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";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on O75030
Front
Top
Side
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.
Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0000978 RNA polymerase II core promoter proximal region sequence-specific DNA binding GO:0000981 RNA polymerase II transcription factor activity, sequence-specific DNA binding GO:0001077 transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding GO:0001227 transcriptional repressor activity, RNA polymerase II transcription regulatory region sequence-specific binding GO:0003677 DNA binding GO:0003682 chromatin binding GO:0003700 transcription factor activity, sequence-specific DNA binding GO:0003705 transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding GO:0005515 protein binding GO:0046983 protein dimerization activity GO:0070888 E-box binding
Biological Process: GO:0000122 negative regulation of transcription from RNA polymerase II promoter GO:0006351 transcription, DNA-templated GO:0006355 regulation of transcription, DNA-templated GO:0006357 regulation of transcription from RNA polymerase II promoter GO:0006366 transcription from RNA polymerase II promoter GO:0007275 multicellular organism development GO:0010468 regulation of gene expression GO:0010628 positive 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 GO:0065003 macromolecular complex assembly GO:2000144 positive regulation of DNA-templated transcription, initiation GO:2001141 regulation of RNA biosynthetic process
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
