MITF_HUMAN
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 03-AUG-2022, entry version 215.
DE RecName: Full=Microphthalmia-associated transcription factor;
DE AltName: Full=Class E basic helix-loop-helix protein 32;
DE Short=bHLHe32;
GN Name=MITF; 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;
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 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 [15]
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 [16]
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 [17]
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 [18]
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 [19]
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 [20]
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 [21]
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 [22]
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 [23]
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 [24]
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 [25]
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 [26]
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 [27]
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 regulates the expression of genes
CC with essential roles in cell differentiation, proliferation and
CC survival. Binds to M-boxes (5'-TCATGTG-3') and symmetrical DNA
CC sequences (E-boxes) (5'-CACGTG-3') found in the promoters of target
CC genes, such as BCL2 and tyrosinase (TYR). Plays an important role in
CC melanocyte development by regulating the expression of tyrosinase (TYR)
CC and tyrosinase-related protein 1 (TYRP1). Plays a critical role in the
CC differentiation of various cell types, such as neural crest-derived
CC melanocytes, mast cells, osteoclasts and optic cup-derived retinal
CC pigment epithelium. {ECO:0000269|PubMed:10587587,
CC ECO:0000269|PubMed:22647378, ECO:0000269|PubMed:27889061,
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 TFEC
CC (PubMed:15507434). Interacts with KARS1 (PubMed:14975237). Identified
CC in a complex with HINT1 and CTNNB1 (PubMed:22647378). Interacts with
CC VSX2 (By similarity). {ECO:0000250|UniProtKB:Q08874,
CC ECO:0000269|PubMed:14975237, ECO:0000269|PubMed:15507434,
CC ECO:0000269|PubMed:22647378, ECO:0000269|PubMed:24631970}.
CC -!- INTERACTION:
CC O75030; Q00610: CLTC; NbExp=3; IntAct=EBI-3910192, EBI-354967;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:27889061,
CC ECO:0000269|PubMed:28842328}. Cytoplasm {ECO:0000269|PubMed:28842328}.
CC Note=Found exclusively in the nucleus upon phosphorylation.
CC {ECO:0000269|PubMed:28842328}.
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:9647758, PubMed:10578055). {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: Phosphorylation at Ser-405 significantly enhances the ability to
CC bind the tyrosinase promoter (PubMed:10587587). Phosphorylated at Ser-
CC 180 and Ser-516 following KIT signaling, triggering a short live
CC activation: 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:28842328}.
CC -!- PTM: Ubiquitinated following phosphorylation at Ser-180, leading to
CC subsequent degradation by the proteasome. Deubiquitinated by USP13,
CC preventing its degradation. {ECO:0000269|PubMed:10673502}.
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 also may
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 ---------------------------------------------------------------------------
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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_000248.3. [O75030-9]
DR RefSeq; NP_001171896.1; NM_001184967.1. [O75030-12]
DR RefSeq; NP_006713.1; NM_006722.2. [O75030-6]
DR RefSeq; NP_937801.1; NM_198158.2. [O75030-10]
DR RefSeq; NP_937802.1; NM_198159.2. [O75030-2]
DR RefSeq; NP_937820.1; NM_198177.2. [O75030-8]
DR RefSeq; NP_937821.2; NM_198178.2. [O75030-11]
DR RefSeq; XP_005264811.1; XM_005264754.1.
DR RefSeq; XP_005264812.1; XM_005264755.3.
DR RefSeq; XP_016861933.1; XM_017006444.1.
DR RefSeq; XP_016861937.1; XM_017006448.1.
DR PDB; 4C7N; X-ray; 2.10 A; A=357-403.
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 PDBsum; 4C7N; -.
DR PDBsum; 7D8R; -.
DR PDBsum; 7D8S; -.
DR PDBsum; 7D8T; -.
DR AlphaFoldDB; O75030; -.
DR SMR; O75030; -.
DR BioGRID; 110432; 41.
DR DIP; DIP-59573N; -.
DR IntAct; O75030; 19.
DR MINT; O75030; -.
DR STRING; 9606.ENSP00000295600; -.
DR ChEMBL; CHEMBL1741165; -.
DR iPTMnet; O75030; -.
DR PhosphoSitePlus; O75030; -.
DR BioMuta; MITF; -.
DR EPD; O75030; -.
DR jPOST; O75030; -.
DR MassIVE; O75030; -.
DR MaxQB; O75030; -.
DR PaxDb; O75030; -.
DR PeptideAtlas; O75030; -.
DR PRIDE; 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 Antibodypedia; 923; 927 antibodies from 46 providers.
DR DNASU; 4286; -.
DR Ensembl; ENST00000314557.10; ENSP00000324246.6; ENSG00000187098.18. [O75030-10]
DR Ensembl; ENST00000314589.10; ENSP00000324443.5; ENSG00000187098.18. [O75030-8]
DR Ensembl; ENST00000352241.9; ENSP00000295600.8; ENSG00000187098.18. [O75030-1]
DR Ensembl; ENST00000394351.9; ENSP00000377880.3; ENSG00000187098.18. [O75030-9]
DR Ensembl; ENST00000448226.9; ENSP00000391803.3; ENSG00000187098.18. [O75030-6]
DR Ensembl; ENST00000472437.5; ENSP00000418845.1; ENSG00000187098.18. [O75030-12]
DR Ensembl; ENST00000531774.1; ENSP00000435909.1; ENSG00000187098.18. [O75030-11]
DR Ensembl; ENST00000642352.1; ENSP00000494105.1; ENSG00000187098.18. [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 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 neXtProt; NX_O75030; -.
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 PharmGKB; PA30823; -.
DR VEuPathDB; HostDB:ENSG00000187098; -.
DR eggNOG; KOG1318; Eukaryota.
DR GeneTree; ENSGT00940000156326; -.
DR HOGENOM; CLU_031638_2_0_1; -.
DR InParanoid; O75030; -.
DR OMA; MANTXCI; -.
DR OrthoDB; 1211990at2759; -.
DR PhylomeDB; O75030; -.
DR TreeFam; TF317174; -.
DR PathwayCommons; O75030; -.
DR Reactome; R-HSA-3232118; SUMOylation of transcription factors.
DR SignaLink; O75030; -.
DR SIGNOR; O75030; -.
DR BioGRID-ORCS; 4286; 28 hits in 1104 CRISPR screens.
DR ChiTaRS; MITF; human.
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 208 other tissues.
DR ExpressionAtlas; O75030; baseline and differential.
DR Genevisible; O75030; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005737; C:cytoplasm; 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:0046849; P:bone remodeling; IEA:Ensembl.
DR GO; GO:0043010; P:camera-type eye development; IEA:Ensembl.
DR GO; GO:0045165; P:cell fate commitment; IEA:Ensembl.
DR GO; GO:1902362; P:melanocyte apoptotic process; IEA:Ensembl.
DR GO; GO:0030318; P:melanocyte differentiation; IBA:GO_Central.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IEA:Ensembl.
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:0030316; P:osteoclast differentiation; IEA:Ensembl.
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:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0065003; P:protein-containing complex assembly; IDA:UniProtKB.
DR GO; GO:0042127; P:regulation of cell population proliferation; IEA:Ensembl.
DR GO; GO:0045670; P:regulation of osteoclast differentiation; IEA:Ensembl.
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 GO; GO:0006355; P:regulation of transcription, DNA-templated; IMP:UniProtKB.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:Ensembl.
DR Gene3D; 4.10.280.10; -; 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 InterPro; IPR030532; MITF.
DR PANTHER; PTHR45776:SF4; PTHR45776:SF4; 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; SSF47459; 1.
DR PROSITE; PS50888; BHLH; 1.
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; Microphthalmia; Nucleus; Osteopetrosis; Phosphoprotein;
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 11..26
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 28..54
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 496..515
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 180
FT /note="Phosphoserine; by MAPK"
FT /evidence="ECO:0000269|PubMed:10673502"
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; unknown pathological significance;
FT dbSNP:rs1559742541)"
FT /evidence="ECO:0000269|PubMed:28236341"
FT /id="VAR_078311"
FT VARIANT 310
FT /note="R -> K (in WS2A; unknown pathological 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 (in CMM8; associated with disease
FT susceptibility; also associated with pheochromocytomas and
FT paragangliomas susceptibility; 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 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 289
FT /note="K->R: Loss of sumoylation; when associated with R-
FT 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 R-
FT 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 327..337
FT /evidence="ECO:0007829|PDB:7D8S"
FT HELIX 357..401
FT /evidence="ECO:0007829|PDB:4C7N"
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
