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FLASH GENE

Symbol

MICA

contributors: mct - updated : 22-04-2011

HGNC name	MHC class I polypeptide-related sequence A
HGNC id	7090

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	66.03 kb     2 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

status

confirmed

Map	see LTA ,MHC1

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_006674 2 - 2547 - 383 - 1998 9480751 NM_001177519 - - 1369 - 332 - 1998 9480751

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Endocrine pancreas         Reproductive male system prostate

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / Hematopoietic bone marrow       Connective bone subchondral     Epithelial secretory glandular endocrine   Muscular striatum skeletal

cells

System Cell Pubmed Species Stage Rna symbol   digestive

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

secondary structure

alpha 1 and alpha 2 domain

HOMOLOGY

intraspecies

homolog to micb

Homologene

FAMILY

CATEGORY

immunity/defense , antigen , receptor membrane

SUBCELLULAR LOCALIZATION	extracellular
	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,endoplasmic reticulum

basic FUNCTION	functioning as a stress-induced antigen that is broadly recognized by intestinal epithelial gamma delta T cells
	MICA, and MICB, ligands of the KLRK1, which activates NK cells and costimulates effector T cells, are inducibly expressed under harmful conditions, such as malignancies and microbial infections
	non-peptide-presenting, tightly regulated, stress-induced MHC-like molecule

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

immunity/defense

text	cellular defense response

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	with KLRK1 (augmenting the activation of natural killer cells)
	synergistic activity of two stress-inducible immunological danger signals, HSP70 and MICA/MICB, leads to activation and enhanced cytotoxicity of human NK cells against tumour cells
	cognate receptor for KLRK1 (MICA-KLRK1 played a role in disease pathogenesis in the majority of patients in our cohort of cases of large granular lymphocyte leukemia and further investigation into this signaling axis may provide potent therapeutic targets)
	ADAM10 is required for the hypoxia-induced shedding of MICA that triggers the cytolytic action of immune effectors, from the surface of tumor cells
	ligand of KLRK1

cell & other

REGULATION

Other	activation of MICA and MICB is the result of DNA damage response activation caused by DICER1 knockdown

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in ovarian cancer highly correlated with that of ULBP2, and high expression of ULBP2 is an indicator of poor prognosis in ovarian cancer and may relate to T cell dysfunction in the tumor microenvironment tumoral     --over   may be an indicator of poor prognosis in breast carcinoma ( constitutional     --over   in the gut of patients with celiac disease

Susceptibility

to IDDM, to Behcet disease to rheumatoid arthritis to viral infection, cancer and allograft rejection or graft-versus-host disease (GVHD) to Alzheimer disease (AD) to idiopathic thrombocytopenic purpura

Variant & Polymorphism other	a repeat polymorphism in TM region possibly associated with Behcet disease, not involved in ankylosing spondylitis
	MICA*A4 associated to HLA-DRB1*0405 increasing the risk of rheumatoid arthritis (RA)
	MICA*A9 having a weak protective effect on the susceptibility to RA
	polymorphisms are associated with a number of diseases related to NK activity, such as viral infection, cancer and allograft rejection or graft-versus-host disease (GVHD)
	possible association of MICA*00801 heterozygotes with AD in subjects positive for the epsilon 4 allele of apolipoprotein E
	only allele MICA*183, also known as A5.1, demonstrated an association to idiopathic thrombocytopenic purpura

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS