MITF_MOUSE
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 03-AUG-2022, entry version 202.
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 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) (PubMed:23207919). Plays an
CC important role in melanocyte development by regulating the expression
CC of tyrosinase (TYR) and tyrosinase-related protein 1 (TYRP1). Plays a
CC critical role in the differentiation of various cell types, such as
CC neural crest-derived melanocytes, mast cells, osteoclasts and optic
CC cup-derived retinal pigment epithelium. {ECO:0000250|UniProtKB:O75030,
CC ECO:0000269|PubMed:23207919}.
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 TFEC (By
CC similarity). Binds DNA as a homodimer (in vitro) (PubMed:23207919).
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:0000255|PROSITE-ProRule:PRU00981,
CC ECO:0000269|PubMed:8622664}. Cytoplasm {ECO:0000250|UniProtKB:O75030}.
CC Note=Found exclusively in the nucleus upon phosphorylation.
CC {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: Phosphorylation at Ser-405 significantly enhances the ability to
CC bind the tyrosinase promoter (By similarity). Phosphorylated at Ser-180
CC 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 (By
CC similarity). Phosphorylated in response to blue light (415nm) (By
CC similarity). {ECO:0000250|UniProtKB:O75030}.
CC -!- PTM: Ubiquitinated following phosphorylation at Ser-180, leading to
CC subsequent degradation by the proteasome. Deubiquitinated by USP13,
CC preventing its degradation (By similarity).
CC {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}.
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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 iPTMnet; Q08874; -.
DR PhosphoSitePlus; Q08874; -.
DR MaxQB; Q08874; -.
DR PaxDb; Q08874; -.
DR PeptideAtlas; Q08874; -.
DR PRIDE; 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 Antibodypedia; 923; 927 antibodies from 46 providers.
DR DNASU; 17342; -.
DR Ensembl; ENSMUST00000043628; ENSMUSP00000044459; ENSMUSG00000035158. [Q08874-8]
DR Ensembl; ENSMUST00000043637; ENSMUSP00000044938; ENSMUSG00000035158. [Q08874-1]
DR Ensembl; ENSMUST00000101123; ENSMUSP00000098683; ENSMUSG00000035158. [Q08874-4]
DR GeneID; 17342; -.
DR KEGG; mmu:17342; -.
DR UCSC; uc009daz.2; mouse.
DR CTD; 4286; -.
DR MGI; MGI:104554; Mitf.
DR VEuPathDB; HostDB:ENSMUSG00000035158; -.
DR eggNOG; KOG1318; Eukaryota.
DR GeneTree; ENSGT00940000156326; -.
DR InParanoid; Q08874; -.
DR OMA; MANTXCI; -.
DR OrthoDB; 1211990at2759; -.
DR PhylomeDB; Q08874; -.
DR TreeFam; TF317174; -.
DR Reactome; R-MMU-3232118; SUMOylation of transcription factors.
DR BioGRID-ORCS; 17342; 5 hits in 74 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 242 other tissues.
DR ExpressionAtlas; Q08874; baseline and differential.
DR Genevisible; Q08874; MM.
DR GO; GO:0005737; C:cytoplasm; 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: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: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:0045893; P:positive regulation of transcription, DNA-templated; IDA:MGI.
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: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:0006355; P:regulation of transcription, DNA-templated; ISO:MGI.
DR GO; GO:0006351; P:transcription, DNA-templated; ISO:MGI.
DR GO; GO:0016055; P:Wnt signaling pathway; IDA:MGI.
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; Alternative splicing; Coiled coil; Cytoplasm;
KW Deafness; Developmental protein; Disease variant; DNA-binding;
KW Isopeptide bond; Nucleus; Phosphoprotein; Reference proteome;
KW Transcription; Transcription regulation; 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 180
FT /note="Phosphoserine; by MAPK"
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 spot/mi-
FT bws)"
FT VARIANT 294..319
FT /note="ACIFPTESEARALAKERQKKDNHNLI -> V (in microphthalmia-
FT 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; AAF81266/AAF81267/AAF81268/
FT 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
