MITF
entrez
4286
canonical
uniprot
O75030
canonical
ensembl
ENSG00000187098
resolver
ensp
ENSP00000295600
resolver
ensp
ENSP00000324246
resolver
ensp
ENSP00000324443
resolver
ensp
ENSP00000377880
resolver
ensp
ENSP00000391803
resolver
ensp
ENSP00000418845
resolver
ensp
ENSP00000435909
resolver
ensp
ENSP00000481286
resolver
ensp
ENSP00000494105
resolver
ensp
ENSP00000510225
resolver
ensp
ENSP00000564557
resolver
ensp
ENSP00000660498
resolver
enst
ENST00000394348
resolver
enst
ENST00000687384
resolver
genesymbol
MITF
resolver
genesymbol_syn
BHLHE32
resolver
hgnc
HGNC:7105
resolver
uniprot
A0A087WXU1
resolver
uniprot
A0A8I5KSZ4
resolver
uniprot
B4DJL2
resolver
uniprot
B4DNC7
resolver
uniprot
D3K197
resolver
uniprot
E9PFN0
resolver
uniprot
Q14841
resolver
uniprot
Q9P2V0
resolver
uniprot
Q9P2V1
resolver
uniprot
Q9P2V2
resolver
uniprot
Q9P2Y8
resolver
uniprot_entry
A0A087WXU1_HUMAN
resolver
uniprot_entry
A0A8I5KSZ4_HUMAN
resolver
uniprot_entry
B4DNC7_HUMAN
resolver
uniprot_entry
MITF_HUMAN
resolver
uniprot_sec
B4DJL2
resolver
uniprot_sec
D3K197
resolver
uniprot_sec
E9PFN0
resolver
uniprot_sec
Q14841
resolver
uniprot_sec
Q9P2V0
resolver
uniprot_sec
Q9P2V1
resolver
uniprot_sec
Q9P2V2
resolver
uniprot_sec
Q9P2Y8
resolver
amino_acid_sequence
MQSESGIVPDFEVGEEFHEEPKTYYELKSQPLKSSSSAEHPGASKPPISSSSMTSRILLRQQLMREQMQEQERREQQQKLQAAQFMQQRVPVSQTPAINVSVPTTLPSATQVPMEVLKVQTHLENPTKYHIQQAQRQQVKQYLSTTLANKHANQVLSLPCPNQPGDHVMPPVPGSSAPNSPMAMLTLNSNCEKEGFYKFEEQNRAESECPGMNTHSRASCMQMDDVIDDIISLESSYNEEILGLMDPALQMANTLPVSGNLIDLYGNQGLPPPGLTISNSCPANLPNIKRELTACIFPTESEARALAKERQKKDNHNLIERRRRFNINDRIKELGTLIPKSNDPDMRWNKGTILKASVDYIRKLQREQQRAKELENRQKKLEHANRHLLLRIQELEMQARAHGLSLIPSTGLCSPDLVNRIIKQEPVLENCSQDLLQHHADLTCTTTLDLTDGTITFNNNLGTGTEANQAYSVPTKMGSKLEDILMDDTLSPVGVTDPLLSSVSPGASKTSSRRSSMSMEETEHTC
uniprot
proteins
disease_involvement
DISEASE: Waardenburg syndrome 2A (WS2A) [MIM:193510]: 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. {ECO:0000269|PubMed:28236341, ECO:0000269|PubMed:8589691, ECO:0000269|PubMed:9647758}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Tietz albinism-deafness syndrome (TADS) [MIM:103500]: An autosomal dominant disorder characterized by generalized hypopigmentation and congenital, bilateral, profound sensorineural deafness. {ECO:0000269|PubMed:10851256}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Melanoma, cutaneous malignant 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 may also involve other sites. {ECO:0000269|PubMed:22012259, ECO:0000269|PubMed:22080950}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.; DISEASE: Coloboma, osteopetrosis, microphthalmia, macrocephaly, albinism, and deafness (COMMAD) [MIM:617306]: 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. {ECO:0000269|PubMed:27889061}. Note=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. {ECO:0000269|PubMed:27889061}.; DISEASE: Note=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. {ECO:0000269|PubMed:27680874}.
uniprot
proteins
function
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). {ECO:0000269|PubMed:10587587, ECO:0000269|PubMed:22647378, ECO:0000269|PubMed:27889061, ECO:0000269|PubMed:36608670, ECO:0000269|PubMed:9647758}.
uniprot
proteins
mass_dalton
58795
uniprot
proteins
mutagenesis
MUTAGEN 5; /note="S->A: Impaired phosphorylation by MTOR, leading to abolished ubiquitination and degradation by the SCF(BTRC) complex."; /evidence="ECO:0000269|PubMed:36608670"; MUTAGEN 180; /note="S->A: Abolishes both transcription factor activity and ubiquitination, leading to an inert and stable protein; when associated with A-516."; /evidence="ECO:0000269|PubMed:10673502"; MUTAGEN 280; /note="S->A: Accumulates in the nucleus due to impaired phosphorylation."; /evidence="ECO:0000269|PubMed:16822840"; MUTAGEN 289; /note="K->R: Loss of sumoylation; when associated with R-423."; /evidence="ECO:0000269|PubMed:15507434"; MUTAGEN 405; /note="S->A,P: Loss of phosphorylation and function."; /evidence="ECO:0000269|PubMed:10587587"; MUTAGEN 423; /note="K->R: Loss of sumoylation; when associated with R-289."; /evidence="ECO:0000269|PubMed:15507434"; MUTAGEN 516; /note="S->A: Abolishes both transcription factor activity and ubiquitination, leading to an inert and stable protein; when associated with A-180."; /evidence="ECO:0000269|PubMed:10673502
uniprot
proteins
post_translational_modification
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). {ECO:0000269|PubMed:10587587, ECO:0000269|PubMed:10673502, ECO:0000269|PubMed:16822840, ECO:0000269|PubMed:28842328, ECO:0000269|PubMed:36608670}.; 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). {ECO:0000269|PubMed:10673502, ECO:0000269|PubMed:36608670}.
uniprot
proteins
protein_family
MiT/TFE family
uniprot
proteins
pubmed
10578055
uniprot
proteins
pubmed
10587587
uniprot
proteins
pubmed
10673502
uniprot
proteins
pubmed
10760582
uniprot
proteins
pubmed
10851256
uniprot
proteins
pubmed
11230166
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
14975237
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15507434
uniprot
proteins
pubmed
16641997
uniprot
proteins
pubmed
16822840
uniprot
proteins
pubmed
18220336
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
20163701
uniprot
proteins
pubmed
22012259
uniprot
proteins
pubmed
22080950
uniprot
proteins
pubmed
22647378
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23401004
uniprot
proteins
pubmed
24631970
uniprot
proteins
pubmed
27680874
uniprot
proteins
pubmed
27889061
uniprot
proteins
pubmed
28236341
uniprot
proteins
pubmed
28842328
uniprot
proteins
pubmed
36608670
uniprot
proteins
pubmed
8069297
uniprot
proteins
pubmed
8589691
uniprot
proteins
pubmed
9647758
uniprot
proteins
sequence_length
526
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:16822840, ECO:0000269|PubMed:27889061, ECO:0000269|PubMed:28842328, ECO:0000269|PubMed:36608670}. Cytoplasm {ECO:0000269|PubMed:16822840, ECO:0000269|PubMed:28842328, ECO:0000269|PubMed:36608670}. Lysosome membrane {ECO:0000269|PubMed:23401004, ECO:0000269|PubMed:36608670}. Note=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). {ECO:0000269|PubMed:16822840, ECO:0000269|PubMed:23401004, ECO:0000269|PubMed:36608670}.
uniprot
proteins