CEBPB_MOUSE
ID CEBPB_MOUSE Reviewed; 296 AA.
AC P28033;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1992, sequence version 1.
DT 03-AUG-2022, entry version 198.
DE RecName: Full=CCAAT/enhancer-binding protein beta {ECO:0000312|MGI:MGI:88373};
DE Short=C/EBP beta;
DE AltName: Full=AGP/EBP;
DE AltName: Full=Interleukin-6-dependent-binding protein;
DE Short=IL-6DBP;
DE AltName: Full=Liver-enriched transcriptional activator;
DE Short=LAP;
GN Name=Cebpb {ECO:0000312|MGI:MGI:88373};
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].
RC STRAIN=BALB/cJ; TISSUE=Liver;
RX PubMed=1701020; DOI=10.1128/mcb.10.12.6642-6653.1990;
RA Chang C.J., Chen T.T., Lei H.Y., Chen D.S., Lee S.C.;
RT "Molecular cloning of a transcription factor, AGP/EBP, that belongs to
RT members of the C/EBP family.";
RL Mol. Cell. Biol. 10:6642-6653(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1840554; DOI=10.1101/gad.5.9.1538;
RA Cao Z., Umek R.M., McKnight S.L.;
RT "Regulated expression of three C/EBP isoforms during adipose conversion of
RT 3T3-L1 cells.";
RL Genes Dev. 5:1538-1552(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-11.
RC TISSUE=Liver;
RX PubMed=7598808; DOI=10.1089/dna.1995.14.529;
RA Chang C.J., Shen B.J., Lee S.C.;
RT "Autoregulated induction of the acute-phase response transcription factor
RT gene, agp/ebp.";
RL DNA Cell Biol. 14:529-537(1995).
RN [4]
RP FUNCTION, PHOSPHORYLATION AT SER-276, AND MUTAGENESIS OF SER-276.
RX PubMed=1314426; DOI=10.1126/science.256.5055.370;
RA Wegner M., Cao Z., Rosenfeld M.G.;
RT "Calcium-regulated phosphorylation within the leucine zipper of C/EBP
RT beta.";
RL Science 256:370-373(1992).
RN [5]
RP FUNCTION, DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=9303532; DOI=10.1101/gad.11.17.2153;
RA Sterneck E., Tessarollo L., Johnson P.F.;
RT "An essential role for C/EBPbeta in female reproduction.";
RL Genes Dev. 11:2153-2162(1997).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=9727068; DOI=10.1172/jci3135;
RA Greenbaum L.E., Li W., Cressman D.E., Peng Y., Ciliberto G., Poli V.,
RA Taub R.;
RT "CCAAT enhancer- binding protein beta is required for normal hepatocyte
RT proliferation in mice after partial hepatectomy.";
RL J. Clin. Invest. 102:996-1007(1998).
RN [7]
RP INTERACTION WITH TRIM28.
RX PubMed=9742105; DOI=10.1128/mcb.18.10.5880;
RA Chang C.J., Chen Y.L., Lee S.C.;
RT "Coactivator TIF1beta interacts with transcription factor C/EBPbeta and
RT glucocorticoid receptor to induce alpha1-acid glycoprotein gene
RT expression.";
RL Mol. Cell. Biol. 18:5880-5887(1998).
RN [8]
RP FUNCTION, PHOSPHORYLATION AT THR-217, AND MUTAGENESIS OF THR-217.
RX PubMed=10635333; DOI=10.1016/s1097-2765(00)80237-3;
RA Buck M., Poli V., van der Geer P., Chojkier M., Hunter T.;
RT "Phosphorylation of rat serine 105 or mouse threonine 217 in C/EBP beta is
RT required for hepatocyte proliferation induced by TGF alpha.";
RL Mol. Cell 4:1087-1092(1999).
RN [9]
RP INTERACTION WITH MYB.
RX PubMed=11792321; DOI=10.1016/s0092-8674(01)00636-5;
RA Tahirov T.H., Sato K., Ichikawa-Iwata E., Sasaki M., Inoue-Bungo T.,
RA Shiina M., Kimura K., Takata S., Fujikawa A., Morii H., Kumasaka T.,
RA Yamamoto M., Ishii S., Ogata K.;
RT "Mechanism of c-Myb-C/EBP beta cooperation from separated sites on a
RT promoter.";
RL Cell 108:57-70(2002).
RN [10]
RP FUNCTION, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=15509779; DOI=10.1128/mcb.24.22.9744-9751.2004;
RA Begay V., Smink J., Leutz A.;
RT "Essential requirement of CCAAT/enhancer binding proteins in
RT embryogenesis.";
RL Mol. Cell. Biol. 24:9744-9751(2004).
RN [11]
RP INTERACTION WITH CCDC85B.
RX PubMed=15644333; DOI=10.1074/jbc.m411741200;
RA Bezy O., Elabd C., Cochet O., Petersen R.K., Kristiansen K., Dani C.,
RA Ailhaud G., Amri E.-Z.;
RT "Delta-interacting protein A, a new inhibitory partner of CCAAT/enhancer-
RT binding protein beta, implicated in adipocyte differentiation.";
RL J. Biol. Chem. 280:11432-11438(2005).
RN [12]
RP INTERACTION WITH PTGES2.
RX PubMed=15879117; DOI=10.4049/jimmunol.174.10.6203;
RA Meng Q., Raha A., Roy S., Hu J., Kalvakolanu D.V.;
RT "IFN-gamma-stimulated transcriptional activation by IFN-gamma-activated
RT transcriptional element-binding factor 1 occurs via an inducible
RT interaction with CAAAT/enhancer-binding protein-beta.";
RL J. Immunol. 174:6203-6211(2005).
RN [13]
RP FUNCTION, PHOSPHORYLATION AT THR-179; SER-184 AND THR-188, DNA-BINDING,
RP MUTAGENESIS OF THR-179; SER-184 AND THR-188, IDENTIFICATION BY MASS
RP SPECTROMETRY, AND TISSUE SPECIFICITY.
RX PubMed=15985551; DOI=10.1073/pnas.0503891102;
RA Tang Q.Q., Gronborg M., Huang H., Kim J.W., Otto T.C., Pandey A.,
RA Lane M.D.;
RT "Sequential phosphorylation of CCAAT enhancer-binding protein beta by MAPK
RT and glycogen synthase kinase 3beta is required for adipogenesis.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:9766-9771(2005).
RN [14]
RP FUNCTION, SUMOYLATION AT LYS-133, TISSUE SPECIFICITY, MUTAGENESIS OF
RP LYS-133, AND SUBCELLULAR LOCATION.
RX PubMed=16585579; DOI=10.4049/jimmunol.176.8.4843;
RA Berberich-Siebelt F., Berberich I., Andrulis M., Santner-Nanan B.,
RA Jha M.K., Klein-Hessling S., Schimpl A., Serfling E.;
RT "SUMOylation interferes with CCAAT/enhancer-binding protein beta-mediated
RT c-myc repression, but not IL-4 activation in T cells.";
RL J. Immunol. 176:4843-4851(2006).
RN [15]
RP FUNCTION, DISRUPTION PHENOTYPE, AND ALTERNATIVE INITIATION.
RX PubMed=17911624; DOI=10.4049/jimmunol.179.8.5378;
RA Uematsu S., Kaisho T., Tanaka T., Matsumoto M., Yamakami M., Omori H.,
RA Yamamoto M., Yoshimori T., Akira S.;
RT "The C/EBP beta isoform 34-kDa LAP is responsible for NF-IL-6-mediated gene
RT induction in activated macrophages, but is not essential for intracellular
RT bacteria killing.";
RL J. Immunol. 179:5378-5386(2007).
RN [16]
RP FUNCTION, ACETYLATION AT LYS-98; LYS-101 AND LYS-102, INTERACTION WITH
RP KAT2A AND KAT2B, AND MUTAGENESIS OF LYS-98; LYS-101 AND LYS-102.
RX PubMed=17301242; DOI=10.1073/pnas.0607378104;
RA Wiper-Bergeron N., Salem H.A., Tomlinson J.J., Wu D., Hache R.J.;
RT "Glucocorticoid-stimulated preadipocyte differentiation is mediated through
RT acetylation of C/EBPbeta by GCN5.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:2703-2708(2007).
RN [17]
RP FUNCTION, PHOSPHORYLATION AT THR-179; SER-184 AND THR-188, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=17601773; DOI=10.1073/pnas.0703771104;
RA Li X., Kim J.W., Gronborg M., Urlaub H., Lane M.D., Tang Q.Q.;
RT "Role of cdk2 in the sequential phosphorylation/activation of C/EBPbeta
RT during adipocyte differentiation.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:11597-11602(2007).
RN [18]
RP METHYLATION AT LYS-39.
RX PubMed=18647749; DOI=10.1074/jbc.m802132200;
RA Pless O., Kowenz-Leutz E., Knoblich M., Lausen J., Beyermann M.,
RA Walsh M.J., Leutz A.;
RT "G9a-mediated lysine methylation alters the function of CCAAT/enhancer-
RT binding protein-beta.";
RL J. Biol. Chem. 283:26357-26363(2008).
RN [19]
RP FUNCTION, INTERACTION WITH EP300, MUTAGENESIS OF LYS-39; LYS-98 AND
RP LYS-215, AND ACETYLATION AT LYS-39.
RX PubMed=18486321; DOI=10.1016/j.mce.2008.03.009;
RA Cesena T.I., Cui T.X., Subramanian L., Fulton C.T., Iniguez-Lluhi J.A.,
RA Kwok R.P., Schwartz J.;
RT "Acetylation and deacetylation regulate CCAAT/enhancer binding protein beta
RT at K39 in mediating gene transcription.";
RL Mol. Cell. Endocrinol. 289:94-101(2008).
RN [20]
RP SUBCELLULAR LOCATION, AND COMPLEX FORMATION WITH THOC5.
RX PubMed=19015024; DOI=10.1016/j.cellsig.2008.10.018;
RA Carney L., Pierce A., Rijnen M., Gonzalez Sanchez M.B., Hamzah H.G.,
RA Zhang L., Tamura T., Whetton A.D.;
RT "THOC5 couples M-CSF receptor signaling to transcription factor
RT expression.";
RL Cell. Signal. 21:309-316(2009).
RN [21]
RP FUNCTION (ISOFORM 1 AND ISOFORM 3), TISSUE SPECIFICITY, DEVELOPMENTAL
RP STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=19440205; DOI=10.1038/emboj.2009.127;
RA Smink J.J., Begay V., Schoenmaker T., Sterneck E., de Vries T.J., Leutz A.;
RT "Transcription factor C/EBPbeta isoform ratio regulates osteoclastogenesis
RT through MafB.";
RL EMBO J. 28:1769-1781(2009).
RN [22]
RP FUNCTION, GLYCOSYLATION AT SER-180 AND SER-181, MUTAGENESIS OF SER-180 AND
RP SER-181, IDENTIFICATION BY MASS SPECTROMETRY, AND PHOSPHORYLATION AT
RP THR-179; SER-184 AND THR-188.
RX PubMed=19478079; DOI=10.1074/jbc.m109.005678;
RA Li X., Molina H., Huang H., Zhang Y.Y., Liu M., Qian S.W., Slawson C.,
RA Dias W.B., Pandey A., Hart G.W., Lane M.D., Tang Q.Q.;
RT "O-linked N-acetylglucosamine modification on CCAAT enhancer-binding
RT protein beta: role during adipocyte differentiation.";
RL J. Biol. Chem. 284:19248-19254(2009).
RN [23]
RP FUNCTION IN ADIPOGENESIS, INTERACTION WITH EP300 AND RORA, ALTERNATIVE
RP SPLICING (ISOFORMS 2 AND 3), AND PHOSPHORYLATION AT THR-188.
RX PubMed=19324970; DOI=10.1210/me.2008-0277;
RA Ohoka N., Kato S., Takahashi Y., Hayashi H., Sato R.;
RT "The orphan nuclear receptor RORalpha restrains adipocyte differentiation
RT through a reduction of C/EBPbeta activity and perilipin gene expression.";
RL Mol. Endocrinol. 23:759-771(2009).
RN [24]
RP IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, DISRUPTION PHENOTYPE,
RP INTERACTION WITH PRDM16, INDUCTION BY COLD EXPOSURE, AND TISSUE
RP SPECIFICITY.
RX PubMed=19641492; DOI=10.1038/nature08262;
RA Kajimura S., Seale P., Kubota K., Lunsford E., Frangioni J.V., Gygi S.P.,
RA Spiegelman B.M.;
RT "Initiation of myoblast to brown fat switch by a PRDM16-C/EBP-beta
RT transcriptional complex.";
RL Nature 460:1154-1158(2009).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-184 AND THR-188, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, and Lung;
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 [26]
RP FUNCTION, INTERACTION WITH MED23; MED26; SMARCA2; SMARCB1 AND SMARCC1,
RP IDENTIFICATION BY MASS SPECTROMETRY, AND METHYLATION AT ARG-3.
RX PubMed=20111005; DOI=10.1038/emboj.2010.3;
RA Kowenz-Leutz E., Pless O., Dittmar G., Knoblich M., Leutz A.;
RT "Crosstalk between C/EBPbeta phosphorylation, arginine methylation, and
RT SWI/SNF/Mediator implies an indexing transcription factor code.";
RL EMBO J. 29:1105-1115(2010).
RN [27]
RP FUNCTION, SUMOYLATION AT LYS-133, DESUMOYLATION AT LYS-133, MUTAGENESIS OF
RP LYS-133 AND GLU-135, AND UBIQUITINATION.
RX PubMed=20194620; DOI=10.1128/mcb.00852-09;
RA Chung S.S., Ahn B.Y., Kim M., Choi H.H., Park H.S., Kang S., Park S.G.,
RA Kim Y.B., Cho Y.M., Lee H.K., Chung C.H., Park K.S.;
RT "Control of adipogenesis by the SUMO-specific protease SENP2.";
RL Mol. Cell. Biol. 30:2135-2146(2010).
RN [28]
RP INTERACTION WITH ZNF638.
RX PubMed=21602272; DOI=10.1074/jbc.m110.212506;
RA Meruvu S., Hugendubler L., Mueller E.;
RT "Regulation of adipocyte differentiation by the zinc finger protein
RT ZNF638.";
RL J. Biol. Chem. 286:26516-26523(2011).
RN [29]
RP INTERACTION WITH CIDEA AND CIDEC.
RX PubMed=22245780; DOI=10.1038/nm.2614;
RA Wang W., Lv N., Zhang S., Shui G., Qian H., Zhang J., Chen Y., Ye J.,
RA Xie Y., Shen Y., Wenk M.R., Li P.;
RT "Cidea is an essential transcriptional coactivator regulating mammary gland
RT secretion of milk lipids.";
RL Nat. Med. 18:235-243(2012).
RN [30]
RP FUNCTION, SUMOYLATION AT LYS-133, MUTAGENESIS OF LYS-133, AND
RP UBIQUITINATION.
RX PubMed=24061474; DOI=10.1128/mcb.00723-13;
RA Liu Y., Zhang Y.D., Guo L., Huang H.Y., Zhu H., Huang J.X., Liu Y.,
RA Zhou S.R., Dang Y.J., Li X., Tang Q.Q.;
RT "Protein inhibitor of activated STAT 1 (PIAS1) is identified as the SUMO E3
RT ligase of CCAAT/enhancer-binding protein beta (C/EBPbeta) during
RT adipogenesis.";
RL Mol. Cell. Biol. 33:4606-4617(2013).
RN [31]
RP FUNCTION, AND INTERACTION WITH ATF5 AND EP300.
RX PubMed=24216764; DOI=10.1128/mcb.00956-13;
RA Zhao Y., Zhang Y.D., Zhang Y.Y., Qian S.W., Zhang Z.C., Li S.F., Guo L.,
RA Liu Y., Wen B., Lei Q.Y., Tang Q.Q., Li X.;
RT "p300-dependent acetylation of activating transcription factor 5 enhances
RT C/EBPbeta transactivation of C/EBPalpha during 3T3-L1 differentiation.";
RL Mol. Cell. Biol. 34:315-324(2014).
RN [32]
RP REVIEW OF PTMS AND FUNCTION.
RX PubMed=25451943; DOI=10.1074/jbc.r114.619957;
RA Guo L., Li X., Tang Q.;
RT "Transcriptional Regulation of Adipocyte Differentiation: A Central Role
RT for CCAAT/Enhancer-binding Protein (C/EBP) beta.";
RL J. Biol. Chem. 290:755-761(2015).
RN [33]
RP INTERACTION WITH SIX1.
RX PubMed=27923061; DOI=10.1371/journal.pgen.1006474;
RA Brunmeir R., Wu J., Peng X., Kim S.Y., Julien S.G., Zhang Q., Xie W.,
RA Xu F.;
RT "Comparative Transcriptomic and Epigenomic Analyses Reveal New Regulators
RT of Murine Brown Adipogenesis.";
RL PLoS Genet. 12:E1006474-E1006474(2016).
RN [34]
RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 224-285 IN COMPLEX WITH ATF4,
RP INTERACTION WITH ATF4, AND DNA-BINDING.
RX PubMed=11018027; DOI=10.1074/jbc.m005594200;
RA Podust L.M., Krezel A.M., Kim Y.;
RT "Crystal structure of the CCAAT box/enhancer-binding protein beta
RT activating transcription factor-4 basic leucine zipper heterodimer in the
RT absence of DNA.";
RL J. Biol. Chem. 276:505-513(2001).
