ID MITF_HUMAN Reviewed; 526 AA. AC O75030; B4DJL2; D3K197; E9PFN0; Q14841; Q9P2V0; Q9P2V1; Q9P2V2; Q9P2Y8; DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot. DT 21-FEB-2001, sequence version 2. DT 02-SEP-2026, entry version 234. DE RecName: Full=Microphthalmia-associated transcription factor; DE AltName: Full=Class E basic helix-loop-helix protein 32; DE Short=bHLHe32; GN Name=MITF {ECO:0000303|PubMed:8069297, ECO:0000312|HGNC:HGNC:7105}; GN Synonyms=BHLHE32; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A2), NUCLEOTIDE SEQUENCE [MRNA] OF 1-35 RP (ISOFORMS H1/H2), FUNCTION, TISSUE SPECIFICITY, AND INVOLVEMENT IN WS2A. RC TISSUE=Kidney; RX PubMed=9647758; DOI=10.1006/bbrc.1998.8838; RA Amae S., Fuse N., Yasumoto K., Sato S., Yajima I., Yamamoto H., Udono T., RA Durlu Y.K., Tamai M., Takahashi K., Shibahara S.; RT "Identification of a novel isoform of microphthalmia-associated RT transcription factor that is enriched in retinal pigment epithelium."; RL Biochem. Biophys. Res. Commun. 247:710-715(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM M1). RC TISSUE=Skin; RX PubMed=8069297; DOI=10.1093/hmg/3.4.553; RA Tachibana M., Perez-Jurado L.A., Nakayama A., Hodgkinson C.A., Li X., RA Schneider M., Miki T., Fex J., Francke U., Arnheiter H.; RT "Cloning of MITF, the human homolog of the mouse microphthalmia gene and RT assignment to chromosome 3p14.1-p12.3."; RL Hum. Mol. Genet. 3:553-557(1994). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM MDEL), AND TISSUE SPECIFICITY. RX PubMed=20163701; DOI=10.1186/1741-7015-8-14; RA Wang Y., Radfar S., Liu S., Riker A.I., Khong H.T.; RT "Mitf-Mdel, a novel melanocyte/melanoma-specific isoform of microphthalmia- RT associated transcription factor-M, as a candidate biomarker for melanoma."; RL BMC Med. 8:14-14(2010). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A2). RC TISSUE=Uterus; RX PubMed=11230166; DOI=10.1101/gr.gr1547r; RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J., RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W., RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B., RA Klein M., Poustka A.; RT "Towards a catalog of human genes and proteins: sequencing and analysis of RT 500 novel complete protein coding human cDNAs."; RL Genome Res. 11:422-435(2001). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 12). RC TISSUE=Thalamus; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16641997; DOI=10.1038/nature04728; RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.; RT "The DNA sequence, annotation and analysis of human chromosome 3."; RL Nature 440:1194-1198(2006). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS M1 AND M2). RC TISSUE=Skin; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP PARTIAL NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS A1/A2; B1/B2; H1/H2 AND RP M1/M2). RX PubMed=10760582; DOI=10.1016/s0167-4781(00)00051-8; RA Udono T., Yasumoto K., Takeda K., Amae S., Watanabe K., Saito H., Fuse N., RA Tachibana M., Takahashi K., Tamai M., Shibahara S.; RT "Structural organization of the human microphthalmia-associated RT transcription factor gene containing four alternative promoters."; RL Biochim. Biophys. Acta 1491:205-219(2000). RN [9] RP ALTERNATIVE SPLICING (ISOFORM C1/C2), AND TISSUE SPECIFICITY. RC TISSUE=Kidney; RX PubMed=10578055; DOI=10.1093/oxfordjournals.jbchem.a022548; RA Fuse N., Yasumoto K., Takeda K., Amae S., Yoshizawa M., Udono T., RA Takahashi K., Tamai M., Tomita Y., Tachibana M., Shibahara S.; RT "Molecular cloning of cDNA encoding a novel microphthalmia-associated RT transcription factor isoform with a distinct amino-terminus."; RL J. Biochem. 126:1043-1051(1999). RN [10] RP PHOSPHORYLATION AT SER-180 AND SER-516, UBIQUITINATION, AND MUTAGENESIS OF RP SER-180 AND SER-516. RX PubMed=10673502; DOI=10.1101/gad.14.3.301; RA Wu M., Hemesath T.J., Takemoto C.M., Horstmann M.A., Wells A.G., RA Price E.R., Fisher D.Z., Fisher D.E.; RT "c-Kit triggers dual phosphorylations, which couple activation and RT degradation of the essential melanocyte factor Mi."; RL Genes Dev. 14:301-312(2000). RN [11] RP FUNCTION, MUTAGENESIS OF SER-405, AND PHOSPHORYLATION AT SER-405. RX PubMed=10587587; DOI=10.1093/hmg/9.1.125; RA Takeda K., Takemoto C., Kobayashi I., Watanabe A., Nobukuni Y., RA Fisher D.E., Tachibana M.; RT "Ser298 of MITF, a mutation site in Waardenburg syndrome type 2, is a RT phosphorylation site with functional significance."; RL Hum. Mol. Genet. 