Detail Information for IndEnz0016000180
IED ID IndEnz0016000180
Enzyme Type ID tyrosinase000180
Protein Name Microphthalmia-associated transcription factor
Gene Name Mitf Bw Mi Vit
Organism Mus musculus (Mouse)
Taxonomic Lineage cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Glires (Rodents and rabbits) Rodentia Myomorpha (mice and others) Muroidea Muridae Murinae Mus Mus Mus musculus (Mouse)
Enzyme Sequence MQSESGIVADFEVGEEFHEEPKTYYELKSQPLKSSSSAEHSGASKPPLSSSTMTSRILLRQQLMREQMQEQERREQQQKLQAAQFMQQRVAVSQTPAINVSVPTTLPSATQVPMEVLKVQTHLENPTKYHIQQAQRHQVKQYLSTTLANKHASQVLSSPCPNQPGDHAMPPVPGSSAPNSPMAMLTLNSNCEKEAFYKFEEQSRAESECPGMNTHSRASCMQMDDVIDDIISLESSYNEEILGLMDPALQMANTLPVSGNLIDLYSNQGLPPPGLTISNSCPANLPNIKRELTACIFPTESEARALAKERQKKDNHNLIERRRRFNINDRIKELGTLIPKSNDPDMRWNKGTILKASVDYIRKLQREQQRAKDLENRQKKLEHANRHLLLRVQELEMQARAHGLSLIPSTGLCSPDLVNRIIKQEPVLENCSQELVQHQADLTCTTTLDLTDGTITFTNNLGTMPESSPAYSIPRKMGSNLEDILMDDALSPVGVTDPLLSSVSPGASKTSSRRSSMSAEETEHAC
Enzyme Length 526
Uniprot Accession Number Q08874
Absorption
Active Site
Activity Regulation
Binding Site
Calcium Binding
catalytic Activity
DNA Binding
EC Number
Enzyme Function FUNCTION: Transcription factor that regulates the expression of genes with essential roles in cell differentiation, proliferation and survival. Binds to M-boxes (5'-TCATGTG-3') and symmetrical DNA sequences (E-boxes) (5'-CACGTG-3') found in the promoters of target genes, such as BCL2 and tyrosinase (TYR) (PubMed:23207919). Plays an important role in melanocyte development by regulating the expression of tyrosinase (TYR) and tyrosinase-related protein 1 (TYRP1). Plays a critical role in the differentiation of various cell types, such as neural crest-derived melanocytes, mast cells, osteoclasts and optic cup-derived retinal pigment epithelium. {ECO:0000250|UniProtKB:O75030, ECO:0000269|PubMed:23207919}.
Temperature Dependency
PH Dependency
Pathway
nucleotide Binding
Features Alternative sequence (8); Beta strand (1); Chain (1); Coiled coil (1); Compositional bias (2); Cross-link (2); Domain (1); Helix (4); Modified residue (5); Mutagenesis (1); Natural variant (9); Region (6); Sequence conflict (7)
Keywords 3D-structure;Activator;Alternative splicing;Coiled coil;Cytoplasm;DNA-binding;Deafness;Developmental protein;Disease variant;Isopeptide bond;Nucleus;Phosphoprotein;Reference proteome;Transcription;Transcription regulation;Ubl conjugation
Interact With
Induction
Subcellular Location SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00981, ECO:0000269|PubMed:8622664}. Cytoplasm {ECO:0000250|UniProtKB:O75030}. Note=Found exclusively in the nucleus upon phosphorylation. {ECO:0000250|UniProtKB:O75030}.
Modified Residue MOD_RES 180; /note=Phosphoserine; by MAPK; /evidence=ECO:0000250|UniProtKB:O75030; MOD_RES 405; /note=Phosphoserine; by GSK3; /evidence=ECO:0000250|UniProtKB:O75030; MOD_RES 414; /note=Phosphoserine; /evidence=ECO:0007744|PubMed:21183079; MOD_RES 491; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:O75030; MOD_RES 516; /note=Phosphoserine; by RPS6KA1; /evidence=ECO:0000250|UniProtKB:O75030
Post Translational Modification PTM: Phosphorylation at Ser-405 significantly enhances the ability to bind the tyrosinase promoter (By similarity). Phosphorylated at Ser-180 and Ser-516 following KIT signaling, triggering a short live activation: Phosphorylation at Ser-180 and Ser-516 by MAPK and RPS6KA1, respectively, activate the transcription factor activity but also promote ubiquitination and subsequent degradation by the proteasome (By similarity). Phosphorylated in response to blue light (415nm) (By similarity). {ECO:0000250|UniProtKB:O75030}.; PTM: Ubiquitinated following phosphorylation at Ser-180, leading to subsequent degradation by the proteasome. Deubiquitinated by USP13, preventing its degradation (By similarity). {ECO:0000250|UniProtKB:O75030}.
