Molecule Information

General Information of the Molecule (ID: Mol04045)

• Name: Microphthalmia-associated transcription factor (MITF) ,Homo sapiens
• Synonyms: Class E basic helix-loop-helix protein 32
• Molecule Type: Protein
• Gene Name: MITF
• Gene ID: 4286
• Location: chr3:69739456-69968336[+]
• Sequence:
  MQSESGIVPDFEVGEEFHEEPKTYYELKSQPLKSSSSAEHPGASKPPISSSSMTSRILLR
  QQLMREQMQEQERREQQQKLQAAQFMQQRVPVSQTPAINVSVPTTLPSATQVPMEVLKVQ
  THLENPTKYHIQQAQRQQVKQYLSTTLANKHANQVLSLPCPNQPGDHVMPPVPGSSAPNS
  PMAMLTLNSNCEKEGFYKFEEQNRAESECPGMNTHSRASCMQMDDVIDDIISLESSYNEE
  ILGLMDPALQMANTLPVSGNLIDLYGNQGLPPPGLTISNSCPANLPNIKRELTACIFPTE
  SEARALAKERQKKDNHNLIERRRRFNINDRIKELGTLIPKSNDPDMRWNKGTILKASVDY
  IRKLQREQQRAKELENRQKKLEHANRHLLLRIQELEMQARAHGLSLIPSTGLCSPDLVNR
  IIKQEPVLENCSQDLLQHHADLTCTTTLDLTDGTITFNNNLGTGTEANQAYSVPTKMGSK
  LEDILMDDTLSPVGVTDPLLSSVSPGASKTSSRRSSMSMEETEHTC
• 3D-structure: PDB ID: 7D8R; Classification: Transcription; Method: X-ray diffraction; Resolution: 3.00 Å
• Function: Transcription factor that acts as a master regulator of melanocyte survival and differentiation as well as melanosome biogenesis (PubMed:10587587, PubMed:22647378, PubMed:27889061, PubMed:9647758). Binds to M-boxes (5'-TCATGTG-3') and symmetrical DNA sequences (E-boxes) (5'-CACGTG-3') found in the promoter of pigmentation genes, such as tyrosinase (TYR) (PubMed:10587587, PubMed:22647378, PubMed:27889061, PubMed:9647758). Involved in the cellular response to amino acid availability by acting downstream of MTOR: in the presence of nutrients, MITF phosphorylation by MTOR promotes its inactivation (PubMed:36608670). Upon starvation or lysosomal stress, inhibition of MTOR induces MITF dephosphorylation, resulting in transcription factor activity (PubMed:36608670). Plays an important role in melanocyte development by regulating the expression of tyrosinase (TYR) and tyrosinase-related protein 1 (TYRP1) (PubMed:10587587, PubMed:22647378, PubMed:27889061, PubMed:9647758). 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 (PubMed:10587587, PubMed:22647378, PubMed:27889061, PubMed:9647758). .
• Uniprot ID: MITF_HUMAN
• Ensembl ID: ENSG00000187098
• HGNC ID: HGNC:7105

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  MRAP: Metabolic Reprogramming via Altered Pathways

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Vemurafenib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Melanoma [ICD-11: 2C30.0] [1]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Melanoma [ICD-11: 2C30.0]
• Resistant Drug: Vemurafenib
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vivo Model: Melanoma patients; Homo Sapiens
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Cell prognosis assay
• Mechanism Description: Our study provides an omics-based comprehensive overview of the molecular mechanisms governing acquired resistance to BRAF inhibitor therapy.

Disease Class: Melanoma [ICD-11: 2C30.0] [1]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Melanoma [ICD-11: 2C30.0]
• Resistant Drug: Vemurafenib
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SK-MEL-28 cells; Skin; Homo sapiens (Human); CVCL_0526
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Microfluidic cdra chip assay
• Mechanism Description: Our study provides an omics-based comprehensive overview of the molecular mechanisms governing acquired resistance to BRAF inhibitor therapy.

Disease Class: Melanoma [ICD-11: 2C30.0] [1]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Melanoma [ICD-11: 2C30.0]
• Resistant Drug: Vemurafenib
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Microfluidic cdra chip assay
• Mechanism Description: Our study provides an omics-based comprehensive overview of the molecular mechanisms governing acquired resistance to BRAF inhibitor therapy.

References

• Ref 1: Elucidating molecular mechanisms of acquired resistance to BRAF inhibitors in melanoma using a microfluidic device and deep sequencing. Genomics Inform. 2021 Mar;19(1):e2.