Cyclic AMP-responsive element-binding protein 1

Details

Name
Cyclic AMP-responsive element-binding protein 1
Kind
protein
Synonyms
  • cAMP-responsive element-binding protein 1
  • CREB-1
Gene Name
CREB1
UniProtKB Entry
P16220Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0055922|Cyclic AMP-responsive element-binding protein 1
MTMESGAENQQSGDAAVTEAENQQMTVQAQPQIATLAQVSMPAAHATSSAPTVTLVQLPN
GQTVQVHGVIQAAQPSVIQSPQVQTVQISTIAESEDSQESVDSVTDSQKRREILSRRPSY
RKILNDLSSDAPGVPRIEEEKSEEETSAPAITTVTVPTPIYQTSSGQYIAITQGGAIQLA
NNGTDGVQGLQTLTMTNAAATQPGTTILQYAQTTDGQQILVPSNQVVVQAASGDVQTYQI
RTAPTSTIAPGVVMASSPALPTQPAEEAARKREVRLMKNREAARECRRKKKEYVKCLENR
VAVLENQNKTLIEELKALKDLYCHKSD
Number of residues
327
Molecular Weight
35136.1
Theoretical pI
5.24
GO Classification
Functions
DNA-binding transcription activator activity, RNA polymerase II-specific / DNA-binding transcription factor activity / DNA-binding transcription factor activity, RNA polymerase II-specific / identical protein binding / RNA polymerase II cis-regulatory region sequence-specific DNA binding / RNA polymerase II-specific DNA-binding transcription factor binding / sequence-specific double-stranded DNA binding
Processes
axonogenesis / cAMP-mediated signaling / cellular response to forskolin / cellular response to hepatocyte growth factor stimulus / cellular response to leukemia inhibitory factor / cellular response to retinoic acid / hormone secretion / mRNA transcription by RNA polymerase II / negative regulation of apoptotic process / osteoclast differentiation / positive regulation of cardiac muscle tissue development / positive regulation of DNA-templated transcription / positive regulation of transcription by RNA polymerase II / regulation of testosterone biosynthetic process / regulation of transcription by RNA polymerase II / response to purine-containing compound / response to xenobiotic stimulus
Components
chromatin / euchromatin / RNA polymerase II transcription regulator complex
General Function
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 (By similarity). Transcription activation is enhanced by the TORC coactivators which act independently of Ser-119 phosphorylation (PubMed:14536081). Involved in different cellular processes including the synchronization of circadian rhythmicity and the differentiation of adipose cells (By similarity). Regulates the expression of apoptotic and inflammatory response factors in cardiomyocytes in response to ERFE-mediated activation of AKT signaling (By similarity)
Specific Function
cAMP response element binding
Pfam Domain Function
Signal Regions
Not Available
Transmembrane Regions
Not Available
Cellular Location
Nucleus
Gene sequence
>lcl|BSEQ0021836|Cyclic AMP-responsive element-binding protein 1 (CREB1)
ATGACCATGGAATCTGGAGCCGAGAACCAGCAGAGTGGAGATGCAGCTGTAACAGAAGCT
GAAAACCAACAAATGACAGTTCAAGCCCAGCCACAGATTGCCACATTAGCCCAGGTATCT
ATGCCAGCAGCTCATGCAACATCATCTGCTCCCACCGTAACTCTAGTACAGCTGCCCAAT
GGGCAGACAGTTCAAGTCCATGGAGTCATTCAGGCGGCCCAGCCATCAGTTATTCAGTCT
CCACAAGTCCAAACAGTTCAGATTTCAACTATTGCAGAAAGTGAAGATTCACAGGAGTCA
GTGGATAGTGTAACTGATTCCCAAAAGCGAAGGGAAATTCTTTCAAGGAGGCCTTCCTAC
AGGAAAATTTTGAATGACTTATCTTCTGATGCACCAGGAGTGCCAAGGATTGAAGAAGAG
AAGTCTGAAGAGGAGACTTCAGCACCTGCCATCACCACTGTAACGGTGCCAACTCCAATT
TACCAAACTAGCAGTGGACAGTATATTGCCATTACCCAGGGAGGAGCAATACAGCTGGCT
AACAATGGTACCGATGGGGTACAGGGCCTGCAAACATTAACCATGACCAATGCAGCAGCC
ACTCAGCCGGGTACTACCATTCTACAGTATGCACAGACCACTGATGGACAGCAGATCTTA
GTGCCCAGCAACCAAGTTGTTGTTCAAGCTGCCTCTGGAGACGTACAAACATACCAGATT
CGCACAGCACCCACTAGCACTATTGCCCCTGGAGTTGTTATGGCATCCTCCCCAGCACTT
CCTACACAGCCTGCTGAAGAAGCAGCACGAAAGAGAGAGGTCCGTCTAATGAAGAACAGG
GAAGCAGCTCGAGAGTGTCGTAGAAAGAAGAAAGAATATGTGAAATGTTTAGAAAACAGA
GTGGCAGTGCTTGAAAATCAAAACAAGACATTGATTGAGGAGCTAAAAGCACTTAAGGAC
CTTTACTGCCACAAATCAGATTAA
Chromosome Location
2
Locus
2q33.3
External Identifiers
ResourceLink
UniProtKB IDP16220
UniProtKB Entry NameCREB1_HUMAN
GenBank Protein ID240429
GenBank Gene IDS72459
GeneCard IDCREB1
GenAtlas IDCREB1
HGNC IDHGNC:2345
PDB ID(s)2LXT, 5ZK1, 5ZKO, 7TBH
KEGG IDhsa:1385
NCBI Gene ID1385
General References
  1. Berkowitz LA, Gilman MZ: Two distinct forms of active transcription factor CREB (cAMP response element binding protein). Proc Natl Acad Sci U S A. 1990 Jul;87(14):5258-62. [Article]
  2. Yoshimura T, Fujisawa J, Yoshida M: 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. EMBO J. 1990 Aug;9(8):2537-42. [Article]
  3. Waeber G, Meyer TE, Hoeffler JP, Habener JF: Diversification of cyclic AMP-responsive enhancer binding proteins-generated by alternative exon splicing. Trans Assoc Am Physicians. 1990;103:28-37. [Article]
  4. Hoeffler JP, Meyer TE, Yun Y, Jameson JL, Habener JF: Cyclic AMP-responsive DNA-binding protein: structure based on a cloned placental cDNA. Science. 1988 Dec 9;242(4884):1430-3. [Article]
  5. Short ML, Manohar CF, Furtado MR, Ghadge GD, Wolinsky SM, Thimmapaya B, Jungmann RA: Nucleotide and derived amino-acid sequences of the CRE-binding proteins from rat C6 glioma and HeLa cells. Nucleic Acids Res. 1991 Aug 11;19(15):4290. [Article]
  6. Huang X, Zhang J, Lu L, Yin L, Xu M, Wang Y, Zhou Z, Sha J: Cloning and expression of a novel CREB mRNA splice variant in human testis. Reproduction. 2004 Dec;128(6):775-82. [Article]
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  8. Meyer TE, Waeber G, Lin J, Beckmann W, Habener JF: 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. Endocrinology. 1993 Feb;132(2):770-80. [Article]
  9. Maguire HF, Hoeffler JP, Siddiqui A: HBV X protein alters the DNA binding specificity of CREB and ATF-2 by protein-protein interactions. Science. 1991 May 10;252(5007):842-4. [Article]
  10. Zhao LJ, Giam CZ: 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. Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):7070-4. [Article]
  11. Matthews RP, Guthrie CR, Wailes LM, Zhao X, Means AR, McKnight GS: Calcium/calmodulin-dependent protein kinase types II and IV differentially regulate CREB-dependent gene expression. Mol Cell Biol. 1994 Sep;14(9):6107-16. [Article]
  12. Lee HJ, Mignacca RC, Sakamoto KM: 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. J Biol Chem. 1995 Jul 7;270(27):15979-83. [Article]
  13. Du K, Montminy M: CREB is a regulatory target for the protein kinase Akt/PKB. J Biol Chem. 1998 Dec 4;273(49):32377-9. [Article]
  14. De Cesare D, Jacquot S, Hanauer A, Sassone-Corsi P: Rsk-2 activity is necessary for epidermal growth factor-induced phosphorylation of CREB protein and transcription of c-fos gene. Proc Natl Acad Sci U S A. 1998 Oct 13;95(21):12202-7. [Article]
  15. Conkright MD, Canettieri G, Screaton R, Guzman E, Miraglia L, Hogenesch JB, Montminy M: TORCs: transducers of regulated CREB activity. Mol Cell. 2003 Aug;12(2):413-23. [Article]
  16. Comerford KM, Leonard MO, Karhausen J, Carey R, Colgan SP, Taylor CT: Small ubiquitin-related modifier-1 modification mediates resolution of CREB-dependent responses to hypoxia. Proc Natl Acad Sci U S A. 2003 Feb 4;100(3):986-91. Epub 2003 Jan 27. [Article]
  17. Iourgenko V, Zhang W, Mickanin C, Daly I, Jiang C, Hexham JM, Orth AP, Miraglia L, Meltzer J, Garza D, Chirn GW, McWhinnie E, Cohen D, Skelton J, Terry R, Yu Y, Bodian D, Buxton FP, Zhu J, Song C, Labow MA: Identification of a family of cAMP response element-binding protein coactivators by genome-scale functional analysis in mammalian cells. Proc Natl Acad Sci U S A. 2003 Oct 14;100(21):12147-52. Epub 2003 Sep 23. [Article]
  18. Screaton RA, Conkright MD, Katoh Y, Best JL, Canettieri G, Jeffries S, Guzman E, Niessen S, Yates JR 3rd, Takemori H, Okamoto M, Montminy M: The CREB coactivator TORC2 functions as a calcium- and cAMP-sensitive coincidence detector. Cell. 2004 Oct 1;119(1):61-74. [Article]
  19. 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: A nuclear function of beta-arrestin1 in GPCR signaling: regulation of histone acetylation and gene transcription. Cell. 2005 Dec 2;123(5):833-47. [Article]
  20. David S, Kalb RG: Serum/glucocorticoid-inducible kinase can phosphorylate the cyclic AMP response element binding protein, CREB. FEBS Lett. 2005 Feb 28;579(6):1534-8. [Article]
  21. Vercauteren K, Pasko RA, Gleyzer N, Marino VM, Scarpulla RC: 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. Mol Cell Biol. 2006 Oct;26(20):7409-19. Epub 2006 Aug 14. [Article]
  22. Antonescu CR, Dal Cin P, Nafa K, Teot LA, Surti U, Fletcher CD, Ladanyi M: EWSR1-CREB1 is the predominant gene fusion in angiomatoid fibrous histiocytoma. Genes Chromosomes Cancer. 2007 Dec;46(12):1051-60. [Article]
  23. Matsuoka S, Ballif BA, Smogorzewska A, McDonald ER 3rd, Hurov KE, Luo J, Bakalarski CE, Zhao Z, Solimini N, Lerenthal Y, Shiloh Y, Gygi SP, Elledge SJ: ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. Science. 2007 May 25;316(5828):1160-6. [Article]
  24. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [Article]
  25. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. [Article]
  26. Sakamoto K, Huang BW, Iwasaki K, Hailemariam K, Ninomiya-Tsuji J, Tsuji Y: Regulation of genotoxic stress response by homeodomain-interacting protein kinase 2 through phosphorylation of cyclic AMP response element-binding protein at serine 271. Mol Biol Cell. 2010 Aug 15;21(16):2966-74. doi: 10.1091/mbc.E10-01-0015. Epub 2010 Jun 23. [Article]
  27. Dittmer S, Kovacs Z, Yuan SH, Siszler G, Kogl M, Summer H, Geerts A, Golz S, Shioda T, Methner A: TOX3 is a neuronal survival factor that induces transcription depending on the presence of CITED1 or phosphorylated CREB in the transcriptionally active complex. J Cell Sci. 2011 Jan 15;124(Pt 2):252-60. doi: 10.1242/jcs.068759. Epub 2010 Dec 15. [Article]
  28. Rigbolt KT, Prokhorova TA, Akimov V, Henningsen J, Johansen PT, Kratchmarova I, Kassem M, Mann M, Olsen JV, Blagoev B: System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci Signal. 2011 Mar 15;4(164):rs3. doi: 10.1126/scisignal.2001570. [Article]
  29. Kitazawa S, Kondo T, Mori K, Yokoyama N, Matsuo M, Kitazawa R: A p.D116G mutation in CREB1 leads to novel multiple malformation syndrome resembling CrebA knockout mouse. Hum Mutat. 2012 Apr;33(4):651-4. doi: 10.1002/humu.22027. Epub 2012 Feb 14. [Article]
  30. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [Article]

Associated Data

Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
Adenosine phosphateapproved, investigational, nutraceutical, withdrawnunknowntargetactivatorDetails
Naloxoneapproved, vet_approvednotargetother/unknownDetails