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FLASH GENE

Symbol

MT2A

contributors: mct/npt - updated : 22-10-2015

HGNC name	metallothionein 2A
HGNC id	7406

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	0.88 kb     3 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_005953 3 - 466 NP_005944 - 61 - 2001 11133866

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 Digestive liver       highly Endocrine adrenal gland       highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Muscular striatum skeletal

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	two metal-binding domains: four divalent ions are chelated
	within cluster A of the alpha domain and are coordinated via cysteinyl thiolate bridges to 11 cysteine ligands

conjugated

MetalloP

HOMOLOGY

Homologene

FAMILY	metallothionein superfamily
	type 1 family

CATEGORY

storage

SUBCELLULAR LOCALIZATION	extracellular
	intracellular
	intracellular,cytoplasm,cytosolic
	intracellular,nucleus
text	synaptic vesicle

basic FUNCTION	having a high content of cysteine residues that bind various heavy metals and playing a role in oxidative stress
	can function as a chaperone for zinc uptake transport into prostate and liver mitochondria (Costello 2004)
	cysteine-rich, metal-binding protein providing protection against cadmium toxicity in mammals (Rigby Duncan 2008)
	have crucial biological functions including cell proliferation and apoptosis, homeostasis of essential metals, cellular free radical scavenging, and metal detoxification (Kayaalti 2009)
	could plausibly modulate cell cycle progression from G1- to S-phase via the ATM/Chk2/cdc25A pathway (Lim 2009)
	down-regulation of MT isoforms in proliferating keloid fibroblast (KF), in particular MT2A, enhances keloidogenesis with the possible involvement of the NFKB1 signalling pathway
	might be involved in insulin resistance through the up-regulation of Metallothioneins (Mts) gene expression, which may lead to the modulation of insulin action in fat cells

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

TTR-MT1A/MT2A protein complex (Goncalves 2008)

INTERACTION

DNA

RNA

small molecule	metal binding,
	heavy metal ions

protein	promotes breast cancer cell invasion by upregulating MMP9 via AP1 and NFKB1 activation
	AHR was recruited to the glucocorticoid response element in the MT2A promoter
	interaction with HMBOX1, that regulated intracellular free zinc level by interacting with MT2A to inhibit apoptosis and promote autophagy in vascular endothelial cells (VECs)

cell & other

REGULATION

induced by

heavy metal ions

Other

transcriptionally regulated by both heavy metals and glucocorticoids

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional       loss of function significantly down-regulated in proliferating keloid fibroblast (KF) constitutional     --over   MT1A/MT2A expression was increased in hippocampi from temporal lobe epilepsy (TLE) patients tumoral     --low   downregulated in colon cancer tissue

Susceptibility

to coronary heart disease (CHD) to metal toxicity

Variant & Polymorphism SNP	polymorphism of MT2A-838G/C is correlated to CHD, and the C allele might be a CHD-susceptible gene and might also have an effect on the extent of coronary artery disease
	the 5-GG genotype individuals may be more sensitive for the metal toxicity and they should be more careful about protecting their health against the toxic effects of the heavy metals

Candidate gene
Marker	levels of MT1F and MT2A mRNA could be considered as new markers of poor prognosis of non-small cell lung cancer patients
Therapy target

ANIMAL & CELL MODELS