ID   MITF_RAT                Reviewed;         526 AA.
AC   O88368; F1LQV3;
DT   21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT   05-JUL-2017, sequence version 2.
DT   24-JAN-2024, entry version 152.
DE   RecName: Full=Microphthalmia-associated transcription factor;
GN   Name=Mitf;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Brown Norway;
RX   PubMed=15057822; DOI=10.1038/nature02426;
RA   Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA   Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA   Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA   Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA   Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA   Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA   Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA   Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA   Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA   Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA   Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA   Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA   Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA   Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA   Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA   Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA   Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA   Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA   Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA   Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA   Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA   Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA   Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA   Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA   Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA   Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA   Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA   Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA   Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA   Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA   Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA   Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA   Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA   Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA   Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA   Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA   Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA   Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA   Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA   Mockrin S., Collins F.S.;
RT   "Genome sequence of the Brown Norway rat yields insights into mammalian
RT   evolution.";
RL   Nature 428:493-521(2004).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 292-401, AND DISEASE.
RX   PubMed=9480987; DOI=10.1084/jem.187.5.775;
RA   Weilbaecher K.N., Hershey C.L., Takemoto C.M., Horstmann M.A.,
RA   Hemesath T.J., Tashjian A.H., Fisher D.E.;
RT   "Age-resolving osteopetrosis: a rat model implicating microphthalmia and
RT   the related transcription factor TFE3.";
RL   J. Exp. Med. 187:775-785(1998).
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:0000250|UniProtKB:O75030}.
CC   -!- SUBUNIT: Homodimer or heterodimer; dimerization is mediated via the
CC       coiled coil region (By similarity). Efficient DNA binding requires
CC       dimerization with another bHLH protein (By similarity). Binds DNA in
CC       the form of homodimer or heterodimer with either TFE3, TFEB or TFEC (By
CC       similarity). Identified in a complex with HINT1 and CTNNB1 (By
CC       similarity). Interacts with KARS1 (By similarity). Interacts with VSX2
CC       (By similarity). {ECO:0000250|UniProtKB:O75030,
CC       ECO:0000250|UniProtKB:Q08874}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:O75030}. Cytoplasm
CC       {ECO:0000250|UniProtKB:O75030}. Note=Found exclusively in the nucleus
CC       upon phosphorylation. {ECO:0000250|UniProtKB:O75030}.
CC   -!- DOMAIN: The leucine zipper region is part of a larger coiled coil.
CC       {ECO:0000250|UniProtKB:O75030}.
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. {ECO:0000250|UniProtKB:O75030}.
CC   -!- DISEASE: Note=Osteopetrotic rat of unknown genetic defect
CC       microphthalmia-blanc (mib) has been described whose skeletal sclerosis
CC       improves dramatically with age and that is associated with pigmentation
CC       defects. Mib at the homozygous state shows absence of skin and fur
CC       pigmentation, small eyes, and defects of incisor tooth eruption.
CC       {ECO:0000269|PubMed:9480987}.
CC   -!- SIMILARITY: Belongs to the MiT/TFE family. {ECO:0000305}.
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DR   EMBL; AABR07061507; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AABR07061508; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AABR07061509; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AABR07061510; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AABR07061511; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AF029886; AAC26170.1; -; mRNA.
DR   RefSeq; NP_001178018.1; NM_001191089.2.
DR   AlphaFoldDB; O88368; -.
DR   SMR; O88368; -.
DR   CORUM; O88368; -.
DR   STRING; 10116.ENSRNOP00000044350; -.
DR   PhosphoSitePlus; O88368; -.
DR   PaxDb; 10116-ENSRNOP00000044350; -.
DR   Ensembl; ENSRNOT00055006260; ENSRNOP00055004780; ENSRNOG00055003910.
DR   Ensembl; ENSRNOT00060007191; ENSRNOP00060005450; ENSRNOG00060004277.
DR   Ensembl; ENSRNOT00065041614; ENSRNOP00065034005; ENSRNOG00065024159.
DR   GeneID; 25094; -.
DR   KEGG; rno:25094; -.
DR   UCSC; RGD:3092; rat.
DR   AGR; RGD:3092; -.
DR   CTD; 4286; -.
DR   RGD; 3092; Mitf.
DR   VEuPathDB; HostDB:ENSRNOG00000008658; -.
DR   eggNOG; KOG1318; Eukaryota.
