CEBPA_BOVIN
ID CEBPA_BOVIN Reviewed; 353 AA.
AC O02754; Q4PLC3;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 1.
DT 03-AUG-2022, entry version 110.
DE RecName: Full=CCAAT/enhancer-binding protein alpha {ECO:0000250|UniProtKB:P49715};
DE Short=C/EBP alpha;
GN Name=CEBPA {ECO:0000250|UniProtKB:P49715};
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=Japanese black;
RX PubMed=8904724; DOI=10.2527/1996.74102554x;
RA Taniguchi Y., Sasaki Y.;
RT "Nucleotide sequence of bovine C/EBP alpha gene.";
RL J. Anim. Sci. 74:2554-2554(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=Korean;
RA Chung E.R., Shin S.C.;
RT "Detection of single nucleotide polymorphisms of enhancer-binding alpha
RT protein (C/EBP alpha) in Korean cattle.";
RL Submitted (MAY-2005) to the EMBL/GenBank/DDBJ databases.
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. During early embryogenesis, plays essential
CC and redundant functions with CEBPB. Essential for the transition from
CC common myeloid progenitors (CMP) to granulocyte/monocyte progenitors
CC (GMP). Critical for the proper development of the liver and the lung.
CC Necessary for terminal adipocyte differentiation, is required for
CC postnatal maintenance of systemic energy homeostasis and lipid storage.
CC To regulate these different processes at the proper moment and tissue,
CC interplays with other transcription factors and modulators. Down-
CC 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. 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. 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. {ECO:0000250|UniProtKB:P05554,
CC ECO:0000250|UniProtKB:P49715, ECO:0000250|UniProtKB:P53566}.
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 (By
CC similarity). 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 (By similarity).
CC Interacts with RB1. Interacts (when phosphorylated at SER-190) with
CC CDK2, CDK4, E2F4 and SMARCA2. Interacts with SREBPF1. Interacts with
CC FOXO1 (via the Fork-head domain); the interaction increases when FOXO1
CC is deacetylated. Interacts with SIX1 (By similarity). Interacts with
CC TAF1A and UBTF. Interacts (via recognition sequence) with TRIB1.
CC {ECO:0000250|UniProtKB:P05554, ECO:0000250|UniProtKB:P49715,
CC ECO:0000250|UniProtKB:P53566}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P53566}.
CC -!- DOMAIN: The recognition sequence (54-72) is required for interaction
CC with TRIB1. {ECO:0000250|UniProtKB:P49715}.
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. 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: 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:0000250|UniProtKB:P49715}.
CC -!- SIMILARITY: Belongs to the bZIP family. C/EBP subfamily. {ECO:0000305}.
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DR EMBL; D82984; BAA20095.1; -; Genomic_DNA.
DR EMBL; DQ068270; AAY79353.1; -; Genomic_DNA.
DR AlphaFoldDB; O02754; -.
DR SMR; O02754; -.
DR PRIDE; O02754; -.
DR InParanoid; O02754; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0003677; F:DNA binding; ISS:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISS:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISS:UniProtKB.
DR GO; GO:0045444; P:fat cell differentiation; ISS:UniProtKB.
DR GO; GO:0042593; P:glucose homeostasis; ISS:UniProtKB.
DR GO; GO:0030851; P:granulocyte differentiation; ISS:UniProtKB.
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:0030099; P:myeloid cell differentiation; IBA:GO_Central.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
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 3: Inferred from homology;
KW Acetylation; Activator; Developmental protein; DNA-binding;
KW Isopeptide bond; Nucleus; Phosphoprotein; Reference proteome;
KW Transcription; Transcription regulation; Ubl conjugation.
FT CHAIN 1..353
FT /note="CCAAT/enhancer-binding protein alpha"
FT /id="PRO_0000076612"
FT DOMAIN 277..340
FT /note="bZIP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT DNA_BIND 280..295
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..56
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..197
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..278
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 240..353
FT /note="Interaction with FOXO1"
FT /evidence="ECO:0000250|UniProtKB:P53566"
FT REGION 281..308
FT /note="Basic motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 312..340
FT /note="Leucine-zipper"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT COMPBIAS 177..195
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 MOD_RES 159
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P49715"
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: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 CONFLICT 189
FT /note="N -> H (in Ref. 2; AAY79353)"
FT /evidence="ECO:0000305"
FT CONFLICT 253
FT /note="V -> A (in Ref. 2; AAY79353)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 353 AA; 37218 MW; 48CDFB726F29C310 CRC64;
MESADFYEAE PRPPMSSHLQ SPPHAPSSAA FGFPRGAGPS QPPAPPAAPE PLGGICEHET
SIDISAYIDP AAFNDEFLAD LFQHSRQQEK AKAAAAPAGG GNDFDYPGAP VGPGGAVMPG
GTHGPPPGYG CAAAGYLDSR LEPLYERVGA PALRPLVIKQ EPREEDEAKQ LALAGLFPYQ
PPPPPPPPNS HPPPAHLAAP HLQFQIAHCG QTTMHLQPGH PTPPPTPVPS PHPAPALGAA
GLPGPGGALK GLVATHPDLR AGGGGGGKAK KSVDKNSNEY RVRRERNNIA VRKSRDKAKQ
RNVETQQKVL ELTSDNDRLR KRVEQLSREL DTLRGIFRQL PESSLVKAMG NCA
