Full text data of CTBP1
CTBP1
(CTBP)
[Confidence: low (only semi-automatic identification from reviews)]
C-terminal-binding protein 1; CtBP1; 1.1.1.-
Note: presumably soluble (membrane word is not in UniProt keywords or features)
C-terminal-binding protein 1; CtBP1; 1.1.1.-
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q13363
ID CTBP1_HUMAN Reviewed; 440 AA.
AC Q13363; Q4W5N3; Q7Z2Q5;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
read moreDT 15-JUL-1999, sequence version 2.
DT 22-JAN-2014, entry version 152.
DE RecName: Full=C-terminal-binding protein 1;
DE Short=CtBP1;
DE EC=1.1.1.-;
GN Name=CTBP1; Synonyms=CTBP;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 98-108,
RP AND INTERACTION WITH RBBP8 AND ADENOVIRUS E1A.
RC TISSUE=B-cell, and Cervix carcinoma;
RX PubMed=7479821; DOI=10.1073/pnas.92.23.10467;
RA Schaeper U., Boyd J.M., Verma S., Uhlmann E., Subramanian T.,
RA Chinnadurai G.;
RT "Molecular cloning and characterization of a cellular phosphoprotein
RT that interacts with a conserved C-terminal domain of adenovirus E1A
RT involved in negative modulation of oncogenic transformation.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:10467-10471(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SEQUENCE REVISION, AND
RP FUNCTION.
RX PubMed=9858600;
RA Sewalt R.G.A.B., Gunster M.J., van der Vlag J., Satijn D.P.E.,
RA Otte A.P.;
RT "C-terminal binding protein is a transcriptional repressor that
RT interacts with a specific class of vertebrate polycomb proteins.";
RL Mol. Cell. Biol. 19:777-787(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H.,
RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
RA Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N.,
RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
RA McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D.,
RA Waterston R.H., Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2
RT and 4.";
RL Nature 434:724-731(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain, and Lung;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP INTERACTION WITH ADENOVIRUS E1A, AND PHOSPHORYLATION.
RX PubMed=8440238;
RA Boyd J.M., Subramanian T., Schaeper U., la Regina M., Bayley S.,
RA Chinnadurai G.;
RT "A region in the C-terminus of adenovirus 2/5 E1a protein is required
RT for association with a cellular phosphoprotein and important for the
RT negative modulation of T24-ras mediated transformation, tumorigenesis
RT and metastasis.";
RL EMBO J. 12:469-478(1993).
RN [7]
RP INTERACTION WITH MECOM.
RX PubMed=11568182; DOI=10.1074/jbc.M106733200;
RA Chakraborty S., Senyuk V., Sitailo S., Chi Y., Nucifora G.;
RT "Interaction of EVI1 with cAMP-responsive element-binding protein-
RT binding protein (CBP) and p300/CBP-associated factor (P/CAF) results
RT in reversible acetylation of EVI1 and in co-localization in nuclear
RT speckles.";
RL J. Biol. Chem. 276:44936-44943(2001).
RN [8]
RP INTERACTION WITH EBV EBNA6.
RX PubMed=11462050; DOI=10.1128/JVI.75.16.7749-7755.2001;
RA Touitou R., Hickabottom M., Parker G., Crook T., Allday M.J.;
RT "Physical and functional interactions between the corepressor CtBP and
RT the Epstein-Barr virus nuclear antigen EBNA3C.";
RL J. Virol. 75:7749-7755(2001).
RN [9]
RP INTERACTION WITH NRIP1.
RX PubMed=11509661; DOI=10.1128/MCB.21.18.6181-6188.2001;
RA Vo N., Fjeld C., Goodman R.H.;
RT "Acetylation of nuclear hormone receptor-interacting protein RIP140
RT regulates binding of the transcriptional corepressor CtBP.";
RL Mol. Cell. Biol. 21:6181-6188(2001).
RN [10]
RP INTERACTION WITH EBV EBNA3.
RX PubMed=12372828; DOI=10.1074/jbc.M208116200;
RA Hickabottom M., Parker G.A., Freemont P., Crook T., Allday M.J.;
RT "Two nonconsensus sites in the Epstein-Barr virus oncoprotein EBNA3A
RT cooperate to bind the co-repressor carboxyl-terminal-binding protein
RT (CtBP).";
RL J. Biol. Chem. 277:47197-47204(2002).
RN [11]
RP SUMOYLATION AT LYS-428, AND SUBCELLULAR LOCATION.
RX PubMed=12679040; DOI=10.1016/S0092-8674(03)00159-4;
RA Kagey M.H., Melhuish T.A., Wotton D.;
RT "The polycomb protein Pc2 is a SUMO E3.";
RL Cell 113:127-137(2003).
RN [12]
RP INTERACTION WITH HIPK2, PHOSPHORYLATION AT SER-422, AND MUTAGENESIS OF
RP SER-422.
RX PubMed=14567915; DOI=10.1016/S0092-8674(03)00802-X;
RA Zhang Q., Yoshimatsu Y., Hildebrand J., Frisch S.M., Goodman R.H.;
RT "Homeodomain interacting protein kinase 2 promotes apoptosis by
RT downregulating the transcriptional corepressor CtBP.";
RL Cell 115:177-186(2003).
RN [13]
RP FUNCTION IN TRANSCRIPTIONAL REPRESSION, AND INTERACTION WITH PNN.
RX PubMed=15542832; DOI=10.1128/MCB.24.23.10223-10235.2004;
RA Alpatov R., Munguba G.C., Caton P., Joo J.H., Shi Y., Shi Y.,
RA Hunt M.E., Sugrue S.P.;
RT "Nuclear speckle-associated protein Pnn/DRS binds to the
RT transcriptional corepressor CtBP and relieves CtBP-mediated repression
RT of the E-cadherin gene.";
RL Mol. Cell. Biol. 24:10223-10235(2004).
RN [14]
RP INTERACTION WITH NRIP1.
RX PubMed=15060175; DOI=10.1093/nar/gkh524;
RA Castet A., Boulahtouf A., Versini G., Bonnet S., Augereau P.,
RA Vignon F., Khochbin S., Jalaguier S., Cavailles V.;
RT "Multiple domains of the receptor-interacting protein 140 contribute
RT to transcription inhibition.";
RL Nucleic Acids Res. 32:1957-1966(2004).
RN [15]
RP INTERACTION WITH ZFHX1B.
RX PubMed=16061479; DOI=10.1074/jbc.M504477200;
RA Long J., Zuo D., Park M.;
RT "Pc2-mediated sumoylation of Smad-interacting protein 1 attenuates
RT transcriptional repression of E-cadherin.";
RL J. Biol. Chem. 280:35477-35489(2005).
RN [16]
RP INTERACTION WITH MECOM.
RX PubMed=15897867; DOI=10.1038/sj.onc.1208754;
RA Nitta E., Izutsu K., Yamaguchi Y., Imai Y., Ogawa S., Chiba S.,
RA Kurokawa M., Hirai H.;
RT "Oligomerization of Evi-1 regulated by the PR domain contributes to
RT recruitment of corepressor CtBP.";
RL Oncogene 24:6165-6173(2005).
RN [17]
RP INTERACTION WITH FOXP1.
RX PubMed=16609867; DOI=10.1007/s00427-006-0073-8;
RA Schoen C., Wochnik A., Roessner A., Donow C., Knoechel W.;
RT "The FoxP subclass in Xenopus laevis development.";
RL Dev. Genes Evol. 216:641-646(2006).
RN [18]
RP INTERACTION WITH WIZ.
RX PubMed=16702210; DOI=10.1074/jbc.M603087200;
RA Ueda J., Tachibana M., Ikura T., Shinkai Y.;
RT "Zinc finger protein Wiz links G9a/GLP histone methyltransferases to
RT the co-repressor molecule CtBP.";
RL J. Biol. Chem. 281:20120-20128(2006).
RN [19]
RP INTERACTION WITH ZNF366.
RX PubMed=17085477; DOI=10.1093/nar/gkl875;
RA Lopez-Garcia J., Periyasamy M., Thomas R.S., Christian M., Leao M.,
RA Jat P., Kindle K.B., Heery D.M., Parker M.G., Buluwela L.,
RA Kamalati T., Ali S.;
RT "ZNF366 is an estrogen receptor corepressor that acts through CtBP and
RT histone deacetylases.";
RL Nucleic Acids Res. 34:6126-6136(2006).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-300, AND MASS
RP SPECTROMETRY.
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III,
RA Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N.,
RA Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [21]
RP FUNCTION AS COREPRESSOR, INTERACTION WITH BCL6, AND TISSUE
RP SPECIFICITY.
RX PubMed=18212045; DOI=10.1128/MCB.01400-07;
RA Mendez L.M., Polo J.M., Yu J.J., Krupski M., Ding B.B., Melnick A.,
RA Ye B.H.;
RT "CtBP is an essential corepressor for BCL6 autoregulation.";
RL Mol. Cell. Biol. 28:2175-2186(2008).
RN [22]
RP FUNCTION, AND INTERACTION WITH SATB1.
RX PubMed=19103759; DOI=10.1128/MCB.00822-08;
RA Purbey P.K., Singh S., Notani D., Kumar P.P., Limaye A.S., Galande S.;
RT "Acetylation-dependent interaction of SATB1 and CtBP1 mediates
RT transcriptional repression by SATB1.";
RL Mol. Cell. Biol. 29:1321-1337(2009).
RN [23]
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.,
RA Buerckstuemmer T., 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 [24]
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 28-353 IN COMPLEX WITH NAD,
RP FUNCTION, COFACTOR, MUTAGENESIS OF CYS-134; ASN-138; ARG-141;
RP 141-ARG-ARG-142; LEU-150; ARG-163; ARG-171; GLY-181; GLY-183; ASP-204;
RP ARG-266; ASP-290; GLU-295 AND HIS-315, AND DIMERIZATION.
RX PubMed=12419229; DOI=10.1016/S1097-2765(02)00650-0;
RA Kumar V., Carlson J.E., Ohgi K.A., Edwards T.A., Rose D.W.,
RA Escalante C.R., Rosenfeld M.G., Aggarwal A.K.;
RT "Transcription corepressor CtBP is an NAD(+)-regulated
RT dehydrogenase.";
RL Mol. Cell 10:857-869(2002).
CC -!- FUNCTION: Corepressor targeting diverse transcription regulators
CC such as GLIS2 or BCL6. Has dehydrogenase activity. Involved in
CC controlling the equilibrium between tubular and stacked structures
CC in the Golgi complex. Functions in brown adipose tissue (BAT)
CC differentiation.
CC -!- COFACTOR: NAD. Required for efficient interaction with E1A.
CC Cofactor binding induces a conformation change.
CC -!- SUBUNIT: Homo- or heterodimer. Heterodimer with CTBP2. Interacts
CC with PRDM16; the interaction represses white adipose tissue (WAT)-
CC specific genes expression. Interacts with GLIS2, FOXP2, HDAC4,
CC HDAC5, HDAC9 and ZNF217. Interacts with adenovirus E1A protein
CC (via its C-terminus); the interaction disrupts the interaction of
CC CTBP1 with RBBP8. Interacts with Epstein-Barr virus EBNA3 and
CC EBNA6. Interacts with ELK3 (via its PXDLS motif). Interacts with
CC RBBP8 (via its PXDLS motif); the interaction is disrupted by
CC binding to adenovirus E1A. Interacts with FOXP1, HIPK2, PNN,
CC NRIP1, MECOM, ZNF366, ZFHX1B and WIZ. Interaction with SATB1 (non-
CC acetylated form); the interaction stabilizes its attachment to DNA
CC and promotes transcription repression. Interacts with BCL6; the
CC interaction is required for BCL6 transcriptional autoinhibition
CC and inhibition of some BCL6 target genes.
CC -!- INTERACTION:
CC Q9BXL5:HEMGN; NbExp=2; IntAct=EBI-908846, EBI-3916399;
CC Q14526:HIC1; NbExp=4; IntAct=EBI-908846, EBI-2507362;
CC O43474:KLF4; NbExp=4; IntAct=EBI-908846, EBI-7232405;
CC Q96EK4:THAP11; NbExp=2; IntAct=EBI-908846, EBI-1790529;
CC A2APF7:Zbp1 (xeno); NbExp=2; IntAct=EBI-908846, EBI-6115394;
CC Q8N895:ZNF366; NbExp=5; IntAct=EBI-908846, EBI-2813661;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q13363-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q13363-2; Sequence=VSP_043305;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Expressed in germinal center B-cells.
CC -!- PTM: The level of phosphorylation appears to be regulated during
CC the cell cycle. Phosphorylation by HIPK2 on Ser-422 induces
CC proteasomal degradation.
CC -!- PTM: ADP-ribosylated; when cells are exposed to brefeldin A (By
CC similarity).
CC -!- PTM: Sumoylation on Lys-428 is promoted by the E3 SUMO-protein
CC ligase CBX4.
CC -!- SIMILARITY: Belongs to the D-isomer specific 2-hydroxyacid
CC dehydrogenase family.
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DR EMBL; U37408; AAC62822.1; -; mRNA.
DR EMBL; AF091555; AAD14597.1; -; mRNA.
DR EMBL; AC092535; AAY40989.1; -; Genomic_DNA.
DR EMBL; CH471131; EAW82599.1; -; Genomic_DNA.
DR EMBL; CH471131; EAW82600.1; -; Genomic_DNA.
DR EMBL; CH471131; EAW82601.1; -; Genomic_DNA.
DR EMBL; BC011655; AAH11655.1; -; mRNA.
DR EMBL; BC053320; AAH53320.1; -; mRNA.
DR RefSeq; NP_001012632.1; NM_001012614.1.
DR RefSeq; NP_001319.1; NM_001328.2.
DR UniGene; Hs.208597; -.
DR PDB; 1MX3; X-ray; 1.95 A; A=28-353.
DR PDBsum; 1MX3; -.
DR ProteinModelPortal; Q13363; -.
DR SMR; Q13363; 28-352.
DR DIP; DIP-24245N; -.
DR IntAct; Q13363; 25.
DR MINT; MINT-94454; -.
DR STRING; 9606.ENSP00000290921; -.
DR PhosphoSite; Q13363; -.
DR DMDM; 6014741; -.
DR PaxDb; Q13363; -.
DR PRIDE; Q13363; -.
DR DNASU; 1487; -.
DR Ensembl; ENST00000290921; ENSP00000290921; ENSG00000159692.
DR Ensembl; ENST00000382952; ENSP00000372411; ENSG00000159692.
DR GeneID; 1487; -.
DR KEGG; hsa:1487; -.
DR UCSC; uc003gcv.1; human.
DR CTD; 1487; -.
DR GeneCards; GC04M001205; -.
DR HGNC; HGNC:2494; CTBP1.
DR HPA; CAB004217; -.
DR HPA; HPA018987; -.
DR HPA; HPA044971; -.
DR MIM; 602618; gene.
DR neXtProt; NX_Q13363; -.
DR PharmGKB; PA26995; -.
DR eggNOG; COG0111; -.
DR HOGENOM; HOG000136701; -.
DR HOVERGEN; HBG001898; -.
DR InParanoid; Q13363; -.
DR KO; K04496; -.
DR OMA; DRDHPSD; -.
DR OrthoDB; EOG761BT9; -.
DR PhylomeDB; Q13363; -.
DR SignaLink; Q13363; -.
DR ChiTaRS; CTBP1; human.
DR EvolutionaryTrace; Q13363; -.
DR GeneWiki; CTBP1; -.
DR GenomeRNAi; 1487; -.
DR NextBio; 6105; -.
DR PRO; PR:Q13363; -.
DR ArrayExpress; Q13363; -.
DR Bgee; Q13363; -.
DR CleanEx; HS_CTBP1; -.
DR Genevestigator; Q13363; -.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005667; C:transcription factor complex; IEA:Ensembl.
DR GO; GO:0017053; C:transcriptional repressor complex; ISS:UniProtKB.
DR GO; GO:0051287; F:NAD binding; ISS:UniProtKB.
DR GO; GO:0016616; F:oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor; IEA:InterPro.
DR GO; GO:0008022; F:protein C-terminus binding; TAS:ProtInc.
DR GO; GO:0019904; F:protein domain specific binding; IDA:BHF-UCL.
DR GO; GO:0001106; F:RNA polymerase II transcription corepressor activity; IDA:BHF-UCL.
DR GO; GO:0003700; F:sequence-specific DNA binding transcription factor activity; IEA:Ensembl.
DR GO; GO:0007030; P:Golgi organization; IEA:Ensembl.
DR GO; GO:0019048; P:modulation by virus of host morphology or physiology; IEA:UniProtKB-KW.
DR GO; GO:0008285; P:negative regulation of cell proliferation; TAS:ProtInc.
DR GO; GO:0090241; P:negative regulation of histone H4 acetylation; IMP:BHF-UCL.
DR GO; GO:0031065; P:positive regulation of histone deacetylation; IMP:BHF-UCL.
DR GO; GO:0006468; P:protein phosphorylation; TAS:ProtInc.
DR GO; GO:0051726; P:regulation of cell cycle; IMP:BHF-UCL.
DR GO; GO:0034401; P:regulation of transcription by chromatin organization; IMP:BHF-UCL.
DR GO; GO:0019079; P:viral genome replication; TAS:ProtInc.
DR GO; GO:0050872; P:white fat cell differentiation; ISS:UniProtKB.
DR Gene3D; 3.40.50.720; -; 2.
DR InterPro; IPR006139; D-isomer_2_OHA_DH_cat_dom.
DR InterPro; IPR006140; D-isomer_2_OHA_DH_NAD-bd.
DR InterPro; IPR016040; NAD(P)-bd_dom.
DR Pfam; PF00389; 2-Hacid_dh; 1.
DR Pfam; PF02826; 2-Hacid_dh_C; 1.
DR PROSITE; PS00065; D_2_HYDROXYACID_DH_1; 1.
DR PROSITE; PS00670; D_2_HYDROXYACID_DH_2; FALSE_NEG.
DR PROSITE; PS00671; D_2_HYDROXYACID_DH_3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ADP-ribosylation; Alternative splicing;
KW Complete proteome; Cytoplasm; Differentiation;
KW Direct protein sequencing; Host-virus interaction; Isopeptide bond;
KW NAD; Nucleus; Oxidoreductase; Phosphoprotein; Reference proteome;
KW Repressor; Transcription; Transcription regulation; Ubl conjugation.
