MHC class III

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MHC class III is a group of proteins belonging the class of major histocompatibility complex (MHC). Unlike other MHC types such as MHC class I and MHC class II, of which their structure and functions in immune response are well defined, MHC class III are poorly defined structurally and functionally. They are not involved in antigen binding (the process called antigen presentation, a classic function of MHC proteins). Only few of them are actually involved in immunity while many are signalling molecules in other cell communications. They are mainly known from their genes because their gene cluster is present between those of class I and class II. [1] The gene cluster was discovered when genes (specifically those of complement components C2, C4, and factor B) were found in between class I and class II genes on the short (p) arm of human chromosome 6. It was later found that it contains many genes for different signalling molecules such as tumour necrosis factors (TNFs) and heat shock proteins. More than 60 MHC class III genes are described, which is about 28% of the total MHC genes (224). [2] The region previously considered within MHC class III gene cluster that contains genes for TNFs is now known as MHC class IV [3] or inflammatory region. [4]

Contents

In contrast to other MHC proteins, MHC class III proteins are produced by liver cells (hepatocytes) and special white blood cells (macrophages), among others.

Gene structure

MHC class III genes are located on chromosome 6 (6p21.3) in humans. It covers 700 kb and contains 61 genes. The gene cluster is the most gene-dense region of the human genome. They are basically similar with those of other animals. The functions of many genes are yet unknown. [5] Many retroelements such as human endogenous retrovirus (HERV) and Alu elements are located in the cluster. [6] The region containing genes STK19(G11)/C4/Z/CYP21/X/Y, varying in size from 142 to 214 kb, is known as the most complex gene cluster in the human genome. [7]

Diversity

MHC class III genes are similar in humans, mouse, frog ( Xenopus tropicalis ), and gray short-tailed opossum, but not all genes are common. For example, human NCR3 , MIC and MCCD1 are absent in mouse. Human NCR3 and LST1 are absent in opossum. [4] However, birds (chicken and quail) have only a single gene, which codes for a complement component gene (C4). [8] In fishes, the genes are distributed in different chromosomes. [9]

Related Research Articles

<span class="mw-page-title-main">MHC class I polypeptide–related sequence B</span> Protein-coding gene in the species Homo sapiens

MHC class I polypeptide-related sequence B (MICB) is a protein that is encoded by the MICB gene located within MHC locus. MICB is related to MHC class I and has similar domain structure, which is made up of external α1α2α3 domain, transmembrane segment and C-terminal cytoplasmic tail. MICB is a stress-induced ligand for NKG2D receptor. The heat shock stress pathway is involved in the regulation of MICB expression as transcription of MICB is regulated by promoter heat shock element.

<span class="mw-page-title-main">Lymphotoxin beta</span> Protein-coding gene in the species Homo sapiens

Lymphotoxin-beta (LT-beta) also known as tumor necrosis factor C (TNF-C) is a protein that in humans is encoded by the LTB gene.

<span class="mw-page-title-main">BAT1</span> Protein-coding gene in the species Homo sapiens

Spliceosome RNA helicase BAT1 is an enzyme that in humans is encoded by the BAT1 gene.

<span class="mw-page-title-main">RDBP</span> Protein

Negative elongation factor E is a protein that in humans is encoded by the RDBP gene.

<span class="mw-page-title-main">HSPA1L</span> Protein-coding gene in the species Homo sapiens

Heat shock 70 kDa protein 1L is a protein that in humans is encoded by the HSPA1L gene on chromosome 6. As a member of the heat shock protein 70 (Hsp70) family and a chaperone protein, it facilitates the proper folding of newly translated and misfolded proteins, as well as stabilize or degrade mutant proteins. Its functions contribute to biological processes including signal transduction, apoptosis, protein homeostasis, and cell growth and differentiation. It has been associated with an extensive number of cancers, neurodegenerative diseases, cell senescence and aging, and Graft-versus-host disease.

<span class="mw-page-title-main">PBX2</span> Protein found in humans

Pre-B-cell leukemia transcription factor 2 is a protein that in humans is encoded by the PBX2 gene.

<span class="mw-page-title-main">BAT2</span> Protein-coding gene in the species Homo sapiens

Large proline-rich protein BAT2 is a protein that in humans is encoded by the BAT2 gene.

<span class="mw-page-title-main">LST1</span> Protein-coding gene in the species Homo sapiens

Leukocyte-specific transcript 1 protein is a protein that in humans is encoded by the LST1 gene.

<span class="mw-page-title-main">Prefoldin subunit 6</span> Protein-coding gene in the species Homo sapiens

Prefoldin subunit 6 is a protein that in humans is encoded by the PFDN6 gene.

<span class="mw-page-title-main">OR2H2</span> Protein-coding gene in the species Homo sapiens

Olfactory receptor 2H2 is a protein that in humans is encoded by the OR2H2 gene.

<span class="mw-page-title-main">PPP1R11</span> Protein-coding gene in the species Homo sapiens

Protein phosphatase 1 regulatory subunit 11 is an enzyme that in humans is encoded by the PPP1R11 gene.

