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Protein

Cyclic AMP-responsive element-binding protein 1

Gene

Creb1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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)DescriptionActionsGraphical viewLength
Sitei314Required for binding TORCsBy similarity1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionActivator, DNA-binding
Biological processBiological rhythms, Differentiation, Transcription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-MMU-198693 AKT phosphorylates targets in the nucleus
R-MMU-199920 CREB phosphorylation
R-MMU-375165 NCAM signaling for neurite out-growth
R-MMU-442717 CREB phosphorylation through the activation of CaMKK
R-MMU-442720 CREB phosphorylation through the activation of Adenylate Cyclase
R-MMU-442729 CREB phosphorylation through the activation of CaMKII
R-MMU-442742 CREB phosphorylation through the activation of Ras
R-MMU-881907 Gastrin-CREB signalling pathway via PKC and MAPK

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 1

Organism-specific databases

MGIiMGI:88494 Creb1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi133S → A: Loss of phosphorylation by RPS6KA4 and RPS6KA5. 1 Publication1
Mutagenesisi137 – 138IL → AA: Abolishes CREBBP binding. 1 Publication2
Mutagenesisi142S → A: Attenuates light-induced phase shifts of locomotion and expression of c-Fos and mPer1 in the SCN. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000765981 – 341Cyclic AMP-responsive element-binding protein 1Add BLAST341

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei133Phosphoserine; by CaMK1, CaMK2, CaMK4, PKB/AKT1 or PKB/AKT2, RPS6KA3, RPS6KA4, RPS6KA5 and SGK1PROSITE-ProRule annotation3 Publications1
Cross-linki136Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei142Phosphoserine; by CaMK2PROSITE-ProRule annotationBy similarity1
Modified residuei271Phosphoserine; by HIPK2PROSITE-ProRule annotationBy similarity1
Cross-linki285Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)By similarity
Cross-linki304Glycyl 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. Phosphorylated by TSSK4 on Ser-133 (By similarity).By similarity4 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).By similarity

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ01147
PaxDbiQ01147
PeptideAtlasiQ01147
PRIDEiQ01147

PTM databases

iPTMnetiQ01147
PhosphoSitePlusiQ01147

Expressioni

Tissue specificityi

Ubiquitously expressed.1 Publication

Gene expression databases

BgeeiENSMUSG00000025958 Expressed in 282 organ(s), highest expression level in mesenteric lymph node
CleanExiMM_CREB1
ExpressionAtlasiQ01147 baseline and differential
GenevisibleiQ01147 MM

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. Interacts with TSSK4; this interaction facilitates phosphorylation on Ser-133 (By similarity).By similarity3 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi198873, 17 interactors
ComplexPortaliCPX-6 ATF4-CREB1 transcription factor complex
CORUMiQ01147
IntActiQ01147, 10 interactors
MINTiQ01147
STRINGi10090.ENSMUSP00000059973

Structurei

Secondary structure

1341
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ01147
SMRiQ01147
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ01147

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini101 – 160KIDPROSITE-ProRule annotationAdd BLAST60
Domaini283 – 341bZIPPROSITE-ProRule annotationAdd BLAST59

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni284 – 309Basic motifPROSITE-ProRule annotationAdd BLAST26
Regioni311 – 332Leucine-zipperPROSITE-ProRule annotationAdd BLAST22

Sequence similaritiesi

Belongs to the bZIP family.Curated

Phylogenomic databases

eggNOGiKOG3584 Eukaryota
ENOG410ZZJZ LUCA
GeneTreeiENSGT00390000008655
HOGENOMiHOG000007365
HOVERGENiHBG011077
InParanoidiQ01147
KOiK05870
OMAiQXISTIA
OrthoDBiEOG091G0FTJ
PhylomeDBiQ01147
TreeFamiTF106464

Family and domain databases

InterProiView protein in InterPro
IPR004827 bZIP
IPR003102 Coactivator_CBP_pKID
IPR029802 CREB1
IPR001630 Leuzip_CREB
PANTHERiPTHR22952:SF200 PTHR22952:SF200, 1 hit
PfamiView protein in Pfam
PF00170 bZIP_1, 1 hit
PF02173 pKID, 1 hit
PRINTSiPR00041 LEUZIPPRCREB
SMARTiView protein in SMART
SM00338 BRLZ, 1 hit
PROSITEiView protein in PROSITE
PS50217 BZIP, 1 hit
PS00036 BZIP_BASIC, 1 hit
PS50953 KID, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket
Note: At least 6 isoforms are produced.

This entry has 2 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All

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
        10         20         30         40         50
MTMESGADNQ QSGDAAVTEA ENQQMTVQAQ PQIATLAQVS MPAAHATSSA
60 70 80 90 100
PTVTLVQLPN GQTVQVHGVI QAAQPSVIQS PQVQTVQSSC KDLKRLFSGT
110 120 130 140 150
QISTIAESED SQESVDSVTD SQKRREILSR RPSYRKILND LSSDAPGVPR
160 170 180 190 200
IEEEKSEEET SAPAITTVTV PTPIYQTSSG QYIAITQGGA IQLANNGTDG
210 220 230 240 250
VQGLQTLTMT NAAATQPGTT ILQYAQTTDG QQILVPSNQV VVQAASGDVQ
260 270 280 290 300
TYQIRTAPTS TIAPGVVMAS SPALPTQPAE EAARKREVRL MKNREAAREC
310 320 330 340
RRKKKEYVKC LENRVAVLEN QNKTLIEELK ALKDLYCHKS D
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

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
Q62347Q62347_MOUSE
Cyclic AMP-responsive element-bindi...
Creb1
287Annotation score:
A0A087WRI6A0A087WRI6_MOUSE
Cyclic AMP-responsive element-bindi...
Creb1
317Annotation score:
Q61441Q61441_MOUSE
C-AMP-responsive-element binding pr...
Creb1 CREB
90Annotation score:

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_00059788 – 101Missing in isoform 2. CuratedAdd BLAST14

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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_006495650.3 [Q01147-1]
XP_006495714.1, XM_006495651.3 [Q01147-2]
XP_017169569.1, XM_017314080.1 [Q01147-1]
XP_017169588.1, XM_017314099.1 [Q01147-2]
UniGeneiMm.422634

Genome annotation databases

EnsembliENSMUST00000049932; ENSMUSP00000059973; ENSMUSG00000025958 [Q01147-1]
ENSMUST00000087366; ENSMUSP00000084624; ENSMUSG00000025958 [Q01147-2]
ENSMUST00000185594; ENSMUSP00000139995; ENSMUSG00000025958 [Q01147-2]
ENSMUST00000190348; ENSMUSP00000140112; ENSMUSG00000025958 [Q01147-1]
GeneIDi12912
KEGGimmu:12912
UCSCiuc007bgr.1 mouse [Q01147-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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_006495650.3 [Q01147-1]
XP_006495714.1, XM_006495651.3 [Q01147-2]
XP_017169569.1, XM_017314080.1 [Q01147-1]
XP_017169588.1, XM_017314099.1 [Q01147-2]
UniGeneiMm.422634

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1DH3X-ray3.00A/C285-339[»]
ProteinModelPortaliQ01147
SMRiQ01147
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi198873, 17 interactors
ComplexPortaliCPX-6 ATF4-CREB1 transcription factor complex
CORUMiQ01147
IntActiQ01147, 10 interactors
MINTiQ01147
STRINGi10090.ENSMUSP00000059973

PTM databases

iPTMnetiQ01147
PhosphoSitePlusiQ01147

Proteomic databases

EPDiQ01147
PaxDbiQ01147
PeptideAtlasiQ01147
PRIDEiQ01147

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000049932; ENSMUSP00000059973; ENSMUSG00000025958 [Q01147-1]
ENSMUST00000087366; ENSMUSP00000084624; ENSMUSG00000025958 [Q01147-2]
ENSMUST00000185594; ENSMUSP00000139995; ENSMUSG00000025958 [Q01147-2]
ENSMUST00000190348; ENSMUSP00000140112; ENSMUSG00000025958 [Q01147-1]
GeneIDi12912
KEGGimmu:12912
UCSCiuc007bgr.1 mouse [Q01147-1]

Organism-specific databases

CTDi1385
MGIiMGI:88494 Creb1

Phylogenomic databases

eggNOGiKOG3584 Eukaryota
ENOG410ZZJZ LUCA
GeneTreeiENSGT00390000008655
HOGENOMiHOG000007365
HOVERGENiHBG011077
InParanoidiQ01147
KOiK05870
OMAiQXISTIA
OrthoDBiEOG091G0FTJ
PhylomeDBiQ01147
TreeFamiTF106464

Enzyme and pathway databases

ReactomeiR-MMU-198693 AKT phosphorylates targets in the nucleus
R-MMU-199920 CREB phosphorylation
R-MMU-375165 NCAM signaling for neurite out-growth
R-MMU-442717 CREB phosphorylation through the activation of CaMKK
R-MMU-442720 CREB phosphorylation through the activation of Adenylate Cyclase
R-MMU-442729 CREB phosphorylation through the activation of CaMKII
R-MMU-442742 CREB phosphorylation through the activation of Ras
R-MMU-881907 Gastrin-CREB signalling pathway via PKC and MAPK

Miscellaneous databases

ChiTaRSiCreb1 mouse
EvolutionaryTraceiQ01147
PROiPR:Q01147
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000025958 Expressed in 282 organ(s), highest expression level in mesenteric lymph node
CleanExiMM_CREB1
ExpressionAtlasiQ01147 baseline and differential
GenevisibleiQ01147 MM

Family and domain databases

InterProiView protein in InterPro
IPR004827 bZIP
IPR003102 Coactivator_CBP_pKID
IPR029802 CREB1
IPR001630 Leuzip_CREB
PANTHERiPTHR22952:SF200 PTHR22952:SF200, 1 hit
PfamiView protein in Pfam
PF00170 bZIP_1, 1 hit
PF02173 pKID, 1 hit
PRINTSiPR00041 LEUZIPPRCREB
SMARTiView protein in SMART
SM00338 BRLZ, 1 hit
PROSITEiView protein in PROSITE
PS50217 BZIP, 1 hit
PS00036 BZIP_BASIC, 1 hit
PS50953 KID, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiCREB1_MOUSE
AccessioniPrimary (citable) accession number: Q01147
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: June 1, 1994
Last modified: October 10, 2018
This is version 190 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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