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Protein

Cyclic AMP-responsive element-binding protein 1

Gene

Creb1

Organism
Rattus norvegicus (Rat)
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-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

GO - Biological processi

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-RNO-198693 AKT phosphorylates targets in the nucleus
R-RNO-199920 CREB phosphorylation
R-RNO-375165 NCAM signaling for neurite out-growth
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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 9

Organism-specific databases

RGDi620218 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 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
Cross-linki136Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
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). Phosphorylated by TSSK4 on Ser-133 (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 Expressed in 9 organ(s), highest expression level in testis
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). Interacts with TSSK4; this interaction facilitates phosphorylation on Ser-133 (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

BioGridi249546, 3 interactors
DIPiDIP-36407N
IntActiP15337, 3 interactors
MINTiP15337
STRINGi10116.ENSRNOP00000018326

Structurei

Secondary structure

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

3D structure databases

DisProtiDP00080
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

Phylogenomic databases

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

Similar proteinsi

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
ProteinModelPortaliP15337
SMRiP15337
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi249546, 3 interactors
DIPiDIP-36407N
IntActiP15337, 3 interactors
MINTiP15337
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-198693 AKT phosphorylates targets in the nucleus
R-RNO-199920 CREB phosphorylation
R-RNO-375165 NCAM signaling for neurite out-growth
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
PROiPR:P15337

Gene expression databases

BgeeiENSRNOG00000013412 Expressed in 9 organ(s), highest expression level in testis
GenevisibleiP15337 RN

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_RAT
AccessioniPrimary (citable) accession number: P15337
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: April 1, 1990
Last modified: October 10, 2018
This is version 191 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, Direct protein sequencing, Reference proteome

Documents

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