| IED ID | IndEnz0002014253 |
| Enzyme Type ID | protease014253 |
| Protein Name |
CCAAT/enhancer-binding protein beta C/EBP beta AGP/EBP Interleukin-6-dependent-binding protein IL-6DBP Liver-enriched transcriptional activator LAP |
| Gene Name | Cebpb |
| Organism | Mus musculus (Mouse) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Glires (Rodents and rabbits) Rodentia Myomorpha (mice and others) Muroidea Muridae Murinae Mus Mus Mus musculus (Mouse) |
| Enzyme Sequence | MHRLLAWDAACLPPPPAAFRPMEVANFYYEPDCLAYGAKAARAAPRAPAAEPAIGEHERAIDFSPYLEPLAPAADFAAPAPAHHDFLSDLFADDYGAKPSKKPADYGYVSLGRAGAKAAPPACFPPPPPAALKAEPGFEPADCKRADDAPAMAAGFPFALRAYLGYQATPSGSSGSLSTSSSSSPPGTPSPADAKAAPAACFAGPPAAPAKAKAKKTVDKLSDEYKMRRERNNIAVRKSRDKAKMRNLETQHKVLELTAENERLQKKVEQLSRELSTLRNLFKQLPEPLLASAGHC |
| Enzyme Length | 296 |
| Uniprot Accession Number | P28033 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | |
| Enzyme Function | FUNCTION: Important transcription factor regulating the expression of genes involved in immune and inflammatory responses (PubMed:16585579, PubMed:17911624, PubMed:18486321, PubMed:20111005). Plays also a significant role in adipogenesis, as well as in the gluconeogenic pathway, liver regeneration, and hematopoiesis (PubMed:9727068, PubMed:10635333, PubMed:17301242, PubMed:17601773, PubMed:19478079, PubMed:24061474, PubMed:24216764). The consensus recognition site is 5'-T[TG]NNGNAA[TG]-3'. Its functional capacity is governed by protein interactions and post-translational protein modifications. During early embryogenesis, plays essential and redundant functions with CEBPA (PubMed:15509779). Has a promitotic effect on many cell types such as hepatocytes and adipocytes but has an antiproliferative effect on T-cells by repressing MYC expression, facilitating differentiation along the T-helper 2 lineage (PubMed:9727068, PubMed:10635333, PubMed:16585579). Binds to regulatory regions of several acute-phase and cytokines genes and plays a role in the regulation of acute-phase reaction and inflammation. Plays also a role in intracellular bacteria killing (PubMed:17911624). During adipogenesis, is rapidly expressed and, after activation by phosphorylation, induces CEBPA and PPARG, which turn on the series of adipocyte genes that give rise to the adipocyte phenotype. The delayed transactivation of the CEBPA and PPARG genes by CEBPB appears necessary to allow mitotic clonal expansion and thereby progression of terminal differentiation (PubMed:15985551, PubMed:17301242, PubMed:17601773, PubMed:20194620). Essential for female reproduction because of a critical role in ovarian follicle development (PubMed:9303532). Restricts osteoclastogenesis (PubMed:19440205). Together with NFE2L1; represses expression of DSPP during odontoblast differentiation (By similarity). {ECO:0000250|UniProtKB:P17676, ECO:0000250|UniProtKB:P21272, ECO:0000269|PubMed:10635333, ECO:0000269|PubMed:1314426, ECO:0000269|PubMed:15509779, ECO:0000269|PubMed:15985551, ECO:0000269|PubMed:16585579, ECO:0000269|PubMed:17301242, ECO:0000269|PubMed:17601773, ECO:0000269|PubMed:17911624, ECO:0000269|PubMed:18486321, ECO:0000269|PubMed:19440205, ECO:0000269|PubMed:19478079, ECO:0000269|PubMed:20111005, ECO:0000269|PubMed:20194620, ECO:0000269|PubMed:24061474, ECO:0000269|PubMed:24216764, ECO:0000269|PubMed:9303532, ECO:0000269|PubMed:9727068, ECO:0000303|PubMed:25451943}.; FUNCTION: [Isoform 2]: Essential for gene expression induction in activated macrophages. Plays a major role in immune responses such as CD4(+) T-cell response, granuloma formation and endotoxin shock. Not essential for intracellular bacteria killing. {ECO:0000269|PubMed:17911624}.; FUNCTION: [Isoform 3]: Acts as a dominant negative through heterodimerization with isoform 2 (By similarity). Promotes osteoblast differentiation and osteoclastogenesis (PubMed:19440205). {ECO:0000250|UniProtKB:P17676, ECO:0000250|UniProtKB:P21272, ECO:0000269|PubMed:19440205}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Alternative sequence (2); Chain (1); Compositional bias (1); Cross-link (7); Domain (1); Glycosylation (2); Helix (1); Modified residue (12); Mutagenesis (16); Region (5) |
| Keywords | 3D-structure;Acetylation;Activator;Alternative initiation;Cytoplasm;DNA-binding;Differentiation;Glycoprotein;Isopeptide bond;Methylation;Nucleus;Phosphoprotein;Reference proteome;Transcription;Transcription regulation;Ubl conjugation |
| Interact With | Q99PV5; Q9JHD2; Q92831 |
| Induction | INDUCTION: Up-regulated by cold exposure. {ECO:0000269|PubMed:19641492}. |
| Subcellular Location | SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:16585579, ECO:0000269|PubMed:19015024}. Cytoplasm {ECO:0000250|UniProtKB:P17676}. Note=In T-cells when sumoylated drawn to pericentric heterochromatin thereby allowing proliferation (PubMed:16585579). Translocates to the nucleus when phosphorylated at Ser-288 (By similarity). {ECO:0000250|UniProtKB:P17676, ECO:0000269|PubMed:16585579}. |
| Modified Residue | MOD_RES 3; /note="Asymmetric dimethylarginine; by CARM1"; /evidence="ECO:0000269|PubMed:20111005"; MOD_RES 39; /note="N6-acetyllysine; alternate"; /evidence="ECO:0000269|PubMed:18486321"; MOD_RES 39; /note="N6-methylated lysine; alternate"; /evidence="ECO:0000305|PubMed:18647749"; MOD_RES 98; /note="N6-acetyllysine; by KAT2A and KAT2B"; /evidence="ECO:0000305|PubMed:17301242"; MOD_RES 101; /note="N6-acetyllysine; by KAT2A and KAT2B"; /evidence="ECO:0000305|PubMed:17301242"; MOD_RES 102; /note="N6-acetyllysine; by KAT2A and KAT2B; alternate"; /evidence="ECO:0000305|PubMed:17301242"; MOD_RES 179; /note="Phosphothreonine; by GSK3-beta"; /evidence="ECO:0000269|PubMed:15985551, ECO:0000269|PubMed:17601773, ECO:0000269|PubMed:19478079"; MOD_RES 184; /note="Phosphoserine; by GSK3-beta"; /evidence="ECO:0000269|PubMed:15985551, ECO:0000269|PubMed:17601773, ECO:0000269|PubMed:19478079, ECO:0007744|PubMed:21183079"; MOD_RES 188; /note="Phosphothreonine; by RPS6KA1, CDK2 and MAPK"; /evidence="ECO:0000269|PubMed:15985551, ECO:0000269|PubMed:17601773, ECO:0000269|PubMed:19324970, ECO:0000269|PubMed:19478079, ECO:0007744|PubMed:21183079"; MOD_RES 217; /note="Phosphothreonine; by RPS6KA1 and PKC/PRKCA"; /evidence="ECO:0000269|PubMed:10635333"; MOD_RES 239; /note="Phosphoserine; by PKC/PRKCA"; /evidence="ECO:0000250|UniProtKB:P17676"; MOD_RES 276; /note="Phosphoserine; by CaMK2"; /evidence="ECO:0000305|PubMed:1314426" |
