Transcription factor that regulates the expression of genes with essential roles in cell differentiation, proliferation and survival. Binds to M-boxes (5'-TCATGTG-3') and symmetrical DNA sequences (E-boxes) (5'-CACGTG-3') found in the promoters of target genes, such as BCL2 and tyrosinase (TYR). Plays an important role in melanocyte development by regulating the expression of tyrosinase (TYR) and tyrosinase-related protein 1 (TYRP1). 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. 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 KARS1 (PubMed:14975237). Identified in a complex with HINT1 and CTNNB1 (PubMed:22647378). Interacts with VSX2 (By similarity). Found exclusively in the nucleus upon phosphorylation. The X2-type isoforms differ from the X1-type isoforms by the absence of a 6 residue insert. Expressed in melanocytes (at protein level). Expressed in the retinal pigment epithelium, brain, and placenta (PubMed:9647758). Expressed in the kidney (PubMed:9647758, PubMed:10578055). Expressed in the kidney and retinal pigment epithelium. Expressed in the kidney. Expressed in the kidney. Expressed in melanocytes. Expressed in melanocytes. The leucine zipper region is part of a larger coiled coil. Phosphorylation at Ser-405 significantly enhances the ability to bind the tyrosinase promoter (PubMed:10587587). Phosphorylated at Ser-180 and Ser-516 following KIT signaling, triggering 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 (PubMed:10673502). Phosphorylated in response to blue light (415nm) (PubMed:28842328). Ubiquitinated following phosphorylation at Ser-180, leading to subsequent degradation by the proteasome. Deubiquitinated by USP13, preventing its degradation. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. Disease susceptibility is associated with variants affecting the gene represented in this entry. 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. Belongs to the MiT/TFE family.