VP26A_MOUSE
ID VP26A_MOUSE Reviewed; 327 AA.
AC P40336; Q3TGY3; Q3THM5; Q3TW99; Q3UD54; Q8C1E9;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 1.
DT 03-AUG-2022, entry version 168.
DE RecName: Full=Vacuolar protein sorting-associated protein 26A;
DE AltName: Full=H58 protein;
DE Short=H beta 58;
DE AltName: Full=Vesicle protein sorting 26A;
DE Short=mVPS26;
GN Name=Vps26a; Synonyms=Vps26;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=1638986; DOI=10.1242/dev.115.1.277;
RA Lee J.J., Radice G., Perkins C.P., Costantini F.;
RT "Identification and characterization of a novel, evolutionarily conserved
RT gene disrupted by the murine H beta 58 embryonic lethal transgene
RT insertion.";
RL Development 115:277-288(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6J, and DBA/2J;
RC TISSUE=Amnion, Bone marrow, Lung, Placenta, and Testis;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=15078902; DOI=10.1083/jcb.200312034;
RA Seaman M.N.J.;
RT "Cargo-selective endosomal sorting for retrieval to the Golgi requires
RT retromer.";
RL J. Cell Biol. 165:111-122(2004).
RN [5]
RP SUBUNIT, MUTAGENESIS OF 235-ILE-MET-236, AND SUBCELLULAR LOCATION.
RX PubMed=18088321; DOI=10.1111/j.1600-0854.2007.00688.x;
RA Collins B.M., Norwood S.J., Kerr M.C., Mahony D., Seaman M.N.,
RA Teasdale R.D., Owen D.J.;
RT "Structure of Vps26B and mapping of its interaction with the retromer
RT protein complex.";
RL Traffic 9:366-379(2008).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [7]
RP SUBUNIT.
RX PubMed=20875039; DOI=10.1111/j.1600-0854.2010.01124.x;
RA Norwood S.J., Shaw D.J., Cowieson N.P., Owen D.J., Teasdale R.D.,
RA Collins B.M.;
RT "Assembly and solution structure of the core retromer protein complex.";
RL Traffic 12:56-71(2011).
RN [8]
RP SUBCELLULAR LOCATION.
RX PubMed=21920005; DOI=10.1111/j.1600-0854.2011.01284.x;
RA Bugarcic A., Zhe Y., Kerr M.C., Griffin J., Collins B.M., Teasdale R.D.;
RT "Vps26A and Vps26B subunits define distinct retromer complexes.";
RL Traffic 12:1759-1773(2011).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 9-327, FUNCTION, INTERACTION WITH
RP SNX27, AND MUTAGENESIS OF ASP-44 AND LEU-154.
RX PubMed=25136126; DOI=10.1073/pnas.1410552111;
RA Gallon M., Clairfeuille T., Steinberg F., Mas C., Ghai R., Sessions R.B.,
RA Teasdale R.D., Collins B.M., Cullen P.J.;
RT "A unique PDZ domain and arrestin-like fold interaction reveals mechanistic
RT details of endocytic recycling by SNX27-retromer.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:E3604-E3613(2014).
CC -!- FUNCTION: Acts as component of the retromer cargo-selective complex
CC (CSC). The CSC is believed to be the core functional component of
CC retromer or respective retromer complex variants acting to prevent
CC missorting of selected transmembrane cargo proteins into the lysosomal
CC degradation pathway. The recruitment of the CSC to the endosomal
CC membrane involves RAB7A and SNX3.The SNX-BAR retromer mediates
CC retrograde transport of cargo proteins from endosomes to the trans-
CC Golgi network (TGN) and is involved in endosome-to-plasma membrane
CC transport for cargo protein recycling. The SNX3-retromer mediates the
CC retrograde endosome-to-TGN transport of WLS distinct from the SNX-BAR
CC retromer pathway. The SNX27-retromer is believed to be involved in
CC endosome-to-plasma membrane trafficking and recycling of a broad
CC spectrum of cargo proteins. The CSC complex seems to act as recruitment
CC hub for other proteins, such as the WASH complex and TBC1D5 (By
CC similarity). Required for retrograde transport of lysosomal enzyme
CC receptor IGF2R (PubMed:15078902). Required to regulate transcytosis of
CC the polymeric immunoglobulin receptor (pIgR-pIgA). Required for the
CC endosomal localization of WASHC2 (indicative for the WASH complex).