CC -!- FUNCTION: Important transcription factor regulating the expression of
CC genes involved in immune and inflammatory responses (PubMed:16585579,
CC PubMed:17911624, PubMed:18486321, PubMed:20111005). Also plays a
CC significant role in adipogenesis, as well as in the gluconeogenic
CC pathway, liver regeneration, and hematopoiesis (PubMed:9727068,
CC PubMed:10635333, PubMed:17301242, PubMed:17601773, PubMed:19478079,
CC PubMed:24061474, PubMed:24216764). The consensus recognition site is
CC 5'-T[TG]NNGNAA[TG]-3'. Its functional capacity is governed by protein
CC interactions and post-translational protein modifications. During early
CC embryogenesis, plays essential and redundant roles with CEBPA
CC (PubMed:15509779). Has a promitotic effect on many cell types such as
CC hepatocytes and adipocytes but has an antiproliferative effect on T-
CC cells by repressing MYC expression, facilitating differentiation along
CC the T-helper 2 lineage (PubMed:9727068, PubMed:10635333,
CC PubMed:16585579). Binds to regulatory regions of several acute-phase
CC and cytokines genes and plays a role in the regulation of acute-phase
CC reaction and inflammation. Also plays a role in intracellular bacteria
CC killing (PubMed:17911624). During adipogenesis, is rapidly expressed
CC and, after activation by phosphorylation, induces CEBPA and PPARG,
CC which turn on the series of adipocyte genes that give rise to the
CC adipocyte phenotype. The delayed transactivation of the CEBPA and PPARG
CC genes by CEBPB appears necessary to allow mitotic clonal expansion and
CC thereby progression of terminal differentiation (PubMed:15985551,
CC PubMed:17301242, PubMed:17601773, PubMed:20194620). Essential for
CC female reproduction because of a critical role in ovarian follicle
CC development (PubMed:9303532). Restricts osteoclastogenesis
CC (PubMed:19440205). Together with NFE2L1; represses expression of DSPP
CC during odontoblast differentiation (By similarity).
CC {ECO:0000250|UniProtKB:P17676, ECO:0000250|UniProtKB:P21272,
CC ECO:0000269|PubMed:10635333, ECO:0000269|PubMed:1314426,
CC ECO:0000269|PubMed:15509779, ECO:0000269|PubMed:15985551,
CC ECO:0000269|PubMed:16585579, ECO:0000269|PubMed:17301242,
CC ECO:0000269|PubMed:17601773, ECO:0000269|PubMed:17911624,
CC ECO:0000269|PubMed:18486321, ECO:0000269|PubMed:19440205,
CC ECO:0000269|PubMed:19478079, ECO:0000269|PubMed:20111005,
CC ECO:0000269|PubMed:20194620, ECO:0000269|PubMed:24061474,
CC ECO:0000269|PubMed:24216764, ECO:0000269|PubMed:9303532,
CC ECO:0000269|PubMed:9727068, ECO:0000303|PubMed:25451943}.
CC -!- FUNCTION: [Isoform 2]: Essential for gene expression induction in
CC activated macrophages. Plays a major role in immune responses such as
CC CD4(+) T-cell response, granuloma formation and endotoxin shock. Not
CC essential for intracellular bacteria killing.
CC {ECO:0000269|PubMed:17911624}.
CC -!- FUNCTION: [Isoform 3]: Acts as a dominant negative through
CC heterodimerization with isoform 2 (By similarity). Promotes osteoblast
CC differentiation and osteoclastogenesis (PubMed:19440205).
CC {ECO:0000250|UniProtKB:P17676, ECO:0000250|UniProtKB:P21272,
CC ECO:0000269|PubMed:19440205}.
CC -!- SUBUNIT: Binds DNA as a homodimer and as a heterodimer. Interacts with
CC ATF4. Binds DNA as a heterodimer with ATF4 (PubMed:11018027). Interacts
CC with MYB; within the complex, MYB and CEBPB bind to different promoter
CC regions (PubMed:11792321). Can form stable heterodimers with CEBPA,
CC CEBPD and CEBPE (By similarity). Interacts with SIX1 (PubMed:27923061).
CC Isoform 2 and isoform 3 also form heterodimers (By similarity).
CC Interacts with TRIM28 and PTGES2 (PubMed:9742105, PubMed:15879117).
CC Interacts with PRDM16 (PubMed:19641492). Interacts with CCDC85B
CC (PubMed:15644333). Forms a complex with THOC5 (PubMed:19015024).
CC Interacts with ZNF638; this interaction increases transcriptional
CC activation (PubMed:21602272). Interacts with CIDEA and CIDEC
CC (PubMed:22245780). Interaction with CIDEA increases transcriptional
CC activation of a subset of CEBPB downstream target genes, including ID2,
CC IGF1, PRLR, SOCS1, SOCS3, XDH. Interaction with CIDEC increases
CC transcriptional activation of SOCS1, SOCS3, TGFB1, TGFBR1, ID2 and XDH.
CC Interacts with DDIT3/CHOP. Interacts with EP300; recruits EP300 to
CC chromatin. Interacts with RORA; the interaction disrupts interaction
CC with EP300 (PubMed:19324970). Interacts (not methylated) with MED23,
CC MED26, SMARCA2, SMARCB1 and SMARCC1 (PubMed:20111005). Interacts with
CC KAT2A and KAT2B (PubMed:17301242). Interacts with ATF5; EP300 is
CC required for ATF5 and CEBPB interaction and DNA binding
CC (PubMed:24216764). Interacts with NFE2L1; the heterodimer represses
CC expression of DSPP during odontoblast differentiation (By similarity).
CC {ECO:0000250|UniProtKB:P21272, ECO:0000269|PubMed:11018027,
CC ECO:0000269|PubMed:11792321, ECO:0000269|PubMed:15644333,
CC ECO:0000269|PubMed:15879117, ECO:0000269|PubMed:17301242,
CC ECO:0000269|PubMed:18486321, ECO:0000269|PubMed:19015024,
CC ECO:0000269|PubMed:19324970, ECO:0000269|PubMed:19641492,
CC ECO:0000269|PubMed:20111005, ECO:0000269|PubMed:21602272,
CC ECO:0000269|PubMed:22245780, ECO:0000269|PubMed:24216764,
CC ECO:0000269|PubMed:27923061, ECO:0000269|PubMed:9742105}.
CC -!- INTERACTION:
CC P28033; Q99PV5: Bhlhe41; NbExp=5; IntAct=EBI-1029979, EBI-6143801;
CC P28033; Q9JHD2: Kat2a; NbExp=5; IntAct=EBI-1029979, EBI-2943116;
CC P28033; Q92831: KAT2B; Xeno; NbExp=2; IntAct=EBI-1029979, EBI-477430;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:16585579,
CC ECO:0000269|PubMed:19015024}. Cytoplasm {ECO:0000250|UniProtKB:P17676}.
CC Note=In T-cells when sumoylated drawn to pericentric heterochromatin
CC thereby allowing proliferation (PubMed:16585579). Translocates to the
CC nucleus when phosphorylated at Ser-288 (By similarity).
CC {ECO:0000250|UniProtKB:P17676, ECO:0000269|PubMed:16585579}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative initiation; Named isoforms=3;
CC Name=1; Synonyms=a, C/EBPbeta-FL, LAP*;
CC IsoId=P28033-1; Sequence=Displayed;
CC Name=2; Synonyms=b, C/EBPbeta-LAP;
CC IsoId=P28033-3; Sequence=VSP_053977;
CC Name=3; Synonyms=c, C/EBPbeta-LIP;
CC IsoId=P28033-2; Sequence=VSP_053976;
CC -!- TISSUE SPECIFICITY: Abundantly expressed in myoblasts. Enriched in
CC brown adipose tissue (BAT) versus white adipose tissue (WAT). Expressed
CC in hepatocytes (at protein level). Expressed in T lymphocytes
CC (PubMed:16585579). The expression in granulosa cells of antral
CC follicles is induced by luteinizing hormone (PubMed:9303532). Expressed
CC in chondrocytes and osteoblasts (at protein level) (PubMed:19440205).
CC {ECO:0000269|PubMed:10635333, ECO:0000269|PubMed:16585579,
CC ECO:0000269|PubMed:19440205, ECO:0000269|PubMed:19641492,
CC ECO:0000269|PubMed:9303532}.
CC -!- DEVELOPMENTAL STAGE: At 9.5 dpc, expressed in the chorionic plate and
CC ectoplacental cone. From 10.5 dpc to at least 11.5 dpc, is also
CC expressed in the trophoblast cells of the three placenta layers
CC (PubMed:15509779). Expressed in monocytic precursors but is vanished
CC during differentiation into osteoclasts. The expression increases
CC during osteoblast differentiation (PubMed:19440205).
CC {ECO:0000269|PubMed:15509779, ECO:0000269|PubMed:19440205}.
CC -!- INDUCTION: Up-regulated by cold exposure.
CC {ECO:0000269|PubMed:19641492}.
CC -!- PTM: Sumoylated by polymeric chains of SUMO2 or SUMO3. Sumoylation at
CC Lys-133 is required for inhibition of T-cells proliferation
CC (PubMed:16585579). In adipocytes, sumoylation at Lys-133 by PIAS1 leads
CC to ubiquitination and subsequent proteasomal degradation
CC (PubMed:24061474). Desumoylated by SENP2, which abolishes
CC ubiquitination and stabilizes protein levels (PubMed:20194620).
CC {ECO:0000250|UniProtKB:P17676, ECO:0000269|PubMed:16585579,
CC ECO:0000269|PubMed:20194620, ECO:0000269|PubMed:24061474}.
CC -!- PTM: Ubiquitinated, leading to proteasomal degradation.
CC {ECO:0000269|PubMed:24061474}.
CC -!- PTM: Phosphorylated at Thr-188 by MAPK and CDK2, serves to prime
CC phosphorylation at Thr-179 and Ser-184 by GSK3B and acquire DNA-binding
CC as well as transactivation activities, required to induce adipogenesis.
CC MAPK and CDK2 act sequentially to maintain Thr-188 in the primed
CC phosphorylated state during mitotical cloning expansion and thereby
CC progression of terminal differentiation. Phosphorylation at Thr-217
CC enhances transactivation activity. Phosphorylation at Ser-276 in
CC response to calcium increases transactivation activity
CC (PubMed:1314426). Phosphorylated at Thr-188 by RPS6KA1 (By similarity).
CC {ECO:0000250|UniProtKB:P17676, ECO:0000269|PubMed:1314426,
CC ECO:0000269|PubMed:15985551, ECO:0000269|PubMed:17601773}.
CC -!- PTM: O-glycosylated, glycosylation at Ser-180 and Ser-181 prevents
CC phosphorylation on Thr-188, Ser-184 and Thr-179 and DNA binding
CC activity which delays the adipocyte differentiation program.
CC {ECO:0000269|PubMed:19478079}.
CC -!- PTM: Acetylated. Acetylation at Lys-39 is an important and dynamic
CC regulatory event that contributes to its ability to transactivate
CC target genes, including those associated with adipogenesis and
CC adipocyte function. Deacetylation by HDAC1 represses its
CC transactivation activity (PubMed:18486321). Acetylated by KAT2A and
CC KAT2B within a cluster of lysine residues between amino acids 98-102,
CC this acetylation is strongly induced by glucocorticoid treatment and
CC enhances transactivation activity (PubMed:17301242).
CC {ECO:0000269|PubMed:17301242, ECO:0000269|PubMed:18486321}.
CC -!- PTM: Methylated. Methylation at Arg-3 by CARM1 and at Lys-39 by EHMT2,
CC inhibits transactivation activity. Methylation is probably inhibited by
CC phosphorylation at Thr-188. {ECO:0000269|PubMed:20111005,
CC ECO:0000305|PubMed:18647749}.
CC -!- DISRUPTION PHENOTYPE: Embryos display defects in brown fat tissue
CC development (PubMed:19641492). Females are sterile, ovaries lack
CC corpora lutea (PubMed:9303532). Upon bacterial infection, animals show
CC impaired bactericidal activity and die within 3 days (PubMed:17911624).
