| General information | | DisProt: | DP00080 | | Name: | Cyclic AMP-responsive element-binding protein 1 | | Synonym(s): | CREB1_RAT
cAMP-responsive element-binding protein 1
CREB-1
| | First appeared in release: | Release 2.0 (02/14/2005) | | UniProt: | P15337 | | UniGene: | Rn.90061 | | SwissProt: | CREB1_RAT | | TrEMBL: | | | NCBI (GI): | 117435 | | Source organism: | Rattus norvegicus (Rat) | | Sequence length: | 341 | | Percent disordered: | 18% | | Homologues: | |
| Native sequence |
10 20 30 40 50 60
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MTMESGAENQ QSGDAAVTEA ENQQMTVQAQ PQIATLAQVS MPAAHATSSA PTVTLVQLPN - 60
GQTVQVHGVI QAAQPSVIQS PQVQTVQSSC KDLKRLFSGT QISTIAESED SQESVDSVTD - 120
SQKRREILSR RPSYRKILND LSSDAPGVPR IEEEKSEEET SAPAITTVTV PTPIYQTSSG - 180
QYIAITQGGA IQLANNGTDG VQGLQTLTMT NAAATQPGTT ILQYAQTTDG QQILVPSNQV - 240
VVQAASGDVQ TYQIRTAPTS TIAPGVVMAS SPALPTQPAE EAARKREVRL MKNREAAREC - 300
RRKKKEYVKC LENRVAVLEN QNKTLIEELK ALKDLYCHKS D
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| Functional narrative |
cAMP response element binding protein (CREB) is a nuclear factor that activates transcription when in complex with its binding protein (CBP). A phosphorylated kinase-inducible domain (pKID) extends from amino acids 101-160 of CREB and binds to the KIX domain of CBP. The protein kinase A (PKA) mediated phosphorylation of Ser-133 is critically dependent for the dimerization and transcriptional efficacy of the complex. Once pKID binds to the KIX domain of CBP, pKID undergoes a coil to helix transition forming two amphipathic helices flanked by regions of the domain that remain disordered. The stimulation of gene expression via protein-protein interactions is mediated by the two newly-formed helices which are stabilized by packing against KIX.
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| Map of ordered and disordered regions |
Note: 'Mouse' over a region to see the start and stop residues. Click on a region to see detailed information.
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| Region 1 | | Type: | Disordered | | Name: | pKID | | Location: | 101 - 120 | | Length: | 20 | | Region sequence: |
QISTIAESEDSQESVDSVTD | | Modification type: | Engineered
Fragment
| | PDB: | 1KDX:B | | Structural/functional type: | Function arises from the disordered state
| | Functional classes: | Unknown
| | Functional subclasses: | Unknown
| Detection methods:
- Nuclear magnetic resonance (NMR) (315 K; pH: 5.5; acetate-d (buffer); guanidinium hydrochloride (solubilization) 0.6 M; NaCl (salt, buffer) 50 mM; Tris-d (buffer) 20 mM)
- Nuclear magnetic resonance (NMR) (290 K; pH: 5.5; acetate-d (buffer); guanidinium hydrochloride (solubilization) 0.6 M; NaCl (salt, buffer) 50 mM; Tris-d (buffer) 20 mM)
| References:
- Radhakrishnan I, Perez-Alvarado GC, Parker D, Dyson HJ, Montminy MR, Wright PE. "Solution structure of the KIX domain of CBP bound to the transactivation domain of CREB: a model for activator:coactivator interactions." Cell. 1997; 91(6): 741-752. PubMed: 9413984
| Comments:Upon binding to the KIX domain of the CREB binding protein this region remains disordered.
The PDB reference 1KDX chain B has the disordered region from residues 101-118.
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| Region 2 | | Type: | Disordered | | Name: | pKID | | Location: | 119 - 146 | | Length: | 28 | | Region sequence: |
TDSQKRREILSRRPSYRKILNDLSSDAP | | Modification type: | Engineered
Fragment
| | PDB: | 1KDX:B | | Structural/functional type: | Function arises via a disorder to order transition
| | Functional classes: | Molecular assembly
| | Functional subclasses: | Protein-protein binding
| Detection methods:
- Nuclear magnetic resonance (NMR) (315 K; pH: 5.5; acetate-d (buffer); guanidinium hydrochloride (solubilization) 0.6 M; NaCl (salt, buffer) 50 mM; Tris-d (buffer) 20 mM)
- Nuclear magnetic resonance (NMR) (290 K; pH: 5.5; acetate-d (buffer); guanidinium hydrochloride (solubilization) 0.6 M; NaCl (salt, buffer) 50 mM; Tris-d (buffer) 20 mM)
| References:
- Radhakrishnan I, Perez-Alvarado GC, Dyson HJ, Wright PE. "Conformational preferences in the Ser133-phosphorylated and non-phosphorylated forms of the kinase inducible transactivation domain of CREB." FEBS Lett. 1998; 430(3): 317-322. PubMed: 9688563
- Radhakrishnan I, Perez-Alvarado GC, Parker D, Dyson HJ, Montminy MR, Wright PE. "Solution structure of the KIX domain of CBP bound to the transactivation domain of CREB: a model for activator:coactivator interactions." Cell. 1997; 91(6): 741-752. PubMed: 9413984
| Comments:Upon binding to the KIX domain of the CREB binding protein this region forms two alpha helices, alphaA and alphaB. The two fold into mutually perpendicular helices that run from Asp-120 to Ser-129 and Pro-132 to Asp-144, respectively.
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| Region 3 | | Type: | Disordered | | Name: | pKID | | Location: | 146 - 160 | | Length: | 15 | | Region sequence: |
PGVPRIEEEKSEEET | | Modification type: | Engineered
Fragment
| | PDB: | 1KDX:B | | Structural/functional type: | Function arises from the disordered state
| | Functional classes: | Unknown
| | Functional subclasses: | Unknown
| Detection methods:
- Nuclear magnetic resonance (NMR) (315 K; pH: 5.5; acetate-d (buffer); guanidinium hydrochloride (solubilization) 0.6 M; NaCl (salt, buffer) 50 mM; Tris-d (buffer) 20 mM)
- Nuclear magnetic resonance (NMR) (290 K; pH: 5.5; acetate-d (buffer); guanidinium hydrochloride (solubilization) 0.6 M; NaCl (salt, buffer) 50 mM; Tris-d (buffer) 20 mM)
| References:
- Radhakrishnan I, Perez-Alvarado GC, Parker D, Dyson HJ, Montminy MR, Wright PE. "Solution structure of the KIX domain of CBP bound to the transactivation domain of CREB: a model for activator:coactivator interactions." Cell. 1997; 91(6): 741-752. PubMed: 9413984
| Comments:Upon binding to the KIX domain of the CREB binding protein this region remains unstructured.
The PDB reference 1KDX chain B has the disordered region from residues 147-160.
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| References |
- Gonzales G, Yamamoto K, Fischer W, Karr D, Menzel P, Biggs W, Vale W, Montminy M. "A cluster of phosphorylation sites on the cyclic AMP-regulated nuclear factor CREB predicted by its sequence." Nature. 1989; 337: 749-752.
- 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; 19(15): 4290. PubMed: 1831258
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