Reviewed, UniProtKB/Swiss-Prot Q01147 (CREB1_MOUSE)

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

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

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

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 By similarity. Implicated in synchronization of circadian rhythmicity.
Subunit structure	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 By similarity. When phosphorylated on Ser-133, binds CREBBP.
Subcellular location	Nucleus.
Tissue specificity	Ubiquitously expressed. Ref.2
Post-translational modification	Phosphorylation of Ser-133 allows CREBBP binding. Phosphorylated upon DNA damage, probably by ATM or ATR By similarity. Stimulated by phosphorylation. Phosphorylated Ser-142 can be detected in the suprachiasmatic nucleus (SCN), the amygdala, the cortex, and the hippocampus but not in the striatum nor in the cerebellum. In the SCN, phosphorylation of Ser-142 and Ser-133 are stimulated by light exposure and submitted to circadian oscillations. In the retina, only phosphorylation of Ser-133 can be detected upon light exposure. Phosphorylation of both Ser-133 and Ser-142 in the SCN regulates the activity of CREB and participates in circadian rhythm generation.
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
Gene Ontology (GO)
Biological process	axonogenesis Inferred from mutant phenotype. Source: MGI lactation Inferred from mutant phenotype. Source: MGI pituitary gland development Inferred from mutant phenotype. Source: MGI positive regulation of hormone secretion Inferred from mutant phenotype. Source: MGI positive regulation of multicellular organism growth Inferred from mutant phenotype. Source: MGI regulation of cell size Inferred from genetic interaction. Source: MGI regulation of transcription, DNA-dependent Inferred from direct assay. Source: MGI response to drug Inferred from direct assay. Source: MGI transcription Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	transcription factor complex Inferred from direct assay. Source: MGI
Molecular function	protein dimerization activity Inferred from electronic annotation. Source: InterPro sequence-specific DNA binding Inferred from electronic annotation. Source: InterPro transcription factor activity Inferred from direct assay. Source: MGI
Complete GO annotation...

Alternative products

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

Note: At least 6 isoforms are produced.

Isoform 1 (identifier: Q01147-1)

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: Q01147-2)

Also known as: CREB-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_0000076598

Regions

Domain

101 – 160

60

KID

Domain

311 – 332

22

Leucine-zipper By similarity

DNA binding

284 – 309

26

Basic motif

Sites

Site

314

1

Required for binding TORCs By similarity

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

Modified residue

142

1

Phosphoserine; by CaMK2 Ref.4

Natural variations

Alternative sequence

88 – 101

14

Missing in isoform 2.

VSP_000597

Experimental info

Mutagenesis

137 – 138

2

IL → AA: Abolishes CREBBP binding. Ref.3

Mutagenesis

142

1

S → A: Attenuates light-induced phase shifts of locomotion and expression of c-Fos and mPer1 in the SCN. Ref.3 Ref.4

Secondary structure

1

.

.

.

341

Helix Strand Turn

Details...

Helix

286 – 333

48

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 1, 1994. Version 1. Checksum: CF2958DE9174968A	FASTA	341	36,674
	10 20 30 40 50 60 MTMESGADNQ QSGDAAVTEA ENQQMTVQAQ 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 (CREB-delta). Checksum: 00D1F26B00D48442	FASTA	327	35,122
	10 20 30 40 50 60 MTMESGADNQ QSGDAAVTEA ENQQMTVQAQ 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]	"Multiple mRNA isoforms of the transcription activator protein CREB: generation by alternative splicing and specific expression in primary spermatocytes." Ruppert S., Cole T.J., Boshart M., Schmid E., Schuetz G. EMBO J. 11:1503-1512(1992) [PubMed: 1532935] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[2]	"The mouse CREB (cAMP responsive element binding protein) gene: structure, promoter analysis, and chromosomal localization." Cole T.J., Copeland N.G., Gilbert D.J., Jenkins N.A., Schuetz G., Ruppert R. Genomics 13:974-982(1992) [PubMed: 1387109] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], TISSUE SPECIFICITY.
[3]	"Phosphorylation of CREB at Ser-133 induces complex formation with CREB-binding protein via a direct mechanism." Parker D., Ferreri K., Nakajima T., LaMorte V.J., Evans R., Koerber S.C., Hoeger C., Montminy M.R. Mol. Cell. Biol. 16:694-703(1996) [PubMed: 8552098] [Abstract] Cited for: INTERACTION WITH CREBBP, PHOSPHORYLATION AT SER-133, MUTAGENESIS OF 137-ILE-LEU-138.
[4]	"Phosphorylation of CREB Ser142 regulates light-induced phase shifts of the circadian clock." Gau D., Lemberger T., von Gall C., Kretz O., Le Minh N., Gass P., Schmid W., Schibler U., Korf H.W., Schuetz G. Neuron 34:245-253(2002) [PubMed: 11970866] [Abstract] Cited for: PHOSPHORYLATION AT SER-133 AND SER-142, MUTAGENESIS OF SER-142, FUNCTION.
[5]	"The structure of a CREB bZIP.somatostatin CRE complex reveals the basis for selective dimerization and divalent cation-enhanced DNA binding." Schumacher M.A., Goodman R.H., Brennan R.G. J. Biol. Chem. 275:35242-35247(2000) [PubMed: 10952992] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) IN COMPLEX WITH THE SOMATOSTATIN CAMP RESPONSE ELEMENT (SSCRE).
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

X67719 , X67721, X67724, X67725, X67726, X67727, X67728 Genomic DNA. Translation: CAA47953.1.
X67719 , X67721, X67722, X67724, X67725, X67726, X67727, X67728 Genomic DNA. Translation: CAA47954.1.
M95106 mRNA. Translation: AAA37456.1.

IPI

IPI00119924.
IPI00320587.

PIR

S20955.
S42699.

RefSeq

NP_034082.1.
NP_598589.2.

UniGene

Mm.466618

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1DH3	X-ray	3.00	A/C	285-339	[»]

ModBase

Search...

Protein-protein interaction databases

STRING

Q01147.

PTM databases

PhosphoSite

Q01147.

Proteomic databases

PRIDE

Q01147.

Genome annotation databases

Ensembl

ENSMUST00000049932; ENSMUSP00000059973; ENSMUSG00000025958; Mus musculus. [Genome view]
ENSMUST00000087366; ENSMUSP00000084624; ENSMUSG00000025958; Mus musculus. [Genome view]

GeneID

12912.

UCSC

uc007bgr.1. mouse.

Organism-specific databases

CTD

12912.

MGI

MGI:88494. Creb1.

Phylogenomic databases

HOGENOM

Q01147.

HOVERGEN

Q01147.

OMA

XKILNDL.

Gene expression databases

ArrayExpress

Q01147.

Bgee

Q01147.

CleanEx

MM_CREB1.

Genevestigator

Q01147.

GermOnline

ENSMUSG00000025958. Mus musculus.

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

282540.

SOURCE

Search...

Entry information

Entry name

CREB1_MOUSE

Accession

Primary (citable) accession number: Q01147

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 1, 1994
Last sequence update:	June 1, 1994
Last modified:	November 3, 2009
This is version 103 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)