Search
microphthalmia associated transcription factor (MITF)
Function:
- transcription factor for tyrosinase & tyrosinase-related protein 1
- binds to a symmetrical DNA sequence (E-boxes) (5'-CACGTG-3') found in the tyrosinase promoter
- role in the differentiation of various cell types as neural crest-derived melanocytes, mast cells, osteoclasts & optic cup-derived retinal pigment epithelium
- efficient DNA binding requires dimerization with another bHLH protein
- binds DNA in the form of homodimer or heterodimer with either TFE3, TFEB or TFEC
- phosphorylation at Ser-405 significantly enhances ability to bind the tyrosinase promoter
Structure:
- belongs to the MiT/TFE family
- contains 1 basic helix-loop-helix (bHLH) domain
Compartment: nucleus
Alternative splicing: named isoforms=10
Expression:
- isoform M is exclusively expressed in melanocytes & melanoma cells
- isoform A & isoform H are widely expressed, including expression in melanocytes & retinal pigment epithelium
- isoform C is expressed in many cell types including retinal pigment epithelium but not in melanocyte-lineage cells
Pathology:
- defects in MITF are the cause of Waardenburg syndrome 2A
- defects in MITF are a cause of Waardenburg syndrome 2-OA
- defects in MITF are the cause of Tietz syndrome
Related
MITF (WS2A) gene
General
basic helix loop helix (bHLH) family transcription factor
phosphoprotein
Properties
SIZE: entity length = 526 aa
MW = 59 kD
COMPARTMENT: cell nucleus
MOTIF: Thr phosphorylation site {T54}
Transactivation {224-295}
basic helix-loop-helix
MOTIF: basic DNA-binding motif
helix-loop-helix
NAME: helix-loop-helix
FOR-BINDING-VIA: helix-loop-helix
FOR-BINDING-OF: DNA motif
FOR-BINDING-VIA: helix-loop-helix
DNA-binding motif
SITE: 309-324
helix-loop-helix
NAME: helix-loop-helix
SITE: 325-365
FOR-BINDING-VIA: helix-loop-helix
leucine zipper
SITE: 374-395
FOR-BINDING-VIA: leucine zipper
DNA-binding motif
SITE: 401-431
MOTIF: Ser phosphorylation site {S405}
Ser phosphorylation site {S414}
Database Correlations
OMIM correlations
MORBIDMAP 156845
UniProt O75030
Pfam PF00010
Entrez Gene 4286
Kegg hsa:4286
References
- Harrison's Principles of Internal Medicine, 14th ed.
Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 317
- Entrez Gene :accession 4286
- GeneReviews
https://www.genecards.org/cgi-bin/carddisp.pl?gene=MITF
- UniProt :accession O75030