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Protein

Cyclic AMP-responsive element-binding protein 1

Gene

CREB1

Organism
Homo sapiens (Human)
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-133 phosphorylation. Involved in different cellular processes including the synchronization of circadian rhythmicity and the differentiation of adipose cells.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei314 – 3141Required for binding TORCs

GO - Molecular functioni

  1. cAMP response element binding Source: BHF-UCL
  2. enzyme binding Source: UniProtKB
  3. RNA polymerase II activating transcription factor binding Source: BHF-UCL
  4. RNA polymerase II core promoter proximal region sequence-specific DNA binding Source: NTNU_SB
  5. RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription Source: NTNU_SB
  6. RNA polymerase II distal enhancer sequence-specific DNA binding Source: BHF-UCL
  7. RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity Source: BHF-UCL
  8. RNA polymerase II transcription factor binding transcription factor activity involved in positive regulation of transcription Source: BHF-UCL
  9. sequence-specific DNA binding transcription factor activity Source: MGI
  10. transcription cofactor activity Source: ProtInc

GO - Biological processi

  1. activation of phospholipase C activity Source: Reactome
  2. axon guidance Source: Reactome
  3. cellular response to zinc ion Source: Ensembl
  4. circadian rhythm Source: UniProtKB
  5. epidermal growth factor receptor signaling pathway Source: Reactome
  6. Fc-epsilon receptor signaling pathway Source: Reactome
  7. fibroblast growth factor receptor signaling pathway Source: Reactome
  8. innate immune response Source: Reactome
  9. lactation Source: Ensembl
  10. lung saccule development Source: Ensembl
  11. memory Source: Ensembl
  12. mitochondrion organization Source: Reactome
  13. MyD88-dependent toll-like receptor signaling pathway Source: Reactome
  14. MyD88-independent toll-like receptor signaling pathway Source: Reactome
  15. negative regulation of transcription by competitive promoter binding Source: BHF-UCL
  16. neurotrophin TRK receptor signaling pathway Source: Reactome
  17. Notch signaling pathway Source: Reactome
  18. organelle organization Source: Reactome
  19. phosphatidylinositol-mediated signaling Source: Reactome
  20. pituitary gland development Source: Ensembl
  21. positive regulation of fat cell differentiation Source: UniProtKB
  22. positive regulation of hormone secretion Source: Ensembl
  23. positive regulation of lipid biosynthetic process Source: UniProtKB
  24. positive regulation of multicellular organism growth Source: Ensembl
  25. positive regulation of osteoclast differentiation Source: Ensembl
  26. positive regulation of transcription, DNA-templated Source: UniProtKB
  27. positive regulation of transcription from RNA polymerase II promoter Source: NTNU_SB
  28. protein phosphorylation Source: MGI
  29. protein stabilization Source: UniProtKB
  30. regulation of cell size Source: Ensembl
  31. response to drug Source: Ensembl
  32. response to glucagon Source: UniProtKB
  33. response to organic substance Source: MGI
  34. secretory granule organization Source: Ensembl
  35. signal transduction Source: Reactome
  36. stress-activated MAPK cascade Source: Reactome
  37. synaptic transmission Source: Reactome
  38. toll-like receptor 10 signaling pathway Source: Reactome
  39. toll-like receptor 2 signaling pathway Source: Reactome
  40. toll-like receptor 3 signaling pathway Source: Reactome
  41. toll-like receptor 4 signaling pathway Source: Reactome
  42. toll-like receptor 5 signaling pathway Source: Reactome
  43. toll-like receptor 9 signaling pathway Source: Reactome
  44. toll-like receptor signaling pathway Source: Reactome
  45. toll-like receptor TLR1:TLR2 signaling pathway Source: Reactome
  46. toll-like receptor TLR6:TLR2 signaling pathway Source: Reactome
  47. transcription from RNA polymerase II promoter Source: GOC
  48. TRIF-dependent toll-like receptor signaling pathway Source: Reactome
  49. Type I pneumocyte differentiation Source: Ensembl
  50. viral process Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Activator

Keywords - Biological processi

Biological rhythms, Differentiation, Host-virus interaction, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

ReactomeiREACT_120966. Gastrin-CREB signalling pathway via PKC and MAPK.
REACT_12442. AKT phosphorylates targets in the nucleus.
REACT_12524. CREB phosphorylation.
REACT_147727. Constitutive PI3K/AKT Signaling in Cancer.
REACT_15497. PKA-mediated phosphorylation of CREB.
REACT_15502. CaMK IV-mediated phosphorylation of CREB.
REACT_163910. NOTCH2 intracellular domain regulates transcription.
REACT_18334. NCAM signaling for neurite out-growth.
REACT_200608. Transcriptional activation of mitochondrial biogenesis.
REACT_20568. CREB phosphorylation through the activation of Ras.
REACT_20625. CREB phosphorylation through the activation of Adenylate Cyclase.
REACT_20642. CREB phosphorylation through the activation of CaMKII.
REACT_20661. CREB phosphorylation through the activation of CaMKK.
REACT_24941. Circadian Clock.
SignaLinkiP16220.

