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Reviewed, UniProtKB/Swiss-Prot P16220 (CREB1_HUMAN)

Last modified February 9, 2010. Version 129. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
    Cyclic AMP-responsive element-binding protein 1
      Short name=cAMP-responsive element-binding protein 1
      Short name=CREB-1
Gene names
Name: CREB1
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length341 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level.

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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. Transcription activation is enhanced by the TORC coactivators which act independently of Ser-133 phosphorylation. 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. When phosphorylated on Ser-133, binds CREBBP By similarity. Interacts with ARRB1. Ref.8 Ref.9 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15

Subcellular location

Nucleus.

Post-translational modification

Stimulated by phosphorylation. Phosphorylation of both Ser-133 and Ser-142 in the SCN regulates the activity of CREB and participates in circadian rhythm generation. Phosphorylation of Ser-133 allows CREBBP binding By similarity. Phosphorylated upon DNA damage, probably by ATM or ATR. Ref.10 Ref.16 Ref.18

Involvement in disease

A chromosomal aberration involving CREB1 is associated with angiomatoid fibrous histiocytoma (AFH) [MIM:612160]. Translocation t(2;22)(q33;q12) with CREB1 generates a EWSR1/CREB1 fusion gene that is most common genetic abnormality in this tumor type.

Sequence similarities

Belongs to the bZIP family.

Contains 1 bZIP domain.

Contains 1 KID (kinase-inducible) domain.

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Binary interactions

With

Entry

#Exp.

IntAct

Notes

ATRQ135351EBI-711855,EBI-968983
CrebbpP454811EBI-711855,EBI-296306From a different organism.
MED15Q96RN51EBI-711855,EBI-394506
RPS6KA1Q154181EBI-711855,EBI-963034
TSSK4Q6SA084EBI-711855,EBI-1202583

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Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform CREB-A (identifier: P16220-1)

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 CREB-B (identifier: P16220-2)

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

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 341341Cyclic AMP-responsive element-binding protein 1
PRO_0000076597

Regions

Domain101 – 16060KID
Domain311 – 33222Leucine-zipper
DNA binding284 – 30522Basic motif

Sites

Site3141Required for binding TORCs

Amino acid modifications

Modified residue1111Phosphoserine Ref.16
Modified residue1191Phosphothreonine Ref.16
Modified residue1331Phosphoserine; by CaMK1, CaMK2 and CaMK4 Ref.10
Modified residue1421Phosphoserine; by CaMK2 By similarity
Modified residue2711Phosphoserine Ref.18

Natural variations

Alternative sequence88 – 10114Missing in isoform CREB-B.
VSP_000596

Experimental info

Sequence conflict41E → D in CAA42620. Ref.5
Sequence conflict81E → D in CAA42620. Ref.5
Sequence conflict1601T → A in CAA42620. Ref.5
Sequence conflict1671T → A in CAA42620. Ref.5
Sequence conflict1691T → A in CAA42620. Ref.5
Sequence conflict1761Q → R in CAA42620. Ref.5
Sequence conflict1841A → T in CAA42620. Ref.5
Sequence conflict1881G → R in CAA42620. Ref.5
Sequence conflict1951N → S in CAA42620. Ref.5
Sequence conflict2101T → A in CAA42620. Ref.5

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Sequences

Sequence LengthMass (Da)Tools
Isoform CREB-A [UniParc].

Last modified May 1, 1992. Version 2.
Checksum: D5E989AE40BF69AF

FASTA34136,688
        10         20         30         40         50         60 
MTMESGAENQ 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

« Hide

Isoform CREB-B.

Checksum: F5BA8200EE5184B7
Show »