FT CHAIN 1 440 C-terminal-binding protein 1.
FT /FTId=PRO_0000076041.
FT NP_BIND 180 185 NAD (By similarity).
FT NP_BIND 237 243 NAD (By similarity).
FT NP_BIND 264 266 NAD (By similarity).
FT NP_BIND 315 318 NAD (By similarity).
FT REGION 1 70 Interaction with GLIS2 1 (By similarity).
FT REGION 288 360 Interaction with GLIS2 2 (By similarity).
FT ACT_SITE 266 266 By similarity.
FT ACT_SITE 295 295 By similarity.
FT ACT_SITE 315 315 Proton donor (By similarity).
FT BINDING 100 100 NAD (By similarity).
FT BINDING 204 204 NAD (By similarity).
FT BINDING 290 290 NAD (By similarity).
FT MOD_RES 300 300 Phosphoserine.
FT MOD_RES 422 422 Phosphoserine; by HIPK2.
FT CROSSLNK 428 428 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in SUMO).
FT VAR_SEQ 1 13 MGSSHLLNKGLPL -> MS (in isoform 2).
FT /FTId=VSP_043305.
FT MUTAGEN 134 134 C->A: Strongly reduces E1A binding; when
FT associated with A-138; A-141 and A-150.
FT MUTAGEN 138 138 N->A: Strongly reduces E1A binding; when
FT associated with A-134; A-141 and A-150.
FT MUTAGEN 141 142 RR->AA: Strongly reduces E1A binding;
FT when associated with A-163 and A-171.
FT MUTAGEN 141 141 R->A: Strongly reduces E1A binding; when
FT associated with A-134; A-138 and A-150.
FT MUTAGEN 150 150 L->A: Strongly reduces E1A binding; when
FT associated with A-134; A-138 and A-141.
FT MUTAGEN 163 163 R->A: Strongly reduces E1A binding; when
FT associated with A-141; A-142 and A-171.
FT MUTAGEN 171 171 R->A: Strongly reduces E1A binding; when
FT associated with A-141; A-142 and A-163.
FT MUTAGEN 181 181 G->V: Strongly reduces E1A binding; when
FT associated with V-183 and A-204.
FT MUTAGEN 183 183 G->V: Strongly reduces E1A binding; when
FT associated with V-181 and A-204.
FT MUTAGEN 204 204 D->A: Strongly reduces E1A binding; when
FT associated with V-181 and V-183.
FT MUTAGEN 266 266 R->A: Strongly reduces E1A binding; when
FT associated with A-290; A-295 and A-315.
FT MUTAGEN 290 290 D->A: Strongly reduces E1A binding; when
FT associated with A-266; A-295 and A-315.
FT MUTAGEN 295 295 E->A: Strongly reduces E1A binding; when
FT associated with A-266; A-290 and A-315.
FT MUTAGEN 315 315 H->A: Strongly reduces E1A binding; when
FT associated with A-266; A-290 and A-295.
FT MUTAGEN 422 422 S->A: Abolishes phosphorylation by HIPK2
FT and prevents UV-induced clearance.
FT STRAND 29 34
FT TURN 39 41
FT HELIX 42 45
FT TURN 46 48
FT STRAND 50 53
FT HELIX 59 61
FT HELIX 64 69
FT STRAND 70 75
FT STRAND 77 79
FT HELIX 83 86
FT STRAND 94 100
FT HELIX 107 112
FT STRAND 116 118
FT HELIX 125 141
FT HELIX 143 151
FT HELIX 159 165
FT TURN 166 168
FT STRAND 176 180
FT HELIX 184 194
FT TURN 195 197
FT STRAND 199 203
FT HELIX 211 215
FT HELIX 223 229
FT STRAND 231 235
FT STRAND 246 248
FT HELIX 249 252
FT STRAND 259 263
FT HELIX 272 280
FT STRAND 283 290
FT STRAND 293 296
FT TURN 303 306
FT STRAND 308 312
FT HELIX 321 340
FT TURN 343 346
FT STRAND 348 350
SQ SEQUENCE 440 AA; 47535 MW; F071DD30B385603F CRC64;
MGSSHLLNKG LPLGVRPPIM NGPLHPRPLV ALLDGRDCTV EMPILKDVAT VAFCDAQSTQ
EIHEKVLNEA VGALMYHTIT LTREDLEKFK ALRIIVRIGS GFDNIDIKSA GDLGIAVCNV
PAASVEETAD STLCHILNLY RRATWLHQAL REGTRVQSVE QIREVASGAA RIRGETLGII
GLGRVGQAVA LRAKAFGFNV LFYDPYLSDG VERALGLQRV STLQDLLFHS DCVTLHCGLN
EHNHHLINDF TVKQMRQGAF LVNTARGGLV DEKALAQALK EGRIRGAALD VHESEPFSFS
QGPLKDAPNL ICTPHAAWYS EQASIEMREE AAREIRRAIT GRIPDSLKNC VNKDHLTAAT
HWASMDPAVV HPELNGAAYR YPPGVVGVAP TGIPAAVEGI VPSAMSLSHG LPPVAHPPHA
PSPGQTVKPE ADRDHASDQL
//
ID CTBP1_HUMAN Reviewed; 440 AA.
AC Q13363; Q4W5N3; Q7Z2Q5;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
read moreDT 15-JUL-1999, sequence version 2.
DT 22-JAN-2014, entry version 152.
DE RecName: Full=C-terminal-binding protein 1;
DE Short=CtBP1;
DE EC=1.1.1.-;
GN Name=CTBP1; Synonyms=CTBP;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 98-108,
RP AND INTERACTION WITH RBBP8 AND ADENOVIRUS E1A.
RC TISSUE=B-cell, and Cervix carcinoma;
RX PubMed=7479821; DOI=10.1073/pnas.92.23.10467;
RA Schaeper U., Boyd J.M., Verma S., Uhlmann E., Subramanian T.,
RA Chinnadurai G.;
RT "Molecular cloning and characterization of a cellular phosphoprotein
RT that interacts with a conserved C-terminal domain of adenovirus E1A
RT involved in negative modulation of oncogenic transformation.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:10467-10471(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SEQUENCE REVISION, AND
RP FUNCTION.
RX PubMed=9858600;
RA Sewalt R.G.A.B., Gunster M.J., van der Vlag J., Satijn D.P.E.,
RA Otte A.P.;
RT "C-terminal binding protein is a transcriptional repressor that
RT interacts with a specific class of vertebrate polycomb proteins.";
RL Mol. Cell. Biol. 19:777-787(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H.,
RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
RA Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N.,
RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
RA McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D.,
RA Waterston R.H., Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2
RT and 4.";
RL Nature 434:724-731(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain, and Lung;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP INTERACTION WITH ADENOVIRUS E1A, AND PHOSPHORYLATION.
RX PubMed=8440238;
RA Boyd J.M., Subramanian T., Schaeper U., la Regina M., Bayley S.,
RA Chinnadurai G.;
RT "A region in the C-terminus of adenovirus 2/5 E1a protein is required
RT for association with a cellular phosphoprotein and important for the
RT negative modulation of T24-ras mediated transformation, tumorigenesis
RT and metastasis.";
RL EMBO J. 12:469-478(1993).
RN [7]
RP INTERACTION WITH MECOM.
RX PubMed=11568182; DOI=10.1074/jbc.M106733200;
RA Chakraborty S., Senyuk V., Sitailo S., Chi Y., Nucifora G.;
RT "Interaction of EVI1 with cAMP-responsive element-binding protein-
RT binding protein (CBP) and p300/CBP-associated factor (P/CAF) results
RT in reversible acetylation of EVI1 and in co-localization in nuclear
RT speckles.";
RL J. Biol. Chem. 276:44936-44943(2001).
RN [8]
RP INTERACTION WITH EBV EBNA6.
RX PubMed=11462050; DOI=10.1128/JVI.75.16.7749-7755.2001;
RA Touitou R., Hickabottom M., Parker G., Crook T., Allday M.J.;
RT "Physical and functional interactions between the corepressor CtBP and
RT the Epstein-Barr virus nuclear antigen EBNA3C.";
RL J. Virol. 75:7749-7755(2001).
RN [9]
RP INTERACTION WITH NRIP1.
RX PubMed=11509661; DOI=10.1128/MCB.21.18.6181-6188.2001;
RA Vo N., Fjeld C., Goodman R.H.;
RT "Acetylation of nuclear hormone receptor-interacting protein RIP140
RT regulates binding of the transcriptional corepressor CtBP.";
RL Mol. Cell. Biol. 21:6181-6188(2001).
RN [10]
RP INTERACTION WITH EBV EBNA3.
RX PubMed=12372828; DOI=10.1074/jbc.M208116200;
RA Hickabottom M., Parker G.A., Freemont P., Crook T., Allday M.J.;
RT "Two nonconsensus sites in the Epstein-Barr virus oncoprotein EBNA3A
RT cooperate to bind the co-repressor carboxyl-terminal-binding protein
RT (CtBP).";
RL J. Biol. Chem. 277:47197-47204(2002).
RN [11]
RP SUMOYLATION AT LYS-428, AND SUBCELLULAR LOCATION.
RX PubMed=12679040; DOI=10.1016/S0092-8674(03)00159-4;
RA Kagey M.H., Melhuish T.A., Wotton D.;
RT "The polycomb protein Pc2 is a SUMO E3.";
RL Cell 113:127-137(2003).
RN [12]
RP INTERACTION WITH HIPK2, PHOSPHORYLATION AT SER-422, AND MUTAGENESIS OF
RP SER-422.
RX PubMed=14567915; DOI=10.1016/S0092-8674(03)00802-X;
RA Zhang Q., Yoshimatsu Y., Hildebrand J., Frisch S.M., Goodman R.H.;
RT "Homeodomain interacting protein kinase 2 promotes apoptosis by
RT downregulating the transcriptional corepressor CtBP.";
RL Cell 115:177-186(2003).
RN [13]
RP FUNCTION IN TRANSCRIPTIONAL REPRESSION, AND INTERACTION WITH PNN.
RX PubMed=15542832; DOI=10.1128/MCB.24.23.10223-10235.2004;
RA Alpatov R., Munguba G.C., Caton P., Joo J.H., Shi Y., Shi Y.,
RA Hunt M.E., Sugrue S.P.;
RT "Nuclear speckle-associated protein Pnn/DRS binds to the
RT transcriptional corepressor CtBP and relieves CtBP-mediated repression
RT of the E-cadherin gene.";
RL Mol. Cell. Biol. 24:10223-10235(2004).
RN [14]
RP INTERACTION WITH NRIP1.
RX PubMed=15060175; DOI=10.1093/nar/gkh524;
RA Castet A., Boulahtouf A., Versini G., Bonnet S., Augereau P.,
RA Vignon F., Khochbin S., Jalaguier S., Cavailles V.;
RT "Multiple domains of the receptor-interacting protein 140 contribute
RT to transcription inhibition.";
RL Nucleic Acids Res. 32:1957-1966(2004).
RN [15]
RP INTERACTION WITH ZFHX1B.
RX PubMed=16061479; DOI=10.1074/jbc.M504477200;
RA Long J., Zuo D., Park M.;
RT "Pc2-mediated sumoylation of Smad-interacting protein 1 attenuates
RT transcriptional repression of E-cadherin.";
RL J. Biol. Chem. 280:35477-35489(2005).
RN [16]
RP INTERACTION WITH MECOM.
RX PubMed=15897867; DOI=10.1038/sj.onc.1208754;
RA Nitta E., Izutsu K., Yamaguchi Y., Imai Y., Ogawa S., Chiba S.,
RA Kurokawa M., Hirai H.;
RT "Oligomerization of Evi-1 regulated by the PR domain contributes to
RT recruitment of corepressor CtBP.";
RL Oncogene 24:6165-6173(2005).
RN [17]
RP INTERACTION WITH FOXP1.
RX PubMed=16609867; DOI=10.1007/s00427-006-0073-8;
RA Schoen C., Wochnik A., Roessner A., Donow C., Knoechel W.;
RT "The FoxP subclass in Xenopus laevis development.";
RL Dev. Genes Evol. 216:641-646(2006).
RN [18]
RP INTERACTION WITH WIZ.
RX PubMed=16702210; DOI=10.1074/jbc.M603087200;
RA Ueda J., Tachibana M., Ikura T., Shinkai Y.;
RT "Zinc finger protein Wiz links G9a/GLP histone methyltransferases to
RT the co-repressor molecule CtBP.";
RL J. Biol. Chem. 281:20120-20128(2006).
RN [19]
RP INTERACTION WITH ZNF366.
RX PubMed=17085477; DOI=10.1093/nar/gkl875;
RA Lopez-Garcia J., Periyasamy M., Thomas R.S., Christian M., Leao M.,
RA Jat P., Kindle K.B., Heery D.M., Parker M.G., Buluwela L.,
RA Kamalati T., Ali S.;
RT "ZNF366 is an estrogen receptor corepressor that acts through CtBP and
RT histone deacetylases.";
RL Nucleic Acids Res. 34:6126-6136(2006).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-300, AND MASS
RP SPECTROMETRY.
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III,
RA Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N.,
RA Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [21]
RP FUNCTION AS COREPRESSOR, INTERACTION WITH BCL6, AND TISSUE
RP SPECIFICITY.
RX PubMed=18212045; DOI=10.1128/MCB.01400-07;
RA Mendez L.M., Polo J.M., Yu J.J., Krupski M., Ding B.B., Melnick A.,
RA Ye B.H.;
RT "CtBP is an essential corepressor for BCL6 autoregulation.";
RL Mol. Cell. Biol. 28:2175-2186(2008).
RN [22]
RP FUNCTION, AND INTERACTION WITH SATB1.
RX PubMed=19103759; DOI=10.1128/MCB.00822-08;
RA Purbey P.K., Singh S., Notani D., Kumar P.P., Limaye A.S., Galande S.;
RT "Acetylation-dependent interaction of SATB1 and CtBP1 mediates
RT transcriptional repression by SATB1.";
RL Mol. Cell. Biol. 29:1321-1337(2009).
RN [23]
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.,
RA Buerckstuemmer T., 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 [24]
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 28-353 IN COMPLEX WITH NAD,
RP FUNCTION, COFACTOR, MUTAGENESIS OF CYS-134; ASN-138; ARG-141;
RP 141-ARG-ARG-142; LEU-150; ARG-163; ARG-171; GLY-181; GLY-183; ASP-204;
RP ARG-266; ASP-290; GLU-295 AND HIS-315, AND DIMERIZATION.
RX PubMed=12419229; DOI=10.1016/S1097-2765(02)00650-0;
RA Kumar V., Carlson J.E., Ohgi K.A., Edwards T.A., Rose D.W.,
RA Escalante C.R., Rosenfeld M.G., Aggarwal A.K.;
RT "Transcription corepressor CtBP is an NAD(+)-regulated
RT dehydrogenase.";
RL Mol. Cell 10:857-869(2002).
CC -!- FUNCTION: Corepressor targeting diverse transcription regulators
CC such as GLIS2 or BCL6. Has dehydrogenase activity. Involved in
CC controlling the equilibrium between tubular and stacked structures
CC in the Golgi complex. Functions in brown adipose tissue (BAT)
CC differentiation.
CC -!- COFACTOR: NAD. Required for efficient interaction with E1A.
CC Cofactor binding induces a conformation change.
CC -!- SUBUNIT: Homo- or heterodimer. Heterodimer with CTBP2. Interacts
CC with PRDM16; the interaction represses white adipose tissue (WAT)-
CC specific genes expression. Interacts with GLIS2, FOXP2, HDAC4,
CC HDAC5, HDAC9 and ZNF217. Interacts with adenovirus E1A protein
CC (via its C-terminus); the interaction disrupts the interaction of
CC CTBP1 with RBBP8. Interacts with Epstein-Barr virus EBNA3 and
CC EBNA6. Interacts with ELK3 (via its PXDLS motif). Interacts with
CC RBBP8 (via its PXDLS motif); the interaction is disrupted by
CC binding to adenovirus E1A. Interacts with FOXP1, HIPK2, PNN,
CC NRIP1, MECOM, ZNF366, ZFHX1B and WIZ. Interaction with SATB1 (non-
CC acetylated form); the interaction stabilizes its attachment to DNA
CC and promotes transcription repression. Interacts with BCL6; the
CC interaction is required for BCL6 transcriptional autoinhibition
CC and inhibition of some BCL6 target genes.
CC -!- INTERACTION:
CC Q9BXL5:HEMGN; NbExp=2; IntAct=EBI-908846, EBI-3916399;
CC Q14526:HIC1; NbExp=4; IntAct=EBI-908846, EBI-2507362;
CC O43474:KLF4; NbExp=4; IntAct=EBI-908846, EBI-7232405;
CC Q96EK4:THAP11; NbExp=2; IntAct=EBI-908846, EBI-1790529;
CC A2APF7:Zbp1 (xeno); NbExp=2; IntAct=EBI-908846, EBI-6115394;
CC Q8N895:ZNF366; NbExp=5; IntAct=EBI-908846, EBI-2813661;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q13363-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q13363-2; Sequence=VSP_043305;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Expressed in germinal center B-cells.
CC -!- PTM: The level of phosphorylation appears to be regulated during
CC the cell cycle. Phosphorylation by HIPK2 on Ser-422 induces
CC proteasomal degradation.
CC -!- PTM: ADP-ribosylated; when cells are exposed to brefeldin A (By
CC similarity).
CC -!- PTM: Sumoylation on Lys-428 is promoted by the E3 SUMO-protein
CC ligase CBX4.
CC -!- SIMILARITY: Belongs to the D-isomer specific 2-hydroxyacid
CC dehydrogenase family.
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DR EMBL; U37408; AAC62822.1; -; mRNA.
DR EMBL; AF091555; AAD14597.1; -; mRNA.
DR EMBL; AC092535; AAY40989.1; -; Genomic_DNA.
DR EMBL; CH471131; EAW82599.1; -; Genomic_DNA.
DR EMBL; CH471131; EAW82600.1; -; Genomic_DNA.
DR EMBL; CH471131; EAW82601.1; -; Genomic_DNA.
DR EMBL; BC011655; AAH11655.1; -; mRNA.
DR EMBL; BC053320; AAH53320.1; -; mRNA.
DR RefSeq; NP_001012632.1; NM_001012614.1.
DR RefSeq; NP_001319.1; NM_001328.2.
DR UniGene; Hs.208597; -.
DR PDB; 1MX3; X-ray; 1.95 A; A=28-353.
DR PDBsum; 1MX3; -.
DR ProteinModelPortal; Q13363; -.
DR SMR; Q13363; 28-352.
DR DIP; DIP-24245N; -.
DR IntAct; Q13363; 25.
DR MINT; MINT-94454; -.
DR STRING; 9606.ENSP00000290921; -.
DR PhosphoSite; Q13363; -.
DR DMDM; 6014741; -.
DR PaxDb; Q13363; -.
DR PRIDE; Q13363; -.
DR DNASU; 1487; -.
DR Ensembl; ENST00000290921; ENSP00000290921; ENSG00000159692.
DR Ensembl; ENST00000382952; ENSP00000372411; ENSG00000159692.
DR GeneID; 1487; -.
DR KEGG; hsa:1487; -.
DR UCSC; uc003gcv.1; human.
DR CTD; 1487; -.
DR GeneCards; GC04M001205; -.
DR HGNC; HGNC:2494; CTBP1.
DR HPA; CAB004217; -.
DR HPA; HPA018987; -.
DR HPA; HPA044971; -.
DR MIM; 602618; gene.
DR neXtProt; NX_Q13363; -.
DR PharmGKB; PA26995; -.
DR eggNOG; COG0111; -.
DR HOGENOM; HOG000136701; -.
DR HOVERGEN; HBG001898; -.
DR InParanoid; Q13363; -.
DR KO; K04496; -.
DR OMA; DRDHPSD; -.
DR OrthoDB; EOG761BT9; -.
DR PhylomeDB; Q13363; -.
DR SignaLink; Q13363; -.
DR ChiTaRS; CTBP1; human.
DR EvolutionaryTrace; Q13363; -.
DR GeneWiki; CTBP1; -.
DR GenomeRNAi; 1487; -.
DR NextBio; 6105; -.
DR PRO; PR:Q13363; -.
DR ArrayExpress; Q13363; -.
DR Bgee; Q13363; -.
DR CleanEx; HS_CTBP1; -.
DR Genevestigator; Q13363; -.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005667; C:transcription factor complex; IEA:Ensembl.
DR GO; GO:0017053; C:transcriptional repressor complex; ISS:UniProtKB.
DR GO; GO:0051287; F:NAD binding; ISS:UniProtKB.
DR GO; GO:0016616; F:oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor; IEA:InterPro.
DR GO; GO:0008022; F:protein C-terminus binding; TAS:ProtInc.
DR GO; GO:0019904; F:protein domain specific binding; IDA:BHF-UCL.
DR GO; GO:0001106; F:RNA polymerase II transcription corepressor activity; IDA:BHF-UCL.
DR GO; GO:0003700; F:sequence-specific DNA binding transcription factor activity; IEA:Ensembl.
DR GO; GO:0007030; P:Golgi organization; IEA:Ensembl.
DR GO; GO:0019048; P:modulation by virus of host morphology or physiology; IEA:UniProtKB-KW.
DR GO; GO:0008285; P:negative regulation of cell proliferation; TAS:ProtInc.
DR GO; GO:0090241; P:negative regulation of histone H4 acetylation; IMP:BHF-UCL.
DR GO; GO:0031065; P:positive regulation of histone deacetylation; IMP:BHF-UCL.
DR GO; GO:0006468; P:protein phosphorylation; TAS:ProtInc.
DR GO; GO:0051726; P:regulation of cell cycle; IMP:BHF-UCL.
DR GO; GO:0034401; P:regulation of transcription by chromatin organization; IMP:BHF-UCL.
DR GO; GO:0019079; P:viral genome replication; TAS:ProtInc.
DR GO; GO:0050872; P:white fat cell differentiation; ISS:UniProtKB.
DR Gene3D; 3.40.50.720; -; 2.
DR InterPro; IPR006139; D-isomer_2_OHA_DH_cat_dom.
DR InterPro; IPR006140; D-isomer_2_OHA_DH_NAD-bd.
DR InterPro; IPR016040; NAD(P)-bd_dom.
DR Pfam; PF00389; 2-Hacid_dh; 1.
DR Pfam; PF02826; 2-Hacid_dh_C; 1.
DR PROSITE; PS00065; D_2_HYDROXYACID_DH_1; 1.
DR PROSITE; PS00670; D_2_HYDROXYACID_DH_2; FALSE_NEG.
DR PROSITE; PS00671; D_2_HYDROXYACID_DH_3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ADP-ribosylation; Alternative splicing;
KW Complete proteome; Cytoplasm; Differentiation;
KW Direct protein sequencing; Host-virus interaction; Isopeptide bond;
KW NAD; Nucleus; Oxidoreductase; Phosphoprotein; Reference proteome;
KW Repressor; Transcription; Transcription regulation; Ubl conjugation.
FT CHAIN 1 440 C-terminal-binding protein 1.
FT /FTId=PRO_0000076041.
FT NP_BIND 180 185 NAD (By similarity).
FT NP_BIND 237 243 NAD (By similarity).
FT NP_BIND 264 266 NAD (By similarity).
FT NP_BIND 315 318 NAD (By similarity).
FT REGION 1 70 Interaction with GLIS2 1 (By similarity).
FT REGION 288 360 Interaction with GLIS2 2 (By similarity).
FT ACT_SITE 266 266 By similarity.
FT ACT_SITE 295 295 By similarity.
FT ACT_SITE 315 315 Proton donor (By similarity).
FT BINDING 100 100 NAD (By similarity).
FT BINDING 204 204 NAD (By similarity).
FT BINDING 290 290 NAD (By similarity).
FT MOD_RES 300 300 Phosphoserine.
FT MOD_RES 422 422 Phosphoserine; by HIPK2.
FT CROSSLNK 428 428 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in SUMO).
FT VAR_SEQ 1 13 MGSSHLLNKGLPL -> MS (in isoform 2).
FT /FTId=VSP_043305.
FT MUTAGEN 134 134 C->A: Strongly reduces E1A binding; when
FT associated with A-138; A-141 and A-150.
FT MUTAGEN 138 138 N->A: Strongly reduces E1A binding; when
FT associated with A-134; A-141 and A-150.
FT MUTAGEN 141 142 RR->AA: Strongly reduces E1A binding;
FT when associated with A-163 and A-171.
FT MUTAGEN 141 141 R->A: Strongly reduces E1A binding; when
FT associated with A-134; A-138 and A-150.
FT MUTAGEN 150 150 L->A: Strongly reduces E1A binding; when
FT associated with A-134; A-138 and A-141.
FT MUTAGEN 163 163 R->A: Strongly reduces E1A binding; when
FT associated with A-141; A-142 and A-171.
FT MUTAGEN 171 171 R->A: Strongly reduces E1A binding; when
FT associated with A-141; A-142 and A-163.
FT MUTAGEN 181 181 G->V: Strongly reduces E1A binding; when
FT associated with V-183 and A-204.
FT MUTAGEN 183 183 G->V: Strongly reduces E1A binding; when
FT associated with V-181 and A-204.
FT MUTAGEN 204 204 D->A: Strongly reduces E1A binding; when
FT associated with V-181 and V-183.
FT MUTAGEN 266 266 R->A: Strongly reduces E1A binding; when
FT associated with A-290; A-295 and A-315.
FT MUTAGEN 290 290 D->A: Strongly reduces E1A binding; when
FT associated with A-266; A-295 and A-315.
FT MUTAGEN 295 295 E->A: Strongly reduces E1A binding; when
FT associated with A-266; A-290 and A-315.
FT MUTAGEN 315 315 H->A: Strongly reduces E1A binding; when
FT associated with A-266; A-290 and A-295.
FT MUTAGEN 422 422 S->A: Abolishes phosphorylation by HIPK2
FT and prevents UV-induced clearance.
FT STRAND 29 34
FT TURN 39 41
FT HELIX 42 45
FT TURN 46 48
FT STRAND 50 53
FT HELIX 59 61
FT HELIX 64 69
FT STRAND 70 75
FT STRAND 77 79
FT HELIX 83 86
FT STRAND 94 100
FT HELIX 107 112
FT STRAND 116 118
FT HELIX 125 141
FT HELIX 143 151
FT HELIX 159 165
FT TURN 166 168
FT STRAND 176 180
FT HELIX 184 194
FT TURN 195 197
FT STRAND 199 203
FT HELIX 211 215
FT HELIX 223 229
FT STRAND 231 235
FT STRAND 246 248
FT HELIX 249 252
FT STRAND 259 263
FT HELIX 272 280
FT STRAND 283 290
FT STRAND 293 296
FT TURN 303 306
FT STRAND 308 312
FT HELIX 321 340
FT TURN 343 346
FT STRAND 348 350
SQ SEQUENCE 440 AA; 47535 MW; F071DD30B385603F CRC64;
MGSSHLLNKG LPLGVRPPIM NGPLHPRPLV ALLDGRDCTV EMPILKDVAT VAFCDAQSTQ
EIHEKVLNEA VGALMYHTIT LTREDLEKFK ALRIIVRIGS GFDNIDIKSA GDLGIAVCNV
PAASVEETAD STLCHILNLY RRATWLHQAL REGTRVQSVE QIREVASGAA RIRGETLGII
GLGRVGQAVA LRAKAFGFNV LFYDPYLSDG VERALGLQRV STLQDLLFHS DCVTLHCGLN
EHNHHLINDF TVKQMRQGAF LVNTARGGLV DEKALAQALK EGRIRGAALD VHESEPFSFS
QGPLKDAPNL ICTPHAAWYS EQASIEMREE AAREIRRAIT GRIPDSLKNC VNKDHLTAAT
HWASMDPAVV HPELNGAAYR YPPGVVGVAP TGIPAAVEGI VPSAMSLSHG LPPVAHPPHA
PSPGQTVKPE ADRDHASDQL
//
MIM
602618
*RECORD*
*FIELD* NO
602618
*FIELD* TI
*602618 C-TERMINAL-BINDING PROTEIN 1; CTBP1
*FIELD* TX
CLONING
The E1a region of group C adenoviruses encodes 2 nearly identical
read moreproteins that are largely responsible for the oncogenic properties of
adenoviruses. Whereas the N-terminal half of these E1A proteins is
sufficient for transformation, the C-terminal half appears to modulate
transformation, tumorigenesis, and metastasis negatively. Boyd et al.
(1993) purified a HeLa cell protein, designated CTBP1, that specifically
binds to the C-terminal half of E1A proteins. CTBP1 is a phosphoprotein
that migrates as a 48-kD doublet by SDS-PAGE. Katsanis and Fisher (1998)
suggested that the doublet consists of CTBP1 and the closely related
CTBP2 (602619).
Schaeper et al. (1995) independently isolated a CTBP1 cDNA from a B-cell
library. The predicted 439-amino acid sequence contains the sequences of
2 peptides prepared from purified CTBP1. The authors
coimmunoprecipitated CTPB1 and an E1A protein from extracts of mammalian
cells that were expressing both proteins.
Furusawa et al. (1999) identified the mouse homologs of CTBP1 and CTBP2
in a yeast 2-hybrid screen for proteins that interact with delta-EF1
(TCF8; 189909), a transcriptional repressor that binds the E2-box
(CACCTG) and related sequences. Using 2-hybrid and direct binding
assays, they concluded that CtBP1 binds to the short medial portion of
delta-EF1 containing the PLDLSL motif. In cotransfection experiments,
they observed that CtBP1 enhanced the transrepression activity of
delta-EF1. Using Northern blot analysis and in situ hybridization with
mouse embryos, Furusawa et al. (1999) detected CtBP1 expression
throughout developmental stages and in a wide range of adult tissues.
CtBP1 and CtBP2 expression correlates with delta-EF1 expression. The
authors hypothesized that CtBP1 and CtBP2 function as corepressors of
delta-EF1 action.
GENE FUNCTION
Polycomb (Pc) is part of a Pc group (PcG) protein complex that is
involved in repression of gene activity during Drosophila and vertebrate
development. Using a yeast 2-hybrid assay, Sewalt et al. (1999) found
that Xenopus Ctbp1 interacts with Xenopus Pc and that human CTBP2
interacts with PC2 (603079), a human Pc homolog. Immunofluorescence
studies indicated that CTBP1 and CTBP2 partially colocalize with PC2 in
large PcG domains in interphase nuclei. As with PC2, chimeric LexA-CTBP2
and LexA-CTBP1 proteins repressed gene activity when targeted to a
reporter gene. Sewalt et al. (1999) suggested that PC2-mediated
repression of gene expression involves an association with corepressors
such as the CTBPs. They speculated that the interference of the
adenoviral E1A protein with the transcription machinery of the infected
cell may involve interference with PcG-mediated repression through
disruption of the CTBP-PcG interaction. Northern blot analysis revealed
that the CTBP1 gene was expressed as a 2.4-kb mRNA in all human tissues
tested.
Pc2 recruits the transcriptional corepressor CTBP to PcG bodies. Kagey
et al. (2003) showed that CTBP is sumoylated at a single lysine. In
vitro, CTBP sumoylation minimally required the SUMO E1 and E2 (UBC9;
601661) and SUMO1 (601912). However, Pc2 dramatically enhanced CTBP
sumoylation. The authors proposed that, in vivo, this is likely due to
the ability of Pc2 to recruit both CTBP and UBC9 to PcG bodies, thereby
bringing together substrate and E2 and stimulating the transfer of SUMO
to CTBP. These results demonstrated that Pc2 is a SUMO E3 and suggested
that PcG bodies may be sumoylation centers.
Zhang et al. (2002) demonstrated that CTBP binding to cellular and viral
transcriptional repressors is regulated by NAD+ and NADH, with NADH
being 2 to 3 orders of magnitude more effective. Levels of free nuclear
nicotinamide adenine dinucleotides, determined using 2-photon
microscopy, corresponded to the levels required for half-maximal CTBP
binding and were considerably lower than those previously reported.
Agents capable of increasing NADH levels stimulated CTBP binding to its
partners in vivo and potentiated CTBP-mediated repression. Zhang et al.
(2002) proposed that this ability to detect changes in nuclear NAD+/NADH
ratio allows CTBP to serve as a redox sensor for transcription.
Kumar et al. (2002) reported biochemical and crystallographic studies
that revealed that CTBP1 is a functional dehydrogenase. In addition,
both a cofactor-dependent conformational change, with NAD+ and NADH
being equivalently effective, and the active site residues were linked
to the binding of the PXDLS consensus recognition motif on repressors,
such as E1A and RIP140 (602490). They concluded that CTBP1 is an
NAD(+)-regulated component of critical complexes for specific repression
events in cells.
CTBP is recruited to DNA by transcription factors that contain a PXDLS
motif. Shi et al. (2003) reported the identification of a CTBP complex
that contains the essential components for both gene targeting and
coordinated histone modifications, allowing for the effective repression
of genes targeted by CTBP. This complex has a molecular mass of about
1.3 to 1.5 million and contains CTBP1 and CTBP2 as well as G9A (604599),
EUHMT (607001), COREST (607675), HDAC1 (601241) and HDAC2 (605164),
NPAO, REBB1, ZNF217 (602967), and KIAA0222. Immunoprecipitation with G9A
antibodies brought down the same components as well as HPC2 (ELAC2;
605367). Shi et al. (2003) found that inhibiting the expression of CTBP
and its associated histone-modifying activities by RNA-interference
resulted in alterations of histone modifications at the promoter of the
tumor invasion suppressor gene E-cadherin (192090) and increased
promoter activity in a reporter assay.
By yeast 3-hybrid analysis, Zhang et al. (2003) found that mouse Hipk2
(606868) interacted with an E1A-Ctbp complex. Expression of Hipk2 or
exposure to ultraviolet (UV) irradiation reduced Ctbp levels via a
proteasome-mediated pathway. Coexpression of kinase-inactive Hipk2 or
small interfering RNA-mediated reduction in Hipk2 levels prevented the
UV effect. Mutation of Ctbp ser422 prevented phosphorylation as well as
UV- and Hipk2-directed Ctbp clearance. Deletion of Ctbp or reduction in
Ctbp levels promoted apoptosis in p53 (191170)-deficient cells.
Gallop et al. (2005) found that the lysophosphatidic acid
acyltransferase, or LPAAT, activity associated with CtBP/BARS (e.g.,
Weigert et al., 1999) is a copurification artifact.
Using a promoter pull-down assay followed by mass spectrometry analysis,
Flajollet et al. (2009) identified RREB1 (602209) as a protein that
bound the HLA-G (142871) promoter. RREB1 exerted repressive activity on
the promoter in HLA-G-negative cells that was mediated by recruitment of
HDAC1 and CTBP1 and/or CTBP2. The HLA-G promoter contains 3 RREB1 target
sites. Flajollet et al. (2009) proposed that the repressive activity of
RREB1 on the HLA-G promoter may be regulated by posttranslational
modifications governing its association with CTBP.
Deng et al. (2011) identified microRNA-137 (MIR137; 614304) as a
regulator of CTBP1 expression. Expression of MIR137 was inversely
correlated with that of CTBP1 in melanoma cell lines. The MIR137-binding
site in the 3-prime UTR of CTBP1 mRNA is conserved from human to
chicken. Pull-down assays revealed that MIR137 interacted with ARGO2
(EIF2C2; 606229) and CTBP1 mRNA. Cotransfection of MIR137 inhibited
expression of a reporter gene containing the CTBP1 3-prime UTR, but not
when the MIR137-binding site was deleted from the CTBP1 3-prime UTR.
Western blot and quantitative RT-PCR analyses showed that MIR137
expression in a melanoma cell line reduced CTBP1 protein levels and
increased expression of the CTBP1 target genes E-cadherin and BAX
(600040).
MAPPING
By PCR of a radiation hybrid panel, Katsanis and Fisher (1998) mapped
the CTBP1 gene to 4p16.
*FIELD* RF
1. Boyd, J. M.; Subramanian, T.; Schaeper, U.; La Regina, M.; Bayley,
S.; Chinnadurai, G.: A region in the C-terminus of adenovirus 2/5
E1a protein is required for association with a cellular phosphoprotein
and important for the negative modulation of T24-ras mediated transformation,
tumorigenesis and metastasis. EMBO J. 12: 469-478, 1993.
2. Deng, Y.; Deng, H.; Bi, F.; Liu, J.; Bemis, L. T.; Norris, D.;
Wang, X.-J.; Zhang, Q.: MicroRNA-137 targets carboxyl-terminal binding
protein 1 in melanoma cell lines. Int. J. Biol. Sci. 7: 133-137,
2011.