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 2

Organism-specific databases

HGNCiHGNC:2345. CREB1.

Subcellular locationi

Nucleus PROSITE-ProRule annotation1 Publication

GO - Cellular componenti

  1. ATF1-CREB1-ATF4 transcription factor complex Source: ParkinsonsUK-UCL
  2. nuclear euchromatin Source: BHF-UCL
  3. nucleoplasm Source: HPA
  4. nucleus Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

Angiomatoid fibrous histiocytoma

The gene represented in this entry may be involved in disease pathogenesis. A chromosomal aberration involving CREB1 is found in a patient with angiomatoid fibrous histiocytoma. Translocation t(2;22)(q33;q12) with CREB1 generates a EWSR1/CREB1 fusion gene that is most common genetic abnormality in this tumor type.

Disease descriptionA distinct variant of malignant fibrous histiocytoma that typically occurs in children and adolescents and is manifest by nodular subcutaneous growth. Characteristic microscopic features include lobulated sheets of histiocyte-like cells intimately associated with areas of hemorrhage and cystic pseudovascular spaces, as well as a striking cuffing of inflammatory cells, mimicking a lymph node metastasis.

See also OMIM:612160

A CREB1 mutation has been found in a patient with multiple congenital anomalies consisting of agenesis of the corpus callosum, cerebellar hypoplasia, severe neonatal respiratory distress refractory to surfactant, thymus hypoplasia, and thyroid follicular hypoplasia.

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi133 – 1331S → A: Does not interact with TOX3 and inhibits induction of transcription by TOX3. Loss of phosphorylation by CaMK4. 2 Publications
Mutagenesisi155 – 1551K → R: No effect on sumoylation. 1 Publication
Mutagenesisi271 – 2711S → A: Impaired phosphorylation by HIPK2 and subsequent transactivation. 1 Publication
Mutagenesisi271 – 2711S → E: Potentiated transactivation. 1 Publication
Mutagenesisi285 – 2851K → R: Decreased sumoylation, in vivo and in vitro. 1 Publication
Mutagenesisi304 – 3041K → R: Decreased sumoylation, in vivo and in vitro. Loss of nuclear localization. 1 Publication

Organism-specific databases

MIMi612160. phenotype.
Orphaneti97338. Melanoma of soft parts.
PharmGKBiPA26864.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 341341Cyclic AMP-responsive element-binding protein 1PRO_0000076597Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei133 – 1331Phosphoserine; by CaMK1, CaMK2, CaMK4, PKB/AKT1 or PKB/AKT2, RPS6KA3, RPS6KA4, RPS6KA5 and SGK1PROSITE-ProRule annotation5 Publications
Modified residuei142 – 1421Phosphoserine; by CaMK2PROSITE-ProRule annotation
Modified residuei271 – 2711Phosphoserine; by HIPK2PROSITE-ProRule annotation1 Publication
Cross-linki285 – 285Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)
Cross-linki304 – 304Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)

Post-translational modificationi

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. In liver, phosphorylation is induced by fasting or glucagon in a circadian fashion (By similarity). CREBL2 positively regulates phosphorylation at Ser-133 thereby stimulating CREB1 transcriptional activity (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 (By similarity). 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 similarity6 Publications
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.1 Publication

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiP16220.
PaxDbiP16220.
PRIDEiP16220.

PTM databases

PhosphoSiteiP16220.

Miscellaneous databases

PMAP-CutDBP16220.

Expressioni

Gene expression databases

BgeeiP16220.
CleanExiHS_CREB1.
ExpressionAtlasiP16220. baseline and differential.
GenevestigatoriP16220.

Organism-specific databases

HPAiCAB003803.
HPA019150.

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-133, binds CREBBP (By similarity). Interacts with CREBL2; regulates CREB1 phosphorylation, stability and transcriptional activity (By similarity). Interacts (phosphorylated form) with TOX3. Interacts with ARRB1. Binds to HIPK2. Interacts with SGK1.By similarity10 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
P03259-22EBI-711855,EBI-7225021From a different organism.
CREBBPQ927932EBI-711855,EBI-81215
EP300Q094722EBI-711855,EBI-447295
MEIS1O004709EBI-711855,EBI-1210694
PASKQ96RG22EBI-711855,EBI-1042651
TSSK4Q6SA085EBI-711855,EBI-1202583

Protein-protein interaction databases

BioGridi107775. 99 interactions.
DIPiDIP-765N.
IntActiP16220. 37 interactions.
MINTiMINT-1338714.
STRINGi9606.ENSP00000387699.

Structurei

Secondary structure

1
341
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi120 – 1289Combined sources
Helixi132 – 14211Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2LXTNMR-C116-149[»]
ProteinModelPortaliP16220.
SMRiP16220. Positions 116-149, 285-339.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini101 – 16060KIDPROSITE-ProRule annotationAdd
BLAST
Domaini283 – 34159bZIPPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni284 – 30926Basic motifPROSITE-ProRule annotationAdd
BLAST
Regioni311 – 33222Leucine-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

eggNOGiNOG300199.
HOGENOMiHOG000007365.
HOVERGENiHBG011077.
InParanoidiP16220.
KOiK05870.
OMAiQXISTIA.
OrthoDBiEOG72G18D.
PhylomeDBiP16220.
TreeFamiTF106464.

Family and domain databases

InterProiIPR004827. bZIP.
IPR003102. Coactivator_CBP_pKID.
IPR029802. CREB1.
IPR001630. Leuzip_CREB.
[Graphical view]
PANTHERiPTHR22952:SF104. PTHR22952:SF104. 1 hit.
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]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform CREB-A (identifier: P16220-1) [UniParc]FASTAAdd to basket

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
MTMESGAENQ QSGDAAVTEA ENQQMTVQAQ 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):36,688
Last modified:May 1, 1992 - v2
Checksum:iD5E989AE40BF69AF
GO
Isoform CREB-B (identifier: P16220-2) [UniParc]FASTAAdd to basket

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

Show »
Length:327
Mass (Da):35,136
Checksum:iF5BA8200EE5184B7
GO
Isoform 3 (identifier: P16220-3) [UniParc]FASTAAdd to basket

Also known as: htCREB

The sequence of this isoform differs from the canonical sequence as follows:
     162-272: Missing.

Note: Highly expressed in adult testis and sperm.

Show »
Length:230
Mass (Da):25,445
Checksum:i9FD8CA28F7632FBD
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti4 – 41E → D in CAA42620 (PubMed:1831258).Curated
Sequence conflicti8 – 81E → D in CAA42620 (PubMed:1831258).Curated
Sequence conflicti160 – 1601T → A in CAA42620 (PubMed:1831258).Curated
Sequence conflicti167 – 1671T → A in CAA42620 (PubMed:1831258).Curated
Sequence conflicti169 – 1691T → A in CAA42620 (PubMed:1831258).Curated
Sequence conflicti176 – 1761Q → R in CAA42620 (PubMed:1831258).Curated
Sequence conflicti184 – 1841A → T in CAA42620 (PubMed:1831258).Curated
Sequence conflicti188 – 1881G → R in CAA42620 (PubMed:1831258).Curated
Sequence conflicti195 – 1951N → S in CAA42620 (PubMed:1831258).Curated
Sequence conflicti210 – 2101T → A in CAA42620 (PubMed:1831258).Curated
Sequence conflicti292 – 2921K → E in AAQ24858 (PubMed:15579595).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti116 – 1161D → G Found in a patient with multiple congenital anomalies; does not affect CREB1 phosphorylation at S-133; fails to interact with CREBBP. 1 Publication
VAR_068077

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei88 – 10114Missing in isoform CREB-B. 2 PublicationsVSP_000596Add
BLAST
Alternative sequencei162 – 272111Missing in isoform 3. 1 PublicationVSP_043914Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
AY347527 mRNA. Translation: AAQ24858.1.
BC010636 mRNA. Translation: AAH10636.1.
S53724 Genomic DNA. Translation: AAD13869.1.
CCDSiCCDS2374.1. [P16220-2]
CCDS2375.1. [P16220-1]
PIRiA37340. A35769.
B37340. B35769.
S22298.
RefSeqiNP_004370.1. NM_004379.3. [P16220-2]
NP_604391.1. NM_134442.3. [P16220-1]
UniGeneiHs.516646.

Genome annotation databases

EnsembliENST00000353267; ENSP00000236995; ENSG00000118260. [P16220-2]
ENST00000430624; ENSP00000405539; ENSG00000118260. [P16220-2]
ENST00000432329; ENSP00000387699; ENSG00000118260. [P16220-1]
GeneIDi1385.
KEGGihsa:1385.
UCSCiuc002vcc.3. human. [P16220-1]

Polymorphism databases

DMDMi117434.

Keywords - Coding sequence diversityi

Alternative splicing, Chromosomal rearrangement, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
AY347527 mRNA. Translation: AAQ24858.1.
BC010636 mRNA. Translation: AAH10636.1.
S53724 Genomic DNA. Translation: AAD13869.1.
CCDSiCCDS2374.1. [P16220-2]
CCDS2375.1. [P16220-1]
PIRiA37340. A35769.
B37340. B35769.
S22298.
RefSeqiNP_004370.1. NM_004379.3. [P16220-2]
NP_604391.1. NM_134442.3. [P16220-1]
UniGeneiHs.516646.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2LXTNMR-C116-149[»]
ProteinModelPortaliP16220.
SMRiP16220. Positions 116-149, 285-339.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107775. 99 interactions.
DIPiDIP-765N.
IntActiP16220. 37 interactions.
MINTiMINT-1338714.
STRINGi9606.ENSP00000387699.

Chemistry

ChEMBLiCHEMBL5587.
DrugBankiDB00131. Adenosine monophosphate.
DB01183. Naloxone.

PTM databases

PhosphoSiteiP16220.

Polymorphism databases

DMDMi117434.

Proteomic databases

MaxQBiP16220.
PaxDbiP16220.
PRIDEiP16220.

Protocols and materials databases

DNASUi1385.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000353267; ENSP00000236995; ENSG00000118260. [P16220-2]
ENST00000430624; ENSP00000405539; ENSG00000118260. [P16220-2]
ENST00000432329; ENSP00000387699; ENSG00000118260. [P16220-1]
GeneIDi1385.
KEGGihsa:1385.
UCSCiuc002vcc.3. human. [P16220-1]

Organism-specific databases

CTDi1385.
GeneCardsiGC02P208394.
HGNCiHGNC:2345. CREB1.
HPAiCAB003803.
HPA019150.
MIMi123810. gene.
612160. phenotype.
neXtProtiNX_P16220.
Orphaneti97338. Melanoma of soft parts.
PharmGKBiPA26864.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG300199.
HOGENOMiHOG000007365.
HOVERGENiHBG011077.
InParanoidiP16220.
KOiK05870.
OMAiQXISTIA.
OrthoDBiEOG72G18D.
PhylomeDBiP16220.
TreeFamiTF106464.

Enzyme and pathway databases

ReactomeiREACT_120966. Gastrin-CREB signalling pathway via PKC and MAPK.
REACT_12442. AKT phosphorylates targets in the nucleus.
REACT_12524. CREB phosphorylation.
REACT_147727. Constitutive PI3K/AKT Signaling in Cancer.
REACT_15497. PKA-mediated phosphorylation of CREB.
REACT_15502. CaMK IV-mediated phosphorylation of CREB.
REACT_163910. NOTCH2 intracellular domain regulates transcription.
REACT_18334. NCAM signaling for neurite out-growth.
REACT_200608. Transcriptional activation of mitochondrial biogenesis.
REACT_20568. CREB phosphorylation through the activation of Ras.
REACT_20625. CREB phosphorylation through the activation of Adenylate Cyclase.
REACT_20642. CREB phosphorylation through the activation of CaMKII.
REACT_20661. CREB phosphorylation through the activation of CaMKK.
REACT_24941. Circadian Clock.
SignaLinkiP16220.

Miscellaneous databases

ChiTaRSiCREB1. human.
GeneWikiiCREB1.
GenomeRNAii1385.
NextBioi5625.
PMAP-CutDBP16220.
PROiP16220.
SOURCEiSearch...

Gene expression databases

BgeeiP16220.
CleanExiHS_CREB1.
ExpressionAtlasiP16220. baseline and differential.
GenevestigatoriP16220.

Family and domain databases

InterProiIPR004827. bZIP.
IPR003102. Coactivator_CBP_pKID.
IPR029802. CREB1.
IPR001630. Leuzip_CREB.
[Graphical view]
PANTHERiPTHR22952:SF104. PTHR22952:SF104. 1 hit.
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. "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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CREB-B).
  6. "Cloning and expression of a novel CREB mRNA splice variant in human testis."
    Huang X., Zhang J., Lu L., Yin L., Xu M., Wang Y., Zhou Z., Sha J.
    Reproduction 128:775-782(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
    Tissue: Testis.
  7. "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] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM CREB-A).
    Tissue: Eye.
  8. "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] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-8.
  9. "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] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH HBV PROTEIN X.
  10. "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] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH HTLV-1 TAX-1.
  11. "Calcium/calmodulin-dependent protein kinase types II and IV differentially regulate CREB-dependent gene expression."
    Matthews R.P., Guthrie C.R., Wailes L.M., Zhao X., Means A.R., McKnight G.S.
    Mol. Cell. Biol. 14:6107-6116(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT SER-133, MUTAGENESIS OF SER-133.
  12. "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] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT SER-133.
  13. "CREB is a regulatory target for the protein kinase Akt/PKB."
    Du K., Montminy M.
    J. Biol. Chem. 273:32377-32379(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT SER-133.
  14. "Rsk-2 activity is necessary for epidermal growth factor-induced phosphorylation of CREB protein and transcription of c-fos gene."
    De Cesare D., Jacquot S., Hanauer A., Sassone-Corsi P.
    Proc. Natl. Acad. Sci. U.S.A. 95:12202-12207(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT SER-133.
  15. Cited for: INTERACTION WITH CRTC1.
  16. "Small ubiquitin-related modifier-1 modification mediates resolution of CREB-dependent responses to hypoxia."
    Comerford K.M., Leonard M.O., Karhausen J., Carey R., Colgan S.P., Taylor C.T.
    Proc. Natl. Acad. Sci. U.S.A. 100:986-991(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUMOYLATION AT LYS-285 AND LYS-304, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-155; LYS-285 AND LYS-304.
  17. "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.
    , Zhu J., Song C., Labow M.A.
    Proc. Natl. Acad. Sci. U.S.A. 100:12147-12152(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH CRTC3.
  18. "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] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH CRTC2.
  19. "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] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH ARRB1.
  20. "Serum/glucocorticoid-inducible kinase can phosphorylate the cyclic AMP response element binding protein, CREB."
    David S., Kalb R.G.
    FEBS Lett. 579:1534-1538(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT SER-133 BY SGK1, INTERACTION WITH SGK1.
  21. "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] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH PPRC1.
  22. "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] [Europe PMC] [Abstract]
    Cited for: CHROMOSOMAL TRANSLOCATION WITH EWSR1, ASSOCIATION WITH ANGIOMATOID FIBROUS HISTIOCYTOMA.
  23. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Embryonic kidney.
  24. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  25. "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] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Leukemic T-cell.
  26. "Regulation of genotoxic stress response by homeodomain-interacting protein kinase 2 through phosphorylation of cyclic AMP response element-binding protein at serine 271."
    Sakamoto K., Huang B.-W., Iwasaki K., Hailemariam K., Ninomiya-Tsuji J., Tsuji Y.
    Mol. Biol. Cell 21:2966-2974(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT SER-271 BY HIPK2, MUTAGENESIS OF SER-271, INTERACTION WITH HIPK2.
  27. "TOX3 is a neuronal survival factor that induces transcription depending on the presence of CITED1 or phosphorylated CREB in the transcriptionally active complex."
    Dittmer S., Kovacs Z., Yuan S.H., Siszler G., Kogl M., Summer H., Geerts A., Golz S., Shioda T., Methner A.
    J. Cell Sci. 124:252-260(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH TOX3, MUTAGENESIS OF SER-133.
  28. "System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
    Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
    Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  29. "A p.D116G mutation in CREB1 leads to novel multiple malformation syndrome resembling CrebA knockout mouse."
    Kitazawa S., Kondo T., Mori K., Yokoyama N., Matsuo M., Kitazawa R.
    Hum. Mutat. 33:651-654(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: POSSIBLE INVOLVEMENT IN MULTIPLE CONGENITAL ANOMALIES, VARIANT GLY-116, CHARACTERIZATION OF VARIANT GLY-116.
  30. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
    Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
    J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.

Entry informationi

Entry nameiCREB1_HUMAN
AccessioniPrimary (citable) accession number: P16220
Secondary accession number(s): P21934, Q6V963, Q9UMA7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: May 1, 1992
Last modified: March 4, 2015
This is version 185 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.