In biochemistry, the KIX domain (kinase-inducible domain (KID) interacting domain) or CREB binding domain is a

protein domain In molecular biology, a protein domain is a region of a protein's polypeptide chain that is self-stabilizing and that folds independently from the rest. Each domain forms a compact folded three-dimensional structure. Many proteins consist of ...

of the

eukaryotic Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacte ...

transcriptional coactivators CBP and P300. It serves as a docking site for the formation of

heterodimer In biochemistry, a protein dimer is a macromolecular complex formed by two protein monomers, or single proteins, which are usually non-covalently bound. Many macromolecules, such as proteins or nucleic acids, form dimers. The word ''dimer'' ha ...

s between the coactivator and specific

transcription factor In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The f ...

s. 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. 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). The

paralogous Sequence homology is the biological homology between DNA, RNA, or protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments of DNA can have shared ancestry because of three phenomena: either a spe ...

coactivators CBP ( CREBBP) and P300 (

EP300 Histone acetyltransferase p300 also known as p300 HAT or E1A-associated protein p300 (where E1A = adenovirus early region 1A) also known as EP300 or p300 is an enzyme that, in humans, is encoded by the ''EP300'' gene. It functions as histone acet ...

) are recruited to DNA-bound

s to activate transcription. Coactivators can associate with promoters and enhancers in the DNA only indirectly through protein-protein contacts with

s. CBP and P300 activate transcription synergistically in two ways: first, by remodelling and relaxing

chromatin Chromatin is a complex of DNA and protein found in eukaryote, eukaryotic cells. The primary function is to package long DNA molecules into more compact, denser structures. This prevents the strands from becoming tangled and also plays important ...

through their intrinsic

histone acetyltransferase Histone acetyltransferases (HATs) are enzymes that acetylate conserved lysine amino acids on histone proteins by transferring an acetyl group from acetyl-CoA to form ε-''N''-acetyllysine. DNA is wrapped around histones, and, by transferring an ...

activity, and second, by recruiting the basal transcription machinery, such as

RNA polymerase II RNA polymerase II (RNAP II and Pol II) is a multiprotein complex that transcribes DNA into precursors of messenger RNA (mRNA) and most small nuclear RNA (snRNA) and microRNA. It is one of the three RNAP enzymes found in the nucleus of euka ...

. 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. Additional instances include

RECQL5 ATP-dependent DNA helicase Q5 is an enzyme that in humans is encoded by the ''RECQL5'' gene. Interactions RECQL5 has been shown to interact with EEF1G Elongation factor 1-gamma is a protein that in humans is encoded by the ''EEF1G'' gene. ...

and related plant proteins. 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.

The full CBP/P300 protein

Aside from the KIX domain, CBP and P300 contain many other protein binding domains that should not be confused (numbers are aa numberings): * CH1/TAZ1 domain, CBP 47–433 P300 23-423ref name="Both UniProt">

UniProt UniProt is a freely accessible database of protein sequence and functional information, many entries being derived from genome sequencing projects. It contains a large amount of information about the biological function of proteins derived from ...

and InterPro entry for CBP () and P300 () * KIX domain, CBP 87–666 P300 66–645ref name="Both UniProt"/> *

Bromodomain A bromodomain is an approximately 110 amino acid protein domain that recognizes acetylated lysine residues, such as those on the ''N''-terminal tails of histones. Bromodomains, as the "readers" of lysine acetylation, are responsible in transducin ...

, CBP 103–1175 P300 067–1139ref name="Both UniProt"/> * CH2 domain (), CBP 191–1317 P300 155-1280 * HAT domain, CBP 323–1700 P300 287–1663ref name="Both UniProt"/> * CH3/ZZ domain, CBP 701-1744 P300 664-1707ref name="Both UniProt"/> * CH3/TAZ2 domain, CBP 765–1846 P300 728-1809ref name="Both UniProt"/> * IRF-3 binding (i-BiD), nuclear receptor coactivator binding (NCBD), or SRC1 interaction domain (SID; ), CBP 020-2113 P300 992-2098 All three CH (cysteine/histidine-rich) domains are

zinc finger A zinc finger is a small protein structural motif that is characterized by the coordination of one or more zinc ions (Zn2+) in order to stabilize the fold. It was originally coined to describe the finger-like appearance of a hypothesized struct ...

Interactions

Human and animal proteins: Yeast proteins: Viral proteins:

References

{{reflist, 30em

External links

KIXBASE
a database of KIX-superfamily domains and PDB structures
HMM training dataset
Protein domains Gene expression