UniProt functional annotation for Q01147



	UniProt functional annotation for Q01147

UniProt code: Q01147.

Organism: Mus musculus (Mouse).

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

Function: Phosphorylation-dependent transcription factor that stimulates transcription upon binding to the DNA cAMP response element (CRE), a sequence present in many viral and cellular promoters. Transcription activation is enhanced by the TORC coactivators which act independently of Ser-119 phosphorylation. Involved in different cellular processes including the synchronization of circadian rhythmicity and the differentiation of adipose cells. {ECO:0000269|PubMed:11970866, ECO:0000269|PubMed:21728997}.

Subunit: Interacts with PPRC1. Binds DNA as a dimer. This dimer is stabilized by magnesium ions. Interacts, through the bZIP domain, with the coactivators TORC1/CRTC1, TORC2/CRTC2 and TORC3/CRTC3. Interacts (phosphorylated form) with TOX3 (By similarity). When phosphorylated on Ser-119, binds CREBBP. Interacts with ARRB1. Binds to HIPK2 (By similarity). Interacts with SGK1 (By similarity). Interacts with CREBL2; regulates CREB1 phosphorylation, stability and transcriptional activity. Interacts with TSSK4; this interaction facilitates phosphorylation on Ser-119 (By similarity). Forms a complex with KMT2A and CREBBP (By similarity). {ECO:0000250|UniProtKB:P16220, ECO:0000269|PubMed:10952992, ECO:0000269|PubMed:21728997, ECO:0000269|PubMed:8552098}.

Subcellular location: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00312, ECO:0000255|PROSITE-ProRule:PRU00978, ECO:0000269|PubMed:21728997}.

Tissue specificity: Ubiquitously expressed. {ECO:0000269|PubMed:1387109}.

Ptm: Phosphorylation of Ser-119 allows CREBBP binding. Stimulated by phosphorylation. Phosphorylated Ser-128 can be detected in the suprachiasmatic nucleus (SCN), the amygdala, the cortex, and the hippocampus but not in the striatum nor in the cerebellum. In the SCN, phosphorylation of Ser-128 and Ser-119 are stimulated by light exposure and submitted to circadian oscillations. In the retina, only phosphorylation of Ser-119 can be detected upon light exposure. Phosphorylation of both Ser-119 and Ser-128 in the SCN regulates the activity of CREB and participates in circadian rhythm generation. Phosphorylated upon calcium influx by CaMK4 and CaMK2 on Ser-119. CaMK4 is much more potent than CAMK2 in activating CREB. Phosphorylated by CaMK2 on Ser-128. Phosphorylation of Ser-128 blocks CREB-mediated transcription even when Ser-119 is phosphorylated. Phosphorylated by CaMK1. Phosphorylation of Ser-271 by HIPK2 in response to genotoxic stress promotes CREB1 activity, facilitating the recruitment of the coactivator CBP (By similarity). Phosphorylated at Ser-119 by RPS6KA3, RPS6KA4 and RPS6KA5 in response to mitogenic or stress stimuli. CREBL2 positively regulates phosphorylation at Ser-119 thereby stimulating CREB1 transcriptional activity. In liver, phosphorylation is induced by fasting or glucagon in a circadian fashion. Phosphorylated by TSSK4 on Ser-119 (By similarity). {ECO:0000250|UniProtKB:P16220, ECO:0000269|PubMed:11970866, ECO:0000269|PubMed:18690222, ECO:0000269|PubMed:20852621, ECO:0000269|PubMed:8552098}.

Ptm: Sumoylated with SUMO1. Sumoylation on Lys-290, but not on Lys-271, is required for nuclear localization of this protein. Sumoylation is enhanced under hypoxia, promoting nuclear localization and stabilization (By similarity). {ECO:0000250}.

Similarity: Belongs to the bZIP 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:		Phosphorylation-dependent transcription factor that stimulates transcription upon binding to the DNA cAMP response element (CRE), a sequence present in many viral and cellular promoters. Transcription activation is enhanced by the TORC coactivators which act independently of Ser-119 phosphorylation. Involved in different cellular processes including the synchronization of circadian rhythmicity and the differentiation of adipose cells. {ECO:0000269\|PubMed:11970866, ECO:0000269\|PubMed:21728997}.


Subunit:		Interacts with PPRC1. Binds DNA as a dimer. This dimer is stabilized by magnesium ions. Interacts, through the bZIP domain, with the coactivators TORC1/CRTC1, TORC2/CRTC2 and TORC3/CRTC3. Interacts (phosphorylated form) with TOX3 (By similarity). When phosphorylated on Ser-119, binds CREBBP. Interacts with ARRB1. Binds to HIPK2 (By similarity). Interacts with SGK1 (By similarity). Interacts with CREBL2; regulates CREB1 phosphorylation, stability and transcriptional activity. Interacts with TSSK4; this interaction facilitates phosphorylation on Ser-119 (By similarity). Forms a complex with KMT2A and CREBBP (By similarity). {ECO:0000250\|UniProtKB:P16220, ECO:0000269\|PubMed:10952992, ECO:0000269\|PubMed:21728997, ECO:0000269\|PubMed:8552098}.
Subcellular location:		Nucleus {ECO:0000255\|PROSITE-ProRule:PRU00312, ECO:0000255\|PROSITE-ProRule:PRU00978, ECO:0000269\|PubMed:21728997}.
Tissue specificity:		Ubiquitously expressed. {ECO:0000269\|PubMed:1387109}.
Ptm:		Phosphorylation of Ser-119 allows CREBBP binding. Stimulated by phosphorylation. Phosphorylated Ser-128 can be detected in the suprachiasmatic nucleus (SCN), the amygdala, the cortex, and the hippocampus but not in the striatum nor in the cerebellum. In the SCN, phosphorylation of Ser-128 and Ser-119 are stimulated by light exposure and submitted to circadian oscillations. In the retina, only phosphorylation of Ser-119 can be detected upon light exposure. Phosphorylation of both Ser-119 and Ser-128 in the SCN regulates the activity of CREB and participates in circadian rhythm generation. Phosphorylated upon calcium influx by CaMK4 and CaMK2 on Ser-119. CaMK4 is much more potent than CAMK2 in activating CREB. Phosphorylated by CaMK2 on Ser-128. Phosphorylation of Ser-128 blocks CREB-mediated transcription even when Ser-119 is phosphorylated. Phosphorylated by CaMK1. Phosphorylation of Ser-271 by HIPK2 in response to genotoxic stress promotes CREB1 activity, facilitating the recruitment of the coactivator CBP (By similarity). Phosphorylated at Ser-119 by RPS6KA3, RPS6KA4 and RPS6KA5 in response to mitogenic or stress stimuli. CREBL2 positively regulates phosphorylation at Ser-119 thereby stimulating CREB1 transcriptional activity. In liver, phosphorylation is induced by fasting or glucagon in a circadian fashion. Phosphorylated by TSSK4 on Ser-119 (By similarity). {ECO:0000250\|UniProtKB:P16220, ECO:0000269\|PubMed:11970866, ECO:0000269\|PubMed:18690222, ECO:0000269\|PubMed:20852621, ECO:0000269\|PubMed:8552098}.
Ptm:		Sumoylated with SUMO1. Sumoylation on Lys-290, but not on Lys-271, is required for nuclear localization of this protein. Sumoylation is enhanced under hypoxia, promoting nuclear localization and stabilization (By similarity). {ECO:0000250}.
Similarity:		Belongs to the bZIP family. {ECO:0000305}.