Reviewed, UniProtKB/Swiss-Prot P15337 (CREB1_RAT)

Names and origin

Protein names

Recommended name:
    Cyclic AMP-responsive element-binding protein 1
      Short name=cAMP-responsive element-binding protein 1
      Short name=CREB-1

Gene names

Name:	Creb1
Synonyms:	Creb-1

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	341 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	This protein binds the cAMP response element (CRE), a sequence present in many viral and cellular promoters. CREB stimulates transcription on binding to the CRE. Transciption activation is enhanced by the TORC coactivators which act independently of Ser-133 phosphorylation. Implicated in synchronization of circadian rhythmicity By similarity.
Subunit structure	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.
Subcellular location	Nucleus.
Post-translational modification	Phosphorylation of Ser-133 allows CREBBP binding. Phosphorylated upon DNA damage, probably by ATM or ATR By similarity. 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. CAMK4 is much more potent than CAMK2 in activating CREB. Phosphorylated by CAMK1 and CAMK4.
Sequence similarities	Belongs to the bZIP family. Contains 1 bZIP domain. Contains 1 KID (kinase-inducible) domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Ligand	DNA-binding
Molecular function	Activator
PTM	Phosphoprotein
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	positive regulation of gene-specific transcription from RNA polymerase II promoter Inferred from mutant phenotype. Source: RGD positive regulation of transforming growth factor-beta3 production Inferred from mutant phenotype. Source: RGD regulation of apoptosis Inferred from direct assay. Source: RGD regulation of circadian rhythm Inferred from mutant phenotype. Source: RGD transcription from RNA polymerase II promoter Inferred from mutant phenotype. Source: RGD transforming growth factor beta receptor signaling pathway Inferred from mutant phenotype. Source: RGD
Cellular component	chromatin Inferred from direct assay. Source: RGD mitochondrion Inferred from direct assay. Source: RGD transcription factor complex Inferred from direct assay. Source: RGD
Molecular function	RNA polymerase II transcription factor activity, enhancer binding Inferred from direct assay. Source: RGD double-stranded DNA binding Inferred from direct assay. Source: RGD protein dimerization activity Inferred from electronic annotation. Source: InterPro sequence-specific DNA binding Inferred from direct assay. Source: RGD specific RNA polymerase II transcription factor activity Inferred from mutant phenotype. Source: RGD transcription factor binding Inferred from physical interaction. Source: RGD
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Carm1	Q4AE70	1	EBI-973322,EBI-973358

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P15337-1)

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.

Isoform 2 (identifier: P15337-2)

Also known as: Delta;

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

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 341

341

Cyclic AMP-responsive element-binding protein 1

PRO_0000076599

Regions

Domain

101 – 160

60

KID

Domain

311 – 332

22

Leucine-zipper

DNA binding

284 – 309

26

Basic motif

Amino acid modifications

Modified residue

111

1

Phosphoserine By similarity

Modified residue

119

1

Phosphothreonine By similarity

Modified residue

133

1

Phosphoserine; by CaMK1, CaMK2 and CaMK4 Ref.3 Ref.4 Ref.5

Modified residue

142

1

Phosphoserine; by CaMK2 Ref.4

Natural variations

Alternative sequence

88 – 101

14

Missing in isoform 2.

VSP_000598

Experimental info

Sequence conflict

135

1

R → K in CAA42619. Ref.2

Sequence conflict

319

1

E → K in CAA42619. Ref.2

Secondary structure

1

.

.

.

.

.

341

Helix Strand Turn

Details...