FASTA32735,136

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References

« Hide 'large scale' references
[1]"Two distinct forms of active transcription factor CREB (cAMP response element binding protein)."
Berkowitz L.A., Gilman M.Z.
Proc. Natl. Acad. Sci. U.S.A. 87:5258-5262(1990) [PubMed: 2142528] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CREB-A).
[2]"Multiple cDNA clones encoding nuclear proteins that bind to the tax-dependent enhancer of HTLV-1: all contain a leucine zipper structure and basic amino acid domain."
Yoshimura T., Fujisawa J., Yoshida M.
EMBO J. 9:2537-2542(1990) [PubMed: 2196176] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CREB-A).
[3]"Diversification of cyclic AMP-responsive enhancer binding proteins-generated by alternative exon splicing."
Waeber G., Meyer T.E., Hoeffler J.P., Habener J.F.
Trans. Assoc. Am. Physicians 103:28-37(1990) [PubMed: 1966745] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CREB-A).
[4]"Cyclic AMP-responsive DNA-binding protein: structure based on a cloned placental cDNA."
Hoeffler J.P., Meyer T.E., Yun Y., Jameson J.L., Habener J.F.
Science 242:1430-1433(1988) [PubMed: 2974179] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CREB-B).
[5]"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 CREB-B).
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM CREB-A).
Tissue: Eye.
[7]"The promoter of the gene encoding 3',5'-cyclic adenosine monophosphate (cAMP) response element binding protein contains cAMP response elements: evidence for positive autoregulation of gene transcription."
Meyer T.E., Waeber G., Lin J., Beckmann W., Habener J.F.
Endocrinology 132:770-780(1993) [PubMed: 8381074] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-8.
[8]"HBV X protein alters the DNA binding specificity of CREB and ATF-2 by protein-protein interactions."
Maguire H.F., Hoeffler J.P., Siddiqui A.
Science 252:842-844(1991) [PubMed: 1827531] [Abstract]
Cited for: INTERACTION WITH HBV PROTEIN X.
[9]"Human T-cell lymphotropic virus type I (HTLV-I) transcriptional activator, Tax, enhances CREB binding to HTLV-I 21-base-pair repeats by protein-protein interaction."
Zhao L.J., Giam C.-Z.
Proc. Natl. Acad. Sci. U.S.A. 89:7070-7074(1992) [PubMed: 1386673] [Abstract]
Cited for: INTERACTION WITH HTLV-1 TAX-1.
[10]"Transcriptional activation of egr-1 by granulocyte-macrophage colony-stimulating factor but not interleukin 3 requires phosphorylation of cAMP response element-binding protein (CREB) on serine 133."
Lee H.-J.J., Mignacca R.C., Sakamoto K.M.
J. Biol. Chem. 270:15979-15983(1995) [PubMed: 7608156] [Abstract]
Cited for: PHOSPHORYLATION AT SER-133.
[11]"TORCs: transducers of regulated CREB activity."
Conkright M.D., Canettieri G., Screaton R., Guzman E., Miraglia L., Hogenesch J.B., Montminy M.
Mol. Cell 12:413-423(2003) [PubMed: 14536081] [Abstract]
Cited for: INTERACTION WITH CRTC1.
[12]"Identification of a family of cAMP response element-binding protein coactivators by genome-scale functional analysis in mammalian cells."
Iourgenko V., Zhang W., Mickanin C., Daly I., Jiang C., Hexham J.M., Orth A.P., Miraglia L., Meltzer J., Garza D., Chirn G.-W., McWhinnie E., Cohen D., Skelton J., Terry R., Yu Y., Bodian D., Buxton F.P. expand/collapse author list , Zhu J., Song C., Labow M.A.
Proc. Natl. Acad. Sci. U.S.A. 100:12147-12152(2003) [PubMed: 14506290] [Abstract]
Cited for: INTERACTION WITH CRTC3.
[13]"The CREB coactivator TORC2 functions as a calcium- and cAMP-sensitive coincidence detector."
Screaton R.A., Conkright M.D., Katoh Y., Best J.L., Canettieri G., Jeffries S., Guzman E., Niessen S., Yates J.R. III, Takemori H., Okamoto M., Montminy M.
Cell 119:61-74(2004) [PubMed: 15454081] [Abstract]
Cited for: INTERACTION WITH CRTC2.
[14]"A nuclear function of beta-arrestin1 in GPCR signaling: regulation of histone acetylation and gene transcription."
Kang J., Shi Y., Xiang B., Qu B., Su W., Zhu M., Zhang M., Bao G., Wang F., Zhang X., Yang R., Fan F., Chen X., Pei G., Ma L.
Cell 123:833-847(2005) [PubMed: 16325578] [Abstract]
Cited for: INTERACTION WITH ARRB1.
[15]"PGC-1-related coactivator: immediate early expression and characterization of a CREB/NRF-1 binding domain associated with cytochrome c promoter occupancy and respiratory growth."
Vercauteren K., Pasko R.A., Gleyzer N., Marino V.M., Scarpulla R.C.
Mol. Cell. Biol. 26:7409-7419(2006) [PubMed: 16908542] [Abstract]
Cited for: INTERACTION WITH PPRC1.
[16]"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage."
Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.
Science 316:1160-1166(2007) [PubMed: 17525332] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-111 AND THR-119, MASS SPECTROMETRY.
[17]"EWSR1-CREB1 is the predominant gene fusion in angiomatoid fibrous histiocytoma."
Antonescu C.R., Dal Cin P., Nafa K., Teot L.A., Surti U., Fletcher C.D., Ladanyi M.
Genes Chromosomes Cancer 46:1051-1060(2007) [PubMed: 17724745] [Abstract]
Cited for: CHROMOSOMAL TRANSLOCATION WITH EWSR1, ASSOCIATION WITH ANGIOMATOID FIBROUS HISTIOCYTOMA.
[18]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-271, MASS SPECTROMETRY.
Tissue: T-cell.
+Additional computationally mapped references.

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Cross-references

Sequence databases

EMBL
GenBank
DDBJ		S72459 Genomic DNA. Translation: AAB20597.1.
X55545 mRNA. Translation: CAA39151.1.
M34356 mRNA. Translation: AAA35717.1.
M34356 mRNA. Translation: AAA35716.1.
M27691 mRNA. Translation: AAA35715.1.
X60003 mRNA. Translation: CAA42620.1.
BC010636 mRNA. Translation: AAH10636.1.
S53724 Genomic DNA. Translation: AAD13869.1.
IPIIPI00027713.
IPI00218334.
PIRA35769. A37340.
B35769. B37340.
S22298.
RefSeqNP_004370.1.
NP_604391.1.
UniGeneHs.516646

3D structure databases

SMRP16220. Positions 119-146, 285-339.
ModBaseSearch...

Protein-protein interaction databases

DIPDIP-765N.
IntActP16220. 11 interactions.
STRINGP16220.

PTM databases

PhosphoSiteP16220.

Proteomic databases

PRIDEP16220.

Genome annotation databases

EnsemblENST00000432329; ENSP00000387699; ENSG00000118260; Homo sapiens. [Genome view]
GeneID1385.
KEGGhsa:1385.
UCSCuc002vcc.1. human.

Organism-specific databases

CTD1385.
GeneCardsGC02P208102.
H-InvDBHIX0023181.
HGNCHGNC:2345. CREB1.
HPACAB003803.
HPA019150.
MIM123810. gene.
612160. phenotype.
PharmGKBPA26864.
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG12083.
HOGENOMHBG446032.
HOVERGENP16220.
InParanoidP16220.
OMAQXISTIA.
OrthoDBEOG9FN73R.
PhylomeDBP16220.

Enzyme and pathway databases

Pathway_Interaction_DBhnf3bpathway. FOXA2 and FOXA3 transcription factor networks.
hif1_tfpathway. HIF-1-alpha transcription factor network.
lpa4_pathway. LPA4-mediated signaling events.
p38_mk2pathway. p38 signaling mediated by MAPKAP kinases.
smad2_3nuclearpathway. Regulation of nuclear SMAD2/3 signaling.
ret_pathway. Signaling events regulated by Ret tyrosine kinase.
p38alphabetadownstreampathway. Signaling mediated by p38-alpha and p38-beta.
pi3kplctrkpathway. Trk receptor signaling mediated by PI3K and PLC-gamma.
mapktrkpathway. Trk receptor signaling mediated by the MAPK pathway.
lymphangiogenesis_pathway. VEGFR3 signaling in lymphatic endothelium.
ReactomeREACT_11061. Signalling by NGF.
REACT_13685. Synaptic Transmission.
REACT_15295. Opioid Signalling.
REACT_18266. Axon guidance.

Gene expression databases

ArrayExpressP16220.
BgeeP16220.
CleanExHS_CREB1.
GenevestigatorP16220.
GermOnlineENSG00000118260. Homo sapiens.

Family and domain databases

InterProIPR011616. bZIP_1.
IPR003102. Coactivator_CBP_pKID.
IPR001630. Leuzip_CREB.
IPR004827. TF_bZIP.
[Graphical view]
PfamPF00170. bZIP_1. 1 hit.
PF02173. pKID. 1 hit.
[Graphical view]
PRINTSPR00041. LEUZIPPRCREB.
SMARTSM00338. BRLZ. 1 hit.
[Graphical view]
PROSITEPS50217. BZIP. 1 hit.
PS00036. BZIP_BASIC. 1 hit.
PS50953. KID. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

DrugBankDB00131. Adenosine monophosphate.
DB01200. Bromocriptine.
DB01183. Naloxone.
NextBio5625.
PMAP-CutDBP16220.
SOURCESearch...

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Entry information

Entry nameCREB1_HUMAN
AccessionPrimary (citable) accession number: P16220
Secondary accession number(s): P21934, Q9UMA7
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: May 1, 1992
Last modified: February 9, 2010
This is version 129 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

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Relevant documents

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents