Transformation/transcription domain-associated protein, also known as TRRAP, is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

that in humans is encoded by the ''TRRAP''

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

. TRRAP belongs to the

phosphatidylinositol 3-kinase-related kinase Phosphatidylinositol 3-kinase-related kinases (PIKKs) are a family of Ser/Thr-protein kinases with sequence similarity to phosphatidylinositol-3 kinases ( PI3Ks). Members The human PIKK family includes six members: Structure PIKKs protei ...

protein family.

Function

TRRAP is an adaptor protein, which is found in various multiprotein

chromatin Chromatin is a complex of DNA and protein found in 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 roles in r ...

complexes with

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 (HAT), which in turn is responsible for

epigenetic In biology, epigenetics is the study of stable phenotypic changes (known as ''marks'') that do not involve alterations in the DNA sequence. The Greek prefix '' epi-'' ( "over, outside of, around") in ''epigenetics'' implies features that are "o ...

transcription Transcription refers to the process of converting sounds (voice, music etc.) into letters or musical notes, or producing a copy of something in another medium, including: Genetics * Transcription (biology), the copying of DNA into RNA, the fir ...

activation. TRRAP has a central role in

MYC ''Myc'' is a family of regulator genes and proto-oncogenes that code for transcription factors. The ''Myc'' family consists of three related human genes: ''c-myc'' (MYC), ''l-myc'' (MYCL), and ''n-myc'' (MYCN). ''c-myc'' (also sometimes referre ...

(c-Myc) transcription activation, and also participates in cell transformation by MYC. It is required for p53/

TP53 p53, also known as Tumor protein P53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory protein that is often mutated in human cancers. The p53 proteins (originally thought to be, and often s ...

E2F1 Transcription factor E2F1 is a protein that in humans is encoded by the ''E2F1'' gene. Function The protein encoded by this gene is a member of the E2F family of transcription factors. The E2F family plays a crucial role in the control of cell ...

-, and

E2F4 Transcription factor E2F4 is a protein that in humans is encoded by the ''E2F4'' gene. Function The protein encoded by this gene is a member of the E2F family of transcription factors. The E2F family plays a crucial role in the control of c ...

-mediated transcription activation. It is also involved in transcription activation mediated by the

adenovirus Adenoviruses (members of the family ''Adenoviridae'') are medium-sized (90–100 nm), nonenveloped (without an outer lipid bilayer) viruses with an icosahedral nucleocapsid containing a double-stranded DNA genome. Their name derives from the ...

E1A, a viral

oncoprotein An oncogene is a gene that has the potential to cause cancer. In tumor cells, these genes are often mutated, or expressed at high levels.

that deregulates transcription of key genes. TRRAP is also required for the

mitotic checkpoint Cell cycle checkpoints are control mechanisms in the eukaryotic cell cycle which ensure its proper progression. Each checkpoint serves as a potential termination point along the cell cycle, during which the conditions of the cell are assessed, wi ...

and normal

cell cycle The cell cycle, or cell-division cycle, is the series of events that take place in a cell that cause it to divide into two daughter cells. These events include the duplication of its DNA (DNA replication) and some of its organelles, and subs ...

progression. The MRN complex (composed of

MRE11 Double-strand break repair protein MRE11 is an enzyme that in humans is encoded by the ''MRE11'' gene. The gene has been designated ''MRE11A'' to distinguish it from the pseudogene ''MRE11B'' that is nowadays named ''MRE11P1''. Function This ge ...

RAD50 DNA repair protein RAD50, also known as RAD50, is a protein that in humans is encoded by the ''RAD50'' gene. Function The protein encoded by this gene is highly similar to ''Saccharomyces cerevisiae'' Rad50, a protein involved in DNA double- ...

, and

NBS1 Nibrin, also known as NBN or NBS1, is a protein which in humans is encoded by the ''NBN'' gene. Function Nibrin is a protein associated with the repair of double strand breaks (DSBs) which pose serious damage to a genome. It is a 754 amino ac ...

) is involved in the detection and repair of DNA

double-strand breaks DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA dama ...

(DSBs). TRRAP associates with the MRN complex and when TRRAP is removed, the complex shows reduced cDNA end-joining activity. Hence, TRRAP may function as a link between DSB repair and chromatin remodeling.

Model organisms

Model organism A model organism (often shortened to model) is a non-human species that is extensively studied to understand particular biological phenomena, with the expectation that discoveries made in the model organism will provide insight into the workin ...

s have been used in the study of TRRAP function. A conditional

knockout mouse A knockout mouse, or knock-out mouse, is a genetically modified mouse (''Mus musculus'') in which researchers have inactivated, or "knocked out", an existing gene by replacing it or disrupting it with an artificial piece of DNA. They are importan ...

line, called ''Trrap^{tm1a(EUCOMM)Wtsi}'' was generated as part of the

International Knockout Mouse Consortium The International Knockout Mouse Consortium (IKMC) is a scientific endeavour to produce a collection of mouse embryonic stem cell lines that together lack every gene in the genome, and then to distribute the cells to scientific researchers to crea ...

program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists. Male and female animals underwent a standardized

phenotypic screen In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological proper ...

to determine the effects of deletion. Twenty four tests were carried out on

mutant In biology, and especially in genetics, a mutant is an organism or a new genetic character arising or resulting from an instance of mutation, which is generally an alteration of the DNA sequence of the genome or chromosome of an organism. It ...

mice and two significant abnormalities were observed. No

homozygous Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism. Mo ...

embryos were identified during gestation, and therefore none survived until

weaning Weaning is the process of gradually introducing an infant human or another mammal to what will be its adult diet while withdrawing the supply of its mother's milk. The process takes place only in mammals, as only mammals produce milk. The infan ...

. The remaining tests were carried out on

heterozygous Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism. Mo ...

mutant adult mice; no significant abnormalities were observed in these animals.

Interactions

Transformation/transcription domain-associated protein has been shown to

interact Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...

with: *

ACTL6A Actin-like protein 6A is a protein that in humans is encoded by the ''ACTL6A'' gene. Function This gene encodes a family member of actin-related proteins (ARPs), which share significant amino acid sequence identity to conventional actins. Both ...

, *

EP400 E1A-binding protein p400 is a protein that in humans is encoded by the ''EP400'' gene. Interactions EP400 has been shown to interact with Transformation/transcription domain-associated protein, RuvB-like 1 RuvB-like 1 (E. coli), also known as R ...

, * MAX, *

Myc ''Myc'' is a family of regulator genes and proto-oncogenes that code for transcription factors. The ''Myc'' family consists of three related human genes: ''c-myc'' (MYC), ''l-myc'' (MYCL), and ''n-myc'' (MYCN). ''c-myc'' (also sometimes referre ...

, *

PCAF P300/CBP-associated factor (PCAF), also known as K(lysine) acetyltransferase 2B (KAT2B), is a human gene and transcriptional coactivator associated with p53. Structure Several domains of PCAF can act independently or in unison to enable its funct ...

, * SUPT3H, and *

TAF9 TAF9 RNA polymerase II, TATA box binding protein (TBP)-associated factor, 32kDa, also known as TAF9, is a protein that in humans is encoded by the ''TAF9'' gene. Function Initiation of transcription by RNA polymerase II requires the activities ...

. and

Function

Model organisms

Interactions

References

Further reading