UniProt functional annotation for P08046



	UniProt functional annotation for P08046

UniProt code: P08046.

Organism: Mus musculus (Mouse).

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

Function: Transcriptional regulator (PubMed:8336701, PubMed:8703054, PubMed:15958557). Recognizes and binds to the DNA sequence 5'- GCG(T/G)GGGCG-3'(EGR-site) in the promoter region of target genes (PubMed:8703054, PubMed:15958557, PubMed:2028256, PubMed:8939742). Binds double-stranded target DNA, irrespective of the cytosine methylation status (By similarity). Regulates the transcription of numerous target genes, and thereby plays an important role in regulating the response to growth factors, DNA damage, and ischemia (PubMed:11100120, PubMed:15958557). Plays a role in the regulation of cell survival, proliferation and cell death (PubMed:15265859, PubMed:15958557). Activates expression of p53/TP53 and TGFB1, and thereby helps prevent tumor formation (PubMed:15958557). Required for normal progress through mitosis and normal proliferation of hepatocytes after partial hepatectomy (PubMed:15265859). Mediates responses to ischemia and hypoxia; regulates the expression of proteins such as IL1B and CXCL2 that are involved in inflammatory processes and development of tissue damage after ischemia (PubMed:11100120). Regulates biosynthesis of luteinizing hormone (LHB) in the pituitary (PubMed:8703054). Regulates the amplitude of the expression rhythms of clock genes: ARNTL/BMAL1, PER2 and NR1D1 in the liver via the activation of PER1 (clock repressor) transcription (PubMed:26471974). Regulates the rhythmic expression of core-clock gene ARNTL/BMAL1 in the suprachiasmatic nucleus (SCN) (PubMed:29138967). {ECO:0000250|UniProtKB:P18146, ECO:0000269|PubMed:11100120, ECO:0000269|PubMed:15265859, ECO:0000269|PubMed:15958557, ECO:0000269|PubMed:2028256, ECO:0000269|PubMed:26471974, ECO:0000269|PubMed:29138967, ECO:0000269|PubMed:8336701, ECO:0000269|PubMed:8703054, ECO:0000269|PubMed:8939742, ECO:0000305}.

Subunit: Interacts with SNAI1 and SP1 upon 12-O-tetradecanoylphorbol- 13-acetate (TPA) induction. {ECO:0000250|UniProtKB:P18146}.

Subcellular location: Nucleus {ECO:0000269|PubMed:11100120, ECO:0000269|PubMed:15958557, ECO:0000269|PubMed:8336701}. Cytoplasm {ECO:0000250|UniProtKB:P18146}.

Tissue specificity: Detected in lung vasculature and in mononuclear phagocytes (PubMed:11100120). Detected in liver (at protein level) (PubMed:15265859). Detected in lung vasculature and in mononuclear phagocytes (PubMed:11100120). Expressed in the liver in a circadian manner (PubMed:26471974). {ECO:0000269|PubMed:11100120, ECO:0000269|PubMed:15265859, ECO:0000269|PubMed:26471974}.

Induction: By growth factors (PubMed:3133658). Up-regulated in lung vasculature in response to reperfusion after ischemia (PubMed:11100120). Up-regulated in liver in response to partial hepatectomy (PubMed:15265859). {ECO:0000269|PubMed:11100120, ECO:0000269|PubMed:15265859, ECO:0000269|PubMed:3133658}.

Domain: Binds to DNA motifs with the sequence 5'-GCG(T/G)GGGCG-3' via its C2H2-type zinc fingers (PubMed:1740423, PubMed:8336701, PubMed:2028256, PubMed:8939742). The first, most N-terminal zinc finger binds to the 3'-GCG motif, the middle zinc finger interacts with the central TGG motif, and the C-terminal zinc finger binds to the 5'-GCG motif (PubMed:2028256, PubMed:8939742). Binds double-stranded target DNA, irrespective of the cytosine methylation status. Has reduced affinity for target DNA where the cytosines have been oxidized to 5- hydroxymethylcytosine. Does not bind target DNA where the cytosines have been oxidized to 5-formylcytosine or 5-carboxylcytosine (By similarity). {ECO:0000250|UniProtKB:P18146, ECO:0000269|PubMed:1740423, ECO:0000269|PubMed:2028256, ECO:0000269|PubMed:8939742}.

Disruption phenotype: Mice appear grossly normal, but females are anestrous and infertile with an uterus weight that is roughly 30% of that of wild-type. Ovaries contain normal numbers of follicles, but lack corpora lutea. Serum progesterone levels are strongly reduced; estradiol levels are normal. The level of luteinizing hormone (LHB) in the pituitary is strongly reduced in males and not detectable in females (PubMed:8703054). Responses to ischemia and hypoxia are blunted, leading to reduced tissue damage in response to ischemia and increased survival (PubMed:11100120). Liver regeneration is impaired after partial hepatectomy, due to impaired mitotic progress and reduced proliferation of hepatocytes (PubMed:15265859). Untreated mutant mice do not display an increased tendency to develop tumors, but develop tumors earlier than wild-type when treated first with a tumor initiator, and then with a tumor promoter (PubMed:15958557). Mice lack daily rhythmicity in the expression of the core-clock gene ARNTL/BMAL1 and display a reduced and altered locomotor activity and altered temperature regulation (PubMed:29138967). {ECO:0000269|PubMed:11100120, ECO:0000269|PubMed:15265859, ECO:0000269|PubMed:15958557, ECO:0000269|PubMed:29138967, ECO:0000269|PubMed:8703054}.

Similarity: Belongs to the EGR C2H2-type zinc-finger protein family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Mus musculus (Mouse).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.