CC Posthepatectomy, animals show a reduced regenerative response with DNA
CC synthesis decreased to 25% of normal in hepatocytes and a prolonged
CC period of hypoglycemia (PubMed:9727068). Animals show osteopenia with
CC decreased bone formation and enhanced ostecolastogenesis. Long bones
CC have a 1.6 fold diminished bone volume with a reduction of the number
CC and thickness of bone trabeculae (PubMed:19440205). Mutants of isoform
CC 2 show impaired CSF3/G-CSF production by macrophages, IFNG production
CC by CD4(+) T-cells and granuloma formation in liver. Upon bacterial
CC infection, mutants of isoform 2 die within 6 days. Resistant to LPS-
CC induced endotoxin shock (PubMed:17911624). Double knockout CEBPA and
CC CEBPB results in embryonic developmental arrest and death at around 10
CC dpc to 11 dpc, associated with a gross placenta failure
CC (PubMed:15509779). {ECO:0000269|PubMed:15509779,
CC ECO:0000269|PubMed:17911624, ECO:0000269|PubMed:19440205,
CC ECO:0000269|PubMed:19641492, ECO:0000269|PubMed:9303532,
CC ECO:0000269|PubMed:9727068}.
CC -!- MISCELLANEOUS: [Isoform 2]: Major isoform. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the bZIP family. C/EBP subfamily. {ECO:0000305}.
CC ---------------------------------------------------------------------------
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DR EMBL; M61007; AAA37192.1; -; mRNA.
DR EMBL; X62600; CAA44484.1; -; mRNA.
DR EMBL; S78572; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS17105.1; -. [P28033-1]
DR PIR; A36366; A36366.
DR RefSeq; NP_001274667.1; NM_001287738.1. [P28033-3]
DR RefSeq; NP_001274668.1; NM_001287739.1. [P28033-2]
DR RefSeq; NP_034013.1; NM_009883.4. [P28033-1]
DR PDB; 1CI6; X-ray; 2.60 A; B=224-285.
DR PDBsum; 1CI6; -.
DR AlphaFoldDB; P28033; -.
DR SMR; P28033; -.
DR BioGRID; 198669; 17.
DR ComplexPortal; CPX-66; bZIP transcription factor complex, Cebpb-Ddit3.
DR ComplexPortal; CPX-68; bZIP transcription factor complex, Cebpb-Cebpb.
DR ComplexPortal; CPX-685; c-Myb-C/EBPbeta complex.
DR DIP; DIP-37539N; -.
DR IntAct; P28033; 14.
DR MINT; P28033; -.
DR STRING; 10090.ENSMUSP00000069850; -.
DR GlyGen; P28033; 2 sites.
DR iPTMnet; P28033; -.
DR PhosphoSitePlus; P28033; -.
DR EPD; P28033; -.
DR jPOST; P28033; -.
DR MaxQB; P28033; -.
DR PaxDb; P28033; -.
DR PeptideAtlas; P28033; -.
DR PRIDE; P28033; -.
DR ProteomicsDB; 283878; -. [P28033-1]
DR ProteomicsDB; 283879; -. [P28033-3]
DR ProteomicsDB; 283880; -. [P28033-2]
DR Antibodypedia; 3782; 686 antibodies from 42 providers.
DR DNASU; 12608; -.
DR Ensembl; ENSMUST00000070642; ENSMUSP00000069850; ENSMUSG00000056501. [P28033-1]
DR GeneID; 12608; -.
DR KEGG; mmu:12608; -.
DR UCSC; uc008oaf.2; mouse. [P28033-1]
DR CTD; 1051; -.
DR MGI; MGI:88373; Cebpb.
DR VEuPathDB; HostDB:ENSMUSG00000056501; -.
DR eggNOG; KOG3119; Eukaryota.
DR GeneTree; ENSGT00940000162137; -.
DR HOGENOM; CLU_043327_1_0_1; -.
DR InParanoid; P28033; -.
DR OMA; RLVAWDA; -.
DR PhylomeDB; P28033; -.
DR TreeFam; TF105008; -.
DR Reactome; R-MMU-2559582; Senescence-Associated Secretory Phenotype (SASP).
DR BioGRID-ORCS; 12608; 12 hits in 75 CRISPR screens.
DR ChiTaRS; Cebpb; mouse.
DR EvolutionaryTrace; P28033; -.
DR PRO; PR:P28033; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; P28033; protein.
DR Bgee; ENSMUSG00000056501; Expressed in granulocyte and 236 other tissues.
DR ExpressionAtlas; P28033; baseline and differential.
DR Genevisible; P28033; MM.
DR GO; GO:1990647; C:C/EBP complex; IPI:ComplexPortal.
DR GO; GO:0036488; C:CHOP-C/EBP complex; ISO:MGI.
DR GO; GO:0000785; C:chromatin; IDA:BHF-UCL.
DR GO; GO:0000779; C:condensed chromosome, centromeric region; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0016363; C:nuclear matrix; IDA:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; IDA:MGI.
DR GO; GO:0003682; F:chromatin binding; IDA:UniProtKB.
DR GO; GO:0031490; F:chromatin DNA binding; IDA:MGI.
DR GO; GO:0003677; F:DNA binding; IDA:MGI.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:MGI.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IDA:UniProtKB.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; ISS:UniProtKB.
DR GO; GO:0035035; F:histone acetyltransferase binding; IPI:UniProtKB.
DR GO; GO:0042826; F:histone deacetylase binding; IPI:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:UniProtKB.
DR GO; GO:0019900; F:kinase binding; IPI:UniProtKB.
DR GO; GO:0035259; F:nuclear glucocorticoid receptor binding; ISO:MGI.
DR GO; GO:0046982; F:protein heterodimerization activity; ISO:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:MGI.
DR GO; GO:0000979; F:RNA polymerase II core promoter sequence-specific DNA binding; IDA:BHF-UCL.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; ISO:MGI.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; ISO:MGI.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:UniProtKB.
DR GO; GO:0044389; F:ubiquitin-like protein ligase binding; IPI:UniProtKB.
DR GO; GO:0050873; P:brown fat cell differentiation; IMP:UniProtKB.
DR GO; GO:0071230; P:cellular response to amino acid stimulus; IDA:MGI.
DR GO; GO:0071347; P:cellular response to interleukin-1; ISO:MGI.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; ISO:MGI.
DR GO; GO:0071407; P:cellular response to organic cyclic compound; IEA:Ensembl.
DR GO; GO:0042742; P:defense response to bacterium; IMP:UniProtKB.
DR GO; GO:0001892; P:embryonic placenta development; IGI:MGI.
DR GO; GO:0045444; P:fat cell differentiation; IDA:MGI.
DR GO; GO:0002432; P:granuloma formation; IMP:UniProtKB.
DR GO; GO:0072574; P:hepatocyte proliferation; IDA:UniProtKB.
DR GO; GO:0070059; P:intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; IMP:ParkinsonsUK-UCL.
DR GO; GO:0097421; P:liver regeneration; IMP:UniProtKB.
DR GO; GO:0060644; P:mammary gland epithelial cell differentiation; IMP:MGI.
DR GO; GO:0033598; P:mammary gland epithelial cell proliferation; IMP:MGI.
DR GO; GO:0007613; P:memory; IEA:Ensembl.
DR GO; GO:0061515; P:myeloid cell development; IC:ComplexPortal.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IDA:MGI.
DR GO; GO:0042130; P:negative regulation of T cell proliferation; IDA:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:MGI.
DR GO; GO:0030182; P:neuron differentiation; IDA:MGI.
DR GO; GO:0001541; P:ovarian follicle development; IMP:UniProtKB.
DR GO; GO:0070169; P:positive regulation of biomineral tissue development; ISO:MGI.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; IMP:YuBioLab.
DR GO; GO:0045600; P:positive regulation of fat cell differentiation; IMP:GO_Central.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:MGI.
DR GO; GO:0050729; P:positive regulation of inflammatory response; IGI:ARUK-UCL.
DR GO; GO:0032753; P:positive regulation of interleukin-4 production; IDA:UniProtKB.
DR GO; GO:0045669; P:positive regulation of osteoblast differentiation; IDA:MGI.
DR GO; GO:2000120; P:positive regulation of sodium-dependent phosphate transport; ISO:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:1990440; P:positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress; ISO:MGI.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:MGI.
DR GO; GO:0045595; P:regulation of cell differentiation; IBA:GO_Central.
DR GO; GO:2001198; P:regulation of dendritic cell differentiation; IGI:ARUK-UCL.
DR GO; GO:0032675; P:regulation of interleukin-6 production; IDA:MGI.
DR GO; GO:1901329; P:regulation of odontoblast differentiation; ISS:UniProtKB.
DR GO; GO:0045670; P:regulation of osteoclast differentiation; IDA:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IMP:GO_Central.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; ISS:UniProtKB.
DR GO; GO:0032496; P:response to lipopolysaccharide; IMP:BHF-UCL.
DR GO; GO:0035711; P:T-helper 1 cell activation; IMP:UniProtKB.
DR GO; GO:0006366; P:transcription by RNA polymerase II; IDA:MGI.
DR InterPro; IPR004827; bZIP.
DR InterPro; IPR046347; bZIP_sf.
DR InterPro; IPR016468; C/EBP_chordates.
DR Pfam; PF07716; bZIP_2; 1.
DR PIRSF; PIRSF005879; CCAAT/enhancer-binding; 1.
DR SMART; SM00338; BRLZ; 1.
DR SUPFAM; SSF57959; SSF57959; 1.
DR PROSITE; PS50217; BZIP; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Activator; Alternative initiation; Cytoplasm;
KW Differentiation; DNA-binding; Glycoprotein; Isopeptide bond; Methylation;
KW Nucleus; Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation; Ubl conjugation.
FT CHAIN 1..296
FT /note="CCAAT/enhancer-binding protein beta"
FT /id="PRO_0000076618"
FT DOMAIN 222..285
FT /note="bZIP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 1..22
FT /note="Required for Lys-133 sumoylation"
FT /evidence="ECO:0000250|UniProtKB:P17676"
FT REGION 22..104
FT /note="Required for MYC transcriptional repression"
FT /evidence="ECO:0000269|PubMed:16585579"
FT REGION 171..199
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 226..246
FT /note="Basic motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 248..255
FT /note="Leucine-zipper"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT COMPBIAS 171..189
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 3
FT /note="Asymmetric dimethylarginine; by CARM1"
FT /evidence="ECO:0000269|PubMed:20111005"
FT MOD_RES 39
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000269|PubMed:18486321"
FT MOD_RES 39
FT /note="N6-methylated lysine; alternate"
FT /evidence="ECO:0000305|PubMed:18647749"
FT MOD_RES 98
FT /note="N6-acetyllysine; by KAT2A and KAT2B"
FT /evidence="ECO:0000305|PubMed:17301242"
FT MOD_RES 101
FT /note="N6-acetyllysine; by KAT2A and KAT2B"
FT /evidence="ECO:0000305|PubMed:17301242"
FT MOD_RES 102
FT /note="N6-acetyllysine; by KAT2A and KAT2B; alternate"
FT /evidence="ECO:0000305|PubMed:17301242"
FT MOD_RES 179
FT /note="Phosphothreonine; by GSK3-beta"
FT /evidence="ECO:0000269|PubMed:15985551,
FT ECO:0000269|PubMed:17601773, ECO:0000269|PubMed:19478079"
FT MOD_RES 184
FT /note="Phosphoserine; by GSK3-beta"
FT /evidence="ECO:0000269|PubMed:15985551,
FT ECO:0000269|PubMed:17601773, ECO:0000269|PubMed:19478079,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 188
FT /note="Phosphothreonine; by RPS6KA1, CDK2 and MAPK"
FT /evidence="ECO:0000269|PubMed:15985551,
FT ECO:0000269|PubMed:17601773, ECO:0000269|PubMed:19324970,
FT ECO:0000269|PubMed:19478079, ECO:0007744|PubMed:21183079"
FT MOD_RES 217
FT /note="Phosphothreonine; by RPS6KA1 and PKC/PRKCA"
FT /evidence="ECO:0000269|PubMed:10635333"
FT MOD_RES 239
FT /note="Phosphoserine; by PKC/PRKCA"
FT /evidence="ECO:0000250|UniProtKB:P17676"
FT MOD_RES 276
FT /note="Phosphoserine; by CaMK2"
FT /evidence="ECO:0000305|PubMed:1314426"
FT CARBOHYD 180
FT /note="O-linked (GlcNAc) serine"
FT /evidence="ECO:0000269|PubMed:19478079"
FT CARBOHYD 181
FT /note="O-linked (GlcNAc) serine"
FT /evidence="ECO:0000269|PubMed:19478079"
FT CROSSLNK 102
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0000250|UniProtKB:P17676"
FT CROSSLNK 133
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO); alternate"
FT /evidence="ECO:0000269|PubMed:16585579,
FT ECO:0000269|PubMed:20194620, ECO:0000269|PubMed:24061474"
FT CROSSLNK 133
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0000250|UniProtKB:P17676"
FT CROSSLNK 144
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P17676"
FT CROSSLNK 211
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P17676"
FT CROSSLNK 213
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P17676"
FT CROSSLNK 283
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P17676"
FT VAR_SEQ 1..151
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_053976"
FT VAR_SEQ 1..21
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_053977"
FT MUTAGEN 39
FT /note="K->A,Q: No effect on interaction with EP300."
