CEBPA_MOUSE
ID CEBPA_MOUSE Reviewed; 359 AA.
AC P53566; Q91XB6;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2002, sequence version 2.
DT 03-AUG-2022, entry version 180.
DE RecName: Full=CCAAT/enhancer-binding protein alpha {ECO:0000312|MGI:MGI:99480};
DE Short=C/EBP alpha {ECO:0000312|MGI:MGI:99480};
GN Name=Cebpa {ECO:0000312|MGI:MGI:99480};
GN Synonyms=Cebp {ECO:0000303|PubMed:1935900};
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 [GENOMIC DNA].
RX PubMed=2006196; DOI=10.1073/pnas.88.6.2593;
RA Christy R.J., Kaestner K.H., Geiman D.E., Lane M.D.;
RT "CCAAT/enhancer binding protein gene promoter: binding of nuclear factors
RT during differentiation of 3T3-L1 preadipocytes.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:2593-2597(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3).
RC STRAIN=FVB/N; TISSUE=Liver;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP FUNCTION.
RX PubMed=1935900; DOI=10.1002/j.1460-2075.1991.tb04948.x;
RA Samuelsson L., Stroemberg K., Vikman K., Bjursell G., Enerbaeck S.;
RT "The CCAAT/enhancer binding protein and its role in adipocyte
RT differentiation: evidence for direct involvement in terminal adipocyte
RT development.";
RL EMBO J. 10:3787-3793(1991).
RN [5]
RP FUNCTION, ALTERNATIVE TRANSLATIONAL INITIATION, TISSUE SPECIFICITY,
RP SUBCELLULAR LOCATION, AND DNA-BINDING.
RX PubMed=8415748; DOI=10.1073/pnas.90.20.9606;
RA Lin F.T., MacDougald O.A., Diehl A.M., Lane M.D.;
RT "A 30-kDa alternative translation product of the CCAAT/enhancer binding
RT protein alpha message: transcriptional activator lacking antimitotic
RT activity.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:9606-9610(1993).
RN [6]
RP FUNCTION.
RX PubMed=8090719; DOI=10.1073/pnas.91.19.8757;
RA Lin F.T., Lane M.D.;
RT "CCAAT/enhancer binding protein alpha is sufficient to initiate the 3T3-L1
RT adipocyte differentiation program.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:8757-8761(1994).
RN [7]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=8798745; DOI=10.1074/jbc.271.40.24753;
RA Flodby P., Barlow C., Kylefjord H., Ahrlund-Richter L., Xanthopoulos K.G.;
RT "Increased hepatic cell proliferation and lung abnormalities in mice
RT deficient in CCAAT/enhancer binding protein alpha.";
RL J. Biol. Chem. 271:24753-24760(1996).
RN [8]
RP FUNCTION, MUTAGENESIS OF TYR-286; VAL-288; GLU-291; ILE-295 AND ARG-298,
RP AND DNA-BINDING.
RX PubMed=11672531; DOI=10.1016/s0092-8674(01)00516-5;
RA Porse B.T., Pedersen T.A., Xu X., Lindberg B., Wewer U.M., Friis-Hansen L.,
RA Nerlov C.;
RT "E2F repression by C/EBPalpha is required for adipogenesis and
RT granulopoiesis in vivo.";
RL Cell 107:247-258(2001).
RN [9]
RP FUNCTION, MUTAGENESIS OF 182-PRO--PRO-188 AND SER-193, INTERACTION WITH
RP CDK2; CDK4 AND SMARCA2, AND PHOSPHORYLATION AT SER-193.
RX PubMed=15107404; DOI=10.1101/gad.1183304;
RA Wang G.L., Iakova P., Wilde M., Awad S., Timchenko N.A.;
RT "Liver tumors escape negative control of proliferation via PI3K/Akt-
RT mediated block of C/EBP alpha growth inhibitory activity.";
RL Genes Dev. 18:912-925(2004).
RN [10]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=15589173; DOI=10.1016/j.immuni.2004.11.006;
RA Zhang P., Iwasaki-Arai J., Iwasaki H., Fenyus M.L., Dayaram T., Owens B.M.,
RA Shigematsu H., Levantini E., Huettner C.S., Lekstrom-Himes J.A., Akashi K.,
RA Tenen D.G.;
RT "Enhancement of hematopoietic stem cell repopulating capacity and self-
RT renewal in the absence of the transcription factor C/EBP alpha.";
RL Immunity 21:853-863(2004).
RN [11]
RP FUNCTION.
RX PubMed=14660596; DOI=10.1074/jbc.m312709200;
RA Muller C., Calkhoven C.F., Sha X., Leutz A.;
RT "The CCAAT enhancer-binding protein alpha (C/EBPalpha) requires a SWI/SNF
RT complex for proliferation arrest.";
RL J. Biol. Chem. 279:7353-7358(2004).
RN [12]
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 [13]
RP FUNCTION, AND INTERACTION WITH FOXO1.
RX PubMed=17090532; DOI=10.1074/jbc.m607215200;
RA Qiao L., Shao J.;
RT "SIRT1 regulates adiponectin gene expression through Foxo1-C/enhancer-
RT binding protein alpha transcriptional complex.";
RL J. Biol. Chem. 281:39915-39924(2006).
RN [14]
RP FUNCTION, INTERACTION WITH SREBF1, MUTAGENESIS OF 222-THR--SER-230, AND
RP PHOSPHORYLATION AT THR-222; THR-226 AND SER-230.
RX PubMed=17290224; DOI=10.1038/sj.emboj.7601563;
RA Pedersen T.A., Bereshchenko O., Garcia-Silva S., Ermakova O., Kurz E.,
RA Mandrup S., Porse B.T., Nerlov C.;
RT "Distinct C/EBPalpha motifs regulate lipogenic and gluconeogenic gene
RT expression in vivo.";
RL EMBO J. 26:1081-1093(2007).
RN [15]
RP FUNCTION, AND INTERACTION WITH FOXO1.
RX PubMed=17627282; DOI=10.1038/sj.emboj.7601784;
RA Sekine K., Chen Y.R., Kojima N., Ogata K., Fukamizu A., Miyajima A.;
RT "Foxo1 links insulin signaling to C/EBPalpha and regulates gluconeogenesis
RT during liver development.";
RL EMBO J. 26:3607-3615(2007).
RN [16]
RP INTERACTION WITH PRDM16.
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 [17]
RP ALTERNATIVE INITIATION, AND IDENTIFICATION OF NON-CANONICAL INITIATION
RP CODON.
RX PubMed=20075868; DOI=10.1038/emboj.2009.404;
RA Muller C., Bremer A., Schreiber S., Eichwald S., Calkhoven C.F.;
RT "Nucleolar retention of a translational C/EBPalpha isoform stimulates rDNA
RT transcription and cell size.";
RL EMBO J. 29:897-909(2010).
RN [18]
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 [19]
RP FUNCTION.
RX PubMed=24367003; DOI=10.1084/jem.20130932;
RA Ohlsson E., Hasemann M.S., Willer A., Lauridsen F.K., Rapin N.,
RA Jendholm J., Porse B.T.;
RT "Initiation of MLL-rearranged AML is dependent on C/EBPalpha.";
RL J. Exp. Med. 211:5-13(2014).
RN [20]
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).
CC -!- FUNCTION: Transcription factor that coordinates proliferation arrest
CC and the differentiation of myeloid progenitors, adipocytes,
CC hepatocytes, and cells of the lung and the placenta (PubMed:8415748,
CC PubMed:15107404, PubMed:15589173). Binds directly to the consensus DNA
CC sequence 5'-T[TG]NNGNAA[TG]-3' acting as an activator on distinct
CC target genes. During early embryogenesis, plays essential and redundant
CC functions with CEBPB (PubMed:15509779). Essential for the transition
CC from common myeloid progenitors (CMP) to granulocyte/monocyte
CC progenitors (GMP) (PubMed:24367003). Critical for the proper
CC development of the liver and the lung (PubMed:8798745). Necessary for
CC terminal adipocyte differentiation, is required for postnatal
CC maintenance of systemic energy homeostasis and lipid storage
CC (PubMed:1935900, PubMed:8090719). To regulate these different processes
CC at the proper moment and tissue, interplays with other transcription
CC factors and modulators. Down-regulates the expression of genes that
CC maintain cells in an undifferentiated and proliferative state through
CC E2F1 repression, which is critical for its ability to induce adipocyte
CC and granulocyte terminal differentiation. Reciprocally E2F1 blocks
CC adipocyte differentiation by binding to specific promoters and
CC repressing CEBPA binding to its target gene promoters
CC (PubMed:11672531). Proliferation arrest also depends on a functional
CC binding to SWI/SNF complex (PubMed:14660596). In liver, regulates
CC gluconeogenesis and lipogenesis through different mechanisms. To
CC regulate gluconeogenesis, functionally cooperates with FOXO1 binding to
CC IRE-controlled promoters and regulating the expression of target genes
CC such as PCK1 or G6PC1 (PubMed:17627282). To modulate lipogenesis,
CC interacts and transcriptionally synergizes with SREBF1 in promoter
CC activation of specific lipogenic target genes such as ACAS2
CC (PubMed:17290224). In adipose tissue, seems to act as FOXO1 coactivator
CC accessing to ADIPOQ promoter through FOXO1 binding sites
CC (PubMed:17090532). {ECO:0000250|UniProtKB:P05554,
CC ECO:0000250|UniProtKB:P49715, ECO:0000269|PubMed:11672531,
CC ECO:0000269|PubMed:14660596, ECO:0000269|PubMed:15107404,
CC ECO:0000269|PubMed:15509779, ECO:0000269|PubMed:15589173,
CC ECO:0000269|PubMed:17090532, ECO:0000269|PubMed:17290224,
CC ECO:0000269|PubMed:17627282, ECO:0000269|PubMed:1935900,
CC ECO:0000269|PubMed:24367003, ECO:0000269|PubMed:8090719,
CC ECO:0000269|PubMed:8415748, ECO:0000269|PubMed:8798745}.
CC -!- FUNCTION: [Isoform 3]: Can act as dominant-negative. Binds DNA and have
CC transctivation activity, even if much less efficiently than isoform 2.
CC Does not inhibit cell proliferation. {ECO:0000250|UniProtKB:P05554,
CC ECO:0000250|UniProtKB:P49715, ECO:0000269|PubMed:8415748}.
CC -!- FUNCTION: [Isoform 4]: Directly and specifically enhances ribosomal DNA
CC transcription interacting with RNA polymerase I-specific cofactors and
CC inducing histone acetylation. {ECO:0000250|UniProtKB:P49715}.
CC -!- SUBUNIT: Binds DNA as a homodimer and as a heterodimer. Can form stable
CC heterodimers with CEBPB, CEBPD, CEBPE and CEBPG (By similarity).
CC Interacts with PRDM16 (PubMed:19641492). Interacts with UBN1 (By
CC similarity). Interacts with ZNF638; this interaction increases
CC transcriptional activation (PubMed:21602272). Interacts with the
CC complex TFDP2:E2F1; the interaction prevents CEBPA binding to target
CC gene promoters and represses its transcriptional activity (By
CC similarity). Interacts with RB1 (PubMed:15107404). Interacts (when
CC phosphorylated at SER-193) with CDK2, CDK4, E2F4 and SMARCA2
CC (PubMed:15107404). Interacts with SREBPF1 (PubMed:17290224). Interacts
CC with FOXO1 (via the Fork-head domain); the interaction increases when
CC FOXO1 is deacetylated (PubMed:17090532, PubMed:17627282). Interacts
CC with SIX1 (PubMed:27923061). Interacts (via recognition sequence) with
CC TRIB1 (By similarity). {ECO:0000250|UniProtKB:P05554,
CC ECO:0000250|UniProtKB:P49715, ECO:0000269|PubMed:15107404,
CC ECO:0000269|PubMed:17090532, ECO:0000269|PubMed:17290224,
CC ECO:0000269|PubMed:17627282, ECO:0000269|PubMed:19641492,
CC ECO:0000269|PubMed:21602272, ECO:0000269|PubMed:27923061}.
CC -!- SUBUNIT: [Isoform 1]: Interacts with TAF1A and UBTF.
CC {ECO:0000250|UniProtKB:P49715}.
CC -!- SUBUNIT: [Isoform 4]: Interacts with TAF1A and UBTF (By similarity).
CC Interacts with NPM1 (By similarity). {ECO:0000250|UniProtKB:P49715}.
CC -!- INTERACTION:
CC P53566; Q9R1E0: Foxo1; NbExp=5; IntAct=EBI-2644207, EBI-1371343;
CC P53566; Q6ZQ88: Kdm1a; NbExp=4; IntAct=EBI-2644207, EBI-1216284;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:8415748}.
CC -!- SUBCELLULAR LOCATION: [Isoform 4]: Nucleus, nucleolus
CC {ECO:0000250|UniProtKB:P05554, ECO:0000250|UniProtKB:P49715}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative initiation; Named isoforms=4;
CC Name=1;
CC IsoId=P53566-1; Sequence=Displayed;
CC Name=2; Synonyms=C/EBPalpha-p42 {ECO:0000303|PubMed:8415748};
CC IsoId=P53566-3; Sequence=VSP_057550;
CC Name=3; Synonyms=C/EBPalpha-p30 {ECO:0000303|PubMed:8415748};
CC IsoId=P53566-4; Sequence=VSP_057549;
CC Name=4; Synonyms=extended-C/EBPalpha {ECO:0000303|PubMed:20075868};
CC IsoId=P53566-5; Sequence=VSP_057608;
CC -!- TISSUE SPECIFICITY: Isoform 2 and isoform 3 are expressed in adipose
CC tissue and liver (at protein level). {ECO:0000269|PubMed:8415748}.
CC -!- DEVELOPMENTAL STAGE: At 9.5 dpc, expressed in the chorionic plate. From
CC 10.5 to at least 11.5 dpc, is also expressed in the trophoblasts of the
CC labyrinthine layer. {ECO:0000269|PubMed:15509779}.
CC -!- DOMAIN: The recognition sequence (54-72) is required for interaction
CC with TRIB1. {ECO:0000250|UniProtKB:P49715}.
CC -!- PTM: Sumoylated, sumoylation blocks the inhibitory effect on cell
CC proliferation by disrupting the interaction with SMARCA2.
CC {ECO:0000250|UniProtKB:P05554}.
CC -!- PTM: Phosphorylation at Ser-193 is required for interaction with CDK2,
CC CDK4 and SWI/SNF complex leading to cell cycle inhibition.
CC Dephosphorylated at Ser-193 by protein phosphatase 2A (PP2A) through
CC PI3K/AKT signaling pathway regulation (PubMed:15107404).
CC Phosphorylation at Thr-222 and Thr-226 by GSK3 is constitutive in
CC adipose tissue and lung. In liver, both Thr-222 and Thr-226 are
CC phosphorylated only during feeding but not during fasting
CC (PubMed:17290224). Phosphorylation of the GSK3 consensus sites
CC selectively decreases transactivation activity on IRE-controlled
CC promoters (PubMed:17290224). {ECO:0000269|PubMed:15107404,
CC ECO:0000269|PubMed:17290224}.
CC -!- PTM: Ubiquitinated by COP1 upon interaction with TRIB1.
