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P15337 (CREB1_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 147. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Cyclic AMP-responsive element-binding protein 1

Short name=CREB-1
Short name=cAMP-responsive element-binding protein 1
Gene names
Name:Creb1
Synonyms:Creb-1
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length341 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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-117 phosphorylation. Involved in different cellular processes including the synchronization of circadian rhythmicity and the differentiation of adipose cells By similarity.

Subunit structure

Interacts with PPRC1. Binds DNA as a dimer. Interacts, through the bZIP domain, with the coactivators TORC1/CRTC1, TORC2/CRTC2 and TORC3/CRTC3 By similarity. When phosphorylated on Ser-133, binds CREBBP. Interacts with ARRB1. Interacts (phosphorylated form) with TOX3. Binds to HIPK2 By similarity. Interacts with SGK1 By similarity. Interacts with CREBL2; regulates CREB1 phosphorylation, stability and transcriptional activity By similarity.

Subcellular location

Nucleus.

Post-translational modification

Phosphorylation of Ser-133 allows CREBBP binding. Stimulated by phosphorylation. Phosphorylation of both Ser-142 and Ser-133 in the SCN regulates the activity of CREB and participate in circadian rhythm generation 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. 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 By similarity. CREBL2 positively regulates phosphorylation at Ser-133 thereby stimulating CREB1 transcriptional activity By similarity. Ref.3 Ref.4 Ref.5

Sumoylated 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 By similarity.

Sequence similarities

Belongs to the bZIP family.

Contains 1 bZIP (basic-leucine zipper) domain.

Contains 1 KID (kinase-inducible) domain.

Ontologies

Keywords
   Biological processDifferentiation
Transcription
Transcription regulation
   Cellular componentNucleus
   Coding sequence diversityAlternative splicing
   LigandDNA-binding
   Molecular functionActivator
   PTMIsopeptide bond
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processcell differentiation

Inferred from electronic annotation. Source: UniProtKB-KW

circadian rhythm

Inferred from expression pattern PubMed 21367864. Source: RGD

positive regulation of RNA polymerase II transcriptional preinitiation complex assembly

Inferred from mutant phenotype PubMed 16891311. Source: RGD

positive regulation of fat cell differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of lipid biosynthetic process

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 12409294. Source: RGD

positive regulation of transcription, DNA-templated

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of transforming growth factor beta3 production

Inferred from mutant phenotype PubMed 16891311. Source: RGD

protein stabilization

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of apoptotic process

Inferred from direct assay PubMed 12939230. Source: RGD

regulation of circadian rhythm

Inferred from mutant phenotype PubMed 12409294. Source: RGD

transcription from RNA polymerase II promoter

Inferred from mutant phenotype PubMed 12697699. Source: RGD

transforming growth factor beta receptor signaling pathway

Inferred from mutant phenotype PubMed 16891311. Source: RGD

   Cellular_componentchromatin

Inferred from direct assay PubMed 15632413. Source: RGD

mitochondrion

Inferred from direct assay PubMed 15663486. Source: RGD

nuclear chromatin

Inferred from direct assay PubMed 16427017. Source: BHF-UCL

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay PubMed 19033670. Source: MGI

transcription factor complex

Inferred from direct assay PubMed 15632413. Source: RGD

   Molecular_functionRNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity

Inferred from direct assay PubMed 12409294. Source: RGD

double-stranded DNA binding

Inferred from direct assay PubMed 12697699. Source: RGD

histone acetyltransferase binding

Inferred from physical interaction PubMed 22357921. Source: RGD

sequence-specific DNA binding

Inferred from direct assay PubMed 12697699PubMed 15632413PubMed 16891311PubMed 16959941. Source: RGD

sequence-specific DNA binding transcription factor activity

Inferred from mutant phenotype PubMed 12697699. Source: RGD

transcription factor binding

Inferred from physical interaction PubMed 11466227. Source: RGD

transcription regulatory region DNA binding

Inferred from direct assay PubMed 21367864. Source: RGD

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P15337-1)

Also known as: Alpha;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: P15337-2)

Also known as: Delta;

The sequence of this isoform differs from the canonical sequence as follows:
     88-101: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 341341Cyclic AMP-responsive element-binding protein 1
PRO_0000076599

Regions

Domain101 – 16060KID
Domain283 – 34159bZIP
Region284 – 30926Basic motif By similarity
Region311 – 33222Leucine-zipper By similarity

Amino acid modifications

Modified residue1331Phosphoserine; by CaMK1, CaMK2, CaMK4, PKB/AKT1 or PKB/AKT2, RPS6KA3, RPS6KA4, RPS6KA5 and SGK1 Ref.3 Ref.4 Ref.5
Modified residue1421Phosphoserine; by CaMK2 Ref.4
Modified residue2711Phosphoserine; by HIPK2 By similarity
Cross-link285Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1) By similarity
Cross-link304Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1) By similarity

Natural variations

Alternative sequence88 – 10114Missing in isoform 2.
VSP_000598

Experimental info

Mutagenesis1331S → A: Loss of activation by CaMK4. Ref.4
Mutagenesis1421S → A: Loss of phosphorylation by CaMK2. Activation by CaMK2. Ref.4
Sequence conflict1351R → K in CAA42619. Ref.2
Sequence conflict3191E → K in CAA42619. Ref.2

Secondary structure

..... 341
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Alpha) [UniParc].

Last modified April 1, 1990. Version 1.
Checksum: FC08AC5A335D4C2F

FASTA34136,633
        10         20         30         40         50         60 
MTMDSGADNQ QSGDAAVTEA ESQQMTVQAQ PQIATLAQVS MPAAHATSSA PTVTLVQLPN 

        70         80         90        100        110        120 
GQTVQVHGVI QAAQPSVIQS PQVQTVQSSC KDLKRLFSGT QISTIAESED SQESVDSVTD 

       130        140        150        160        170        180 
SQKRREILSR RPSYRKILND LSSDAPGVPR IEEEKSEEET SAPAITTVTV PTPIYQTSSG 

       190        200        210        220        230        240 
QYIAITQGGA IQLANNGTDG VQGLQTLTMT NAAATQPGTT ILQYAQTTDG QQILVPSNQV 

       250        260        270        280        290        300 
VVQAASGDVQ TYQIRTAPTS TIAPGVVMAS SPALPTQPAE EAARKREVRL MKNREAAREC 

       310        320        330        340 
RRKKKEYVKC LENRVAVLEN QNKTLIEELK ALKDLYCHKS D 

« Hide

Isoform 2 (Delta) [UniParc].

Checksum: D6D715DEED679FF2
Show »

FASTA32735,081

References

[1]"A cluster of phosphorylation sites on the cyclic AMP-regulated nuclear factor CREB predicted by its sequence."
Gonzalez G.A., Yamamoto K.K., Fischer W.H., Karr D., Menzel P., Biggs W. III, Vale W.W., Montminy M.R.
Nature 337:749-752(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE.
[2]"Nucleotide and derived amino-acid sequences of the CRE-binding proteins from rat C6 glioma and HeLa cells."
Short M.L., Manohar C.F., Furtado M.R., Ghadge G.D., Wolinsky S.M., Thimmapaya B., Jungmann R.A.
Nucleic Acids Res. 19:4290-4290(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[3]"CREB: a Ca(2+)-regulated transcription factor phosphorylated by calmodulin-dependent kinases."
Sheng M., Thompson M.A., Greenberg M.E.
Science 252:1427-1430(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-133, PHOSPHORYLATION BY CAMK1 AND CAMK4.
[4]"Differential activation of CREB by Ca2+/calmodulin-dependent protein kinases type II and type IV involves phosphorylation of a site that negatively regulates activity."
Sun P., Enslen H., Myung P.S., Maurer R.A.
Genes Dev. 8:2527-2539(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-133 AND SER-142, MUTAGENESIS OF SER-133 AND SER-142.
[5]"Regulation of activating transcription factor-1 and the cAMP response element-binding protein by Ca2+/calmodulin-dependent protein kinases type I, II, and IV."
Sun P., Lou L., Maurer R.A.
J. Biol. Chem. 271:3066-3073(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-133, PHOSPHORYLATION BY CAMK1.
[6]"Structural analyses of CREB-CBP transcriptional activator-coactivator complexes by NMR spectroscopy: implications for mapping the boundaries of structural domains."
Radhakrishnan I., Perez-Alvarado G.C., Parker D., Dyson H.J., Montminy M.R., Wright P.E.
J. Mol. Biol. 287:859-865(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 119-146 IN COMPLEX WITH CREBBP.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X14788 mRNA. Translation: CAA32890.1.
X60002 mRNA. Translation: CAA42619.1.
PIRA35663.
S03343.
S22299.
RefSeqNP_112279.1. NM_031017.1.
NP_604392.1. NM_134443.1.
XP_006245127.1. XM_006245065.1.
XP_006245128.1. XM_006245066.1.
UniGeneRn.90061.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1KDXNMR-B119-146[»]
DisProtDP00080.
DP00682.
ProteinModelPortalP15337.
SMRP15337. Positions 119-146, 285-339.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid249546. 1 interaction.
DIPDIP-36407N.
IntActP15337. 2 interactions.
MINTMINT-1529999.
STRING10116.ENSRNOP00000018326.

PTM databases

PhosphoSiteP15337.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000018326; ENSRNOP00000018326; ENSRNOG00000013412. [P15337-1]
ENSRNOT00000049654; ENSRNOP00000049369; ENSRNOG00000013412. [P15337-2]
GeneID81646.
KEGGrno:81646.
UCSCRGD:620218. rat. [P15337-1]

Organism-specific databases

CTD1385.
RGD620218. Creb1.

Phylogenomic databases

eggNOGNOG300199.
GeneTreeENSGT00390000008655.
HOGENOMHOG000007365.
HOVERGENHBG011077.
InParanoidP15337.
KOK05870.
OMAQXISTIA.
OrthoDBEOG72G18D.
PhylomeDBP15337.
TreeFamTF106464.

Gene expression databases

GenevestigatorP15337.

Family and domain databases

InterProIPR004827. bZIP.
IPR003102. Coactivator_CBP_pKID.
IPR001630. Leuzip_CREB.
[Graphical view]
PfamPF00170. bZIP_1. 1 hit.
PF02173. pKID. 1 hit.
[Graphical view]
PRINTSPR00041. LEUZIPPRCREB.
SMARTSM00338. BRLZ. 1 hit.
[Graphical view]
PROSITEPS50217. BZIP. 1 hit.
PS00036. BZIP_BASIC. 1 hit.
PS50953. KID. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP15337.
NextBio615164.
PROP15337.

Entry information

Entry nameCREB1_RAT
AccessionPrimary (citable) accession number: P15337
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: April 1, 1990
Last modified: April 16, 2014
This is version 147 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references