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cAMP-responsive element [CRE]-binding protein 1 (CREB1)

Function: - binds the cAMP response element (CRE), a sequence present in many viral & cellular promoters - CREB stimulates transcription on binding to the CRE - transcription activation is enhanced by the TORC coactivators which act independently of Ser-133 phosphorylation - implicated in synchronization of circadian rhythmicity interacts with PPRC1 - binds DNA as a dimer - this dimer is stabilized by Mg+2 - interacts, through the bZIP domain, with the coactivators CRTC1, CRTC2 & CRTC3 - when phosphorylated on Ser-133, binds CREBBP (putative) - stimulated by phosphorylation - phosphorylation may not modulate DNA-binding activity but rather may influence transcriptional activation domain - phosphorylation of both Ser-133 & Ser-142 in the SCN regulates the activity of CREB & participates in circadian rhythm generation - phosphorylation of Ser-133 allows CREBBP binding (putative) - phosphorylated upon DNA damage, probably by ATM or ATR - sumoylated by SUMO1 - sumoylation on Lys-304 required for nuclear localization - sumoylation is enhanced under hypoxia, promoting nuclear localization & stabilization - interacts with PPRC1 - interacts (phosporylated form) with TOX - interacts with ARRB1 - binds to HIPK2 - interacts with SGK1 Structure: - belongs to the bZIP family - contains 1 bZIP domain - contains 1 KID (kinase-inducible) domain Compartment: nucleus Alternative splicing: named isoforms=2 Pathology: - defects in CREB1 may be a cause of angiomatoid fibrous histiocytoma

General

cAMP-responsive element [CRE]-binding protein (CREB) phosphoprotein

Properties

SIZE: entity length = 341 aa MW = 37 kD COMPARTMENT: cell nucleus MOTIF: KID {101-160} MOTIF: Ser phosphorylation site {S111} Thr phosphorylation site {T119} Ser phosphorylation site {S133} Ser phosphorylation site {S142} DNA-binding motif SITE: 284-305 leucine zipper SITE: 311-332 FOR-BINDING-VIA: leucine zipper MOTIF: arginine residue {314}

Database Correlations

OMIM correlations UniProt P16220 PFAM correlations Entrez Gene 1385 Kegg hsa:1385

References

  1. UniProt :accession P16220
  2. Dwarki VJ, Montminy M, Verma IM. Both the basic region and the 'leucine zipper' domain of the cyclic AMP response element binding (CREB) protein are essential for transcriptional activation. EMBO J. 1990 Jan;9(1):225-32. PMID: 2136830
  3. Struthers RS, Vale WW, Arias C, Sawchenko PE, Montminy MR. Somatotroph hypoplasia and dwarfism in transgenic mice expressing a non-phosphorylatable CREB mutant. Nature. 1991 Apr 18;350(6319):622-4. PMID: 1826763
  4. Morgan & Curran The Neuroscientist 1:68 1995