Function:		Transcriptional regulator (PubMed:8336701, PubMed:8703054, PubMed:15958557). Recognizes and binds to the DNA sequence 5'- GCG(T/G)GGGCG-3'(EGR-site) in the promoter region of target genes (PubMed:8703054, PubMed:15958557, PubMed:2028256, PubMed:8939742). Binds double-stranded target DNA, irrespective of the cytosine methylation status (By similarity). Regulates the transcription of numerous target genes, and thereby plays an important role in regulating the response to growth factors, DNA damage, and ischemia (PubMed:11100120, PubMed:15958557). Plays a role in the regulation of cell survival, proliferation and cell death (PubMed:15265859, PubMed:15958557). Activates expression of p53/TP53 and TGFB1, and thereby helps prevent tumor formation (PubMed:15958557). Required for normal progress through mitosis and normal proliferation of hepatocytes after partial hepatectomy (PubMed:15265859). Mediates responses to ischemia and hypoxia; regulates the expression of proteins such as IL1B and CXCL2 that are involved in inflammatory processes and development of tissue damage after ischemia (PubMed:11100120). Regulates biosynthesis of luteinizing hormone (LHB) in the pituitary (PubMed:8703054). Regulates the amplitude of the expression rhythms of clock genes: ARNTL/BMAL1, PER2 and NR1D1 in the liver via the activation of PER1 (clock repressor) transcription (PubMed:26471974). Regulates the rhythmic expression of core-clock gene ARNTL/BMAL1 in the suprachiasmatic nucleus (SCN) (PubMed:29138967). {ECO:0000250\|UniProtKB:P18146, ECO:0000269\|PubMed:11100120, ECO:0000269\|PubMed:15265859, ECO:0000269\|PubMed:15958557, ECO:0000269\|PubMed:2028256, ECO:0000269\|PubMed:26471974, ECO:0000269\|PubMed:29138967, ECO:0000269\|PubMed:8336701, ECO:0000269\|PubMed:8703054, ECO:0000269\|PubMed:8939742, ECO:0000305}.


Subunit:		Interacts with SNAI1 and SP1 upon 12-O-tetradecanoylphorbol- 13-acetate (TPA) induction. {ECO:0000250\|UniProtKB:P18146}.
Subcellular location:		Nucleus {ECO:0000269\|PubMed:11100120, ECO:0000269\|PubMed:15958557, ECO:0000269\|PubMed:8336701}. Cytoplasm {ECO:0000250\|UniProtKB:P18146}.
Tissue specificity:		Detected in lung vasculature and in mononuclear phagocytes (PubMed:11100120). Detected in liver (at protein level) (PubMed:15265859). Detected in lung vasculature and in mononuclear phagocytes (PubMed:11100120). Expressed in the liver in a circadian manner (PubMed:26471974). {ECO:0000269\|PubMed:11100120, ECO:0000269\|PubMed:15265859, ECO:0000269\|PubMed:26471974}.
Induction:		By growth factors (PubMed:3133658). Up-regulated in lung vasculature in response to reperfusion after ischemia (PubMed:11100120). Up-regulated in liver in response to partial hepatectomy (PubMed:15265859). {ECO:0000269\|PubMed:11100120, ECO:0000269\|PubMed:15265859, ECO:0000269\|PubMed:3133658}.
Domain:		Binds to DNA motifs with the sequence 5'-GCG(T/G)GGGCG-3' via its C2H2-type zinc fingers (PubMed:1740423, PubMed:8336701, PubMed:2028256, PubMed:8939742). The first, most N-terminal zinc finger binds to the 3'-GCG motif, the middle zinc finger interacts with the central TGG motif, and the C-terminal zinc finger binds to the 5'-GCG motif (PubMed:2028256, PubMed:8939742). Binds double-stranded target DNA, irrespective of the cytosine methylation status. Has reduced affinity for target DNA where the cytosines have been oxidized to 5- hydroxymethylcytosine. Does not bind target DNA where the cytosines have been oxidized to 5-formylcytosine or 5-carboxylcytosine (By similarity). {ECO:0000250\|UniProtKB:P18146, ECO:0000269\|PubMed:1740423, ECO:0000269\|PubMed:2028256, ECO:0000269\|PubMed:8939742}.
Disruption phenotype:		Mice appear grossly normal, but females are anestrous and infertile with an uterus weight that is roughly 30% of that of wild-type. Ovaries contain normal numbers of follicles, but lack corpora lutea. Serum progesterone levels are strongly reduced; estradiol levels are normal. The level of luteinizing hormone (LHB) in the pituitary is strongly reduced in males and not detectable in females (PubMed:8703054). Responses to ischemia and hypoxia are blunted, leading to reduced tissue damage in response to ischemia and increased survival (PubMed:11100120). Liver regeneration is impaired after partial hepatectomy, due to impaired mitotic progress and reduced proliferation of hepatocytes (PubMed:15265859). Untreated mutant mice do not display an increased tendency to develop tumors, but develop tumors earlier than wild-type when treated first with a tumor initiator, and then with a tumor promoter (PubMed:15958557). Mice lack daily rhythmicity in the expression of the core-clock gene ARNTL/BMAL1 and display a reduced and altered locomotor activity and altered temperature regulation (PubMed:29138967). {ECO:0000269\|PubMed:11100120, ECO:0000269\|PubMed:15265859, ECO:0000269\|PubMed:15958557, ECO:0000269\|PubMed:29138967, ECO:0000269\|PubMed:8703054}.
Similarity:		Belongs to the EGR C2H2-type zinc-finger protein family. {ECO:0000305}.