C2CD5_HUMAN
ID C2CD5_HUMAN Reviewed; 1000 AA.
AC Q86YS7; B4DJ03; B4DRN7; B7ZLL0; F5H2A1; F5H5R1; O60280; Q17RY7; Q7Z619;
AC Q86SU3;
DT 25-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=C2 domain-containing protein 5;
DE AltName: Full=C2 domain-containing phosphoprotein of 138 kDa;
GN Name=C2CD5; Synonyms=CDP138, KIAA0528;
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 [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=9628581; DOI=10.1093/dnares/5.1.31;
RA Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N.,
RA Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. IX. The
RT complete sequences of 100 new cDNA clones from brain which can code for
RT large proteins in vitro.";
RL DNA Res. 5:31-39(1998).
RN [2]
RP SEQUENCE REVISION.
RA Ohara O., Nagase T., Ishikawa K.;
RL Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RA Guo J.H., Yu L.;
RL Submitted (OCT-2002) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 5).
RC TISSUE=Hippocampus;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 4).
RC TISSUE=Brain, Cerebellum, and Lung carcinoma;
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 [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-643, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
RT phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-601; SER-643 AND SER-852, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-643; SER-659 AND SER-852, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-317; SER-643 AND SER-852, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-643 AND SER-659, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-295, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [16]
RP FUNCTION, PHOSPHORYLATION AT SER-197 AND SER-200, INTERACTION WITH
RP PHOSPHOLIPIDS, CALCIUM-BINDING, SUBCELLULAR LOCATION, MUTAGENESIS OF
RP ASP-19; ASP-26; ASP-76; ASP-78; ASP-84; SER-197 AND SER-200, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=21907143; DOI=10.1016/j.cmet.2011.06.015;
RA Xie X., Gong Z., Mansuy-Aubert V., Zhou Q.L., Tatulian S.A., Sehrt D.,
RA Gnad F., Brill L.M., Motamedchaboki K., Chen Y., Czech M.P., Mann M.,
RA Kruger M., Jiang Z.Y.;
RT "C2 domain-containing phosphoprotein CDP138 regulates GLUT4 insertion into
RT the plasma membrane.";
RL Cell Metab. 14:378-389(2011).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-293; SER-295 AND SER-852, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-260; SER-295; SER-305;
RP SER-323; SER-659; SER-662; THR-807 AND SER-852, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-666 AND SER-671, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
CC -!- FUNCTION: Required for insulin-stimulated glucose transport and glucose
CC transporter SLC2A4/GLUT4 translocation from intracellular glucose
CC storage vesicle (GSV) to the plasma membrane (PM) in adipocytes. Binds
CC phospholipid membranes in a calcium-dependent manner and is necessary
CC for the optimal membrane fusion between SLC2A4/GLUT4 GSV and the PM.
CC {ECO:0000269|PubMed:21907143}.
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00041};
CC Note=Binds 3 Ca(2+) ions per C2 domain. {ECO:0000255|PROSITE-
CC ProRule:PRU00041};
CC -!- INTERACTION:
CC Q86YS7-2; Q9NRD5: PICK1; NbExp=3; IntAct=EBI-12380221, EBI-79165;
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle membrane
CC {ECO:0000269|PubMed:21907143}. Cytoplasm, cell cortex
CC {ECO:0000269|PubMed:21907143}. Cell membrane
CC {ECO:0000269|PubMed:21907143}. Cell projection, ruffle
CC {ECO:0000269|PubMed:21907143}. Note=Dynamically associated with GLUT4-
CC containing glucose storage vesicles (GSV) and plasma membrane in
CC response to insulin stimulation.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=Q86YS7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q86YS7-2; Sequence=VSP_028255, VSP_028256;
CC Name=3;
CC IsoId=Q86YS7-3; Sequence=VSP_028256;
CC Name=4;
CC IsoId=Q86YS7-4; Sequence=VSP_028255, VSP_055638, VSP_028256;
CC Name=5;
CC IsoId=Q86YS7-5; Sequence=VSP_028255, VSP_055639, VSP_055640;
CC -!- DOMAIN: The C2 domain binds to calcium and membrane lipids.
CC -!- PTM: Phosphorylated on Ser-197 by active myristoylated kinase AKT2;
CC insulin-stimulated phosphorylation by AKT2 regulates SLC2A4/GLUT4
CC translocation into the plasma membrane. {ECO:0000269|PubMed:21907143}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA25454.3; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAG58665.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AB011100; BAA25454.3; ALT_INIT; mRNA.
DR EMBL; AY166851; AAO17290.1; -; mRNA.
DR EMBL; AK295862; BAG58665.1; ALT_FRAME; mRNA.
DR EMBL; AK299353; BAG61349.1; -; mRNA.
DR EMBL; AC053513; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC042498; AAH42498.2; -; mRNA.
DR EMBL; BC053885; AAH53885.1; -; mRNA.
DR EMBL; BC117143; AAI17144.1; -; mRNA.
DR EMBL; BC143878; AAI43879.1; -; mRNA.
DR CCDS; CCDS31758.1; -. [Q86YS7-1]
DR CCDS; CCDS66337.1; -. [Q86YS7-3]
DR CCDS; CCDS66338.1; -. [Q86YS7-2]
DR CCDS; CCDS66339.1; -. [Q86YS7-5]
DR CCDS; CCDS66340.1; -. [Q86YS7-4]
DR PIR; T00072; T00072.
DR RefSeq; NP_001273102.1; NM_001286173.1. [Q86YS7-4]
DR RefSeq; NP_001273103.1; NM_001286174.1. [Q86YS7-3]
DR RefSeq; NP_001273104.1; NM_001286175.1. [Q86YS7-5]
DR RefSeq; NP_001273105.1; NM_001286176.1. [Q86YS7-3]
DR RefSeq; NP_001273106.1; NM_001286177.1. [Q86YS7-2]
DR RefSeq; NP_055617.1; NM_014802.2. [Q86YS7-1]
DR AlphaFoldDB; Q86YS7; -.
DR SMR; Q86YS7; -.
DR BioGRID; 115182; 85.
DR IntAct; Q86YS7; 34.
DR GlyGen; Q86YS7; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q86YS7; -.
DR PhosphoSitePlus; Q86YS7; -.
DR BioMuta; C2CD5; -.
DR DMDM; 74750574; -.
DR EPD; Q86YS7; -.
DR jPOST; Q86YS7; -.
DR MassIVE; Q86YS7; -.
DR MaxQB; Q86YS7; -.
DR PaxDb; Q86YS7; -.
DR PeptideAtlas; Q86YS7; -.
DR PRIDE; Q86YS7; -.
DR ProteomicsDB; 25908; -.
DR ProteomicsDB; 26956; -.
DR ProteomicsDB; 4964; -.
DR ProteomicsDB; 70464; -. [Q86YS7-1]
DR ProteomicsDB; 70465; -. [Q86YS7-2]
DR Antibodypedia; 24138; 58 antibodies from 19 providers.
DR DNASU; 9847; -.
DR Ensembl; ENST00000333957.8; ENSP00000334229.4; ENSG00000111731.13. [Q86YS7-1]
DR Ensembl; ENST00000396028.6; ENSP00000379345.2; ENSG00000111731.13. [Q86YS7-2]
DR Ensembl; ENST00000446597.6; ENSP00000388756.1; ENSG00000111731.13. [Q86YS7-3]
DR Ensembl; ENST00000536386.5; ENSP00000439392.1; ENSG00000111731.13. [Q86YS7-4]
DR Ensembl; ENST00000542676.5; ENSP00000441951.1; ENSG00000111731.13. [Q86YS7-3]
DR Ensembl; ENST00000545552.5; ENSP00000443204.1; ENSG00000111731.13. [Q86YS7-5]
DR GeneID; 9847; -.
DR KEGG; hsa:9847; -.
DR MANE-Select; ENST00000446597.6; ENSP00000388756.1; NM_001286176.2; NP_001273105.1. [Q86YS7-3]
DR UCSC; uc001rfq.5; human. [Q86YS7-1]
DR CTD; 9847; -.
DR DisGeNET; 9847; -.
DR GeneCards; C2CD5; -.
DR HGNC; HGNC:29062; C2CD5.
DR HPA; ENSG00000111731; Low tissue specificity.
DR MIM; 618044; gene.
DR neXtProt; NX_Q86YS7; -.
DR OpenTargets; ENSG00000111731; -.
DR PharmGKB; PA143485515; -.
DR VEuPathDB; HostDB:ENSG00000111731; -.
DR eggNOG; KOG1031; Eukaryota.
DR GeneTree; ENSGT00390000000212; -.
DR HOGENOM; CLU_003204_0_0_1; -.
DR InParanoid; Q86YS7; -.
DR OMA; PSYEKTM; -.
DR OrthoDB; 266134at2759; -.
DR PhylomeDB; Q86YS7; -.
DR TreeFam; TF323431; -.
DR PathwayCommons; Q86YS7; -.
DR Reactome; R-HSA-1445148; Translocation of SLC2A4 (GLUT4) to the plasma membrane.
DR SignaLink; Q86YS7; -.
