ID   VP26C_HUMAN             Reviewed;         297 AA.
AC   O14972; B2R6T8; B7Z6B1; D3DSH4; Q2TAY6;
DT   15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT   01-JAN-1998, sequence version 1.
DT   27-MAR-2024, entry version 168.
DE   RecName: Full=Vacuolar protein sorting-associated protein 26C {ECO:0000305};
DE   AltName: Full=Down syndrome critical region protein 3;
DE   AltName: Full=Down syndrome critical region protein A;
GN   Name=VPS26C {ECO:0000312|HGNC:HGNC:3044};
GN   Synonyms=DCRA, DSCR3 {ECO:0000312|HGNC:HGNC:3044}, DSCRA;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC   TISSUE=Fetal brain;
RX   PubMed=9399594; DOI=10.1093/oxfordjournals.jbchem.a021835;
RA   Nakamura A., Hattori M., Sakaki Y.;
RT   "Isolation of a novel human gene from the Down syndrome critical region of
RT   chromosome 21q22.2.";
RL   J. Biochem. 122:872-877(1997).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC   TISSUE=Thymus;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=10830953; DOI=10.1038/35012518;
RA   Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T., Park H.-S.,
RA   Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y., Soeda E., Ohki M.,
RA   Takagi T., Sakaki Y., Taudien S., Blechschmidt K., Polley A., Menzel U.,
RA   Delabar J., Kumpf K., Lehmann R., Patterson D., Reichwald K., Rump A.,
RA   Schillhabel M., Schudy A., Zimmermann W., Rosenthal A., Kudoh J.,
RA   Shibuya K., Kawasaki K., Asakawa S., Shintani A., Sasaki T., Nagamine K.,
RA   Mitsuyama S., Antonarakis S.E., Minoshima S., Shimizu N., Nordsiek G.,
RA   Hornischer K., Brandt P., Scharfe M., Schoen O., Desario A., Reichelt J.,
RA   Kauer G., Bloecker H., Ramser J., Beck A., Klages S., Hennig S.,
RA   Riesselmann L., Dagand E., Wehrmeyer S., Borzym K., Gardiner K.,
RA   Nizetic D., Francis F., Lehrach H., Reinhardt R., Yaspo M.-L.;
RT   "The DNA sequence of human chromosome 21.";
RL   Nature 405:311-319(2000).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Skin;
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   [6]
RP   FUNCTION, INTERACTION WITH SNX17 AND SNX31, IDENTIFICATION IN THE RETRIEVER
RP   COMPLEX, SUBCELLULAR LOCATION, AND FUNCTION (MICROBIAL INFECTION).
RX   PubMed=28892079; DOI=10.1038/ncb3610;
RA   McNally K.E., Faulkner R., Steinberg F., Gallon M., Ghai R., Pim D.,
RA   Langton P., Pearson N., Danson C.M., Naegele H., Morris L.L., Singla A.,
RA   Overlee B.L., Heesom K.J., Sessions R., Banks L., Collins B.M., Berger I.,
RA   Billadeau D.D., Burstein E., Cullen P.J.;
RT   "Retriever is a multiprotein complex for retromer-independent endosomal
RT   cargo recycling.";
RL   Nat. Cell Biol. 19:1214-1225(2017).
CC   -!- FUNCTION: Acts as a component of the retriever complex. The retriever
CC       complex is a heterotrimeric complex related to retromer cargo-selective
CC       complex (CSC) and essential for retromer-independent retrieval and
CC       recycling of numerous cargos such as integrin alpha-5/beta-1
CC       (ITGA5:ITGB1) (PubMed:28892079). The recruitment of the retriever
CC       complex to the endosomal membrane involves CCC and WASH complexes
CC       (PubMed:28892079). In the endosomes, drives the retriever and recycling
CC       of NxxY-motif-containing cargo proteins by coupling to SNX17, a cargo
CC       essential for the homeostatic maintenance of numerous cell surface
CC       proteins associated with processes that include cell migration, cell
CC       adhesion, nutrient supply and cell signaling (PubMed:28892079).
CC       {ECO:0000269|PubMed:28892079}.
CC   -!- FUNCTION: (Microbial infection) The heterotrimeric retriever complex,
CC       in collaboration with the CCC complex, mediates the exit of human
CC       papillomavirus to the cell surface. {ECO:0000269|PubMed:28892079}.
CC   -!- SUBUNIT: Component of the heterotrimeric retriever complex formed by
CC       VPS26C, VPS29 and VPS35L (PubMed:28892079). Interacts with SNX17; the
CC       interaction is direct and associates SNX17 with the retriever complex
CC       (PubMed:28892079). Interacts with SNX31; the interaction is direct
CC       (PubMed:28892079). {ECO:0000269|PubMed:28892079}.
CC   -!- INTERACTION:
CC       O14972; Q13191: CBLB; NbExp=3; IntAct=EBI-7207091, EBI-744027;
CC       O14972; Q9NUI1: DECR2; NbExp=3; IntAct=EBI-7207091, EBI-3937367;
CC       O14972; Q0VD86: INCA1; NbExp=3; IntAct=EBI-7207091, EBI-6509505;
CC       O14972; Q5T3J3: LRIF1; NbExp=3; IntAct=EBI-7207091, EBI-473196;
CC       O14972; O15151: MDM4; NbExp=3; IntAct=EBI-7207091, EBI-398437;
CC       O14972; A8MW99: MEI4; NbExp=3; IntAct=EBI-7207091, EBI-19944212;
CC       O14972; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-7207091, EBI-16439278;
CC       O14972; Q16825: PTPN21; NbExp=3; IntAct=EBI-7207091, EBI-2860264;
CC       O14972; Q96DA2: RAB39B; NbExp=3; IntAct=EBI-7207091, EBI-9089467;
CC       O14972; Q96N21: TEPSIN; NbExp=3; IntAct=EBI-7207091, EBI-11139477;
CC       O14972; Q7Z3J2: VPS35L; NbExp=7; IntAct=EBI-7207091, EBI-11080070;
CC       O14972; P23025: XPA; NbExp=3; IntAct=EBI-7207091, EBI-295222;
CC       O14972; Q8N720: ZNF655; NbExp=3; IntAct=EBI-7207091, EBI-625509;
CC   -!- SUBCELLULAR LOCATION: Endosome {ECO:0000305|PubMed:28892079}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=O14972-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=O14972-2; Sequence=VSP_056598;
CC   -!- TISSUE SPECIFICITY: Ubiquitously expressed.
CC   -!- SIMILARITY: Belongs to the VPS26 family. {ECO:0000305}.
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DR   EMBL; D87343; BAA23225.1; -; mRNA.
DR   EMBL; AK300024; BAH13197.1; -; mRNA.
DR   EMBL; AK312707; BAG35585.1; -; mRNA.
DR   EMBL; AK316460; BAH14831.1; -; mRNA.
DR   EMBL; AP001412; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AP001432; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471079; EAX09714.1; -; Genomic_DNA.
DR   EMBL; BC110655; AAI10656.1; -; mRNA.
DR   CCDS; CCDS33553.1; -. [O14972-1]
DR   CCDS; CCDS82673.1; -. [O14972-2]
DR   PIR; JC5698; JC5698.
DR   RefSeq; NP_001317947.1; NM_001331018.1.
DR   RefSeq; NP_001317951.1; NM_001331022.1. [O14972-2]
DR   RefSeq; NP_006043.1; NM_006052.1. [O14972-1]
DR   PDB; 8SYN; EM; 2.94 A; C=1-297.
DR   PDB; 8SYO; EM; 2.94 A; C=1-297.
DR   PDBsum; 8SYN; -.
DR   PDBsum; 8SYO; -.
DR   AlphaFoldDB; O14972; -.
DR   EMDB; EMD-40885; -.
DR   EMDB; EMD-40886; -.
DR   SMR; O14972; -.
DR   BioGRID; 115596; 50.
DR   ComplexPortal; CPX-2211; Commander complex.
DR   DIP; DIP-47317N; -.
DR   IntAct; O14972; 60.
DR   MINT; O14972; -.
DR   STRING; 9606.ENSP00000311399; -.
DR   iPTMnet; O14972; -.
DR   PhosphoSitePlus; O14972; -.
DR   BioMuta; DSCR3; -.
DR   EPD; O14972; -.
DR   jPOST; O14972; -.
DR   MassIVE; O14972; -.
DR   MaxQB; O14972; -.
DR   PaxDb; 9606-ENSP00000311399; -.
DR   PeptideAtlas; O14972; -.
DR   ProteomicsDB; 48343; -. [O14972-1]
DR   ProteomicsDB; 6766; -.
DR   Pumba; O14972; -.
DR   Antibodypedia; 8571; 161 antibodies from 23 providers.
DR   DNASU; 10311; -.
DR   Ensembl; ENST00000309117.11; ENSP00000311399.6; ENSG00000157538.14. [O14972-1]
DR   Ensembl; ENST00000476950.5; ENSP00000419496.1; ENSG00000157538.14. [O14972-2]
DR   GeneID; 10311; -.
DR   KEGG; hsa:10311; -.
DR   MANE-Select; ENST00000309117.11; ENSP00000311399.6; NM_006052.2; NP_006043.1.
DR   UCSC; uc002ywf.2; human. [O14972-1]
DR   AGR; HGNC:3044; -.
DR   CTD; 10311; -.
DR   DisGeNET; 10311; -.
DR   GeneCards; VPS26C; -.
DR   HGNC; HGNC:3044; VPS26C.
DR   HPA; ENSG00000157538; Low tissue specificity.
DR   MIM; 605298; gene.
DR   neXtProt; NX_O14972; -.
DR   OpenTargets; ENSG00000157538; -.
DR   PharmGKB; PA27496; -.
DR   VEuPathDB; HostDB:ENSG00000157538; -.
DR   eggNOG; KOG2717; Eukaryota.
DR   GeneTree; ENSGT00950000183064; -.
DR   HOGENOM; CLU_056829_0_0_1; -.
DR   InParanoid; O14972; -.
DR   OMA; RCDIKRS; -.
DR   OrthoDB; 1201889at2759; -.
DR   PhylomeDB; O14972; -.
DR   TreeFam; TF323199; -.
DR   PathwayCommons; O14972; -.
DR   SignaLink; O14972; -.
DR   BioGRID-ORCS; 10311; 28 hits in 1154 CRISPR screens.
DR   ChiTaRS; VPS26C; human.
DR   GenomeRNAi; 10311; -.
DR   Pharos; O14972; Tbio.
DR   PRO; PR:O14972; -.
DR   Proteomes; UP000005640; Chromosome 21.
DR   RNAct; O14972; Protein.
DR   Bgee; ENSG00000157538; Expressed in monocyte and 187 other cell types or tissues.
DR   ExpressionAtlas; O14972; baseline and differential.
DR   GO; GO:0005768; C:endosome; IBA:GO_Central.
DR   GO; GO:0005634; C:nucleus; HDA:UniProtKB.
DR   GO; GO:0032456; P:endocytic recycling; IMP:UniProtKB.
DR   GO; GO:0006886; P:intracellular protein transport; IBA:GO_Central.
DR   Gene3D; 2.60.40.640; -; 2.
DR   InterPro; IPR014752; Arrestin-like_C.
DR   InterPro; IPR014756; Ig_E-set.
DR   InterPro; IPR028934; Vps26-related.
DR   PANTHER; PTHR12233; VACUOLAR PROTEIN SORTING 26 RELATED; 1.
DR   PANTHER; PTHR12233:SF2; VACUOLAR PROTEIN SORTING-ASSOCIATED PROTEIN 26C; 1.
DR   Pfam; PF03643; Vps26; 1.
DR   SUPFAM; SSF81296; E set domains; 1.
DR   Genevisible; O14972; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Endosome; Reference proteome.
FT   CHAIN           1..297
FT                   /note="Vacuolar protein sorting-associated protein 26C"
FT                   /id="PRO_0000073016"
FT   VAR_SEQ         118..144
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_056598"
SQ   SEQUENCE   297 AA;  33010 MW;  5CE40FEE9E6664D5 CRC64;
     MGTALDIKIK RANKVYHAGE VLSGVVVISS KDSVQHQGVS LTMEGTVNLQ LSAKSVGVFE
     AFYNSVKPIQ IINSTIEMVK PGKFPSGKTE IPFEFPLHLK GNKVLYETYH GVFVNIQYTL
     RCDMKRSLLA KDLTKTCEFI VHSAPQKGKF TPSPVDFTIT PETLQNVKER ALLPKFLLRG
     HLNSTNCVIT QPLTGELVVE SSEAAIRSVE LQLVRVETCG CAEGYARDAT EIQNIQIADG
     DVCRGLSVPI YMVFPRLFTC PTLETTNFKV EFEVNIVVLL HPDHLITENF PLKLCRI
//