CIITA is a human
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
which encodes a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
called the class II, major histocompatibility complex, transactivator.
Mutations in this gene are responsible for the
bare lymphocyte syndrome in which the
immune system
The immune system is a network of biological systems that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to bacteria, as well as Tumor immunology, cancer cells, Parasitic worm, parasitic ...
is severely compromised and cannot effectively fight
infection
An infection is the invasion of tissue (biology), tissues by pathogens, their multiplication, and the reaction of host (biology), host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmis ...
.
Chromosomal rearrangement of CIITA is involved in the pathogenesis of
Hodgkin lymphoma and
primary mediastinal B cell lymphoma.
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 Protein biosynthesis, synthesizing a protein.
mRNA is ...
can only be detected in
human leukocyte antigen
The human leukocyte antigen (HLA) system is a complex of genes on chromosome 6 in humans that encode cell-surface proteins responsible for regulation of the immune system. The HLA system is also known as the human version of the major histo ...
(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 (genetics), transcription of genetics, genetic information from DNA to messenger RNA, by binding t ...
RFX5
DNA-binding protein RFX5 is a protein that in humans is encoded by the ''RFX5'' gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is ...
.
Hence CIITA is classified as a transcriptional
coactivator.
The CIITA protein contains an acidic
transcriptional activation domain, 4 LRRs (
leucine-rich repeats) 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, and is often referred to as the "master control factor" for the expression of these genes.
CIITA expression is induced by
interferon gamma, possibly assisted by other signals.
expression in
intestinal epithelial cells is upregulated under
inflammation
Inflammation (from ) is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. The five cardinal signs are heat, pain, redness, swelling, and loss of function (Latin ''calor'', '' ...
.
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 advocating for the legal and human rights of children with intersex traits. The organization was founded in 2006 and fo ...
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 extracell ...
,
*
Nuclear receptor coactivator 1
The nuclear receptor coactivator 1 (NCOA1), also called steroid receptor coactivator-1 (SRC-1), is a transcriptional coregulatory protein that contains several nuclear receptor–interacting domains and possesses intrinsic histone acetyltransfer ...
,
*
RFX5
DNA-binding protein RFX5 is a protein that in humans is encoded by the ''RFX5'' gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is ...
,
*
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 ''Schizosacchar ...
,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) MHC Class I, class I and MHC Class II, II. For binding to occur, ZXDC must form an olig ...
.
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, macrophages, some endothelial cells, thymic epithelial cells, and B cell ...
References
External links
*
*
LRR proteins
NOD-like receptors
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