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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

  • arrestin family protein binding Source: RGD
  • cAMP response element binding Source: Ensembl
  • double-stranded DNA binding Source: RGD
  • histone acetyltransferase binding Source: RGD
  • Hsp70 protein binding Source: RGD
  • regulatory region DNA binding Source: RGD
  • RNA polymerase II core promoter proximal region sequence-specific DNA binding Source: Ensembl
  • RNA polymerase II distal enhancer sequence-specific DNA binding Source: Ensembl
  • sequence-specific DNA binding Source: RGD
  • transcriptional activator activity, RNA polymerase II transcription factor binding Source: Ensembl
  • transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding Source: RGD
  • transcription factor activity, sequence-specific DNA binding Source: RGD
  • transcription factor binding Source: RGD
  • transcription regulatory region DNA binding Source: RGD

GO - Biological processi

  • aging Source: RGD
  • axonogenesis Source: Ensembl
  • cellular response to fatty acid Source: RGD
  • cellular response to hepatocyte growth factor stimulus Source: Ensembl
  • cellular response to insulin-like growth factor stimulus Source: RGD
  • cellular response to nerve growth factor stimulus Source: RGD
  • cellular response to platelet-derived growth factor stimulus Source: RGD
  • cellular response to transforming growth factor beta stimulus Source: RGD
  • cellular response to zinc ion Source: Ensembl
  • chemotaxis to arachidonic acid Source: RGD
  • circadian rhythm Source: RGD
  • lactation Source: Ensembl
  • lung saccule development Source: Ensembl
  • memory Source: Ensembl
  • negative regulation of gene expression Source: RGD
  • negative regulation of neuron death Source: RGD
  • negative regulation of transcription by competitive promoter binding Source: Ensembl
  • pituitary gland development Source: Ensembl
  • positive regulation of apoptotic process Source: RGD
  • positive regulation of cardiac muscle tissue development Source: Ensembl
  • positive regulation of fat cell differentiation Source: UniProtKB
  • positive regulation of hormone secretion Source: Ensembl
  • positive regulation of lipid biosynthetic process Source: UniProtKB
  • positive regulation of long-term synaptic potentiation Source: RGD
  • positive regulation of multicellular organism growth Source: Ensembl
  • positive regulation of osteoclast differentiation Source: Ensembl
  • 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 phosphorylation Source: Ensembl
  • protein stabilization Source: UniProtKB
  • regulation of apoptotic process Source: RGD
  • regulation of cell size Source: Ensembl
  • regulation of circadian rhythm Source: RGD
  • regulation of fibroblast proliferation Source: RGD
  • regulation of glial cell proliferation Source: RGD
  • response to activity Source: RGD
  • response to drug Source: RGD
  • response to glucagon Source: UniProtKB
  • response to hypoxia Source: RGD
  • response to L-glutamate Source: RGD
  • response to nicotine Source: RGD
  • secretory granule organization Source: Ensembl
  • transcription from RNA polymerase II promoter Source: RGD
  • transforming growth factor beta receptor signaling pathway Source: RGD
  • Type I pneumocyte differentiation Source: Ensembl
  • visual learning 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

ReactomeiR-RNO-111931. PKA-mediated phosphorylation of CREB.
R-RNO-111932. CaMK IV-mediated phosphorylation of CREB.
R-RNO-198693. AKT phosphorylates targets in the nucleus.
R-RNO-199920. CREB phosphorylation.
R-RNO-375165. NCAM signaling for neurite out-growth.
R-RNO-442717. CREB phosphorylation through the activation of CaMKK.
R-RNO-442720. CREB phosphorylation through the activation of Adenylate Cyclase.
R-RNO-442729. CREB phosphorylation through the activation of CaMKII.
R-RNO-442742. CREB phosphorylation through the activation of Ras.
R-RNO-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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 9

Organism-specific databases

RGDi620218. Creb1.

Subcellular locationi

GO - Cellular componenti

  • ATF4-CREB1 transcription factor complex Source: Ensembl
  • axon Source: RGD
  • chromatin Source: RGD
  • mitochondrial matrix Source: RGD
  • mitochondrion Source: RGD
  • nuclear chromatin Source: BHF-UCL
  • nuclear euchromatin Source: Ensembl
  • nucleoplasm Source: Reactome
  • nucleus Source: RGD
  • transcription factor complex Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi133S → A: Loss of activation by CaMK4. 1 Publication1
Mutagenesisi142S → A: Loss of phosphorylation by CaMK2. Activation by CaMK2. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000765991 – 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
Modified residuei142Phosphoserine; by CaMK2PROSITE-ProRule annotationCombined sources1 Publication1
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. 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

Proteomic databases

PaxDbiP15337.
PRIDEiP15337.

PTM databases

iPTMnetiP15337.
PhosphoSitePlusiP15337.

Expressioni

Gene expression databases

BgeeiENSRNOG00000013412.
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

GO - Molecular functioni

  • arrestin family protein binding Source: RGD
  • histone acetyltransferase binding Source: RGD
  • Hsp70 protein binding Source: RGD
  • transcription factor binding Source: RGD

Protein-protein interaction databases

BioGridi249546. 3 interactors.
DIPiDIP-36407N.
IntActiP15337. 2 interactors.
MINTiMINT-1529999.
STRINGi10116.ENSRNOP00000018326.

Structurei

Secondary structure

1341
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi120 – 128Combined sources9
Helixi133 – 144Combined sources12

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1KDXNMR-B119-146[»]
DisProtiDP00080.
DP00682.
ProteinModelPortaliP15337.
SMRiP15337.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP15337.

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
Contains 1 bZIP (basic-leucine zipper) domain.PROSITE-ProRule annotation
Contains 1 KID (kinase-inducible) domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG3584. Eukaryota.
ENOG410ZZJZ. LUCA.
GeneTreeiENSGT00390000008655.
HOGENOMiHOG000007365.
HOVERGENiHBG011077.
InParanoidiP15337.
KOiK05870.
OMAiQXISTIA.
OrthoDBiEOG091G0FTJ.
PhylomeDBiP15337.
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. 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)DescriptionActionsGraphical viewLength
Sequence conflicti135R → K in CAA42619 (PubMed:1831258).Curated1
Sequence conflicti319E → K in CAA42619 (PubMed:1831258).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_00059888 – 101Missing in isoform 2. 1 PublicationAdd BLAST14

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_006245065.3. [P15337-1]
XP_006245128.1. XM_006245066.3. [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_006245065.3. [P15337-1]
XP_006245128.1. XM_006245066.3. [P15337-2]
UniGeneiRn.90061.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1KDXNMR-B119-146[»]
DisProtiDP00080.
DP00682.
ProteinModelPortaliP15337.
SMRiP15337.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi249546. 3 interactors.
DIPiDIP-36407N.
IntActiP15337. 2 interactors.
MINTiMINT-1529999.
STRINGi10116.ENSRNOP00000018326.

PTM databases

iPTMnetiP15337.
PhosphoSitePlusiP15337.

Proteomic databases

PaxDbiP15337.
PRIDEiP15337.

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

eggNOGiKOG3584. Eukaryota.
ENOG410ZZJZ. LUCA.
GeneTreeiENSGT00390000008655.
HOGENOMiHOG000007365.
HOVERGENiHBG011077.
InParanoidiP15337.
KOiK05870.
OMAiQXISTIA.
OrthoDBiEOG091G0FTJ.
PhylomeDBiP15337.
TreeFamiTF106464.

Enzyme and pathway databases

ReactomeiR-RNO-111931. PKA-mediated phosphorylation of CREB.
R-RNO-111932. CaMK IV-mediated phosphorylation of CREB.
R-RNO-198693. AKT phosphorylates targets in the nucleus.
R-RNO-199920. CREB phosphorylation.
R-RNO-375165. NCAM signaling for neurite out-growth.
R-RNO-442717. CREB phosphorylation through the activation of CaMKK.
R-RNO-442720. CREB phosphorylation through the activation of Adenylate Cyclase.
R-RNO-442729. CREB phosphorylation through the activation of CaMKII.
R-RNO-442742. CREB phosphorylation through the activation of Ras.
R-RNO-881907. Gastrin-CREB signalling pathway via PKC and MAPK.

Miscellaneous databases

EvolutionaryTraceiP15337.
PROiP15337.

Gene expression databases

BgeeiENSRNOG00000013412.
GenevisibleiP15337. RN.

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]
ProtoNetiSearch...

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: November 2, 2016
This is version 172 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

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 one 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.