Signal Peptide
Structure 3D X-ray crystallography (5)
Cross Reference PDB 4ATH; 4ATI; 4ATK; 6FX5; 6G1L;
Mapped Pubmed ID 10036191; 10320095; 10350149; 10361115; 10381505; 10385706; 10586063; 10623832; 10711712; 10760605; 10828017; 10886015; 10898786; 10903182; 10982026; 11076759; 11113541; 11124539; 11156606; 11157480; 11217851; 11231058; 11264169; 11264174; 11456441; 11481336; 11493524; 11520113; 11543611; 11543618; 11588059; 11684011; 11748141; 11751862; 11764295; 11792706; 1184950; 11853768; 11929848; 11930005; 1198094; 12028584; 12039954; 12086670; 12093801; 12128226; 12217379; 12220516; 12235125; 12393515; 12456501; 12466851; 12586714; 12652657; 12695521; 1270792; 12753399; 12756174; 12756179; 12771178; 1280821; 13162938; 1381628; 1382713; 14421250; 14527958; 14575270; 14575687; 1460250; 14632202; 14643677; 14645519; 14706856; 14716319; 14726002; 14737107; 14744763; 1486944; 14962802; 15037118; 15050900; 15081122; 15147727; 15158462; 15172970; 15226356; 15254223; 15277223; 15277526; 15304486; 15305064; 15375155; 15459106; 15466381; 15492754; 15572665; 15576400; 1559545; 15618488; 15618518; 15619674; 15715979; 15716956; 15729346; 15937937; 15983061; 16029420; 16034081; 16038893; 16076961; 16117796; 16129781; 16140982; 16185282; 16186160; 16203745; 16322470; 16337607; 16368885; 16386209; 16412618; 16420417; 16539717; 16605125; 16757562; 16765103; 16790476; 16822840; 16854970; 1689261; 16919269; 16959241; 16998588; 17000761; 17011173; 17083486; 17085443; 17105730; 17182576; 17202193; 17247639; 17403683; 17403896; 17438132; 17442941; 17478475; 17516925; 17516926; 1764248; 18089649; 18191835; 18202372; 18272592; 18281284; 18313864; 18353144; 18397875; 18424556; 18454205; 18557763; 18582859; 18627530; 18703590; 18715234; 18759249; 18778700; 18799693; 18873488; 18902556; 18983533; 18985738; 19192212; 19207217; 19220779; 19288495; 19321441; 19346468; 19416500; 19435791; 19436707; 19469902; 19493314; 19515996; 19553286; 19587010; 19596317; 19635938; 19659570; 19666824; 19805117; 19837037; 19855129; 19906857; 19912887; 19913010; 20058232; 20059953; 20144603; 20147377; 20150232; 20214879; 20237281; 20362542; 20374522; 2040452; 20437053; 20530484; 20550935; 20644734; 20819186; 20890044; 21138975; 21203491; 21205789; 21267068; 21273305; 21297615; 21398290; 21501420; 21576358; 21610032; 21768379; 21779340; 21791431; 21823251; 21886788; 21932325; 21949878; 21996743; 22138449; 22186729; 22290434; 22367038; 22401855; 2246770; 22563733; 22564683; 22570637; 22573620; 22627278; 22711280; 22771905; 22792072; 22927467; 22967998; 23020089; 23098757; 2310824; 23240058; 23277114; 23382837; 23389444; 23426374; 23515312; 23555005; 23595746; 23610061; 23615280; 23624311; 23720040; 23787126; 2379821; 23858437; 23871207; 23913827; 23935512; 23980096; 24080013; 24257758; 24304702; 24324671; 24335901; 24730534; 24753163; 24769727; 24824743; 24875170; 24884952; 24924521; 24925909; 2494194; 24952961; 25045707; 25065405; 25079316; 25155577; 25444235; 25451153; 25466249; 25502142; 25689933; 25715397; 25803486; 25875108; 25927996; 26025865; 26062936; 26212662; 26218069; 26284703; 26341476; 26388265; 26440048; 26475433; 26522736; 26530832; 26545946; 26628093; 26670829; 26814135; 26876013; 26930598; 26952979; 27097562; 27151576; 27220989; 27345838; 27543340; 27616714; 27701636; 28030585; 28158928; 28249010; 28376192; 28402857; 28431046; 28579317; 28607030; 28666097; 28684471; 28729440; 28778798; 29044103; 29080681; 29091026; 29117559; 29166577; 29240767; 29249622; 29277702; 29385729; 29486165; 29496358; 29723194; 29803170; 30076217; 30169530; 30273664; 30333037; 30348676; 30352686; 30471646; 30590377; 30651300; 30705290; 31017901; 31336386; 31527310; 31562697; 31659211; 31777941; 31801063; 31877112; 31924792; 31949107; 31978189; 32169553; 32193365; 32290105; 32361183; 32531202; 32797202; 33323974; 33428890; 33795534; 34160901; 34233163; 34274976; 3443296; 34757798; 34787639; 35108651; 3525691; 3578491; 3665767; 3994857; 4015615; 4092923; 4392283; 4761674; 4963367; 5021438; 5088022; 5424503; 6049665; 6127714; 6264778; 6403657; 6696991; 7042901; 7152259; 7495310; 7517699; 7522503; 7524330; 7524763; 7556499; 7558712; 7588749; 7629107; 7720808; 7789413; 7802662; 7828669; 7852195; 7874167; 7896277; 7920028; 7958932; 7983371; 8069297; 8082834; 8088952; 8206731; 8238251; 8318738; 8402531; 8446583; 8479820; 8513335; 8530057; 8578601; 8603923; 8630510; 8631154; 8631625; 8631626; 8695840; 870607; 8749302; 8776879; 8789737; 879046; 8792932; 8812432; 8837770; 8839840; 8947051; 8983972; 8987786; 9108421; 9119213; 9199364; 9207863; 9227283; 9268589; 9326226; 9327738; 9352446; 9376586; 9383334; 9408245; 9412510; 9440696; 9501313; 9510032; 9546825; 9558376; 9593634; 9630426; 9677380; 9680380; 9731055; 9806836; 9819381; 9825864; 9870544; 9918847; 9931354; 9949161;
Motif
Gene Encoded By
Mass 58,605
Kinetics
Metal Binding
Rhea ID
Cross Reference Brenda