CCAR2_HUMAN
ID CCAR2_HUMAN Reviewed; 923 AA.
AC Q8N163; A6NL03; B2RB79; D3DSR6; Q6P0Q9; Q8N3G7; Q8N8M1; Q8TF34; Q9H9Q9;
AC Q9HD12; Q9NT55;
DT 24-JAN-2006, integrated into UniProtKB/Swiss-Prot.
DT 24-JAN-2006, sequence version 2.
DT 03-AUG-2022, entry version 184.
DE RecName: Full=Cell cycle and apoptosis regulator protein 2;
DE AltName: Full=Cell division cycle and apoptosis regulator protein 2;
DE AltName: Full=DBIRD complex subunit KIAA1967;
DE AltName: Full=Deleted in breast cancer gene 1 protein;
DE Short=DBC-1;
DE Short=DBC.1;
DE AltName: Full=NET35;
DE AltName: Full=p30 DBC;
GN Name=CCAR2; Synonyms=DBC1, KIAA1967;
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=Placenta;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Amygdala, and Testis;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16421571; DOI=10.1038/nature04406;
RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M.,
RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L.,
RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S.,
RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A.,
RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III,
RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K.,
RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B.,
RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K.,
RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L.,
RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G.,
RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W.,
RA Platzer M., Shimizu N., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 8.";
RL Nature 439:331-335(2006).
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=Lymph, and Placenta;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 133-923 (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=11853319; DOI=10.1093/dnares/8.6.319;
RA Nagase T., Kikuno R., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XXII. The
RT complete sequences of 50 new cDNA clones which code for large proteins.";
RL DNA Res. 8:319-327(2001).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 439-845, AND TISSUE SPECIFICITY.
RX PubMed=12370419; DOI=10.1073/pnas.212516099;
RA Hamaguchi M., Meth J.L., von Klitzing C., Wei W., Esposito D., Rodgers L.,
RA Walsh T., Welcsh P., King M.C., Wigler M.H.;
RT "DBC2, a candidate for a tumor suppressor gene involved in breast cancer.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:13647-13652(2002).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-675; SER-678 AND SER-681, AND
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 [9]
RP SUBCELLULAR LOCATION.
RX PubMed=18445686; DOI=10.1242/jcs.019174;
RA Tegha-Dunghu J., Neumann B., Reber S., Krause R., Erfle H., Walter T.,
RA Held M., Rogers P., Hupfeld K., Ruppert T., Ellenberg J., Gruss O.J.;
RT "EML3 is a nuclear microtubule-binding protein required for the correct
RT alignment of chromosomes in metaphase.";
RL J. Cell Sci. 121:1718-1726(2008).
RN [10]
RP FUNCTION AS SIRT1 INHIBITOR, INTERACTION WITH SIRT1, MUTAGENESIS OF
RP 243-LEU--LEU-264, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=18235501; DOI=10.1038/nature06500;
RA Kim J.-E., Chen J., Lou Z.;
RT "DBC1 is a negative regulator of SIRT1.";
RL Nature 451:583-586(2008).
RN [11]
RP FUNCTION IN APOPTOSIS, AND INTERACTION WITH SIRT1.
RX PubMed=18235502; DOI=10.1038/nature06515;
RA Zhao W., Kruse J.-P., Tang Y., Jung S.Y., Qin J., Gu W.;
RT "Negative regulation of the deacetylase SIRT1 by DBC1.";
RL Nature 451:587-590(2008).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-124; SER-675; SER-678 AND
RP SER-681, AND 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 [13]
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 [14]
RP FUNCTION, IDENTIFICATION IN A NUCLEAR RECEPTOR HORMONE COMPLEX, AND
RP INTERACTION WITH ZNF335; ASH2L; EMSY.
RX PubMed=19131338; DOI=10.1074/jbc.m805872200;
RA Garapaty S., Xu C.F., Trojer P., Mahajan M.A., Neubert T.A., Samuels H.H.;
RT "Identification and characterization of a novel nuclear protein complex
RT involved in nuclear hormone receptor-mediated gene regulation.";
RL J. Biol. Chem. 284:7542-7552(2009).
RN [15]
RP FUNCTION AS SUV39H1 INHIBITOR, AND INTERACTION WITH SUV39H1.
RX PubMed=19218236; DOI=10.1074/jbc.m900956200;
RA Li Z., Chen L., Kabra N., Wang C., Fang J., Chen J.;
RT "Inhibition of SUV39H1 methyltransferase activity by DBC1.";
RL J. Biol. Chem. 284:10361-10366(2009).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-35; SER-675; SER-678 AND
RP SER-681, AND 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 [17]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-215, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [18]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH ESR1 AND ESR2.
RX PubMed=20074560; DOI=10.1016/j.bbrc.2010.01.025;
RA Koyama S., Wada-Hiraike O., Nakagawa S., Tanikawa M., Hiraike H.,
RA Miyamoto Y., Sone K., Oda K., Fukuhara H., Nakagawa K., Kato S., Yano T.,
RA Taketani Y.;
RT "Repression of estrogen receptor beta function by putative tumor suppressor
RT DBC1.";
RL Biochem. Biophys. Res. Commun. 392:357-362(2010).
RN [19]
RP FUNCTION, INTERACTION WITH BRCA1, AND SUBCELLULAR LOCATION.
RX PubMed=20160719; DOI=10.1038/sj.bjc.6605577;
RA Hiraike H., Wada-Hiraike O., Nakagawa S., Koyama S., Miyamoto Y., Sone K.,
RA Tanikawa M., Tsuruga T., Nagasaka K., Matsumoto Y., Oda K., Shoji K.,
RA Fukuhara H., Saji S., Nakagawa K., Kato S., Yano T., Taketani Y.;
RT "Identification of DBC1 as a transcriptional repressor for BRCA1.";
RL Br. J. Cancer 102:1061-1067(2010).
RN [20]
RP FUNCTION, AND INTERACTION WITH HDAC1; HDAC3; SIRT1 AND MEF2D.
RX PubMed=21030595; DOI=10.1074/jbc.m110.153270;
RA Chini C.C., Escande C., Nin V., Chini E.N.;
RT "HDAC3 is negatively regulated by the nuclear protein DBC1.";
RL J. Biol. Chem. 285:40830-40837(2010).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-35; SER-124; SER-675; SER-678
RP AND SER-681, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP 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 [22]
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 [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-678, AND IDENTIFICATION BY
RP 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 [24]
RP PHOSPHORYLATION AT THR-454, MUTAGENESIS OF THR-454, AND INTERACTION WITH
RP SIRT1.
RX PubMed=22735644; DOI=10.1093/jmcb/mjs035;
RA Zannini L., Buscemi G., Kim J.E., Fontanella E., Delia D.;
RT "DBC1 phosphorylation by ATM/ATR inhibits SIRT1 deacetylase in response to
RT DNA damage.";
RL J. Mol. Cell Biol. 4:294-303(2012).
RN [25]
RP IDENTIFICATION IN THE DBIRD COMPLEX, FUNCTION, AND INTERACTION WITH ZNF326.
RX PubMed=22446626; DOI=10.1038/nature10925;
RA Close P., East P., Dirac-Svejstrup A.B., Hartmann H., Heron M., Maslen S.,
RA Chariot A., Soding J., Skehel M., Svejstrup J.Q.;
RT "DBIRD complex integrates alternative mRNA splicing with RNA polymerase II
RT transcript elongation.";
RL Nature 484:386-389(2012).
RN [26]
RP FUNCTION, AND INTERACTION WITH NR1D1.
RX PubMed=23398316; DOI=10.1042/bj20121085;
RA Chini C.C., Escande C., Nin V., Chini E.N.;
RT "DBC1 (Deleted in Breast Cancer 1) modulates the stability and function of
RT the nuclear receptor Rev-erbalpha.";
RL Biochem. J. 451:453-461(2013).
RN [27]
RP REVIEW.
RX PubMed=23841676; DOI=10.1042/bsr20130062;
RA Chini E.N., Chini C.C., Nin V., Escande C.;
RT "Deleted in breast cancer-1 (DBC-1) in the interface between metabolism,
RT aging and cancer.";
RL Biosci. Rep. 33:0-0(2013).
RN [28]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH SIRT1.
RX PubMed=23352644; DOI=10.1016/j.canlet.2013.01.026;
RA Kim W., Kim J.E.;
RT "Deleted in breast cancer 1 (DBC1) deficiency results in apoptosis of
RT breast cancer cells through impaired responses to UV-induced DNA damage.";
RL Cancer Lett. 333:180-186(2013).
RN [29]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-124; THR-454; SER-569;
RP SER-675; SER-678; SER-681; SER-687; SER-808 AND THR-897, AND IDENTIFICATION
RP BY MASS 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 [30]
RP REVIEW.
RX PubMed=24273392;
RA Joshi P., Quach O.L., Giguere S.S., Cristea I.M.;
RT "A functional proteomics perspective of dbc1 as a regulator of
RT transcription.";
RL J. Proteomics Bioinform. 0:0-0(2013).
RN [31]
RP ACETYLATION AT LYS-112 AND LYS-215, AND INTERACTION WITH SIRT1.
