ID MITF_MOUSE Reviewed; 526 AA. AC Q08874; A0A0N4SVJ5; O08885; O88203; Q08843; Q3U2D2; Q60781; Q60782; Q9JIJ0; AC Q9JIJ1; Q9JIJ2; Q9JIJ3; Q9JIJ4; Q9JIJ5; Q9JIJ6; Q9JKX9; DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot. DT 05-JUL-2017, sequence version 4. DT 27-MAR-2024, entry version 211. DE RecName: Full=Microphthalmia-associated transcription factor; GN Name=Mitf; Synonyms=Bw, Mi, Vit; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS M AND M1), TISSUE SPECIFICITY, AND RP VARIANTS MI AND MI-WS. RC TISSUE=Melanocyte; RX PubMed=8343963; DOI=10.1016/0092-8674(93)90429-t; RA Hodgkinson C.A., Moore K.J., Nakayama A., Steingrimsson E., Copeland N.G., RA Jenkins N.A., Arnheiter H.; RT "Mutations at the mouse microphthalmia locus are associated with defects in RT a gene encoding a novel basic-helix-loop-helix-zipper protein."; RL Cell 74:395-404(1993). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING, AND MUTAGENESIS. RC STRAIN=129/Sv; TISSUE=Heart; RX PubMed=10790403; DOI=10.1093/genetics/155.1.291; RA Hallsson J.H., Favor J., Hodgkinson C., Glaser T., Lamoreux M.L., RA Magnusdottir R., Gunnarsson G.J., Sweet H.O., Copeland N.G., Jenkins N.A., RA Steingrimsson E.; RT "Genomic, transcriptional and mutational analysis of the mouse RT microphthalmia locus."; RL Genetics 155:291-300(2000). RN [3] RP SEQUENCE REVISION TO 41; 48; 52 AND 91. RA Hallsson J.H., Favor J., Hodgkinson C., Glaser T., Lamoreux M.L., RA Magnusdottir R., Gunnarsson G.J., Sweet H.O., Copeland N.G., Jenkins N.A., RA Steingrimsson E.; RL Submitted (FEB-2004) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=NOD {ECO:0000312|EMBL:BAE33209.1}; RX PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J., RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=C57BL/6J; RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112; RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S., RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., RA Eichler E.E., Ponting C.P.; RT "Lineage-specific biology revealed by a finished genome assembly of the RT mouse."; RL PLoS Biol. 7:E1000112-E1000112(2009). RN [6] RP PARTIAL NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS H AND M), AND VARIANTS. RC STRAIN=C57BL/6J; TISSUE=Heart, and Melanocyte; RX PubMed=7874168; DOI=10.1038/ng1194-256; RA Steingrimsson E., Moore K.J., Lamoreux M.L., Ferre-D'Amare A.R., RA Burley S.K., Sanders Zimring D.C., Skow L.C., Hodgkinson C.A., RA Arnheiter H., Copeland N.G., Jenkins N.A.; RT "Molecular basis of mouse microphthalmia (mi) mutations helps explain their RT developmental and phenotypic consequences."; RL Nat. Genet. 8:256-263(1994). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] OF 345-392. RC STRAIN=C57BL/6J; TISSUE=Heart; RX PubMed=8407885; DOI=10.1016/s0021-9258(19)36830-9; RA Hughes M.J., Lingrel J.B., Krakowsky J.M., Anderson K.P.; RT "A helix-loop-helix transcription factor-like gene is located at the mi RT locus."; RL J. Biol. Chem. 268:20687-20690(1993). RN [8] RP PARTIAL NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A). 