Mouse anti-Human sapiens (Human) MITF Monoclonal Antibody

Function

Transcription factor that acts as a master regulator of melanocyte survival and differentiation as well as melanosome biogenesis (PubMed:10587587, PubMed:22647378, PubMed:27889061, PubMed:9647758). Binds to M-boxes (5'-TCATGTG-3') and symmetrical DNA sequences (E-boxes) (5'-CACGTG-3') found in the promoter of pigmentation genes, such as tyrosinase (TYR) (PubMed:10587587, PubMed:22647378, PubMed:27889061, PubMed:9647758). Involved in the cellular response to amino acid availability by acting downstream of MTOR: in the presence of nutrients, MITF phosphorylation by MTOR promotes its inactivation (PubMed:36608670). Upon starvation or lysosomal stress, inhibition of MTOR induces MITF dephosphorylation, resulting in transcription factor activity (PubMed:36608670). Plays an important role in melanocyte development by regulating the expression of tyrosinase (TYR) and tyrosinase-related protein 1 (TYRP1) (PubMed:10587587, PubMed:22647378, PubMed:27889061, PubMed:9647758). 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 (PubMed:10587587, PubMed:22647378, PubMed:27889061, PubMed:9647758)

Subcellular Location

Nucleus; Cytoplasm; Lysosome membrane

Disease Association

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. [The disease is caused by variants affecting the gene represented in this entry] | Tietz albinism-deafness syndrome (TADS) : An autosomal dominant disorder characterized by generalized hypopigmentation and congenital, bilateral, profound sensorineural deafness. [The disease is caused by variants affecting the gene represented in this entry] | 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 may also involve other sites. [Disease susceptibility is associated with variants affecting the gene represented in this entry] | 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. [The disease is caused by variants affecting the gene represented in this entry. An allelic combination involving at least one dominant-negative mutation, inherited in a recessive manner, represents the underlying molecular mechanism leading to COMMAD syndrome] | [Variations affecting this gene are associated with susceptibility to pheochromocytomas and paragangliomas, rare neural crest-derived tumors with an approximate incidence of 1:300,000/year]

Tissue Specificity

Expressed in melanocytes

Subunit

Homodimer or heterodimer; dimerization is mediated via the coiled coil region (PubMed:24631970). Efficient DNA binding requires dimerization with another bHLH protein (PubMed:14975237). Binds DNA in the form of homodimer or heterodimer with either TFE3, TFEB or TFEC (PubMed:15507434). Interacts with small GTPases Rag (RagA/RRAGA, RagB/RRAGB, RagC/RRAGC and/or RagD/RRAGD); promoting its recruitment to lysosomal membrane in the presence of nutrients (PubMed:23401004, PubMed:36608670). Interacts with KARS1 (PubMed:14975237). Identified in a complex with HINT1 and CTNNB1 (PubMed:22647378). Interacts with VSX2 (By similarity)

• Amae S. et al. Identification of a novel isoform of microphthalmia-associated transcription factor that is enriched in retinal pigment epithelium. — Biochem. Biophys. Res. Commun. (1998)
• Tachibana M. et al. Cloning of MITF, the human homolog of the mouse microphthalmia gene and assignment to chromosome 3p14.1-p12.3. — Hum. Mol. Genet. (1994)
• Wang Y. et al. Mitf-Mdel, a novel melanocyte/melanoma-specific isoform of microphthalmia-associated transcription factor-M, as a candidate biomarker for melanoma. — BMC Med. (2010)
• Wiemann S. et al. Towards a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs. — Genome Res. (2001)
• Ota T. et al. Complete sequencing and characterization of 21,243 full-length human cDNAs. — Nat. Genet. (2004)
• Muzny D.M. et al. The DNA sequence, annotation and analysis of human chromosome 3. — Nature (2006)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Udono T. et al. Structural organization of the human microphthalmia-associated transcription factor gene containing four alternative promoters. — Biochim. Biophys. Acta (2000)