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 02-SEP-2026, entry version 216. 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:10635333, CC PubMed:17301242, PubMed:17601773, PubMed:19478079, PubMed:24061474, CC PubMed:24216764, PubMed:9727068). The consensus recognition site is 5'- CC 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:10635333, PubMed:16585579, CC PubMed:9727068). Binds to regulatory regions of several acute-phase and CC 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:15879117, PubMed:9742105). 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 CC CIDEC (PubMed:22245780). Interaction with CIDEA increases CC transcriptional activation of a subset of CEBPB downstream target CC genes, including ID2, IGF1, PRLR, SOCS1, SOCS3, XDH. Interaction with CC CIDEC increases transcriptional activation of SOCS1, SOCS3, TGFB1, CC TGFBR1, ID2 and XDH. Interacts with DDIT3/CHOP. Interacts with EP300; CC recruits EP300 to chromatin. Interacts with RORA; the interaction CC disrupts interaction with EP300 (PubMed:19324970). Interacts (not CC methylated) with MED23, MED26, SMARCA2, SMARCB1 and SMARCC1 CC (PubMed:20111005). Interacts with KAT2A and KAT2B (PubMed:17301242). CC Interacts with ATF5; EP300 is required for ATF5 and CEBPB interaction CC and DNA binding (PubMed:24216764). Interacts with NFE2L1; the CC heterodimer represses expression of DSPP during odontoblast CC differentiation (By similarity). {ECO:0000250|UniProtKB:P21272, CC ECO:0000269|PubMed:11018027, ECO:0000269|PubMed:11792321, CC ECO:0000269|PubMed:15644333, ECO:0000269|PubMed:15879117, CC ECO:0000269|PubMed:17301242, ECO:0000269|PubMed:18486321, CC ECO:0000269|PubMed:19015024, ECO:0000269|PubMed:19324970, CC ECO:0000269|PubMed:19641492, ECO:0000269|PubMed:20111005, CC ECO:0000269|PubMed:21602272, ECO:0000269|PubMed:22245780, CC ECO:0000269|PubMed:24216764, ECO:0000269|PubMed:27923061, CC ECO:0000269|PubMed:9742105}. CC -!- INTERACTION: CC P28033; Q99PV5: Bhlhe41; NbExp=5; IntAct=EBI-1029979, EBI-6143801; CC P28033; Q09XV5: Chd8; NbExp=2; IntAct=EBI-1029979, EBI-1169080; 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 --------------------------------------------------------------------------- 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; 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 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 CORUM; P28033; -. DR DIP; DIP-37539N; -. DR FunCoup; P28033; 1513. DR IntAct; P28033; 16. DR MINT; P28033; -. DR STRING; 10090.ENSMUSP00000069850; -. DR GlyCosmos; P28033; 2 sites, No reported glycans. DR GlyGen; P28033; 4 sites, 1 O-linked glycan (2 sites). DR iPTMnet; P28033; -. DR PhosphoSitePlus; P28033; -. DR SwissPalm; P28033; -. DR jPOST; P28033; -. DR PaxDb; 10090-ENSMUSP00000069850; -. DR PeptideAtlas; P28033; -. DR ProteomicsDB; 283878; -. [P28033-1] DR ProteomicsDB; 283879; -. [P28033-3] DR ProteomicsDB; 283880; -. [P28033-2] DR Pumba; P28033; -. DR Antibodypedia; 3782; 673 antibodies from 44 providers. DR DNASU; 12608; -. DR Ensembl; ENSMUST00000070642.4; ENSMUSP00000069850.4; ENSMUSG00000056501.4. [P28033-1] DR GeneID; 12608; -. DR KEGG; mmu:12608; -. DR UCSC; uc008oaf.2; mouse. [P28033-1] DR AGR; MGI:88373; -. 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; RLVAWDQ; -. DR OrthoDB; 10032067at2759; -. DR PhylomeDB; P28033; -. DR Reactome; R-MMU-2559582; Senescence-Associated Secretory Phenotype (SASP). DR BioGRID-ORCS; 12608; 12 hits in 80 CRISPR screens. DR EvolutionaryTrace; P28033; -. DR PRO; PR:P28033; -. DR Proteomes; UP000000589; Chromosome 2. DR RNAct; P28033; protein. DR Bgee; ENSMUSG00000056501; Expressed in granulocyte and 238 other cell types or tissues. DR ExpressionAtlas; P28033; baseline and differential. DR GO; GO:1990647; C:C/EBP complex; IPI:ComplexPortal. DR GO; GO:0036488; C:CHOP-C/EBP complex; ISO:GO_Central. 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:GO_Central. 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:0140297; F:DNA-binding transcription factor binding; ISO:GO_Central. 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:GO_Central. DR GO; GO:0046982; F:protein heterodimerization activity; ISO:GO_Central. DR GO; GO:0042803; F:protein homodimerization activity; ISO:GO_Central. DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:GO_Central. 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:GO_Central. DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:UniProtKB. DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:GO_Central. 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:GO_Central. DR GO; GO:0071222; P:cellular response to lipopolysaccharide; ISO:GO_Central. DR GO; GO:0042742; P:defense response to bacterium; IMP:UniProtKB. DR GO; GO:0006351; P:DNA-templated transcription; IEA:InterPro. 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; NAS:ComplexPortal. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; IDA:MGI. 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: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:0045893; P:positive regulation of DNA-templated transcription; IDA:MGI. 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:GO_Central. 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: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:0006355; P:regulation of DNA-templated transcription; ISS:UniProtKB. 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: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 CDD; cd14712; bZIP_CEBPB; 1. DR FunFam; 1.20.5.170:FF:000028; CCAAT/enhancer-binding protein beta; 1. DR Gene3D; 1.20.5.170; -; 1. DR InterPro; IPR004827; bZIP. DR InterPro; IPR046347; bZIP_sf. DR InterPro; IPR031106; C/EBP. DR InterPro; IPR016468; C/EBP_chordates. DR PANTHER; PTHR23334; CCAAT/ENHANCER BINDING PROTEIN; 1. DR PANTHER; PTHR23334:SF21; CCAAT_ENHANCER-BINDING PROTEIN BETA; 1. DR Pfam; PF07716; bZIP_2; 1. DR PIRSF; PIRSF005879; CCAAT/enhancer-binding; 1. DR SMART; SM00338; BRLZ; 1. DR SUPFAM; SSF57959; Leucine zipper domain; 1. DR PROSITE; PS50217; BZIP; 1. DR PDBsum; 1CI6; -. 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 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 FT glucocorticoid-stimulation and no increase of FT transactivation activity; when associated with R-98 and FT 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 FT A-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 FT A-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 FT A-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 //