RX PubMed=24126058; DOI=10.1128/mcb.00874-13;
RA Zheng H., Yang L., Peng L., Izumi V., Koomen J., Seto E., Chen J.;
RT "hMOF acetylation of DBC1/CCAR2 prevents binding and inhibition of SirT1.";
RL Mol. Cell. Biol. 33:4960-4970(2013).
RN [32]
RP FUNCTION.
RX PubMed=24415752; DOI=10.1074/jbc.m113.512913;
RA Nin V., Chini C.C., Escande C., Capellini V., Chini E.N.;
RT "Deleted in breast cancer 1 (DBC1) protein regulates hepatic
RT gluconeogenesis.";
RL J. Biol. Chem. 289:5518-5527(2014).
RN [33]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-484; SER-569; SER-627 AND
RP SER-687, AND 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).
RN [34]
RP METHYLATION [LARGE SCALE ANALYSIS] AT LYS-123 AND ARG-180, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Colon carcinoma;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
RN [35]
RP SUMOYLATION AT LYS-591, DESUMOYLATION, PHOSPHORYLATION AT THR-454,
RP MUTAGENESIS OF THR-454; LYS-591; LYS-667 AND LYS-839, AND INTERACTION WITH
RP SIRT1; PSIA3 AND SENP1.
RX PubMed=25406032; DOI=10.1038/ncomms6483;
RA Park J.H., Lee S.W., Yang S.W., Yoo H.M., Park J.M., Seong M.W., Ka S.H.,
RA Oh K.H., Jeon Y.J., Chung C.H.;
RT "Modification of DBC1 by SUMO2/3 is crucial for p53-mediated apoptosis in
RT response to DNA damage.";
RL Nat. Commun. 5:5483-5483(2014).
RN [36]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-591, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25218447; DOI=10.1038/nsmb.2890;
RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M.,
RA Vertegaal A.C.;
RT "Uncovering global SUMOylation signaling networks in a site-specific
RT manner.";
RL Nat. Struct. Mol. Biol. 21:927-936(2014).
RN [37]
RP FUNCTION, AND INTERACTION WITH CHEK2 AND PSEM3.
RX PubMed=25361978; DOI=10.1093/nar/gku1065;
RA Magni M., Ruscica V., Buscemi G., Kim J.E., Nachimuthu B.T., Fontanella E.,
RA Delia D., Zannini L.;
RT "Chk2 and REGgamma-dependent DBC1 regulation in DNA damage induced
RT apoptosis.";
RL Nucleic Acids Res. 42:13150-13160(2014).
RN [38]
RP FUNCTION, AND INTERACTION WITH TP53.
RX PubMed=25732823; DOI=10.1016/j.celrep.2015.01.066;
RA Qin B., Minter-Dykhouse K., Yu J., Zhang J., Liu T., Zhang H., Lee S.,
RA Kim J., Wang L., Lou Z.;
RT "DBC1 functions as a tumor suppressor by regulating p53 stability.";
RL Cell Rep. 10:1324-1334(2015).
RN [39]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH MCC.
RX PubMed=24824780; DOI=10.1002/ijc.28967;
RA Pangon L., Mladenova D., Watkins L., Van Kralingen C., Currey N.,
RA Al-Sohaily S., Lecine P., Borg J.P., Kohonen-Corish M.R.;
RT "MCC inhibits beta-catenin transcriptional activity by sequestering DBC1 in
RT the cytoplasm.";
RL Int. J. Cancer 136:55-64(2015).
RN [40]
RP PHOSPHORYLATION AT THR-454, MUTAGENESIS OF THR-454, SUBCELLULAR LOCATION,
RP TISSUE SPECIFICITY, AND INTERACTION WITH CSNK2A1.
RX PubMed=24962073; DOI=10.1002/ijc.29043;
RA Bae J.S., Park S.H., Kim K.M., Kwon K.S., Kim C.Y., Lee H.K., Park B.H.,
RA Park H.S., Lee H., Moon W.S., Chung M.J., Sylvester K.G., Jang K.Y.;
RT "CK2alpha phosphorylates DBC1 and is involved in the progression of gastric
RT carcinoma and predicts poor survival of gastric carcinoma patients.";
RL Int. J. Cancer 136:797-809(2015).
RN [41]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH NR1H2 AND NR1H3.
RX PubMed=25661920; DOI=10.1016/j.jsbmb.2015.02.001;
RA Sakurabashi A., Wada-Hiraike O., Hirano M., Fu H., Isono W., Fukuda T.,
RA Morita Y., Tanikawa M., Miyamoto Y., Oda K., Kawana K., Osuga Y., Fujii T.;
RT "CCAR2 negatively regulates nuclear receptor LXRalpha by competing with
RT SIRT1 deacetylase.";
RL J. Steroid Biochem. Mol. Biol. 149:80-88(2015).
RN [42]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-591, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
CC -!- FUNCTION: Core component of the DBIRD complex, a multiprotein complex
CC that acts at the interface between core mRNP particles and RNA
CC polymerase II (RNAPII) and integrates transcript elongation with the
CC regulation of alternative splicing: the DBIRD complex affects local
CC transcript elongation rates and alternative splicing of a large set of
CC exons embedded in (A + T)-rich DNA regions (PubMed:22446626). Inhibits
CC SIRT1 deacetylase activity leading to increasing levels of p53/TP53
CC acetylation and p53-mediated apoptosis (PubMed:18235501,
CC PubMed:18235502, PubMed:23352644). Inhibits SUV39H1 methyltransferase
CC activity (PubMed:19218236). Mediates ligand-dependent transcriptional
CC activation by nuclear hormone receptors (PubMed:19131338). Plays a
CC critical role in maintaining genomic stability and cellular integrity
CC following UV-induced genotoxic stress (PubMed:23398316). Regulates the
CC circadian expression of the core clock components NR1D1 and ARNTL/BMAL1
CC (PubMed:23398316). Enhances the transcriptional repressor activity of
CC NR1D1 through stabilization of NR1D1 protein levels by preventing its
CC ubiquitination and subsequent degradation (PubMed:23398316). Represses
CC the ligand-dependent transcriptional activation function of ESR2
CC (PubMed:20074560). Acts as a regulator of PCK1 expression and
CC gluconeogenesis by a mechanism that involves, at least in part, both
CC NR1D1 and SIRT1 (PubMed:24415752). Negatively regulates the deacetylase
CC activity of HDAC3 and can alter its subcellular localization
CC (PubMed:21030595). Positively regulates the beta-catenin pathway
CC (canonical Wnt signaling pathway) and is required for MCC-mediated
CC repression of the beta-catenin pathway (PubMed:24824780). Represses
CC ligand-dependent transcriptional activation function of NR1H2 and NR1H3
CC and inhibits the interaction of SIRT1 with NR1H3 (PubMed:25661920).
CC Plays an important role in tumor suppression through p53/TP53
CC regulation; stabilizes p53/TP53 by affecting its interaction with
CC ubiquitin ligase MDM2 (PubMed:25732823). Represses the transcriptional
CC activator activity of BRCA1 (PubMed:20160719). Inhibits SIRT1 in a
CC CHEK2 and PSEM3-dependent manner and inhibits the activity of CHEK2 in
CC vitro (PubMed:25361978). {ECO:0000269|PubMed:18235501,
CC ECO:0000269|PubMed:18235502, ECO:0000269|PubMed:19131338,
CC ECO:0000269|PubMed:19218236, ECO:0000269|PubMed:20074560,
CC ECO:0000269|PubMed:20160719, ECO:0000269|PubMed:21030595,
CC ECO:0000269|PubMed:22446626, ECO:0000269|PubMed:23352644,
CC ECO:0000269|PubMed:23398316, ECO:0000269|PubMed:24415752,
CC ECO:0000269|PubMed:24824780, ECO:0000269|PubMed:25361978,
CC ECO:0000269|PubMed:25661920, ECO:0000269|PubMed:25732823}.
CC -!- SUBUNIT: Component of the DBIRD complex (PubMed:22446626). Interacts
CC with ZNF326/ZIRD; the interaction is direct (PubMed:22446626).
CC Interacts (via N-terminus) with SIRT1, which inhibits the deacetylation
CC of substrates (PubMed:18235501, PubMed:18235502, PubMed:21030595,
CC PubMed:22735644, PubMed:23352644, PubMed:24126058, PubMed:25406032).
CC Interacts (via N-terminus) with SUV39H1; this interaction abolishes the
CC interaction with SIRT1 (PubMed:19218236). Component of a nuclear
CC receptor-mediated transcription complex composed of at least ZNF335,
CC CCAR2 and EMSY; the complex stimulates the transcription of nuclear
CC receptor target genes such as SOX9 and HOXA1 (PubMed:19131338). Within
CC the complex interacts with EMSY and interacts with ZNF335 (via C-
CC terminus) (PubMed:19131338). Components of this complex may associate
CC with components of a histone methylation complex to form a complex at
CC least composed of ZNF335, HCFC1, CCAR2, EMSY, MKI67, RBBP5, ASH2L and
CC WDR5 (PubMed:19131338). Within this complex, interacts with ASH2L
CC (PubMed:19131338). Interacts with NR1D1 (PubMed:23398316). Interacts
CC (via N-terminus) with ESR1 and ESR2 (PubMed:20074560). Interacts (via
CC N-terminus) with HDAC3 (via C-terminus) (PubMed:21030595). Interacts
CC with HDAC1 and MED2F (PubMed:21030595). Interacts with MCC
CC (PubMed:24824780). Interacts (via N-terminus) with NR1H2 and NR1H3 in a
CC ligand-independent manner (PubMed:25661920). Interacts with CSNK2A1
CC (PubMed:24962073). Interacts (via N-terminus) with p53/TP53
CC (PubMed:25732823). Interacts (via N-terminus) with BRCA1 (via the BRCT
CC domains) (PubMed:20160719). Interacts (via N-terminus) with CHEK2 (via
CC protein kinase domain) (PubMed:25361978). Interacts with PSEM3
CC (PubMed:25361978). Interacts (via N-terminus) with PSIA3 and SENP1
CC (PubMed:25406032). The sumoylated form shows a preferential interaction
CC with SIRT1 as compared to its unmodified form (PubMed:25406032).
CC {ECO:0000269|PubMed:18235501, ECO:0000269|PubMed:18235502,
CC ECO:0000269|PubMed:19131338, ECO:0000269|PubMed:19218236,
CC ECO:0000269|PubMed:20074560, ECO:0000269|PubMed:20160719,
CC ECO:0000269|PubMed:21030595, ECO:0000269|PubMed:22446626,
CC ECO:0000269|PubMed:22735644, ECO:0000269|PubMed:23352644,
CC ECO:0000269|PubMed:23398316, ECO:0000269|PubMed:24126058,
CC ECO:0000269|PubMed:24824780, ECO:0000269|PubMed:24962073,
CC ECO:0000269|PubMed:25361978, ECO:0000269|PubMed:25406032,
CC ECO:0000269|PubMed:25661920, ECO:0000269|PubMed:25732823}.
CC -!- INTERACTION:
CC Q8N163; P01106: MYC; NbExp=8; IntAct=EBI-355410, EBI-447544;
CC Q8N163; Q96EB6: SIRT1; NbExp=16; IntAct=EBI-355410, EBI-1802965;
CC Q8N163; P02766: TTR; NbExp=3; IntAct=EBI-355410, EBI-711909;
CC Q8N163; O76024: WFS1; NbExp=3; IntAct=EBI-355410, EBI-720609;
CC Q8N163; Q9H4Z2: ZNF335; NbExp=5; IntAct=EBI-355410, EBI-2795590;
CC Q8N163; Q9Q2G4: ORF; Xeno; NbExp=5; IntAct=EBI-355410, EBI-6248094;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:18445686,
CC ECO:0000269|PubMed:20074560, ECO:0000269|PubMed:20160719,
CC ECO:0000269|PubMed:23352644, ECO:0000269|PubMed:24824780,
CC ECO:0000269|PubMed:24962073, ECO:0000269|PubMed:25661920}. Cytoplasm
CC {ECO:0000269|PubMed:20160719, ECO:0000269|PubMed:24824780}. Cytoplasm,
CC cytoskeleton, spindle {ECO:0000269|PubMed:18445686}. Note=Recruited to
CC chromatin, post-UV irradiation. Sequestered to the cytoplasm in the
CC presence of MCC. Translocated to the cytoplasm during UV-induced
CC apoptosis. {ECO:0000269|PubMed:20160719, ECO:0000269|PubMed:24824780}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8N163-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8N163-2; Sequence=VSP_017092;
CC -!- TISSUE SPECIFICITY: Expressed in gastric carcinoma tissue and the
CC expression gradually increases with the progression of the carcinoma
CC (at protein level). Expressed ubiquitously in normal tissues. Expressed
CC in 84 to 100% of neoplastic breast, lung, and colon tissues.
CC {ECO:0000269|PubMed:12370419, ECO:0000269|PubMed:24962073}.
CC -!- PTM: ATM/ATR-mediated phosphorylation at Thr-454 upon DNA damage
CC promotes binding to SIRT1. Phosphorylation at Thr-454 promotes its
CC sumoylation by switching the binding partner of CCAR2 from SENP1 to
CC PIAS3. {ECO:0000269|PubMed:22735644, ECO:0000269|PubMed:25406032}.
CC -!- PTM: Acetylation at Lys-112 and Lys-215 by KAT8 prevents inhibitory
CC binding to SIRT1 and increases its deacetylase activity.
CC {ECO:0000269|PubMed:24126058}.
CC -!- PTM: Genotoxic stress induces its sumoylation and sumoylation promotes
CC the SIRT1-CCAR2 interaction which in turn inhibits SIRT1-mediated
CC deacetylation of p53/TP53. Sumoylation leads to transcriptional
CC activation of p53/TP53 by sequestering SIRT1 from p53/TP53.
CC Desumoylated by SENP1. {ECO:0000269|PubMed:25406032}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAG02472.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAB85553.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/KIAA1967ID46056ch8p21.html";
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DR EMBL; AK096547; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AK314535; BAG37126.1; -; mRNA.
DR EMBL; AL834162; CAD38866.1; -; mRNA.
DR EMBL; AL834351; CAD39016.1; -; mRNA.
DR EMBL; AL834352; CAD39017.1; -; mRNA.
DR EMBL; BX640952; CAE45976.1; -; mRNA.
DR EMBL; AL137523; CAB70788.3; -; mRNA.
DR EMBL; AC037459; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471080; EAW63658.1; -; Genomic_DNA.
DR EMBL; CH471080; EAW63661.1; -; Genomic_DNA.
DR EMBL; BC018269; AAH18269.2; -; mRNA.
DR EMBL; BC065495; AAH65495.1; -; mRNA.
DR EMBL; AB075847; BAB85553.1; ALT_INIT; mRNA.
DR EMBL; AF293335; AAG02472.1; ALT_FRAME; mRNA.
DR CCDS; CCDS34863.1; -. [Q8N163-1]
DR PIR; T46368; T46368.
DR RefSeq; NP_066997.3; NM_021174.5. [Q8N163-1]
DR AlphaFoldDB; Q8N163; -.
DR SMR; Q8N163; -.
DR BioGRID; 121775; 260.
DR CORUM; Q8N163; -.
DR DIP; DIP-38122N; -.
DR IntAct; Q8N163; 121.
DR MINT; Q8N163; -.
DR STRING; 9606.ENSP00000310670; -.
DR GlyGen; Q8N163; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q8N163; -.
DR PhosphoSitePlus; Q8N163; -.
DR SwissPalm; Q8N163; -.
DR BioMuta; CCAR2; -.
DR DMDM; 85701135; -.
DR EPD; Q8N163; -.
DR jPOST; Q8N163; -.
DR MassIVE; Q8N163; -.
DR MaxQB; Q8N163; -.
DR PaxDb; Q8N163; -.
DR PeptideAtlas; Q8N163; -.
DR PRIDE; Q8N163; -.
DR ProteomicsDB; 71566; -. [Q8N163-1]
DR ProteomicsDB; 71567; -. [Q8N163-2]
DR Antibodypedia; 9629; 315 antibodies from 37 providers.
DR CPTC; Q8N163; 2 antibodies.
DR DNASU; 57805; -.
DR Ensembl; ENST00000308511.9; ENSP00000310670.4; ENSG00000158941.17. [Q8N163-1]
DR Ensembl; ENST00000389279.7; ENSP00000373930.3; ENSG00000158941.17. [Q8N163-1]
DR GeneID; 57805; -.
DR KEGG; hsa:57805; -.
DR MANE-Select; ENST00000308511.9; ENSP00000310670.4; NM_001393997.1; NP_001380926.1.
DR UCSC; uc003xch.4; human. [Q8N163-1]
DR CTD; 57805; -.
DR DisGeNET; 57805; -.
DR GeneCards; CCAR2; -.
DR HGNC; HGNC:23360; CCAR2.
DR HPA; ENSG00000158941; Low tissue specificity.
DR MIM; 607359; gene.
DR neXtProt; NX_Q8N163; -.
DR OpenTargets; ENSG00000158941; -.
DR PharmGKB; PA134993792; -.
DR VEuPathDB; HostDB:ENSG00000158941; -.
DR eggNOG; KOG4246; Eukaryota.
DR GeneTree; ENSGT00530000063672; -.
DR HOGENOM; CLU_008030_2_0_1; -.
DR InParanoid; Q8N163; -.
DR OMA; VAQNICQ; -.
DR OrthoDB; 614048at2759; -.
DR PhylomeDB; Q8N163; -.
DR TreeFam; TF316387; -.
DR PathwayCommons; Q8N163; -.
DR Reactome; R-HSA-3371453; Regulation of HSF1-mediated heat shock response.
DR SignaLink; Q8N163; -.
DR SIGNOR; Q8N163; -.
DR BioGRID-ORCS; 57805; 29 hits in 1071 CRISPR screens.
DR ChiTaRS; CCAR2; human.
DR GeneWiki; KIAA1967; -.
DR GenomeRNAi; 57805; -.
DR Pharos; Q8N163; Tbio.
DR PRO; PR:Q8N163; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; Q8N163; protein.
DR Bgee; ENSG00000158941; Expressed in cortical plate and 173 other tissues.
DR ExpressionAtlas; Q8N163; baseline and differential.
DR Genevisible; Q8N163; HS.
DR GO; GO:0000785; C:chromatin; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0044609; C:DBIRD complex; IDA:UniProtKB.
DR GO; GO:0005759; C:mitochondrial matrix; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005819; C:spindle; IDA:UniProtKB.
DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
DR GO; GO:0004857; F:enzyme inhibitor activity; IDA:UniProtKB.
DR GO; GO:0030374; F:nuclear receptor coactivator activity; IBA:GO_Central.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0000993; F:RNA polymerase II complex binding; IDA:UniProtKB.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IEA:UniProtKB-KW.
DR GO; GO:0043653; P:mitochondrial fragmentation involved in apoptotic process; IDA:UniProtKB.
DR GO; GO:0006397; P:mRNA processing; IEA:UniProtKB-KW.
DR GO; GO:0043086; P:negative regulation of catalytic activity; IMP:UniProtKB.
DR GO; GO:0030308; P:negative regulation of cell growth; IMP:UniProtKB.
DR GO; GO:1902230; P:negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage; IMP:UniProtKB.
DR GO; GO:0032435; P:negative regulation of proteasomal ubiquitin-dependent protein catabolic process; IDA:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IMP:UniProtKB.
DR GO; GO:2000003; P:positive regulation of DNA damage checkpoint; IMP:UniProtKB.
DR GO; GO:0042752; P:regulation of circadian rhythm; ISS:UniProtKB.
DR GO; GO:0032784; P:regulation of DNA-templated transcription, elongation; IMP:UniProtKB.
DR GO; GO:0090311; P:regulation of protein deacetylation; IDA:UniProtKB.
DR GO; GO:0031647; P:regulation of protein stability; IDA:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IBA:GO_Central.
DR GO; GO:0009411; P:response to UV; IMP:UniProtKB.
DR GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW.
DR GO; GO:0008380; P:RNA splicing; IMP:UniProtKB.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR InterPro; IPR045354; BURAN.
DR InterPro; IPR025224; CCAR1/CCAR2.
DR InterPro; IPR028811; CCAR2.
DR InterPro; IPR025954; DBC1/CARP1_inactive_NUDIX_dom.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR045353; LAIKA.
DR InterPro; IPR025223; S1-like_RNA-bd_dom.
DR PANTHER; PTHR14304; PTHR14304; 1.
DR PANTHER; PTHR14304:SF12; PTHR14304:SF12; 1.
DR Pfam; PF19257; BURAN; 1.
DR Pfam; PF14443; DBC1; 1.
DR Pfam; PF19256; LAIKA; 1.
DR Pfam; PF14444; S1-like; 1.
DR SMART; SM01122; DBC1; 1.
DR SUPFAM; SSF47473; SSF47473; 1.
PE 1: Evidence at protein level;
KW Acetylation; Activator; Alternative splicing; Apoptosis;
KW Biological rhythms; Cell cycle; Coiled coil; Cytoplasm; Cytoskeleton;
KW DNA damage; Isopeptide bond; Metalloenzyme inhibitor; Methylation;
KW mRNA processing; mRNA splicing; Nucleus; Phosphoprotein;
KW Reference proteome; Repressor; Transcription; Transcription regulation;
KW Tumor suppressor; Ubl conjugation; Wnt signaling pathway.
FT CHAIN 1..923
FT /note="Cell cycle and apoptosis regulator protein 2"
FT /id="PRO_0000050813"
FT REGION 1..35
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 178..218
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 446..510
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 568..643
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 610..670
FT /note="Interaction with MCC"
FT /evidence="ECO:0000269|PubMed:24824780"
FT REGION 704..923
FT /note="Interaction with NR1D1"
FT /evidence="ECO:0000269|PubMed:23398316"
FT COILED 829..909
FT /evidence="ECO:0000255"
FT COMPBIAS 14..28
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 187..218
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 477..496
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 569..606
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 627..643
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 35
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231"
FT MOD_RES 112
FT /note="N6-acetyllysine; by KAT8"
FT /evidence="ECO:0000269|PubMed:24126058"
FT MOD_RES 123
FT /note="N6-methyllysine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 124
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 180
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 215
FT /note="N6-acetyllysine; by KAT8"
FT /evidence="ECO:0000269|PubMed:24126058,
FT ECO:0007744|PubMed:19608861"
FT MOD_RES 454
FT /note="Phosphothreonine; by ATM, ATR and CK2"
FT /evidence="ECO:0000269|PubMed:22735644,
FT ECO:0000269|PubMed:24962073, ECO:0007744|PubMed:23186163"
FT MOD_RES 484
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 569
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 627
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 675
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 678
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 681
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 687
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 808
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 897
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT CROSSLNK 591
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2 and SUMO3); alternate"
FT /evidence="ECO:0000269|PubMed:25406032"
FT CROSSLNK 591
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0007744|PubMed:25218447,
FT ECO:0007744|PubMed:28112733"
FT VAR_SEQ 910..923
FT /note="ADSWVEKEEPAPSN -> VRWGWTRRQHSSFP (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11853319"
FT /id="VSP_017092"
FT MUTAGEN 243..264
FT /note="Missing: Abolishes binding to SIRT1."
