CEBPA_RAT
ID CEBPA_RAT Reviewed; 358 AA.
AC P05554;
DT 01-NOV-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 3.
DT 25-MAY-2022, entry version 173.
DE RecName: Full=CCAAT/enhancer-binding protein alpha {ECO:0000312|RGD:2326};
DE Short=C/EBP alpha;
GN Name=Cebpa {ECO:0000312|RGD:2326};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND PROTEIN SEQUENCE OF 253-269.
RC STRAIN=Sprague-Dawley;
RX PubMed=2850264; DOI=10.1101/gad.2.7.786;
RA Landschulz W.H., Johnson P.F., Adashi E.Y., Graves B.J., McKnight S.L.;
RT "Isolation of a recombinant copy of the gene encoding C/EBP.";
RL Genes Dev. 2:786-800(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND SEQUENCE REVISION.
RC STRAIN=Sprague-Dawley; TISSUE=Liver;
RX PubMed=7926792; DOI=10.1101/gad.8.9.1131;
RA Lincoln A.J., Williams S.C., Johnson P.F.;
RT "A revised sequence of the rat c/ebp gene.";
RL Genes Dev. 8:1131-1132(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [4]
RP FUNCTION, AND SUBUNIT.
RX PubMed=1884998; DOI=10.1101/gad.5.9.1553;
RA Williams S.C., Cantwell C.A., Johnson P.F.;
RT "A family of C/EBP-related proteins capable of forming covalently linked
RT leucine zipper dimers in vitro.";
RL Genes Dev. 5:1553-1567(1991).
RN [5]
RP SUBUNIT.
RX PubMed=1377818; DOI=10.1093/nar/20.12.3091;
RA Thomassin H., Hamel D., Bernier D., Guertin M., Belanger L.;
RT "Molecular cloning of two C/EBP-related proteins that bind to the promoter
RT and the enhancer of the alpha 1-fetoprotein gene. Further analysis of C/EBP
RT beta and C/EBP gamma.";
RL Nucleic Acids Res. 20:3091-3098(1992).
RN [6]
RP FUNCTION, ALTERNATIVE TRANSLATIONAL INITIATION, SUBCELLULAR LOCATION,
RP DEVELOPMENTAL STAGE, TISSUE SPECIFICITY, SUBUNIT, AND DNA-BINDING.
RX PubMed=8367486; DOI=10.1073/pnas.90.17.8219;
RA Ossipow V., Descombes P., Schibler U.;
RT "CCAAT/enhancer-binding protein mRNA is translated into multiple proteins
RT with different transcription activation potentials.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:8219-8223(1993).
RN [7]
RP FUNCTION, AND MUTAGENESIS OF TYR-285; VAL-287; GLU-290; ILE-294; ARG-297;
RP ASP-301 AND LYS-304.
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 [8]
RP FUNCTION, INTERACTION WITH SMARCA2, SUMOYLATION AT LYS-159, AND MUTAGENESIS
RP OF LYS-159.
RX PubMed=16735515; DOI=10.1074/jbc.m600852200;
RA Sato Y., Miyake K., Kaneoka H., Iijima S.;
RT "Sumoylation of CCAAT/enhancer-binding protein alpha and its functional
RT roles in hepatocyte differentiation.";
RL J. Biol. Chem. 281:21629-21639(2006).
RN [9]
RP ALTERNATIVE INITIATION, IDENTIFICATION OF NON-CANONICAL INITIATION CODON,
RP SUBCELLULAR LOCATION (ISOFORM 4), MUTAGENESIS (ISOFORM 4), MUTAGENESIS OF
RP SER-299, AND 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 [10]
RP FUNCTION, INTERACTION WITH TFDP1; TFDP2 AND E2F1, AND MUTAGENESIS OF
RP GLU-290; ILE-294; ARG-297; ASP-301 AND LYS-304.
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 [11]
RP X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 281-340 IN COMPLEX WITH DNA,
RP SUBUNIT, MUTAGENESIS OF TYR-285; ARG-289; ASN-293 AND VAL-296, AND
RP SPECIFICITY.
RX PubMed=12578822; DOI=10.1074/jbc.m300417200;
RA Miller M., Shuman J.D., Sebastian T., Dauter Z., Johnson P.F.;
RT "Structural basis for DNA recognition by the basic region leucine zipper
RT transcription factor CCAAT/enhancer-binding protein alpha.";
RL J. Biol. Chem. 278:15178-15184(2003).
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:8367486,
CC PubMed:11672531, PubMed:16735515, PubMed:20176812). Binds directly to
CC the consensus DNA sequence 5'-T[TG]NNGNAA[TG]-3' acting as an activator
CC on distinct target genes. During early embryogenesis, plays essential
CC and redundant functions with CEBPB (By similarity). Essential for the
CC transition from common myeloid progenitors (CMP) to
CC granulocyte/monocyte progenitors (GMP) (PubMed:11672531). Critical for
CC the proper development of the liver and the lung (By similarity).
CC Necessary for terminal adipocyte differentiation, is required for
CC postnatal maintenance of systemic energy homeostasis and lipid storage
CC (PubMed:11672531). To regulate these different processes at the proper
CC moment and tissue, interplays with other transcription factors and
CC modulators. Down-regulates the expression of genes that maintain cells
CC in an undifferentiated and proliferative state through E2F1 repression,
CC which 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 (PubMed:11672531). Proliferation
CC arrest also depends on a functional binding to SWI/SNF complex (By
CC similarity). In liver, regulates gluconeogenesis and lipogenesis
CC through different mechanisms. To regulate gluconeogenesis, functionally
CC cooperates with FOXO1 binding to IRE-controlled promoters and
CC regulating the expression of target genes such as PCK1 or G6PC1. To
CC modulate lipogenesis, interacts and transcriptionally synergizes with
CC SREBF1 in promoter activation of specific lipogenic target genes such
CC as ACAS2. In adipose tissue, seems to act as FOXO1 coactivator
CC accessing to ADIPOQ promoter through FOXO1 binding sites (By
CC similarity). {ECO:0000250|UniProtKB:P49715,
CC ECO:0000250|UniProtKB:P53566, ECO:0000269|PubMed:11672531,
CC ECO:0000269|PubMed:16735515, ECO:0000269|PubMed:20176812,
CC ECO:0000269|PubMed:8367486}.
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:P49715,
CC ECO:0000250|UniProtKB:P53566, ECO:0000269|PubMed:8367486}.
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 (PubMed:1884998,
CC PubMed:8367486, PubMed:12578822). Can form stable heterodimers with
CC CEBPB, CEBPD, CEBPE and CEBPG (PubMed:1884998, PubMed:1377818). Can
CC form stable homodimers (also isoform 2 and isoform 3 dimers) and
CC heterodimers with CEBPB (with isoform 2 and isoform 3) and CEBPG
CC (PubMed:1377818, PubMed:8367486). Interacts with PRDM16 (By
CC similarity). Interacts with UBN1 (By similarity). Interacts with
CC ZNF638; this interaction increases transcriptional activation (By
CC similarity). Interacts with the complex TFDP2:E2F1; the interaction
CC prevents CEBPA binding to target gene promoters and represses its
CC transcriptional activity (By similarity). Interacts with RB1 (By
CC similarity). Interacts (when phosphorylated at SER-193) with CDK2,
CC CDK4, E2F4 and SMARCA2 (By similarity). Interacts with SREBPF1 (By
CC similarity). Interacts with FOXO1 (via the Fork-head domain); the
CC interaction increases when FOXO1 is deacetylated (By similarity).
CC Interacts with SIX1 (By similarity). Interacts (via recognition
CC sequence) with TRIB1 (By similarity). {ECO:0000250|UniProtKB:P49715,
CC ECO:0000250|UniProtKB:P53566, ECO:0000269|PubMed:12578822,
CC ECO:0000269|PubMed:1377818, ECO:0000269|PubMed:1884998,
CC ECO:0000269|PubMed:20075868, ECO:0000269|PubMed:8367486}.
