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Q01147

- CREB1_MOUSE

UniProt

Q01147 - CREB1_MOUSE

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Protein
Cyclic AMP-responsive element-binding protein 1
Gene
Creb1, Creb-1
Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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.2 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei314 – 3141Required for binding TORCs By similarity

GO - Molecular functioni

  1. DNA binding Source: MGI
  2. RNA polymerase II distal enhancer sequence-specific DNA binding Source: Ensembl
  3. RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity Source: Ensembl
  4. RNA polymerase II transcription factor binding transcription factor activity involved in positive regulation of transcription Source: Ensembl
  5. cAMP response element binding Source: Ensembl
  6. protein binding Source: IntAct
  7. sequence-specific DNA binding Source: MGI
  8. sequence-specific DNA binding transcription factor activity Source: MGI

GO - Biological processi

  1. Type I pneumocyte differentiation Source: MGI
  2. axonogenesis Source: MGI
  3. cellular response to growth factor stimulus Source: BHF-UCL
  4. cellular response to zinc ion Source: MGI
  5. circadian rhythm Source: UniProtKB
  6. lactation Source: MGI
  7. lung epithelium development Source: MGI
  8. lung saccule development Source: MGI
  9. mammary gland development Source: MGI
  10. memory Source: MGI
  11. negative regulation of transcription by competitive promoter binding Source: Ensembl
  12. pituitary gland development Source: MGI
  13. positive regulation of fat cell differentiation Source: UniProtKB
  14. positive regulation of hormone secretion Source: MGI
  15. positive regulation of lipid biosynthetic process Source: UniProtKB
  16. positive regulation of multicellular organism growth Source: MGI
  17. positive regulation of osteoclast differentiation Source: MGI
  18. positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  19. positive regulation of transcription, DNA-templated Source: UniProtKB
  20. protein phosphorylation Source: MGI
  21. protein stabilization Source: UniProtKB
  22. regulation of cell size Source: MGI
  23. regulation of transcription, DNA-templated Source: MGI
  24. response to drug Source: MGI
  25. response to glucagon Source: UniProtKB
  26. response to organic substance Source: MGI
  27. secretory granule organization Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Activator

Keywords - Biological processi

Biological rhythms, Differentiation, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

ReactomeiREACT_188573. Gastrin-CREB signalling pathway via PKC and MAPK.
REACT_196588. Constitutive PI3K/AKT Signaling in Cancer.
REACT_196593. NOTCH2 intracellular domain regulates transcription.
REACT_198242. CREB phosphorylation through the activation of Adenylate Cyclase.
REACT_198246. CREB phosphorylation through the activation of Ras.
REACT_198248. CREB phosphorylation through the activation of CaMKII.
REACT_205251. Transcriptional activation of mitochondrial biogenesis.
REACT_213852. PKA-mediated phosphorylation of CREB.
REACT_215503. CREB phosphorylation through the activation of CaMKK.
REACT_216520. CaMK IV-mediated phosphorylation of CREB.
REACT_218211. AKT phosphorylates targets in the nucleus.
REACT_224314. CREB phosphorylation.

Names & Taxonomyi

Protein namesi
Recommended name:
Cyclic AMP-responsive element-binding protein 1
Short name:
CREB-1
Short name:
cAMP-responsive element-binding protein 1
Gene namesi
Name:Creb1
Synonyms:Creb-1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 1

Organism-specific databases

MGIiMGI:88494. Creb1.

Subcellular locationi

Nucleus 1 Publication

GO - Cellular componenti

  1. nuclear chromatin Source: BHF-UCL
  2. nuclear euchromatin Source: Ensembl
  3. nucleoplasm Source: Reactome
  4. nucleus Source: UniProtKB
  5. transcription factor complex Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi133 – 1331S → A: Loss of phosphorylation by RPS6KA4 and RPS6KA5. 2 Publications
Mutagenesisi137 – 1382IL → AA: Abolishes CREBBP binding. 1 Publication
Mutagenesisi142 – 1421S → A: Attenuates light-induced phase shifts of locomotion and expression of c-Fos and mPer1 in the SCN. 2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 341341Cyclic AMP-responsive element-binding protein 1
PRO_0000076598Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei133 – 1331Phosphoserine; by CaMK1, CaMK2, CaMK4, PKB/AKT1 or PKB/AKT2, RPS6KA3, RPS6KA4, RPS6KA5 and SGK13 Publications
Modified residuei142 – 1421Phosphoserine; by CaMK2 By similarity
Modified residuei271 – 2711Phosphoserine; by HIPK2 By similarity
Cross-linki285 – 285Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1) By similarity
Cross-linki304 – 304Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1) By similarity

Post-translational modificationi

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.4 Publications
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.

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiQ01147.
PaxDbiQ01147.
PRIDEiQ01147.

PTM databases

PhosphoSiteiQ01147.

Expressioni

Tissue specificityi

Ubiquitously expressed.1 Publication

Gene expression databases

ArrayExpressiQ01147.
BgeeiQ01147.
CleanExiMM_CREB1.
GenevestigatoriQ01147.

Interactioni

Subunit structurei

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.2 Publications

Binary interactionsi

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

Protein-protein interaction databases

BioGridi198873. 13 interactions.
IntActiQ01147. 9 interactions.
MINTiMINT-263062.

Structurei

Secondary structure

Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi286 – 33348

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1DH3X-ray3.00A/C285-339[»]
ProteinModelPortaliQ01147.
SMRiQ01147. Positions 116-149, 285-339.

Miscellaneous databases

EvolutionaryTraceiQ01147.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini101 – 16060KID
Add
BLAST
Domaini283 – 34159bZIP
Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni284 – 30926Basic motif By similarity
Add
BLAST
Regioni311 – 33222Leucine-zipper By similarity
Add
BLAST

Sequence similaritiesi

Belongs to the bZIP family.

Phylogenomic databases

eggNOGiNOG300199.
HOGENOMiHOG000007365.
HOVERGENiHBG011077.
InParanoidiQ01147.
KOiK05870.
OMAiQXISTIA.
OrthoDBiEOG72G18D.
PhylomeDBiQ01147.
TreeFamiTF106464.

Family and domain databases

InterProiIPR004827. bZIP.
IPR003102. Coactivator_CBP_pKID.
IPR001630. Leuzip_CREB.
[Graphical view]
PfamiPF00170. bZIP_1. 1 hit.
PF02173. pKID. 1 hit.
[Graphical view]
PRINTSiPR00041. LEUZIPPRCREB.
SMARTiSM00338. BRLZ. 1 hit.
[Graphical view]
PROSITEiPS50217. BZIP. 1 hit.
PS00036. BZIP_BASIC. 1 hit.
PS50953. KID. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. Align

Note: At least 6 isoforms are produced.

Isoform 1 (identifier: Q01147-1) [UniParc]FASTAAdd to Basket

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.

« Hide

MTMESGADNQ QSGDAAVTEA ENQQMTVQAQ PQIATLAQVS MPAAHATSSA    50
PTVTLVQLPN GQTVQVHGVI QAAQPSVIQS PQVQTVQSSC KDLKRLFSGT 100
QISTIAESED SQESVDSVTD SQKRREILSR RPSYRKILND LSSDAPGVPR 150
IEEEKSEEET SAPAITTVTV PTPIYQTSSG QYIAITQGGA IQLANNGTDG 200
VQGLQTLTMT NAAATQPGTT ILQYAQTTDG QQILVPSNQV VVQAASGDVQ 250
TYQIRTAPTS TIAPGVVMAS SPALPTQPAE EAARKREVRL MKNREAAREC 300
RRKKKEYVKC LENRVAVLEN QNKTLIEELK ALKDLYCHKS D 341
Length:341
Mass (Da):36,674
Last modified:June 1, 1994 - v1
Checksum:iCF2958DE9174968A
GO
Isoform 2 (identifier: Q01147-2) [UniParc]FASTAAdd to Basket

Also known as: CREB-delta

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

Show »
Length:327
Mass (Da):35,122
Checksum:i00D1F26B00D48442
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei88 – 10114Missing in isoform 2.
VSP_000597Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
X67719
, X67721, X67724, X67725, X67726, X67727, X67728 Genomic DNA. Translation: CAA47953.1.
X67719
, X67721, X67722, X67724, X67725, X67726, X67727, X67728 Genomic DNA. Translation: CAA47954.1.
M95106 mRNA. Translation: AAA37456.1.
CCDSiCCDS15004.1. [Q01147-1]
CCDS15005.1. [Q01147-2]
PIRiS20955.
S42699.
RefSeqiNP_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]
UniGeneiMm.422634.

