ID:MITF_HUMAN DESCRIPTION: RecName: Full=Microphthalmia-associated transcription factor; AltName: Full=Class E basic helix-loop-helix protein 32; Short=bHLHe32; FUNCTION: Transcription factor for tyrosinase (TYR) and tyrosinase-related protein 1 (TYRP1) that plays a key role in melanocyte development. Binds to a symmetrical DNA sequence (E- boxes) (5'-CACGTG-3') found in the tyrosinase promoter. Plays a critical role in the differentiation of various cell types as neural crest-derived melanocytes, mast cells, osteoclasts and optic cup-derived retinal pigment epithelium. SUBUNIT: Efficient DNA binding requires dimerization with another bHLH protein. Binds DNA in the form of homodimer or heterodimer with either TFE3, TFEB or TFEC. Interacts with KARS. SUBCELLULAR LOCATION: Nucleus. TISSUE SPECIFICITY: Isoform M is exclusively expressed in melanocytes and melanoma cells. Isoform A and isoform H are widely expressed in many cell types including melanocytes and retinal pigment epithelium (RPE). Isoform C is expressed in many cell types including RPE but not in melanocyte-lineage cells. PTM: Phosphorylation at Ser-405 significantly enhances the ability to bind the tyrosinase promoter. Phosphorylated at Ser-180 and Ser-516 following KIT signaling, trigerring 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. PTM: Ubiquitinated following phosphorylation at Ser-180, leading to subsequent degradation by the proteasome. Deubiquitinated by USP13, preventing its degradation. DISEASE: Defects in MITF are the cause of Waardenburg syndrome type 2A (WS2A) [MIM:193510]. It is a dominant inherited disorder characterized by sensorineural hearing loss and patches of depigmentation. The features show variable expression and penetrance. DISEASE: Defects in MITF are a cause of Waardenburg syndrome type 2 with ocular albinism (WS2-OA) [MIM:103470]. It is an ocular albinism with sensorineural deafness. DISEASE: Defects in MITF are the cause of Tietz syndrome (TIETZS) [MIM:103500]. It is an autosomal dominant disorder characterized by generalized hypopigmentation and profound, congenital, bilateral deafness. Penetrance is complete. DISEASE: Defects in MITF are a cause of susceptibility to cutaneous malignant melanoma type 8 (CMM8) [MIM:614456]. 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. SIMILARITY: Belongs to the MiT/TFE family. SIMILARITY: Contains 1 bHLH (basic helix-loop-helix) domain. WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/MITF";
Protein Domain and Structure Information
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