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Details on Person UniProt:O75030 MITF

Class:Id	ReferenceGeneProduct:59279
_chainChangeLog	chain:1-526 added on Sat February 7 2015
_displayName	UniProt:O75030 MITF
_timestamp	2024-11-03 19:41:54
chain	chain:1-526
checksum	136EBED3044C1986
comment	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).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).INTERACTION When nutrients are present, recruited to the lysosomal membrane via association with GDP-bound RagC/RRAGC (or RagD/RRAGD): it is then phosphorylated by MTOR (PubMed:23401004, PubMed:36608670). Phosphorylation by MTOR promotes ubiquitination and degradation (PubMed:36608670). Conversely, inhibition of mTORC1, starvation and lysosomal disruption, promotes dephosphorylation and translocation to the nucleus (PubMed:36608670). Phosphorylation by MARK3/cTAK1 promotes association with 14-3-3/YWHA adapters and retention in the cytosol (PubMed:16822840).ALTERNATIVE PRODUCTS The X2-type isoforms differ from the X1-type isoforms by the absence of a 6 residue insert.TISSUE SPECIFICITY Expressed in melanocytes (at protein level).TISSUE SPECIFICITY Expressed in the retinal pigment epithelium, brain, and placenta (PubMed:9647758). Expressed in the kidney (PubMed:10578055, PubMed:9647758).TISSUE SPECIFICITY Expressed in the kidney and retinal pigment epithelium.TISSUE SPECIFICITY Expressed in the kidney.TISSUE SPECIFICITY Expressed in the kidney.TISSUE SPECIFICITY Expressed in melanocytes.TISSUE SPECIFICITY Expressed in melanocytes.DOMAIN The leucine zipper region is part of a larger coiled coil.PTM When nutrients are present, phosphorylation by MTOR at Ser-5 via non-canonical mTORC1 pathway promotes ubiquitination by the SCF(BTRC) complex, followed by degradation (PubMed:36608670). Phosphorylation at Ser-405 significantly enhances the ability to bind the tyrosinase promoter (PubMed:10587587). Phosphorylation by MARK3/cTAK1 at Ser-280 promotes association with 14-3-3/YWHA adapters and retention in the cytosol (PubMed:16822840). 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).PTM Ubiquitinated by the SCF(BTRC) and SCF(FBXW11) complexes following phosphorylation ar Ser-5 by MTOR, leading to its degradation by the proteasome (PubMed:36608670). Ubiquitinated following phosphorylation at Ser-180, leading to subsequent degradation by the proteasome (PubMed:10673502). Deubiquitinated by USP13, preventing its degradation (PubMed:10673502).DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE Disease susceptibility is associated with variants affecting the gene represented in this entry.DISEASE 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.DISEASE 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.SIMILARITY Belongs to the MiT/TFE family.
description	recommendedName: Microphthalmia-associated transcription factor alternativeName: Class E basic helix-loop-helix protein 32 shortName: bHLHe32
geneName	MITF BHLHE32
identifier	O75030
isSequenceChanged	FALSE
keyword	3D-structure Activator Albinism Alternative splicing Coiled coil Cytoplasm Deafness Developmental protein Disease variant DNA-binding Isopeptide bond Lysosome Membrane Microphthalmia Nucleus Osteopetrosis Phosphoprotein Proteomics identification Reference proteome Transcription Transcription regulation Ubl conjugation Waardenburg syndrome
modified	[InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9862192] Weiser, Joel, 2024-02-26 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03
name	MITF
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:8989631] ENSEMBL:ENSG00000187098 MITF [Homo sapiens]
secondaryIdentifier	MITF_HUMAN B4DJL2 D3K197 E9PFN0 Q14841 Q9P2V0 Q9P2V1 Q9P2V2 Q9P2Y8
sequenceLength	526
species	[Species:48887] Homo sapiens
(isoformParent)	[ReferenceIsoform:150325] UniProt:O75030-2 MITF [Homo sapiens] [ReferenceIsoform:150326] UniProt:O75030-3 MITF [Homo sapiens] [ReferenceIsoform:150327] UniProt:O75030-4 MITF [Homo sapiens] [ReferenceIsoform:150328] UniProt:O75030-5 MITF [Homo sapiens] [ReferenceIsoform:150329] UniProt:O75030-6 MITF [Homo sapiens] [ReferenceIsoform:150330] UniProt:O75030-7 MITF [Homo sapiens] [ReferenceIsoform:150331] UniProt:O75030-8 MITF [Homo sapiens] [ReferenceIsoform:150332] UniProt:O75030-9 MITF [Homo sapiens] [ReferenceIsoform:150333] UniProt:O75030-10 MITF [Homo sapiens] [ReferenceIsoform:401796] UniProt:O75030-1 MITF [Homo sapiens] List all 12 refering instances
(referenceEntity)	[EntityWithAccessionedSequence:201592] MITF [nucleoplasm] [Homo sapiens] [EntityWithAccessionedSequence:3232153] monoSUMO1-K289,423-MITF [nucleoplasm] [Homo sapiens]
(referenceSequence)	[GroupModifiedResidue:3232147] sumoylated lysine (monoSUMO1 [nucleoplasm]) at 289 [GroupModifiedResidue:3232154] sumoylated lysine (monoSUMO1 [nucleoplasm]) at 423
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