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Q01147 (CREB1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 146. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·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
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

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-133 phosphorylation. Involved in different cellular processes including the synchronization of circadian rhythmicity and the differentiation of adipose cells. Ref.4 Ref.7

Subunit structure

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-133, 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. Ref.3 Ref.7

Subcellular location

Nucleus Ref.7.

Tissue specificity

Ubiquitously expressed. Ref.2

Post-translational modification

Phosphorylation of Ser-133 allows CREBBP binding. Stimulated by phosphorylation. Phosphorylated Ser-142 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-142 and Ser-133 are stimulated by light exposure and submitted to circadian oscillations. In the retina, only phosphorylation of Ser-133 can be detected upon light exposure. Phosphorylation of both Ser-133 and Ser-142 in the SCN regulates the activity of CREB and participates in circadian rhythm generation. 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 By similarity. Phosphorylated at Ser-133 by RPS6KA3, RPS6KA4 and RPS6KA5 in response to mitogenic or stress stimuli. CREBL2 positively regulates phosphorylation at Ser-133 thereby stimulating CREB1 transcriptional activity. In liver, phosphorylation is induced by fasting or glucagon in a circadian fashion. Ref.3 Ref.4 Ref.5 Ref.6

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 processBiological rhythms
Differentiation
Transcription
Transcription regulation
   Cellular componentNucleus
   Coding sequence diversityAlternative splicing
   LigandDNA-binding
   Molecular functionActivator
   PTMIsopeptide bond
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processType I pneumocyte differentiation

Inferred from mutant phenotype PubMed 21408140. Source: MGI

axonogenesis

Inferred from mutant phenotype PubMed 11988169. Source: MGI

cellular response to growth factor stimulus

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

cellular response to zinc ion

Inferred from direct assay PubMed 23716681. Source: MGI

circadian rhythm

Inferred from direct assay Ref.6. Source: UniProtKB

lactation

Inferred from mutant phenotype PubMed 16141355. Source: MGI

lung epithelium development

Inferred from mutant phenotype PubMed 21408140. Source: MGI

lung saccule development

Inferred from mutant phenotype PubMed 21408140. Source: MGI

mammary gland development

Inferred from mutant phenotype PubMed 16141355. Source: MGI

memory

Inferred from mutant phenotype PubMed 23223304. Source: MGI

negative regulation of transcription by competitive promoter binding

Inferred from electronic annotation. Source: Ensembl

pituitary gland development

Inferred from mutant phenotype PubMed 16141355. Source: MGI

positive regulation of fat cell differentiation

Inferred from genetic interaction Ref.7. Source: UniProtKB

positive regulation of hormone secretion

Inferred from mutant phenotype PubMed 16141355. Source: MGI

positive regulation of lipid biosynthetic process

Inferred from genetic interaction Ref.7. Source: UniProtKB

positive regulation of multicellular organism growth

Inferred from mutant phenotype PubMed 16141355. Source: MGI

positive regulation of osteoclast differentiation

Inferred from direct assay PubMed 23395171. Source: MGI

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay Ref.6. Source: UniProtKB

positive regulation of transcription, DNA-templated

Inferred from genetic interaction Ref.7. Source: UniProtKB

protein phosphorylation

Inferred from sequence orthology PubMed 8798441. Source: MGI

protein stabilization

Inferred from mutant phenotype Ref.7. Source: UniProtKB

regulation of cell size

Inferred from genetic interaction PubMed 12015964. Source: MGI

regulation of transcription, DNA-templated

Inferred from direct assay PubMed 12220541. Source: MGI

response to drug

Inferred from direct assay PubMed 9098922. Source: MGI

response to glucagon

Inferred from mutant phenotype Ref.6. Source: UniProtKB

response to organic substance

Inferred from sequence orthology PubMed 8798441. Source: MGI

secretory granule organization

Inferred from mutant phenotype PubMed 21408140. Source: MGI

   Cellular_componentnuclear chromatin

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

nuclear euchromatin

Inferred from electronic annotation. Source: Ensembl

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay Ref.7. Source: UniProtKB

transcription factor complex

Inferred from direct assay PubMed 11354513. Source: MGI

   Molecular_functionDNA binding

Inferred from direct assay PubMed 11354513PubMed 14594818. Source: MGI

RNA polymerase II distal enhancer sequence-specific DNA binding

Inferred from electronic annotation. Source: Ensembl

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

Inferred from electronic annotation. Source: Ensembl

RNA polymerase II transcription factor binding transcription factor activity involved in positive regulation of transcription

Inferred from electronic annotation. Source: Ensembl

cAMP response element binding

Inferred from electronic annotation. Source: Ensembl

protein binding

Inferred from physical interaction PubMed 17525731Ref.7PubMed 24315104. Source: IntAct

sequence-specific DNA binding

Inferred from direct assay PubMed 15030764. Source: MGI

sequence-specific DNA binding transcription factor activity

Inferred from direct assay PubMed 12220541. Source: MGI

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

CrebbpP454812EBI-2291098,EBI-296306
Crebl2Q32M004EBI-2291098,EBI-5314489
EP300Q094722EBI-2291098,EBI-447295From a different organism.
Ncor1Q609745EBI-2291098,EBI-349004

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Note: At least 6 isoforms are produced.
Isoform 1 (identifier: Q01147-1)

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: Q01147-2)

Also known as: CREB-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_0000076598

Regions

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

Sites

Site3141Required for binding TORCs 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 By similarity
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_000597

Experimental info

Mutagenesis1331S → A: Loss of phosphorylation by RPS6KA4 and RPS6KA5. Ref.3 Ref.5
Mutagenesis137 – 1382IL → AA: Abolishes CREBBP binding. Ref.3
Mutagenesis1421S → A: Attenuates light-induced phase shifts of locomotion and expression of c-Fos and mPer1 in the SCN. Ref.3 Ref.4

Secondary structure

... 341
Helix Strand Turn

Details...

Sequences

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

Last modified June 1, 1994. Version 1.
Checksum: CF2958DE9174968A

FASTA34136,674
        10         20         30         40         50         60 
MTMESGADNQ QSGDAAVTEA ENQQMTVQAQ 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 (CREB-delta) [UniParc].

Checksum: 00D1F26B00D48442
Show »

