| IED ID | IndEnz0016000179 |
| Enzyme Type ID | tyrosinase000179 |
| Protein Name |
Microphthalmia-associated transcription factor Class E basic helix-loop-helix protein 32 bHLHe32 |
| Gene Name | MITF BHLHE32 |
| Organism | Homo sapiens (Human) |
| 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 Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MQSESGIVPDFEVGEEFHEEPKTYYELKSQPLKSSSSAEHPGASKPPISSSSMTSRILLRQQLMREQMQEQERREQQQKLQAAQFMQQRVPVSQTPAINVSVPTTLPSATQVPMEVLKVQTHLENPTKYHIQQAQRQQVKQYLSTTLANKHANQVLSLPCPNQPGDHVMPPVPGSSAPNSPMAMLTLNSNCEKEGFYKFEEQNRAESECPGMNTHSRASCMQMDDVIDDIISLESSYNEEILGLMDPALQMANTLPVSGNLIDLYGNQGLPPPGLTISNSCPANLPNIKRELTACIFPTESEARALAKERQKKDNHNLIERRRRFNINDRIKELGTLIPKSNDPDMRWNKGTILKASVDYIRKLQREQQRAKELENRQKKLEHANRHLLLRIQELEMQARAHGLSLIPSTGLCSPDLVNRIIKQEPVLENCSQDLLQHHADLTCTTTLDLTDGTITFNNNLGTGTEANQAYSVPTKMGSKLEDILMDDTLSPVGVTDPLLSSVSPGASKTSSRRSSMSMEETEHTC |
| Enzyme Length | 526 |
| Uniprot Accession Number | O75030 |
| 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). 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:0000269|PubMed:10587587, ECO:0000269|PubMed:22647378, ECO:0000269|PubMed:27889061, ECO:0000269|PubMed:9647758}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Alternative sequence (8); Chain (1); Coiled coil (1); Compositional bias (3); Cross-link (2); Domain (1); Helix (2); Modified residue (5); Mutagenesis (5); Natural variant (10); Region (5); Sequence conflict (1) |
| Keywords | 3D-structure;Activator;Albinism;Alternative splicing;Coiled coil;Cytoplasm;DNA-binding;Deafness;Developmental protein;Disease variant;Isopeptide bond;Microphthalmia;Nucleus;Osteopetrosis;Phosphoprotein;Reference proteome;Transcription;Transcription regulation;Ubl conjugation;Waardenburg syndrome |
| Interact With | Q00610 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:27889061, ECO:0000269|PubMed:28842328}. Cytoplasm {ECO:0000269|PubMed:28842328}. Note=Found exclusively in the nucleus upon phosphorylation. {ECO:0000269|PubMed:28842328}. |
| Modified Residue | MOD_RES 180; /note="Phosphoserine; by MAPK"; /evidence="ECO:0000269|PubMed:10673502"; MOD_RES 405; /note="Phosphoserine; by GSK3"; /evidence="ECO:0000269|PubMed:10587587"; MOD_RES 414; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:18220336, ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:23186163"; MOD_RES 491; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:20068231"; MOD_RES 516; /note="Phosphoserine; by RPS6KA1"; /evidence="ECO:0000269|PubMed:10673502" |
| Post Translational Modification | PTM: Phosphorylation at Ser-405 significantly enhances the ability to bind the tyrosinase promoter (PubMed:10587587). 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 (PubMed:10673502). Phosphorylated in response to blue light (415nm) (PubMed:28842328). {ECO:0000269|PubMed:10587587, ECO:0000269|PubMed:10673502, ECO:0000269|PubMed:28842328}.; PTM: Ubiquitinated following phosphorylation at Ser-180, leading to subsequent degradation by the proteasome. Deubiquitinated by USP13, preventing its degradation. {ECO:0000269|PubMed:10673502}. |
| Signal Peptide | |
| Structure 3D | X-ray crystallography (4) |
| Cross Reference PDB | 4C7N; 7D8R; 7D8S; 7D8T; |
| Mapped Pubmed ID | 11751862; 11764295; 12032083; 12048204; 12086670; 12204775; 12235125; 12666593; 12753399; 12819038; 12944398; 14645519; 14737107; 14744763; 15205688; 15623583; 15715979; 15884099; 15983061; 16001072; 16129781; 16140982; 16411896; 16420247; 16455654; 16489066; 16524430; 16586042; 16766266; 16822840; 17159916; 17182868; 17250547; 17464203; 17516926; 17627390; 17975146; 18039926; 18281284; 18284417; 18316599; 18424413; 18451137; 18457359; 18478240; 18595666; 18628967; 18636124; 18829533; 18971960; 19188590; 19320733; 19422606; 19464596; 19659611; 19784067; 19805117; 19895547; 20083088; 20099279; 20201954; 20379614; 20478267; 20482673; 20485200; 20513998; 20514666; 20530484; 20550935; 20573688; 20644734; 20701798; 20801516; 20807369; 20952536; 20973930; 21070662; 21203491; 21273305; 21324898; 21326905; 21358674; 21362015; 21438779; 21577209; 21610457; 21771814; 21796150; 21797920; 21801332; 21811243; 21873430; 21887372; 21949374; 21981993; 21988832; 21996743; 22046555; 22115973; 22196401; 22258527; 22320238; 22441367; 22496449; 22523078; 22571403; 22594792; 22668579; 22833560; 22848417; 22848661; 22898827; 23098757; 23167872; 23201126; 23223141; 23275444; 23349796; 23477830; 23480510; 23728343; 23774529; 23787126; 23802662; 23921446; 23923085; 23962556; 24039954; 24107097; 24194866; 24226203; 24287867; 24290354; 24335901; 24379252; 24390218; 24406078; 24706302; 24733089; 24767713; 24771846; 24789918; 24824743; 24862846; 25030625; 25065405; 25141921; 25238448; 25414259; 25433395; 25447045; 25502142; 25605940; 25648896; 25705847; 25789707; 25803486; 25853464; 25865119; 25866058; 25889792; 25975176; 26236014; 26252099; 26301891; 26317170; 26414466; 26512583; 26522736; 26530832; 26599548; 26650189; 26663053; 26663054; 26675354; 26773496; 26782007; 26845432; 26876013; 26927636; 26962685; 26973244; 26999813; 27055402; 27181209; 27185926; 27327535; 27378491; 27391157; 27515936; 27604145; 27702651; 27827420; 27869170; 27919990; 27939378; 28096186; 28119061; 28165011; 28182633; 28249010; 28263292; 28376192; 28380427; 28392346; 28545079; 28584020; 28759004; 28794318; 28819321; 28825724; 28855355; 29094203; 29171181; 29240767; 29359158; 29369499; 29408204; 29484430; 29507054; 29531335; 29665239; 29679610; 29938923; 30150413; 30254208; 30277012; 30290719; 30310055; 30515787; 30548162; 30549420; 30651597; 30842276; 30910803; 31162548; 31171711; 31207090; 31216476; 31347172; 31562697; 31595650; 31733993; 31877112; 31898538; 31960627; 32034251; 32054529; 32221274; 32422366; 32495878; 32513537; 32531202; 32636443; 32673666; 32728090; 32740552; 32854423; 32881934; 33045145; 33082558; 33293474; 33371469; 33438577; 33571247; 33642520; 33789714; 33940580; 33942382; 34160901; 34233163; 34296805; 34323021; 34356645; 34536557; 34573422; 34710701; |
| Motif | |
| Gene Encoded By | |
| Mass | 58,795 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |