UniProt functional annotation for P05554



	UniProt functional annotation for P05554

UniProt code: P05554.

Organism: Rattus norvegicus (Rat).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus.

Function: Transcription factor that coordinates proliferation arrest and the differentiation of myeloid progenitors, adipocytes, hepatocytes, and cells of the lung and the placenta (PubMed:8367486, PubMed:11672531, PubMed:16735515, PubMed:20176812). Binds directly to the consensus DNA sequence 5'-T[TG]NNGNAA[TG]-3' acting as an activator on distinct target genes. During early embryogenesis, plays essential and redundant functions with CEBPB (By similarity). Essential for the transition from common myeloid progenitors (CMP) to granulocyte/monocyte progenitors (GMP) (PubMed:11672531). Critical for the proper development of the liver and the lung (By similarity). Necessary for terminal adipocyte differentiation, is required for postnatal maintenance of systemic energy homeostasis and lipid storage (PubMed:11672531). To regulate these different processes at the proper moment and tissue, interplays with other transcription factors and modulators. Downregulates the expression of genes that maintain cells in an undifferentiated and proliferative state through E2F1 repression, which is critical for its ability to induce adipocyte and granulocyte terminal differentiation. Reciprocally E2F1 blocks adipocyte differentiation by binding to specific promoters and repressing CEBPA binding to its target gene promoters (PubMed:11672531). Proliferation arrest also depends on a functional binding to SWI/SNF complex (By similarity). In liver, regulates gluconeogenesis and lipogenesis through different mechanisms. To regulate gluconeogenesis, functionally cooperates with FOXO1 binding to IRE-controlled promoters and regulating the expression of target genes such as PCK1 or G6PC1. To modulate lipogenesis, interacts and transcriptionally synergizes with SREBF1 in promoter activation of specific lipogenic target genes such as ACAS2. In adipose tissue, seems to act as FOXO1 coactivator accessing to ADIPOQ promoter through FOXO1 binding sites (By similarity). {ECO:0000250|UniProtKB:P49715, ECO:0000250|UniProtKB:P53566, ECO:0000269|PubMed:11672531, ECO:0000269|PubMed:16735515, ECO:0000269|PubMed:20176812, ECO:0000269|PubMed:8367486}.

Function: [Isoform 3]: Can act as dominant-negative. Binds DNA and have transctivation activity, even if much less efficiently than isoform 2. Does not inhibit cell proliferation. {ECO:0000250|UniProtKB:P49715, ECO:0000250|UniProtKB:P53566, ECO:0000269|PubMed:8367486}.

Function: [Isoform 4]: Directly and specifically enhances ribosomal DNA transcription interacting with RNA polymerase I-specific cofactors and inducing histone acetylation. {ECO:0000250|UniProtKB:P49715}.

Subunit: Binds DNA as a homodimer and as a heterodimer (PubMed:1884998, PubMed:8367486, PubMed:12578822). Can form stable heterodimers with CEBPB, CEBPD, CEBPE and CEBPG (PubMed:1884998, PubMed:1377818). Can form stable homodimers (also isoform 2 and isoform 3 dimers) and heterodimers with CEBPB (with isoform 2 and isoform 3) and CEBPG (PubMed:1377818, PubMed:8367486). Interacts with PRDM16 (By similarity). Interacts with UBN1 (By similarity). Interacts with ZNF638; this interaction increases transcriptional activation (By similarity). Interacts with the complex TFDP2:E2F1; the interaction prevents CEBPA binding to target gene promoters and represses its transcriptional activity (By similarity). Interacts with RB1 (By similarity). Interacts (when phosphorylated at SER-193) with CDK2, CDK4, E2F4 and SMARCA2 (By similarity). Interacts with SREBPF1 (By similarity). Interacts with FOXO1 (via the Fork-head domain); the interaction increases when FOXO1 is deacetylated (By similarity). Interacts with SIX1 (By similarity). Interacts (via recognition sequence) with TRIB1 (By similarity). {ECO:0000250|UniProtKB:P49715, ECO:0000250|UniProtKB:P53566, ECO:0000269|PubMed:12578822, ECO:0000269|PubMed:1377818, ECO:0000269|PubMed:1884998, ECO:0000269|PubMed:20075868, ECO:0000269|PubMed:8367486}.

Subunit: [Isoform 1]: Interacts with TAF1A and UBTF. {ECO:0000269|PubMed:20075868}.

Subunit: [Isoform 4]: Interacts with NPM1. {ECO:0000269|PubMed:20075868}.

Subcellular location: Nucleus {ECO:0000269|PubMed:8367486}.

Subcellular location: [Isoform 4]: Nucleus, nucleolus {ECO:0000269|PubMed:20075868}.

Tissue specificity: Isoform 2 and isoform 3 are expressed in liver (at protein level). {ECO:0000269|PubMed:8367486}.

Developmental stage: Isoform 2 and isoform 3 are not expressed at 1 day before birth, relative concentration of both isoforms increases with the age of the animal, reaching maximal levels in the adulthood. {ECO:0000269|PubMed:8367486}.

Domain: The recognition sequence (54-72) is required for interaction with TRIB1. {ECO:0000250|UniProtKB:P49715}.

Ptm: Sumoylated, sumoylation blocks the inhibitory effect on cell proliferation by disrupting the interaction with SMARCA2. {ECO:0000269|PubMed:16735515}.

Ptm: Phosphorylation at Ser-193 is required for interaction with CDK2, CDK4 and SWI/SNF complex leading to cell cycle inhibition. Dephosphorylated at Ser-193 by protein phosphatase 2A (PP2A) through PI3K/AKT signaling pathway regulation. Phosphorylation at Thr-222 and Thr-226 by GSK3 is constitutive in adipose tissue and lung. In liver, both Thr-222 and Thr-226 are phosphorylated only during feeding but not during fasting. Phosphorylation of the GSK3 consensus sites selectively decreases transactivation activity on IRE-controlled promoters. {ECO:0000250|UniProtKB:P53566}.

Ptm: Ubiquitinated by COP1 upon interaction with TRIB1. {ECO:0000250|UniProtKB:P49715}.

Miscellaneous: The V296A substitution has little effect on the binding of CEBPA to its consensus site (5'-GCAAT-3'), while greatly increasing affinity for cAMP response element (CRE) sites (5'-GTCAT-3'). {ECO:0000269|PubMed:12578822}.

Miscellaneous: [Isoform 4]: Mutagenesis in position: 14: RRQR -> AAAA abolishes nucleolar localization and prevents induction of 45S pre-RNA. {ECO:0000269|PubMed:20075868}.

Similarity: Belongs to the bZIP family. C/EBP subfamily. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Rattus norvegicus (Rat).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus.



Function:		Transcription factor that coordinates proliferation arrest and the differentiation of myeloid progenitors, adipocytes, hepatocytes, and cells of the lung and the placenta (PubMed:8367486, PubMed:11672531, PubMed:16735515, PubMed:20176812). Binds directly to the consensus DNA sequence 5'-T[TG]NNGNAA[TG]-3' acting as an activator on distinct target genes. During early embryogenesis, plays essential and redundant functions with CEBPB (By similarity). Essential for the transition from common myeloid progenitors (CMP) to granulocyte/monocyte progenitors (GMP) (PubMed:11672531). Critical for the proper development of the liver and the lung (By similarity). Necessary for terminal adipocyte differentiation, is required for postnatal maintenance of systemic energy homeostasis and lipid storage (PubMed:11672531). To regulate these different processes at the proper moment and tissue, interplays with other transcription factors and modulators. Downregulates the expression of genes that maintain cells in an undifferentiated and proliferative state through E2F1 repression, which is critical for its ability to induce adipocyte and granulocyte terminal differentiation. Reciprocally E2F1 blocks adipocyte differentiation by binding to specific promoters and repressing CEBPA binding to its target gene promoters (PubMed:11672531). Proliferation arrest also depends on a functional binding to SWI/SNF complex (By similarity). In liver, regulates gluconeogenesis and lipogenesis through different mechanisms. To regulate gluconeogenesis, functionally cooperates with FOXO1 binding to IRE-controlled promoters and regulating the expression of target genes such as PCK1 or G6PC1. To modulate lipogenesis, interacts and transcriptionally synergizes with SREBF1 in promoter activation of specific lipogenic target genes such as ACAS2. In adipose tissue, seems to act as FOXO1 coactivator accessing to ADIPOQ promoter through FOXO1 binding sites (By similarity). {ECO:0000250\|UniProtKB:P49715, ECO:0000250\|UniProtKB:P53566, ECO:0000269\|PubMed:11672531, ECO:0000269\|PubMed:16735515, ECO:0000269\|PubMed:20176812, ECO:0000269\|PubMed:8367486}.



Function:		[Isoform 3]: Can act as dominant-negative. Binds DNA and have transctivation activity, even if much less efficiently than isoform 2. Does not inhibit cell proliferation. {ECO:0000250\|UniProtKB:P49715, ECO:0000250\|UniProtKB:P53566, ECO:0000269\|PubMed:8367486}.



Function:		[Isoform 4]: Directly and specifically enhances ribosomal DNA transcription interacting with RNA polymerase I-specific cofactors and inducing histone acetylation. {ECO:0000250\|UniProtKB:P49715}.


Subunit:		Binds DNA as a homodimer and as a heterodimer (PubMed:1884998, PubMed:8367486, PubMed:12578822). Can form stable heterodimers with CEBPB, CEBPD, CEBPE and CEBPG (PubMed:1884998, PubMed:1377818). Can form stable homodimers (also isoform 2 and isoform 3 dimers) and heterodimers with CEBPB (with isoform 2 and isoform 3) and CEBPG (PubMed:1377818, PubMed:8367486). Interacts with PRDM16 (By similarity). Interacts with UBN1 (By similarity). Interacts with ZNF638; this interaction increases transcriptional activation (By similarity). Interacts with the complex TFDP2:E2F1; the interaction prevents CEBPA binding to target gene promoters and represses its transcriptional activity (By similarity). Interacts with RB1 (By similarity). Interacts (when phosphorylated at SER-193) with CDK2, CDK4, E2F4 and SMARCA2 (By similarity). Interacts with SREBPF1 (By similarity). Interacts with FOXO1 (via the Fork-head domain); the interaction increases when FOXO1 is deacetylated (By similarity). Interacts with SIX1 (By similarity). Interacts (via recognition sequence) with TRIB1 (By similarity). {ECO:0000250\|UniProtKB:P49715, ECO:0000250\|UniProtKB:P53566, ECO:0000269\|PubMed:12578822, ECO:0000269\|PubMed:1377818, ECO:0000269\|PubMed:1884998, ECO:0000269\|PubMed:20075868, ECO:0000269\|PubMed:8367486}.
Subunit:		[Isoform 1]: Interacts with TAF1A and UBTF. {ECO:0000269\|PubMed:20075868}.
Subunit:		[Isoform 4]: Interacts with NPM1. {ECO:0000269\|PubMed:20075868}.
Subcellular location:		Nucleus {ECO:0000269\|PubMed:8367486}.
Subcellular location:		[Isoform 4]: Nucleus, nucleolus {ECO:0000269\|PubMed:20075868}.
Tissue specificity:		Isoform 2 and isoform 3 are expressed in liver (at protein level). {ECO:0000269\|PubMed:8367486}.
Developmental stage:		Isoform 2 and isoform 3 are not expressed at 1 day before birth, relative concentration of both isoforms increases with the age of the animal, reaching maximal levels in the adulthood. {ECO:0000269\|PubMed:8367486}.
Domain:		The recognition sequence (54-72) is required for interaction with TRIB1. {ECO:0000250\|UniProtKB:P49715}.
Ptm:		Sumoylated, sumoylation blocks the inhibitory effect on cell proliferation by disrupting the interaction with SMARCA2. {ECO:0000269\|PubMed:16735515}.
Ptm:		Phosphorylation at Ser-193 is required for interaction with CDK2, CDK4 and SWI/SNF complex leading to cell cycle inhibition. Dephosphorylated at Ser-193 by protein phosphatase 2A (PP2A) through PI3K/AKT signaling pathway regulation. Phosphorylation at Thr-222 and Thr-226 by GSK3 is constitutive in adipose tissue and lung. In liver, both Thr-222 and Thr-226 are phosphorylated only during feeding but not during fasting. Phosphorylation of the GSK3 consensus sites selectively decreases transactivation activity on IRE-controlled promoters. {ECO:0000250\|UniProtKB:P53566}.
Ptm:		Ubiquitinated by COP1 upon interaction with TRIB1. {ECO:0000250\|UniProtKB:P49715}.
Miscellaneous:		The V296A substitution has little effect on the binding of CEBPA to its consensus site (5'-GCAAT-3'), while greatly increasing affinity for cAMP response element (CRE) sites (5'-GTCAT-3'). {ECO:0000269\|PubMed:12578822}.
Miscellaneous:		[Isoform 4]: Mutagenesis in position: 14: RRQR -> AAAA abolishes nucleolar localization and prevents induction of 45S pre-RNA. {ECO:0000269\|PubMed:20075868}.
Similarity:		Belongs to the bZIP family. C/EBP subfamily. {ECO:0000305}.