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 [9] RP SUBCELLULAR LOCATION. RX PubMed=8622664; DOI=10.1128/mcb.16.3.1203; RA Takebayashi K., Chida K., Tsukamoto I., Morii E., Munakata H., RA Arnheiter H., Kuroki T., Kitamura Y., Nomura S.; RT "The recessive phenotype displayed by a dominant negative microphthalmia- RT associated transcription factor mutant is a result of impaired nucleation RT potential."; RL Mol. Cell. Biol. 16:1203-1211(1996). RN [10] 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 [11] RP INVOLVEMENT IN MI-BW. RX PubMed=10400990; DOI=10.1093/hmg/8.8.1431; RA Yajima I., Sato S., Kimura T., Yasumoto K., Shibahara S., Goding C.R., RA Yamamoto H.; RT "An L1 element intronic insertion in the black-eyed white (Mitfmi-bw) gene: RT the loss of a single Mitf isoform responsible for the pigmentary defect and RT inner ear deafness."; RL Hum. Mol. Genet. 8:1431-1441(1999). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-414, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Kidney; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). RN [13] RP INTERACTION WITH VSX2. RX PubMed=23028343; DOI=10.1371/journal.pgen.1002924; RA Zou C., Levine E.M.; RT "Vsx2 controls eye organogenesis and retinal progenitor identity via RT homeodomain and non-homeodomain residues required for high affinity DNA RT binding."; RL PLoS Genet. 8:E1002924-E1002924(2012). RN [14] {ECO:0007744|PDB:4ATH, ECO:0007744|PDB:4ATI, ECO:0007744|PDB:4ATK} RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 324-403, FUNCTION, SUBUNIT, RP DOMAIN, COILED COIL, DNA-BINDING, AND MUTAGENESIS OF 367-GLU--GLN-369. RX PubMed=23207919; DOI=10.1101/gad.198192.112; RA Pogenberg V., Ogmundsdottir M.H., Bergsteinsdottir K., Schepsky A., RA Phung B., Deineko V., Milewski M., Steingrimsson E., Wilmanns M.; RT "Restricted leucine zipper dimerization and specificity of DNA recognition RT of the melanocyte master regulator MITF."; RL Genes Dev. 26:2647-2658(2012). CC -!- FUNCTION: Transcription factor that acts as a master regulator of CC melanocyte survival and differentiation as well as melanosome CC biogenesis (By similarity). Binds to M-boxes (5'-TCATGTG-3') and CC symmetrical DNA sequences (E-boxes) (5'-CACGTG-3') found in the CC promoter of pigmentation genes, such as tyrosinase (TYR) (By CC similarity). Involved in the cellular response to amino acid CC availability by acting downstream of MTOR: in the presence of CC nutrients, MITF phosphorylation by MTOR promotes its inactivation (By CC similarity). Upon starvation or lysosomal stress, inhibition of MTOR CC induces MITF dephosphorylation, resulting in transcription factor CC activity (By similarity). Plays an important role in melanocyte CC development by regulating the expression of tyrosinase (TYR) and CC tyrosinase-related protein 1 (TYRP1) (By similarity). Plays a critical CC role in the differentiation of various cell types, such as neural CC crest-derived melanocytes, mast cells, osteoclasts and optic cup- CC derived retinal pigment epithelium (By similarity). CC {ECO:0000250|UniProtKB:O75030}. CC -!