DR   InParanoid; O88368; -.
DR   OrthoDB; 3061893at2759; -.
DR   TreeFam; TF317174; -.
DR   Reactome; R-RNO-3232118; SUMOylation of transcription factors.
DR   PRO; PR:O88368; -.
DR   Proteomes; UP000002494; Chromosome 4.
DR   Bgee; ENSRNOG00000008658; Expressed in heart and 19 other cell types or tissues.
DR   ExpressionAtlas; O88368; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR   GO; GO:0005765; C:lysosomal membrane; ISO:RGD.
DR   GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR   GO; GO:0032991; C:protein-containing complex; ISO:RGD.
DR   GO; GO:0003682; F:chromatin binding; ISO:RGD.
DR   GO; GO:0003677; F:DNA binding; ISO:RGD.
DR   GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISO:RGD.
DR   GO; GO:0003700; F:DNA-binding transcription factor activity; ISO:RGD.
DR   GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISS:UniProtKB.
DR   GO; GO:0070888; F:E-box binding; ISS:UniProtKB.
DR   GO; GO:0046983; F:protein dimerization activity; ISO:RGD.
DR   GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:RGD.
DR   GO; GO:0046849; P:bone remodeling; ISO:RGD.
DR   GO; GO:0043010; P:camera-type eye development; ISO:RGD.
DR   GO; GO:0030154; P:cell differentiation; ISO:RGD.
DR   GO; GO:0045165; P:cell fate commitment; ISO:RGD.
DR   GO; GO:0034224; P:cellular response to zinc ion starvation; IEP:RGD.
DR   GO; GO:0006351; P:DNA-templated transcription; IDA:CAFA.
DR   GO; GO:1902362; P:melanocyte apoptotic process; ISO:RGD.
DR   GO; GO:0030318; P:melanocyte differentiation; ISO:RGD.
DR   GO; GO:0043066; P:negative regulation of apoptotic process; ISO:RGD.
DR   GO; GO:0030336; P:negative regulation of cell migration; ISO:RGD.
DR   GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:RGD.
DR   GO; GO:0030316; P:osteoclast differentiation; IEP:RGD.
DR   GO; GO:0043473; P:pigmentation; ISO:RGD.
DR   GO; GO:0045893; P:positive regulation of DNA-templated transcription; ISO:RGD.
DR   GO; GO:2000144; P:positive regulation of DNA-templated transcription initiation; ISO:RGD.
DR   GO; GO:0010628; P:positive regulation of gene expression; ISO:RGD.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR   GO; GO:0065003; P:protein-containing complex assembly; ISO:RGD.
DR   GO; GO:0042127; P:regulation of cell population proliferation; ISO:RGD.
DR   GO; GO:0006355; P:regulation of DNA-templated transcription; ISO:RGD.
DR   GO; GO:0010468; P:regulation of gene expression; ISO:RGD.
DR   GO; GO:0045670; P:regulation of osteoclast differentiation; ISO:RGD.
DR   GO; GO:2001141; P:regulation of RNA biosynthetic process; ISO:RGD.
DR   GO; GO:0006357; P:regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR   GO; GO:0045471; P:response to ethanol; IEP:RGD.
DR   GO; GO:0016055; P:Wnt signaling pathway; ISO:RGD.
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.
PE   2: Evidence at transcript level;
KW   Activator; Coiled coil; Cytoplasm; Developmental protein; 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_0000127278"
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          374..395
FT                   /note="Leucine-zipper"
FT                   /evidence="ECO:0000305"
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:0000250|UniProtKB:O75030"
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"
SQ   SEQUENCE   526 AA;  58585 MW;  DC08692AEEE4CF59 CRC64;
     MQSESGIVAD FEVGEEFHEE PKTYYELKSQ PLKSSSSAEH SGASKPPLSS STMTSRILLR
     QQLMREQMQE QERREQQQKL QAAQFMQQRV AVSQTPAINV SVPTTLPSAT QVPMEVLKVQ
     THLENPTKYH IQQAQRHQVK QYLSTTLANK HAGQVLSPPC 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 TDGTISFTNN LGTMPESSPA YSIPRKMASN
     LEDILMDDAL SPVGVTDPLL SSVSPGASKT SSRRSSMSAE ETEHAC
//