<span class="mw-page-title-main">NFKBIL1</span> Protein-coding gene in the species Homo sapiens

NF-kappa-B inhibitor-like protein 1 is a protein that in humans is encoded by the NFKBIL1 gene.

<span class="mw-page-title-main">STK19</span> Protein-coding gene in the species Homo sapiens

Serine/threonine-protein kinase 19 is an enzyme that in humans is encoded by the STK19 gene.

<span class="mw-page-title-main">DOM3Z</span> Protein-coding gene in the species Homo sapiens

Protein Dom3Z is a protein that in humans is encoded by the DOM3Z gene.

<span class="mw-page-title-main">Transmembrane protein 222</span> Protein-coding gene in the species Homo sapiens

Transmembrane protein 222 is a protein that in humans is encoded by the TMEM222 gene. One notable feature of the protein encoded by this gene is the presence of three predicted transmembrane domains. The TMEM222 protein is predicted to most likely localize to the secretory vesicles.

<span class="mw-page-title-main">BAT4</span> Protein-coding gene in the species Homo sapiens

Protein BAT4 is a protein that in humans is encoded by the BAT4 gene.

<span class="mw-page-title-main">PRSS16</span> Protein-coding gene in the species Homo sapiens

Thymus-specific serine protease is an enzyme that in humans is encoded by the PRSS16 gene.

<span class="mw-page-title-main">Complement component 4B</span> Protein-coding gene in the species Homo sapiens

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Lymphocyte antigen 6 complex, locus G6E (pseudogene) is a protein that in humans is encoded by the LY6G6E gene.

RCCX is a complex, multiallelic, and tandem copy number variation (CNV) human DNA locus on chromosome 6p21.3, a cluster located in the major histocompatibility complex (MHC) class III region. CNVs are segments of DNA that vary in copy number compared to a reference genome and play a significant role in human phenotypic variation and disease development. The RCCX cluster consists of one or more modules each having a series of genes close to each other: serine/threonine kinase 19 (STK19), complement 4 (C4), steroid 21-hydroxylase (CYP21), and tenascin-X (TNX).

References

  1. ↑ Gruen, JR; Weissman, SM (2001). "Human MHC class III and IV genes and disease associations". Frontiers in Bioscience. 6 (3): D960-172. doi:10.2741/A658. PMID   11487469.
  2. ↑ The MHC sequencing consortium (1999). "Complete sequence and gene map of a human major histocompatibility complex". Nature. 401 (6756): 921–923. Bibcode:1999Natur.401..921T. doi:10.1038/44853. PMID   10553908. S2CID   186243515.
  3. ↑ Gruen JR, Weissman SM. Human MHC class III and IV genes and disease associations. Front Biosci. 2001 Aug 1;6:D960-72. doi: 10.2741/gruen. PMID 11487469.
  4. 1 2 Deakin, Janine E; Papenfuss, Anthony T; Belov, Katherine; Cross, Joseph GR; Coggill, Penny; Palmer, Sophie; Sims, Sarah; Speed, Terence P; Beck, Stephan; Graves, Jennifer (2006). "Evolution and comparative analysis of the MHC Class III inflammatory region". BMC Genomics. 7 (1): 281. doi: 10.1186/1471-2164-7-281 . PMC   1654159 . PMID   17081307.
  5. ↑ Xie, T; Rowen, L; Aguado, B; Ahearn, ME; Madan, A; Qin, S; Campbell, RD; Hood, L (2003). "Analysis of the gene-dense major histocompatibility complex class III region and its comparison to mouse". Genome Research. 13 (12): 2621–36. doi:10.1101/gr.1736803. PMC   403804 . PMID   14656967.
  6. ↑ Dawkins, R; Leelayuwat, C; Gaudieri, S; Tay, G; Hui, J; Cattley, S; Martinez, P; Kulski, J (1999). "Genomics of the major histocompatibility complex: haplotypes, duplication, retroviruses and disease". Immunological Reviews. 167: 275–304. doi:10.1111/j.1600-065X.1999.tb01399.x. PMID   10319268. S2CID   9924684.
  7. ↑ Milner, CM; Campbell, RD (2001). "Genetic organization of the human MHC class III region". Frontiers in Bioscience. 6 (3): D914-926. doi:10.2741/A653. PMID   11487476.
  8. ↑ Shiina, T; Shimizu, S; Hosomichi, K; Kohara, S; Watanabe, S; Hanzawa, K; Beck, S; Kulski, JK; Inoko, H (2004). "Comparative genomic analysis of two avian (quail and chicken) MHC regions". Journal of Immunology. 172 (11): 6751–63. doi: 10.4049/jimmunol.172.11.6751 . PMID   15153492.
  9. ↑ Sambrook, JG; Figueroa, F; Beck, S (2005). "A genome-wide survey of Major Histocompatibility Complex (MHC) genes and their paralogues in zebrafish". BMC Genomics. 6: 152. doi: 10.1186/1471-2164-6-152 . PMC   1309616 . PMID   16271140.
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