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Protein

Cyclic AMP-responsive element-binding protein 1

Gene

CREB1

Organism
Bos taurus (Bovine)
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.3 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei298 – 2981Required for binding TORCsBy similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Activator

Keywords - Biological processi

Biological rhythms, Differentiation, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

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
Alternative name(s):
Cyclic AMP-responsive DNA-binding protein
Gene namesi
Name:CREB1
Synonyms:CREB, CREB2
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Unplaced

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 325325Cyclic AMP-responsive element-binding protein 1PRO_0000076600Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei117 – 1171Phosphoserine; by CaMK1, CaMK2, CaMK4, PKB/AKT1 or PKB/AKT2, RPS6KA3, RPS6KA4, RPS6KA5 and SGK1PROSITE-ProRule annotation1 Publication
Modified residuei126 – 1261Phosphoserine; by CaMK2PROSITE-ProRule annotationBy similarity
Modified residuei255 – 2551Phosphoserine; by HIPK2PROSITE-ProRule annotationBy similarity
Cross-linki269 – 269Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)By similarity
Cross-linki288 – 288Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)By similarity

Post-translational modificationi

Sumoylated with SUMO1. Sumoylation on Lys-288, but not on Lys-269, is required for nuclear localization of this protein. Sumoylation is enhanced under hypoxia, promoting nuclear localization and stabilization (By similarity).By similarity
Stimulated by phosphorylation. Phosphorylation of both Ser-117 and Ser-126 in the SCN regulates the activity of CREB and participates in circadian rhythm generation. Phosphorylation of Ser-117 allows CREBBP binding. Phosphorylated upon calcium influx by CaMK4 and CaMK2 on Ser-117. CaMK4 is much more potent than CaMK2 in activating CREB. Phosphorylated by CaMK2 on Ser-126. Phosphorylation of Ser-126 blocks CREB-mediated transcription even when Ser-117 is phosphorylated. Phosphorylated by CaMK1. Phosphorylation of Ser-255 by HIPK2 in response to genotoxic stress promotes CREB1 activity, facilitating the recruitment of the coactivator CBP. Phosphorylated at Ser-117 by RPS6KA3, RPS6KA4 and RPS6KA5 in response to mitogenic or stress stimuli. CREBL2 positively regulates phosphorylation at Ser-117 thereby stimulating CREB1 transcriptional activity. In liver, phosphorylation is induced by fasting or glucagon in a circadian fashion (By similarity).By similarity

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiP27925.
PRIDEiP27925.

PTM databases

iPTMnetiP27925.

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. When phosphorylated on Ser-117, binds CREBBP. 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

STRINGi9913.ENSBTAP00000007201.

Structurei

3D structure databases

ProteinModelPortaliP27925.
SMRiP27925. Positions 103-130, 269-323.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini85 – 14460KIDPROSITE-ProRule annotationAdd
BLAST
Domaini267 – 32559bZIPPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni268 – 29326Basic motifPROSITE-ProRule annotationAdd
BLAST
Regioni295 – 31622Leucine-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

eggNOGiKOG3584. Eukaryota.
ENOG410ZZJZ. LUCA.
HOVERGENiHBG011077.
InParanoidiP27925.
KOiK05870.

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]

Sequencei

Sequence statusi: Complete.

P27925-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MESGAENQQS GDAAVTEAES QQMTVQAQPQ IATLAQVSMP AAHATSSAPT
60 70 80 90 100
VTLVQLPNGQ TVQVHGVIQA AQPSVIQSPQ VQTVQISTIA ESEDSQESVD
110 120 130 140 150
SVTDSQKRRE ILSRRPSYRK ILNDLSSDAP GVPRIEEEKS EEETSAPAIT
160 170 180 190 200
TVTVPTPIYQ TSSGQYIAIT QGGAIQLANN GTDGVQGLQT LTMTNAAATQ
210 220 230 240 250
PGTTILQYAQ TTDGQQILVP SNQVVVQAAS GDVQTYQIRT APTSTIAPGV
260 270 280 290 300
VMASSPALPT QPAEEAARKR EVRLMKNREA ARECRRKKKE YVKCLENRVA
310 320
VLENQNKTLI EELKALKDLY CHKSD
Length:325
Mass (Da):34,877
Last modified:December 1, 2000 - v2
Checksum:i61B4B4244FAB474B
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti60 – 612QT → TK in CAA40347 (PubMed:1837490).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X57031 mRNA. Translation: CAA40347.1.
AF006042 mRNA. Translation: AAB62381.1.
BC142303 mRNA. Translation: AAI42304.1.
PIRiS23007.
RefSeqiNP_776710.1. NM_174285.1.
UniGeneiBt.4183.

Genome annotation databases

GeneIDi281713.
KEGGibta:281713.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X57031 mRNA. Translation: CAA40347.1.
AF006042 mRNA. Translation: AAB62381.1.
BC142303 mRNA. Translation: AAI42304.1.
PIRiS23007.
RefSeqiNP_776710.1. NM_174285.1.
UniGeneiBt.4183.

3D structure databases

ProteinModelPortaliP27925.
SMRiP27925. Positions 103-130, 269-323.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000007201.

PTM databases

iPTMnetiP27925.

Proteomic databases

PaxDbiP27925.
PRIDEiP27925.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi281713.
KEGGibta:281713.

Organism-specific databases

CTDi1385.

Phylogenomic databases

eggNOGiKOG3584. Eukaryota.
ENOG410ZZJZ. LUCA.
HOVERGENiHBG011077.
InParanoidiP27925.
KOiK05870.

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...

Publicationsi

« Hide 'large scale' publications
  1. "Nucleotide sequence of the bovine cyclic-AMP responsive DNA binding protein (CREB2) cDNA."
    Willems L., Kettmann R., Chen G., Portetelle D., Burny A., Derse D.
    DNA Seq. 1:415-417(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "Nucleotide sequence of the CREB protein involved in bovine leukemia virus expression."
    Adam E., Twizere J.C., Burny A., Kettmann R., Willems L.
    Submitted (MAY-1997) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  3. NIH - Mammalian Gene Collection (MGC) project
    Submitted (JUN-2007) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: Hereford.
    Tissue: Thymus.
  4. "A cyclic AMP-responsive DNA-binding protein (CREB2) is a cellular transactivator of the bovine leukemia virus long terminal repeat."
    Willems L., Kettmann R., Chen G., Portetelle D., Burny A., Derse D.
    J. Virol. 66:766-772(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  5. "Involvement of the cyclic AMP-responsive element binding protein in bovine leukemia virus expression in vivo."
    Adam E., Kerkhofs P., Mammerickx M., Kettmann R., Burny A., Droogmans L., Willems L.
    J. Virol. 68:5845-5853(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  6. "The CREB, ATF-1, and ATF-2 transcription factors from bovine leukemia virus-infected B lymphocytes activate viral expression."
    Adam E., Kerkhofs P., Mammerickx M., Burny A., Kettman R., Willems L.
    J. Virol. 70:1990-1999(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  7. "Angiotensin II promotes the phosphorylation of cyclic AMP-responsive element binding protein (CREB) at Ser133 through an ERK1/2-dependent mechanism."
    Cammarota M., Bevilaqua L.R., Dunkley P.R., Rostas J.A.
    J. Neurochem. 79:1122-1128(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT SER-117.

Entry informationi

Entry nameiCREB1_BOVIN
AccessioniPrimary (citable) accession number: P27925
Secondary accession number(s): A5PK02, O18957
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: December 1, 2000
Last modified: July 6, 2016
This is version 135 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 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.