

EvolutionaryTraceⁱ	O75436

EvolutionaryTraceⁱ

O75436

Family & Domainsⁱ

Sequence similaritiesⁱ

Belongs to the VPS26 family.Curated

Phylogenomic databases

eggNOGⁱ	KOG3063 Eukaryota ENOG410XSI1 LUCA
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00390000002588
HOGENOMⁱ	HOG000191799
HOVERGENⁱ	HBG082914
InParanoidⁱ	O75436
KEGG Orthology (KO) More...KOⁱ	K18466
OMAⁱ	PVCEIDV
Database of Orthologous Groups More...OrthoDBⁱ	EOG091G09TQ
PhylomeDBⁱ	O75436
TreeFamⁱ	TF300907

Family and domain databases

Gene3Dⁱ	2.60.40.640, 2 hits
InterProⁱ	View protein in InterPro IPR014752 Arrestin_C IPR028934 Vps26-related
PANTHERⁱ	PTHR12233 PTHR12233, 1 hit
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF03643 Vps26, 1 hit

Sequences (2+)ⁱ

Sequence statusⁱ: Complete.

This entry describes 2 isoformsⁱ produced by alternative splicing. Align Add to basket

This entry has 2 described isoforms and 2 potential isoforms that are computationally mapped.ⁱShow all

Isoform 1 (identifier: O75436-1) [UniParc]FASTA Add 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]FASTA Add to basket

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

« 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 VKGDNFMEKS 

S

Note: No experimental confirmation available.Curated

Show »

Length:251

Mass (Da):28,938

Checksum:ⁱ1140DC4C2D80D257

GO

Computationally mapped potential isoform sequencesⁱ

There are 2 potential isoforms mapped to this entry.BLAST Align Show all Add to basket

	Entry	Entry name		Protein names	Gene names	Length	Annotation
	S4R3Q6	S4R3Q6_HUMAN		Vacuolar protein sorting-associated... Vacuolar protein sorting-associated protein 26A	VPS26A	226	Annotation score:
	S4R2Y3	S4R2Y3_HUMAN		Vacuolar protein sorting-associated... Vacuolar protein sorting-associated protein 26A	VPS26A	63	Annotation score:

Experimental Info

Feature key	Position(s)	DescriptionActions	Length
Sequence conflictⁱ	75	Q → R in BAB14351 (PubMed:14702039).Curated	1
Sequence conflictⁱ	242	K → Q in BQ048905 (PubMed:15489334).Curated	1
Sequence conflictⁱ	285 – 286	RY → SS in AAF89954 (PubMed:11102511).Curated	2
Sequence conflictⁱ	285 – 286	RY → SS in AAC39912 (PubMed:9653160).Curated	2
Isoform 2 (identifier: O75436-2)
Sequence conflictⁱ	243	G → R in BQ048905 (PubMed:15489334).Curated	1

Alternative sequence

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Alternative sequenceⁱVSP_044910	243 – 327	GESIP…EQPEM → GDNFMEKSS in isoform 2. 1 PublicationAdd BLAST		85

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 Genomic DNA No translation available. AL442635 Genomic DNA No translation available. CH471083 Genomic DNA Translation: EAW54313.1 BC022505 mRNA Translation: AAH22505.1 BQ048905 mRNA No translation available.
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS41536.1 [O75436-2] CCDS7286.1 [O75436-1]
NCBI Reference Sequences More...RefSeqⁱ	NP_001030337.1, NM_001035260.2 [O75436-2] NP_001305875.1, NM_001318946.1 NP_004887.2, NM_004896.4 [O75436-1]
UniGeneⁱ	Hs.499925

Genome annotation databases

Ensemblⁱ	ENST00000263559; ENSP00000263559; ENSG00000122958 [O75436-1] ENST00000373382; ENSP00000362480; ENSG00000122958 [O75436-1] ENST00000395098; ENSP00000378532; ENSG00000122958 [O75436-2]
GeneIDⁱ	9559
KEGGⁱ	hsa:9559
UCSC genome browser More...UCSCⁱ	uc001jpb.4 human [O75436-1]

Keywords - Coding sequence diversityⁱ

Alternative splicing

Similar proteinsⁱ

100% Identity
90% Identity
50% Identity

Protein	Similar proteins		Species	Score	Length	Source
O75436	VPS26, retromer complex component A		CALJA		327	UniRef100_O75436
VPS26A isoform 1		PANTR		327
VPS26, retromer complex component A		MACMU		327
Macaca fascicularis brain cDNA clone: QflA-17517, similar to human vacuolar protein sorting 26 (yeast) (VPS26), mRNA, RefSeq: NM_004896.2		MACFA		327
VPS26, retromer complex component A		PONAB		327
+14
O75436-2	Vacuolar protein sorting-associated protein 26A		HUMAN		226	UniRef100_S4R3Q6
VPS26A isoform 2		PANTR		251
VPS26, retromer complex component A		MACMU		251
VPS26, retromer complex component A		COLAP		251
VPS26A isoform 2		PONAB		251
+11

Protein	Similar proteins		Species	Score	Length	Source
O75436	VPS26, retromer complex component A		CALJA		327	UniRef90_O75436
VPS26A isoform 1		PANTR		327
VPS26, retromer complex component A		MACMU		327
Macaca fascicularis brain cDNA clone: QflA-17517, similar to human vacuolar protein sorting 26 (yeast) (VPS26), mRNA, RefSeq: NM_004896.2		MACFA		327
VPS26, retromer complex component A		PONAB		327
+104
O75436-2	Vacuolar protein sorting-associated protein 26A		HUMAN		226	UniRef90_S4R3Q6
VPS26A isoform 2		PANTR		251
VPS26, retromer complex component A		MACMU		251
VPS26, retromer complex component A		COLAP		251
VPS26A isoform 2		PONAB		251
+19

Protein	Similar proteins		Species	Score	Length	Source
O75436	Vacuolar protein sorting-associated protein 26		CAEEL		356	UniRef50_O75436
Vacuolar protein sorting-associated protein 26		DROME		478
VPS26, retromer complex component A		CALJA		327
VPS26A isoform 1		PANTR		327
VPS26, retromer complex component A		MACMU		327
+157
O75436-2	VPS26, retromer complex component A		MACMU		230	UniRef50_F6Z637
Uncharacterized protein		GORGO		276
Uncharacterized protein		GOSBA		301
vacuolar protein sorting-associated protein 26B-like isoform X3		GOSHI		283
Uncharacterized protein		ORYRU		278
+85

Entry informationⁱ

Entry nameⁱ	VP26A_HUMAN
Accessionⁱ	O75436Primary (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:	September 12, 2018
	This is version 164 of the entry and version 2 of the sequence. See complete history.
Entry statusⁱ	Reviewed (UniProtKB/Swiss-Prot)
Annotation program	Chordata Protein Annotation Program
Disclaimer	Any 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

UniProtKB

UniParc

Help

UniRef

Proteomes

Annotation systems

Supporting data

UniProtKB - O75436 (VP26A_HUMAN)

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Vacuolar protein sorting-associated protein 26A

Select a section on the left to see content.

<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

<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

GO - Biological processi

Enzyme and pathway databases

<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

Organism-specific databases

<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

Endosome

Other locations

Cytosol

Endosome

Lysosome

Other locations

Keywords - Cellular componenti

<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

Mutagenesis

Organism-specific databases

Polymorphism and mutation databases

<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

Amino acid modifications

Keywords - PTMi

Proteomic databases

PTM databases

<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

Gene expression databases

Organism-specific databases

<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

Protein-protein interaction databases

<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

3D structure databases

Miscellaneous databases

<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

<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

Phylogenomic databases

Family and domain databases

Computationally mapped potential isoform sequencesi

Experimental Info

Alternative sequence

Sequence databases

Genome annotation databases

Keywords - Coding sequence diversityi

<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 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

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Functionⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Keywords - Cellular componentⁱ

Pathology & Biotechⁱ

PTM / Processingⁱ

Keywords - PTMⁱ

Expressionⁱ

Interactionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Computationally mapped potential isoform sequencesⁱ

Keywords - Coding sequence diversityⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