CC Required for the endosomal localization of TBC1D5. Mediates retromer
CC cargo recognition of SORL1 and is involved in trafficking of SORL1
CC implicated in sorting and processing of APP (By similarity). Involved
CC in retromer-independent lysosomal sorting of F2R. Involved in recycling
CC of ADRB2 (By similarity). Acts redundantly with VSP26B in SNX-27
CC mediated endocytic recycling of SLC2A1/GLUT1. Enhances the affinity of
CC SNX27 for PDZ-binding motifs in cargo proteins (PubMed:25136126).
CC {ECO:0000250|UniProtKB:O75436, ECO:0000269|PubMed:15078902,
CC ECO:0000269|PubMed:25136126}.
CC -!- SUBUNIT: Component of the heterotrimeric retromer cargo-selective
CC complex (CSC), also described as vacuolar protein sorting subcomplex
CC (VPS), formed by VPS26 (VPS26A or VPS26B), VPS29 and VPS35
CC (PubMed:18088321, PubMed:20875039). The CSC has a highly elongated
CC structure with VPS26 and VPS29 binding independently at opposite distal
CC ends of VPS35 as central platform (Probable). The CSC is believed to
CC associate with variable sorting nexins to form functionally distinct
CC retromer complex variants. The originally described retromer complex
CC (also called SNX-BAR retromer) is a pentamer containing the CSC and a
CC heterodimeric membrane-deforming subcomplex formed between SNX1 or SNX2
CC and SNX5 or SNX6 (also called SNX-BAR subcomplex); the respective CSC
CC and SNX-BAR subcomplexes associate with low affinity. The CSC
CC associates with SNX3 to form a SNX3-retromer complex. The CSC
CC associates with SNX27, the WASH complex and the SNX-BAR subcomplex to
CC form the SNX27-retromer complex (By similarity). Interacts with VPS29,
CC VPS35, SNX27 (PubMed:18088321, PubMed:20875039, PubMed:25136126).
CC Interacts with SNX1, SNX2, SNX5, SNX6, SNX3, RAB7A, ECPAS, EHD1,
CC WASHC5, SORL1 (By similarity). {ECO:0000250|UniProtKB:O75436,
CC ECO:0000269|PubMed:18088321, ECO:0000269|PubMed:20875039,
CC ECO:0000269|PubMed:25136126, ECO:0000303|PubMed:20875039}.
CC -!- INTERACTION:
CC P40336-1; Q9EQH3: Vps35; NbExp=2; IntAct=EBI-15553779, EBI-775825;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15078902}. Endosome
CC membrane {ECO:0000269|PubMed:15078902}; Peripheral membrane protein
CC {ECO:0000269|PubMed:15078902}. Early endosome
CC {ECO:0000269|PubMed:18088321, ECO:0000269|PubMed:21920005}.
CC Note=Predominantly found in early not late endosomes.
CC {ECO:0000269|PubMed:21920005}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P40336-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P40336-2; Sequence=VSP_019926;
CC -!- SIMILARITY: Belongs to the VPS26 family. {ECO:0000305}.
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DR EMBL; S41204; AAB22718.1; -; mRNA.
DR EMBL; AK028096; BAC25745.1; -; mRNA.
DR EMBL; AK150244; BAE29408.1; -; mRNA.
DR EMBL; AK147989; BAE28271.1; -; mRNA.
DR EMBL; AK151360; BAE30335.1; -; mRNA.
DR EMBL; AK159783; BAE35367.1; -; mRNA.
DR EMBL; AK167592; BAE39650.1; -; mRNA.
DR EMBL; AK165853; BAE38415.1; -; mRNA.
DR EMBL; AK168213; BAE40171.1; -; mRNA.
DR EMBL; AK168537; BAE40415.1; -; mRNA.
DR EMBL; BC007148; AAH07148.1; -; mRNA.
DR CCDS; CCDS35921.1; -. [P40336-1]
DR CCDS; CCDS48579.1; -. [P40336-2]
DR PIR; A44882; A44882.
DR PIR; B44882; B44882.