DR BioGRID-ORCS; 9847; 10 hits in 1075 CRISPR screens.
DR ChiTaRS; C2CD5; human.
DR GenomeRNAi; 9847; -.
DR Pharos; Q86YS7; Tbio.
DR PRO; PR:Q86YS7; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q86YS7; protein.
DR Bgee; ENSG00000111731; Expressed in secondary oocyte and 207 other tissues.
DR ExpressionAtlas; Q86YS7; baseline and differential.
DR Genevisible; Q86YS7; HS.
DR GO; GO:0005938; C:cell cortex; IDA:UniProtKB.
DR GO; GO:0034451; C:centriolar satellite; IDA:HPA.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0032587; C:ruffle membrane; IDA:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB.
DR GO; GO:0005544; F:calcium-dependent phospholipid binding; IDA:UniProtKB.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IDA:UniProtKB.
DR GO; GO:0038028; P:insulin receptor signaling pathway via phosphatidylinositol 3-kinase; ISS:UniProtKB.
DR GO; GO:0065002; P:intracellular protein transmembrane transport; IMP:UniProtKB.
DR GO; GO:0010828; P:positive regulation of glucose transmembrane transport; ISS:UniProtKB.
DR GO; GO:0090314; P:positive regulation of protein targeting to membrane; IMP:UniProtKB.
DR GO; GO:0031340; P:positive regulation of vesicle fusion; IMP:UniProtKB.
DR GO; GO:0072659; P:protein localization to plasma membrane; IBA:GO_Central.
DR CDD; cd08688; C2_KIAA0528-like; 1.
DR Gene3D; 2.60.40.150; -; 1.
DR InterPro; IPR037785; C2_C2CD5.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR038983; C2CD5.
DR PANTHER; PTHR37412; PTHR37412; 1.
DR Pfam; PF00168; C2; 1.
DR SMART; SM00239; C2; 1.
DR SUPFAM; SSF49562; SSF49562; 1.
DR PROSITE; PS50004; C2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Calcium; Cell membrane; Cell projection; Cytoplasm;
KW Cytoplasmic vesicle; Lipid-binding; Membrane; Metal-binding;
KW Phosphoprotein; Protein transport; Reference proteome; Transport.
FT CHAIN 1..1000
FT /note="C2 domain-containing protein 5"
FT /id="PRO_0000247450"
FT DOMAIN 1..109
FT /note="C2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT REGION 265..330
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 639..669
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 273..319
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 653..669
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 19
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 19
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 26
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 76
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 76
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 78
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 78
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 78
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 81
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 84
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 84
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT MOD_RES 197
FT /note="Phosphoserine; by PKB/AKT2"
FT /evidence="ECO:0000269|PubMed:21907143"
FT MOD_RES 200
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:21907143"
FT MOD_RES 260
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 293
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 295
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 304
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7TPS5"
FT MOD_RES 305
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 306
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7TPS5"
FT MOD_RES 317
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 323
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 601
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18691976"
FT MOD_RES 643
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18220336,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:19690332"
FT MOD_RES 657
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7TPS5"
FT MOD_RES 659
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163"
FT MOD_RES 661
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7TPS5"
FT MOD_RES 662
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 666
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 671
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 807
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 817
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7TPS5"
FT MOD_RES 852
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT VAR_SEQ 268..316
FT /note="IPFNEDPNPNTHSSGPSTPLKNQTYSFSPSKSYSRQSSSSDTDLSLTPK ->
FT SPLVHPPSHGCRSTHNSPIHTATGSRLTQNFSVSVPTLIY (in isoform 2,
FT isoform 4 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_028255"
FT VAR_SEQ 345
FT /note="Q -> QRGGSPHRFCRR (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_055638"
FT VAR_SEQ 382
FT /note="P -> PAFVGIMGNTRSYKLLDWNSFNS (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_055639"
FT VAR_SEQ 845
FT /note="A -> EHLESASSNSGIPAAQRATSVDYSSFADRCSSWIELIKLKAQTIRRG
FT SIKTT (in isoform 2, isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_028256"
FT VAR_SEQ 845
FT /note="A -> EHLESASSNSGIPAAQRDRCSSWIELIKLKAQTIRRGSIKTT (in
FT isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_055640"
FT MUTAGEN 19
FT /note="D->A: Reduces calcium-binding, phospholipid
FT membrane-binding and insulin-stimulated SLC2A4/GLUT4
FT translocation; when associated with A-26; A-76; A-78 and A-
FT 84."