9:125-132(2000). RN [12] RP INTERACTION WITH KARS1. RX PubMed=14975237; DOI=10.1016/s1074-7613(04)00020-2; RA Lee Y.N., Nechushtan H., Figov N., Razin E.; RT "The function of lysyl-tRNA synthetase and Ap4A as signaling regulators of RT MITF activity in FcepsilonRI-activated mast cells."; RL Immunity 20:145-151(2004). RN [13] RP SUBUNIT, SUMOYLATION AT LYS-289 AND LYS-423, AND MUTAGENESIS OF LYS-289 AND RP LYS-423. RX PubMed=15507434; DOI=10.1074/jbc.m411757200; RA Miller A.J., Levy C., Davis I.J., Razin E., Fisher D.E.; RT "Sumoylation of MITF and its related family members TFE3 and TFEB."; RL J. Biol. Chem. 280:146-155(2005). RN [14] RP SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-280, AND MUTAGENESIS OF RP SER-280. RX PubMed=16822840; DOI=10.1091/mbc.e06-05-0470; RA Bronisz A., Sharma S.M., Hu R., Godlewski J., Tzivion G., Mansky K.C., RA Ostrowski M.C.; RT "Microphthalmia-associated transcription factor interactions with 14-3-3 RT modulate differentiation of committed myeloid precursors."; RL Mol. Biol. Cell 17:3897-3906(2006). RN [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-414, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18220336; DOI=10.1021/pr0705441; RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III; RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient RT phosphoproteomic analysis."; RL J. Proteome Res. 7:1346-1351(2008). RN [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-414, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-491, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [18] RP FUNCTION, AND IDENTIFICATION IN A COMPLEX WITH HINT1 AND CTNNB1. RX PubMed=22647378; DOI=10.4161/cc.20765; RA Genovese G., Ghosh P., Li H., Rettino A., Sioletic S., Cittadini A., RA Sgambato A.; RT "The tumor suppressor HINT1 regulates MITF and beta-catenin transcriptional RT activity in melanoma cells."; RL Cell Cycle 11:2206-2215(2012). RN [19] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-414, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [20] RP SUBCELLULAR LOCATION, AND INTERACTION WITH SMALL GTPASES RAG. RX PubMed=23401004; DOI=10.1083/jcb.201209135; RA Martina J.A., Puertollano R.; RT "Rag GTPases mediate amino acid-dependent recruitment of TFEB and MITF to RT lysosomes."; RL J. Cell Biol. 200:475-491(2013). RN [21] RP FUNCTION, SUBCELLULAR LOCATION, INVOLVEMENT IN COMMAD, VARIANTS COMMAD RP ASN-313; ARG-324 DEL AND GLY-324, AND CHARACTERIZATION OF VARIANTS COMMAD RP ASN-313 AND ARG-324 DEL. RX PubMed=27889061; DOI=10.1016/j.ajhg.2016.11.004; RA George A., Zand D.J., Hufnagel R.B., Sharma R., Sergeev Y.V., Legare J.M., RA Rice G.M., Scott Schwoerer J.A., Rius M., Tetri L., Gamm D.M., Bharti K., RA Brooks B.P.; RT "Biallelic mutations in MITF cause coloboma, osteopetrosis, microphthalmia, RT macrocephaly, albinism, and deafness."; RL Am. J. Hum. Genet. 99:1388-1394(2016). RN [22] RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND PHOSPHORYLATION. RX PubMed=28842328; DOI=10.1016/j.jid.2017.07.833; RA Regazzetti C., Sormani L., Debayle D., Bernerd F., Tulic M.K., RA De Donatis G.M., Chignon-Sicard B., Rocchi S., Passeron T.; RT "Melanocytes Sense Blue Light and Regulate Pigmentation through Opsin-3."; RL J. Invest. Dermatol. 138:171-178(2018). RN [23] RP INVOLVEMENT IN DISEASE, AND VARIANT LYS-425. RX PubMed=27680874; DOI=10.1210/jc.2016-2103; RA Castro-Vega L.J., Kiando S.R., Burnichon N., Buffet A., Amar L., Simian C., RA Berdelou A., Galan P., Schlumberger M., Bouatia-Naji N., Favier J., RA Bressac-de Paillerets B., Gimenez-Roqueplo A.P.; RT "The MITF, p.E318K Variant, as a Risk Factor for Pheochromocytoma and RT Paraganglioma."; RL J. Clin. Endocrinol. Metab. 101:4764-4768(2016). RN [24] RP FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-5 AND SER-280, RP UBIQUITINATION, AND MUTAGENESIS OF SER-5. RX PubMed=36608670; DOI=10.1016/j.molcel.2022.12.013; RA Nardone C., Palanski B.A., Scott D.C., Timms R.T., Barber K.W., Gu X., RA Mao A., Leng Y., Watson E.V., Schulman B.A., Cole P.A., Elledge S.J.; RT "A central role for regulated protein stability in the control of TFE3 and RT MITF by nutrients."; RL Mol. Cell 83:57-73(2023). RN [25] RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 357-403, SUBUNIT, AND COILED RP COIL. RX PubMed=24631970; DOI=10.1016/j.jsb.2014.03.002; RA Kukenshoner T., Wohlwend D., Niemoller C., Dondapati P., Speck J., RA Adeniran A.V., Nieth A., Gerhardt S., Einsle O., Muller K.M., Arndt K.M.; RT "Improving coiled coil stability while maintaining specificity by a RT bacterial hitchhiker selection system."; RL J. Struct. Biol. 186:335-348(2014). RN [26] RP VARIANTS WS2A LYS-310; ARG-324 DEL; PRO-357; ASP-385 AND PRO-405. RX PubMed=8589691; DOI=10.1093/hmg/4.11.2131; RA Tassabehji M., Newton V.E., Liu X.-Z., Brady A., Donnai D., RA Krajewska-Walasek M., Murday V., Norman A., Obersztyn E., Reardon W., RA Rice J.C., Trembath R., Wieacker P., Whiteford M., Winter R., Read A.P.; RT "The mutational spectrum in Waardenburg syndrome."; RL Hum. Mol. Genet. 4:2131-2137(1995). RN [27] RP VARIANT TADS LYS-317. RC TISSUE=Blood; RX PubMed=10851256; DOI=10.1136/jmg.37.6.446; RA Smith S.D., Kelley P.M., Kenyon J.B., Hoover D.; RT "Tietz syndrome (hypopigmentation/deafness) caused by mutation of MITF."; RL J. Med. Genet. 37:446-448(2000). RN [28] RP INVOLVEMENT IN CMM8, AND VARIANT CMM8 LYS-425. RX PubMed=22012259; DOI=10.1038/nature10539; RA Bertolotto C., Lesueur F., Giuliano S., Strub T., de Lichy M., Bille K., RA Dessen P., d'Hayer B., Mohamdi H., Remenieras A., Maubec E., RA de la Fouchardiere A., Molinie V., Vabres P., Dalle S., Poulalhon N., RA Martin-Denavit T., Thomas L., Andry-Benzaquen P., Dupin N., Boitier F., RA Rossi A., Perrot J.L., Labeille B., Robert C., Escudier B., Caron O., RA Brugieres L., Saule S., Gardie B., Gad S., Richard S., Couturier J., RA Teh B.T., Ghiorzo P., Pastorino L., Puig S., Badenas C., Olsson H., RA Ingvar C., Rouleau E., Lidereau R., Bahadoran P., Vielh P., Corda E., RA Blanche H., Zelenika D., Galan P., Aubin F., Bachollet B., Becuwe C., RA Berthet P., Bignon Y.J., Bonadona V., Bonafe J.L., Bonnet-Dupeyron M.N., RA Cambazard F., Chevrant-Breton J., Coupier I., Dalac S., Demange L., RA d'Incan M., Dugast C., Faivre L., Vincent-Fetita L., Gauthier-Villars M., RA Gilbert B., Grange F., Grob J.J., Humbert P., Janin N., Joly P., Kerob D., RA Lasset C., Leroux D., Levang J., Limacher J.M., Livideanu C., Longy M., RA Lortholary A., Stoppa-Lyonnet D., Mansard S., Mansuy L., Marrou K., RA Mateus C., Maugard C., Meyer N., Nogues C., Souteyrand P., Venat-Bouvet L., RA Zattara H., Chaudru V., Lenoir G.M., Lathrop M., Davidson I., Avril M.F., RA Demenais F., Ballotti R., Bressac-de Paillerets B.; RT "A SUMOylation-defective MITF germline mutation predisposes to melanoma and RT renal carcinoma."; RL Nature 480:94-98(2011). RN [29] RP INVOLVEMENT IN CMM8, VARIANT CMM8 LYS-425, AND CHARACTERIZATION OF VARIANT RP CMM8 LYS-425. RX PubMed=22080950; DOI=10.1038/nature10630; RA Yokoyama S., Woods S.L., Boyle G.M., Aoude L.G., MacGregor S., Zismann V., RA Gartside M., Cust A.E., Haq R., Harland M., Taylor J.C., Duffy D.L., RA Holohan K., Dutton-Regester K., Palmer J.M., Bonazzi V., Stark M.S., RA Symmons J., Law M.H., Schmidt C., Lanagan C., O'Connor L., Holland E.A., RA Schmid H., Maskiell J.A., Jetann J., Ferguson M., Jenkins M.A., RA Kefford R.F., Giles G.G., Armstrong B.K., Aitken J.F., Hopper J.L., RA Whiteman D.C., Pharoah P.D., Easton D.F., Dunning A.M., Newton-Bishop J.A., RA Montgomery G.W., Martin N.G., Mann G.J., Bishop D.T., Tsao H., Trent J.M., RA Fisher D.E., Hayward N.K., Brown K.M.; RT "A novel recurrent mutation in MITF predisposes to familial and sporadic RT melanoma."; RL Nature 480:99-103(2011). RN [30] RP VARIANT WS2A THR-294. RX PubMed=28236341; DOI=10.1002/humu.23206; RA Issa S., Bondurand N., Faubert E., Poisson S., Lecerf L., Nitschke P., RA Deggouj N., Loundon N., Jonard L., David A., Sznajer Y., Blanchet P., RA Marlin S., Pingault V.; RT "EDNRB mutations cause Waardenburg syndrome type II in the heterozygous RT state."; RL Hum. Mutat. 38:581-593(2017). CC -!- FUNCTION: Transcription factor that acts as a master regulator of CC melanocyte survival and differentiation as well as melanosome CC biogenesis (PubMed:10587587, PubMed:22647378, PubMed:27889061, CC PubMed:9647758). Binds to M-boxes (5'-TCATGTG-3') and symmetrical DNA CC sequences (E-boxes) (5'-CACGTG-3') found in the promoter of CC pigmentation genes, such as tyrosinase (TYR) (PubMed:10587587, CC PubMed:22647378, PubMed:27889061, PubMed:9647758). Involved in the CC cellular response to amino acid availability by acting downstream of CC MTOR: in the presence of nutrients, MITF phosphorylation by MTOR CC promotes its inactivation (PubMed:36608670). Upon starvation or CC lysosomal stress, inhibition of MTOR induces MITF dephosphorylation, CC resulting in transcription factor activity (PubMed:36608670). Plays an CC important role in melanocyte development by regulating the expression CC of tyrosinase (TYR) and tyrosinase-related protein 1 (TYRP1) CC (PubMed:10587587, PubMed:22647378, PubMed:27889061, PubMed:9647758). CC Plays a critical role in the differentiation of various cell types, CC such as neural crest-derived melanocytes, mast cells, osteoclasts and CC optic cup-derived retinal pigment epithelium (PubMed:10587587, CC PubMed:22647378, PubMed:27889061, PubMed:9647758). CC {ECO:0000269|PubMed:10587587, ECO:0000269|PubMed:22647378, CC ECO:0000269|PubMed:27889061, ECO:0000269|PubMed:36608670, CC ECO:0000269|PubMed:9647758}. CC -!- SUBUNIT: Homodimer or heterodimer; dimerization is mediated via the CC coiled coil region (PubMed:24631970). Efficient DNA binding requires CC dimerization with another bHLH protein (PubMed:14975237). Binds DNA in CC the form of homodimer or heterodimer with either TFE3, TFEB or CC TFEC (PubMed:15507434). Interacts with small GTPases Rag (RagA/RRAGA, CC RagB/RRAGB, RagC/RRAGC and/or RagD/RRAGD); promoting its recruitment to CC lysosomal membrane in the presence of nutrients (PubMed:23401004, CC PubMed:36608670). Interacts with KARS1 (PubMed:14975237). Identified in CC a complex with HINT1 and CTNNB1 (PubMed:22647378). Interacts with VSX2 CC (By similarity). {ECO:0000250|UniProtKB:Q08874, CC ECO:0000269|PubMed:14975237, ECO:0000269|PubMed:15507434, CC ECO:0000269|PubMed:22647378, ECO:0000269|PubMed:23401004, CC ECO:0000269|PubMed:24631970, ECO:0000269|PubMed:36608670}. CC -!- INTERACTION: CC O75030; P63165: SUMO1; NbExp=2; IntAct=EBI-3910192, EBI-80140; CC O75030; P19532: TFE3; NbExp=2; IntAct=EBI-3910192, EBI-1048957; CC O75030; P19484: TFEB; NbExp=3; IntAct=EBI-3910192, EBI-2814208; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:16822840, CC ECO:0000269|PubMed:27889061, ECO:0000269|PubMed:28842328, CC ECO:0000269|PubMed:36608670}. Cytoplasm {ECO:0000269|PubMed:16822840, CC ECO:0000269|PubMed:28842328, ECO:0000269|PubMed:36608670}. Lysosome CC membrane {ECO:0000269|PubMed:23401004, ECO:0000269|PubMed:36608670}. CC Note=When nutrients are present, recruited to the lysosomal membrane CC via association with GDP-bound RagC/RRAGC (or RagD/RRAGD): it is then CC phosphorylated by MTOR (PubMed:23401004, PubMed:36608670). CC Phosphorylation by MTOR promotes ubiquitination and degradation CC (PubMed:36608670). Conversely, inhibition of mTORC1, starvation and CC lysosomal disruption, promotes dephosphorylation and translocation to CC the nucleus (PubMed:36608670). Phosphorylation by MARK3/cTAK1 promotes CC association with 14-3-3/YWHA adapters and retention in the cytosol CC (PubMed:16822840). {ECO:0000269|PubMed:16822840, CC ECO:0000269|PubMed:23401004, ECO:0000269|PubMed:36608670}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=12; CC Comment=The X2-type isoforms differ from the X1-type isoforms by the CC absence of a 6 residue insert.; CC Name=A1; CC IsoId=O75030-1; Sequence=Displayed; CC Name=A2; CC IsoId=O75030-2; Sequence=VSP_002128; CC Name=B1; CC IsoId=O75030-3; Sequence=VSP_002124; CC Name=B2; CC IsoId=O75030-4; Sequence=VSP_002124, VSP_002128; CC Name=C1; CC IsoId=O75030-5; Sequence=VSP_002125; CC Name=C2; CC IsoId=O75030-6; Sequence=VSP_002125, VSP_002128; CC Name=H1; CC IsoId=O75030-7; Sequence=VSP_002126; CC Name=H2; CC IsoId=O75030-8; Sequence=VSP_002126, VSP_002128; CC Name=M1; CC IsoId=O75030-9; Sequence=VSP_002127; CC Name=M2; CC IsoId=O75030-10; Sequence=VSP_002127, VSP_002128; CC Name=Mdel; CC IsoId=O75030-11; Sequence=VSP_002127, VSP_045178, VSP_045179; CC Name=12; CC IsoId=O75030-12; Sequence=VSP_046438, VSP_045179; CC -!- TISSUE SPECIFICITY: Expressed in melanocytes (at protein level). CC {ECO:0000269|PubMed:28842328}. CC -!- TISSUE SPECIFICITY: [Isoform A2]: Expressed in the retinal pigment CC epithelium, brain, and placenta (PubMed:9647758). Expressed in the CC kidney (PubMed:10578055, PubMed:9647758). {ECO:0000269|PubMed:10578055, CC ECO:0000269|PubMed:9647758}. CC -!- TISSUE SPECIFICITY: [Isoform C2]: Expressed in the kidney and retinal CC pigment epithelium. {ECO:0000269|PubMed:10578055}. CC -!- TISSUE SPECIFICITY: [Isoform H1]: Expressed in the kidney. CC {ECO:0000269|PubMed:10578055, ECO:0000269|PubMed:9647758}. CC -!- TISSUE SPECIFICITY: [Isoform H2]: Expressed in the kidney. CC {ECO:0000269|PubMed:10578055, ECO:0000269|PubMed:9647758}. CC -!- TISSUE SPECIFICITY: [Isoform M1]: Expressed in melanocytes. CC {ECO:0000269|PubMed:20163701}. CC -!- TISSUE SPECIFICITY: [Isoform Mdel]: Expressed in melanocytes. CC {ECO:0000269|PubMed:20163701}. CC -!- DOMAIN: The leucine zipper region is part of a larger coiled coil. CC {ECO:0000305|PubMed:24631970}. CC -!- PTM: When nutrients are present, phosphorylation by MTOR at Ser-5 via CC non-canonical mTORC1 pathway promotes ubiquitination by the SCF(BTRC) CC complex, followed by degradation (PubMed:36608670). Phosphorylation at CC Ser-405 significantly enhances the ability to bind the tyrosinase CC promoter (PubMed:10587587). Phosphorylation by MARK3/cTAK1 at Ser-280 CC promotes association with 14-3-3/YWHA adapters and retention in the CC cytosol (PubMed:16822840). Phosphorylated at Ser-180 and Ser-516 CC following KIT signaling, triggering a short live activation: CC Phosphorylation at Ser-180 and Ser-516 by MAPK and RPS6KA1, CC respectively, activate the transcription factor activity but also CC promote ubiquitination and subsequent degradation by the proteasome CC (PubMed:10673502). Phosphorylated in response to blue light (415nm) CC (PubMed:28842328). {ECO:0000269|PubMed:10587587, CC ECO:0000269|PubMed:10673502, ECO:0000269|PubMed:16822840, CC ECO:0000269|PubMed:28842328, ECO:0000269|PubMed:36608670}. CC -!- PTM: Ubiquitinated by the SCF(BTRC) and SCF(FBXW11) complexes following CC phosphorylation ar Ser-5 by MTOR, leading to its degradation by the CC proteasome (PubMed:36608670). Ubiquitinated following phosphorylation CC at Ser-180, leading to subsequent degradation by the proteasome CC (PubMed:10673502). Deubiquitinated by USP13, preventing its degradation CC (PubMed:10673502). {ECO:0000269|PubMed:10673502, CC ECO:0000269|PubMed:36608670}. CC -!- DISEASE: Waardenburg syndrome 2A (WS2A) [MIM:193510]: WS2 is a CC genetically heterogeneous, autosomal dominant disorder characterized by CC sensorineural deafness, pigmentary disturbances, and absence of CC dystopia canthorum. The frequency of deafness is higher in WS2 than in CC WS1. {ECO:0000269|PubMed:28236341, ECO:0000269|PubMed:8589691, CC ECO:0000269|PubMed:9647758}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Tietz albinism-deafness syndrome (TADS) [MIM:103500]: An CC autosomal dominant disorder characterized by generalized CC hypopigmentation and congenital, bilateral, profound sensorineural CC deafness. {ECO:0000269|PubMed:10851256}. Note=The disease is caused by CC variants affecting the gene represented in this entry. CC -!- DISEASE: Melanoma, cutaneous malignant 8 (CMM8) [MIM:614456]: A CC malignant neoplasm of melanocytes, arising de novo or from a pre- CC existing benign nevus, which occurs most often in the skin but may also CC involve other sites. {ECO:0000269|PubMed:22012259, CC ECO:0000269|PubMed:22080950}. Note=Disease susceptibility is associated CC with variants affecting the gene represented in this entry. CC -!- DISEASE: Coloboma, osteopetrosis, microphthalmia, macrocephaly, CC albinism, and deafness (COMMAD) [MIM:617306]: An autosomal recessive CC syndrome characterized by severe microphthalmia, profound congenital CC sensorineural hearing loss, lack of pigment in the hair, skin, and CC eyes, macrocephaly, facial dysmorphism, and osteopetrosis. CC {ECO:0000269|PubMed:27889061}. Note=The disease is caused by variants CC affecting the gene represented in this entry. An allelic combination CC involving at least one dominant-negative mutation, inherited in a CC recessive manner, represents the underlying molecular mechanism leading CC to COMMAD syndrome. {ECO:0000269|PubMed:27889061}. CC -!- DISEASE: Note=Variations affecting this gene are associated with CC susceptibility to pheochromocytomas and paragangliomas, rare neural CC crest-derived tumors with an approximate incidence of 1:300,000/year. CC {ECO:0000269|PubMed:27680874}. CC -!- SIMILARITY: Belongs to the MiT/TFE family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AB006909; BAA32288.1; -; mRNA. DR EMBL; AB006989; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; Z29678; CAA82775.1; -; mRNA. DR EMBL; GU355676; ADB90411.1; -; mRNA. DR EMBL; AL110195; CAB53672.1; -; mRNA. DR EMBL; AK296129; BAG58874.1; -; mRNA. DR EMBL; AC099326; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC104445; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC104449; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC124915; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC026961; AAH26961.1; -; mRNA. DR EMBL; BC065243; AAH65243.1; -; mRNA. DR EMBL; AF034755; AAC39639.1; -; Genomic_DNA. DR EMBL; AB032359; BAA95208.1; -; Genomic_DNA. DR EMBL; AB032358; BAA95207.1; -; Genomic_DNA. DR EMBL; AB032357; BAA95206.1; -; Genomic_DNA. DR EMBL; AB009608; BAA95209.1; ALT_TERM; Genomic_DNA. DR CCDS; CCDS2913.1; -. [O75030-9] DR CCDS; CCDS43106.1; -. [O75030-2] DR CCDS; CCDS43107.1; -. [O75030-10] DR CCDS; CCDS46865.1; -. [O75030-8] DR CCDS; CCDS46866.2; -. [O75030-11] DR CCDS; CCDS54607.1; -. [O75030-12] DR CCDS; CCDS87108.1; -. [O75030-1] DR PIR; I38024; I38024. DR PIR; T14752; T14752. DR RefSeq; NP_000239.1; NM_000248.4. [O75030-9] DR RefSeq; NP_001171896.1; NM_001184967.2. [O75030-12] DR RefSeq; NP_001341533.1; NM_001354604.2. [O75030-1] DR RefSeq; NP_001341537.1; NM_001354608.2. [O75030-12] DR RefSeq; NP_006713.1; NM_006722.3. [O75030-6] DR RefSeq; NP_937801.1; NM_198158.3. [O75030-10] DR RefSeq; NP_937802.1; NM_198159.3. [O75030-2] DR RefSeq; NP_937820.1; NM_198177.3. [O75030-8] DR RefSeq; NP_937821.2; NM_198178.3. [O75030-11] DR PDB; 4C7N; X-ray; 2.10 A; A=356-403. DR PDB; 7D8R; X-ray; 3.00 A; A/B/C/D=324-395. DR PDB; 7D8S; X-ray; 2.28 A; A/B/C/D=306-395. DR PDB; 7D8T; X-ray; 3.20 A; A/B=306-395. DR PDB; 7EOD; X-ray; 1.90 A; A/B/C/D=323-395. DR PDB; 8E1D; NMR; -; B=216-248. DR PDB; 9H5F; X-ray; 2.30 A; A/B/C=324-403. DR PDB; 9H5H; X-ray; 1.74 A; A/B/C=324-403. DR PDB; 9H7Q; X-ray; 1.72 A; A/B/C=324-403. DR PDB; 9H7R; X-ray; 2.52 A; A/B/C=324-403. DR PDB; 9H7S; X-ray; 1.99 A; A/B/C=324-403. DR PDB; 9H7T; X-ray; 1.85 A; A/B/C=324-403. DR AlphaFoldDB; O75030; -. DR SMR; O75030; -. DR BioGRID; 110432; 52. DR CORUM; O75030; -. DR DIP; DIP-59573N; -. DR FunCoup; O75030; 2684. DR IntAct; O75030; 28. DR MINT; O75030; -. DR NDEx; IQUERY-CP-MITF; 14 NDEx IQuery Curated Pathways. DR STRING; 9606.ENSP00000391803; -. DR ChEMBL; CHEMBL1741165; -. DR GlyGen; O75030; 5 sites, 1 O-linked glycan (5 sites). DR iPTMnet; O75030; -. DR PhosphoSitePlus; O75030; -. DR BioMuta; MITF; -. DR jPOST; O75030; -. DR MassIVE; O75030; -. DR PaxDb; 9606-ENSP00000391803; -. DR PeptideAtlas; O75030; -. DR ProteomicsDB; 12779; -. DR ProteomicsDB; 20138; -. DR ProteomicsDB; 49704; -. [O75030-1] DR ProteomicsDB; 49705; -. [O75030-10] DR ProteomicsDB; 49706; -. [O75030-2] DR ProteomicsDB; 49707; -. [O75030-3] DR ProteomicsDB; 49708; -. [O75030-4] DR ProteomicsDB; 49709; -. [O75030-5] DR ProteomicsDB; 49710; -. [O75030-6] DR ProteomicsDB; 49711; -. [O75030-7] DR ProteomicsDB; 49712; -. [O75030-8] DR ProteomicsDB; 49713; -. [O75030-9] DR Pumba; O75030; -. DR Antibodypedia; 923; 979 antibodies from 48 providers. DR DNASU; 4286; -. DR Ensembl; ENST00000314557.10; ENSP00000324246.6; ENSG00000187098.19. [O75030-10] DR Ensembl; ENST00000314589.11; ENSP00000324443.5; ENSG00000187098.19. [O75030-8] DR Ensembl; ENST00000352241.9; ENSP00000295600.8; ENSG00000187098.19. [O75030-1] DR Ensembl; ENST00000394351.9; ENSP00000377880.3; ENSG00000187098.19. [O75030-9] DR Ensembl; ENST00000448226.9; ENSP00000391803.3; ENSG00000187098.19. [O75030-6] DR Ensembl; ENST00000472437.5; ENSP00000418845.1; ENSG00000187098.19. [O75030-12] DR Ensembl; ENST00000531774.1; ENSP00000435909.1; ENSG00000187098.19. [O75030-11] DR Ensembl; ENST00000642352.1; ENSP00000494105.1; ENSG00000187098.19. [O75030-2] DR Ensembl; ENST00000956040.1; ENSP00000626099.1; ENSG00000187098.19. [O75030-2] DR GeneID; 4286; -. DR KEGG; hsa:4286; -. DR MANE-Select; ENST00000352241.9; ENSP00000295600.8; NM_001354604.2; NP_001341533.1. DR UCSC; uc003dnz.4; human. [O75030-1] DR AGR; HGNC:7105; -. DR CIViC; 4286; 2 evidence items across 2 molecular profiles. DR ClinPGx; PA30823; -. DR CTD; 4286; -. DR DisGeNET; 4286; -. DR GeneCards; MITF; -. DR HGNC; HGNC:7105; MITF. DR HPA; ENSG00000187098; Low tissue specificity. DR MalaCards; MITF; -. DR MIM; 103500; phenotype. DR MIM; 156845; gene. DR MIM; 193510; phenotype. DR MIM; 614456; phenotype. DR MIM; 617306; phenotype. DR OpenTargets; ENSG00000187098; -. DR Orphanet; 404511; Clear cell papillary renal cell carcinoma. DR Orphanet; 618; Familial melanoma. DR Orphanet; 293822; MITF-related melanoma and renal cell carcinoma predisposition syndrome. DR Orphanet; 319298; Papillary renal cell carcinoma. DR Orphanet; 42665; Tietz syndrome. DR Orphanet; 895; Waardenburg syndrome type 2. DR Orphanet; 897; Waardenburg-Shah syndrome. DR VEuPathDB; HostDB:ENSG00000187098; -. DR eggNOG; KOG1318; Eukaryota. DR GeneTree; ENSGT00940000156326; -. DR HOGENOM; CLU_031638_2_0_1; -. DR InParanoid; O75030; -. DR OMA; GIPMANT; -. DR OrthoDB; 6242697at2759; -. DR PAN-GO; O75030; 5 GO annotations based on evolutionary models. DR PhylomeDB; O75030; -. DR PathwayCommons; O75030; -. DR Reactome; R-HSA-3232118; SUMOylation of transcription factors. DR Reactome; R-HSA-9824585; Regulation of MITF-M-dependent genes involved in pigmentation. [O75030-9] DR Reactome; R-HSA-9824594; Regulation of MITF-M-dependent genes involved in apoptosis. [O75030-9] DR Reactome; R-HSA-9825892; Regulation of MITF-M-dependent genes involved in cell cycle and proliferation. [O75030-9] DR Reactome; R-HSA-9825895; Regulation of MITF-M-dependent genes involved in DNA replication, damage repair and senescence. [O75030-9] DR Reactome; R-HSA-9854907; Regulation of MITF-M dependent genes involved in metabolism. [O75030-9] DR Reactome; R-HSA-9854909; Regulation of MITF-M dependent genes involved in invasion. [O75030-9] DR Reactome; R-HSA-9856649; Transcriptional and post-translational regulation of MITF-M expression and activity. DR Reactome; R-HSA-9857377; Regulation of MITF-M-dependent genes involved in lysosome biogenesis and autophagy. [O75030-9] DR Reactome; R-HSA-9926550; Regulation of MITF-M-dependent genes involved in extracellular matrix, focal adhesion and epithelial-to-mesenchymal transition. [O75030-9] DR SignaLink; O75030; -. DR SIGNOR; O75030; -. DR Agora; ENSG00000187098; Agora Nominated Target for Alzheimer's Disease. DR BioGRID-ORCS; 4286; 28 hits in 1188 CRISPR screens. DR ChiTaRS; MITF; human. DR EvolutionaryTrace; O75030; -. DR GeneWiki; Microphthalmia-associated_transcription_factor; -. DR GenomeRNAi; 4286; -. DR Pharos; O75030; Tchem. DR PRO; PR:O75030; -. DR Proteomes; UP000005640; Chromosome 3. DR RNAct; O75030; protein. DR Bgee; ENSG00000187098; Expressed in pigmented layer of retina and 210 other cell types or tissues. DR ExpressionAtlas; O75030; baseline and differential. DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005765; C:lysosomal membrane; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB. DR GO; GO:0003682; F:chromatin binding; IEA:Ensembl. DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:UniProtKB. DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB. DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; NAS:BHF-UCL. DR GO; GO:0070888; F:E-box binding; IDA:UniProtKB. DR GO; GO:0046983; F:protein dimerization activity; IEA:Ensembl. DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:NTNU_SB. DR GO; GO:0030318; P:melanocyte differentiation; IBA:GO_Central. DR GO; GO:0030336; P:negative regulation of cell migration; IMP:BHF-UCL. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:BHF-UCL. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:2000144; P:positive regulation of DNA-templated transcription initiation; IDA:CACAO. DR GO; GO:0010628; P:positive regulation of gene expression; IDA:CACAO. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB. DR GO; GO:0065003; P:protein-containing complex assembly; IDA:UniProtKB. DR GO; GO:0006355; P:regulation of DNA-templated transcription; IMP:UniProtKB. DR GO; GO:2001141; P:regulation of RNA biosynthetic process; IDA:CACAO. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central. DR CDD; cd18926; bHLHzip_MITF; 1. DR FunFam; 4.10.280.10:FF:000003; microphthalmia-associated transcription factor isoform X1; 1. DR Gene3D; 4.10.280.10; Helix-loop-helix DNA-binding domain; 1. DR InterPro; IPR011598; bHLH_dom. DR InterPro; IPR036638; HLH_DNA-bd_sf. DR InterPro; IPR021802; MiT/TFE_C. DR InterPro; IPR031867; MiT/TFE_N. DR PANTHER; PTHR45776:SF4; MICROPHTHALMIA-ASSOCIATED TRANSCRIPTION FACTOR; 1. DR PANTHER; PTHR45776; MIP04163P; 1. DR Pfam; PF11851; DUF3371; 1. DR Pfam; PF00010; HLH; 1. DR Pfam; PF15951; MITF_TFEB_C_3_N; 1. DR SMART; SM00353; HLH; 1. DR SUPFAM; SSF47459; HLH, helix-loop-helix DNA-binding domain; 1. DR PROSITE; PS50888; BHLH; 1. DR PDBsum; 4C7N; -. DR PDBsum; 7D8R; -. DR PDBsum; 7D8S; -. DR PDBsum; 7D8T; -. DR PDBsum; 7EOD; -. DR PDBsum; 8E1D; -. DR PDBsum; 9H5F; -. DR PDBsum; 9H5H; -. DR PDBsum; 9H7Q; -. DR PDBsum; 9H7R; -. DR PDBsum; 9H7S; -. DR PDBsum; 9H7T; -. PE 1: Evidence at protein level; KW 3D-structure; Activator; Albinism; Alternative splicing; Coiled coil; KW Cytoplasm; Deafness; Developmental protein; Disease variant; DNA-binding; KW Isopeptide bond; Lysosome; Membrane; Microphthalmia; Nucleus; KW Osteopetrosis; Phosphoprotein; Proteomics identification; KW Reference proteome; Transcription; Transcription regulation; KW Ubl conjugation; Waardenburg syndrome. FT CHAIN 1..526 FT /note="Microphthalmia-associated transcription factor" FT /id="PRO_0000127276" FT DOMAIN 311..364 FT /note="bHLH" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981" FT REGION 1..54 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 224..295 FT /note="Transactivation" FT REGION 374..395 FT /note="Leucine-zipper" FT /evidence="ECO:0000305|PubMed:24631970" FT REGION 401..431 FT /note="DNA-binding regulation" FT REGION 496..526 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COILED 355..402 FT /evidence="ECO:0000305|PubMed:24631970" FT COMPBIAS 15..25 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 41..54 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 499..509 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 5 FT /note="Phosphoserine; by MTOR" FT /evidence="ECO:0000269|PubMed:36608670" FT MOD_RES 180 FT /note="Phosphoserine; by MAPK" FT /evidence="ECO:0000269|PubMed:10673502" FT MOD_RES 280 FT /note="Phosphoserine; by MARK3" FT /evidence="ECO:0000269|PubMed:36608670" FT MOD_RES 405 FT /note="Phosphoserine; by GSK3" FT /evidence="ECO:0000269|PubMed:10587587" FT MOD_RES 414 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18220336, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:23186163" FT MOD_RES 491 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231" FT MOD_RES 516 FT /note="Phosphoserine; by RPS6KA1" FT /evidence="ECO:0000269|PubMed:10673502" FT CROSSLNK 289 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO)" FT /evidence="ECO:0000269|PubMed:15507434" FT CROSSLNK 423 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO)" FT /evidence="ECO:0000269|PubMed:15507434" FT VAR_SEQ 1..118 FT /note="MQSESGIVPDFEVGEEFHEEPKTYYELKSQPLKSSSSAEHPGASKPPISSSS FT MTSRILLRQQLMREQMQEQERREQQQKLQAAQFMQQRVPVSQTPAINVSVPTTLPSATQ FT VPMEVLK -> MLEMLEYNHYQ (in isoform M1, isoform M2 and FT isoform Mdel)" FT /evidence="ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:20163701, ECO:0000303|PubMed:8069297" FT /id="VSP_002127" FT VAR_SEQ 1..52 FT /note="Missing (in isoform 12)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_046438" FT VAR_SEQ 1..35 FT /note="MQSESGIVPDFEVGEEFHEEPKTYYELKSQPLKSS -> MEALRVQMFMPCS FT FESLYL (in isoform H1 and isoform H2)" FT /evidence="ECO:0000305" FT /id="VSP_002126" FT VAR_SEQ 1..34 FT /note="MQSESGIVPDFEVGEEFHEEPKTYYELKSQPLKS -> MLYAFWFSH (in FT isoform B1 and isoform B2)" FT /evidence="ECO:0000305" FT /id="VSP_002124" FT VAR_SEQ 1..34 FT /note="MQSESGIVPDFEVGEEFHEEPKTYYELKSQPLKS -> MGHLENTSVVFPRA FT IFSLCEKETRKLTLCLFSR (in isoform C1 and isoform C2)" FT /evidence="ECO:0000305" FT /id="VSP_002125" FT VAR_SEQ 139..194 FT /note="Missing (in isoform Mdel)" FT /evidence="ECO:0000303|PubMed:20163701" FT /id="VSP_045178" FT VAR_SEQ 293..298 FT /note="Missing (in isoform Mdel and isoform 12)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:20163701" FT /id="VSP_045179" FT VAR_SEQ 294..299 FT /note="Missing (in isoform A2, isoform B2, isoform C2, FT isoform H2 and isoform M2)" FT /evidence="ECO:0000303|PubMed:11230166, FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:9647758" FT /id="VSP_002128" FT VARIANT 294 FT /note="A -> T (in WS2A; uncertain significance; FT dbSNP:rs1559742541)" FT /evidence="ECO:0000269|PubMed:28236341" FT /id="VAR_078311" FT VARIANT 310 FT /note="R -> K (in WS2A; uncertain significance)" FT /evidence="ECO:0000269|PubMed:8589691" FT /id="VAR_010297" FT VARIANT 313 FT /note="K -> N (in COMMAD; has both cytoplasmic and nuclear FT localization; decreased binding to M-box or E-box DNA FT sequences; dbSNP:rs1057519325)" FT /evidence="ECO:0000269|PubMed:27889061" FT /id="VAR_077922" FT VARIANT 317 FT /note="N -> K (in TADS; dbSNP:rs104893745)" FT /evidence="ECO:0000269|PubMed:10851256" FT /id="VAR_010298" FT VARIANT 324 FT /note="R -> G (in COMMAD; dbSNP:rs1057519326)" FT /evidence="ECO:0000269|PubMed:27889061" FT /id="VAR_077923" FT VARIANT 324 FT /note="Missing (in WS2A and COMMAD; does not localize to FT the nucleus; does not bind M-box or E-box DNA sequences; FT loss of function in transcriptional regulation; dominant FT negative effect; dbSNP:rs1553704814)" FT /evidence="ECO:0000269|PubMed:27889061, FT ECO:0000269|PubMed:8589691" FT /id="VAR_010299" FT VARIANT 357 FT /note="S -> P (in WS2A; dbSNP:rs104893744)" FT /evidence="ECO:0000269|PubMed:8589691" FT /id="VAR_010300" FT VARIANT 385 FT /note="N -> D (in WS2A)" FT /evidence="ECO:0000269|PubMed:8589691" FT /id="VAR_010301" FT VARIANT 405 FT /note="S -> P (in WS2A; dbSNP:rs104893747)" FT /evidence="ECO:0000269|PubMed:8589691" FT /id="VAR_010302" FT VARIANT 425 FT /note="E -> K (risk factor for CMM8; risk factor for FT pheochromocytomas and paragangliomas; results in impaired FT sumoylation; dbSNP:rs149617956)" FT /evidence="ECO:0000269|PubMed:22012259, FT ECO:0000269|PubMed:22080950, ECO:0000269|PubMed:27680874" FT /id="VAR_067367" FT MUTAGEN 5 FT /note="S->A: Impaired phosphorylation by MTOR, leading to FT abolished ubiquitination and degradation by the SCF(BTRC) FT complex." FT /evidence="ECO:0000269|PubMed:36608670" FT MUTAGEN 180 FT /note="S->A: Abolishes both transcription factor activity FT and ubiquitination, leading to an inert and stable protein; FT when associated with A-516." FT /evidence="ECO:0000269|PubMed:10673502" FT MUTAGEN 280 FT /note="S->A: Accumulates in the nucleus due to impaired FT phosphorylation." FT /evidence="ECO:0000269|PubMed:16822840" FT MUTAGEN 289 FT /note="K->R: Loss of sumoylation; when associated with FT R-423." FT /evidence="ECO:0000269|PubMed:15507434" FT MUTAGEN 405 FT /note="S->A,P: Loss of phosphorylation and function." FT /evidence="ECO:0000269|PubMed:10587587" FT MUTAGEN 423 FT /note="K->R: Loss of sumoylation; when associated with FT R-289." FT /evidence="ECO:0000269|PubMed:15507434" FT MUTAGEN 516 FT /note="S->A: Abolishes both transcription factor activity FT and ubiquitination, leading to an inert and stable protein; FT when associated with A-180." FT /evidence="ECO:0000269|PubMed:10673502" FT CONFLICT 241 FT /note="I -> T (in Ref. 5; BAG58874)" FT /evidence="ECO:0000305" FT HELIX 217..221 FT /evidence="ECO:0007829|PDB:8E1D" FT HELIX 225..236 FT /evidence="ECO:0007829|PDB:8E1D" FT HELIX 239..242 FT /evidence="ECO:0007829|PDB:8E1D" FT HELIX 326..337 FT /evidence="ECO:0007829|PDB:7EOD" FT HELIX 350..370 FT /evidence="ECO:0007829|PDB:7EOD" FT HELIX 374..394 FT /evidence="ECO:0007829|PDB:7EOD" SQ SEQUENCE 526 AA; 58795 MW; 136EBED3044C1986 CRC64; MQSESGIVPD FEVGEEFHEE PKTYYELKSQ PLKSSSSAEH PGASKPPISS SSMTSRILLR QQLMREQMQE QERREQQQKL QAAQFMQQRV PVSQTPAINV SVPTTLPSAT QVPMEVLKVQ THLENPTKYH IQQAQRQQVK QYLSTTLANK HANQVLSLPC PNQPGDHVMP PVPGSSAPNS PMAMLTLNSN CEKEGFYKFE EQNRAESECP GMNTHSRASC MQMDDVIDDI ISLESSYNEE ILGLMDPALQ MANTLPVSGN LIDLYGNQGL PPPGLTISNS CPANLPNIKR ELTACIFPTE SEARALAKER QKKDNHNLIE RRRRFNINDR IKELGTLIPK SNDPDMRWNK GTILKASVDY IRKLQREQQR AKELENRQKK LEHANRHLLL RIQELEMQAR AHGLSLIPST GLCSPDLVNR IIKQEPVLEN CSQDLLQHHA DLTCTTTLDL TDGTITFNNN LGTGTEANQA YSVPTKMGSK LEDILMDDTL SPVGVTDPLL SSVSPGASKT SSRRSSMSME ETEHTC //