| Post Translational Modification | PTM: Sumoylated by polymeric chains of SUMO2 or SUMO3. Sumoylation at Lys-133 is required for inhibition of T-cells proliferation (PubMed:16585579). In adipocytes, sumoylation at Lys-133 by PIAS1 leads to ubiquitination and subsequent proteasomal degradation (PubMed:24061474). Desumoylated by SENP2, which abolishes ubiquitination and stabilizes protein levels (PubMed:20194620). {ECO:0000250|UniProtKB:P17676, ECO:0000269|PubMed:16585579, ECO:0000269|PubMed:20194620, ECO:0000269|PubMed:24061474}.; PTM: Ubiquitinated, leading to proteasomal degradation. {ECO:0000269|PubMed:24061474}.; PTM: Phosphorylated at Thr-188 by MAPK and CDK2, serves to prime phosphorylation at Thr-179 and Ser-184 by GSK3B and acquire DNA-binding as well as transactivation activities, required to induce adipogenesis. MAPK and CDK2 act sequentially to maintain Thr-188 in the primed phosphorylated state during mitotical cloning expansion and thereby progression of terminal differentiation. Phosphorylation at Thr-217 enhances transactivation activity. Phosphorylation at Ser-276 in response to calcium increases transactivation activity (PubMed:1314426). Phosphorylated at Thr-188 by RPS6KA1 (By similarity). {ECO:0000250|UniProtKB:P17676, ECO:0000269|PubMed:1314426, ECO:0000269|PubMed:15985551, ECO:0000269|PubMed:17601773}.; PTM: O-glycosylated, glycosylation at Ser-180 and Ser-181 prevents phosphorylation on Thr-188, Ser-184 and Thr-179 and DNA binding activity which delays the adipocyte differentiation program. {ECO:0000269|PubMed:19478079}.; PTM: Acetylated. Acetylation at Lys-39 is an important and dynamic regulatory event that contributes to its ability to transactivate target genes, including those associated with adipogenesis and adipocyte function. Deacetylation by HDAC1 represses its transactivation activity (PubMed:18486321). Acetylated by KAT2A and KAT2B within a cluster of lysine residues between amino acids 98-102, this acetylation is strongly induced by glucocorticoid treatment and enhances transactivation activity (PubMed:17301242). {ECO:0000269|PubMed:17301242, ECO:0000269|PubMed:18486321}.; PTM: Methylated. Methylation at Arg-3 by CARM1 and at Lys-39 by EHMT2, inhibits transactivation activity. Methylation is probably inhibited by phosphorylation at Thr-188. {ECO:0000269|PubMed:20111005, ECO:0000305|PubMed:18647749}. |
| Signal Peptide | |
| Structure 3D | X-ray crystallography (1) |
| Cross Reference PDB | 1CI6; |
| Mapped Pubmed ID | 10082561; 10092809; 10224054; 10319019; 10455174; 10490653; 10510303; 10528209; 10588870; 10600708; 10683373; 10707954; 10747954; 10859308; 10982846; 11024029; 11151091; 11159172; 11196172; 11217851; 11684016; 11726507; 11726661; 11733516; 11756662; 11877276; 11940593; 11976687; 12048207; 12048245; 12071851; 12072435; 12095417; 12177065; 12184911; 12213825; 12215258; 12355443; 12379662; 12456789; 12466851; 12524424; 12525691; 12556485; 12558604; 12821655; 12832471; 12837957; 12847250; 12871593; 1371974; 1371993; 14576085; 14593102; 14670999; 14681479; 14688407; 14697236; 14736879; 14981542; 15005571; 15051496; 15060147; 15130516; 15143161; 15158467; 15175325; 15187136; 15289464; 15308669; 15314150; 15367685; 15383601; 15504955; 15509789; 15519652; 15598659; 15601867; 15613028; 15618518; 15632071; 15659391; 15665733; 15713650; 15721291; 15737626; 15762841; 15775988; 