MITF_RAT
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 03-AUG-2022, entry version 145.
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 PaxDb; O88368; -.
DR GeneID; 25094; -.
DR KEGG; rno:25094; -.
DR UCSC; RGD:3092; rat.
DR CTD; 4286; -.
DR RGD; 3092; Mitf.
DR VEuPathDB; HostDB:ENSRNOG00000008658; -.
DR eggNOG; KOG1318; Eukaryota.
DR InParanoid; O88368; -.
DR OMA; MANTXCI; -.
DR OrthoDB; 1211990at2759; -.
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 tissues.
DR ExpressionAtlas; O88368; baseline and differential.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
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:0044336; P:canonical Wnt signaling pathway involved in negative regulation of apoptotic process; ISO:RGD.
DR GO; GO:0030154; P:cell differentiation; ISO:RGD.
DR GO; GO:0045165; P:cell fate commitment; 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; ISO:RGD.
DR GO; GO:0043473; P:pigmentation; 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:0045893; P:positive regulation of transcription, DNA-templated; ISO:RGD.
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: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:0006355; P:regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0006351; P:transcription, DNA-templated; IDA:CAFA.
DR GO; GO:0016055; P:Wnt signaling pathway; ISO:RGD.
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 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
