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

More general terms

• basic helix loop helix (bHLH) family transcription factor
• phosphoprotein

Database

• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:4286
• OMIM: https://mirror.omim.org/entry/103470
• OMIM: https://mirror.omim.org/entry/103500
• OMIM: https://mirror.omim.org/entry/156845
• OMIM: https://mirror.omim.org/entry/193510
• UniProt: http://www.uniprot.org/uniprot/O75030.html
• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=4286