Genome annotation databases

EnsembliENSMUST00000049932; ENSMUSP00000059973; ENSMUSG00000025958. [Q01147-1]
ENSMUST00000087366; ENSMUSP00000084624; ENSMUSG00000025958. [Q01147-2]
GeneIDi12912.
KEGGimmu:12912.
UCSCiuc007bgr.1. mouse. [Q01147-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
X67719
, X67721 , X67724 , X67725 , X67726 , X67727 , X67728 Genomic DNA. Translation: CAA47953.1 .
X67719
, X67721 , X67722 , X67724 , X67725 , X67726 , X67727 , X67728 Genomic DNA. Translation: CAA47954.1 .
M95106 mRNA. Translation: AAA37456.1 .
CCDSi CCDS15004.1. [Q01147-1 ]
CCDS15005.1. [Q01147-2 ]
PIRi S20955.
S42699.
RefSeqi NP_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 ]
UniGenei Mm.422634.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1DH3 X-ray 3.00 A/C 285-339 [» ]
ProteinModelPortali Q01147.
SMRi Q01147. Positions 116-149, 285-339.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 198873. 13 interactions.
IntActi Q01147. 9 interactions.
MINTi MINT-263062.

PTM databases

PhosphoSitei Q01147.

Proteomic databases

MaxQBi Q01147.
PaxDbi Q01147.
PRIDEi Q01147.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000049932 ; ENSMUSP00000059973 ; ENSMUSG00000025958 . [Q01147-1 ]
ENSMUST00000087366 ; ENSMUSP00000084624 ; ENSMUSG00000025958 . [Q01147-2 ]
GeneIDi 12912.
KEGGi mmu:12912.
UCSCi uc007bgr.1. mouse. [Q01147-1 ]

Organism-specific databases

CTDi 1385.
MGIi MGI:88494. Creb1.

Phylogenomic databases

eggNOGi NOG300199.
HOGENOMi HOG000007365.
HOVERGENi HBG011077.
InParanoidi Q01147.
KOi K05870.
OMAi QXISTIA.
OrthoDBi EOG72G18D.
PhylomeDBi Q01147.
TreeFami TF106464.

Enzyme and pathway databases

Reactomei REACT_188573. Gastrin-CREB signalling pathway via PKC and MAPK.
REACT_196588. Constitutive PI3K/AKT Signaling in Cancer.
REACT_196593. NOTCH2 intracellular domain regulates transcription.
REACT_198242. CREB phosphorylation through the activation of Adenylate Cyclase.
REACT_198246. CREB phosphorylation through the activation of Ras.
REACT_198248. CREB phosphorylation through the activation of CaMKII.
REACT_205251. Transcriptional activation of mitochondrial biogenesis.
REACT_213852. PKA-mediated phosphorylation of CREB.
REACT_215503. CREB phosphorylation through the activation of CaMKK.
REACT_216520. CaMK IV-mediated phosphorylation of CREB.
REACT_218211. AKT phosphorylates targets in the nucleus.
REACT_224314. CREB phosphorylation.

Miscellaneous databases

EvolutionaryTracei Q01147.
NextBioi 282540.
PROi Q01147.
SOURCEi Search...

Gene expression databases

ArrayExpressi Q01147.
Bgeei Q01147.
CleanExi MM_CREB1.
Genevestigatori Q01147.

Family and domain databases

InterProi IPR004827. bZIP.
IPR003102. Coactivator_CBP_pKID.
IPR001630. Leuzip_CREB.
[Graphical view ]
Pfami PF00170. bZIP_1. 1 hit.
PF02173. pKID. 1 hit.
[Graphical view ]
PRINTSi PR00041. LEUZIPPRCREB.
SMARTi SM00338. BRLZ. 1 hit.
[Graphical view ]
PROSITEi PS50217. BZIP. 1 hit.
PS00036. BZIP_BASIC. 1 hit.
PS50953. KID. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  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).

Entry informationi

Entry nameiCREB1_MOUSE
AccessioniPrimary (citable) accession number: Q01147
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: June 1, 1994
Last modified: September 3, 2014
This is version 147 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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