FASTA32735,122

References

[1]"Multiple mRNA isoforms of the transcription activator protein CREB: generation by alternative splicing and specific expression in primary spermatocytes."
Ruppert S., Cole T.J., Boshart M., Schmid E., Schuetz G.
EMBO J. 11:1503-1512(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[2]"The mouse CREB (cAMP responsive element binding protein) gene: structure, promoter analysis, and chromosomal localization."
Cole T.J., Copeland N.G., Gilbert D.J., Jenkins N.A., Schuetz G., Ruppert R.
Genomics 13:974-982(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], TISSUE SPECIFICITY.
[3]"Phosphorylation of CREB at Ser-133 induces complex formation with CREB-binding protein via a direct mechanism."
Parker D., Ferreri K., Nakajima T., LaMorte V.J., Evans R., Koerber S.C., Hoeger C., Montminy M.R.
Mol. Cell. Biol. 16:694-703(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CREBBP, PHOSPHORYLATION AT SER-133, MUTAGENESIS OF 137-ILE-LEU-138.
[4]"Phosphorylation of CREB Ser142 regulates light-induced phase shifts of the circadian clock."
Gau D., Lemberger T., von Gall C., Kretz O., Le Minh N., Gass P., Schmid W., Schibler U., Korf H.W., Schuetz G.
Neuron 34:245-253(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-133 AND SER-142, MUTAGENESIS OF SER-142, FUNCTION.
[5]"The kinases MSK1 and MSK2 act as negative regulators of Toll-like receptor signaling."
Ananieva O., Darragh J., Johansen C., Carr J.M., McIlrath J., Park J.M., Wingate A., Monk C.E., Toth R., Santos S.G., Iversen L., Arthur J.S.
Nat. Immunol. 9:1028-1036(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-133, MUTAGENESIS OF SER-133.
[6]"Cryptochrome mediates circadian regulation of cAMP signaling and hepatic gluconeogenesis."
Zhang E.E., Liu Y., Dentin R., Pongsawakul P.Y., Liu A.C., Hirota T., Nusinow D.A., Sun X., Landais S., Kodama Y., Brenner D.A., Montminy M., Kay S.A.
Nat. Med. 16:1152-1156(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION.
[7]"CREBL2, interacting with CREB, induces adipogenesis in 3T3-L1 adipocytes."
Ma X., Zhang H., Yuan L., Jing H., Thacker P., Li D.
Biochem. J. 439:27-38(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN ADIPOCYTE DIFFERENTIATION, INTERACTION WITH CREBL2, SUBCELLULAR LOCATION.
[8]"The structure of a CREB bZIP.somatostatin CRE complex reveals the basis for selective dimerization and divalent cation-enhanced DNA binding."
Schumacher M.A., Goodman R.H., Brennan R.G.
J. Biol. Chem. 275:35242-35247(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) IN COMPLEX WITH THE SOMATOSTATIN CAMP RESPONSE ELEMENT (SSCRE).
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X67719 expand/collapse EMBL AC list , X67721, X67724, X67725, X67726, X67727, X67728 Genomic DNA. Translation: CAA47953.1.
X67719 expand/collapse EMBL AC list , X67721, X67722, X67724, X67725, X67726, X67727, X67728 Genomic DNA. Translation: CAA47954.1.
M95106 mRNA. Translation: AAA37456.1.
CCDSCCDS15004.1. [Q01147-1]
CCDS15005.1. [Q01147-2]
PIRS20955.
S42699.
RefSeqNP_034082.1. NM_009952.2. [Q01147-1]
NP_598589.2. NM_133828.2. [Q01147-2]
XP_006495713.1. XM_006495650.1. [Q01147-1]
XP_006495714.1. XM_006495651.1. [Q01147-2]
UniGeneMm.422634.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1DH3X-ray3.00A/C285-339[»]
ProteinModelPortalQ01147.
SMRQ01147. Positions 116-149, 285-339.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid198873. 13 interactions.
IntActQ01147. 9 interactions.
MINTMINT-263062.

PTM databases

PhosphoSiteQ01147.

Proteomic databases

MaxQBQ01147.
PaxDbQ01147.
PRIDEQ01147.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000049932; ENSMUSP00000059973; ENSMUSG00000025958. [Q01147-1]
ENSMUST00000087366; ENSMUSP00000084624; ENSMUSG00000025958. [Q01147-2]
GeneID12912.
KEGGmmu:12912.
UCSCuc007bgr.1. mouse. [Q01147-1]

Organism-specific databases

CTD1385.
MGIMGI:88494. Creb1.

Phylogenomic databases

eggNOGNOG300199.
HOGENOMHOG000007365.
HOVERGENHBG011077.
InParanoidQ01147.
KOK05870.
OMAQXISTIA.
OrthoDBEOG72G18D.
PhylomeDBQ01147.
TreeFamTF106464.

Enzyme and pathway databases

ReactomeREACT_188257. Signal Transduction.

Gene expression databases

ArrayExpressQ01147.
BgeeQ01147.
CleanExMM_CREB1.
GenevestigatorQ01147.

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

EvolutionaryTraceQ01147.
NextBio282540.
PROQ01147.
SOURCESearch...

Entry information

Entry nameCREB1_MOUSE
AccessionPrimary (citable) accession number: Q01147
Entry history
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: June 1, 1994
Last modified: July 9, 2014
This is version 146 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

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot