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FLASH GENE

Symbol

MTF1

contributors: SGE/npt - updated : 26-09-2015

HGNC name	metal-regulatory transcription factor 1
HGNC id	7428

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_005955 11 - 7986 NP_005946 - 753 - 2004 1522626

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       highly   thyroid       highly Reproductive female system breast mammary gland   highly Visual eye       highly

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	six C2H2-type zinc fingers
	a SUMO-interacting motif (SIM)
	conserved C-terminus of the cysteine-rich domain provides cadmium specificity

HOMOLOGY

Homologene

FAMILY

CATEGORY

transcription factor

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm
	intracellular,nucleus,nucleoplasm
text	localizes to both the cytoplasm and the nucleus but quantitatively accumulates in the nucleus upon metal load and under other stress conditions (Lindert 2009)

basic FUNCTION	activating the metallothionein 1 promoter
	having a critical role in embryonic liver formation, heavy metal toxicity, and hematopoiesis (Wang 2004)
	plays a central role in hypoxic cells by contributing to HIF-1 activity (Murphy 2005)
	required for copper-mediated regulation of the PRNP gene (Bellingham 2009)
	direct role of MTF1 in promoter-specific binding and initiation
	essential mammalian protein for embryonic development and modulates the expression of genes involving in zinc homoeostasis and responding to oxidative stress
	recognizes a specific DNA sequence motif termed the metal response element (MRE), located in the promoter/enhancer region of its target genes
	is essential for the induction of genes encoding metallothionein by metals and hypoxia
	is a sequence-specific DNA binding protein that activates the transcription of metal responsive genes
	MTF1 chooses different DNA binding sites depending on the specific nature of the metal insult
	zinc-SLC39A8-MTF1 axis is an essential catabolic regulator of osteoarthritis pathogenesis
	Metallothionein (MT) and MTF1 are important regulatory proteins involved in the mediation of intracellular metal ion balance (pMID: 25405524)

CELLULAR PROCESS

nucleotide, transcription

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component	cysteine cluster mediates homodimerization of MTF1, and dimer formation is important for basal and especially metal-induced transcriptional activity
	forms complexes with cellular factors through SIM and SUMO moiety in the cytoplasm

INTERACTION

DNA	binds to metal responsive element

RNA

small molecule

protein	SLC30A2 participates in zinc transport into pancreatic zymogen granules through a glucocorticoid pathway requiring glucocorticoid receptor and STAT5, and zinc-regulated signaling pathways requiring MTF1
	associates with MTF1 in the cells, and protein but not lipid phosphatase activity of PTEN was involved in the regulation of MTF1 activity

cell & other

REGULATION

activated by

prolyl-hydroxylase inhibitors that can activate MTF1, but this activation requires the presence of HIF1A

Other

MTF1 DNA-binding activity was strongly enhanced in the presence of zinc but not by hypoxia

ASSOCIATED DISORDERS

corresponding disease(s)

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS