CTBP2_MOUSE
ID CTBP2_MOUSE Reviewed; 445 AA.
AC P56546; O54855; O88462;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2000, sequence version 2.
DT 03-AUG-2022, entry version 180.
DE RecName: Full=C-terminal-binding protein 2;
DE Short=CtBP2;
GN Name=Ctbp2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=9479502; DOI=10.1006/geno.1997.5115;
RA Katsanis N., Fisher E.M.C.;
RT "A novel C-terminal binding protein (CTBP2) is closely related to CTBP1, an
RT adenovirus E1A-binding protein, and maps to human chromosome 21q21.3.";
RL Genomics 47:294-299(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=9724649; DOI=10.1093/emboj/17.17.5129;
RA Turner J., Crossley M.;
RT "Cloning and characterization of mCtBP2, a co-repressor that associates
RT with basic krueppel-like factor and other mammalian transcriptional
RT regulators.";
RL EMBO J. 17:5129-5140(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC STRAIN=ICR;
RX PubMed=10567582; DOI=10.1128/mcb.19.12.8581;
RA Furusawa T., Moribe H., Kondoh H., Higashi Y.;
RT "Identification of CtBP1 and CtBP2 as corepressors of zinc finger-
RT homeodomain factor deltaEF1.";
RL Mol. Cell. Biol. 19:8581-8590(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND ALTERNATIVE SPLICING
RP (ISOFORM 2).
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [5]
RP INTERACTION WITH NRIP1.
RX PubMed=14736873; DOI=10.1074/jbc.m313906200;
RA Christian M., Tullet J.M.A., Parker M.G.;
RT "Characterization of four autonomous repression domains in the corepressor
RT receptor interacting protein 140.";
RL J. Biol. Chem. 279:15645-15651(2004).
RN [6]
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 the
RT co-repressor molecule CtBP.";
RL J. Biol. Chem. 281:20120-20128(2006).
RN [7]
RP INTERACTION WITH ZNF217.
RX PubMed=16940172; DOI=10.1128/mcb.00680-06;
RA Quinlan K.G.R., Nardini M., Verger A., Francescato P., Yaswen P., Corda D.,
RA Bolognesi M., Crossley M.;
RT "Specific recognition of ZNF217 and other zinc finger proteins at a surface
RT groove of C-terminal binding proteins.";
RL Mol. Cell. Biol. 26:8159-8172(2006).
RN [8]
RP FUNCTION, INTERACTION WITH PRDM16, AND SUBCELLULAR LOCATION.
RX PubMed=18483224; DOI=10.1101/gad.1666108;
RA Kajimura S., Seale P., Tomaru T., Erdjument-Bromage H., Cooper M.P.,
RA Ruas J.L., Chin S., Tempst P., Lazar M.A., Spiegelman B.M.;
RT "Regulation of the brown and white fat gene programs through a PRDM16/CtBP
RT transcriptional complex.";
RL Genes Dev. 22:1397-1409(2008).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, Lung, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [10]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-22, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, and Embryo;
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).
CC -!- FUNCTION: Corepressor targeting diverse transcription regulators.
CC Isoform 2 probably acts as a scaffold for specialized synapses (By
CC similarity). Functions in brown adipose tissue (BAT) differentiation.
CC {ECO:0000250, ECO:0000269|PubMed:18483224}.
CC -!- SUBUNIT: Interacts with HIPK2 and PNN (By similarity). Interacts with
CC the transcription factors ZNF217, BKLF, delta EF1/AREB6/ZEB, EVI-1 and
CC Friend of GATA (FOG) via the consensus motif P-X-[DNS]-L-[STVA].
CC Interacts also with the C-terminus of adenovirus E1A protein. Can form
CC a complex with BKLF on a CACCC-box oligonucleotide. Can form homodimers
CC or heterodimers of CTBP1 and CTBP2. Interacts with NRIP1 and WIZ.
CC Interacts with PRDM16; represses white adipose tissue (WAT)-specific
CC genes expression. Interacts with MCRIP1 (By similarity). {ECO:0000250,
CC ECO:0000250|UniProtKB:P56545, ECO:0000269|PubMed:14736873,
CC ECO:0000269|PubMed:16702210, ECO:0000269|PubMed:16940172,
CC ECO:0000269|PubMed:18483224}.
CC -!- INTERACTION:
CC P56546; Q14526: HIC1; Xeno; NbExp=2; IntAct=EBI-1384883, EBI-2507362;
CC P56546; Q03112: MECOM; Xeno; NbExp=3; IntAct=EBI-1384883, EBI-1384862;
CC P56546; Q9HAZ2-2: PRDM16; Xeno; NbExp=2; IntAct=EBI-1384883, EBI-5282871;
CC P56546; Q9HAZ2-4: PRDM16; Xeno; NbExp=2; IntAct=EBI-1384883, EBI-4566658;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}. Synapse {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P56546-1; Sequence=Displayed;
CC Name=2; Synonyms=Ribeye;
CC IsoId=P56546-2; Sequence=VSP_027616;
CC -!- TISSUE SPECIFICITY: Found in all tissues except spleen and liver.
CC -!- DEVELOPMENTAL STAGE: Strong expression confined to the embryonic
CC stages.
CC -!- PTM: Phosphorylation by HIPK2 on Ser-428 induces proteasomal
CC degradation. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the D-isomer specific 2-hydroxyacid
CC dehydrogenase family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC40043.1; Type=Frameshift; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF016508; AAC40043.1; ALT_FRAME; mRNA.
DR EMBL; AF059735; AAC33873.1; -; mRNA.
DR EMBL; AB033123; BAA85181.1; -; mRNA.
DR EMBL; AC119806; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS21930.1; -. [P56546-1]
DR CCDS; CCDS52417.1; -. [P56546-2]
DR RefSeq; NP_001164215.1; NM_001170744.1. [P56546-2]
DR RefSeq; NP_034110.1; NM_009980.4. [P56546-1]
DR RefSeq; XP_006507371.1; XM_006507308.3. [P56546-1]
DR RefSeq; XP_006507372.1; XM_006507309.3. [P56546-1]
DR RefSeq; XP_006507373.1; XM_006507310.3. [P56546-1]
DR RefSeq; XP_006507374.1; XM_006507311.3. [P56546-1]
DR RefSeq; XP_006507375.1; XM_006507312.3. [P56546-1]
DR AlphaFoldDB; P56546; -.
DR SMR; P56546; -.
DR BioGRID; 198962; 25.
DR IntAct; P56546; 9.
DR STRING; 10090.ENSMUSP00000130294; -.
DR iPTMnet; P56546; -.
DR PhosphoSitePlus; P56546; -.
DR REPRODUCTION-2DPAGE; P56546; -.
DR MaxQB; P56546; -.
DR PaxDb; P56546; -.
DR PeptideAtlas; P56546; -.
DR PRIDE; P56546; -.
DR ProteomicsDB; 285386; -. [P56546-1]
DR ProteomicsDB; 285387; -. [P56546-2]
DR Antibodypedia; 19137; 393 antibodies from 37 providers.
DR DNASU; 13017; -.
DR Ensembl; ENSMUST00000033269; ENSMUSP00000033269; ENSMUSG00000030970. [P56546-1]
DR Ensembl; ENSMUST00000169570; ENSMUSP00000130294; ENSMUSG00000030970. [P56546-2]
DR GeneID; 13017; -.
DR KEGG; mmu:13017; -.
DR UCSC; uc009kcy.1; mouse. [P56546-1]
DR UCSC; uc012fve.1; mouse. [P56546-2]
DR CTD; 1488; -.
DR MGI; MGI:1201686; Ctbp2.
DR VEuPathDB; HostDB:ENSMUSG00000030970; -.
DR eggNOG; KOG0067; Eukaryota.
DR GeneTree; ENSGT00940000154430; -.
DR HOGENOM; CLU_012460_0_0_1; -.
DR InParanoid; P56546; -.
DR OMA; TCHTAFY; -.
DR OrthoDB; 700058at2759; -.
DR PhylomeDB; P56546; -.
DR TreeFam; TF313593; -.
DR Reactome; R-MMU-4641265; Repression of WNT target genes.
DR BioGRID-ORCS; 13017; 3 hits in 71 CRISPR screens.
DR ChiTaRS; Ctbp2; mouse.
DR PRO; PR:P56546; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; P56546; protein.
DR Bgee; ENSMUSG00000030970; Expressed in saccule of membranous labyrinth and 271 other tissues.
DR ExpressionAtlas; P56546; baseline and differential.
DR Genevisible; P56546; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0098982; C:GABA-ergic synapse; IDA:SynGO.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0098684; C:photoreceptor ribbon synapse; IDA:SynGO.
DR GO; GO:0098831; C:presynaptic active zone cytoplasmic component; IDA:SynGO.
DR GO; GO:0099523; C:presynaptic cytosol; IDA:SynGO.
DR GO; GO:0097470; C:ribbon synapse; IDA:MGI.
DR GO; GO:0045202; C:synapse; IDA:MGI.
DR GO; GO:0017053; C:transcription repressor complex; IDA:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; IDA:MGI.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0051287; F:NAD binding; IEA:InterPro.
DR GO; GO:0042974; F:nuclear retinoic acid receptor binding; IPI:MGI.
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:0019901; F:protein kinase binding; ISO:MGI.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0098882; F:structural constituent of presynaptic active zone; IDA:SynGO.
DR GO; GO:0003713; F:transcription coactivator activity; IGI:MGI.
DR GO; GO:0001221; F:transcription coregulator binding; IPI:BHF-UCL.
DR GO; GO:0003714; F:transcription corepressor activity; IDA:MGI.
DR GO; GO:0001222; F:transcription corepressor binding; ISO:MGI.
DR GO; GO:1990830; P:cellular response to leukemia inhibitory factor; IEP:MGI.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0035563; P:positive regulation of chromatin binding; IMP:MGI.
DR GO; GO:0048386; P:positive regulation of retinoic acid receptor signaling pathway; IMP:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0016081; P:synaptic vesicle docking; IDA:SynGO.
DR GO; GO:0050872; P:white fat cell differentiation; IDA:UniProtKB.
DR CDD; cd05299; CtBP_dh; 1.
DR InterPro; IPR043322; CtBP.
DR InterPro; IPR006139; D-isomer_2_OHA_DH_cat_dom.
DR InterPro; IPR029753; D-isomer_DH_CS.
DR InterPro; IPR006140; D-isomer_DH_NAD-bd.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR Pfam; PF00389; 2-Hacid_dh; 1.
DR Pfam; PF02826; 2-Hacid_dh_C; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR PROSITE; PS00671; D_2_HYDROXYACID_DH_3; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Differentiation; Methylation; NAD; Nucleus;
KW Oxidoreductase; Phosphoprotein; Reference proteome; Repressor; Synapse;
KW Transcription; Transcription regulation.
FT CHAIN 1..445
FT /note="C-terminal-binding protein 2"
FT /id="PRO_0000076045"
FT REGION 414..445
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 418..433
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 272
FT /evidence="ECO:0000250"
FT ACT_SITE 301
FT /evidence="ECO:0000250"
FT ACT_SITE 321
FT /note="Proton donor"
FT /evidence="ECO:0000250"
FT BINDING 106
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 186..191
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 210
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 243..249
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 270..272
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 296
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 321..324
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT MOD_RES 22
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 428
FT /note="Phosphoserine; by HIPK2"
FT /evidence="ECO:0000250|UniProtKB:P56545"
FT VAR_SEQ 1..20
FT /note="MALVDKHKVKRQRLDRICEG -> MPVPSRHINIGRSQSWDAAGWYEGPWEN
FT AGPPGRRSSLTYGPGEGTWCELLNHRAQDTESYLSREAFYNSLASRKGSVPDFTFYDSR
FT QAVMSGRGSVLPQDYYGDPSRGTRVPKEPPFYRDPGTSRPVPSYGMLGSRMPWEQVQGQ
FT LPALQDTGHLYPESGGKTVPHGQRTHGRAPSPGRYGREQPDTRLGIEVPTYSPNSSQVY
FT NDICERPVDSTPARQVAPTCLVVDPSSAVPTENSTGVAPGSLNRGYGPTRESIHSKLAY
FT ENYEADLSTFQGPGGKRTMYPEFLALLRAEGVAEATLAALLQQGFDSPAVLATLEDADI
FT KSVAPNLGQARVLSRLASSCRTEMQFRRQDRTGPLPRNRSSSFSHRSELLPNDMASLGT
FT TALQFHPAGPLQTPSPRAGDLGRRPSSAPSQHLLETAATYSTPVVGSQTPHLPSNSGYS
FT SPTPCALTARLASSYPSQAGVALTANPGPSAPLHSNPRTAYSTSYTVPMELLKRERSMT
FT ASPLPSPHGSPQLLRKPGAAPVEPSTLPPVSQSLHTPHSPYQKVARRTGAPIIVSTMLT
FT PEPS (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_027616"
FT CONFLICT 49
FT /note="P -> H (in Ref. 1; AAC40043)"
FT /evidence="ECO:0000305"
FT CONFLICT 170
FT /note="E -> D (in Ref. 1; AAC40043)"
FT /evidence="ECO:0000305"
FT CONFLICT 288
FT /note="G -> A (in Ref. 1; AAC40043)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 445 AA; 48957 MW; 5A81B9D75A9E493B CRC64;
MALVDKHKVK RQRLDRICEG IRPQIMNGPL HPRPLVALLD GRDCTVEMPI LKDLATVAFC
DAQSTQEIHE KVLNEAVGAM MYHTITLTRE DLEKFKALRV IVRIGSGYDN VDIKAAGELG
IAVCNIPSAA VEETADSTVC HILNLYRRNT WLYQALREGT RVQSVEQIRE VASGAARIRG
ETLGLIGFGR TGQAVAVRAK AFGFSVIFYD PYLQDGIERS LGVQRVYTLQ DLLYQSDCVS
LHCNLNEHNH HLINDFTIKQ MRQGAFLVNA ARGGLVDEKA LAQALKEGRI RGAALDVHES
EPFSFAQGPL KDAPNLICTP HTAWYSEQAS LEMREAAATE IRRAITGRIP ESLRNCVNKE
FFVTSAPWSV IDQQAIHPEL NGATYRYPPG IVGVAPGGLP PAMEGIIPGG IPVTHNLPTV
AHPSQAPSPN QPTKHGDNRE HPNEQ