Helix

120 – 128

9

Helix

133 – 144

12

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Alpha) [UniParc]. Last modified April 1, 1990. Version 1. Checksum: FC08AC5A335D4C2F	FASTA	341	36,633
	10 20 30 40 50 60 MTMDSGADNQ QSGDAAVTEA ESQQMTVQAQ PQIATLAQVS MPAAHATSSA PTVTLVQLPN 70 80 90 100 110 120 GQTVQVHGVI QAAQPSVIQS PQVQTVQSSC KDLKRLFSGT QISTIAESED SQESVDSVTD 130 140 150 160 170 180 SQKRREILSR RPSYRKILND LSSDAPGVPR IEEEKSEEET SAPAITTVTV PTPIYQTSSG 190 200 210 220 230 240 QYIAITQGGA IQLANNGTDG VQGLQTLTMT NAAATQPGTT ILQYAQTTDG QQILVPSNQV 250 260 270 280 290 300 VVQAASGDVQ TYQIRTAPTS TIAPGVVMAS SPALPTQPAE EAARKREVRL MKNREAAREC 310 320 330 340 RRKKKEYVKC LENRVAVLEN QNKTLIEELK ALKDLYCHKS D
	Isoform 2 (Delta). Checksum: D6D715DEED679FF2	FASTA	327	35,081
	10 20 30 40 50 60 MTMDSGADNQ QSGDAAVTEA ESQQMTVQAQ PQIATLAQVS MPAAHATSSA PTVTLVQLPN 70 80 90 100 110 120 GQTVQVHGVI QAAQPSVIQS PQVQTVQIST IAESEDSQES VDSVTDSQKR REILSRRPSY 130 140 150 160 170 180 RKILNDLSSD APGVPRIEEE KSEEETSAPA ITTVTVPTPI YQTSSGQYIA ITQGGAIQLA 190 200 210 220 230 240 NNGTDGVQGL QTLTMTNAAA TQPGTTILQY AQTTDGQQIL VPSNQVVVQA ASGDVQTYQI 250 260 270 280 290 300 RTAPTSTIAP GVVMASSPAL PTQPAEEAAR KREVRLMKNR EAARECRRKK KEYVKCLENR 310 320 VAVLENQNKT LIEELKALKD LYCHKSD

References

[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: 2521922] [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: 1831258] [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: 1646483] [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: 7958915] [Abstract] Cited for: PHOSPHORYLATION AT 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: 8621702] [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: 10222196] [Abstract] Cited for: STRUCTURE BY NMR OF 119-146 IN COMPLEX WITH CREBBP.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

X14788 mRNA. Translation: CAA32890.1.
X60002 mRNA. Translation: CAA42619.1.

IPI

IPI00208239.
IPI00327194.

PIR

A35663.
S03343.
S22299.

RefSeq

NP_112279.1.
NP_604392.1.

UniGene

Rn.90061

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1KDX	NMR	-	B	119-146	[»]

SMR

P15337. Positions 285-339.

DisProt

DP00080.

ModBase

Search...

Protein-protein interaction databases

IntAct

P15337. 1 interaction.

STRING

P15337.

PTM databases

PhosphoSite

P15337.

Genome annotation databases

Ensembl

ENSRNOT00000018326; ENSRNOP00000018326; ENSRNOG00000013412; Rattus norvegicus. [Genome view]
ENSRNOT00000049654; ENSRNOP00000049369; ENSRNOG00000013412; Rattus norvegicus. [Genome view]

GeneID

81646.

KEGG

rno:81646.

UCSC

NM_031017. rat.

Organism-specific databases

CTD

81646.

RGD

620218. Creb1.

Phylogenomic databases

HOVERGEN

P15337.

OMA

XKILNDL.

Gene expression databases

ArrayExpress

P15337.

Genevestigator

P15337.

GermOnline

ENSRNOG00000013412. Rattus norvegicus.

Family and domain databases

InterPro

IPR011616. bZIP_1.
IPR003102. Coactivator_CBP_pKID.
IPR001630. Leuzip_CREB.
IPR004827. TF_bZIP.
[Graphical view]

Pfam

PF00170. bZIP_1. 1 hit.
PF02173. pKID. 1 hit.
[Graphical view]

PRINTS

PR00041. LEUZIPPRCREB.

SMART

SM00338. BRLZ. 1 hit.
[Graphical view]

PROSITE

PS50217. BZIP. 1 hit.
PS00036. BZIP_BASIC. 1 hit.
PS50953. KID. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

615164.

Entry information

Entry name

CREB1_RAT

Accession

Primary (citable) accession number: P15337

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1990
Last sequence update:	April 1, 1990
Last modified:	November 3, 2009
This is version 108 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)