MICA

Official Full Name

MHC class I polypeptide-related sequence A

Organism

Homo sapiens

GeneID

100507436

Background

This gene encodes the highly polymorphic major histocompatability complex class I chain-related protein A. The protein product is expressed on the cell surface, although unlike canonical class I molecules it does not seem to associate with beta-2-microglobulin. It is a ligand for the NKG2-D type II integral membrane protein receptor. The protein functions as a stress-induced antigen that is broadly recognized by intestinal epithelial gamma delta T cells. Variations in this gene have been associated with susceptibility to psoriasis 1 and psoriatic arthritis, and the shedding of MICA-related antibodies and ligands is involved in the progression from monoclonal gammopathy of undetermined significance to multiple myeloma. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jan 2014]

Synonyms

MIC-A; PERB11.1;

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Detailed Information

Brief Introduction

MICA is a tumor-related gene located on the short arm of human chromosome 6 with ectensive polymorphism. MICA gene contains 6 exons, exon 1 encodes L-precursor peptide, exon 2-4 encode extracellular alpha 1, alpha 2 and alpha 3 domains, exon 5 encodes transmembrane (TM) region, and exon 6 encodes cytoplasmic region.

The MICA gene is highly polymorphic. Up to now, more than 70 MICA alleles have been identified and numbered from MICA*001-MICA*065. Exons encoding the extracellular domain are the concentrated regions of the MICA allele polymorphism. In addition, there is a microsatellite polypeptide site (GCT) in the transmembrane region with a trinucleotide repeat sequence. According to the difference of GCT, they are named A4, A5, A5.1, A6, A7, A8 and A9. A5.1 inserts a G on the basis of A5, resulting in early termination in the transmembrane region.

In recent years, MICA has been found to be a ligand of NKG2D, which can significantly activate NK cells and T cells, so it plays an important role in anti-infective and anti-tumor immunity.

MICA Gene and Cancer

It was found that the MICA-A5.1 allele may be closely related to the occurrence of esophageal cancer and is a susceptible marker for esophageal cancer.

Studies have found that the occurrence and development of colorectal cancer is related to the polymorphism of MICA gene. It is speculated that the possible pathogenesis is due to the low affinity between the protein molecules encoded by certain types of MICA and NKG2D receptor genes on NK cells and CD8⁺ T cells, which results in the inability of these immune cells to activate effectively and the inability to perform normal immune surveillance function on tumor cells.

Studies have found that the frequency of MICA* 008: 01 in breast cancer patients is lower than that in normal persons. The possible reason is that the polymorphism of MICA gene makes the activation of NK cells different.

Five allele fragments including A4 (179 bp), A5 (182 bp), A5.1 (183 bp), A6 (185 bp) and A 9 (194 bp) have been found in exon 5 of MICA gene. Among them, A5.1 inserts a base G on the basis of A5, resulting in code-shift mutation. The microsatellite polymorphism in exon 5 is associated with autoimmune diseases such as head and neck squamous cell carcinoma, breast cancer, and diabetes mellitus. MICA microsatellite polymorphisms are associated with some tumors and may be related to their linkage imbalance with classical HLA I and II loci. In addition, studies have shown that the microsatellite polymorphism in exon 5 exists racial differences among different populations.

References:

Zheng Qingfeng, et al. Microsatellite Polymorphism of Exon 5 of MICA and Correlation Study of Esophageal Cancer [J]. Chinese Journal of Immunology, 2017, (5).
Chen En, et al. MICA gene polymorphism and susceptibility to colorectal cancer [J]. Experimental and Laboratory Medicine, 2016, (5).
Feng Zhizhi, et al. MICA gene polymorphism and breast cancer [J]. Chinese Journal of Blood Transfusion, 2016, (9).
Guo Jiaquan, et al. Correlation between breast cancer and MICA gene polymorphism [J]. Laser Biology Journal, 2015, (2).

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