InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Mitf

Summary

InnateDB Protein

IDBP-172467.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

Mitf

Protein Name

microphthalmia-associated transcription factor

Synonyms

BCC2; Bhlhe32; bw; Gsfbcc2; mi; vit; Vitiligo; Wh;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000044459

InnateDB Gene

IDBG-172461 (Mitf)

Protein Structure

UniProt Annotation

Function

Transcription factor that regulates the expression of genes with essential roles in cell differentiation, proliferation and survival. Binds to symmetrical DNA sequences (E-boxes) (5'- CACGTG-3') found in the promoters of target genes, such as BCL2 and tyrosinase (TYR). Plays an important role in melanocyte development by regulating the expression of tyrosinase (TYR) and tyrosinase-related protein 1 (TYRP1). Plays a critical role in the differentiation of various cell types, such as neural crest- derived melanocytes, mast cells, osteoclasts and optic cup-derived retinal pigment epithelium.

Subcellular Localization

Nucleus {ECO:0000255PROSITE- ProRule:PRU00981, ECO:0000269PubMed:8622664}.

Disease Associations

Note=Defects in Mitf are the cause of microphthalmia (mi), a condition characterized by loss of pigmentation; reduced eye size; failure of secondary bone resorption; reduced numbers of mast cells; early onset of deafness, and which gives rise to a number of different phenotypes. Among them, microphthalmia-eyeless white (mi-ew) has a normal appearance at the heterozygous state, but shows white coat; eyes almost absent and eyelids never open at homozygosity. Microphthalmia-black and white spot (mi-bws) is normal at heterozygosity, and presents white spots and black eyes at homozygous state. Microphthalmia-white (mi-wh) has reduced coat color and eye pigmentation; spots on toes, tail and belly; inner ear defects at heterozygosity, and at homozygosity shows white coat; eyes small and inner iris slightly pigmented; spinal ganglia, adrenal medulla and dermis smaller than normal, and inner ear defects. Microphthalmia-vitiligo (mi-vi) has normal phenotype at heterozygosity, but shows gradual depigmentation of coat, skin and eyes; and retinal degeneration at homozygosity. Microphthalmia-spotted (mi-sp) shows normal phenotype; at homozygosity, however, tyrosinase activity in skin is reduced. Microphthalmia-defective irism (mi-di) has reduced retinal pigmentation at heterozygosity and shows white coat; eyes of reduced sized and possible mild osteoporosis at homozygosity. Microphthalmia-cloudy eyed (mi-ce) has a normal appearance at the heterozygous state, but shows white coat; eyes of reduced size and unpigmented at homozygosity. Microphthalmia-red-eyed white (mi-rw) has a normal appearance at the homozygous state, but shows white coat with one or more pigmented spots around the head/and or tail; eyes are small and red at heterozygosity. Microphthalmia-black- eyed white (mi-bw) shows a white coat but normal sized eyes which reamin black at homozygosity.

Tissue Specificity

In the adult, expressed at high levels in the heart, skin, skeletal muscle, intestine, stomach, kidney, ovary, lung, spleen and brain. In the embryo, expressed in developing eye, ear, skin and heart. Isoform M is expressed in melanocytes and also in the embryonic and adult heart while isoform A and isoform H are more widely expressed. {ECO:0000269PubMed:8343963}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 13 experimentally validated interaction(s) in this database.
They are also associated with 29 interaction(s) predicted by orthology.

Experimentally validated
Total	13 [view]
Protein-Protein	11 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	2 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	29 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0000978	RNA polymerase II core promoter proximal region sequence-specific DNA binding
GO:0000979	RNA polymerase II core promoter sequence-specific DNA binding
GO:0001077	RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription
GO:0003677	DNA binding
GO:0003682	chromatin binding
GO:0003700	sequence-specific DNA binding transcription factor activity
GO:0003705	RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity
GO:0043565	sequence-specific DNA binding
GO:0046983	protein dimerization activity

Biological Process

GO:0006355	regulation of transcription, DNA-templated
GO:0006366	transcription from RNA polymerase II promoter
GO:0010468	regulation of gene expression
GO:0016055	Wnt signaling pathway
GO:0030154	cell differentiation
GO:0030316	osteoclast differentiation
GO:0030318	melanocyte differentiation
GO:0042127	regulation of cell proliferation
GO:0043010	camera-type eye development
GO:0043066	negative regulation of apoptotic process
GO:0043473	pigmentation
GO:0044336	canonical Wnt signaling pathway involved in negative regulation of apoptotic process
GO:0045165	cell fate commitment
GO:0045670	regulation of osteoclast differentiation
GO:0045893	positive regulation of transcription, DNA-templated
GO:0045944	positive regulation of transcription from RNA polymerase II promoter
GO:0046849	bone remodeling