KIX domain
| KIX | |||||||||
|---|---|---|---|---|---|---|---|---|---|
 Complex between the KIX domain of CBP (yellow, green and cyan) and the C-terminal transactivation domain of p65/RELA (red)[1] | |||||||||
| Identifiers | |||||||||
| Symbol | KIX | ||||||||
| Pfam | PF02172 | ||||||||
| InterPro | IPR003101 | ||||||||
| |||||||||
In biochemistry, the KIX domain (kinase-inducible domain (KID) interacting domain) or CREB binding domain is a protein domain of the eukaryotic transcriptional coactivators CBP and P300. It serves as a docking site for the formation of heterodimers between the coactivator and specific transcription factors. Structurally, the KIX domain is a globular domain consisting of three α-helices and two short 310-helices.
The KIX domain was originally discovered in 1996 as the specific and minimal region in CBP that binds and interacts with phosphorylated CREB to activate transcription.[2] It was thus first termed CREB-binding domain. However, when it was later discovered that it also binds many other proteins, the more general name KIX domain became favoured.
The coactivators CBP (CREBBP) and P300 (EP300) are recruited to DNA-bound transcription factors to activate transcription. Coactivators can associate with promoters and enhancers in the DNA only indirectly through protein-protein contacts with transcription factors. CBP and P300 activate transcription synergistically in two ways: first, by remodelling and relaxing chromatin through their intrinsic histone acetyltransferase activity, and second, by recruiting the basal transcription machinery, such as RNA polymerase II.[3]
Aside from the KIX domain, CBP and P300 contain many other protein binding domains that should not be confused:
- TAZ1 domain, aa 347–433 of 2442 in human CBP[4]
- KIX domain, aa 587–666[4]
- CH2 (cysteine/histidine-rich) domain, aa 1192–1318 in mouse CBP, directly preceding the HAT domain[5]
- TAZ2 domain, aa 1765–1846[4]
- IBiD (IRF-3 binding) domain,[6] also known as NCBD (nuclear receptor coactivator binding) domain[7] and SID (SRC1 interaction domain),[8] and mapped to aa 2067–2112, aa 2059–2117, or aa 2058–2130, respectively.
The KIX domain contains two separate binding sites: the "c-Myb site", named after the oncoprotein c-Myb, and the "MLL site", named after the proto-oncogene MLL (Mixed Lineage Leukemia, KMT2A).[9]
The KIX domain belongs to the proposed GACKIX domain superfamily. GACKIX comprises structurally and functionally highly homologous domains in related proteins. It is named after the protein GAL11 / ARC105 (MED15), the plant protein CBP-like, and the KIX domain from CBP and P300.[10] All of these contain a KIX domain or KIX-related domain that interacts with the transactivation domain of many different transcription factors. The distinction between a KIX domain, a KIX-related domain and a GACKIX domain is subject to an ongoing debate and not clearly defined.
Interactions
Human and animal proteins:
- ARNTL (BMAL1)[11][12]
- ATF1[13]
- ATF4 (CREB2)[13]
- BRCA1[3][13]
- CREB[6]
- Cubitus interruptus (in D. melanogaster)[3][13]
- ELK4 (SAP1)[13]
- FOXO3 (FOXO3a)[14]
- GLI3[13]
- JUN (c-Jun)[3][13]
- KMT2A (MLL)[15][3]
- MYB (c-Myb)[3][13]
- NFE2 (NF-E2 p45)[13]
- RELA (NF-κB p65)[1]
- SREBP[3][13]
- STAT1[3]
- TCF3 (E2A)[16]
- TP53 (p53)[3]
- YY1[13]
Yeast proteins:
Viral proteins:
- Regulatory protein E2 (from Human papillomavirus)[3][13]
- Tat (from HIV-1)[3]
- Tax (from Deltaretrovirus)[3][13]
References
- 1 2 Lecoq, Lauriane; Raiola, Luca; Chabot, Philippe R.; Cyr, Normand; Arseneault, Geneviève; Legault, Pascale; Omichinski, James G. (2017). "Structural characterization of interactions between transactivation domain 1 of the p65 subunit of NF-κB and transcription regulatory factors". Nucleic Acids Research. 45 (9): 5564. PMID 28334776. doi:10.1093/nar/gkx146.
- ↑ Parker, D; Ferreri, K; Nakajima, T; Lamorte, V J; Evans, R; Koerber, S C; Hoeger, C; Montminy, M R (1996). "Phosphorylation of CREB at Ser-133 induces complex formation with CREB-binding protein via a direct mechanism". Molecular and Cellular Biology. 16 (2): 694. PMID 8552098. doi:10.1128/MCB.16.2.694.
- 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 Thakur, J. K.; Yadav, A.; Yadav, G. (2013). "Molecular recognition by the KIX domain and its role in gene regulation". Nucleic Acids Research. 42 (4): 2112. PMID 24253305. doi:10.1093/nar/gkt1147.
- 1 2 3 UniProt entry for CBP, ID Q92793
- ↑ Park, Sangho; Martinez-Yamout, Maria A.; Dyson, H. Jane; Wright, Peter E. (2013). "The CH2 domain of CBP/p300 is a novel zinc finger". FEBS Letters. 587 (16): 2506. PMID 23831576. doi:10.1016/j.febslet.2013.06.051.
- 1 2 Lin CH, Hare BJ, Wagner G, Harrison SC, Maniatis T, Fraenkel E (September 2001). "A small domain of CBP/p300 binds diverse proteins: solution structure and functional studies". Mol. Cell. 8 (3): 581–90. PMID 11583620. doi:10.1016/S1097-2765(01)00333-1.
- ↑ Demarest, S. J.; Deechongkit, S; Dyson, H. J.; Evans, R. M.; Wright, P. E. (2004). "Packing, specificity, and mutability at the binding interface between the p160 coactivator and CREB-binding protein". Protein Science. 13 (1): 203–10. PMC 2286511
. PMID 14691235. doi:10.1110/ps.03366504. - ↑ Sheppard, H. M.; Harries, J. C.; Hussain, S; Bevan, C; Heery, D. M. (2001). "Analysis of the steroid receptor coactivator 1 (SRC1)-CREB binding protein interaction interface and its importance for the function of SRC1". Molecular and Cellular Biology. 21 (1): 39–50. PMC 86566 . PMID 11113179. doi:10.1128/MCB.21.1.39-50.2001.
- ↑ Goto, N. K.; Zor, T; Martinez-Yamout, M; Dyson, H. J.; Wright, P. E. (2002). "Cooperativity in transcription factor binding to the coactivator CREB-binding protein (CBP). The mixed lineage leukemia protein (MLL) activation domain binds to an allosteric site on the KIX domain". Journal of Biological Chemistry. 277 (45): 43168–74. PMID 12205094. doi:10.1074/jbc.M207660200.
- ↑ Novatchkova, Maria; Eisenhaber, Frank (2004). "Linking transcriptional mediators via the GACKIX domain super family". Current Biology. 14 (2): R54. PMID 14738747. doi:10.1016/j.cub.2003.12.042.
- ↑ Takahata, Sho; Ozaki, Takahiro; Mimura, Junsei; Kikuchi, Yasuo; Sogawa, Kazuhiro; Fujii-Kuriyama, Yoshiaki (2000). "Transactivation mechanisms of mouse clock transcription factors, mClock and mArnt3". Genes to Cells. 5 (9): 739. PMID 10971655. doi:10.1046/j.1365-2443.2000.00363.x.
- ↑ Xu, Haiyan; Gustafson, Chelsea L; Sammons, Patrick J; Khan, Sanjoy K; Parsley, Nicole C; Ramanathan, Chidambaram; Lee, Hsiau-Wei; Liu, Andrew C; Partch, Carrie L (2015). "Cryptochrome 1 regulates the circadian clock through dynamic interactions with the BMAL1 C terminus". Nature Structural & Molecular Biology. 22 (6): 476. PMC 4456216 . PMID 25961797. doi:10.1038/nsmb.3018.
- 1 2 3 4 5 6 7 8 9 10 11 12 13 Vo, Ngan; Goodman, Richard H. (2001). "CREB-binding Protein and p300 in Transcriptional Regulation". Journal of Biological Chemistry. 276 (17): 13505. PMID 11279224. doi:10.1074/jbc.R000025200.
- ↑ Wang, Feng; Marshall, Christopher B.; Li, Guang-Yao; Yamamoto, Kazuo; Mak, Tak W.; Ikura, Mitsuhiko (2009). "Synergistic Interplay between Promoter Recognition and CBP/p300 Coactivator Recruitment by FOXO3a". ACS Chemical Biology. 4 (12): 1017. PMID 19821614. doi:10.1021/cb900190u.
- ↑ Ernst, P; Wang, J; Huang, M; Goodman, R. H.; Korsmeyer, S. J. (2001). "MLL and CREB bind cooperatively to the nuclear coactivator CREB-binding protein". Molecular and Cellular Biology. 21 (7): 2249–58. PMC 86859 . PMID 11259575. doi:10.1128/MCB.21.7.2249-2258.2001.
- ↑ Bradney C, Hjelmeland M, Komatsu Y, Yoshida M, Yao TP, Zhuang Y (Jan 2003). "Regulation of E2A activities by histone acetyltransferases in B lymphocyte development". The Journal of Biological Chemistry. 278 (4): 2370–6. PMID 12435739. doi:10.1074/jbc.M211464200.