CC -!- SUBUNIT: [Isoform 1]: Interacts with TAF1A and UBTF.
CC {ECO:0000269|PubMed:20075868}.
CC -!- SUBUNIT: [Isoform 4]: Interacts with NPM1.
CC {ECO:0000269|PubMed:20075868}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:8367486}.
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=P05554-1; Sequence=Displayed;
CC Name=2; Synonyms=CEBPalpha-p42 {ECO:0000303|PubMed:8367486};
CC IsoId=P05554-2; Sequence=VSP_057552;
CC Name=3; Synonyms=C/EBPalpha-p30 {ECO:0000303|PubMed:8367486};
CC IsoId=P05554-3; Sequence=VSP_057551;
CC Name=4; Synonyms=extended-C/EBPalpha {ECO:0000303|PubMed:20075868};
CC IsoId=P05554-4; Sequence=VSP_057609;
CC -!- TISSUE SPECIFICITY: Isoform 2 and isoform 3 are expressed in liver (at
CC protein level). {ECO:0000269|PubMed:8367486}.
CC -!- DEVELOPMENTAL STAGE: Isoform 2 and isoform 3 are not expressed at 1 day
CC before birth, relative concentration of both isoforms increases with
CC the age of the animal, reaching maximal levels in the adulthood.
CC {ECO:0000269|PubMed:8367486}.
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:0000269|PubMed:16735515}.
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. Phosphorylation at Thr-222 and
CC Thr-226 by GSK3 is constitutive in adipose tissue and lung. In liver,
CC both Thr-222 and Thr-226 are phosphorylated only during feeding but not
CC during fasting. Phosphorylation of the GSK3 consensus sites selectively
CC decreases transactivation activity on IRE-controlled promoters.
CC {ECO:0000250|UniProtKB:P53566}.
CC -!- PTM: Ubiquitinated by COP1 upon interaction with TRIB1.
CC {ECO:0000250|UniProtKB:P49715}.
CC -!- MISCELLANEOUS: The V296A substitution has little effect on the binding
CC of CEBPA to its consensus site (5'-GCAAT-3'), while greatly increasing
CC affinity for cAMP response element (CRE) sites (5'-GTCAT-3').
CC {ECO:0000269|PubMed:12578822}.
CC -!- MISCELLANEOUS: [Isoform 4]: Mutagenesis in position: 14: RRQR -> AAAA
CC abolishes nucleolar localization and prevents induction of 45S pre-RNA.
CC {ECO:0000269|PubMed:20075868}.
CC -!- SIMILARITY: Belongs to the bZIP family. C/EBP subfamily. {ECO:0000305}.
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DR EMBL; X12752; CAA31242.1; -; Genomic_DNA.
DR EMBL; AC109741; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR PIR; S06890; A54265.
DR RefSeq; NP_001274506.1; NM_001287577.1. [P05554-4]
DR RefSeq; NP_001274507.1; NM_001287578.1. [P05554-2]
DR RefSeq; NP_001274508.1; NM_001287579.1. [P05554-3]
DR RefSeq; NP_036656.1; NM_012524.3. [P05554-1]
DR PDB; 1NWQ; X-ray; 2.80 A; A/C=281-340.
DR PDBsum; 1NWQ; -.
DR AlphaFoldDB; P05554; -.
DR SMR; P05554; -.
DR BioGRID; 246437; 148.
DR ComplexPortal; CPX-60; bZIP transcription factor complex, Cebpa-Ddit3.
DR ComplexPortal; CPX-64; bZIP transcription factor complex, Cebpa-Cebpa.
DR DIP; DIP-28138N; -.
DR IntAct; P05554; 5.
DR STRING; 10116.ENSRNOP00000063123; -.
DR iPTMnet; P05554; -.
DR PhosphoSitePlus; P05554; -.
DR PaxDb; P05554; -.
DR PRIDE; P05554; -.
DR GeneID; 24252; -.
DR KEGG; rno:24252; -.
DR UCSC; RGD:2326; rat. [P05554-1]
DR CTD; 1050; -.
DR RGD; 2326; Cebpa.
DR eggNOG; KOG3119; Eukaryota.
DR HOGENOM; CLU_043327_2_0_1; -.
DR InParanoid; P05554; -.
DR OrthoDB; 1284308at2759; -.
DR PhylomeDB; P05554; -.
DR TreeFam; TF105008; -.
DR Reactome; R-RNO-9616222; Transcriptional regulation of granulopoiesis.
DR EvolutionaryTrace; P05554; -.
DR PRO; PR:P05554; -.
DR Proteomes; UP000002494; Unplaced.
DR Genevisible; P05554; RN.
DR GO; GO:1990647; C:C/EBP complex; ISO:RGD.
DR GO; GO:0036488; C:CHOP-C/EBP complex; IPI:ParkinsonsUK-UCL.
DR GO; GO:0016363; C:nuclear matrix; IDA:RGD.
DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IDA:RGD.
DR GO; GO:0035189; C:Rb-E2F complex; IDA:RGD.
DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; ISO:RGD.
DR GO; GO:0005667; C:transcription regulator complex; IDA:RGD.
DR GO; GO:0003682; F:chromatin binding; ISO:RGD.
DR GO; GO:0031490; F:chromatin DNA binding; ISO:RGD.
DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB.
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; ISO:RGD.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISO:RGD.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; IPI:UniProtKB.
DR GO; GO:0042826; F:histone deacetylase binding; IPI:RGD.
DR GO; GO:0071837; F:HMG box domain binding; IPI:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0019900; F:kinase binding; ISO:RGD.
DR GO; GO:0019904; F:protein domain specific binding; IPI:RGD.
DR GO; GO:0046982; F:protein heterodimerization activity; IPI:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0044877; F:protein-containing complex binding; IDA:RGD.
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:RGD.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:0097677; F:STAT family protein binding; ISO:RGD.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISO:RGD.
DR GO; GO:0006953; P:acute-phase response; IEP:RGD.
DR GO; GO:0031100; P:animal organ regeneration; IEP:RGD.
DR GO; GO:0050873; P:brown fat cell differentiation; ISO:RGD.
DR GO; GO:0030154; P:cell differentiation; IEP:RGD.
DR GO; GO:0048469; P:cell maturation; ISO:RGD.
DR GO; GO:0071285; P:cellular response to lithium ion; ISO:RGD.
DR GO; GO:0071407; P:cellular response to organic cyclic compound; ISO:RGD.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; ISO:RGD.
DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0008203; P:cholesterol metabolic process; ISO:RGD.
DR GO; GO:0001892; P:embryonic placenta development; ISO:RGD.
DR GO; GO:0045444; P:fat cell differentiation; IDA:UniProtKB.
DR GO; GO:0042593; P:glucose homeostasis; ISS:UniProtKB.
DR GO; GO:0030851; P:granulocyte differentiation; ISS:UniProtKB.
DR GO; GO:0048839; P:inner ear development; ISO:RGD.
DR GO; GO:0070102; P:interleukin-6-mediated signaling pathway; ISO:RGD.
DR GO; GO:0055088; P:lipid homeostasis; ISS:UniProtKB.
DR GO; GO:0001889; P:liver development; IEP:RGD.
DR GO; GO:0030324; P:lung development; ISS:UniProtKB.
DR GO; GO:0030225; P:macrophage differentiation; ISO:RGD.
DR GO; GO:0007613; P:memory; IEP:RGD.
DR GO; GO:0007005; P:mitochondrion organization; ISO:RGD.
DR GO; GO:0030099; P:myeloid cell differentiation; ISO:RGD.
DR GO; GO:0045786; P:negative regulation of cell cycle; ISO:RGD.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:ComplexPortal.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0007219; P:Notch signaling pathway; ISO:RGD.
DR GO; GO:0002076; P:osteoblast development; IEP:RGD.
DR GO; GO:0045600; P:positive regulation of fat cell differentiation; IMP:RGD.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:RGD.
DR GO; GO:0050729; P:positive regulation of inflammatory response; ISO:RGD.
DR GO; GO:0043032; P:positive regulation of macrophage activation; ISO:RGD.
DR GO; GO:0045669; P:positive regulation of osteoblast differentiation; ISO:RGD.
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:RGD.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0042127; P:regulation of cell population proliferation; ISO:RGD.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0071548; P:response to dexamethasone; IEP:RGD.
DR GO; GO:0007584; P:response to nutrient; IEP:RGD.
DR GO; GO:0080184; P:response to phenylpropanoid; IEP:RGD.
DR GO; GO:0033274; P:response to vitamin B2; IEP:RGD.
DR GO; GO:0006360; P:transcription by RNA polymerase I; ISS:UniProtKB.
DR GO; GO:0000050; P:urea cycle; ISO:RGD.
DR GO; GO:0050872; P:white fat cell differentiation; ISO:RGD.
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; Direct protein sequencing; DNA-binding;
KW Isopeptide bond; Nucleus; Phosphoprotein; Reference proteome;
KW Transcription; Transcription regulation; Ubl conjugation.
FT CHAIN 1..358
FT /note="CCAAT/enhancer-binding protein alpha"
FT /id="PRO_0000076615"
FT DOMAIN 282..345
FT /note="bZIP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT DNA_BIND 285..300
FT /evidence="ECO:0000269|PubMed:12578822"
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:0000269|PubMed:11672531"
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:0000269|PubMed:11672531"
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:0000250|UniProtKB:P53566"
FT REGION 213..310
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 240..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 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..238
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 277..309
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:0000250|UniProtKB:P53566"
FT MOD_RES 222
FT /note="Phosphothreonine; by GSK3"
FT /evidence="ECO:0000250|UniProtKB:P53566"
FT MOD_RES 226
FT /note="Phosphothreonine; by GSK3"
FT /evidence="ECO:0000250|UniProtKB:P53566"
FT MOD_RES 230
FT /note="Phosphoserine; by GSK3"
FT /evidence="ECO:0000250|UniProtKB:P53566"
FT CROSSLNK 159
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO); alternate"
FT /evidence="ECO:0000269|PubMed:16735515"
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:8367486"
FT /id="VSP_057551"
FT VAR_SEQ 1..14
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000269|PubMed:8367486"
FT /id="VSP_057552"
FT VAR_SEQ 1
FT /note="M -> MRGRGRVGVLGGRRRQRRHAQAGGRRGSPCRENSNSPM (in
FT isoform 4)"
FT /id="VSP_057609"
FT MUTAGEN 159
FT /note="K->A,R: Not sumoylated. No effect of sumoylation on
FT cell cycle inhibition."
FT /evidence="ECO:0000269|PubMed:16735515"
FT MUTAGEN 285
FT /note="Y->A: Decreased transcription factor activity.
FT Strongly decreased transcription factor activity; when
FT associated with R-293."
FT /evidence="ECO:0000269|PubMed:12578822"
FT MUTAGEN 285
FT /note="Y->A: Increases interaction with TFDP1 and TFDP2,
FT reduces DNA-binding, transactivation activity and represses
FT E2F1:TFDP1-mediated transcription, loss of cell cycle
FT inhibition and adipogenesis induction."
FT /evidence="ECO:0000269|PubMed:11672531,
FT ECO:0000269|PubMed:20176812"
FT MUTAGEN 287
FT /note="V->A: No effect on repression of E2F1:TFDP1-mediated
FT transcription, no effect on cell cycle inhibition or
FT adipogenesis; when associated with A-290."
FT /evidence="ECO:0000269|PubMed:11672531"
FT MUTAGEN 289
FT /note="R->A: Loss of DNA-binding and transcription factor
FT activity."
FT /evidence="ECO:0000269|PubMed:12578822"
FT MUTAGEN 290
FT /note="E->A: No effect on repression of E2F1:TFDP1-mediated
FT transcription, no effect on cell cycle inhibition or
FT adipogenesis; when associated with A-287."
FT /evidence="ECO:0000269|PubMed:11672531"
FT MUTAGEN 293
FT /note="N->R: Decreased transcription factor activity.
FT Strongly decreased transcription factor activity; when
FT associated with A-285."
FT /evidence="ECO:0000269|PubMed:12578822"
FT MUTAGEN 294
FT /note="I->A: Increases interaction with TFDP1 and TFDP2,
FT reduces transactivation activity and represses E2F1:TFDP1-
FT mediated transcription, loss of cell cycle inhibition and
FT adipogenesis induction, no effect on DNA-binding; when
FT associated with A-297."
FT /evidence="ECO:0000269|PubMed:11672531,
FT ECO:0000269|PubMed:20176812"
FT MUTAGEN 296
FT /note="V->A: No effect on DNA-binding and transcription
FT factor activity, but modified sequence specificity."
FT /evidence="ECO:0000269|PubMed:12578822"
FT MUTAGEN 297
FT /note="R->A: Increases interaction with TFDP1 and TFDP2,
FT reduces transactivation activity and represses E2F1:TFDP1-
FT mediated transcription, loss of cell cycle inhibition and
FT adipogenesis induction, no effect on DNA-binding; when
FT associated with A-294."
FT /evidence="ECO:0000269|PubMed:11672531,
FT ECO:0000269|PubMed:20176812"
FT MUTAGEN 299
FT /note="S->D: Isoform 4: Stimulates nucleolar retention of
FT isoform 4. No effect on interaction with NPM1, TAF1A and
FT UBTF."
FT /evidence="ECO:0000269|PubMed:20075868"
FT MUTAGEN 301
FT /note="D->A: No effect neither on interaction with TFDP1 or
FT TFDP2 nor on transactivation activity or repression of
FT E2F1:TFDP1-mediated transcription, no effect on cell cycle
FT inhibition or adipogenesis; when associated with A-304."
FT /evidence="ECO:0000269|PubMed:11672531,
FT ECO:0000269|PubMed:20176812"
FT MUTAGEN 304
FT /note="K->A: No effect neither on interaction with TFDP1 or
FT TFDP2 nor on transactivation activity or repression of
FT E2F1:TFDP1-mediated transcription, no effect on cell cycle
FT inhibition or adipogenesis; when associated with A-301."
FT /evidence="ECO:0000269|PubMed:11672531,
FT ECO:0000269|PubMed:20176812"
FT HELIX 282..338
FT /evidence="ECO:0007829|PDB:1NWQ"
SQ SEQUENCE 358 AA; 37371 MW; 4DA8F112F6EA95D0 CRC64;
MESADFYEAE PRPPMSSHLQ SPPHAPSNAA FGFPRGAGPA PPPAPPAAPE PLGGICEHET
SIDISAYIDP AAFNDEFLAD LFQHSRQQEK AKAAAGPAGG GGDFDYPGAP AGPGGAVMSA
GAHGPPPGYG CAAAGYLDGR LEPLYERVGA PALRPLVIKQ EPREEDEAKQ LALAGLFPYQ
PPPPPPPPHP HASPAHLAAP HLQFQIAHCG QTTMHLQPGH PTPPPTPVPS PHPAPAMGAA
GLPGPGGSLK GLAGPHPDLR TGGGGGGGAG AGKAKKSVDK NSNEYRVRRE RNNIAVRKSR
DKAKQRNVET QQKVLELTSD NDRLRKRVEQ LSRELDTLRG IFRQLPESSL VKAMGNCA