CC {ECO:0000250|UniProtKB:P49715}.
CC -!- DISRUPTION PHENOTYPE: Mutants die of hypoglycemia at 7-10h after bith.
CC They have defects in the control of hepatic growth and lung
CC development. The liver architecture is disturbed with acinar formation.
CC They show hyperproliferation of type II pneumocytes and disturbed
CC alveolar architecture. At the molecular level, accumulation of glycogen
CC and lipids in the liver and adipose tissues is impaired, and the mutant
CC animals are severely hypoglycemic (PubMed:8798745). In very few cases
CC (less than 1%) mutants are able to survive up to 4 weeks but they are
CC sevrely retarded in development. At 2 weeks, they are about half the
CC size of their littermates, very thin and with skin problems.
CC Conditional knockout in adults leads to a lack of granulopoiesis in all
CC hematopoietic organs with no mature peripheral blood granulocytes and
CC the presence of >30% immature myeloid cells in the bone marrow, but
CC without anemia or thrombocytopenia. Animals rarely survive 4 to 5 weeks
CC of age due to sepsis as a result of granulocytopenia (PubMed:15589173).
CC Double knockout CEBPA and CEBPB results in embryonic developmental
CC arrest and death at around 10 dpc to 11 dpc, associated with a gross
CC placenta failure (PubMed:15509779). {ECO:0000269|PubMed:15509779,
CC ECO:0000269|PubMed:15589173, ECO:0000269|PubMed:8798745}.
CC -!- SIMILARITY: Belongs to the bZIP family. C/EBP subfamily. {ECO:0000305}.
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DR EMBL; M62362; AAA37374.1; -; Genomic_DNA.
DR EMBL; AC150683; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC011118; AAH11118.1; -; mRNA.
DR EMBL; BC028890; AAH28890.1; -; mRNA.
DR EMBL; BC051102; AAH51102.1; -; mRNA.
DR EMBL; BC058161; AAH58161.1; -; mRNA.
DR CCDS; CCDS21145.1; -. [P53566-1]
DR PIR; I49575; I49575.
DR RefSeq; NP_001274443.1; NM_001287514.1. [P53566-5]
DR RefSeq; NP_001274444.1; NM_001287515.1. [P53566-3]
DR RefSeq; NP_001274450.1; NM_001287521.1. [P53566-4]
DR RefSeq; NP_031704.2; NM_007678.3. [P53566-1]
DR AlphaFoldDB; P53566; -.
DR SMR; P53566; -.
DR BioGRID; 198667; 122.
DR ComplexPortal; CPX-65; bZIP transcription factor complex, Cebpa-Ddit3.
DR ComplexPortal; CPX-67; bZIP transcription factor complex, Cebpa-Cebpa.
DR CORUM; P53566; -.
DR DIP; DIP-44054N; -.
DR IntAct; P53566; 13.
DR MINT; P53566; -.
DR STRING; 10090.ENSMUSP00000096129; -.
DR ChEMBL; CHEMBL3616358; -.
DR iPTMnet; P53566; -.
DR PhosphoSitePlus; P53566; -.
DR MaxQB; P53566; -.
DR PaxDb; P53566; -.
DR PRIDE; P53566; -.
DR ProteomicsDB; 280052; -. [P53566-1]
DR ProteomicsDB; 280053; -. [P53566-3]
DR ProteomicsDB; 280054; -. [P53566-4]
DR ProteomicsDB; 280055; -. [P53566-5]
DR Antibodypedia; 38083; 723 antibodies from 40 providers.
DR DNASU; 12606; -.
DR Ensembl; ENSMUST00000042985; ENSMUSP00000096129; ENSMUSG00000034957. [P53566-1]
DR GeneID; 12606; -.
DR KEGG; mmu:12606; -.
DR UCSC; uc009gjl.2; mouse. [P53566-1]
DR CTD; 1050; -.
DR MGI; MGI:99480; Cebpa.
DR VEuPathDB; HostDB:ENSMUSG00000034957; -.
DR eggNOG; KOG3119; Eukaryota.
DR GeneTree; ENSGT00940000162646; -.
DR HOGENOM; CLU_043327_2_0_1; -.
DR InParanoid; P53566; -.
DR OMA; MPHLQYQ; -.
DR OrthoDB; 1284308at2759; -.
DR PhylomeDB; P53566; -.
DR TreeFam; TF105008; -.
DR Reactome; R-MMU-9616222; Transcriptional regulation of granulopoiesis.
DR BioGRID-ORCS; 12606; 4 hits in 76 CRISPR screens.
DR PRO; PR:P53566; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; P53566; protein.
DR Bgee; ENSMUSG00000034957; Expressed in thoracic mammary gland and 168 other tissues.
DR ExpressionAtlas; P53566; baseline and differential.
DR Genevisible; P53566; MM.
DR GO; GO:1990647; C:C/EBP complex; ISO:MGI.
DR GO; GO:0036488; C:CHOP-C/EBP complex; ISO:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0016363; C:nuclear matrix; ISO:MGI.
DR GO; GO:0005730; C:nucleolus; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0035189; C:Rb-E2F complex; ISO:MGI.
DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; ISO:MGI.
DR GO; GO:0005667; C:transcription regulator complex; IDA:MGI.
DR GO; GO:0003682; F:chromatin binding; IDA:MGI.
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:NTNU_SB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:MGI.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IDA:MGI.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; IPI:UniProtKB.
DR GO; GO:0042826; F:histone deacetylase binding; ISO:MGI.
DR GO; GO:0071837; F:HMG box domain binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; IPI:MGI.
DR GO; GO:0019900; F:kinase binding; IPI:UniProtKB.
DR GO; GO:0019904; F:protein domain specific 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:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0001163; F:RNA polymerase I transcription regulatory region sequence-specific DNA binding; ISS:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:NTNU_SB.
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:0097677; F:STAT family protein binding; ISS:UniProtKB.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:MGI.
DR GO; GO:0008134; F:transcription factor binding; IPI:GO_Central.
DR GO; GO:0050873; P:brown fat cell differentiation; IDA:MGI.
DR GO; GO:0008283; P:cell population proliferation; IMP:MGI.
DR GO; GO:0071285; P:cellular response to lithium ion; IDA:MGI.
DR GO; GO:0071407; P:cellular response to organic cyclic compound; IDA:MGI.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IDA:MGI.
DR GO; GO:0008203; P:cholesterol metabolic process; IMP:MGI.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; NAS:UniProtKB.
DR GO; GO:0001892; P:embryonic placenta development; IGI:MGI.
DR GO; GO:0002070; P:epithelial cell maturation; IMP:MGI.
DR GO; GO:0045444; P:fat cell differentiation; IDA:UniProtKB.
DR GO; GO:0042593; P:glucose homeostasis; IMP:UniProtKB.
DR GO; GO:0030851; P:granulocyte differentiation; IDA:UniProtKB.
DR GO; GO:0071425; P:hematopoietic stem cell proliferation; IMP:MGI.
DR GO; GO:0048839; P:inner ear development; IDA:MGI.
DR GO; GO:0070102; P:interleukin-6-mediated signaling pathway; ISO:MGI.
DR GO; GO:0055088; P:lipid homeostasis; IMP:UniProtKB.
DR GO; GO:0001889; P:liver development; IMP:UniProtKB.
DR GO; GO:0030324; P:lung development; IMP:UniProtKB.
DR GO; GO:0030225; P:macrophage differentiation; IMP:MGI.
DR GO; GO:0007005; P:mitochondrion organization; IMP:MGI.
DR GO; GO:0030099; P:myeloid cell differentiation; IDA:UniProtKB.
DR GO; GO:0045786; P:negative regulation of cell cycle; IDA:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:UniProtKB.
DR GO; GO:1902034; P:negative regulation of hematopoietic stem cell proliferation; IMP:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0007219; P:Notch signaling pathway; IDA:MGI.
DR GO; GO:2000144; P:positive regulation of DNA-templated transcription, initiation; ISO:MGI.
DR GO; GO:0045600; P:positive regulation of fat cell differentiation; IDA:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:ARUK-UCL.
DR GO; GO:0050729; P:positive regulation of inflammatory response; IMP:ARUK-UCL.
DR GO; GO:0043032; P:positive regulation of macrophage activation; IMP:ARUK-UCL.
DR GO; GO:0045669; P:positive regulation of osteoblast differentiation; IDA:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:NTNU_SB.
DR GO; GO:0045945; P:positive regulation of transcription by RNA polymerase III; ISO:MGI.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:MGI.
DR GO; GO:0042127; P:regulation of cell population proliferation; IMP:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:GO_Central.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:MGI.
DR GO; GO:0006360; P:transcription by RNA polymerase I; ISS:UniProtKB.
DR GO; GO:0000050; P:urea cycle; IDA:MGI.
DR GO; GO:0050872; P:white fat cell differentiation; IMP: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 Acetylation; Activator; Alternative initiation; Developmental protein;
KW DNA-binding; Isopeptide bond; Nucleus; Phosphoprotein; Reference proteome;
KW Transcription; Transcription regulation; Ubl conjugation.
FT CHAIN 1..359
FT /note="CCAAT/enhancer-binding protein alpha"
FT /id="PRO_0000076614"
FT DOMAIN 283..346
FT /note="bZIP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT DNA_BIND 286..301
FT /evidence="ECO:0000250|UniProtKB:P05554"
FT REGION 1..70
FT /note="Required to repress E2F1:TFDP1-mediated
FT transcription, to inhibit cell cycle and to induce
FT adipocyte differentiation"
FT /evidence="ECO:0000250|UniProtKB:P05554"
FT REGION 1..55
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 54..72
FT /note="Required for interaction with TRIB1"
FT /evidence="ECO:0000250|UniProtKB:P49715"
FT REGION 126..200
FT /note="Required to induce adipocyte differentiation"
FT /evidence="ECO:0000250|UniProtKB:P05554"
FT REGION 176..195
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 180..194
FT /note="Required to functionally cooperate with SREBF1 in
FT promoter activation"
FT /evidence="ECO:0000269|PubMed:17290224"
FT REGION 213..293
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 240..359
FT /note="Interaction with FOXO1"
FT /evidence="ECO:0000269|PubMed:17627282"
FT REGION 287..314
FT /note="Basic motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 318..346
FT /note="Leucine-zipper"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT COMPBIAS 36..50
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 177..194
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 218..232
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 278..293
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 159
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P49715"
FT MOD_RES 193
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:15107404"
FT MOD_RES 222
FT /note="Phosphothreonine; by GSK3"
FT /evidence="ECO:0000269|PubMed:17290224"
FT MOD_RES 226
FT /note="Phosphothreonine; by GSK3"
FT /evidence="ECO:0000269|PubMed:17290224"
FT MOD_RES 230
FT /note="Phosphoserine; by GSK3"
FT /evidence="ECO:0000305|PubMed:17290224"
FT CROSSLNK 159
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO); alternate"
FT /evidence="ECO:0000250|UniProtKB:P05554"
FT CROSSLNK 159
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0000250|UniProtKB:P49715"
FT VAR_SEQ 1..117
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000269|PubMed:8415748"
FT /id="VSP_057549"
FT VAR_SEQ 1..14
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000269|PubMed:8415748"
FT /id="VSP_057550"
FT VAR_SEQ 1
FT /note="M -> MRGREPVGALGGRRRQRRHAQAGGRRGSPCRENSNSPM (in
FT isoform 4)"
FT /id="VSP_057608"
FT MUTAGEN 182..188
FT /note="PPPPPPP->APPPAPA: No effect on DNA-binding or
FT interaction with CDK2 and CDK4. No effect on cell cycle
FT inhibition."
FT /evidence="ECO:0000269|PubMed:15107404"
FT MUTAGEN 184..186
FT /note="PPP->AAA: No effect on DNA-binding or interaction
FT with CDK2 and CDK4. No effect on cell cycle inhibition."
FT /evidence="ECO:0000269|PubMed:15107404"
FT MUTAGEN 193
FT /note="S->A: No effect on DNA-binding. Loss of interaction
FT with CDK2 and CDK4 as well as cell cycle inhibition."
FT /evidence="ECO:0000269|PubMed:15107404"
FT MUTAGEN 222..230
FT /note="TPPPTPVPS->APPPAPVPA: Decreases phosphorylated form.
FT Deregulation of hepatic glucose metabolism."
FT /evidence="ECO:0000269|PubMed:17290224"
FT MUTAGEN 286
FT /note="Y->A: No effect on DNA-binding, represses
FT E2F1:TFDP1-mediated transcription and causes adipose
FT hypoplasia and myeloid dysplasia."
FT /evidence="ECO:0000269|PubMed:11672531"
FT MUTAGEN 288
FT /note="V->A: No effect on DNA-binding, no effect on
FT repression of E2F1:TFDP1-mediated transcription and no
FT effect on adipogenesis and granulopoiesis; when associated
FT with A-291."
FT /evidence="ECO:0000269|PubMed:11672531"
FT MUTAGEN 291
FT /note="E->A: No effect on DNA-binding, no effect on
FT repression of E2F1:TFDP1-mediated transcription and no
FT effect on adipogenesis and granulopoiesis; when associated
FT with A-288."
FT /evidence="ECO:0000269|PubMed:11672531"
FT MUTAGEN 295
FT /note="I->A: No effect on DNA-binding, represses
FT E2F1:TFDP1-mediated transcription and causes adipose
FT hypoplasia and myeloid dysplasia; when associated with A-
FT 298."
FT /evidence="ECO:0000269|PubMed:11672531"
FT MUTAGEN 298
FT /note="R->A: No effect on DNA-binding, represses
FT E2F1:TFDP1-mediated transcription and causes adipose
FT hypoplasia and myeloid dysplasia; when associated with A-
FT 295."
FT /evidence="ECO:0000269|PubMed:11672531"
FT CONFLICT 30..54
FT /note="AFGFPRGAGPAPPPAPPAAPEPLGG -> RLWLSPGRGPRAAPSPTCRPGAA
FT GR (in Ref. 1; AAA37374)"
FT /evidence="ECO:0000305"
FT CONFLICT 356..359
FT /note="GNCA -> ATAREARGCGTALGRPPGWRPRGWFRVAGSLGCPGRASQD (in
FT Ref. 1; AAA37374)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 359 AA; 37430 MW; 1E6CC09A330BEFEF CRC64;
MESADFYEVE PRPPMSSHLQ SPPHAPSNAA FGFPRGAGPA PPPAPPAAPE PLGGICEHET
SIDISAYIDP AAFNDEFLAD LFQHSRQQEK AKAAAGPAGG GGDFDYPGAP AGPGGAVMSA
GAHGPPPGYG CAAAGYLDGR LEPLYERVGA PALRPLVIKQ EPREEDEAKQ LALAGLFPYQ
PPPPPPPPHP HASPAHLAAP HLQFQIAHCG QTTMHLQPGH PTPPPTPVPS PHAAPALGAA
GLPGPGSALK GLAGAHPDLR TGGGGGGSGA GAGKAKKSVD KNSNEYRVRR ERNNIAVRKS
RDKAKQRNVE TQQKVLELTS DNDRLRKRVE QLSRELDTLR GIFRQLPESS LVKAMGNCA
