MITF (microphthalmia-associated transcription factor) is a basic helix-loop-helix leucine-zipper (bHLH-LZ) transcription factor of the MiT/TFE family (with TFE3, TFEB and TFEC). It binds DNA as a homodimer or as a heterodimer with other MiT/TFE members, recognising E-box (CACGTG) and M-box (TCATGTG) elements, and predominantly activates RNA polymerase II transcription of target genes. In melanocytes and retinal pigment epithelium it is the master regulator of differentiation and pigmentation, directly activating the melanogenic genes TYR, TYRP1 and MC1R as well as genes for melanosome biogenesis and transport, survival and proliferation; it also acts in mast cell and osteoclast differentiation, and can repress some targets such as ZEB1. Alternative promoters generate isoforms with distinct N-termini (melanocyte-specific MITF-M; widely expressed MITF-A, -C, -H), which differ in target selectivity. MITF activity is controlled by signalling-dependent phosphorylation, sumoylation and ubiquitination: phosphorylation promotes 14-3-3-mediated cytoplasmic retention, and in nutrient-replete cells the N-terminally extended isoforms are recruited by Rag GTPases to the lysosomal surface and phosphorylated by mTORC1, promoting their degradation. Heterozygous MITF variants cause Waardenburg syndrome type 2A and Tietz albinism-deafness syndrome, biallelic dominant-negative combinations cause COMMAD syndrome, and the E318K variant predisposes to melanoma.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000122 negative regulation of transcription by RNA polymerase II | IMP PMID:24769727 Identification of a ZEB2-MITF-ZEB1 transcriptional network t... | KEEP AS NON CORE | Summary: MITF knockdown/loss experiments in the ZEB2-MITF-ZEB1 network paper support MITF-dependent repression of target genes such as ZEB1. Reason: The cached record is abstract-only, so the specific readout cannot be checked, but MITF-M occupancy of the ZEB1 locus with repression is independently documented (Reactome, CUT&RUN/ChIP-seq). Repression is a genuine but secondary activity of a factor whose primary output is activation; non-core. Deferring to the curator who read the full text. Supporting Evidence: PMID:24769727 We identify a transcriptional signaling network in which the EMT transcription factor ZEB2 regulates MITF levels to control melanocyte differentiation. Reactome:R-HSA-9926484 MITF-M binds to a cognate element in the ZEB1 locus to repress its expression as assessed by CUT-and-RUN DNA binding analysis and ChIP-seq |
| GO:0000785 chromatin | ISA GO_REF:0000113 | ACCEPT | Summary: MITF is a sequence-specific bHLH-LZ transcription factor that occupies chromatin at target loci (ChIP at FOS, BEST1; CUT&RUN/ChIP-seq at ZEB1). Reason: Chromatin location is the expected consequence of sequence-specific binding at cis-regulatory elements, shown directly by ChIP in human cells. Supporting Evidence: PMID:14737107 Promoter analysis and chromatin immunoprecipitation assay suggested that both STAT3 and MITF can cooperatively upregulate the c-fos gene. Reactome:R-HSA-9926484 MITF-M binds to a cognate element in the ZEB1 locus to repress its expression as assessed by CUT-and-RUN DNA binding analysis and ChIP-seq |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT root-node (PTN005248237) inference; MITF is itself a seed for this IBD. MITF binds M-box (TCATGTG) and E-box (CACGTG) elements in Pol II-transcribed target promoters. Reason: Core molecular function. Sequence-specific binding to E-box/M-box elements is shown by EMSA for wild-type human MITF and by in vitro binding to the tyrosinase-family M box; the IBA reflects inheritance of this function from the MiT/TFE family root. Supporting Evidence: PMID:27889061 strong M-box (TCATGTG) and E-box (CACGTG) binding PMID:8995290 Their human gene promoters share the 11-base pair M box containing a CATGTG motif, which was shown here to be bound in vitro by microphthalmia-associated transcription factor (MITF). |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IDA PMID:14737107 STAT3 and MITF cooperatively induce cellular transformation ... | ACCEPT | Summary: ChIP/promoter analysis shows MITF binding to the FOS promoter region. MITF binds M-box (TCATGTG) and E-box (CACGTG) elements in Pol II-transcribed target promoters. Reason: Core molecular function. Sequence-specific binding to E-box/M-box elements is shown by EMSA for wild-type human MITF and by in vitro binding to the tyrosinase-family M box; the IBA reflects inheritance of this function from the MiT/TFE family root. Supporting Evidence: PMID:27889061 strong M-box (TCATGTG) and E-box (CACGTG) binding PMID:8995290 Their human gene promoters share the 11-base pair M box containing a CATGTG motif, which was shown here to be bound in vitro by microphthalmia-associated transcription factor (MITF). PMID:14737107 Promoter analysis and chromatin immunoprecipitation assay suggested that both STAT3 and MITF can cooperatively upregulate the c-fos gene. |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IEA GO_REF:0000107 | ACCEPT | Summary: Ortholog-based transfer consistent with direct human data. MITF binds M-box (TCATGTG) and E-box (CACGTG) elements in Pol II-transcribed target promoters. Reason: Core molecular function. Sequence-specific binding to E-box/M-box elements is shown by EMSA for wild-type human MITF and by in vitro binding to the tyrosinase-family M box; the IBA reflects inheritance of this function from the MiT/TFE family root. Supporting Evidence: PMID:27889061 strong M-box (TCATGTG) and E-box (CACGTG) binding PMID:8995290 Their human gene promoters share the 11-base pair M box containing a CATGTG motif, which was shown here to be bound in vitro by microphthalmia-associated transcription factor (MITF). PMID:14737107 Promoter analysis and chromatin immunoprecipitation assay suggested that both STAT3 and MITF can cooperatively upregulate the c-fos gene. |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IBA GO_REF:0000033 | ACCEPT | Summary: MITF is a DNA-binding transcription factor acting at RNA polymerase II promoters/enhancers (IBA). Reason: Correct and core; this is the umbrella activity inherited at the MiT/TFE family root (PTN005248237, MITF a seed). It covers both the predominant activator activity (GO:0001228, accepted separately) and context-specific repression (e.g. ZEB1), so it is appropriately kept alongside the more specific activator term. Supporting Evidence: file:human/MITF/MITF-uniprot.txt 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) PMID:8995290 MITF overexpression increased the expression of a reporter gene under the control of the human tyrosinase or TRP-1 gene promoter |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IEA GO_REF:0000107 | ACCEPT | Summary: MITF is a DNA-binding transcription factor acting at RNA polymerase II promoters/enhancers (IEA). Reason: Correct and core; this is the umbrella activity inherited at the MiT/TFE family root (PTN005248237, MITF a seed). It covers both the predominant activator activity (GO:0001228, accepted separately) and context-specific repression (e.g. ZEB1), so it is appropriately kept alongside the more specific activator term. Supporting Evidence: file:human/MITF/MITF-uniprot.txt 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) PMID:8995290 MITF overexpression increased the expression of a reporter gene under the control of the human tyrosinase or TRP-1 gene promoter |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | ISA GO_REF:0000113 | ACCEPT | Summary: MITF is a DNA-binding transcription factor acting at RNA polymerase II promoters/enhancers (ISA). Reason: Correct and core; this is the umbrella activity inherited at the MiT/TFE family root (PTN005248237, MITF a seed). It covers both the predominant activator activity (GO:0001228, accepted separately) and context-specific repression (e.g. ZEB1), so it is appropriately kept alongside the more specific activator term. Supporting Evidence: file:human/MITF/MITF-uniprot.txt 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) PMID:8995290 MITF overexpression increased the expression of a reporter gene under the control of the human tyrosinase or TRP-1 gene promoter |
| GO:0001227 DNA-binding transcription repressor activity, RNA polymerase II-specific | NAS PMID:24769727 Identification of a ZEB2-MITF-ZEB1 transcriptional network t... | KEEP AS NON CORE | Summary: Author statement that MITF acts as a repressor in the ZEB2-MITF-ZEB1 network. Reason: Direct repression of ZEB1 by MITF-M binding to a cognate element in the ZEB1 locus is independently documented by Reactome from CUT&RUN/ChIP-seq. Accepted as a real but secondary activity; MITF is predominantly an activator. Supporting Evidence: Reactome:R-HSA-9926484 MITF-M binds to a cognate element in the ZEB1 locus to repress its expression as assessed by CUT-and-RUN DNA binding analysis and ChIP-seq |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | IDA PMID:14737107 STAT3 and MITF cooperatively induce cellular transformation ... | ACCEPT | Summary: MITF activates transcription of Pol II target genes through E-box/M-box elements (tyrosinase family, FOS, BEST1, MC1R, PRKCB). Reason: Core function, supported by multiple independent human reporter, ChIP and loss-of-function studies; the C-terminal region acts as a transactivation domain. Supporting Evidence: PMID:14737107 Promoter analysis and chromatin immunoprecipitation assay suggested that both STAT3 and MITF can cooperatively upregulate the c-fos gene. PMID:8995290 MITF overexpression increased the expression of a reporter gene under the control of the human tyrosinase or TRP-1 gene promoter |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | IDA PMID:20530484 SOX9, through interaction with microphthalmia-associated tra... | ACCEPT | Summary: MITF activates transcription of Pol II target genes through E-box/M-box elements (tyrosinase family, FOS, BEST1, MC1R, PRKCB). Reason: Core function, supported by multiple independent human reporter, ChIP and loss-of-function studies; the C-terminal region acts as a transactivation domain. Supporting Evidence: PMID:20530484 SOX9 physically interacted with MITF and OTX2 and orchestrated synergistic activation of the BEST1 promoter PMID:8995290 MITF overexpression increased the expression of a reporter gene under the control of the human tyrosinase or TRP-1 gene promoter |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | IEA GO_REF:0000107 | ACCEPT | Summary: MITF activates transcription of Pol II target genes through E-box/M-box elements (tyrosinase family, FOS, BEST1, MC1R, PRKCB). Reason: Core function, supported by multiple independent human reporter, ChIP and loss-of-function studies; the C-terminal region acts as a transactivation domain. Supporting Evidence: PMID:8995290 MITF overexpression increased the expression of a reporter gene under the control of the human tyrosinase or TRP-1 gene promoter PMID:9647758 MITF-A activated transcription of the tyrosinase and tyrosinase-related protein 1 genes |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | IMP PMID:14737107 STAT3 and MITF cooperatively induce cellular transformation ... | ACCEPT | Summary: MITF activates transcription of Pol II target genes through E-box/M-box elements (tyrosinase family, FOS, BEST1, MC1R, PRKCB). Reason: Core function, supported by multiple independent human reporter, ChIP and loss-of-function studies; the C-terminal region acts as a transactivation domain. Supporting Evidence: PMID:14737107 Promoter analysis and chromatin immunoprecipitation assay suggested that both STAT3 and MITF can cooperatively upregulate the c-fos gene. |
| GO:0003677 DNA binding | IEA GO_REF:0000107 | TOO GENERAL | Summary: MITF binds DNA. Reason: True but entailed by the accepted RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978) and E-box binding (GO:0070888). Supporting Evidence: PMID:27889061 strong M-box (TCATGTG) and E-box (CACGTG) binding |
| GO:0003682 chromatin binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog-transferred chromatin binding. Reason: MITF occupancy of chromatin at target loci is well documented (ChIP, CUT&RUN), and MITF recruits chromatin-remodelling partners (SWI/SNF per Reactome), so the claim is reasonable; however the informative activity is sequence-specific DNA binding, so this is kept as non-core. Supporting Evidence: PMID:14737107 Promoter analysis and chromatin immunoprecipitation assay suggested that both STAT3 and MITF can cooperatively upregulate the c-fos gene. Reactome:R-HSA-9926484 MITF-M binds to a cognate element in the ZEB1 locus to repress its expression as assessed by CUT-and-RUN DNA binding analysis and ChIP-seq |
| GO:0003700 DNA-binding transcription factor activity | IEA GO_REF:0000107 | TOO GENERAL | Summary: MITF is a DNA-binding transcription factor. Reason: True but entailed by the accepted GO:0000981 and GO:0001228 RNA polymerase II-specific activity terms. Supporting Evidence: file:human/MITF/MITF-uniprot.txt 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) |
| GO:0005515 protein binding | IPI PMID:15507434 Sumoylation of MITF and its related family members TFE3 and ... | MODIFY | Summary: IntAct interaction of MITF with TFEB from the sumoylation study. Reason: Bare protein binding is uninformative. The paper reports that MITF heterodimerizes with TFE3 and TFEB, so the interaction is better captured as protein heterodimerization activity. Proposed replacements: protein heterodimerization activity Supporting Evidence: PMID:15507434 MITF and its related family members TFE3 and TFEB heterodimerize with each other, recognize the same DNA sequences |
| GO:0005515 protein binding | IPI PMID:15507434 Sumoylation of MITF and its related family members TFE3 and ... | MODIFY | Summary: IntAct interaction of MITF with TFE3 from the sumoylation study. Reason: Bare protein binding is uninformative. The paper reports that MITF heterodimerizes with TFE3 and TFEB; replace with protein heterodimerization activity. Proposed replacements: protein heterodimerization activity Supporting Evidence: PMID:15507434 MITF and its related family members TFE3 and TFEB heterodimerize with each other, recognize the same DNA sequences |
| GO:0005515 protein binding | IPI PMID:15507434 Sumoylation of MITF and its related family members TFE3 and ... | REMOVE | Summary: IntAct interaction of MITF with SUMO1. Reason: MITF is a substrate of SUMO conjugation (sumoylation at conserved lysines); covalent modification by SUMO1 does not describe an MITF molecular function. Bare protein binding is uninformative and removed; the modification itself is not in doubt. Supporting Evidence: PMID:15507434 lysine residues within conserved small ubiquitin-like modifier (SUMO) consensus sites in these family members are subject to SUMO modification |
| GO:0005515 protein binding | IPI PMID:20530484 SOX9, through interaction with microphthalmia-associated tra... | MODIFY | Summary: In vitro co-immunoprecipitation of MITF-M with SOX9 (and OTX2) and synergistic activation of the BEST1 promoter. Reason: Bare protein binding is uninformative. SOX9 is a DNA-binding transcription factor and the interaction underlies cooperative activation of BEST1, so DNA-binding transcription factor binding is the informative replacement. Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: PMID:20530484 SOX9 physically interacted with MITF and OTX2 and orchestrated synergistic activation of the BEST1 promoter PMID:20530484 we first examined physical interactions by in vitro co-immunoprecipitation using proteins generated by in vitro transcription and translation |
| GO:0005515 protein binding | IPI PMID:21811243 Regulation of MITF stability by the USP13 deubiquitinase. | REMOVE | Summary: USP13 interaction; USP13 deubiquitinates and stabilizes MITF. Reason: MITF is the substrate of the deubiquitinase; this enzyme-substrate interaction describes USP13 function, not an MITF activity. Bare protein binding is uninformative and removed; the interaction is not disputed. Supporting Evidence: PMID:21811243 USP13 that appears to be responsible for MITF deubiquitination |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: BioPlex 3.0 affinity-purification mass spectrometry co-purification of MITF with TFEB. Reason: Bare protein binding is uninformative. Co-purification with MiT/TFE partners is consistent with the established heterodimerization of MITF with TFE3/TFEB; replace with protein heterodimerization activity. Proposed replacements: protein heterodimerization activity Supporting Evidence: PMID:33961781 Through affinity-purification mass spectrometry, we have created two proteome-scale, cell-line-specific interaction networks. PMID:15507434 MITF and its related family members TFE3 and TFEB heterodimerize with each other, recognize the same DNA sequences |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: BioPlex 3.0 affinity-purification mass spectrometry co-purification of MITF with TFE3. Reason: Bare protein binding is uninformative. Co-purification is consistent with established MITF-TFE3 heterodimerization; replace with protein heterodimerization activity. Proposed replacements: protein heterodimerization activity Supporting Evidence: PMID:33961781 Through affinity-purification mass spectrometry, we have created two proteome-scale, cell-line-specific interaction networks. PMID:15507434 MITF and its related family members TFE3 and TFEB heterodimerize with each other, recognize the same DNA sequences |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: MITF acts in the nucleus, where it binds target promoters; nuclear entry is regulated by phosphorylation-dependent 14-3-3 retention and mTORC1/Rag signalling. Reason: Core location for a transcription factor; WT human MITF is predominantly nuclear, and nuclear localization is also the PAINT root-node inference. Supporting Evidence: PMID:27889061 In our study, GFP-tagged wild-type (WT) MITF demonstrated predominantly nuclear localization |
| GO:0005634 nucleus | IDA PMID:16822840 Microphthalmia-associated transcription factor interactions ... | ACCEPT | Summary: MITF acts in the nucleus, where it binds target promoters; nuclear entry is regulated by phosphorylation-dependent 14-3-3 retention and mTORC1/Rag signalling. Reason: Core location for a transcription factor; WT human MITF is predominantly nuclear, and nuclear localization is also the PAINT root-node inference. Supporting Evidence: PMID:16822840 MITF can shuttle from cytoplasm to nucleus dependent upon RANKL/CSF-1 action |
| GO:0005634 nucleus | IDA PMID:27889061 Biallelic Mutations in MITF Cause Coloboma, Osteopetrosis, M... | ACCEPT | Summary: MITF acts in the nucleus, where it binds target promoters; nuclear entry is regulated by phosphorylation-dependent 14-3-3 retention and mTORC1/Rag signalling. Reason: Core location for a transcription factor; WT human MITF is predominantly nuclear, and nuclear localization is also the PAINT root-node inference. Supporting Evidence: PMID:27889061 In our study, GFP-tagged wild-type (WT) MITF demonstrated predominantly nuclear localization |
| GO:0005634 nucleus | IDA PMID:28842328 Melanocytes Sense Blue Light and Regulate Pigmentation throu... | ACCEPT | Summary: MITF acts in the nucleus, where it binds target promoters; nuclear entry is regulated by phosphorylation-dependent 14-3-3 retention and mTORC1/Rag signalling. Reason: Core location for a transcription factor; WT human MITF is predominantly nuclear, and nuclear localization is also the PAINT root-node inference. Supporting Evidence: PMID:28842328 leading to the phosphorylation of MITF and ultimately to the increase of the melanogenesis enzymes PMID:27889061 In our study, GFP-tagged wild-type (WT) MITF demonstrated predominantly nuclear localization |
| GO:0005634 nucleus | IDA PMID:36608670 A central role for regulated protein stability in the contro... | ACCEPT | Summary: MITF acts in the nucleus, where it binds target promoters; nuclear entry is regulated by phosphorylation-dependent 14-3-3 retention and mTORC1/Rag signalling. Reason: Core location for a transcription factor; WT human MITF is predominantly nuclear, and nuclear localization is also the PAINT root-node inference. Supporting Evidence: PMID:36608670 Previous work established that mutagenesis of S321 and S280 within TFE3 and MITF-A, respectively, increases their nuclear localization and entirely abolishes their retention by 14-3-3 chaperones. |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: MITF acts in the nucleus, where it binds target promoters; nuclear entry is regulated by phosphorylation-dependent 14-3-3 retention and mTORC1/Rag signalling. Reason: Core location for a transcription factor; WT human MITF is predominantly nuclear, and nuclear localization is also the PAINT root-node inference. Supporting Evidence: PMID:27889061 In our study, GFP-tagged wild-type (WT) MITF demonstrated predominantly nuclear localization |
| GO:0005634 nucleus | NAS PMID:10578055 Molecular cloning of cDNA encoding a novel microphthalmia-as... | ACCEPT | Summary: MITF acts in the nucleus, where it binds target promoters; nuclear entry is regulated by phosphorylation-dependent 14-3-3 retention and mTORC1/Rag signalling. Reason: Core location for a transcription factor; WT human MITF is predominantly nuclear, and nuclear localization is also the PAINT root-node inference. Supporting Evidence: PMID:10578055 MITF-C, like other MITF isoforms, functions as a transcriptional activator of certain target genes |
| GO:0005634 nucleus | NAS PMID:9647758 Identification of a novel isoform of microphthalmia-associat... | ACCEPT | Summary: MITF acts in the nucleus, where it binds target promoters; nuclear entry is regulated by phosphorylation-dependent 14-3-3 retention and mTORC1/Rag signalling. Reason: Core location for a transcription factor; WT human MITF is predominantly nuclear, and nuclear localization is also the PAINT root-node inference. Supporting Evidence: PMID:9647758 MITF-A activated transcription of the tyrosinase and tyrosinase-related protein 1 genes |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-3232162 | ACCEPT | Summary: Reactome places MITF (mostly MITF-M) in the nucleoplasm in reactions where the MITF dimer binds target genes (melanogenic, cell-cycle, survival genes) or is modified. Reason: Nucleoplasm is the correct, specific nuclear sub-compartment for a chromatin-bound transcription factor; consistent with direct localization data. Supporting Evidence: PMID:27889061 In our study, GFP-tagged wild-type (WT) MITF demonstrated predominantly nuclear localization |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9730412 | ACCEPT | Summary: Reactome places MITF (mostly MITF-M) in the nucleoplasm in reactions where the MITF dimer binds target genes (melanogenic, cell-cycle, survival genes) or is modified. Reason: Nucleoplasm is the correct, specific nuclear sub-compartment for a chromatin-bound transcription factor; consistent with direct localization data. Supporting Evidence: PMID:27889061 In our study, GFP-tagged wild-type (WT) MITF demonstrated predominantly nuclear localization |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9824598 | ACCEPT | Summary: Reactome places MITF (mostly MITF-M) in the nucleoplasm in reactions where the MITF dimer binds target genes (melanogenic, cell-cycle, survival genes) or is modified. Reason: Nucleoplasm is the correct, specific nuclear sub-compartment for a chromatin-bound transcription factor; consistent with direct localization data. Supporting Evidence: PMID:27889061 In our study, GFP-tagged wild-type (WT) MITF demonstrated predominantly nuclear localization |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9824977 | ACCEPT | Summary: Reactome places MITF (mostly MITF-M) in the nucleoplasm in reactions where the MITF dimer binds target genes (melanogenic, cell-cycle, survival genes) or is modified. Reason: Nucleoplasm is the correct, specific nuclear sub-compartment for a chromatin-bound transcription factor; consistent with direct localization data. Supporting Evidence: PMID:27889061 In our study, GFP-tagged wild-type (WT) MITF demonstrated predominantly nuclear localization |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9824979 | ACCEPT | Summary: Reactome places MITF (mostly MITF-M) in the nucleoplasm in reactions where the MITF dimer binds target genes (melanogenic, cell-cycle, survival genes) or is modified. Reason: Nucleoplasm is the correct, specific nuclear sub-compartment for a chromatin-bound transcription factor; consistent with direct localization data. Supporting Evidence: PMID:27889061 In our study, GFP-tagged wild-type (WT) MITF demonstrated predominantly nuclear localization |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9824986 | ACCEPT | Summary: Reactome places MITF (mostly MITF-M) in the nucleoplasm in reactions where the MITF dimer binds target genes (melanogenic, cell-cycle, survival genes) or is modified. Reason: Nucleoplasm is the correct, specific nuclear sub-compartment for a chromatin-bound transcription factor; consistent with direct localization data. Supporting Evidence: PMID:27889061 In our study, GFP-tagged wild-type (WT) MITF demonstrated predominantly nuclear localization |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9824994 | ACCEPT | Summary: Reactome places MITF (mostly MITF-M) in the nucleoplasm in reactions where the MITF dimer binds target genes (melanogenic, cell-cycle, survival genes) or is modified. Reason: Nucleoplasm is the correct, specific nuclear sub-compartment for a chromatin-bound transcription factor; consistent with direct localization data. Supporting Evidence: PMID:27889061 In our study, GFP-tagged wild-type (WT) MITF demonstrated predominantly nuclear localization |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9824995 | ACCEPT | Summary: Reactome places MITF (mostly MITF-M) in the nucleoplasm in reactions where the MITF dimer binds target genes (melanogenic, cell-cycle, survival genes) or is modified. Reason: Nucleoplasm is the correct, specific nuclear sub-compartment for a chromatin-bound transcription factor; consistent with direct localization data. Supporting Evidence: PMID:27889061 In our study, GFP-tagged wild-type (WT) MITF demonstrated predominantly nuclear localization |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9824999 | ACCEPT | Summary: Reactome places MITF (mostly MITF-M) in the nucleoplasm in reactions where the MITF dimer binds target genes (melanogenic, cell-cycle, survival genes) or is modified. Reason: Nucleoplasm is the correct, specific nuclear sub-compartment for a chromatin-bound transcription factor; consistent with direct localization data. Supporting Evidence: PMID:27889061 In our study, GFP-tagged wild-type (WT) MITF demonstrated predominantly nuclear localization |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9825751 | ACCEPT | Summary: Reactome places MITF (mostly MITF-M) in the nucleoplasm in reactions where the MITF dimer binds target genes (melanogenic, cell-cycle, survival genes) or is modified. Reason: Nucleoplasm is the correct, specific nuclear sub-compartment for a chromatin-bound transcription factor; consistent with direct localization data. Supporting Evidence: PMID:27889061 In our study, GFP-tagged wild-type (WT) MITF demonstrated predominantly nuclear localization |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9825754 | ACCEPT | Summary: Reactome places MITF (mostly MITF-M) in the nucleoplasm in reactions where the MITF dimer binds target genes (melanogenic, cell-cycle, survival genes) or is modified. Reason: Nucleoplasm is the correct, specific nuclear sub-compartment for a chromatin-bound transcription factor; consistent with direct localization data. Supporting Evidence: PMID:27889061 In our study, GFP-tagged wild-type (WT) MITF demonstrated predominantly nuclear localization |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9825756 | ACCEPT | Summary: Reactome places MITF (mostly MITF-M) in the nucleoplasm in reactions where the MITF dimer binds target genes (melanogenic, cell-cycle, survival genes) or is modified. Reason: Nucleoplasm is the correct, specific nuclear sub-compartment for a chromatin-bound transcription factor; consistent with direct localization data. Supporting Evidence: PMID:27889061 In our study, GFP-tagged wild-type (WT) MITF demonstrated predominantly nuclear localization |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9825782 | ACCEPT | Summary: Reactome places MITF (mostly MITF-M) in the nucleoplasm in reactions where the MITF dimer binds target genes (melanogenic, cell-cycle, survival genes) or is modified. Reason: Nucleoplasm is the correct, specific nuclear sub-compartment for a chromatin-bound transcription factor; consistent with direct localization data. Supporting Evidence: PMID:27889061 In our study, GFP-tagged wild-type (WT) MITF demonstrated predominantly nuclear localization |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9825788 | ACCEPT | Summary: Reactome places MITF (mostly MITF-M) in the nucleoplasm in reactions where the MITF dimer binds target genes (melanogenic, cell-cycle, survival genes) or is modified. Reason: Nucleoplasm is the correct, specific nuclear sub-compartment for a chromatin-bound transcription factor; consistent with direct localization data. Supporting Evidence: PMID:27889061 In our study, GFP-tagged wild-type (WT) MITF demonstrated predominantly nuclear