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P15337

- CREB1_RAT

UniProt

P15337 - CREB1_RAT

Protein

Cyclic AMP-responsive element-binding protein 1

Gene

Creb1

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 152 (01 Oct 2014)
      Sequence version 1 (01 Apr 1990)
      Previous versions | rss
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    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 By similarity.By similarity

    GO - Molecular functioni

    1. double-stranded DNA binding Source: RGD
    2. histone acetyltransferase binding Source: RGD
    3. protein binding Source: UniProtKB
    4. RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity Source: RGD
    5. sequence-specific DNA binding Source: RGD
    6. sequence-specific DNA binding transcription factor activity Source: RGD
    7. transcription factor binding Source: RGD
    8. transcription regulatory region DNA binding Source: RGD

    GO - Biological processi

    1. cell differentiation Source: UniProtKB-KW
    2. circadian rhythm Source: RGD
    3. positive regulation of fat cell differentiation Source: UniProtKB
    4. positive regulation of lipid biosynthetic process Source: UniProtKB
    5. positive regulation of RNA polymerase II transcriptional preinitiation complex assembly Source: RGD
    6. positive regulation of transcription, DNA-templated Source: UniProtKB
    7. positive regulation of transcription from RNA polymerase II promoter Source: RGD
    8. positive regulation of transforming growth factor beta3 production Source: RGD
    9. protein stabilization Source: UniProtKB
    10. regulation of apoptotic process Source: RGD
    11. regulation of circadian rhythm Source: RGD
    12. response to glucagon Source: UniProtKB
    13. transcription from RNA polymerase II promoter Source: RGD
    14. transforming growth factor beta receptor signaling pathway Source: RGD

    Keywords - Molecular functioni

    Activator

    Keywords - Biological processi

    Biological rhythms, Differentiation, Transcription, Transcription regulation

    Keywords - Ligandi

    DNA-binding

    Enzyme and pathway databases

    ReactomeiREACT_195028. Gastrin-CREB signalling pathway via PKC and MAPK.
    REACT_196391. CREB phosphorylation through the activation of Ras.
    REACT_196392. CREB phosphorylation through the activation of CaMKII.
    REACT_196394. CREB phosphorylation through the activation of Adenylate Cyclase.
    REACT_198729. Constitutive PI3K/AKT Signaling in Cancer.
    REACT_216049. Transcriptional activation of mitochondrial biogenesis.

    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
    Synonyms:Creb-1
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494: Chromosome 9

    Organism-specific databases

    RGDi620218. Creb1.

    Subcellular locationi

    GO - Cellular componenti

    1. chromatin Source: RGD
    2. mitochondrion Source: RGD
    3. nuclear chromatin Source: BHF-UCL
    4. nucleoplasm Source: Reactome
    5. nucleus Source: MGI
    6. transcription factor complex Source: RGD

    Keywords - Cellular componenti

    Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi133 – 1331S → A: Loss of activation by CaMK4. 1 Publication
    Mutagenesisi142 – 1421S → A: Loss of phosphorylation by CaMK2. Activation by CaMK2. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 341341Cyclic AMP-responsive element-binding protein 1PRO_0000076599Add
    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 SGK13 PublicationsPROSITE-ProRule annotation
    Modified residuei142 – 1421Phosphoserine; by CaMK21 PublicationPROSITE-ProRule annotation
    Modified residuei271 – 2711Phosphoserine; by HIPK2PROSITE-ProRule annotation
    Cross-linki285 – 285Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)By similarity
    Cross-linki304 – 304Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)By similarity

    Post-translational modificationi

    Phosphorylation of Ser-133 allows CREBBP binding. 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. 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. 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 similarity. CREBL2 positively regulates phosphorylation at Ser-133 thereby stimulating CREB1 transcriptional activity. In liver, phosphorylation is induced by fasting or glucagon in a circadian fashion By similarity.By similarity
    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 By similarity.By similarity

    Keywords - PTMi

    Isopeptide bond, Phosphoprotein, Ubl conjugation

    PTM databases

    PhosphoSiteiP15337.

    Expressioni

    Gene expression databases

    GenevestigatoriP15337.

    Interactioni

    Subunit structurei

    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. Interacts with ARRB1. 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

    BioGridi249546. 1 interaction.
    DIPiDIP-36407N.
    IntActiP15337. 2 interactions.
    MINTiMINT-1529999.
    STRINGi10116.ENSRNOP00000018326.

    Structurei

    Secondary structure

    1
    341
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi120 – 1289
    Helixi133 – 14412

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1KDXNMR-B119-146[»]
    DisProtiDP00080.
    DP00682.
    ProteinModelPortaliP15337.
    SMRiP15337. Positions 119-146, 285-339.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP15337.

    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.
    GeneTreeiENSGT00390000008655.
    HOGENOMiHOG000007365.
    HOVERGENiHBG011077.
    InParanoidiP15337.
    KOiK05870.
    OMAiQXISTIA.
    OrthoDBiEOG72G18D.
    PhylomeDBiP15337.
    TreeFamiTF106464.

    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]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: P15337-1) [UniParc]FASTAAdd to Basket

    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.