FT /evidence="ECO:0000269|PubMed:18486321"
FT MUTAGEN 39
FT /note="K->R: Dominant negative. Loss of transactivation
FT activity. No effect on interaction with EP300."
FT /evidence="ECO:0000269|PubMed:18486321"
FT MUTAGEN 98
FT /note="K->R: No effect on transactivation activity. Not
FT acetylated after glucocorticoid-stimulation and no increase
FT of transactivation activity; when associated with R-101 and
FT R-102."
FT /evidence="ECO:0000269|PubMed:17301242,
FT ECO:0000269|PubMed:18486321"
FT MUTAGEN 101
FT /note="K->R: Not acetylated after glucocorticoid-
FT stimulation and no increase of transactivation activity;
FT when associated with R-98 and R-102."
FT /evidence="ECO:0000269|PubMed:17301242"
FT MUTAGEN 102
FT /note="K->R: Not acetylated and no increase of
FT transactivation activity after glucocorticoid-stimulation;
FT when associated with R-98 and R-101."
FT /evidence="ECO:0000269|PubMed:17301242"
FT MUTAGEN 133
FT /note="K->R: Not sumoylated. Decreases ubiquitination and
FT increases stability. Loss of proliferation inhibition in T
FT cells. No effect on transactivation activity."
FT /evidence="ECO:0000269|PubMed:16585579,
FT ECO:0000269|PubMed:20194620, ECO:0000269|PubMed:24061474"
FT MUTAGEN 135
FT /note="E->A: Not sumoylated and not ubiquitinated."
FT /evidence="ECO:0000269|PubMed:20194620"
FT MUTAGEN 179
FT /note="T->A: Disruption of phosphorylation by MAPK and
FT GSK3B, acquisition of DNA-binding activity and
FT transactivation function; when associated with A-184 and A-
FT 188."
FT /evidence="ECO:0000269|PubMed:15985551"
FT MUTAGEN 180
FT /note="S->A: Highly increases transactivation activity;
FT when associated with A-181."
FT /evidence="ECO:0000269|PubMed:19478079"
FT MUTAGEN 181
FT /note="S->A: Highly increases transactivation activity;
FT when associated with A-180."
FT /evidence="ECO:0000269|PubMed:19478079"
FT MUTAGEN 184
FT /note="S->A: Disruption of phosphorylation by MAPK and
FT GSK3B, acquisition of DNA-binding activity and
FT transactivation function; when associated with A-179 and A-
FT 188."
FT /evidence="ECO:0000269|PubMed:15985551"
FT MUTAGEN 188
FT /note="T->A: Disruption of phosphorylation by MAPK and
FT GSK3B, acquisition of DNA-binding activity and
FT transactivation function; when associated with A-179 and A-
FT 184."
FT /evidence="ECO:0000269|PubMed:15985551"
FT MUTAGEN 215
FT /note="K->R: No effect on transactivation activity."
FT /evidence="ECO:0000269|PubMed:18486321"
FT MUTAGEN 217
FT /note="T->A: Loss of hepatocyte proliferation induction by
FT TGFA."
FT /evidence="ECO:0000269|PubMed:10635333"
FT MUTAGEN 217
FT /note="T->E: Induces hepatocyte proliferation."
FT /evidence="ECO:0000269|PubMed:10635333"
FT MUTAGEN 276
FT /note="S->A: Reduces phosphorylation in response to
FT calcium."
FT /evidence="ECO:0000269|PubMed:1314426"
FT HELIX 240..282
FT /evidence="ECO:0007829|PDB:1CI6"
SQ SEQUENCE 296 AA; 31446 MW; 827AC4AFC209AE89 CRC64;
MHRLLAWDAA CLPPPPAAFR PMEVANFYYE PDCLAYGAKA ARAAPRAPAA EPAIGEHERA
IDFSPYLEPL APAADFAAPA PAHHDFLSDL FADDYGAKPS KKPADYGYVS LGRAGAKAAP
PACFPPPPPA ALKAEPGFEP ADCKRADDAP AMAAGFPFAL RAYLGYQATP SGSSGSLSTS
SSSSPPGTPS PADAKAAPAA CFAGPPAAPA KAKAKKTVDK LSDEYKMRRE RNNIAVRKSR
DKAKMRNLET QHKVLELTAE NERLQKKVEQ LSRELSTLRN LFKQLPEPLL ASAGHC