localization |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9825790 | ACCEPT | Summary: Reactome places MITF (mostly MITF-M) in the nucleoplasm in reactions where the MITF dimer binds target genes (melanogenic, cell-cycle, survival genes) or is modified. Reason: Nucleoplasm is the correct, specific nuclear sub-compartment for a chromatin-bound transcription factor; consistent with direct localization data. Supporting Evidence: PMID:27889061 In our study, GFP-tagged wild-type (WT) MITF demonstrated predominantly nuclear localization |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9825835 | ACCEPT | Summary: Reactome places MITF (mostly MITF-M) in the nucleoplasm in reactions where the MITF dimer binds target genes (melanogenic, cell-cycle, survival genes) or is modified. Reason: Nucleoplasm is the correct, specific nuclear sub-compartment for a chromatin-bound transcription factor; consistent with direct localization data. Supporting Evidence: PMID:27889061 In our study, GFP-tagged wild-type (WT) MITF demonstrated predominantly nuclear localization |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9825836 | ACCEPT | Summary: Reactome places MITF (mostly MITF-M) in the nucleoplasm in reactions where the MITF dimer binds target genes (melanogenic, cell-cycle, survival genes) or is modified. Reason: Nucleoplasm is the correct, specific nuclear sub-compartment for a chromatin-bound transcription factor; consistent with direct localization data. Supporting Evidence: PMID:27889061 In our study, GFP-tagged wild-type (WT) MITF demonstrated predominantly nuclear localization |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9825842 | ACCEPT | Summary: Reactome places MITF (mostly MITF-M) in the nucleoplasm in reactions where the MITF dimer binds target genes (melanogenic, cell-cycle, survival genes) or is modified. Reason: Nucleoplasm is the correct, specific nuclear sub-compartment for a chromatin-bound transcription factor; consistent with direct localization data. Supporting Evidence: PMID:27889061 In our study, GFP-tagged wild-type (WT) MITF demonstrated predominantly nuclear localization |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9825844 | ACCEPT | Summary: Reactome places MITF (mostly MITF-M) in the nucleoplasm in reactions where the MITF dimer binds target genes (melanogenic, cell-cycle, survival genes) or is modified. Reason: Nucleoplasm is the correct, specific nuclear sub-compartment for a chromatin-bound transcription factor; consistent with direct localization data. Supporting Evidence: PMID:27889061 In our study, GFP-tagged wild-type (WT) MITF demonstrated predominantly nuclear localization |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9825845 | ACCEPT | Summary: Reactome places MITF (mostly MITF-M) in the nucleoplasm in reactions where the MITF dimer binds target genes (melanogenic, cell-cycle, survival genes) or is modified. Reason: Nucleoplasm is the correct, specific nuclear sub-compartment for a chromatin-bound transcription factor; consistent with direct localization data. Supporting Evidence: PMID:27889061 In our study, GFP-tagged wild-type (WT) MITF demonstrated predominantly nuclear localization |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9825847 | ACCEPT | Summary: Reactome places MITF (mostly MITF-M) in the nucleoplasm in reactions where the MITF dimer binds target genes (melanogenic, cell-cycle, survival genes) or is modified. Reason: Nucleoplasm is the correct, specific nuclear sub-compartment for a chromatin-bound transcription factor; consistent with direct localization data. Supporting Evidence: PMID:27889061 In our study, GFP-tagged wild-type (WT) MITF demonstrated predominantly nuclear localization |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9825848 | ACCEPT | Summary: Reactome places MITF (mostly MITF-M) in the nucleoplasm in reactions where the MITF dimer binds target genes (melanogenic, cell-cycle, survival genes) or is modified. Reason: Nucleoplasm is the correct, specific nuclear sub-compartment for a chromatin-bound transcription factor; consistent with direct localization data. Supporting Evidence: PMID:27889061 In our study, GFP-tagged wild-type (WT) MITF demonstrated predominantly nuclear localization |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9854912 | ACCEPT | Summary: Reactome places MITF (mostly MITF-M) in the nucleoplasm in reactions where the MITF dimer binds target genes (melanogenic, cell-cycle, survival genes) or is modified. Reason: Nucleoplasm is the correct, specific nuclear sub-compartment for a chromatin-bound transcription factor; consistent with direct localization data. Supporting Evidence: PMID:27889061 In our study, GFP-tagged wild-type (WT) MITF demonstrated predominantly nuclear localization |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9854920 | ACCEPT | Summary: Reactome places MITF (mostly MITF-M) in the nucleoplasm in reactions where the MITF dimer binds target genes (melanogenic, cell-cycle, survival genes) or is modified. Reason: Nucleoplasm is the correct, specific nuclear sub-compartment for a chromatin-bound transcription factor; consistent with direct localization data. Supporting Evidence: PMID:27889061 In our study, GFP-tagged wild-type (WT) MITF demonstrated predominantly nuclear localization |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9856056 | ACCEPT | Summary: Reactome places MITF (mostly MITF-M) in the nucleoplasm in reactions where the MITF dimer binds target genes (melanogenic, cell-cycle, survival genes) or is modified. Reason: Nucleoplasm is the correct, specific nuclear sub-compartment for a chromatin-bound transcription factor; consistent with direct localization data. Supporting Evidence: PMID:27889061 In our study, GFP-tagged wild-type (WT) MITF demonstrated predominantly nuclear localization |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9856062 | ACCEPT | Summary: Reactome places MITF (mostly MITF-M) in the nucleoplasm in reactions where the MITF dimer binds target genes (melanogenic, cell-cycle, survival genes) or is modified. Reason: Nucleoplasm is the correct, specific nuclear sub-compartment for a chromatin-bound transcription factor; consistent with direct localization data. Supporting Evidence: PMID:27889061 In our study, GFP-tagged wild-type (WT) MITF demonstrated predominantly nuclear localization |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9856464 | ACCEPT | Summary: Reactome places MITF (mostly MITF-M) in the nucleoplasm in reactions where the MITF dimer binds target genes (melanogenic, cell-cycle, survival genes) or is modified. Reason: Nucleoplasm is the correct, specific nuclear sub-compartment for a chromatin-bound transcription factor; consistent with direct localization data. Supporting Evidence: PMID:27889061 In our study, GFP-tagged wild-type (WT) MITF demonstrated predominantly nuclear localization |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9856466 | ACCEPT | Summary: Reactome places MITF (mostly MITF-M) in the nucleoplasm in reactions where the MITF dimer binds target genes (melanogenic, cell-cycle, survival genes) or is modified. Reason: Nucleoplasm is the correct, specific nuclear sub-compartment for a chromatin-bound transcription factor; consistent with direct localization data. Supporting Evidence: PMID:27889061 In our study, GFP-tagged wild-type (WT) MITF demonstrated predominantly nuclear localization |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9857359 | ACCEPT | Summary: Reactome places MITF (mostly MITF-M) in the nucleoplasm in reactions where the MITF dimer binds target genes (melanogenic, cell-cycle, survival genes) or is modified. Reason: Nucleoplasm is the correct, specific nuclear sub-compartment for a chromatin-bound transcription factor; consistent with direct localization data. Supporting Evidence: PMID:27889061 In our study, GFP-tagged wild-type (WT) MITF demonstrated predominantly nuclear localization |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9857574 | ACCEPT | Summary: Reactome places MITF (mostly MITF-M) in the nucleoplasm in reactions where the MITF dimer binds target genes (melanogenic, cell-cycle, survival genes) or is modified. Reason: Nucleoplasm is the correct, specific nuclear sub-compartment for a chromatin-bound transcription factor; consistent with direct localization data. Supporting Evidence: PMID:27889061 In our study, GFP-tagged wild-type (WT) MITF demonstrated predominantly nuclear localization |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9857578 | ACCEPT | Summary: Reactome places MITF (mostly MITF-M) in the nucleoplasm in reactions where the MITF dimer binds target genes (melanogenic, cell-cycle, survival genes) or is modified. Reason: Nucleoplasm is the correct, specific nuclear sub-compartment for a chromatin-bound transcription factor; consistent with direct localization data. Supporting Evidence: PMID:27889061 In our study, GFP-tagged wild-type (WT) MITF demonstrated predominantly nuclear localization |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9858287 | ACCEPT | Summary: Reactome places MITF (mostly MITF-M) in the nucleoplasm in reactions where the MITF dimer binds target genes (melanogenic, cell-cycle, survival genes) or is modified. Reason: Nucleoplasm is the correct, specific nuclear sub-compartment for a chromatin-bound transcription factor; consistent with direct localization data. Supporting Evidence: PMID:27889061 In our study, GFP-tagged wild-type (WT) MITF demonstrated predominantly nuclear localization |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9858288 | ACCEPT | Summary: Reactome places MITF (mostly MITF-M) in the nucleoplasm in reactions where the MITF dimer binds target genes (melanogenic, cell-cycle, survival genes) or is modified. Reason: Nucleoplasm is the correct, specific nuclear sub-compartment for a chromatin-bound transcription factor; consistent with direct localization data. Supporting Evidence: PMID:27889061 In our study, GFP-tagged wild-type (WT) MITF demonstrated predominantly nuclear localization |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9858401 | ACCEPT | Summary: Reactome places MITF (mostly MITF-M) in the nucleoplasm in reactions where the MITF dimer binds target genes (melanogenic, cell-cycle, survival genes) or is modified. Reason: Nucleoplasm is the correct, specific nuclear sub-compartment for a chromatin-bound transcription factor; consistent with direct localization data. Supporting Evidence: PMID:27889061 In our study, GFP-tagged wild-type (WT) MITF demonstrated predominantly nuclear localization |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9858559 | ACCEPT | Summary: Reactome places MITF (mostly MITF-M) in the nucleoplasm in reactions where the MITF dimer binds target genes (melanogenic, cell-cycle, survival genes) or is modified. Reason: Nucleoplasm is the correct, specific nuclear sub-compartment for a chromatin-bound transcription factor; consistent with direct localization data. Supporting Evidence: PMID:27889061 In our study, GFP-tagged wild-type (WT) MITF demonstrated predominantly nuclear localization |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9858560 | ACCEPT | Summary: Reactome places MITF (mostly MITF-M) in the nucleoplasm in reactions where the MITF dimer binds target genes (melanogenic, cell-cycle, survival genes) or is modified. Reason: Nucleoplasm is the correct, specific nuclear sub-compartment for a chromatin-bound transcription factor; consistent with direct localization data. Supporting Evidence: PMID:27889061 In our study, GFP-tagged wild-type (WT) MITF demonstrated predominantly nuclear localization |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9858639 | ACCEPT | Summary: Reactome places MITF (mostly MITF-M) in the nucleoplasm in reactions where the MITF dimer binds target genes (melanogenic, cell-cycle, survival genes) or is modified. Reason: Nucleoplasm is the correct, specific nuclear sub-compartment for a chromatin-bound transcription factor; consistent with direct localization data. Supporting Evidence: PMID:27889061 In our study, GFP-tagged wild-type (WT) MITF demonstrated predominantly nuclear localization |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9858643 | ACCEPT | Summary: Reactome places MITF (mostly MITF-M) in the nucleoplasm in reactions where the MITF dimer binds target genes (melanogenic, cell-cycle, survival genes) or is modified. Reason: Nucleoplasm is the correct, specific nuclear sub-compartment for a chromatin-bound transcription factor; consistent with direct localization data. Supporting Evidence: PMID:27889061 In our study, GFP-tagged wild-type (WT) MITF demonstrated predominantly nuclear localization |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9858650 | ACCEPT | Summary: Reactome places MITF (mostly MITF-M) in the nucleoplasm in reactions where the MITF dimer binds target genes (melanogenic, cell-cycle, survival genes) or is modified. Reason: Nucleoplasm is the correct, specific nuclear sub-compartment for a chromatin-bound transcription factor; consistent with direct localization data. Supporting Evidence: PMID:27889061 In our study, GFP-tagged wild-type (WT) MITF demonstrated predominantly nuclear localization |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9858652 | ACCEPT | Summary: Reactome places MITF (mostly MITF-M) in the nucleoplasm in reactions where the MITF dimer binds target genes (melanogenic, cell-cycle, survival genes) or is modified. Reason: Nucleoplasm is the correct, specific nuclear sub-compartment for a chromatin-bound transcription factor; consistent with direct localization data. Supporting Evidence: PMID:27889061 In our study, GFP-tagged wild-type (WT) MITF demonstrated predominantly nuclear localization |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9858713 | ACCEPT | Summary: Reactome places MITF (mostly MITF-M) in the nucleoplasm in reactions where the MITF dimer binds target genes (melanogenic, cell-cycle, survival genes) or is modified. Reason: Nucleoplasm is the correct, specific nuclear sub-compartment for a chromatin-bound transcription factor; consistent with direct localization data. Supporting Evidence: PMID:27889061 In our study, GFP-tagged wild-type (WT) MITF demonstrated predominantly nuclear localization |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9858721 | ACCEPT | Summary: Reactome places MITF (mostly MITF-M) in the nucleoplasm in reactions where the MITF dimer binds target genes (melanogenic, cell-cycle, survival genes) or is modified. Reason: Nucleoplasm is the correct, specific nuclear sub-compartment for a chromatin-bound transcription factor; consistent with direct localization data. Supporting Evidence: PMID:27889061 In our study, GFP-tagged wild-type (WT) MITF demonstrated predominantly nuclear localization |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9858883 | ACCEPT | Summary: Reactome places MITF (mostly MITF-M) in the nucleoplasm in reactions where the MITF dimer binds target genes (melanogenic, cell-cycle, survival genes) or is modified. Reason: Nucleoplasm is the correct, specific nuclear sub-compartment for a chromatin-bound transcription factor; consistent with direct localization data. Supporting Evidence: PMID:27889061 In our study, GFP-tagged wild-type (WT) MITF demonstrated predominantly nuclear localization |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9859098 | ACCEPT | Summary: Reactome places MITF (mostly MITF-M) in the nucleoplasm in reactions where the MITF dimer binds target genes (melanogenic, cell-cycle, survival genes) or is modified. Reason: Nucleoplasm is the correct, specific nuclear sub-compartment for a chromatin-bound transcription factor; consistent with direct localization data. Supporting Evidence: PMID:27889061 In our study, GFP-tagged wild-type (WT) MITF demonstrated predominantly nuclear localization |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9907144 | ACCEPT | Summary: Reactome places MITF (mostly MITF-M) in the nucleoplasm in reactions where the MITF dimer binds target genes (melanogenic, cell-cycle, survival genes) or is modified. Reason: Nucleoplasm is the correct, specific nuclear sub-compartment for a chromatin-bound transcription factor; consistent with direct localization data. Supporting Evidence: PMID:27889061 In our study, GFP-tagged wild-type (WT) MITF demonstrated predominantly nuclear localization |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9926472 | ACCEPT | Summary: Reactome places MITF (mostly MITF-M) in the nucleoplasm in reactions where the MITF dimer binds target genes (melanogenic, cell-cycle, survival genes) or is modified. Reason: Nucleoplasm is the correct, specific nuclear sub-compartment for a chromatin-bound transcription factor; consistent with direct localization data. Supporting Evidence: PMID:27889061 In our study, GFP-tagged wild-type (WT) MITF demonstrated predominantly nuclear localization |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9926474 | ACCEPT | Summary: Reactome places MITF (mostly MITF-M) in the nucleoplasm in reactions where the MITF dimer binds target genes (melanogenic, cell-cycle, survival genes) or is modified. Reason: Nucleoplasm is the correct, specific nuclear sub-compartment for a chromatin-bound transcription factor; consistent with direct localization data. Supporting Evidence: PMID:27889061 In our study, GFP-tagged wild-type (WT) MITF demonstrated predominantly nuclear localization |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9926476 | ACCEPT | Summary: Reactome places MITF (mostly MITF-M) in the nucleoplasm in reactions where the MITF dimer binds target genes (melanogenic, cell-cycle, survival genes) or is modified. Reason: Nucleoplasm is the correct, specific nuclear sub-compartment for a chromatin-bound transcription factor; consistent with direct localization data. Supporting Evidence: PMID:27889061 In our study, GFP-tagged wild-type (WT) MITF demonstrated predominantly nuclear localization |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9926477 | ACCEPT | Summary: Reactome places MITF (mostly MITF-M) in the nucleoplasm in reactions where the MITF dimer binds target genes (melanogenic, cell-cycle, survival genes) or is modified. Reason: Nucleoplasm is the correct, specific nuclear sub-compartment for a chromatin-bound transcription factor; consistent with direct localization data. Supporting Evidence: PMID:27889061 In our study, GFP-tagged wild-type (WT) MITF demonstrated predominantly nuclear localization |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9926478 | ACCEPT | Summary: Reactome places MITF (mostly MITF-M) in the nucleoplasm in reactions where the MITF dimer binds target genes (melanogenic, cell-cycle, survival genes) or is modified. Reason: Nucleoplasm is the correct, specific nuclear sub-compartment for a chromatin-bound transcription factor; consistent with direct localization data. Supporting Evidence: PMID:27889061 In our study, GFP-tagged wild-type (WT) MITF demonstrated predominantly nuclear localization |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9926480 | ACCEPT | Summary: Reactome places MITF (mostly MITF-M) in the nucleoplasm in reactions where the MITF dimer binds target genes (melanogenic, cell-cycle, survival genes) or is modified. Reason: Nucleoplasm is the correct, specific nuclear sub-compartment for a chromatin-bound transcription factor; consistent with direct localization data. Supporting Evidence: PMID:27889061 In our study, GFP-tagged wild-type (WT) MITF demonstrated predominantly nuclear localization |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9926481 | ACCEPT | Summary: Reactome places MITF (mostly MITF-M) in the nucleoplasm in reactions where the MITF dimer binds target genes (melanogenic, cell-cycle, survival genes) or is modified. Reason: Nucleoplasm is the correct, specific nuclear sub-compartment for a chromatin-bound transcription factor; consistent with direct localization data. Supporting Evidence: PMID:27889061 In our study, GFP-tagged wild-type (WT) MITF demonstrated predominantly nuclear localization |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9926484 | ACCEPT | Summary: Reactome places MITF (mostly MITF-M) in the nucleoplasm in reactions where the MITF dimer binds target genes (melanogenic, cell-cycle, survival genes) or is modified. Reason: Nucleoplasm is the correct, specific nuclear sub-compartment for a chromatin-bound transcription factor; consistent with direct localization data. Supporting Evidence: PMID:27889061 In our study, GFP-tagged wild-type (WT) MITF demonstrated predominantly nuclear localization |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9926486 | ACCEPT | Summary: Reactome places MITF (mostly MITF-M) in the nucleoplasm in reactions where the MITF dimer binds target genes (melanogenic, cell-cycle, survival genes) or is modified. Reason: Nucleoplasm is the correct, specific nuclear sub-compartment for a chromatin-bound transcription factor; consistent with direct localization data. Supporting Evidence: PMID:27889061 In our study, GFP-tagged wild-type (WT) MITF demonstrated predominantly nuclear localization |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9926487 | ACCEPT | Summary: Reactome places MITF (mostly MITF-M) in the nucleoplasm in reactions where the MITF dimer binds target genes (melanogenic, cell-cycle, survival genes) or is modified. Reason: Nucleoplasm is the correct, specific nuclear sub-compartment for a chromatin-bound transcription factor; consistent with direct localization data. Supporting Evidence: PMID:27889061 In our study, GFP-tagged wild-type (WT) MITF demonstrated predominantly nuclear localization |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9926488 | ACCEPT | Summary: Reactome places MITF (mostly MITF-M) in the nucleoplasm in reactions where the MITF dimer binds target genes (melanogenic, cell-cycle, survival genes) or is modified. Reason: Nucleoplasm is the correct, specific nuclear sub-compartment for a chromatin-bound transcription factor; consistent with direct localization data. Supporting Evidence: PMID:27889061 In our study, GFP-tagged wild-type (WT) MITF demonstrated predominantly nuclear localization |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9926489 | ACCEPT | Summary: Reactome places MITF (mostly MITF-M) in the nucleoplasm in reactions where the MITF dimer binds target genes (melanogenic, cell-cycle, survival genes) or is modified. Reason: Nucleoplasm is the correct, specific nuclear sub-compartment for a chromatin-bound transcription factor; consistent with direct localization data. Supporting Evidence: PMID:27889061 In our study, GFP-tagged wild-type (WT) MITF demonstrated predominantly nuclear localization |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9926490 | ACCEPT | Summary: Reactome places MITF (mostly MITF-M) in the nucleoplasm in reactions where the MITF dimer binds target genes (melanogenic, cell-cycle, survival genes) or is modified. Reason: Nucleoplasm is the correct, specific nuclear sub-compartment for a chromatin-bound transcription factor; consistent with direct localization data. Supporting Evidence: PMID:27889061 In our study, GFP-tagged wild-type (WT) MITF demonstrated predominantly nuclear localization |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9926491 | ACCEPT | Summary: Reactome places MITF (mostly MITF-M) in the nucleoplasm in reactions where the MITF dimer binds target genes (melanogenic, cell-cycle, survival genes) or is modified. Reason: Nucleoplasm is the correct, specific nuclear sub-compartment for a chromatin-bound transcription factor; consistent with direct localization data. Supporting Evidence: PMID:27889061 In our study, GFP-tagged wild-type (WT) MITF demonstrated predominantly nuclear localization |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9926492 | ACCEPT | Summary: Reactome places MITF (mostly MITF-M) in the nucleoplasm in reactions where the MITF dimer binds target genes (melanogenic, cell-cycle, survival genes) or is modified. Reason: Nucleoplasm is the correct, specific nuclear sub-compartment for a chromatin-bound transcription factor; consistent with direct localization data. Supporting Evidence: PMID:27889061 In our study, GFP-tagged wild-type (WT) MITF demonstrated predominantly nuclear localization |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9926493 | ACCEPT | Summary: Reactome places MITF (mostly MITF-M) in the nucleoplasm in reactions where the MITF dimer binds target genes (melanogenic, cell-cycle, survival genes) or is modified. Reason: Nucleoplasm is the correct, specific nuclear sub-compartment for a chromatin-bound transcription factor; consistent with direct localization data. Supporting Evidence: PMID:27889061 In our study, GFP-tagged wild-type (WT) MITF demonstrated predominantly nuclear localization |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9926495 | ACCEPT | Summary: Reactome places MITF (mostly MITF-M) in the nucleoplasm in reactions where the MITF dimer binds target genes (melanogenic, cell-cycle, survival genes) or is modified. Reason: Nucleoplasm is the correct, specific nuclear sub-compartment for a chromatin-bound transcription factor; consistent with direct localization data. Supporting Evidence: PMID:27889061 In our study, GFP-tagged wild-type (WT) MITF demonstrated predominantly nuclear localization |
| GO:0005737 cytoplasm | IDA PMID:16822840 Microphthalmia-associated transcription factor interactions ... | KEEP AS NON CORE | Summary: A pool of MITF is retained in the cytoplasm, by phospho-dependent 14-3-3 binding and via mTORC1/Rag-regulated pathways, as an inactive regulated reservoir. Reason: Cytoplasmic localization is real and well documented but reflects regulation of MITF (sequestration away from its site of action) rather than where it executes its function; non-core. Supporting Evidence: PMID:16822840 MITF can shuttle from cytoplasm to nucleus dependent upon RANKL/CSF-1 action PMID:16822840 14-3-3 regulates MITF activity by promoting the cytosolic localization of MITF |
| GO:0005737 cytoplasm | IDA PMID:28842328 Melanocytes Sense Blue Light and Regulate Pigmentation throu... | KEEP AS NON CORE | Summary: A pool of MITF is retained in the cytoplasm, by phospho-dependent 14-3-3 binding and via mTORC1/Rag-regulated pathways, as an inactive regulated reservoir. Reason: Cytoplasmic localization is real and well documented but reflects regulation of MITF (sequestration away from its site of action) rather than where it executes its function; non-core. Supporting Evidence: PMID:28842328 leading to the phosphorylation of MITF and ultimately to the increase of the melanogenesis enzymes PMID:16822840 14-3-3 regulates MITF activity by promoting the cytosolic localization of MITF |
| GO:0005737 cytoplasm | IDA PMID:36608670 A central role for regulated protein stability in the contro... | KEEP AS NON CORE | Summary: A pool of MITF is retained in the cytoplasm, by phospho-dependent 14-3-3 binding and via mTORC1/Rag-regulated pathways, as an inactive regulated reservoir. Reason: Cytoplasmic localization is real and well documented but reflects regulation of MITF (sequestration away from its site of action) rather than where it executes its function; non-core. Supporting Evidence: PMID:36608670 Previous work established that mutagenesis of S321 and S280 within TFE3 and MITF-A, respectively, increases their nuclear localization and entirely abolishes their retention by 14-3-3 chaperones. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: A pool of MITF is retained in the cytoplasm, by phospho-dependent 14-3-3 binding and via mTORC1/Rag-regulated pathways, as an inactive regulated reservoir. Reason: Cytoplasmic localization is real and well documented but reflects regulation of MITF (sequestration away from its site of action) rather than where it executes its function; non-core. Supporting Evidence: PMID:16822840 14-3-3 regulates MITF activity by promoting the cytosolic localization of MITF |
| GO:0005765 lysosomal membrane | IDA PMID:23401004 Rag GTPases mediate amino acid-dependent recruitment of TFEB... | KEEP AS NON CORE | Summary: In the presence of nutrients, N-terminally extended MITF isoforms (MITF-A) are recruited to the lysosomal surface by active Rag GTPases, where mTORC1 phosphorylates them. Reason: Experimentally established in human cells, but this is a regulatory docking site rather than the location where MITF executes its transcriptional function; non-core. Note this applies to isoforms carrying the Rag-binding N-terminus, not to MITF-M. Supporting Evidence: PMID:23401004 overexpression of active Rags was sufficient to induce relocation of MITF-1 to lysosomal membranes, whereas expression of inactive Rags caused accumulation of MITF-1 into the nucleus |
| GO:0005765 lysosomal membrane | IDA PMID:36608670 A central role for regulated protein stability in the contro... | KEEP AS NON CORE | Summary: In the presence of nutrients, N-terminally extended MITF isoforms (MITF-A) are recruited to the lysosomal surface by active Rag GTPases, where mTORC1 phosphorylates them. Reason: Experimentally established in human cells, but this is a regulatory docking site rather than the location where MITF executes its transcriptional function; non-core. Note this applies to isoforms carrying the Rag-binding N-terminus, not to MITF-M. Supporting Evidence: PMID:36608670 Our efforts revealed that TFE3 and MITF-A are recruited to the lysosomal surface by interacting with Rag GTPases |
| GO:0005765 lysosomal membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: In the presence of nutrients, N-terminally extended MITF isoforms (MITF-A) are recruited to the lysosomal surface by active Rag GTPases, where mTORC1 phosphorylates them. Reason: Experimentally established in human cells, but this is a regulatory docking site rather than the location where MITF executes its transcriptional function; non-core. Note this applies to isoforms carrying the Rag-binding N-terminus, not to MITF-M. Supporting Evidence: file:human/MITF/MITF-uniprot.txt Interacts with small GTPases Rag (RagA/RRAGA, RagB/RRAGB, RagC/RRAGC and/or RagD/RRAGD); promoting its recruitment to lysosomal membrane in the presence of nutrients |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9824986 | KEEP AS NON CORE | Summary: Reactome cytosol location for MITF-M exported by XPO1, phosphorylated by MARK3 and bound by 14-3-3 dimers. Reason: Cytosolic sequestration of MITF is documented and regulatory; non-core location. Supporting Evidence: PMID:16822840 MITF can shuttle from cytoplasm to nucleus dependent upon RANKL/CSF-1 action |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9926483 | KEEP AS NON CORE | Summary: Reactome cytosol location for MITF-M exported by XPO1, phosphorylated by MARK3 and bound by 14-3-3 dimers. Reason: Cytosolic sequestration of MITF is documented and regulatory; non-core location. Supporting Evidence: PMID:16822840 14-3-3 regulates MITF activity by promoting the cytosolic localization of MITF |
| GO:0005829 cytosol | TAS Reactome:R-NUL-9926485 | KEEP AS NON CORE | Summary: Reactome cytosol location for MITF-M exported by XPO1, phosphorylated by MARK3 and bound by 14-3-3 dimers. Reason: Cytosolic sequestration of MITF is documented and regulatory; non-core location. Supporting Evidence: PMID:16822840 14-3-3 regulates MITF activity by promoting the cytosolic localization of MITF |
| GO:0006355 regulation of DNA-templated transcription | IEA GO_REF:0000002 | MODIFY | Summary: MITF regulates transcription of its target genes. Reason: Correct but general. MITF regulates RNA polymerase II-transcribed genes (and predominantly activates them); replace with regulation of transcription by RNA polymerase II, which the gene already carries by IBA, and positive regulation of transcription by RNA polymerase II. Proposed replacements: regulation of transcription by RNA polymerase II positive regulation of transcription by RNA polymerase II Supporting Evidence: file:human/MITF/MITF-uniprot.txt 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) |
| GO:0006355 regulation of DNA-templated transcription | IMP PMID:27889061 Biallelic Mutations in MITF Cause Coloboma, Osteopetrosis, M... | MODIFY | Summary: MITF regulates transcription of its target genes. Reason: Correct but general. MITF regulates RNA polymerase II-transcribed genes (and predominantly activates them); replace with regulation of transcription by RNA polymerase II, which the gene already carries by IBA, and positive regulation of transcription by RNA polymerase II. Proposed replacements: regulation of transcription by RNA polymerase II positive regulation of transcription by RNA polymerase II Supporting Evidence: PMID:27889061 strong M-box (TCATGTG) and E-box (CACGTG) binding |
| GO:0006355 regulation of DNA-templated transcription | NAS PMID:10578055 Molecular cloning of cDNA encoding a novel microphthalmia-as... | MODIFY | Summary: MITF regulates transcription of its target genes. Reason: Correct but general. MITF regulates RNA polymerase II-transcribed genes (and predominantly activates them); replace with regulation of transcription by RNA polymerase II, which the gene already carries by IBA, and positive regulation of transcription by RNA polymerase II. Proposed replacements: regulation of transcription by RNA polymerase II positive regulation of transcription by RNA polymerase II Supporting Evidence: PMID:10578055 MITF-C, like other MITF isoforms, functions as a transcriptional activator of certain target genes |
| GO:0006355 regulation of DNA-templated transcription | NAS PMID:9647758 Identification of a novel isoform of microphthalmia-associat... | MODIFY | Summary: MITF regulates transcription of its target genes. Reason: Correct but general. MITF regulates RNA polymerase II-transcribed genes (and predominantly activates them); replace with regulation of transcription by RNA polymerase II, which the gene already carries by IBA, and positive regulation of transcription by RNA polymerase II. Proposed replacements: regulation of transcription by RNA polymerase II positive regulation of transcription by RNA polymerase II Supporting Evidence: PMID:9647758 MITF-A activated transcription of the tyrosinase and tyrosinase-related protein 1 genes |
| GO:0006357 regulation of transcription by RNA polymerase II | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT root-node inference (PTN005248237) for MiT/TFE family members, with MITF among the seeds. Reason: Appropriate umbrella process for a factor that both activates (predominantly) and represses (e.g. ZEB1) Pol II targets; the activating direction is captured separately by GO:0045944. Supporting Evidence: file:human/MITF/MITF-uniprot.txt 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) Reactome:R-HSA-9926484 MITF-M binds to a cognate element in the ZEB1 locus to repress its expression as assessed by CUT-and-RUN DNA binding analysis and ChIP-seq |
| GO:0010628 positive regulation of gene expression | IDA PMID:22234890 HERC2 rs12913832 modulates human pigmentation by attenuating... | MODIFY | Summary: MITF promotes expression of target genes (OCA2 via the HERC2 rs12913832 enhancer; miR-204/211 in RPE). Reason: Correct but general. The mechanism is transcriptional activation of Pol II-transcribed loci (MITF bound at the OCA2 enhancer; MIR211 lies in the MITF target TRPM1), so positive regulation of transcription by RNA polymerase II is the specific supported term, already carried by the gene. Proposed replacements: positive regulation of transcription by RNA polymerase II Supporting Evidence: PMID:22234890 we detected binding of the transcription factors HLTF, LEF1, and MITF to the HERC2 rs12913832 enhancer |
| GO:0010628 positive regulation of gene expression | IMP PMID:22234890 HERC2 rs12913832 modulates human pigmentation by attenuating... | MODIFY | Summary: MITF promotes expression of target genes (OCA2 via the HERC2 rs12913832 enhancer; miR-204/211 in RPE). Reason: Correct but general. The mechanism is transcriptional activation of Pol II-transcribed loci (MITF bound at the OCA2 enhancer; MIR211 lies in the MITF target TRPM1), so positive regulation of transcription by RNA polymerase II is the specific supported term, already carried by the gene. Proposed replacements: positive regulation of transcription by RNA polymerase II Supporting Evidence: PMID:22234890 we detected binding of the transcription factors HLTF, LEF1, and MITF to the HERC2 rs12913832 enhancer |
| GO:0010628 positive regulation of gene expression | IMP PMID:22523078 Microphthalmia-associated transcription factor (MITF) promot... | MODIFY | Summary: MITF promotes expression of target genes (OCA2 via the HERC2 rs12913832 enhancer; miR-204/211 in RPE). Reason: Correct but general. The mechanism is transcriptional activation of Pol II-transcribed loci (MITF bound at the OCA2 enhancer; MIR211 lies in the MITF target TRPM1), so positive regulation of transcription by RNA polymerase II is the specific supported term, already carried by the gene. Proposed replacements: positive regulation of transcription by RNA polymerase II Supporting Evidence: PMID:22523078 MITF knockdown decreased miR-204/211 expression and caused hfRPE dedifferentiation. |
| GO:0030318 melanocyte differentiation | IBA GO_REF:0000033 | ACCEPT | Summary: Tetrapod-node IBD (PTN000000820) seeded by mouse Mitf. Reason: MITF is the master transcriptional regulator of melanocyte differentiation: it directly activates the melanogenic gene battery (TYR, TYRP1, MC1R), and heterozygous loss causes the pigmentation defects of Waardenburg syndrome 2A/Tietz syndrome. A transcription factor that drives the lineage program does part of the work of the process. Core. Supporting Evidence: file:human/MITF/MITF-uniprot.txt Transcription factor that acts as a master regulator of melanocyte survival and differentiation as well as melanosome biogenesis PMID:8995290 MITF overexpression increased the expression of a reporter gene under the control of the human tyrosinase or TRP-1 gene promoter |
| GO:0030318 melanocyte differentiation | NAS PMID:9647758 Identification of a novel isoform of microphthalmia-associat... | ACCEPT | Summary: Author statement on MITF role in melanocyte (and RPE) differentiation. Reason: Consistent with the IBA and with direct activation of melanogenic genes by MITF isoforms; core. Supporting Evidence: PMID:9647758 MITF-A activated transcription of the tyrosinase and tyrosinase-related protein 1 genes file:human/MITF/MITF-uniprot.txt Transcription factor that acts as a master regulator of melanocyte survival and differentiation as well as melanosome biogenesis |
| GO:0030336 negative regulation of cell migration | IMP PMID:19188590 Aberrant miR-182 expression promotes melanoma metastasis by ... | KEEP AS NON CORE | Summary: MITF depletion increases melanoma cell migration in vitro. Reason: The loss-of-function result is clear in the full text, but anti-migratory effects are an indirect consequence of the MITF-driven differentiation program (e.g. via DIAPH1) in melanoma cells, not a core function; non-core. Supporting Evidence: PMID:19188590 abolition of MITF expression promoted the migratory behavior of melanoma cells |
| GO:0032991 protein-containing complex | IDA PMID:20530484 SOX9, through interaction with microphthalmia-associated tra... | MARK AS OVER ANNOTATED | Summary: MITF co-immunoprecipitated with SOX9 and OTX2 using in vitro translated proteins. Reason: The interaction was shown only by in vitro co-immunoprecipitation of in vitro translated proteins; the authors themselves only raise the possibility of a complex at the BEST1 promoter. A protein-containing complex location is not established. Supporting Evidence: PMID:20530484 we first examined physical interactions by in vitro co-immunoprecipitation using proteins generated by in vitro transcription and translation |
| GO:0045893 positive regulation of DNA-templated transcription | IDA PMID:9647758 Identification of a novel isoform of microphthalmia-associat... | MODIFY | Summary: MITF-A activates tyrosinase and TYRP1 promoter reporters. Reason: Correct but general; the targets are Pol II promoters. Replace with positive regulation of transcription by RNA polymerase II, already carried by the gene. Proposed replacements: positive regulation of transcription by RNA polymerase II Supporting Evidence: PMID:9647758 MITF-A activated transcription of the tyrosinase and tyrosinase-related protein 1 genes |
| GO:0045893 positive regulation of DNA-templated transcription | NAS PMID:10578055 Molecular cloning of cDNA encoding a novel microphthalmia-as... | MODIFY | Summary: MITF-C (and other isoforms) act as transcriptional activators of target promoters. Reason: Correct but general; replace with positive regulation of transcription by RNA polymerase II. Proposed replacements: positive regulation of transcription by RNA polymerase II Supporting Evidence: PMID:10578055 MITF-C, like other MITF isoforms, functions as a transcriptional activator of certain target genes |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:20530484 SOX9, through interaction with microphthalmia-associated tra... | ACCEPT | Summary: MITF positively regulates Pol II transcription of target genes (BEST1, GPNMB, FOS, tyrosinase family). Reason: Core process; directly supported by reporter, ChIP and knockdown experiments in human cells. Supporting Evidence: PMID:20530484 SOX9 physically interacted with MITF and OTX2 and orchestrated synergistic activation of the BEST1 promoter |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:21209915 Inactivation of the FLCN tumor suppressor gene induces TFE3 ... | ACCEPT | Summary: MITF positively regulates Pol II transcription of target genes (BEST1, GPNMB, FOS, tyrosinase family). Reason: Core process; directly supported by reporter, ChIP and knockdown experiments in human cells. Supporting Evidence: PMID:21209915 However, MiTF-induced GPNMB promoter activity was not reduced by FLCN or FLCN/FNIPs. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IEA GO_REF:0000120 | ACCEPT | Summary: MITF positively regulates Pol II transcription of target genes (BEST1, GPNMB, FOS, tyrosinase family). Reason: Core process; directly supported by reporter, ChIP and knockdown experiments in human cells. Supporting Evidence: PMID:8995290 MITF overexpression increased the expression of a reporter gene under the control of the human tyrosinase or TRP-1 gene promoter |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:14737107 STAT3 and MITF cooperatively induce cellular transformation ... | ACCEPT | Summary: MITF positively regulates Pol II transcription of target genes (BEST1, GPNMB, FOS, tyrosinase family). Reason: Core process; directly supported by reporter, ChIP and knockdown experiments in human cells. Supporting Evidence: PMID:14737107 Promoter analysis and chromatin immunoprecipitation assay suggested that both STAT3 and MITF can cooperatively upregulate the c-fos gene. |
| GO:0046983 protein dimerization activity | IEA GO_REF:0000120 | ACCEPT | Summary: bHLH-LZ dimerization (InterPro-based). Reason: MITF binds DNA as a homodimer or heterodimer with TFE3/TFEB/TFEC; dimerization via the HLH-LZ is required for DNA binding and is preserved even in dominant-negative patient mutants. Supporting Evidence: PMID:27889061 mutations do not affect dimerization of MITF with other MiT family transcription factors but rather alter nuclear migration and DNA binding of homo- and heterodimers PMID:15507434 MITF and its related family members TFE3 and TFEB heterodimerize with each other, recognize the same DNA sequences |
| GO:0048066 developmental pigmentation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog-transferred developmental pigmentation. Reason: MITF drives the melanogenic program of melanocytes and RPE, and human MITF variants cause pigmentation disorders (WS2A, Tietz, COMMAD); pigmentation is a downstream organismal outcome of the core melanocyte differentiation function, kept as non-core. Supporting Evidence: file:human/MITF/MITF-uniprot.txt Transcription factor that acts as a master regulator of melanocyte survival and differentiation as well as melanosome biogenesis PMID:9647758 MITF-A activated transcription of the tyrosinase and tyrosinase-related protein 1 genes |
| GO:0048069 eye pigmentation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog-transferred eye pigmentation. Reason: MITF-A is the predominant isoform in RPE and activates melanogenic genes there; ocular pigment defects accompany COMMAD. Downstream outcome, non-core. Supporting Evidence: PMID:9647758 MITF-A activated transcription of the tyrosinase and tyrosinase-related protein 1 genes |
| GO:0065003 protein-containing complex assembly | IDA PMID:20530484 SOX9, through interaction with microphthalmia-associated tra... | MARK AS OVER ANNOTATED | Summary: Based on in vitro co-immunoprecipitation of MITF with SOX9/OTX2. Reason: The paper shows a pairwise physical interaction in vitro and functional synergy at BEST1; it does not show MITF executing a complex-assembly process. Over-interpretation of interaction data. Supporting Evidence: PMID:20530484 we first examined physical interactions by in vitro co-immunoprecipitation using proteins generated by in vitro transcription and translation |
| GO:0070888 E-box binding | IDA PMID:27889061 Biallelic Mutations in MITF Cause Coloboma, Osteopetrosis, M... | ACCEPT | Summary: EMSA shows strong binding of wild-type human MITF to consensus E-box (CACGTG) and M-box elements. Reason: Core, directly demonstrated. Supporting Evidence: PMID:27889061 strong M-box (TCATGTG) and E-box (CACGTG) binding |
| GO:0070888 E-box binding | IEA GO_REF:0000107 | ACCEPT | Summary: Ortholog-transferred E-box binding. Reason: Consistent with direct human EMSA data; core. Supporting Evidence: PMID:27889061 strong M-box (TCATGTG) and E-box (CACGTG) binding file:human/MITF/MITF-uniprot.txt 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) |
| GO:2000144 positive regulation of DNA-templated transcription initiation | IDA PMID:12204775 Involvement of microphthalmia-associated transcription facto... | MODIFY | Summary: MITF activates the MC1R promoter (reporter assay; EMSA of E-box-binding nuclear protein). Reason: The data are promoter-reporter activation; they do not resolve a specific effect on initiation. Replace with positive regulation of transcription by RNA polymerase II. Proposed replacements: positive regulation of transcription by RNA polymerase II Supporting Evidence: PMID:12204775 MC1R promoter activity was induced to the extent of approximately 5-fold in the presence of MITF. |
| GO:2000144 positive regulation of DNA-templated transcription initiation | IDA PMID:8995290 Functional analysis of microphthalmia-associated transcripti... | MODIFY | Summary: MITF activates tyrosinase and TRP-1 promoters via M box/initiator E box CATGTG motifs. Reason: Reporter activation does not specifically establish regulation of initiation (even though one motif is the initiator E box); positive regulation of transcription by RNA polymerase II is the supported term. Proposed replacements: positive regulation of transcription by RNA polymerase II Supporting Evidence: PMID:8995290 MITF overexpression increased the expression of a reporter gene under the control of the human tyrosinase or TRP-1 gene promoter PMID:8995290 Their human gene promoters share the 11-base pair M box containing a CATGTG motif, which was shown here to be bound in vitro by microphthalmia-associated transcription factor (MITF). |
| GO:2001141 regulation of RNA biosynthetic process | IDA PMID:16411896 MITF mediates cAMP-induced protein kinase C-beta expression ... | MODIFY | Summary: MITF-M (but not MITF-A) transactivates the PRKCB promoter; dominant-negative MITF reduces PKC-beta in melanocytes. Reason: Correct but very general; replace with positive regulation of transcription by RNA polymerase II. Proposed replacements: positive regulation of transcription by RNA polymerase II Supporting Evidence: PMID:16411896 these results demonstrate that MITF, specifically MITF-M, is a key transcription factor for PKC-beta |
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Download this section (compressed HTML)Q: MITF-A is recruited to lysosomes by Rag GTPases like TFEB/TFE3, yet PAINT propagates lysosome organization and autophagy regulation only to the TFEB/TFE3 clade. Does MITF (outside melanoma) contribute measurably to CLEAR-network lysosomal gene activation in vivo?
Q: Which MITF isoform-specific N-terminal features determine target selectivity (e.g. MITF-M but not MITF-A activating PRKCB)?
Experiment: Isoform-specific CRISPR deletion of MITF-A exon 1 in TFEB/TFE3 double-knockout RPE cells, followed by RNA-seq and CUT&RUN after Torin-1 treatment, to test whether MITF-A occupies and activates CLEAR elements.
Hypothesis: MITF-A, but not MITF-M, contributes to nutrient-responsive lysosomal gene expression in non-melanocytic cells.
Type: genomics
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