ID CEBPA_HUMAN Reviewed; 358 AA. AC P49715; A7LNP2; P78319; Q05CA4; DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot. DT 05-FEB-2008, sequence version 3. DT 27-MAR-2024, entry version 212. DE RecName: Full=CCAAT/enhancer-binding protein alpha {ECO:0000312|HGNC:HGNC:1833}; DE Short=C/EBP alpha {ECO:0000312|HGNC:HGNC:1833}; GN Name=CEBPA {ECO:0000312|HGNC:HGNC:1833}; GN Synonyms=CEBP {ECO:0000312|HGNC:HGNC:1833}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC TISSUE=Umbilical cord; RX PubMed=7575576; DOI=10.1006/bbrc.1995.2439; RA Antonson P., Xanthopoulos K.G.; RT "Molecular cloning, sequence, and expression patterns of the human gene RT encoding CCAAT/enhancer binding protein alpha (C/EBP alpha)."; RL Biochem. Biophys. Res. Commun. 215:106-113(1995). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Liver; RA Swart G.W.M., van Groningen J.J.M., van Ruissen F., Bergers M., RA Schalwijk J.; RT "Transcription factor C/EBP-alpha: novel sites of expression and cloning of RT the human gene."; RL Biol. Chem. Hoppe-Seyler 378:373-379(1997). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RG SeattleSNPs variation discovery resource; RL Submitted (JUL-2007) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15057824; DOI=10.1038/nature02399; RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A., RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., RA Rubin E.M., Lucas S.M.; RT "The DNA sequence and biology of human chromosome 19."; RL Nature 428:529-535(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-133. RC TISSUE=Pancreas; 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 [6] RP INTERACTION WITH HBV PROTEIN X (MICROBIAL INFECTION). RX PubMed=9915821; DOI=10.1074/jbc.274.5.2858; RA Choi B.H., Park G.T., Rho H.M.; RT "Interaction of hepatitis B viral X protein and CCAAT/enhancer-binding RT protein alpha synergistically activates the hepatitis B viral enhancer RT II/pregenomic promoter."; RL J. Biol. Chem. 274:2858-2865(1999). RN [7] RP INTERACTION WITH UBN1. RX PubMed=10725330; DOI=10.1083/jcb.148.6.1165; RA Aho S., Buisson M., Pajunen T., Ryoo Y.W., Giot J.-F., Gruffat H., RA Sergeant A., Uitto J.; RT "Ubinuclein, a novel nuclear protein interacting with cellular and viral RT transcription factors."; RL J. Cell Biol. 148:1165-1176(2000). RN [8] RP INVOLVEMENT IN AML. RX PubMed=12661007; DOI=10.1002/gcc.10185; RA Snaddon J., Smith M.L., Neat M., Cambal-Parrales M., Dixon-McIver A., RA Arch R., Amess J.A., Rohatiner A.Z., Lister T.A., Fitzgibbon J.; RT "Mutations of CEBPA in acute myeloid leukemia FAB types M1 and M2."; RL Genes Chromosomes Cancer 37:72-78(2003). RN [9] RP INTERACTION WITH CDK2; CDK4; E2F4; RB1 AND SMARCA2, AND PHOSPHORYLATION AT RP SER-190. 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 INTERACTION WITH EPSTEIN-BARR VIRUS BZLF1 PROTEIN (MICROBIAL INFECTION). RX PubMed=15078966; DOI=10.1128/jvi.78.9.4847-4865.2004; RA Wu F.Y., Wang S.E., Chen H., Wang L., Hayward S.D., Hayward G.S.; RT "CCAAT/enhancer binding protein alpha binds to the Epstein-Barr virus (EBV) RT ZTA protein through oligomeric interactions and contributes to cooperative RT transcriptional activation of the ZTA promoter through direct binding to RT the ZII and ZIIIB motifs during induction of the EBV lytic cycle."; RL J. Virol. 78:4847-4865(2004). RN [11] RP FUNCTION (ISOFORMS 1 AND 3). 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 INVOLVEMENT IN AML. RX PubMed=15575056; DOI=10.1056/nejmoa041331; RA Smith M.L., Cavenagh J.D., Lister T.A., Fitzgibbon J.; RT "Mutation of CEBPA in familial acute myeloid leukemia."; RL N. Engl. J. Med. 351:2403-2407(2004). RN [13] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-161, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [14] RP INTERACTION WITH TRIB1. RX PubMed=20410507; DOI=10.1182/blood-2009-07-229450; RA Dedhia P.H., Keeshan K., Uljon S., Xu L., Vega M.E., Shestova O., RA Zaks-Zilberman M., Romany C., Blacklow S.C., Pear W.S.; RT "Differential ability of Tribbles family members to promote degradation of RT C/EBPalpha and induce acute myelogenous leukemia."; RL Blood 116:1321-1328(2010). RN [15] RP FUNCTION (ISOFORM 4), ALTERNATIVE INITIATION, IDENTIFICATION OF RP NON-CANONICAL INITIATION CODON, SUBCELLULAR LOCATION (ISOFORM 4), AND RP INTERACTION WITH NPM1; TAF1A AND UBTF. 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 [16] RP INTERACTION WITH TFDP1; TFDP2 AND E2F1. RX PubMed=20176812; DOI=10.1128/mcb.01619-09; RA Zaragoza K., Begay V., Schuetz A., Heinemann U., Leutz A.; RT "Repression of transcriptional activity of C/EBPalpha by E2F-dimerization RT partner complexes."; RL Mol. Cell. Biol. 30:2293-2304(2010). RN [17] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-161, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25218447; DOI=10.1038/nsmb.2890; RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M., RA Vertegaal A.C.; RT "Uncovering global SUMOylation signaling networks in a site-specific RT manner."; RL Nat. Struct. Mol. Biol. 21:927-936(2014). RN [18] RP INTERACTION WITH TRIB1, DOMAIN, AND MUTAGENESIS OF ILE-55; GLU-57; HIS-58; RP GLU-59; SER-61; ILE-62; ASP-63; ILE-64; SER-65; TYR-67; ILE-68 AND ASP-69. RX PubMed=26455797; DOI=10.1016/j.str.2015.08.017; RA Murphy J.M., Nakatani Y., Jamieson S.A., Dai W., Lucet I.S., Mace P.D.; RT "Molecular mechanism of CCAAT-enhancer binding protein recruitment by the RT TRIB1 pseudokinase."; RL Structure 23:2111-2121(2015). RN [19] 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 [20] RP UBIQUITINATION. RX PubMed=27041596; DOI=10.1016/j.str.2016.03.002; RA Uljon S., Xu X., Durzynska I., Stein S., Adelmant G., Marto J.A., RA Pear W.S., Blacklow S.C.; RT "Structural basis for substrate selectivity of the E3 ligase COP1."; RL Structure 24:687-696(2016). RN [21] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-161, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=28112733; DOI=10.1038/nsmb.3366; RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C., RA Nielsen M.L.; RT "Site-specific mapping of the human SUMO proteome reveals co-modification RT with phosphorylation."; RL Nat. Struct. Mol. Biol. 24:325-336(2017). RN [22] RP VARIANTS AML LEU-84 AND LYS-312 INS, CHARACTERIZATION OF VARIANTS AML RP LEU-84 AND LYS-312 INS, INVOLVEMENT IN AML, FUNCTION, SUBCELLULAR LOCATION, RP ALTERNATIVE TRANSLATIONAL INITIATION, AND DNA-BINDING. RX PubMed=11242107; DOI=10.1038/85820; RA Pabst T., Mueller B.U., Zhang P., Radomska H.S., Narravula S., RA Schnittger S., Behre G., Hiddemann W., Tenen D.G.; RT "Dominant-negative mutations of CEBPA, encoding CCAAT/enhancer binding RT protein-alpha (C/EBPalpha), in acute myeloid leukemia."; RL Nat. Genet. 27:263-270(2001). 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. Binds directly to CC the consensus DNA sequence 5'-T[TG]NNGNAA[TG]-3' acting as an activator CC on distinct target genes (PubMed:11242107). During early embryogenesis, CC plays essential and redundant functions with CEBPB. Essential for the CC transition from common myeloid progenitors (CMP) to CC granulocyte/monocyte progenitors (GMP). Critical for the proper CC development of the liver and the lung (By similarity). Necessary for CC terminal adipocyte differentiation, is required for postnatal CC maintenance of systemic energy homeostasis and lipid storage (By CC similarity). To regulate these different processes at the proper moment CC and tissue, interplays with other transcription factors and modulators. CC Down-regulates the expression of genes that maintain cells in an CC undifferentiated and proliferative state through E2F1 repression, which CC is critical for its ability to induce adipocyte and granulocyte CC terminal differentiation. Reciprocally E2F1 blocks adipocyte CC differentiation by binding to specific promoters and repressing CEBPA CC binding to its target gene promoters. Proliferation arrest also depends CC on a functional binding to SWI/SNF complex (PubMed:14660596). In liver, CC regulates gluconeogenesis and lipogenesis through different mechanisms. CC To regulate gluconeogenesis, functionally cooperates with FOXO1 binding CC to IRE-controlled promoters and regulating the expression of target CC genes such as PCK1 or G6PC1. To modulate lipogenesis, interacts and CC transcriptionally synergizes with SREBF1 in promoter activation of CC specific lipogenic target genes such as ACAS2. In adipose tissue, seems CC to act as FOXO1 coactivator accessing to ADIPOQ promoter through FOXO1 CC binding sites (By similarity). {ECO:0000250|UniProtKB:P05554, CC ECO:0000250|UniProtKB:P53566, ECO:0000269|PubMed:11242107, CC ECO:0000269|PubMed:14660596}. 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 (PubMed:14660596). CC {ECO:0000250|UniProtKB:P05554, ECO:0000250|UniProtKB:P53566, CC ECO:0000269|PubMed:14660596}. 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:0000269|PubMed:20075868}. 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 (By similarity). Interacts with UBN1 CC (PubMed:10725330). Interacts with ZNF638; this interaction increases CC transcriptional activation (By similarity). Interacts with the complex CC TFDP2:E2F1; the interaction prevents CEBPA binding to target gene CC promoters and represses its transcriptional activity (PubMed:20176812). CC Interacts with RB1 (PubMed:15107404). Interacts (when phosphorylated at CC Ser-190) with CDK2, CDK4, E2F4 and SMARCA2 (PubMed:15107404). Interacts CC with SREBPF1 (By similarity). Interacts with FOXO1 (via the Fork-head CC domain); the interaction increases when FOXO1 is deacetylated (By CC similarity). Interacts with SIX1 (PubMed:27923061). Interacts (via CC recognition sequence) with TRIB1 (PubMed:20410507, PubMed:26455797). CC Interacts (via bZIP domain) with OVOL2 (via zinc-finger domains); the CC interaction inhibits the transcription factor activity of CEBPA and is CC required to repress adipogenesis (By similarity). CC {ECO:0000250|UniProtKB:P05554, ECO:0000250|UniProtKB:P53566, CC ECO:0000269|PubMed:10725330, ECO:0000269|PubMed:15107404, CC ECO:0000269|PubMed:20075868, ECO:0000269|PubMed:20176812, CC ECO:0000269|PubMed:20410507, ECO:0000269|PubMed:26455797, CC ECO:0000269|PubMed:27923061}. CC -!- SUBUNIT: [Isoform 1]: Interacts with TAF1A and UBTF. CC {ECO:0000269|PubMed:20075868}. CC -!- SUBUNIT: [Isoform 4]: Interacts with TAF1A and UBTF (PubMed:20075868). CC Interacts with NPM1 (PubMed:20075868). {ECO:0000269|PubMed:20075868}. CC -!- SUBUNIT: (Microbial infection) Interacts with HBV protein X. CC {ECO:0000269|PubMed:9915821}. CC -!- SUBUNIT: (Microbial infection) Interacts with Epstein-Barr virus lytic CC switch protein BZLF1; this interaction induces G1 cell cycle arrest. CC {ECO:0000269|PubMed:15078966}. CC -!- INTERACTION: CC P49715; P18847: ATF3; NbExp=2; IntAct=EBI-1172054, EBI-712767; CC P49715; P18848: ATF4; NbExp=4; IntAct=EBI-1172054, EBI-492498; CC P49715; Q9Y2D1: ATF5; NbExp=2; IntAct=EBI-1172054, EBI-492509; CC P49715; Q16520: BATF; NbExp=3; IntAct=EBI-1172054, EBI-749503; CC P49715; Q8N1L9: BATF2; NbExp=2; IntAct=EBI-1172054, EBI-742695; CC P49715; Q9NR55: BATF3; NbExp=2; IntAct=EBI-1172054, EBI-10312707; CC P49715; P47902: CDX1; NbExp=3; IntAct=EBI-1172054, EBI-8514176; CC P49715; P49715: CEBPA; NbExp=2; IntAct=EBI-1172054, EBI-1172054; CC P49715; P17676: CEBPB; NbExp=2; IntAct=EBI-1172054, EBI-969696; CC P49715; P49716: CEBPD; NbExp=2; IntAct=EBI-1172054, EBI-7962058; CC P49715; Q15744: CEBPE; NbExp=2; IntAct=EBI-1172054, EBI-3907048; CC P49715; P53567: CEBPG; NbExp=4; IntAct=EBI-1172054, EBI-740209; CC P49715; P35638: DDIT3; NbExp=4; IntAct=EBI-1172054, EBI-742651; CC P49715; P01100: FOS; NbExp=2; IntAct=EBI-1172054, EBI-852851; CC P49715; P24001-2: IL32; NbExp=7; IntAct=EBI-1172054, EBI-8800907; CC P49715; P09874: PARP1; NbExp=2; IntAct=EBI-1172054, EBI-355676; CC P49715; P03122: E2; Xeno; NbExp=2; IntAct=EBI-1172054, EBI-7028618; CC P49715; P06422: E2; Xeno; NbExp=4; IntAct=EBI-1172054, EBI-7136851; CC P49715-1; Q96RU8-1: TRIB1; NbExp=2; IntAct=EBI-16180754, EBI-16180744; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11242107}. CC -!- SUBCELLULAR LOCATION: [Isoform 4]: Nucleus, nucleolus CC {ECO:0000269|PubMed:20075868}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative initiation; Named isoforms=4; CC Name=1; CC IsoId=P49715-1; Sequence=Displayed; CC Name=2; Synonyms=C/EBPalpha-p42 {ECO:0000303|PubMed:11242107}; CC IsoId=P49715-2; Sequence=VSP_057548; CC Name=3; Synonyms=C/EBPalpha-p30 {ECO:0000303|PubMed:11242107}; CC IsoId=P49715-3; Sequence=VSP_057547; CC Name=4; Synonyms=extended-C/EBPalpha {ECO:0000303|PubMed:20075868}; CC IsoId=P49715-4; Sequence=VSP_057607; CC -!- DOMAIN: The recognition sequence (54-72) is required for interaction CC with TRIB1. {ECO:0000269|PubMed:26455797}. CC -!- PTM: Phosphorylation at Ser-190 is required for interaction with CDK2, CC CDK4 and SWI/SNF complex leading to cell cycle inhibition. CC Dephosphorylated at Ser-190 by protein phosphatase 2A (PP2A) through CC PI3K/AKT signaling pathway regulation (PubMed:15107404). CC Phosphorylation at Thr-226 and Thr-230 by GSK3 is constitutive in CC adipose tissue and lung. In liver, both Thr-226 and Thr-230 are CC phosphorylated only during feeding but not during fasting. CC Phosphorylation of the GSK3 consensus sites selectively decreases CC transactivation activity on IRE-controlled promoters. CC {ECO:0000250|UniProtKB:P53566}. 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: Ubiquitinated by COP1 upon interaction with TRIB1. CC {ECO:0000303|PubMed:27041596}. CC -!- DISEASE: Leukemia, acute myelogenous (AML) [MIM:601626]: A subtype of CC acute leukemia, a cancer of the white blood cells. AML is a malignant CC disease of bone marrow characterized by maturational arrest of CC hematopoietic precursors at an early stage of development. Clonal CC expansion of myeloid blasts occurs in bone marrow, blood, and other CC tissue. Myelogenous leukemias develop from changes in cells that CC normally produce neutrophils, basophils, eosinophils and monocytes. CC {ECO:0000269|PubMed:11242107, ECO:0000269|PubMed:12661007, CC ECO:0000269|PubMed:15575056}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the bZIP family. C/EBP subfamily. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/40050/CEBPA"; CC -!- WEB RESOURCE: Name=SeattleSNPs; CC URL="http://pga.gs.washington.edu/data/cebpa/"; 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; U34070; AAC50235.1; -; Genomic_DNA. DR EMBL; Y11525; CAA72289.1; -; mRNA. DR EMBL; EU048234; ABS82765.1; -; Genomic_DNA. DR EMBL; AC008738; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC027902; AAH27902.1; -; mRNA. DR CCDS; CCDS54243.1; -. [P49715-1] DR PIR; JC4311; JC4311. DR RefSeq; NP_001272758.1; NM_001285829.1. [P49715-3] DR RefSeq; NP_001274353.1; NM_001287424.1. [P49715-4] DR RefSeq; NP_001274364.1; NM_001287435.1. [P49715-2] DR RefSeq; NP_004355.2; NM_004364.4. [P49715-1] DR PDB; 6DC0; X-ray; 2.80 A; A/B=51-75. DR PDBsum; 6DC0; -. DR AlphaFoldDB; P49715; -. DR SMR; P49715; -. DR BioGRID; 107479; 110. DR ComplexPortal; CPX-509; bZIP transcription factor complex, CEBPA-CEBPB. DR ComplexPortal; CPX-6469; bZIP transcription factor complex, ATF3-CEBPA. DR ComplexPortal; CPX-6525; bZIP transcription factor complex, ATF4-CEBPA. DR ComplexPortal; CPX-6586; bZIP transcription factor complex, ATF5-CEBPA. DR ComplexPortal; CPX-69; bZIP transcription factor complex, CEBPA-DDIT3. DR ComplexPortal; CPX-7006; bZIP transcription factor complex, BATF-CEBPA. DR ComplexPortal; CPX-7065; bZIP transcription factor complex, BATF2-CEBPA. DR ComplexPortal; CPX-7095; bZIP transcription factor complex, BATF3-CEBPA. DR ComplexPortal; CPX-71; bZIP transcription factor complex, CEBPA-CEBPA. DR CORUM; P49715; -. DR DIP; DIP-37882N; -. DR ELM; P49715; -. DR IntAct; P49715; 31. DR MINT; P49715; -. DR STRING; 9606.ENSP00000427514; -. DR iPTMnet; P49715; -. DR PhosphoSitePlus; P49715; -. DR BioMuta; CEBPA; -. DR DMDM; 166898082; -. DR EPD; P49715; -. DR jPOST; P49715; -. DR MassIVE; P49715; -. DR MaxQB; P49715; -. DR PaxDb; 9606-ENSP00000427514; -. DR PeptideAtlas; P49715; -. DR ProteomicsDB; 56054; -. DR Antibodypedia; 38083; 828 antibodies from 40 providers. DR DNASU; 1050; -. DR Ensembl; ENST00000498907.3; ENSP00000427514.1; ENSG00000245848.3. [P49715-1] DR GeneID; 1050; -. DR KEGG; hsa:1050; -. DR MANE-Select; ENST00000498907.3; ENSP00000427514.1; NM_004364.5; NP_004355.2. DR UCSC; uc002nun.4; human. [P49715-1] DR AGR; HGNC:1833; -. DR CTD; 1050; -. DR DisGeNET; 1050; -. DR GeneCards; CEBPA; -. DR GeneReviews; CEBPA; -. DR HGNC; HGNC:1833; CEBPA. DR HPA; ENSG00000245848; Group enriched (adipose tissue, breast, liver, skin). DR MalaCards; CEBPA; -. DR MIM; 116897; gene. DR MIM; 601626; phenotype. DR neXtProt; NX_P49715; -. DR OpenTargets; ENSG00000245848; -. DR Orphanet; 319480; Acute myeloid leukemia with CEBPA somatic mutations. DR Orphanet; 102724; Acute myeloid leukemia with t(8;21)(q22;q22) translocation. DR Orphanet; 319465; Inherited acute myeloid leukemia. DR PharmGKB; PA26376; -. DR VEuPathDB; HostDB:ENSG00000245848; -. DR eggNOG; KOG3119; Eukaryota. DR GeneTree; ENSGT00940000162646; -. DR HOGENOM; CLU_043327_2_0_1; -. DR InParanoid; P49715; -. DR OMA; QMPHLQY; -. DR OrthoDB; 2959124at2759; -. DR PhylomeDB; P49715; -. DR TreeFam; TF105008; -. DR PathwayCommons; P49715; -. DR Reactome; R-HSA-381340; Transcriptional regulation of white adipocyte differentiation. DR Reactome; R-HSA-9616222; Transcriptional regulation of granulopoiesis. DR SignaLink; P49715; -. DR SIGNOR; P49715; -. DR BioGRID-ORCS; 1050; 82 hits in 1196 CRISPR screens. DR ChiTaRS; CEBPA; human. DR GeneWiki; CEBPA; -. DR GenomeRNAi; 1050; -. DR Pharos; P49715; Tbio. DR PRO; PR:P49715; -. DR Proteomes; UP000005640; Chromosome 19. DR RNAct; P49715; Protein. DR Bgee; ENSG00000245848; Expressed in nipple and 187 other cell types or tissues. DR GO; GO:1990647; C:C/EBP complex; IPI:ComplexPortal. DR GO; GO:0036488; C:CHOP-C/EBP complex; IPI:ComplexPortal. DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA. DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; IMP:BHF-UCL. DR GO; GO:0005667; C:transcription regulator complex; IDA:ARUK-UCL. DR GO; GO:0031490; F:chromatin DNA binding; IEA:Ensembl. DR GO; GO:0003677; F:DNA binding; TAS:ProtInc. DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IMP:BHF-UCL. DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:UniProtKB. DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0019900; F:kinase binding; IPI:UniProtKB. DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB. DR GO; GO:0001163; F:RNA polymerase I transcription regulatory region sequence-specific DNA binding; IDA:UniProtKB. DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central. DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:ARUK-UCL. DR GO; GO:0097677; F:STAT family protein binding; IPI:UniProtKB. DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:UniProtKB. DR GO; GO:0050873; P:brown fat cell differentiation; IEA:Ensembl. DR GO; GO:0071285; P:cellular response to lithium ion; IEA:Ensembl. DR GO; GO:0071407; P:cellular response to organic cyclic compound; IEA:Ensembl. DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IEA:Ensembl. DR GO; GO:0008203; P:cholesterol metabolic process; IEA:Ensembl. DR GO; GO:0019221; P:cytokine-mediated signaling pathway; NAS:UniProtKB. DR GO; GO:0006351; P:DNA-templated transcription; IEA:InterPro. DR GO; GO:0001892; P:embryonic placenta development; IEA:Ensembl. DR GO; GO:0002070; P:epithelial cell maturation; IEA:Ensembl. DR GO; GO:0045444; P:fat cell differentiation; ISS:UniProtKB. DR GO; GO:0006091; P:generation of precursor metabolites and energy; TAS:ProtInc. DR GO; GO:0042593; P:glucose homeostasis; ISS:UniProtKB. DR GO; GO:0030851; P:granulocyte differentiation; ISS:UniProtKB. DR GO; GO:0071425; P:hematopoietic stem cell proliferation; IEA:Ensembl. DR GO; GO:0048839; P:inner ear development; IEA:Ensembl. DR GO; GO:0140467; P:integrated stress response signaling; NAS:ComplexPortal. DR GO; GO:0070102; P:interleukin-6-mediated signaling pathway; IDA:ARUK-UCL. DR GO; GO:0055088; P:lipid homeostasis; ISS:UniProtKB. DR GO; GO:0001889; P:liver development; ISS:UniProtKB. DR GO; GO:0030324; P:lung development; ISS:UniProtKB. DR GO; GO:0030225; P:macrophage differentiation; IEA:Ensembl. DR GO; GO:0007005; P:mitochondrion organization; IEA:Ensembl. DR GO; GO:0030099; P:myeloid cell differentiation; IBA:GO_Central. DR GO; GO:0045786; P:negative regulation of cell cycle; IEA:Ensembl. DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:UniProtKB. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; ISS:UniProtKB. DR GO; GO:1902034; P:negative regulation of hematopoietic stem cell proliferation; IEA:Ensembl. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:ComplexPortal. DR GO; GO:0007219; P:Notch signaling pathway; IEA:Ensembl. DR GO; GO:2000144; P:positive regulation of DNA-templated transcription initiation; IDA:UniProtKB. DR GO; GO:0045600; P:positive regulation of fat cell differentiation; IEA:Ensembl. DR GO; GO:0010628; P:positive regulation of gene expression; IEA:Ensembl. DR GO; GO:0050729; P:positive regulation of inflammatory response; ISS:ARUK-UCL. DR GO; GO:0043032; P:positive regulation of macrophage activation; ISS:ARUK-UCL. DR GO; GO:0045669; P:positive regulation of osteoblast differentiation; IEA:Ensembl. DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; TAS:ParkinsonsUK-UCL. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB. DR GO; GO:0051726; P:regulation of cell cycle; TAS:ParkinsonsUK-UCL. DR GO; GO:0006355; P:regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central. DR GO; GO:0006360; P:transcription by RNA polymerase I; IDA:UniProtKB. DR GO; GO:0000050; P:urea cycle; IEA:Ensembl. DR GO; GO:0050872; P:white fat cell differentiation; IEA:Ensembl. DR CDD; cd14711; bZIP_CEBPA; 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:SF5; CCAAT_ENHANCER-BINDING PROTEIN ALPHA; 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 Genevisible; P49715; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Activator; Alternative initiation; KW Developmental protein; Disease variant; DNA-binding; KW Host-virus interaction; Isopeptide bond; Nucleus; Phosphoprotein; KW Reference proteome; Transcription; Transcription regulation; KW Ubl conjugation. FT CHAIN 1..358 FT /note="CCAAT/enhancer-binding protein alpha" FT /id="PRO_0000076613" FT DOMAIN 282..345 FT /note="bZIP" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978" FT DNA_BIND 285..300 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:0000269|PubMed:26455797" FT REGION 128..204 FT /note="Required to induce adipocyte differentiation" FT /evidence="ECO:0000250|UniProtKB:P05554" FT REGION 178..201 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 182..198 FT /note="Required to functionally cooperate with SREBF1 in FT promoter activation" FT /evidence="ECO:0000250|UniProtKB:P53566" FT REGION 217..291 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 244..358 FT /note="Interaction with FOXO1" FT /evidence="ECO:0000250|UniProtKB:P53566" FT REGION 286..313 FT /note="Basic motif" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978" FT REGION 317..345 FT /note="Leucine-zipper" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978" FT COMPBIAS 179..201 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 222..242 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 277..291 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 161 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 190 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:15107404" FT MOD_RES 226 FT /note="Phosphothreonine; by GSK3" FT /evidence="ECO:0000250|UniProtKB:P53566" FT MOD_RES 230 FT /note="Phosphothreonine; by GSK3" FT /evidence="ECO:0000250|UniProtKB:P53566" FT MOD_RES 234 FT /note="Phosphoserine; by GSK3" FT /evidence="ECO:0000250|UniProtKB:P53566" FT CROSSLNK 161 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0007744|PubMed:25218447, FT ECO:0007744|PubMed:28112733" FT VAR_SEQ 1..119 FT /note="Missing (in isoform 3)" FT /id="VSP_057547" FT VAR_SEQ 1..14 FT /note="Missing (in isoform 2)" FT /id="VSP_057548" FT VAR_SEQ 1 FT /note="M -> MRGRGRAGSPGGRRRRPAQAGGRRGSPCRENSNSPM (in FT isoform 4)" FT /id="VSP_057607" FT VARIANT 84 FT /note="H -> L (in AML; no effect on expression; no effect FT on DNA-binding or transactivation activity; FT dbSNP:rs28931590)" FT /evidence="ECO:0000269|PubMed:11242107" FT /id="VAR_072677" FT VARIANT 312 FT /note="Q -> QK (in AML; nuclear; no effect on expression; FT loss of DNA-binding and transactivation activity)" FT /evidence="ECO:0000269|PubMed:11242107" FT /id="VAR_072678" FT MUTAGEN 55 FT /note="I->A: Decreased interaction with TRIB1." FT /evidence="ECO:0000269|PubMed:26455797" FT MUTAGEN 57 FT /note="E->T: No effect on interaction with TRIB1." FT /evidence="ECO:0000269|PubMed:26455797" FT MUTAGEN 58 FT /note="H->D: No effect on interaction with TRIB1." FT /evidence="ECO:0000269|PubMed:26455797" FT MUTAGEN 59 FT /note="E->A: Decreased interaction with TRIB1." FT /evidence="ECO:0000269|PubMed:26455797" FT MUTAGEN 61 FT /note="S->A: Decreased interaction with TRIB1." FT /evidence="ECO:0000269|PubMed:26455797" FT MUTAGEN 62 FT /note="I->A: Decreased interaction with TRIB1." FT /evidence="ECO:0000269|PubMed:26455797" FT MUTAGEN 63 FT /note="D->A: No effect on interaction with TRIB1." FT /evidence="ECO:0000269|PubMed:26455797" FT MUTAGEN 64 FT /note="I->A: Decreased interaction with TRIB1." FT /evidence="ECO:0000269|PubMed:26455797" FT MUTAGEN 65 FT /note="S->A: No effect on interaction with TRIB1." FT /evidence="ECO:0000269|PubMed:26455797" FT MUTAGEN 67 FT /note="Y->A: Decreased interaction with TRIB1." FT /evidence="ECO:0000269|PubMed:26455797" FT MUTAGEN 67 FT /note="Y->F: No effect on interaction with TRIB1." FT /evidence="ECO:0000269|PubMed:26455797" FT MUTAGEN 68 FT /note="I->A: Decreased interaction with TRIB1." FT /evidence="ECO:0000269|PubMed:26455797" FT MUTAGEN 69 FT /note="D->A: No effect on interaction with TRIB1." FT /evidence="ECO:0000269|PubMed:26455797" FT CONFLICT 40..41 FT /note="AQ -> PK (in Ref. 1; AAC50235)" FT /evidence="ECO:0000305" FT CONFLICT 95..98 FT /note="VGPT -> WAH (in Ref. 2; CAA72289)" FT /evidence="ECO:0000305" FT CONFLICT 241 FT /note="L -> V (in Ref. 2; CAA72289)" FT /evidence="ECO:0000305" FT CONFLICT 248..250 FT /note="GPG -> ALA (in Ref. 2; CAA72289)" FT /evidence="ECO:0000305" FT CONFLICT 269 FT /note="S -> T (in Ref. 1; AAC50235)" FT /evidence="ECO:0000305" FT HELIX 64..66 FT /evidence="ECO:0007829|PDB:6DC0" FT HELIX 70..73 FT /evidence="ECO:0007829|PDB:6DC0" SQ SEQUENCE 358 AA; 37561 MW; 574C0A049E25BCAC CRC64; MESADFYEAE PRPPMSSHLQ SPPHAPSSAA FGFPRGAGPA QPPAPPAAPE PLGGICEHET SIDISAYIDP AAFNDEFLAD LFQHSRQQEK AKAAVGPTGG GGGGDFDYPG APAGPGGAVM PGGAHGPPPG YGCAAAGYLD GRLEPLYERV GAPALRPLVI KQEPREEDEA KQLALAGLFP YQPPPPPPPS HPHPHPPPAH LAAPHLQFQI AHCGQTTMHL QPGHPTPPPT PVPSPHPAPA LGAAGLPGPG SALKGLGAAH PDLRASGGSG AGKAKKSVDK NSNEYRVRRE RNNIAVRKSR DKAKQRNVET QQKVLELTSD NDRLRKRVEQ LSRELDTLRG IFRQLPESSL VKAMGNCA //