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

More general terms

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

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=1385
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:1385
• OMIM: https://mirror.omim.org/entry/123810
• OMIM: https://mirror.omim.org/entry/612160
• UniProt: http://www.uniprot.org/uniprot/P16220.html