    « Hide

    MTMDSGADNQ QSGDAAVTEA ESQQMTVQAQ PQIATLAQVS MPAAHATSSA    50
    PTVTLVQLPN GQTVQVHGVI QAAQPSVIQS PQVQTVQSSC KDLKRLFSGT 100
    QISTIAESED SQESVDSVTD SQKRREILSR RPSYRKILND LSSDAPGVPR 150
    IEEEKSEEET SAPAITTVTV PTPIYQTSSG QYIAITQGGA IQLANNGTDG 200
    VQGLQTLTMT NAAATQPGTT ILQYAQTTDG QQILVPSNQV VVQAASGDVQ 250
    TYQIRTAPTS TIAPGVVMAS SPALPTQPAE EAARKREVRL MKNREAAREC 300
    RRKKKEYVKC LENRVAVLEN QNKTLIEELK ALKDLYCHKS D 341
    Length:341
    Mass (Da):36,633
    Last modified:April 1, 1990 - v1
    Checksum:iFC08AC5A335D4C2F
    GO
    Isoform 2 (identifier: P15337-2) [UniParc]FASTAAdd to Basket

    Also known as: Delta

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

    Show »
    Length:327
    Mass (Da):35,081
    Checksum:iD6D715DEED679FF2
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti135 – 1351R → K in CAA42619. (PubMed:1831258)Curated
    Sequence conflicti319 – 3191E → K in CAA42619. (PubMed:1831258)Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei88 – 10114Missing in isoform 2. 1 PublicationVSP_000598Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X14788 mRNA. Translation: CAA32890.1.
    X60002 mRNA. Translation: CAA42619.1.
    PIRiA35663.
    S03343.
    S22299.
    RefSeqiNP_112279.1. NM_031017.1. [P15337-1]
    NP_604392.1. NM_134443.1.
    XP_006245127.1. XM_006245065.1. [P15337-1]
    XP_006245128.1. XM_006245066.1. [P15337-2]
    UniGeneiRn.90061.

    Genome annotation databases

    EnsembliENSRNOT00000018326; ENSRNOP00000018326; ENSRNOG00000013412. [P15337-1]
    ENSRNOT00000049654; ENSRNOP00000049369; ENSRNOG00000013412. [P15337-2]
    GeneIDi81646.
    KEGGirno:81646.
    UCSCiRGD:620218. rat. [P15337-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X14788 mRNA. Translation: CAA32890.1 .
    X60002 mRNA. Translation: CAA42619.1 .
    PIRi A35663.
    S03343.
    S22299.
    RefSeqi NP_112279.1. NM_031017.1. [P15337-1 ]
    NP_604392.1. NM_134443.1.
    XP_006245127.1. XM_006245065.1. [P15337-1 ]
    XP_006245128.1. XM_006245066.1. [P15337-2 ]
    UniGenei Rn.90061.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1KDX NMR - B 119-146 [» ]
    DisProti DP00080.
    DP00682.
    ProteinModelPortali P15337.
    SMRi P15337. Positions 119-146, 285-339.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 249546. 1 interaction.
    DIPi DIP-36407N.
    IntActi P15337. 2 interactions.
    MINTi MINT-1529999.
    STRINGi 10116.ENSRNOP00000018326.

    PTM databases

    PhosphoSitei P15337.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSRNOT00000018326 ; ENSRNOP00000018326 ; ENSRNOG00000013412 . [P15337-1 ]
    ENSRNOT00000049654 ; ENSRNOP00000049369 ; ENSRNOG00000013412 . [P15337-2 ]
    GeneIDi 81646.
    KEGGi rno:81646.
    UCSCi RGD:620218. rat. [P15337-1 ]

    Organism-specific databases

    CTDi 1385.
    RGDi 620218. Creb1.

    Phylogenomic databases

    eggNOGi NOG300199.
    GeneTreei ENSGT00390000008655.
    HOGENOMi HOG000007365.
    HOVERGENi HBG011077.
    InParanoidi P15337.
    KOi K05870.
    OMAi QXISTIA.
    OrthoDBi EOG72G18D.
    PhylomeDBi P15337.
    TreeFami TF106464.

    Enzyme and pathway databases

    Reactomei REACT_195028. Gastrin-CREB signalling pathway via PKC and MAPK.
    REACT_196391. CREB phosphorylation through the activation of Ras.
    REACT_196392. CREB phosphorylation through the activation of CaMKII.
    REACT_196394. CREB phosphorylation through the activation of Adenylate Cyclase.
    REACT_198729. Constitutive PI3K/AKT Signaling in Cancer.
    REACT_216049. Transcriptional activation of mitochondrial biogenesis.

    Miscellaneous databases

    EvolutionaryTracei P15337.
    NextBioi 615164.
    PROi P15337.

    Gene expression databases

    Genevestigatori P15337.

    Family and domain databases

    InterProi IPR004827. bZIP.
    IPR003102. Coactivator_CBP_pKID.
    IPR001630. Leuzip_CREB.
    [Graphical view ]
    Pfami PF00170. bZIP_1. 1 hit.
    PF02173. pKID. 1 hit.
    [Graphical view ]
    PRINTSi PR00041. LEUZIPPRCREB.
    SMARTi SM00338. BRLZ. 1 hit.
    [Graphical view ]
    PROSITEi PS50217. BZIP. 1 hit.
    PS00036. BZIP_BASIC. 1 hit.
    PS50953. KID. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT SER-133 AND SER-142, MUTAGENESIS OF 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] [Europe PMC] [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] [Europe PMC] [Abstract]
      Cited for: STRUCTURE BY NMR OF 119-146 IN COMPLEX WITH CREBBP.

    Entry informationi

    Entry nameiCREB1_RAT
    AccessioniPrimary (citable) accession number: P15337
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 1, 1990
    Last sequence update: April 1, 1990
    Last modified: October 1, 2014
    This is version 152 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3