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
Pfam clan
CL0589
InterPro
IPR003101
CATH
1sb0
SCOP2
1sb0 / SCOPe / SUPFAM
Available protein structures:
Pfam
structures / ECOD
PDB
RCSB PDB; PDBe; PDBj
PDBsum
structure summary
KIX (MED15)
Identifiers
Symbol
KIX_2
Pfam
PF16987
InterPro
IPR036546
Available protein structures:
Pfam
structures / ECOD
PDB
RCSB PDB; PDBe; PDBj
PDBsum
structure summary
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 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).[3]
The paralogous 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.[4]
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.[5] Additional instances include RECQL5 and related plant proteins.[6][7] 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.
^Lecoq L, Raiola L, Chabot PR, Cyr N, Arseneault G, Legault P, Omichinski JG (May 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): 5564–5576. doi:10.1093/nar/gkx146. PMC 5435986. PMID 28334776.
^Parker D, Ferreri K, Nakajima T, LaMorte VJ, Evans R, Koerber SC, et al. (February 1996). "Phosphorylation of CREB at Ser-133 induces complex formation with CREB-binding protein via a direct mechanism". Molecular and Cellular Biology. 16 (2): 694–703. doi:10.1128/MCB.16.2.694. PMC 231049. PMID 8552098.
^Goto NK, Zor T, Martinez-Yamout M, Dyson HJ, Wright PE (November 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". The Journal of Biological Chemistry. 277 (45): 43168–74. CiteSeerX 10.1.1.615.9401. doi:10.1074/jbc.M207660200. PMID 12205094.
^Thakur JK, Yadav A, Yadav G (February 2014). "Molecular recognition by the KIX domain and its role in gene regulation". Nucleic Acids Research. 42 (4): 2112–25. doi:10.1093/nar/gkt1147. PMC 3936767. PMID 24253305.
^Novatchkova M, Eisenhaber F (January 2004). "Linking transcriptional mediators via the GACKIX domain super family". Current Biology. 14 (2): R54-5. doi:10.1016/j.cub.2003.12.042. PMID 14738747.
^Popuri V, Ramamoorthy M, Tadokoro T, Singh DK, Karmakar P, Croteau DL, Bohr VA (July 2012). "Recruitment and retention dynamics of RECQL5 at DNA double strand break sites". DNA Repair. 11 (7): 624–35. doi:10.1016/j.dnarep.2012.05.001. PMC 3374033. PMID 22633600.
^Yadav A, Thakur JK, Yadav G (November 2017). "KIXBASE: A comprehensive web resource for identification and exploration of KIX domains". Scientific Reports. 7 (1): 14924. Bibcode:2017NatSR...714924Y. doi:10.1038/s41598-017-14617-0. PMC 5668377. PMID 29097748.
In biochemistry, the KIXdomain (kinase-inducible domain (KID) interacting domain) or CREB binding domain is a protein domain of the eukaryotic transcriptional...
Look up kix in Wiktionary, the free dictionary. Kix or KIX may refer to: Kix Brooks (born 1955), member of the country music duo Brooks & Dunn Kix (band)...
interact with TAF9, GCN5 and with multiple domains of CBP/p300 (KIX, TAZ1,TAZ2 and IBiD). The KIXdomain of general coactivators Med15(Gal11) interacts...
mixed lineage leukemia protein (MLL) activation domain binds to an allosteric site on the KIXdomain" (PDF). The Journal of Biological Chemistry. 277...
by one or more of p300 domains: the nuclear receptor interaction domain (RID), the KIXdomain (CREB and MYB interaction domain), the cysteine/histidine...
However, TSA treatments in CBP mutants lacking KIXdomains did not effect LTP in mice (Fig 1D). The KIXdomain allows for interaction between CREB and CBP...
Wright PE (Dec 1997). "Solution structure of the KIXdomain of CBP bound to the transactivation domain of CREB: a model for activator:coactivator interactions"...
chloride. INCYPRO has also been applied to stabilize the human adaptor KIXdomain utilizing different crosslinker molecules. Here, a dependency of protein...
factors. The 9aaTAD transactivation domains of E proteins and MLL are very similar and both bind to the KIXdomain of general transcriptional mediator...
"Roles of Phosphorylation and Helix Propensity in the Binding of the KIXDomain of CREB-binding Protein by Constitutive (c-Myb) and Inducible (CREB) Activators"...
transcription factors share the same transactivation domain, 9aaTAD, which directly interacts with KIXdomain of the MED15. Furthermore, human MED15 cooperates...
– Eternity Kataklysm - Sorcery Katatonia - For Funerals to Come... (EP) Kix – Show Business King Diamond – The Spider's Lullabye Konkhra – Spit or Swallow...
Viking, 2004. (Chapter on Betty Crocker in a popular book with footnotes.) Official website Works by Betty Crocker at LibriVox (public domain audiobooks)...
managed by one or more CREB domains: the nuclear receptor interaction domain (RID), the CREB and MYB interaction domain (KIX), the cysteine/histidine regions...
program offered the Kix Blackout Kit. Some premiums were rather anachronistic for a 19th-century hero. In 1947, the program offered the Kix Atomic Bomb Ring...
United States Postal Service (no international standard available) RM4SCC / KIX Discrete 4 bar heights Royal Mail / PostNL RM Mailmark C Discrete 4 bar heights...
Exchange (NYC - Manhattan)". "New York Internet Exchange Home". "IIX". "This Domain Has Expired". Archived from the original on 2007-04-05. Retrieved 2015-04-29...
Earth Day-themed single in 1990 entitled "Tomorrow's World", written by Kix Brooks (who would later become one-half of Brooks & Dunn) and Pam Tillis...
First Post. Retrieved on 2009-06-16. Shaziya Ramji, Video Interview with Kix Magazine on YouTube. March 23, 2011. Accessed May 5, 2011 Sparks, Marvin...
Global Information