MITF (Concentrate)

The protein encoded by this gene is a transcription factor that contains both basic helix-loop-helix and leucine zipper structural features. The encoded protein regulates melanocyte development and is responsible for pigment cell-specific transcription of the melanogenesis enzyme genes. Heterozygous mutations in the this gene cause auditory-pigmentary syndromes, such as Waardenburg syndrome type 2 and Tietz syndrome. [provided by RefSeq, Aug 2017]

Full Name

Melanogenesis Associated Transcription Factor

Function

Transcription factor that regulates the expression of genes with essential roles in cell differentiation, proliferation and survival. Binds to M-boxes (5'-TCATGTG-3') and 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.

Biological Process

Bone remodeling Source: Ensembl
Camera-type eye development Source: Ensembl
Canonical Wnt signaling pathway involved in negative regulation of apoptotic process Source: Ensembl
Cell fate commitment Source: Ensembl
Melanocyte differentiation Source: GO_Central
Negative regulation of cell migration Source: BHF-UCL
Negative regulation of transcription by RNA polymerase II Source: BHF-UCL
Osteoclast differentiation Source: Ensembl
Positive regulation of DNA-templated transcription, initiation Source: CACAO
Positive regulation of gene expression Source: CACAO
Positive regulation of transcription, DNA-templated Source: UniProtKB
Positive regulation of transcription by RNA polymerase II Source: UniProtKB
Protein-containing complex assembly Source: UniProtKB
Regulation of cell population proliferation Source: Ensembl
Regulation of osteoclast differentiation Source: Ensembl
Regulation of RNA biosynthetic process Source: CACAO
Regulation of transcription, DNA-templated Source: UniProtKB
Regulation of transcription by RNA polymerase II Source: GO_Central

Cellular Location

Cytoplasm 1 Publication
Nucleus
Note: Found exclusively in the nucleus upon phosphorylation.

Involvement in disease

Waardenburg syndrome 2A (WS2A):
WS2 is a genetically heterogeneous, autosomal dominant disorder characterized by sensorineural deafness, pigmentary disturbances, and absence of dystopia canthorum. The frequency of deafness is higher in WS2 than in WS1.
Tietz albinism-deafness syndrome (TADS):
An autosomal dominant disorder characterized by generalized hypopigmentation and congenital, bilateral, profound sensorineural deafness.
Melanoma, cutaneous malignant 8 (CMM8):
A malignant neoplasm of melanocytes, arising de novo or from a pre-existing benign nevus, which occurs most often in the skin but also may involve other sites.
Coloboma, osteopetrosis, microphthalmia, macrocephaly, albinism, and deafness (COMMAD):
An autosomal recessive syndrome characterized by severe microphthalmia, profound congenital sensorineural hearing loss, lack of pigment in the hair, skin, and eyes, macrocephaly, facial dysmorphism, and osteopetrosis.

PTM

Phosphorylation at Ser-405 significantly enhances the ability to bind the tyrosinase promoter (PubMed:10587587). Phosphorylated at Ser-180 and Ser-516 following KIT signaling, triggering a short live activation: Phosphorylation at Ser-180 and Ser-516 by MAPK and RPS6KA1, respectively, activate the transcription factor activity but also promote ubiquitination and subsequent degradation by the proteasome (PubMed:10673502). Phosphorylated in response to blue light (415nm) (PubMed:28842328).
Ubiquitinated following phosphorylation at Ser-180, leading to subsequent degradation by the proteasome. Deubiquitinated by USP13, preventing its degradation.