FT /evidence="ECO:0000269|PubMed:18235501"
FT MUTAGEN 454
FT /note="T->A: Significantly reduces association with SIRT1.
FT Decreases sumoylation and the interaction of the sumoylated
FT form with SIRT1. Inhibits CCAR2-PSIA3 interaction.
FT Increases CCAR2-SENP1 interaction. Down-regulation of the
FT signals related with the epithelial-mesenchymal transition
FT of gastric cancer cells."
FT /evidence="ECO:0000269|PubMed:22735644,
FT ECO:0000269|PubMed:24962073, ECO:0000269|PubMed:25406032"
FT MUTAGEN 454
FT /note="T->D: Significantly increases association with SIRT1
FT and induces p53 acetylation and apoptosis. Increases
FT sumoylation and the interaction of the sumoylated form with
FT SIRT1. Promotes CCAR2-PSIA3 interaction. Decreases CCAR2-
FT SENP1 interaction."
FT /evidence="ECO:0000269|PubMed:22735644,
FT ECO:0000269|PubMed:25406032"
FT MUTAGEN 591
FT /note="K->R: Loss of sumoylation."
FT /evidence="ECO:0000269|PubMed:25406032"
FT MUTAGEN 667
FT /note="K->R: No effect on sumoylation."
FT /evidence="ECO:0000269|PubMed:25406032"
FT MUTAGEN 839
FT /note="K->R: No effect on sumoylation."
FT /evidence="ECO:0000269|PubMed:25406032"
FT CONFLICT 47
FT /note="R -> S (in Ref. 2; CAD38866/CAD39017)"
FT /evidence="ECO:0000305"
FT CONFLICT 850
FT /note="T -> S (in Ref. 5; AAH65495)"
FT /evidence="ECO:0000305"
FT CONFLICT 908
FT /note="E -> G (in Ref. 2; CAD38866/CAD39017)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 923 AA; 102902 MW; 1733934377E35D21 CRC64;
MSQFKRQRIN PLPGGRNFSG TASTSLLGPP PGLLTPPVAT ELSQNARHLQ GGEKQRVFTG
IVTSLHDYFG VVDEEVFFQL SVVKGRLPQL GEKVLVKAAY NPGQAVPWNA VKVQTLSNQP
LLKSPAPPLL HVAALGQKQG ILGAQPQLIF QPHRIPPLFP QKPLSLFQTS HTLHLSHLNR
FPARGPHGRL DQGRSDDYDS KKRKQRAGGE PWGAKKPRHD LPPYRVHLTP YTVDSPICDF
LELQRRYRSL LVPSDFLSVH LSWLSAFPLS QPFSLHHPSR IQVSSEKEAA PDAGAEPITA
DSDPAYSSKV LLLSSPGLEE LYRCCMLFVD DMAEPRETPE HPLKQIKFLL GRKEEEAVLV
GGEWSPSLDG LDPQADPQVL VRTAIRCAQA QTGIDLSGCT KWWRFAEFQY LQPGPPRRLQ
TVVVYLPDVW TIMPTLEEWE ALCQQKAAEA APPTQEAQGE TEPTEQAPDA LEQAADTSRR
NAETPEATTQ QETDTDLPEA PPPPLEPAVI ARPGCVNLSL HGIVEDRRPK ERISFEVMVL
AELFLEMLQR DFGYRVYKML LSLPEKVVSP PEPEKEEAAK EEATKEEEAI KEEVVKEPKD
EAQNEGPATE SEAPLKEDGL LPKPLSSGGE EEEKPRGEAS EDLCEMALDP ELLLLRDDGE
EEFAGAKLED SEVRSVASNQ SEMEFSSLQD MPKELDPSAV LPLDCLLAFV FFDANWCGYL
HRRDLERILL TLGIRLSAEQ AKQLVSRVVT QNICQYRSLQ YSRQEGLDGG LPEEVLFGNL
DLLPPPGKST KPGAAPTEHK ALVSHNGSLI NVGSLLQRAE QQDSGRLYLE NKIHTLELKL
EESHNRFSAT EVTNKTLAAE MQELRVRLAE AEETARTAER QKSQLQRLLQ ELRRRLTPLQ
LEIQRVVEKA DSWVEKEEPA PSN