3. Flajollet, S.; Poras, I.; Carosella, E. D.; Moreau, P.: RREB-1
is a transcriptional repressor of HLA-G. J. Immun. 183: 6948-6959,
2009.
4. Furusawa, T.; Moribe, H.; Kondoh, H.; Higashi, Y.: Identification
of CtBP1 and CtBP2 as corepressors of zinc finger-homeodomain factor
delta-EF1. Molec. Cell. Biol. 19: 8581-8590, 1999.
5. Gallop, J. L.; Butler, P. J. G.; McMahon, H. T.: Endophilin and
CtBP/BARS are not acyl transferases in endocytosis or Golgi fission. Nature 438:
675-678, 2005.
6. Kagey, M. H.; Melhuish, T. A.; Wotton, D.: The polycomb protein
Pc2 is a SUMO E3. Cell 113: 127-137, 2003.
7. Katsanis, N.; Fisher, E. M. C.: A novel C-terminal binding protein
(CTBP2) is closely related to CTBP1, an adenovirus E1A-binding protein,
and maps to human chromosome 21q21.3. Genomics 47: 294-299, 1998.
8. Kumar, V.; Carlson, J. E. Ohgi, K. A.; Edwards, T. A.; Rose, D.
W.; Escalante, C. R.; Rosenfeld, M. G.; Aggarwal, A. K.: Transcription
corepressor CtBP is an NAD(+)-regulated dehydrogenase. Molec. Cell 10:
857-869, 2002.
9. Schaeper, U.; Boyd, J. M.; Verma, S.; Uhlmann, E.; Subramanian,
T.; Chinnadurai, G.: Molecular cloning and characterization of a
cellular phosphoprotein that interacts with a conserved C-terminal
domain of adenovirus E1A involved in negative modulation of oncogenic
transformation. Proc. Nat. Acad. Sci. 92: 10467-10471, 1995. Note:
Erratum: Proc. Nat. Acad. Sci. 95: 14584 only, 1998.
10. Sewalt, R. G. A. B.; Gunster, M. J.; van der Vlag, J.; Satijn,
D. P. E.; Otte, A. P.: C-terminal binding protein is a transcriptional
repressor that interacts with a specific class of vertebrate polycomb
proteins. Molec. Cell. Biol. 19: 777-787, 1999.
11. Shi, Y.; Sawada, J.; Sui, G.; Affar, E. B.; Whetstine, J. R.;
Lan, F.; Ogawa, H.; Luke, M. P.-S.; Nakatani, Y.; Shi, Y.: Coordinated
histone modifications mediated by a CtBP co-repressor complex. Nature 422:
735-738, 2003.
12. Weigert, R.; Silletta, M. G.; Spano, S.; Turacchio, G.; Cericola,
C.; Colanzi, A.; Senatore, S.; Mancini, R.; Polishchuk, E. V.; Salmona,
M.; Facchiano, F.; Burger, K. N. J.; Mironov, A.; Luini, A.; Corda,
D.: CtBP/BARS induces fission of Golgi membranes by acylating lysophosphatidic
acid. Nature 402: 429-433, 1999.
13. Zhang, Q.; Piston, D. W.; Goodman, R. H.: Regulation of corepressor
function by nuclear NADH. Science 295: 1895-1897, 2002.
14. Zhang, Q.; Yoshimatsu, Y.; Hildebrand, J.; Frisch, S. M.; Goodman,
R. H.: Homeodomain interacting protein kinase 2 promotes apoptosis
by downregulating the transcriptional corepressor CtBP. Cell 115:
177-186, 2003.
*FIELD* CN
Paul J. Converse - updated: 11/19/2012
Patricia A. Hartz - updated: 10/24/2011
Paul J. Converse - updated: 6/20/2006
Ada Hamosh - updated: 1/30/2006
Ada Hamosh - updated: 5/6/2003
Stylianos E. Antonarakis - updated: 5/2/2003
Stylianos E. Antonarakis - updated: 4/29/2003
Ada Hamosh - updated: 4/2/2002
Dawn Watkins-Chow - updated: 10/24/2001
Rebekah S. Rasooly - updated: 4/9/1999
*FIELD* CD
Rebekah S. Rasooly: 5/13/1998
*FIELD* ED
terry: 11/28/2012
mgross: 11/26/2012
terry: 11/19/2012
carol: 7/19/2012
mgross: 10/24/2011
carol: 12/26/2007
mgross: 6/20/2006
alopez: 2/1/2006
terry: 1/30/2006
mgross: 3/9/2005
alopez: 7/26/2004
terry: 7/26/2004
alopez: 9/30/2003
alopez: 5/8/2003
terry: 5/6/2003
mgross: 5/2/2003
mgross: 5/1/2003
terry: 4/29/2003
alopez: 4/5/2002
terry: 4/2/2002
carol: 10/24/2001
mgross: 4/12/1999
mgross: 4/9/1999
carol: 3/16/1999
psherman: 5/13/1998
*RECORD*
*FIELD* NO
602618
*FIELD* TI
*602618 C-TERMINAL-BINDING PROTEIN 1; CTBP1
*FIELD* TX
CLONING
The E1a region of group C adenoviruses encodes 2 nearly identical
read moreproteins that are largely responsible for the oncogenic properties of
adenoviruses. Whereas the N-terminal half of these E1A proteins is
sufficient for transformation, the C-terminal half appears to modulate
transformation, tumorigenesis, and metastasis negatively. Boyd et al.
(1993) purified a HeLa cell protein, designated CTBP1, that specifically
binds to the C-terminal half of E1A proteins. CTBP1 is a phosphoprotein
that migrates as a 48-kD doublet by SDS-PAGE. Katsanis and Fisher (1998)
suggested that the doublet consists of CTBP1 and the closely related
CTBP2 (602619).
Schaeper et al. (1995) independently isolated a CTBP1 cDNA from a B-cell
library. The predicted 439-amino acid sequence contains the sequences of
2 peptides prepared from purified CTBP1. The authors
coimmunoprecipitated CTPB1 and an E1A protein from extracts of mammalian
cells that were expressing both proteins.
Furusawa et al. (1999) identified the mouse homologs of CTBP1 and CTBP2
in a yeast 2-hybrid screen for proteins that interact with delta-EF1
(TCF8; 189909), a transcriptional repressor that binds the E2-box
(CACCTG) and related sequences. Using 2-hybrid and direct binding
assays, they concluded that CtBP1 binds to the short medial portion of
delta-EF1 containing the PLDLSL motif. In cotransfection experiments,
they observed that CtBP1 enhanced the transrepression activity of
delta-EF1. Using Northern blot analysis and in situ hybridization with
mouse embryos, Furusawa et al. (1999) detected CtBP1 expression
throughout developmental stages and in a wide range of adult tissues.
CtBP1 and CtBP2 expression correlates with delta-EF1 expression. The
authors hypothesized that CtBP1 and CtBP2 function as corepressors of
delta-EF1 action.
GENE FUNCTION
Polycomb (Pc) is part of a Pc group (PcG) protein complex that is
involved in repression of gene activity during Drosophila and vertebrate
development. Using a yeast 2-hybrid assay, Sewalt et al. (1999) found
that Xenopus Ctbp1 interacts with Xenopus Pc and that human CTBP2
interacts with PC2 (603079), a human Pc homolog. Immunofluorescence
studies indicated that CTBP1 and CTBP2 partially colocalize with PC2 in
large PcG domains in interphase nuclei. As with PC2, chimeric LexA-CTBP2
and LexA-CTBP1 proteins repressed gene activity when targeted to a
reporter gene. Sewalt et al. (1999) suggested that PC2-mediated
repression of gene expression involves an association with corepressors
such as the CTBPs. They speculated that the interference of the
adenoviral E1A protein with the transcription machinery of the infected
cell may involve interference with PcG-mediated repression through
disruption of the CTBP-PcG interaction. Northern blot analysis revealed
that the CTBP1 gene was expressed as a 2.4-kb mRNA in all human tissues
tested.
Pc2 recruits the transcriptional corepressor CTBP to PcG bodies. Kagey
et al. (2003) showed that CTBP is sumoylated at a single lysine. In
vitro, CTBP sumoylation minimally required the SUMO E1 and E2 (UBC9;
601661) and SUMO1 (601912). However, Pc2 dramatically enhanced CTBP
sumoylation. The authors proposed that, in vivo, this is likely due to
the ability of Pc2 to recruit both CTBP and UBC9 to PcG bodies, thereby
bringing together substrate and E2 and stimulating the transfer of SUMO
to CTBP. These results demonstrated that Pc2 is a SUMO E3 and suggested
that PcG bodies may be sumoylation centers.
Zhang et al. (2002) demonstrated that CTBP binding to cellular and viral
transcriptional repressors is regulated by NAD+ and NADH, with NADH
being 2 to 3 orders of magnitude more effective. Levels of free nuclear
nicotinamide adenine dinucleotides, determined using 2-photon
microscopy, corresponded to the levels required for half-maximal CTBP
binding and were considerably lower than those previously reported.
Agents capable of increasing NADH levels stimulated CTBP binding to its
partners in vivo and potentiated CTBP-mediated repression. Zhang et al.
(2002) proposed that this ability to detect changes in nuclear NAD+/NADH
ratio allows CTBP to serve as a redox sensor for transcription.
Kumar et al. (2002) reported biochemical and crystallographic studies
that revealed that CTBP1 is a functional dehydrogenase. In addition,
both a cofactor-dependent conformational change, with NAD+ and NADH
being equivalently effective, and the active site residues were linked
to the binding of the PXDLS consensus recognition motif on repressors,
such as E1A and RIP140 (602490). They concluded that CTBP1 is an
NAD(+)-regulated component of critical complexes for specific repression
events in cells.
CTBP is recruited to DNA by transcription factors that contain a PXDLS
motif. Shi et al. (2003) reported the identification of a CTBP complex
that contains the essential components for both gene targeting and
coordinated histone modifications, allowing for the effective repression
of genes targeted by CTBP. This complex has a molecular mass of about
1.3 to 1.5 million and contains CTBP1 and CTBP2 as well as G9A (604599),
EUHMT (607001), COREST (607675), HDAC1 (601241) and HDAC2 (605164),
NPAO, REBB1, ZNF217 (602967), and KIAA0222. Immunoprecipitation with G9A
antibodies brought down the same components as well as HPC2 (ELAC2;
605367). Shi et al. (2003) found that inhibiting the expression of CTBP
and its associated histone-modifying activities by RNA-interference
resulted in alterations of histone modifications at the promoter of the
tumor invasion suppressor gene E-cadherin (192090) and increased
promoter activity in a reporter assay.
By yeast 3-hybrid analysis, Zhang et al. (2003) found that mouse Hipk2
(606868) interacted with an E1A-Ctbp complex. Expression of Hipk2 or
exposure to ultraviolet (UV) irradiation reduced Ctbp levels via a
proteasome-mediated pathway. Coexpression of kinase-inactive Hipk2 or
small interfering RNA-mediated reduction in Hipk2 levels prevented the
UV effect. Mutation of Ctbp ser422 prevented phosphorylation as well as
UV- and Hipk2-directed Ctbp clearance. Deletion of Ctbp or reduction in
Ctbp levels promoted apoptosis in p53 (191170)-deficient cells.
Gallop et al. (2005) found that the lysophosphatidic acid
acyltransferase, or LPAAT, activity associated with CtBP/BARS (e.g.,
Weigert et al., 1999) is a copurification artifact.
Using a promoter pull-down assay followed by mass spectrometry analysis,
Flajollet et al. (2009) identified RREB1 (602209) as a protein that
bound the HLA-G (142871) promoter. RREB1 exerted repressive activity on
the promoter in HLA-G-negative cells that was mediated by recruitment of
HDAC1 and CTBP1 and/or CTBP2. The HLA-G promoter contains 3 RREB1 target
sites. Flajollet et al. (2009) proposed that the repressive activity of
RREB1 on the HLA-G promoter may be regulated by posttranslational
modifications governing its association with CTBP.
Deng et al. (2011) identified microRNA-137 (MIR137; 614304) as a
regulator of CTBP1 expression. Expression of MIR137 was inversely
correlated with that of CTBP1 in melanoma cell lines. The MIR137-binding
site in the 3-prime UTR of CTBP1 mRNA is conserved from human to
chicken. Pull-down assays revealed that MIR137 interacted with ARGO2
(EIF2C2; 606229) and CTBP1 mRNA. Cotransfection of MIR137 inhibited
expression of a reporter gene containing the CTBP1 3-prime UTR, but not
when the MIR137-binding site was deleted from the CTBP1 3-prime UTR.
Western blot and quantitative RT-PCR analyses showed that MIR137
expression in a melanoma cell line reduced CTBP1 protein levels and
increased expression of the CTBP1 target genes E-cadherin and BAX
(600040).
MAPPING
By PCR of a radiation hybrid panel, Katsanis and Fisher (1998) mapped
the CTBP1 gene to 4p16.
*FIELD* RF
1. Boyd, J. M.; Subramanian, T.; Schaeper, U.; La Regina, M.; Bayley,
S.; Chinnadurai, G.: A region in the C-terminus of adenovirus 2/5
E1a protein is required for association with a cellular phosphoprotein
and important for the negative modulation of T24-ras mediated transformation,
tumorigenesis and metastasis. EMBO J. 12: 469-478, 1993.
2. Deng, Y.; Deng, H.; Bi, F.; Liu, J.; Bemis, L. T.; Norris, D.;
Wang, X.-J.; Zhang, Q.: MicroRNA-137 targets carboxyl-terminal binding
protein 1 in melanoma cell lines. Int. J. Biol. Sci. 7: 133-137,
2011.
3. Flajollet, S.; Poras, I.; Carosella, E. D.; Moreau, P.: RREB-1
is a transcriptional repressor of HLA-G. J. Immun. 183: 6948-6959,
2009.
4. Furusawa, T.; Moribe, H.; Kondoh, H.; Higashi, Y.: Identification
of CtBP1 and CtBP2 as corepressors of zinc finger-homeodomain factor
delta-EF1. Molec. Cell. Biol. 19: 8581-8590, 1999.
5. Gallop, J. L.; Butler, P. J. G.; McMahon, H. T.: Endophilin and
CtBP/BARS are not acyl transferases in endocytosis or Golgi fission. Nature 438:
675-678, 2005.
6. Kagey, M. H.; Melhuish, T. A.; Wotton, D.: The polycomb protein
Pc2 is a SUMO E3. Cell 113: 127-137, 2003.
7. Katsanis, N.; Fisher, E. M. C.: A novel C-terminal binding protein
(CTBP2) is closely related to CTBP1, an adenovirus E1A-binding protein,
and maps to human chromosome 21q21.3. Genomics 47: 294-299, 1998.
8. Kumar, V.; Carlson, J. E. Ohgi, K. A.; Edwards, T. A.; Rose, D.
W.; Escalante, C. R.; Rosenfeld, M. G.; Aggarwal, A. K.: Transcription
corepressor CtBP is an NAD(+)-regulated dehydrogenase. Molec. Cell 10:
857-869, 2002.
9. Schaeper, U.; Boyd, J. M.; Verma, S.; Uhlmann, E.; Subramanian,
T.; Chinnadurai, G.: Molecular cloning and characterization of a
cellular phosphoprotein that interacts with a conserved C-terminal
domain of adenovirus E1A involved in negative modulation of oncogenic
transformation. Proc. Nat. Acad. Sci. 92: 10467-10471, 1995. Note:
Erratum: Proc. Nat. Acad. Sci. 95: 14584 only, 1998.
10. Sewalt, R. G. A. B.; Gunster, M. J.; van der Vlag, J.; Satijn,
D. P. E.; Otte, A. P.: C-terminal binding protein is a transcriptional
repressor that interacts with a specific class of vertebrate polycomb
proteins. Molec. Cell. Biol. 19: 777-787, 1999.
11. Shi, Y.; Sawada, J.; Sui, G.; Affar, E. B.; Whetstine, J. R.;
Lan, F.; Ogawa, H.; Luke, M. P.-S.; Nakatani, Y.; Shi, Y.: Coordinated
histone modifications mediated by a CtBP co-repressor complex. Nature 422:
735-738, 2003.
12. Weigert, R.; Silletta, M. G.; Spano, S.; Turacchio, G.; Cericola,
C.; Colanzi, A.; Senatore, S.; Mancini, R.; Polishchuk, E. V.; Salmona,
M.; Facchiano, F.; Burger, K. N. J.; Mironov, A.; Luini, A.; Corda,
D.: CtBP/BARS induces fission of Golgi membranes by acylating lysophosphatidic
acid. Nature 402: 429-433, 1999.
13. Zhang, Q.; Piston, D. W.; Goodman, R. H.: Regulation of corepressor
function by nuclear NADH. Science 295: 1895-1897, 2002.
14. Zhang, Q.; Yoshimatsu, Y.; Hildebrand, J.; Frisch, S. M.; Goodman,
R. H.: Homeodomain interacting protein kinase 2 promotes apoptosis
by downregulating the transcriptional corepressor CtBP. Cell 115:
177-186, 2003.
*FIELD* CN
Paul J. Converse - updated: 11/19/2012
Patricia A. Hartz - updated: 10/24/2011
Paul J. Converse - updated: 6/20/2006
Ada Hamosh - updated: 1/30/2006
Ada Hamosh - updated: 5/6/2003
Stylianos E. Antonarakis - updated: 5/2/2003
Stylianos E. Antonarakis - updated: 4/29/2003
Ada Hamosh - updated: 4/2/2002
Dawn Watkins-Chow - updated: 10/24/2001
Rebekah S. Rasooly - updated: 4/9/1999
*FIELD* CD
Rebekah S. Rasooly: 5/13/1998
*FIELD* ED
terry: 11/28/2012
mgross: 11/26/2012
terry: 11/19/2012
carol: 7/19/2012
mgross: 10/24/2011
carol: 12/26/2007
mgross: 6/20/2006
alopez: 2/1/2006
terry: 1/30/2006
mgross: 3/9/2005
alopez: 7/26/2004
terry: 7/26/2004
alopez: 9/30/2003
alopez: 5/8/2003
terry: 5/6/2003
mgross: 5/2/2003
mgross: 5/1/2003
terry: 4/29/2003
alopez: 4/5/2002
terry: 4/2/2002
carol: 10/24/2001
mgross: 4/12/1999
mgross: 4/9/1999
carol: 3/16/1999
psherman: 5/13/1998