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Protein

Cyclic AMP-responsive element-binding protein 1

Gene

Creb1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: 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-117 phosphorylation. Involved in different cellular processes including the synchronization of circadian rhythmicity and the differentiation of adipose cells (By similarity).By similarity

GO - Molecular functioni

  • double-stranded DNA binding Source: RGD
  • histone acetyltransferase binding Source: RGD
  • RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity Source: RGD
  • sequence-specific DNA binding Source: RGD
  • sequence-specific DNA binding transcription factor activity Source: RGD
  • transcription factor binding Source: RGD
  • transcription regulatory region DNA binding Source: RGD

GO - Biological processi

  • cell differentiation Source: UniProtKB-KW
  • circadian rhythm Source: RGD
  • positive regulation of fat cell differentiation Source: UniProtKB
  • positive regulation of lipid biosynthetic process Source: UniProtKB
  • positive regulation of RNA polymerase II transcriptional preinitiation complex assembly Source: RGD
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: RGD
  • positive regulation of transforming growth factor beta3 production Source: RGD
  • protein stabilization Source: UniProtKB
  • regulation of apoptotic process Source: RGD
  • regulation of circadian rhythm Source: RGD
  • response to glucagon Source: UniProtKB
  • transcription from RNA polymerase II promoter Source: RGD
  • transforming growth factor beta receptor signaling pathway Source: RGD
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_271496. CREB phosphorylation through the activation of CaMKK.
REACT_276289. CREB phosphorylation through the activation of CaMKII.
REACT_282745. NCAM signaling for neurite out-growth.
REACT_286203. CREB phosphorylation.
REACT_287614. CREB phosphorylation through the activation of Ras.
REACT_290840. Gastrin-CREB signalling pathway via PKC and MAPK.
REACT_314508. PKA-mediated phosphorylation of CREB.
REACT_333484. CaMK IV-mediated phosphorylation of CREB.
REACT_342628. AKT phosphorylates targets in the nucleus.
REACT_343941. CREB phosphorylation through the activation of Adenylate Cyclase.

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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494 Componenti: Chromosome 9

Organism-specific databases

RGDi620218. Creb1.

Subcellular locationi

GO - Cellular componenti

  • chromatin Source: RGD
  • mitochondrion Source: RGD
  • nuclear chromatin Source: BHF-UCL
  • nucleoplasm Source: Reactome
  • nucleus Source: RGD
  • transcription factor complex Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi133 – 1331S → A: Loss of activation by CaMK4. 1 Publication
Mutagenesisi142 – 1421S → A: Loss of phosphorylation by CaMK2. Activation by CaMK2. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 341341Cyclic AMP-responsive element-binding protein 1PRO_0000076599Add
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 SGK1PROSITE-ProRule annotation3 Publications
Modified residuei142 – 1421Phosphoserine; by CaMK2PROSITE-ProRule annotation1 Publication
Modified residuei271 – 2711Phosphoserine; by HIPK2PROSITE-ProRule annotation
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. 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. In liver, phosphorylation is induced by fasting or glucagon in a circadian fashion (By similarity).By similarity
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

PTM databases

PhosphoSiteiP15337.

Expressioni

Gene expression databases

GenevisibleiP15337. RN.

Interactioni

Subunit structurei

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).By similarity

Protein-protein interaction databases

BioGridi249546. 2 interactions.
DIPiDIP-36407N.
IntActiP15337. 2 interactions.
MINTiMINT-1529999.
STRINGi10116.ENSRNOP00000018326.

Structurei

Secondary structure

1
341
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi120 – 1289Combined sources
Helixi133 – 14412Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1KDXNMR-B119-146[»]
DisProtiDP00080.
DP00682.
ProteinModelPortaliP15337.
SMRiP15337. Positions 119-146, 285-339.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP15337.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini101 – 16060KIDPROSITE-ProRule annotationAdd
BLAST
Domaini283 – 34159bZIPPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni284 – 30926Basic motifPROSITE-ProRule annotationAdd
BLAST
Regioni311 – 33222Leucine-zipperPROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Belongs to the bZIP family.Curated
Contains 1 bZIP (basic-leucine zipper) domain.PROSITE-ProRule annotation
Contains 1 KID (kinase-inducible) domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiNOG300199.
GeneTreeiENSGT00390000008655.
HOGENOMiHOG000007365.
HOVERGENiHBG011077.
InParanoidiP15337.
KOiK05870.
OMAiQXISTIA.
OrthoDBiEOG72G18D.
PhylomeDBiP15337.
TreeFamiTF106464.

Family and domain databases

InterProiIPR004827. bZIP.
IPR003102. Coactivator_CBP_pKID.
IPR029802. CREB1.
IPR001630. Leuzip_CREB.
[Graphical view]
PANTHERiPTHR22952:SF104. PTHR22952:SF104. 1 hit.
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. AlignAdd to basket

Isoform 1 (identifier: P15337-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MTMDSGADNQ QSGDAAVTEA ESQQMTVQAQ 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):36,633
Last modified:April 1, 1990 - v1
Checksum:iFC08AC5A335D4C2F
GO
Isoform 2 (identifier: P15337-2) [UniParc]FASTAAdd to basket

Also known as: Delta

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

Show »
Length:327
Mass (Da):35,081
Checksum:iD6D715DEED679FF2
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti135 – 1351R → K in CAA42619 (PubMed:1831258).Curated
Sequence conflicti319 – 3191E → K in CAA42619 (PubMed:1831258).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei88 – 10114Missing in isoform 2. 1 PublicationVSP_000598Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X14788 mRNA. Translation: CAA32890.1.
X60002 mRNA. Translation: CAA42619.1.
PIRiA35663.
S03343.
S22299.
RefSeqiNP_112279.1. NM_031017.1. [P15337-1]
NP_604392.1. NM_134443.1.
XP_006245127.1. XM_006245065.2. [P15337-1]
XP_006245128.1. XM_006245066.2. [P15337-2]
UniGeneiRn.90061.

Genome annotation databases

EnsembliENSRNOT00000018326; ENSRNOP00000018326; ENSRNOG00000013412. [P15337-1]
ENSRNOT00000049654; ENSRNOP00000049369; ENSRNOG00000013412. [P15337-2]
GeneIDi81646.
KEGGirno:81646.
UCSCiRGD:620218. rat. [P15337-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X14788 mRNA. Translation: CAA32890.1.
X60002 mRNA. Translation: CAA42619.1.
PIRiA35663.
S03343.
S22299.
RefSeqiNP_112279.1. NM_031017.1. [P15337-1]
NP_604392.1. NM_134443.1.
XP_006245127.1. XM_006245065.2. [P15337-1]
XP_006245128.1. XM_006245066.2. [P15337-2]
UniGeneiRn.90061.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1KDXNMR-B119-146[»]
DisProtiDP00080.
DP00682.
ProteinModelPortaliP15337.
SMRiP15337. Positions 119-146, 285-339.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi249546. 2 interactions.
DIPiDIP-36407N.
IntActiP15337. 2 interactions.
MINTiMINT-1529999.
STRINGi10116.ENSRNOP00000018326.

PTM databases

PhosphoSiteiP15337.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000018326; ENSRNOP00000018326; ENSRNOG00000013412. [P15337-1]
ENSRNOT00000049654; ENSRNOP00000049369; ENSRNOG00000013412. [P15337-2]
GeneIDi81646.
KEGGirno:81646.
UCSCiRGD:620218. rat. [P15337-1]

Organism-specific databases

CTDi1385.
RGDi620218. Creb1.

Phylogenomic databases

eggNOGiNOG300199.
GeneTreeiENSGT00390000008655.
HOGENOMiHOG000007365.
HOVERGENiHBG011077.
InParanoidiP15337.
KOiK05870.
OMAiQXISTIA.
OrthoDBiEOG72G18D.
PhylomeDBiP15337.
TreeFamiTF106464.

Enzyme and pathway databases

ReactomeiREACT_271496. CREB phosphorylation through the activation of CaMKK.
REACT_276289. CREB phosphorylation through the activation of CaMKII.
REACT_282745. NCAM signaling for neurite out-growth.
REACT_286203. CREB phosphorylation.
REACT_287614. CREB phosphorylation through the activation of Ras.
REACT_290840. Gastrin-CREB signalling pathway via PKC and MAPK.
REACT_314508. PKA-mediated phosphorylation of CREB.
REACT_333484. CaMK IV-mediated phosphorylation of CREB.
REACT_342628. AKT phosphorylates targets in the nucleus.
REACT_343941. CREB phosphorylation through the activation of Adenylate Cyclase.

Miscellaneous databases

EvolutionaryTraceiP15337.
NextBioi615164.
PROiP15337.

Gene expression databases

GenevisibleiP15337. RN.

Family and domain databases

InterProiIPR004827. bZIP.
IPR003102. Coactivator_CBP_pKID.
IPR029802. CREB1.
IPR001630. Leuzip_CREB.
[Graphical view]
PANTHERiPTHR22952:SF104. PTHR22952:SF104. 1 hit.
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]
ProtoNetiSearch...

Publicationsi

  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.

Entry informationi

Entry nameiCREB1_RAT
AccessioniPrimary (citable) accession number: P15337
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: April 1, 1990
Last modified: June 24, 2015
This is version 159 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, Direct protein sequencing, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.