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MGP000679

UniProt Annotations

Entry Information
Gene NamecAMP responsive element binding protein 1
Protein EntryCREB1_HUMAN
UniProt IDP16220
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=3; Name=CREB-A; IsoId=P16220-1; Sequence=Displayed; Name=CREB-B; IsoId=P16220-2; Sequence=VSP_000596; Name=3; Synonyms=htCREB; IsoId=P16220-3; Sequence=VSP_043914; Note=Highly expressed in adult testis and sperm.;
DiseaseAngiomatoid fibrous histiocytoma (AFH) [MIM:612160]: A distinct variant of malignant fibrous histiocytoma that typically occurs in children and adolescents and is manifest by nodular subcutaneous growth. Characteristic microscopic features include lobulated sheets of histiocyte-like cells intimately associated with areas of hemorrhage and cystic pseudovascular spaces, as well as a striking cuffing of inflammatory cells, mimicking a lymph node metastasis. Note=The gene represented in this entry may be involved in disease pathogenesis. A chromosomal aberration involving CREB1 is found in a patient with angiomatoid fibrous histiocytoma. Translocation t(2;22)(q33;q12) with CREB1 generates a EWSR1/CREB1 fusion gene that is most common genetic abnormality in this tumor type.
DiseaseNote=A CREB1 mutation has been found in a patient with multiple congenital anomalies consisting of agenesis of the corpus callosum, cerebellar hypoplasia, severe neonatal respiratory distress refractory to surfactant, thymus hypoplasia, and thyroid follicular hypoplasia. {ECO:0000269|PubMed:22267179}.
FunctionPhosphorylation-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-133 phosphorylation. Involved in different cellular processes including the synchronization of circadian rhythmicity and the differentiation of adipose cells.
InteractionP03259-2:- (xeno); NbExp=2; IntAct=EBI-711855, EBI-7225021; Q92793:CREBBP; NbExp=2; IntAct=EBI-711855, EBI-81215; Q09472:EP300; NbExp=2; IntAct=EBI-711855, EBI-447295; O00470:MEIS1; NbExp=9; IntAct=EBI-711855, EBI-1210694; Q96RG2:PASK; NbExp=2; IntAct=EBI-711855, EBI-1042651; Q6SA08:TSSK4; NbExp=5; IntAct=EBI-711855, EBI-1202583;
PtmStimulated by phosphorylation. Phosphorylation of both Ser- 133 and Ser-142 in the SCN regulates the activity of CREB and participates in circadian rhythm generation. Phosphorylation of Ser-133 allows CREBBP binding. In liver, phosphorylation is induced by fasting or glucagon in a circadian fashion (By similarity). CREBL2 positively regulates phosphorylation at Ser- 133 thereby stimulating CREB1 transcriptional activity (By similarity). Phosphorylated upon calcium influx by CaMK4 and CaMK2 on Ser-133. CaMK4 is much more potent than CaMK2 in activating CREB. Phosphorylated by CaMK2 on Ser-142. Phosphorylation of Ser- 142 blocks CREB-mediated transcription even when Ser-133 is phosphorylated. Phosphorylated by CaMK1 (By similarity). Phosphorylation of Ser-271 by HIPK2 in response to genotoxic stress promotes CREB1 activity, facilitating the recruitment of the coactivator CBP. Phosphorylated at Ser-133 by RPS6KA3, RPS6KA4 and RPS6KA5 in response to mitogenic or stress stimuli. {ECO:0000250, ECO:0000269|PubMed:15733869, ECO:0000269|PubMed:20573984, ECO:0000269|PubMed:7608156, ECO:0000269|PubMed:8065343, ECO:0000269|PubMed:9770464, ECO:0000269|PubMed:9829964}.
PtmSumoylated with SUMO1. Sumoylation on Lys-304, but not on Lys-285, is required for nuclear localization of this protein. Sumoylation is enhanced under hypoxia, promoting nuclear localization and stabilization. {ECO:0000269|PubMed:12552083}.
SimilarityBelongs to the bZIP family. {ECO:0000305}.
SimilarityContains 1 bZIP (basic-leucine zipper) domain. {ECO:0000255|PROSITE-ProRule:PRU00978}.
SimilarityContains 1 KID (kinase-inducible) domain. {ECO:0000255|PROSITE-ProRule:PRU00312}.
Subcellular LocationNucleus {ECO:0000255|PROSITE- ProRule:PRU00312, ECO:0000255|PROSITE-ProRule:PRU00978, ECO:0000269|PubMed:12552083}.
SubunitInteracts 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. When phosphorylated on Ser-133, binds CREBBP (By similarity). Interacts with CREBL2; regulates CREB1 phosphorylation, stability and transcriptional activity (By similarity). Interacts (phosphorylated form) with TOX3. Interacts with ARRB1. Binds to HIPK2. Interacts with SGK1. {ECO:0000250, ECO:0000269|PubMed:1386673, ECO:0000269|PubMed:14506290, ECO:0000269|PubMed:14536081, ECO:0000269|PubMed:15454081, ECO:0000269|PubMed:15733869, ECO:0000269|PubMed:16325578, ECO:0000269|PubMed:16908542, ECO:0000269|PubMed:1827531, ECO:0000269|PubMed:20573984, ECO:0000269|PubMed:21172805}.
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