O75436 (VP26A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Vacuolar protein sorting-associated protein 26A

Alternative name(s):
Vesicle protein sorting 26A
Short name=hVPS26

Gene names

Name:	VPS26A
Synonyms:	VPS26

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	327 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Essential component of the retromer complex, a complex required to retrieve lysosomal enzyme receptors (IGF2R and M6PR) from endosomes to the trans-Golgi network. Also required to regulate transcytosis of the polymeric immunoglobulin receptor (pIgR-pIgA). Ref.8 Ref.11
Subunit structure	Component of the retromer complex composed of VPS26 (VPS26A or VPS26B), VPS29, VPS35, SNX1 and SNX2. Interacts directly with VPS35. Found in a complex with XPO7, EIF4A1, ARHGAP1, VPS26A, VPS29, VPS35 and SFN. Interacts with ECM29. Ref.1 Ref.7 Ref.10 Ref.14 Ref.17
Subcellular location	Cytoplasm. Endosome membrane; Peripheral membrane protein Ref.10 Ref.14 Ref.17.
Induction	Down-regulated in Alzheimer disease. No polymorphism or variant is however associated with Alzheimer disease for VPS26A. Ref.9 Ref.13
Sequence similarities	Belongs to the VPS26 family.

Ontologies

Keywords
Biological process	Protein transport Transport
Cellular component	Cytoplasm Endosome Membrane
Coding sequence diversity	Alternative splicing
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	retrograde transport, endosome to Golgi Non-traceable author statement Ref.1. Source: UniProtKB vacuolar transport Inferred from electronic annotation. Source: InterPro
Cellular_component	cytosol Inferred from direct assay Ref.1. Source: UniProtKB endosome Inferred from direct assay Ref.14. Source: UniProtKB endosome membrane Inferred from electronic annotation. Source: UniProtKB-SubCell retromer complex Inferred from electronic annotation. Source: InterPro vesicle Inferred from direct assay Ref.14. Source: UniProtKB
Molecular_function	protein transporter activity Non-traceable author statement Ref.1. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O75436-1)

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.

Isoform 2 (identifier: O75436-2)

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

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 327

327

Vacuolar protein sorting-associated protein 26A

PRO_0000073007

Amino acid modifications

Modified residue

315

1

Phosphoserine Ref.15

Natural variations

Alternative sequence

243 – 327

85

GESIP…EQPEM → GDNFMEKSS in isoform 2.

VSP_044910

Experimental info

Mutagenesis

235 – 236

2

IM → DD: Abolishes interaction with VPS35 and endosomal subcellular location. Ref.17

Sequence conflict

75

1

Q → R in BAB14351. Ref.3

Sequence conflict

242

1

K → Q in BQ048905. Ref.6

Sequence conflict

285 – 286

2

RY → SS in AAF89954. Ref.1

Sequence conflict

285 – 286

2

RY → SS in AAC39912. Ref.2

Isoform 2:

Sequence conflict

243

1

G → R in BQ048905. Ref.6

Secondary structure

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327

Helix Strand Turn

Details...

Turn

7 – 11

5

Beta strand

12 – 18

7

Helix

21 – 23

3

Beta strand

26 – 30

5

Beta strand

36 – 42

7

Beta strand

48 – 60

13

Beta strand

63 – 66

4

Beta strand

68 – 78

11

Beta strand

85 – 96

12

Beta strand

98 – 101

4

Beta strand

105 – 111

7

Beta strand

124 – 136

13

Beta strand

139 – 141

3

Beta strand

143 – 151

9

Beta strand

164 – 170

7

Turn

171 – 173

3

Beta strand

174 – 181

8

Beta strand

183 – 186

4

Beta strand

190 – 200

11

Beta strand

204 – 218

15

Helix

220 – 222

3

Beta strand

224 – 234

11

Beta strand

246 – 252

7

Turn

253 – 255

3

Beta strand

261 – 265

5

Beta strand

268 – 280

13

Beta strand

285 – 295

11

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 25, 2002. Version 2. Checksum: BD3B2EAA6CFCBFA9	FASTA	327	38,170
	10 20 30 40 50 60 MSFLGGFFGP ICEIDIVLND GETRKMAEMK TEDGKVEKHY LFYDGESVSG KVNLAFKQPG 70 80 90 100 110 120 KRLEHQGIRI EFVGQIELFN DKSNTHEFVN LVKELALPGE LTQSRSYDFE FMQVEKPYES 130 140 150 160 170 180 YIGANVRLRY FLKVTIVRRL TDLVKEYDLI VHQLATYPDV NNSIKMEVGI EDCLHIEFEY 190 200 210 220 230 240 NKSKYHLKDV IVGKIYFLLV RIKIQHMELQ LIKKEITGIG PSTTTETETI AKYEIMDGAP 250 260 270 280 290 300 VKGESIPIRL FLAGYDPTPT MRDVNKKFSV RYFLNLVLVD EEDRRYFKQQ EIILWRKAPE 310 320 KLRKQRTNFH QRFESPESQA SAEQPEM
	Isoform 2 [UniParc]. Checksum: 1140DC4C2D80D257	FASTA	251	28,938
	10 20 30 40 50 60 MSFLGGFFGP ICEIDIVLND GETRKMAEMK TEDGKVEKHY LFYDGESVSG KVNLAFKQPG 70 80 90 100 110 120 KRLEHQGIRI EFVGQIELFN DKSNTHEFVN LVKELALPGE LTQSRSYDFE FMQVEKPYES 130 140 150 160 170 180 YIGANVRLRY FLKVTIVRRL TDLVKEYDLI VHQLATYPDV NNSIKMEVGI EDCLHIEFEY 190 200 210 220 230 240 NKSKYHLKDV IVGKIYFLLV RIKIQHMELQ LIKKEITGIG PSTTTETETI AKYEIMDGAP 250 VKGDNFMEKS S

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human orthologs of yeast vacuolar protein sorting proteins Vps26, 29, and 35: assembly into multimeric complexes." Renfrew Haft C., de la Luz Sierra M., Bafford R., Lesniak M.A., Barr V.A., Taylor S.I. Mol. Biol. Cell 11:4105-4116(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH VPS29; VPS35; SNX1 AND SNX2. Tissue: Colon.
[2]	"Identification of genes expressed in human CD34(+) hematopoietic stem/progenitor cells by expressed sequence tags and efficient full-length cDNA cloning." Mao M., Fu G., Wu J.-S., Zhang Q.-H., Zhou J., Kan L.-X., Huang Q.-H., He K.-L., Gu B.-W., Han Z.-G., Shen Y., Gu J., Yu Y.-P., Xu S.-H., Wang Y.-X., Chen S.-J., Chen Z. Proc. Natl. Acad. Sci. U.S.A. 95:8175-8180(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Umbilical cord blood.
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Tongue.
[4]	"The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J. Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 3-249 (ISOFORM 2). Tissue: Brain and Embryonic testis carcinoma.
[7]	"Exportin 7 defines a novel general nuclear export pathway." Mingot J.-M., Bohnsack M.T., Jaekle U., Goerlich D. EMBO J. 23:3227-3236(2004) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN A COMPLEX WITH XPO7; ARHGAP1; EIF4A1; VPS29; VPS35 AND SFN.
[8]	"The mammalian retromer regulates transcytosis of the polymeric immunoglobulin receptor." Verges M., Luton F., Gruber C., Tiemann F., Reinders L.G., Huang L., Burlingame A.L., Haft C.R., Mostov K.E. Nat. Cell Biol. 6:763-769(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[9]	"Model-guided microarray implicates the retromer complex in Alzheimer's disease." Small S.A., Kent K., Pierce A., Leung C., Kang M.S., Okada H., Honig L., Vonsattel J.-P., Kim T.-W. Ann. Neurol. 58:909-919(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION.
[10]	"A novel mammalian retromer component, Vps26B." Kerr M.C., Bennetts J.S., Simpson F., Thomas E.C., Flegg C., Gleeson P.A., Wicking C., Teasdale R.D. Traffic 6:991-1001(2005) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH VPS35.
[11]	"An essential role for SNX1 in lysosomal sorting of protease-activated receptor-1: evidence for retromer-, Hrs-, and Tsg101-independent functions of sorting nexins." Gullapalli A., Wolfe B.L., Griffin C.T., Magnuson T., Trejo J. Mol. Biol. Cell 17:1228-1238(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[12]	"A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[13]	"No association of vacuolar protein sorting 26 polymorphisms with Alzheimer's disease." Riemenschneider M., Schoepfer-Wendels A., Friedrich P., Konta L., Laws S.M., Mueller J.C., Kurz A., Forstl H. Neurobiol. Aging 28:883-884(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION.
[14]	"A protein interaction network for Ecm29 links the 26 S proteasome to molecular motors and endosomal components." Gorbea C., Pratt G., Ustrell V., Bell R., Sahasrabudhe S., Hughes R.E., Rechsteiner M. J. Biol. Chem. 285:31616-31633(2010) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH ECM29.
[15]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-315, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[16]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[17]	"The retromer subunit Vps26 has an arrestin fold and binds Vps35 through its C-terminal domain." Shi H., Rojas R., Bonifacino J.S., Hurley J.H. Nat. Struct. Mol. Biol. 13:540-548(2006) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS), SUBCELLULAR LOCATION, INTERACTION WITH VPS35, MUTAGENESIS OF 236-ILE-MET-237.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.

IPI

IPI00411426.
IPI00656002.

RefSeq

NP_001030337.1. NM_001035260.1.
NP_004887.2. NM_004896.3.

UniGene

Hs.499925.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2FAU	X-ray	2.10	A	1-327	[»]

ProteinModelPortal

O75436.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29075N.

IntAct

O75436. 2 interactions.

STRING

9606.ENSP00000263559.

PTM databases

PhosphoSite

O75436.

Proteomic databases

PaxDb

O75436.

PeptideAtlas

O75436.

PRIDE

O75436.

Protocols and materials databases

DNASU

9559.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000263559; ENSP00000263559; ENSG00000122958.
ENST00000373382; ENSP00000362480; ENSG00000122958.
ENST00000395098; ENSP00000378532; ENSG00000122958.

GeneID

9559.

KEGG

hsa:9559.

UCSC

uc001jpb.3. human.

Organism-specific databases

CTD

9559.

GeneCards

GC10P070885.

HGNC

HGNC:12711. VPS26A.

HPA

CAB011602.

MIM

605506. gene.

neXtProt

NX_O75436.

PharmGKB

PA37326.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG256244.

HOGENOM

HOG000191799.

HOVERGEN

HBG082914.

InParanoid

O75436.

OMA

SDKSNTH.

OrthoDB

EOG470THM.

PhylomeDB

O75436.

Gene expression databases

ArrayExpress

O75436.

Bgee

O75436.

CleanEx

HS_VPS26A.

Genevestigator

O75436.

GermOnline

ENSG00000122958. Homo sapiens.

Family and domain databases

InterPro

IPR005377. VPS26.
[Graphical view]

Pfam

PF03643. Vps26. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

VPS26A. human.

EvolutionaryTrace

O75436.

GenomeRNAi

9559.

NextBio

35853.

SOURCE

Search...

Entry information

Entry name

VP26A_HUMAN

Accession

Primary (citable) accession number: O75436
Secondary accession number(s): A8MZ56 , B2RDD3, Q8TBH4, Q9H982

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 21, 2001
Last sequence update:	November 25, 2002
Last modified:	May 1, 2013
This is version 113 of the entry and version 2 of the sequence. [Complete history]

Entry status

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.