FT /evidence="ECO:0000269|PubMed:21907143"
FT MUTAGEN 26
FT /note="D->A: Reduces calcium-binding, phospholipid
FT membrane-binding and insulin-stimulated SLC2A4/GLUT4
FT translocation; when associated with A-19; A-76; A-78 and A-
FT 84."
FT /evidence="ECO:0000269|PubMed:21907143"
FT MUTAGEN 76
FT /note="D->A: Reduces calcium-binding, phospholipid
FT membrane-binding and insulin-stimulated SLC2A4/GLUT4
FT translocation; when associated with A-19; A-26; A-78 and A-
FT 84."
FT /evidence="ECO:0000269|PubMed:21907143"
FT MUTAGEN 78
FT /note="D->A: Reduces calcium-binding, phospholipid
FT membrane-binding and insulin-stimulated SLC2A4/GLUT4
FT translocation; when associated with A-19; A-26; A-76 and A-
FT 84."
FT /evidence="ECO:0000269|PubMed:21907143"
FT MUTAGEN 84
FT /note="D->A: Reduces calcium-binding, phospholipid
FT membrane-binding and insulin-stimulated SLC2A4/GLUT4
FT translocation; when associated with A-19; A-26; A-76 and A-
FT 78."
FT /evidence="ECO:0000269|PubMed:21907143"
FT MUTAGEN 197
FT /note="S->A: Inhibits insulin-stimulated AKT2-induced
FT phosphorylation, SLC2A4/GLUT4 translocation to the cell
FT surface and GSV-PM fusion."
FT /evidence="ECO:0000269|PubMed:21907143"
FT MUTAGEN 200
FT /note="S->A: Does not inhibit insulin-stimulated
FT SLC2A4/GLUT4 translocation."
FT /evidence="ECO:0000269|PubMed:21907143"
FT CONFLICT 997
FT /note="E -> G (in Ref. 4; BAG58665)"
FT /evidence="ECO:0000305"
FT CONFLICT Q86YS7-4:895
FT /note="I -> F (in Ref. 6; AAI43879)"
FT /evidence="ECO:0000305"
FT CONFLICT Q86YS7-5:895
FT /note="S -> P (in Ref. 4; BAG58665)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1000 AA; 110447 MW; 7C51961F54CBBACD CRC64;
MPGKLKVKIV AGRHLPVMDR ASDLTDAFVE VKFGNTTFKT DVYLKSLNPQ WNSEWFKFEV
DDEDLQDEPL QITVLDHDTY SANDAIGKVY IDIDPLLYSE AATVISGWFP IYDTIHGIRG
EINVVVKVDL FNDLNRFRQS SCGVKFFCTT SIPKCYRAVI IHGFVEELVV NEDPEYQWID
RIRTPRASNE ARQRLISLMS GELQRKIGLK VLEMRGNAVV GYLQCFDLEG ESGLVVRAIG
TACTLDKLSS PAAFLPACNS PSKEMKEIPF NEDPNPNTHS SGPSTPLKNQ TYSFSPSKSY
SRQSSSSDTD LSLTPKTGMG SGSAGKEGGP FKALLRQQTQ SALEQREFPF FTLTAFPPGF
LVHVGGVVSA RSVKLLDRIH NPDEPETRDA WWAEIRQEIK SHAKALGCHA VVGYSESTSI
CEEVCILSAS GTAAVLNPRF LQDGTVEGCL EQRLEENLPT RCGFCHIPYD ELNMPFPAHL
TYCYNCRKQK VPDVLFTTID LPTDATVIGK GCLIQARLCR LKKKAQAEAN ATAISNLLPF
MEYEVHTQLM NKLKLKGMNA LFGLRIQITV GENMLMGLAS ATGVYLAALP TPGGIQIAGK
TPNDGSYEQH ISHMQKKIND TIAKNKELYE INPPEISEEI IGSPIPEPRQ RSRLLRSQSE
SSDEVTELDL SHGKKDAFVL EIDDTDAMED VHSLLTDVPP PSGFYSCNTE IMPGINNWTS
EIQMFTSVRV IRLSSLNLTN QALNKNFNDL CENLLKSLYF KLRSMIPCCL CHVNFTVSLP
EDELIQVTVT AVAITFDKNQ ALQTTKTPVE KSLQRASTDN EELLQFPLEL CSDSLPSHPF
PPAKAMTVEK ASPVGDGNFR NRSAPPCANS TVGVVKMTPL SFIPGAKITK YLGIINMFFI
RETTSLREEG GVSGFLHAFI AEVFAMVRAH VAALGGNAVV SYIMKQCVFM ENPNKNQAQC
LINVSGDAVV FVRESDLEVV SSQQPTTNCQ SSCTEGEVTT