DR RefSeq; NP_001106826.1; NM_001113355.1. [P40336-2]
DR RefSeq; NP_598433.1; NM_133672.3. [P40336-1]
DR PDB; 4P2A; X-ray; 2.70 A; A=9-327.
DR PDB; 6VAC; EM; 5.70 A; B=1-327.
DR PDBsum; 4P2A; -.
DR PDBsum; 6VAC; -.
DR AlphaFoldDB; P40336; -.
DR SMR; P40336; -.
DR BioGRID; 206007; 22.
DR CORUM; P40336; -.
DR DIP; DIP-32041N; -.
DR IntAct; P40336; 3.
DR STRING; 10090.ENSMUSP00000090130; -.
DR iPTMnet; P40336; -.
DR PhosphoSitePlus; P40336; -.
DR SwissPalm; P40336; -.
DR EPD; P40336; -.
DR jPOST; P40336; -.
DR MaxQB; P40336; -.
DR PaxDb; P40336; -.
DR PeptideAtlas; P40336; -.
DR PRIDE; P40336; -.
DR ProteomicsDB; 297967; -. [P40336-1]
DR ProteomicsDB; 297968; -. [P40336-2]
DR Antibodypedia; 28695; 224 antibodies from 36 providers.
DR DNASU; 30930; -.
DR Ensembl; ENSMUST00000092473; ENSMUSP00000090130; ENSMUSG00000020078. [P40336-2]
DR Ensembl; ENSMUST00000105447; ENSMUSP00000101087; ENSMUSG00000020078. [P40336-1]
DR GeneID; 30930; -.
DR KEGG; mmu:30930; -.
DR UCSC; uc007fhf.2; mouse. [P40336-2]
DR UCSC; uc007fhg.2; mouse. [P40336-1]
DR CTD; 9559; -.
DR MGI; MGI:1353654; Vps26a.
DR VEuPathDB; HostDB:ENSMUSG00000020078; -.
DR eggNOG; KOG3063; Eukaryota.
DR GeneTree; ENSGT00950000183064; -.
DR HOGENOM; CLU_031077_0_0_1; -.
DR InParanoid; P40336; -.
DR OMA; FKQHGKR; -.
DR OrthoDB; 987411at2759; -.
DR PhylomeDB; P40336; -.
DR TreeFam; TF300907; -.
DR Reactome; R-MMU-3238698; WNT ligand biogenesis and trafficking.
DR BioGRID-ORCS; 30930; 6 hits in 73 CRISPR screens.
DR ChiTaRS; Vps26a; mouse.
DR PRO; PR:P40336; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; P40336; protein.
DR Bgee; ENSMUSG00000020078; Expressed in spermatocyte and 272 other tissues.
DR ExpressionAtlas; P40336; baseline and differential.
DR Genevisible; P40336; MM.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005769; C:early endosome; IDA:UniProtKB.
DR GO; GO:0005768; C:endosome; IDA:MGI.
DR GO; GO:0010008; C:endosome membrane; ISO:MGI.
DR GO; GO:0005764; C:lysosome; ISO:MGI.
DR GO; GO:0030904; C:retromer complex; IDA:UniProtKB.
DR GO; GO:0030906; C:retromer, cargo-selective complex; ISO:MGI.
DR GO; GO:0097422; C:tubular endosome; ISS:UniProtKB.
DR GO; GO:0031982; C:vesicle; ISS:UniProtKB.
DR GO; GO:0032456; P:endocytic recycling; ISS:UniProtKB.
DR GO; GO:0006886; P:intracellular protein transport; IBA:GO_Central.
DR GO; GO:0042147; P:retrograde transport, endosome to Golgi; IDA:MGI.
DR Gene3D; 2.60.40.640; -; 2.
DR InterPro; IPR014752; Arrestin-like_C.
DR InterPro; IPR028934; Vps26-related.
DR PANTHER; PTHR12233; PTHR12233; 1.
DR Pfam; PF03643; Vps26; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cytoplasm; Endosome; Membrane;
KW Phosphoprotein; Protein transport; Reference proteome; Transport.
FT CHAIN 1..327
FT /note="Vacuolar protein sorting-associated protein 26A"
FT /id="PRO_0000073008"
FT REGION 306..327
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 312..327
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 315
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O75436"
FT VAR_SEQ 1
FT /note="M -> MSEPLPAFLDRLWGPWLGTRSPPSRSSAASPSK (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_019926"
FT MUTAGEN 44
FT /note="D->A: Decreases interaction with SNX27."
FT /evidence="ECO:0000269|PubMed:25136126"
FT MUTAGEN 154
FT /note="L->A: Decreases interaction with SNX27."
FT /evidence="ECO:0000269|PubMed:25136126"
FT MUTAGEN 235..236
FT /note="IM->DN: Disrupts interaction with VPS35:VPS29 dimer;
FT no endosomal localization."
FT CONFLICT 37
FT /note="E -> Q (in Ref. 2; BAC25745)"
FT /evidence="ECO:0000305"
FT CONFLICT 71
FT /note="E -> G (in Ref. 2; BAE35367)"
FT /evidence="ECO:0000305"
FT CONFLICT 79
FT /note="F -> L (in Ref. 2; BAE40171)"
FT /evidence="ECO:0000305"
FT CONFLICT 188
FT /note="K -> R (in Ref. 2; BAE40415)"
FT /evidence="ECO:0000305"
FT STRAND 11..20
FT /evidence="ECO:0007829|PDB:4P2A"
FT TURN 21..23
FT /evidence="ECO:0007829|PDB:4P2A"
FT STRAND 26..30
FT /evidence="ECO:0007829|PDB:4P2A"
FT STRAND 36..42
FT /evidence="ECO:0007829|PDB:4P2A"
FT STRAND 48..58
FT /evidence="ECO:0007829|PDB:4P2A"
FT STRAND 63..77
FT /evidence="ECO:0007829|PDB:4P2A"
FT STRAND 79..83
FT /evidence="ECO:0007829|PDB:4P2A"
FT STRAND 86..96
FT /evidence="ECO:0007829|PDB:4P2A"
FT STRAND 98..103
FT /evidence="ECO:0007829|PDB:4P2A"
FT STRAND 105..111
FT /evidence="ECO:0007829|PDB:4P2A"
FT STRAND 127..137
FT /evidence="ECO:0007829|PDB:4P2A"
FT STRAND 143..151
FT /evidence="ECO:0007829|PDB:4P2A"
FT STRAND 154..156
FT /evidence="ECO:0007829|PDB:4P2A"
FT STRAND 164..169
FT /evidence="ECO:0007829|PDB:4P2A"
FT STRAND 171..181
FT /evidence="ECO:0007829|PDB:4P2A"
FT STRAND 183..186
FT /evidence="ECO:0007829|PDB:4P2A"
FT STRAND 190..202
FT /evidence="ECO:0007829|PDB:4P2A"
FT STRAND 204..216
FT /evidence="ECO:0007829|PDB:4P2A"
FT STRAND 225..238
FT /evidence="ECO:0007829|PDB:4P2A"
FT STRAND 246..251
FT /evidence="ECO:0007829|PDB:4P2A"
FT HELIX 252..254
FT /evidence="ECO:0007829|PDB:4P2A"
FT STRAND 261..264
FT /evidence="ECO:0007829|PDB:4P2A"
FT TURN 265..267
FT /evidence="ECO:0007829|PDB:4P2A"
FT STRAND 268..280
FT /evidence="ECO:0007829|PDB:4P2A"
FT STRAND 285..297
FT /evidence="ECO:0007829|PDB:4P2A"
SQ SEQUENCE 327 AA; 38114 MW; 419DAED54264AC13 CRC64;
MSFLGGFFGP ICEIDVALND GETRKMAEMK TEDGKVEKHY LFYDGESVSG KVNLAFKQPG
KRLEHQGIRI EFVGQIELFN DKSNTHEFVN LVKELALPGE LTQSRSYDFE FMQVEKPYES
YIGANVRLRY FLKVTIVRRL TDLVKEYDLI VHQLATYPDV NNSIKMEVGI EDCLHIEFEY
NKSKYHLKDV IVGKIYFLLV RIKIQHMELQ LIKKEITGIG PSTTTETETI AKYEIMDGAP
VKGESIPIRL FLAGYDPTPT MRDVNKKFSV RYFLNLVLVD EEDRRYFKQQ EIILWRKAPE
KLRKQRTNFH QRFESPDSQA SAEQPEM