15788409; 15809228; 15850785; 15860545; 15863502; 15870285; 15878863; 15936952; 16046404; 16054042; 16054051; 16107878; 16120603; 16141072; 16150866; 16166081; 16205634; 16288022; 16318580; 16431920; 16439483; 16492136; 16632469; 16682266; 16698852; 16751774; 16784777; 16837772; 16850160; 16892179; 16899075; 16959612; 17064678; 17078024; 17110376; 17177178; 17192478; 17210130; 17244625; 17254333; 17264204; 17288991; 17387171; 17433708; 17464987; 17504763; 17510195; 17524357; 17525287; 17576771; 17584738; 17599912; 17646392; 17702848; 17724128; 17855774; 17888405; 17913887; 17975479; 17982082; 18056834; 18092000; 18159255; 18174271; 18195020; 18250155; 18339625; 18346930; 18388310; 18439838; 18448564; 18467525; 18478268; 18550528; 18596980; 18622014; 18636078; 18678862; 18703634; 18760339; 18761321; 18824566; 18843047; 18981473; 18996961; 19026986; 19029947; 19056928; 19103292; 19126543; 19164449; 19169276; 19218285; 19228596; 19229324; 19297554; 19344698; 19353522; 19398579; 19443782; 19454718; 19520806; 19563810; 19581927; 19628693; 19652026; 19749746; 19805133; 19811452; 19833158; 19875812; 19885945; 19940121; 19955657; 20047998; 20048163; 20052801; 20054865; 20086097; 20194724; 20209087; 20351173; 20352127; 20371871; 20410440; 20446924; 20479126; 20498378; 20501671; 20529561; 20548288; 20605485; 20686481; 20730378; 20876575; 20960217; 20962249; 20966351; 20979051; 21047912; 21072215; 21122806; 21148742; 21167261; 21177758; 21183071; 21185356; 21267068; 21268070; 21292824; 21303932; 21308778; 21346244; 21353395; 21455770; 21464964; 21471197; 21487015; 21521687; 21558273; 21562127; 21562223; 21606199; 21847090; 21897364; 21899882; 21933012; 21982742; 21998664; 22003384; 22011580; 22044243; 22068055; 22074460; 22078933; 22082962; 22095691; 22138520; 22147692; 22172035; 22260630; 22306325; 22355693; 22369944; 22411169; 22503555; 22521691; 22556424; 22573614; 22581863; 22634316; 22662254; 22707723; 22722334; 22732594; 22737085; 22742194; 22751693; 22859371; 22865229; 22902781; 22948537; 22977257; 23024276; 23034923; 23065276; 23159614; 23160954; 23177475; 23251594; 23266643; 23375831; 23382991; 23456364; 23472114; 23475960; 23512806; 23515163; 23524343; 23541989; 23547050; 23564453; 23564995; 23568773; 23585399; 23643813; 23665916; 23754749; 23755188; 23775115; 23782693; 23798556; 23810419; 23813955; 23840343; 23889939; 23893854; 23900421; 23907538; 23911420; 23987512; 24023826; 24078688; 24115241; 24128855; 24220850; 24238961; 24244291; 24256641; 24265756; 24273171; 24344131; 24368734; 24440820; 24466171; 24618682; 24635384; 24673832; 24881817; 24885110; 25034893; 25105964; 25156364; 25266931; 25365223; 25382637; 25401168; 25403356; 25463758; 25472717; 25617152; 25720496; 25749148; 25767874; 25779641; 25802132; 25804385; 25813145; 25848030; 25921091; 26017382; 26065429; 26066982; 26113365; 26147683; 26168729; 26217013; 26220403; 26243869; 26271478; 26317211; 26372225; 26476039; 26526992; 26646662; 26667036; 26709824; 26740594; 26913600; 26941360; 26963625; 26966068; 26984772; 27072340; 27122162; 27135215; 27147263; 27297958; 27382175; 27430527; 27522676; 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|
| Motif | |
| Gene Encoded By | |
| Mass | 31,446 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |