CEBPA_HUMAN
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 03-AUG-2022, entry version 203.
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 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 [11]
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 [12]
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 [13]
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 [14]
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 [15]
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 [16]
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 [17]
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 [18]
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 [19]
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 [20]
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 [21]
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 {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 -!- 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="http://atlasgeneticsoncology.org/Genes/CEBPAID40050ch19q13.html";
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/cebpa/";
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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; 106.
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; P49715; -.
DR PeptideAtlas; P49715; -.
DR PRIDE; P49715; -.
DR ProteomicsDB; 56054; -.
DR Antibodypedia; 38083; 723 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 CTD; 1050; -.
DR DisGeNET; 1050; -.
DR GeneCards; CEBPA; -.
DR GeneReviews; CEBPA; -.
DR HGNC; HGNC:1833; CEBPA.
DR HPA; ENSG00000245848; Tissue enhanced (adipose tissue, 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; MPHLQYQ; -.
DR OrthoDB; 1284308at2759; -.
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; 72 hits in 1100 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 185 other tissues.
DR Genevisible; P49715; HS.
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: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; IC: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:0008285; P:negative regulation of cell population proliferation; IDA:UniProtKB.
DR GO; GO:0045736; P:negative regulation of cyclin-dependent protein serine/threonine kinase activity; TAS:ParkinsonsUK-UCL.
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; IEA:Ensembl.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
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:BHF-UCL.
DR GO; GO:0045945; P:positive regulation of transcription by RNA polymerase III; IDA:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:UniProtKB.
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 InterPro; IPR004827; bZIP.
DR InterPro; IPR046347; bZIP_sf.
DR InterPro; IPR016468; C/EBP_chordates.
DR Pfam; PF07716; bZIP_2; 1.
DR PIRSF; PIRSF005879; CCAAT/enhancer-binding; 1.
DR SMART; SM00338; BRLZ; 1.
DR SUPFAM; SSF57959; SSF57959; 1.
DR PROSITE; PS50217; BZIP; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Activator; Alternative initiation;
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
