CIITA is a human
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 b ...
which encodes 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, respon ...
called the class II, major histocompatibility complex, transactivator.
Mutations in this gene are responsible for the
bare lymphocyte syndrome
Bare lymphocyte syndrome is a condition caused by mutations in certain genes of the major histocompatibility complex or involved with the processing and presentation of MHC molecules. It is a form of severe combined immunodeficiency.
Presentation
...
in which the
immune system
The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as Tumor immunology, cancer cells and objects such ...
is severely compromised and cannot effectively fight
infection
An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable d ...
.
Chromosomal rearrangement of CIITA is involved in the pathogenesis of
Hodgkin lymphoma
Hodgkin lymphoma (HL) is a type of lymphoma, in which cancer originates from a specific type of white blood cell called lymphocytes, where multinucleated Reed–Sternberg cells (RS cells) are present in the patient's lymph nodes. The condition ...
and
primary mediastinal B cell lymphoma
Primary mediastinal B-cell lymphoma, abbreviated PMBL, is a rare type of lymphoma that forms in the mediastinum (the space in between the lungs) and predominantly affects young adults.
It is a subtype of diffuse large B-cell lymphoma; however, it ...
.
Function
CIITA
mRNA
In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of synthesizing a protein.
mRNA is created during the ...
can only be detected in
human leukocyte antigen
The human leukocyte antigen (HLA) system or complex is a complex of genes on chromosome 6 in humans which encode cell-surface proteins responsible for the regulation of the immune system. The HLA system is also known as the human version of t ...
(HLA) system class II-positive cell lines and tissues. This highly restricted tissue distribution suggests that expression of HLA class II genes is to a large extent under the control of CIITA.
However CIITA does not appear to directly bind to DNA.
Instead CIITA functions through activation of the
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 fu ...
RFX5
DNA-binding protein RFX5 is a protein that in humans is encoded by the ''RFX5'' gene.
Function
A lack of MHC-II expression results in a severe immunodeficiency syndrome called MHC-II deficiency, or the bare lymphocyte syndrome (BLS; MIM 209920 ...
.
Hence CIITA is classified as a transcriptional
coactivator
A coactivator is a type of transcriptional coregulator that binds to an activator (a transcription factor) to increase the rate of transcription of a gene or set of genes. The activator contains a DNA binding domain that binds either to a DNA ...
.
The CIITA protein contains an acidic
transcriptional activation domain, 4 LRRs (
leucine-rich repeat
A leucine-rich repeat (LRR) is a protein structural motif that forms an α/β horseshoe fold. It is composed of repeating 20–30 amino acid stretches that are unusually rich in the hydrophobic amino acid leucine. These tandem repeats common ...
s) and a
GTP binding domain.
The protein uses GTP binding to facilitate its own transport into the nucleus.
Once in the nucleus, the protein acts as a positive regulator of class II major histocompatibility complex
gene transcription
Transcription is the process of copying a segment of DNA into RNA. The segments of DNA transcribed into RNA molecules that can encode proteins are said to produce messenger RNA (mRNA). Other segments of DNA are copied into RNA molecules calle ...
, and is often referred to as the "master control factor" for the expression of these genes.
CIITA expression is induced by
interferon gamma
Interferon gamma (IFN-γ) is a dimerized soluble cytokine that is the only member of the type II class of interferons. The existence of this interferon, which early in its history was known as immune interferon, was described by E. F. Wheelock ...
, possibly assisted by other signals.
expression in
intestinal epithelial cells is upregulated under
inflammation
Inflammation (from la, wikt:en:inflammatio#Latin, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or Irritation, irritants, and is a protective response involving im ...
.
Interactions
CIITA 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 organizat ...
with:
*
MAPK1
Mitogen-activated protein kinase 1, (MAPK 1), also known as ERK2, is an enzyme that in humans is encoded by the ''MAPK1'' gene.
Function
The protein encoded by this gene is a member of the MAP kinase family. MAP kinases, also known as extrace ...
,
*
Nuclear receptor coactivator 1
The nuclear receptor coactivator 1 (''NCOA1'') is a transcriptional coregulatory protein that contains several nuclear receptor interacting domains and an intrinsic histone acetyltransferase activity. NCOA1 is recruited to DNA promotion sites by l ...
,
*
RFX5
DNA-binding protein RFX5 is a protein that in humans is encoded by the ''RFX5'' gene.
Function
A lack of MHC-II expression results in a severe immunodeficiency syndrome called MHC-II deficiency, or the bare lymphocyte syndrome (BLS; MIM 209920 ...
,
*
RFXANK
DNA-binding protein RFXANK is a protein that in humans is encoded by the ''RFXANK'' gene.
Function
Major histocompatibility (MHC) class II molecules are transmembrane proteins that have a central role in development and control of the immune s ...
,
XPO1
Exportin 1 (XPO1), also known as chromosomal region maintenance 1 (CRM1), is a eukaryotic protein that mediates the nuclear export of various proteins and RNAs.
History
XPO1 (CRM1) originally was identified in the fission yeast ''Schizosaccharom ...
,ZXDC Zinc finger, X-linked, duplicated family member C (ZXDC) is a human CIITA-binding protein involved in the activation of major histocompatibility complex (MHC) class I and II. For binding to occur, ZXDC must form an oligomeric complex with another ...
.
See also
* MHC class II
MHC Class II molecules are a class of major histocompatibility complex (MHC) molecules normally found only on professional antigen-presenting cells such as dendritic cells, mononuclear phagocytes, some endothelial cells, thymic epithelial cells, ...
References
External links
*
*
LRR proteins
NOD-like receptors
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