- SUBUNIT: Homodimer or heterodimer; dimerization is mediated via the CC coiled coil region (PubMed:23207919). Efficient DNA binding requires CC dimerization with another bHLH protein (PubMed:23207919). Binds DNA in CC the form of homodimer or heterodimer with either TFE3, TFEB or CC TFEC (PubMed:23207919). 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 (By similarity). CC Interacts with KARS1 (PubMed:14975237). Identified in a complex with CC HINT1 and CTNNB1 (By similarity). Interacts with VSX2 CC (PubMed:23028343). {ECO:0000250|UniProtKB:O75030, CC ECO:0000269|PubMed:14975237, ECO:0000269|PubMed:23028343, CC ECO:0000269|PubMed:23207919}. CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:8622664}. Cytoplasm CC {ECO:0000250|UniProtKB:O75030}. Lysosome membrane CC {ECO:0000250|UniProtKB:O75030}. Note=When nutrients are present, CC recruited to the lysosomal membrane via association with GDP-bound CC RagC/RRAGC (or RagD/RRAGD): it is then phosphorylated by MTOR. CC Phosphorylation by MTOR promotes ubiquitination and degradation. CC Conversely, inhibition of mTORC1, starvation and lysosomal disruption, CC promotes dephosphorylation and translocation to the nucleus. CC Phosphorylation by MARK3/cTAK1 promotes association with 14-3-3/YWHA CC adapters and retention in the cytosol. {ECO:0000250|UniProtKB:O75030}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=9; CC Name=A; CC IsoId=Q08874-1; Sequence=Displayed; CC Name=A1; CC IsoId=Q08874-2; Sequence=VSP_002133; CC Name=A2; CC IsoId=Q08874-3; Sequence=VSP_002131, VSP_002134, VSP_002136; CC Name=H; CC IsoId=Q08874-4; Sequence=VSP_002129; CC Name=H1; CC IsoId=Q08874-5; Sequence=VSP_002129, VSP_002132; CC Name=H2; CC IsoId=Q08874-6; Sequence=VSP_002129, VSP_002132, VSP_002135; CC Name=H3; CC IsoId=Q08874-7; Sequence=VSP_002129, VSP_002133; CC Name=M; CC IsoId=Q08874-8; Sequence=VSP_002130; CC Name=M1; CC IsoId=Q08874-9; Sequence=VSP_002130, VSP_002134; CC -!- TISSUE SPECIFICITY: In the adult, expressed at high levels in the CC heart, skin, skeletal muscle, intestine, stomach, kidney, ovary, lung, CC spleen and brain. In the embryo, expressed in developing eye, ear, skin CC and heart. Isoform M is expressed in melanocytes and also in the CC embryonic and adult heart while isoform A and isoform H are more widely CC expressed. {ECO:0000269|PubMed:8343963}. CC -!- DOMAIN: The leucine zipper region is part of a larger coiled coil. CC {ECO:0000305|PubMed:23207919}. 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 (By similarity). Phosphorylation at CC Ser-405 significantly enhances the ability to bind the tyrosinase CC promoter (By similarity). Phosphorylation by MARK3/cTAK1 at Ser-280 CC promotes association with 14-3-3/YWHA adapters and retention in the CC cytosol (By similarity). 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 (By CC similarity). Phosphorylated in response to blue light (415nm) (By CC similarity). {ECO:0000250|UniProtKB:O75030}. 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 (By similarity). Ubiquitinated following phosphorylation at CC Ser-180, leading to subsequent degradation by the proteasome (By CC similarity). Deubiquitinated by USP13, preventing its degradation (By CC similarity). {ECO:0000250|UniProtKB:O75030}. CC -!- DISEASE: Note=Defects in Mitf are the cause of microphthalmia (mi), a CC condition characterized by loss of pigmentation; reduced eye size; CC failure of secondary bone resorption; reduced numbers of mast cells; CC early onset of deafness, and which gives rise to a number of different CC phenotypes. Among them, microphthalmia-eyeless white (mi-ew) has a CC normal appearance at the heterozygous state, but shows white coat; eyes CC almost absent and eyelids never open at homozygosity. Microphthalmia- CC black and white spot (mi-bws) is normal at heterozygosity, and presents CC white spots and black eyes at homozygous state. Microphthalmia-white CC (mi-wh) has reduced coat color and eye pigmentation; spots on toes, CC tail and belly; inner ear defects at heterozygosity, and at CC homozygosity shows white coat; eyes small and inner iris slightly CC pigmented; spinal ganglia, adrenal medulla and dermis smaller than CC normal, and inner ear defects. Microphthalmia-vitiligo (mi-vi) has CC normal phenotype at heterozygosity, but shows gradual depigmentation of CC coat, skin and eyes; and retinal degeneration at homozygosity. CC Microphthalmia-spotted (mi-sp) shows normal phenotype; at homozygosity, CC however, tyrosinase activity in skin is reduced. Microphthalmia- CC defective irism (mi-di) has reduced retinal pigmentation at CC heterozygosity and shows white coat; eyes of reduced sized and possible CC mild osteoporosis at homozygosity. Microphthalmia-cloudy eyed (mi-ce) CC has a normal appearance at the heterozygous state, but shows white CC coat; eyes of reduced size and unpigmented at homozygosity. CC Microphthalmia-red-eyed white (mi-rw) has a normal appearance at the CC homozygous state, but shows white coat with one or more pigmented spots CC around the head/and or tail; eyes are small and red at heterozygosity. CC Microphthalmia-black-eyed white (mi-bw) shows a white coat but normal CC sized eyes which reamin black at homozygosity. CC {ECO:0000269|PubMed:10400990, ECO:0000269|PubMed:7874168}. 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; Z23066; CAA80600.1; -; mRNA. DR EMBL; AF222344; AAF63466.1; -; Genomic_DNA. DR EMBL; AF222959; AAF81266.2; -; Genomic_DNA. DR EMBL; AF222949; AAF81266.2; JOINED; Genomic_DNA. DR EMBL; AF222951; AAF81266.2; JOINED; Genomic_DNA. DR EMBL; AF222953; AAF81266.2; JOINED; Genomic_DNA. DR EMBL; AF222954; AAF81266.2; JOINED; Genomic_DNA. DR EMBL; AF222955; AAF81266.2; JOINED; Genomic_DNA. DR EMBL; AF222956; AAF81266.2; JOINED; Genomic_DNA. DR EMBL; AF222957; AAF81266.2; JOINED; Genomic_DNA. DR EMBL; AF222958; AAF81266.2; JOINED; Genomic_DNA. DR EMBL; AF222959; AAF81267.2; -; Genomic_DNA. DR EMBL; AF222950; AAF81267.2; JOINED; Genomic_DNA. DR EMBL; AF222951; AAF81267.2; JOINED; Genomic_DNA. DR EMBL; AF222953; AAF81267.2; JOINED; Genomic_DNA. DR EMBL; AF222954; AAF81267.2; JOINED; Genomic_DNA. DR EMBL; AF222955; AAF81267.2; JOINED; Genomic_DNA. DR EMBL; AF222956; AAF81267.2; JOINED; Genomic_DNA. DR EMBL; AF222957; AAF81267.2; JOINED; Genomic_DNA. DR EMBL; AF222958; AAF81267.2; JOINED; Genomic_DNA. DR EMBL; AF222959; AAF81268.2; -; Genomic_DNA. DR EMBL; AF222950; AAF81268.2; JOINED; Genomic_DNA. DR EMBL; AF222951; AAF81268.2; JOINED; Genomic_DNA. DR EMBL; AF222956; AAF81268.2; JOINED; Genomic_DNA. DR EMBL; AF222957; AAF81268.2; JOINED; Genomic_DNA. DR EMBL; AF222958; AAF81268.2; JOINED; Genomic_DNA. DR EMBL; AF222959; AAF81269.2; -; Genomic_DNA. DR EMBL; AF222950; AAF81269.2; JOINED; Genomic_DNA. DR EMBL; AF222951; AAF81269.2; JOINED; Genomic_DNA. DR EMBL; AF222956; AAF81269.2; JOINED; Genomic_DNA. DR EMBL; AF222958; AAF81269.2; JOINED; Genomic_DNA. DR EMBL; AF222959; AAF81270.2; -; Genomic_DNA. DR EMBL; AF222950; AAF81270.2; JOINED; Genomic_DNA. DR EMBL; AF222951; AAF81270.2; JOINED; Genomic_DNA. DR EMBL; AF222953; AAF81270.2; JOINED; Genomic_DNA. DR EMBL; AF222954; AAF81270.2; JOINED; Genomic_DNA. DR EMBL; AF222955; AAF81270.2; JOINED; Genomic_DNA. DR EMBL; AF222956; AAF81270.2; JOINED; Genomic_DNA. DR EMBL; AF222957; AAF81270.2; JOINED; Genomic_DNA. DR EMBL; AF222958; AAF81270.2; JOINED; Genomic_DNA. DR EMBL; AF222959; AAF81271.2; -; Genomic_DNA. DR EMBL; AF222949; AAF81271.2; JOINED; Genomic_DNA. DR EMBL; AF222951; AAF81271.2; JOINED; Genomic_DNA. DR EMBL; AF222953; AAF81271.2; JOINED; Genomic_DNA. DR EMBL; AF222954; AAF81271.2; JOINED; Genomic_DNA. DR EMBL; AF222955; AAF81271.2; JOINED; Genomic_DNA. DR EMBL; AF222956; AAF81271.2; JOINED; Genomic_DNA. DR EMBL; AF222957; AAF81271.2; JOINED; Genomic_DNA. DR EMBL; AF222958; AAF81271.2; JOINED; Genomic_DNA. DR EMBL; AF222959; AAF81272.2; -; Genomic_DNA. DR EMBL; AF222949; AAF81272.2; JOINED; Genomic_DNA. DR EMBL; AF222951; AAF81272.2; JOINED; Genomic_DNA. DR EMBL; AF222955; AAF81272.2; JOINED; Genomic_DNA. DR EMBL; AF222956; AAF81272.2; JOINED; Genomic_DNA. DR EMBL; AF222957; AAF81272.2; JOINED; Genomic_DNA. DR EMBL; AF222958; AAF81272.2; JOINED; Genomic_DNA. DR EMBL; AF222952; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AK155350; BAE33209.1; -; mRNA. DR EMBL; AC131676; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC157098; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC158650; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; U19874; AAC52155.1; -; mRNA. DR EMBL; U19875; AAC52156.1; -; mRNA. DR EMBL; L22958; AAB47773.1; -; mRNA. DR EMBL; AB009397; BAA32329.1; -; mRNA. DR CCDS; CCDS20385.1; -. [Q08874-8] DR CCDS; CCDS51861.1; -. [Q08874-1] DR CCDS; CCDS51862.1; -. [Q08874-4] DR PIR; A40728; A40728. DR PIR; I49244; I49244. DR PIR; PD0026; PD0026. DR RefSeq; NP_001106669.1; NM_001113198.1. [Q08874-1] DR RefSeq; NP_032627.1; NM_008601.3. [Q08874-8] DR RefSeq; XP_006505758.1; XM_006505695.3. [Q08874-9] DR PDB; 4ATH; X-ray; 1.95 A; A/B=324-403. DR PDB; 4ATI; X-ray; 2.60 A; A/B=287-403. DR PDB; 4ATK; X-ray; 2.95 A; A/B=287-403. DR PDB; 6FX5; X-ray; 2.05 A; A/B=324-403. DR PDB; 6G1L; X-ray; 2.40 A; A=287-403. DR PDBsum; 4ATH; -. DR PDBsum; 4ATI; -. DR PDBsum; 4ATK; -. DR PDBsum; 6FX5; -. DR PDBsum; 6G1L; -. DR AlphaFoldDB; Q08874; -. DR SMR; Q08874; -. DR BioGRID; 201427; 11. DR IntAct; Q08874; 1. DR MINT; Q08874; -. DR STRING; 10090.ENSMUSP00000044938; -. DR ChEMBL; CHEMBL1075142; -. DR GlyGen; Q08874; 3 sites, 1 O-linked glycan (3 sites). DR iPTMnet; Q08874; -. DR PhosphoSitePlus; Q08874; -. DR MaxQB; Q08874; -. DR PaxDb; 10090-ENSMUSP00000044938; -. DR PeptideAtlas; Q08874; -. DR ProteomicsDB; 295620; -. [Q08874-1] DR ProteomicsDB; 295621; -. [Q08874-2] DR ProteomicsDB; 295622; -. [Q08874-3] DR ProteomicsDB; 295623; -. [Q08874-4] DR ProteomicsDB; 295624; -. [Q08874-5] DR ProteomicsDB; 295625; -. [Q08874-6] DR ProteomicsDB; 295626; -. [Q08874-7] DR ProteomicsDB; 295627; -. [Q08874-8] DR ProteomicsDB; 295628; -. [Q08874-9] DR Pumba; Q08874; -. DR Antibodypedia; 923; 1037 antibodies from 46 providers. DR DNASU; 17342; -. DR Ensembl; ENSMUST00000043628.13; ENSMUSP00000044459.7; ENSMUSG00000035158.16. [Q08874-8] DR Ensembl; ENSMUST00000043637.14; ENSMUSP00000044938.8; ENSMUSG00000035158.16. [Q08874-1] DR Ensembl; ENSMUST00000101123.10; ENSMUSP00000098683.4; ENSMUSG00000035158.16. [Q08874-4] DR GeneID; 17342; -. DR KEGG; mmu:17342; -. DR UCSC; uc009daz.2; mouse. DR AGR; MGI:104554; -. DR CTD; 4286; -. DR MGI; MGI:104554; Mitf. DR VEuPathDB; HostDB:ENSMUSG00000035158; -. DR eggNOG; KOG1318; Eukaryota. DR GeneTree; ENSGT00940000156326; -. DR InParanoid; Q08874; -. DR OMA; GIPMANT; -. DR OrthoDB; 3061893at2759; -. DR PhylomeDB; Q08874; -. DR TreeFam; TF317174; -. DR Reactome; R-MMU-3232118; SUMOylation of transcription factors. DR BioGRID-ORCS; 17342; 5 hits in 79 CRISPR screens. DR ChiTaRS; Mitf; mouse. DR PRO; PR:Q08874; -. DR Proteomes; UP000000589; Chromosome 6. DR RNAct; Q08874; Protein. DR Bgee; ENSMUSG00000035158; Expressed in pineal body and 244 other cell types or tissues. DR ExpressionAtlas; Q08874; baseline and differential. DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB. DR GO; GO:0005765; C:lysosomal membrane; ISS:UniProtKB. DR GO; GO:0005634; C:nucleus; IDA:MGI. DR GO; GO:0032991; C:protein-containing complex; ISO:MGI. DR GO; GO:0003682; F:chromatin binding; IDA:MGI. DR GO; GO:0003677; F:DNA binding; IDA:MGI. DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:NTNU_SB. DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:MGI. DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IDA:MGI. DR GO; GO:0070888; F:E-box binding; IDA:UniProtKB. DR GO; GO:0046983; F:protein dimerization activity; IPI:UniProtKB. DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:NTNU_SB. DR GO; GO:0043565; F:sequence-specific DNA binding; ISA:MGI. DR GO; GO:0046849; P:bone remodeling; IMP:MGI. DR GO; GO:0043010; P:camera-type eye development; IGI:MGI. DR GO; GO:0030154; P:cell differentiation; IMP:MGI. DR GO; GO:0045165; P:cell fate commitment; IMP:MGI. DR GO; GO:0006351; P:DNA-templated transcription; ISO:MGI. DR GO; GO:1902362; P:melanocyte apoptotic process; IMP:MGI. DR GO; GO:0030318; P:melanocyte differentiation; IMP:MGI. DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:MGI. DR GO; GO:0030336; P:negative regulation of cell migration; ISO:MGI. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:MGI. DR GO; GO:0030316; P:osteoclast differentiation; IMP:MGI. DR GO; GO:0043473; P:pigmentation; IMP:MGI. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:MGI. DR GO; GO:2000144; P:positive regulation of DNA-templated transcription initiation; ISO:MGI. DR GO; GO:0010628; P:positive regulation of gene expression; ISO:MGI. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL. DR GO; GO:0065003; P:protein-containing complex assembly; ISO:MGI. DR GO; GO:0042127; P:regulation of cell population proliferation; IDA:MGI. DR GO; GO:0006355; P:regulation of DNA-templated transcription; ISO:MGI. DR GO; GO:0010468; P:regulation of gene expression; IMP:MGI. DR GO; GO:0045670; P:regulation of osteoclast differentiation; IMP:MGI. DR GO; GO:2001141; P:regulation of RNA biosynthetic process; ISO:MGI. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:MGI. DR GO; GO:0016055; P:Wnt signaling pathway; IDA:MGI. DR CDD; cd18926; bHLHzip_MITF; 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 Genevisible; Q08874; MM. PE 1: Evidence at protein level; KW 3D-structure; Activator; Alternative splicing; Coiled coil; Cytoplasm; KW Deafness; Developmental protein; Disease variant; DNA-binding; KW Isopeptide bond; Lysosome; Membrane; Nucleus; Phosphoprotein; KW Reference proteome; Transcription; Transcription regulation; KW Ubl conjugation. FT CHAIN 1..526 FT /note="Microphthalmia-associated transcription factor" FT /id="PRO_0000127277" FT DOMAIN 311..364 FT /note="bHLH" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981" FT REGION 20..54 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 155..179 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 224..291 FT /note="Transactivation" FT /evidence="ECO:0000250" FT REGION 374..395 FT /note="Leucine-zipper" FT /evidence="ECO:0000305|PubMed:23207919" FT REGION 401..431 FT /note="DNA-binding regulation" FT /evidence="ECO:0000250" FT REGION 496..526 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COILED 355..401 FT /evidence="ECO:0000255" FT COMPBIAS 28..54 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 497..515 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 5 FT /note="Phosphoserine; by MTOR" FT /evidence="ECO:0000250|UniProtKB:O75030" FT MOD_RES 180 FT /note="Phosphoserine; by MAPK" FT /evidence="ECO:0000250|UniProtKB:O75030" FT MOD_RES 280 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O75030" FT MOD_RES 405 FT /note="Phosphoserine; by GSK3" FT /evidence="ECO:0000250|UniProtKB:O75030" FT MOD_RES 414 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 491 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O75030" FT MOD_RES 516 FT /note="Phosphoserine; by RPS6KA1" FT /evidence="ECO:0000250|UniProtKB:O75030" FT CROSSLNK 289 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO)" FT /evidence="ECO:0000250|UniProtKB:O75030" FT CROSSLNK 423 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO)" FT /evidence="ECO:0000250|UniProtKB:O75030" FT VAR_SEQ 1..118 FT /note="MQSESGIVADFEVGEEFHEEPKTYYELKSQPLKSSSSAEHSGASKPPLSSST FT MTSRILLRQQLMREQMQEQERREQQQKLQAAQFMQQRVAVSQTPAINVSVPTTLPSATQ FT VPMEVLK -> MLEMLEYSHYQ (in isoform M and isoform M1)" FT /evidence="ECO:0000303|PubMed:8343963" FT /id="VSP_002130" FT VAR_SEQ 1..35 FT /note="MQSESGIVADFEVGEEFHEEPKTYYELKSQPLKSS -> MEALRFEMLIPCS FT FESLCL (in isoform H, isoform H1, isoform H2 and isoform FT H3)" FT /evidence="ECO:0000305" FT /id="VSP_002129" FT VAR_SEQ 119..254 FT /note="Missing (in isoform H1 and isoform H2)" FT /evidence="ECO:0000305" FT /id="VSP_002132" FT VAR_SEQ 119..222 FT /note="Missing (in isoform A2)" FT /evidence="ECO:0000305" FT /id="VSP_002131" FT VAR_SEQ 139..194 FT /note="Missing (in isoform A1 and isoform H3)" FT /evidence="ECO:0000305" FT /id="VSP_002133" FT VAR_SEQ 294..319 FT /note="ACIFPTESEARALAKERQKKDNHNLI -> V (in isoform H2)" FT /evidence="ECO:0000305" FT /id="VSP_002135" FT VAR_SEQ 294..299 FT /note="Missing (in isoform A2 and isoform M1)" FT /evidence="ECO:0000303|PubMed:8343963" FT /id="VSP_002134" FT VAR_SEQ 318..319 FT /note="LI -> LSKFV (in isoform A2)" FT /evidence="ECO:0000305" FT /id="VSP_002136" FT VARIANT 36..118 FT /note="Missing (in microphthalmia-red-eyed white/mi-rw)" FT VARIANT 119..254 FT /note="Missing (in microphthalmia-white spot/mi-ws)" FT /evidence="ECO:0000269|PubMed:8343963" FT VARIANT 139..194 FT /note="Missing (in microphthalmia-black and white FT spot/mi-bws)" FT VARIANT 294..319 FT /note="ACIFPTESEARALAKERQKKDNHNLI -> V (in FT microphthalmia-eyeless-white/mi-ew)" FT VARIANT 294..299 FT /note="Missing (in microphthalmia-spotted/mi-sp)" FT VARIANT 319 FT /note="I -> N (in microphthalmia-white/mi-wh)" FT VARIANT 323 FT /note="Missing (in microphthalmia/mi)" FT /evidence="ECO:0000269|PubMed:8343963" FT VARIANT 329 FT /note="D -> N (in microphthalmia-vitiligo/mi-vi)" FT VARIANT 370..526 FT /note="Missing (in microphthalmia-cloudy-eyed/mi-ce and FT microphthalmia-defective iris/mi-di)" FT MUTAGEN 367..369 FT /note="EQQ->AAA: Changes the structure of the leucine FT zipper and thereby confers the ability to form heterodimers FT with MAX." FT /evidence="ECO:0000269|PubMed:23207919" FT CONFLICT 9 FT /note="A -> P (in Ref. 2; FT AAF81266/AAF81267/AAF81268/AAF81269/AAF81270/AAF81271/AAF81272)" FT HELIX 311..315 FT /evidence="ECO:0007829|PDB:4ATI" FT HELIX 324..337 FT /evidence="ECO:0007829|PDB:4ATH" FT STRAND 338..340 FT /evidence="ECO:0007829|PDB:6FX5" FT HELIX 350..366 FT /evidence="ECO:0007829|PDB:4ATH" FT HELIX 368..401 FT /evidence="ECO:0007829|PDB:4ATH" SQ SEQUENCE 526 AA; 58605 MW; A3CB0E4F27C8DCDB CRC64; MQSESGIVAD FEVGEEFHEE PKTYYELKSQ PLKSSSSAEH SGASKPPLSS STMTSRILLR QQLMREQMQE QERREQQQKL QAAQFMQQRV AVSQTPAINV SVPTTLPSAT QVPMEVLKVQ THLENPTKYH IQQAQRHQVK QYLSTTLANK HASQVLSSPC PNQPGDHAMP PVPGSSAPNS PMAMLTLNSN CEKEAFYKFE EQSRAESECP GMNTHSRASC MQMDDVIDDI ISLESSYNEE ILGLMDPALQ MANTLPVSGN LIDLYSNQGL PPPGLTISNS CPANLPNIKR ELTACIFPTE SEARALAKER QKKDNHNLIE RRRRFNINDR IKELGTLIPK SNDPDMRWNK GTILKASVDY IRKLQREQQR AKDLENRQKK LEHANRHLLL RVQELEMQAR AHGLSLIPST GLCSPDLVNR IIKQEPVLEN CSQELVQHQA DLTCTTTLDL TDGTITFTNN LGTMPESSPA YSIPRKMGSN LEDILMDDAL SPVGVTDPLL SSVSPGASKT SSRRSSMSAE ETEHAC //