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    MITF microphthalmia-associated transcription factor [ Homo sapiens ]

    Gene ID: 4286, updated on 5-Feb-2012
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    Summary

    Official Symbol
    MITFprovided by HGNC
    Official Full Name
    microphthalmia-associated transcription factorprovided by HGNC
    Primary source
    HGNC:7105
    See related
    Ensembl:ENSG00000187098; HPRD:01138; MIM:156845; Vega:OTTHUMG00000149921
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    MI; WS2; WS2A; bHLHe32
    Summary
    This gene encodes a transcription factor that contains both basic helix-loop-helix and leucine zipper structural features. It regulates the differentiation and development of melanocytes retinal pigment epithelium and is also responsible for pigment cell-specific transcription of the melanogenesis enzyme genes. Heterozygous mutations in the this gene cause auditory-pigmentary syndromes, such as Waardenburg syndrome type 2 and Tietz syndrome. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]
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    Genomic context

    Location :
    3p14.2-p14.1
    Sequence :
    Chromosome: 3; NC_000003.11 (69788586..70017488)
    See MITF in Epigenomics, MapViewer

    Chromosome 3 - NC_000003.11Genomic Context describing neighboring genes Neighboring gene RNA binding motif protein 43 pseudogene Neighboring gene H1 histone family, member O, oocyte-specific pseudogene Neighboring gene RNA-binding region (RNP1, RRM) containing 3 pseudogene Neighboring gene ubiquinol-cytochrome c reductase hinge protein pseudogene 4

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    Genomic regions, transcripts, and products

    Go to nucleotideGraphics FASTA GenBank

    Go to reference sequence details
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    Bibliography

    Related articles in PubMed

    1. Hypoxia-induced transcriptional repression of the melanoma-associated oncogene MITF. Feige E, et al. Proc Natl Acad Sci U S A, 2011 Oct 25. PMID 21949374.
    2. The E-box binding factors Max/Mnt, MITF, and USF1 act coordinately with FoxO to regulate expression of proapoptotic and cell cycle control genes by phosphatidylinositol 3-kinase/Akt/glycogen synthase kinase 3 signaling. Terragni J, et al. J Biol Chem, 2011 Oct 21. PMID 21873430.
    3. Regulation of MITF stability by the USP13 deubiquitinase. Zhao X, et al. Nat Commun, 2011 Aug 2. PMID 21811243.
    4. Quantitative comparison of MiTF, Melan-A, HMB-45 and Mel-5 in solar lentigines and melanoma in situ. Kim J, et al. J Cutan Pathol, 2011 Oct. PMID 21797920.
    5. Human cutaneous melanomas lacking MITF and melanocyte differentiation antigens express a functional Axl receptor kinase. Sensi M, et al. J Invest Dermatol, 2011 Dec. PMID 21796150.

    See all (137) citations in PubMed

    See citations in PubMed for homologs of this gene provided by HomoloGene

    GeneRIFs: Gene References Into Functions What's a GeneRIF?

    1. the cell-type-specific presence of MITF in melanoma affects beta-catenin's pro-invasive properties otherwise active in colon or liver cancer.
      Title: In melanoma, beta-catenin is a suppressor of invasion.
    2. Axl-positive melanomas did not express microphthalmia transcription factor (MITF) and melanocyte differentiation antigens such as MART-1 and gp100 and possessed a greater in vitro invasive potential compared with Axl-negative ones.
      Title: Human cutaneous melanomas lacking MITF and melanocyte differentiation antigens express a functional Axl receptor kinase.
    3. MiTF is a superior marker for quantification of melanocytes in the evaluation of subtle intraepidermal melanocytic proliferations and in the differential diagnosis of solar lentigo.
      Title: Quantitative comparison of MiTF, Melan-A, HMB-45 and Mel-5 in solar lentigines and melanoma in situ.
    4. MITF expression is potently reduced under hypoxic conditions in primary melanocytes and melanoma and clear cell sarcoma cells through hypoxia inducible factor 1 (HIF1)-mediated induction of DEC1.
      Title: Hypoxia-induced transcriptional repression of the melanoma-associated oncogene MITF.
    5. The E-box binding factors Max/Mnt, MITF, and USF1 act coordinately with FoxO to regulate expression of proapoptotic and cell cycle control genes by phosphatidylinositol 3-kinase/Akt/glycogen synthase kinase 3 signaling.
      Title: The E-box binding factors Max/Mnt, MITF, and USF1 act coordinately with FoxO to regulate expression of proapoptotic and cell cycle control genes by phosphatidylinositol 3-kinase/Akt/glycogen synthase kinase 3 signaling.
    6. demonstrated through linkage, genomic sequence analysis, and expression studies a novel splice mutation in MITF that was previously unrecognized in a large family with Waardenbrug syndrome.
      Title: Novel splice mutation in microthalmia-associated transcription factor in Waardenburg Syndrome.
    7. Through deubiquitination, USP13 stabilizes and upregulates MITF protein levels.
      Title: Regulation of MITF stability by the USP13 deubiquitinase.
    8. find reduced levels of Mitf activity using an mitfa temperature-sensitive line results in a dramatic increase in differentiated melanocyte cell division
      Title: Differentiated melanocyte cell division occurs in vivo and is promoted by mutations in Mitf.
    9. MiTF is as effective as MART-1/Azure blue in identifying melanocytes in the context of solar lentigo or melanoma in situ
      Title: An immunohistochemical comparison between MiTF and MART-1 with Azure blue counterstaining in the setting of solar lentigo and melanoma in situ.
    10. The HMB45/MITF stains may serve as adjuncts to predict malignancy of melanocytic lesions.
      Title: Immunohistochemical double stains against Ki67/MART1 and HMB45/MITF: promising diagnostic tools in melanocytic lesions.
    Submit: New GeneRIF Correction See all (93)
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    Phenotypes

    Review eQTL and phenotype association data in this region using PheGenI

    Tietz albinism-deafness syndrome

    Waardenburg syndrome, type 2A

    Waardenburg syndrome/ocular albinism, digenic

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    Interactions

    Products Interactant Other Gene Complex Source Pubs Description
    O75030 P35222 CTNNB1    HPRD  PubMed  
    O75030 Q09472 EP300    HPRD  PubMed  
    O75030 P01100 FOS    HPRD  PubMed  
    O75030 P49841 GSK3B    HPRD  PubMed  
    O75030 Q9UJU2 LEF1    HPRD  PubMed  
    O75030 P28482 MAPK1    HPRD  PubMed  
    O75030 Q16539 MAPK14    HPRD  PubMed  
    O75030 P32243 OTX2    HPRD  PubMed  
    O75030 Q9HBE1 PATZ1    HPRD  PubMed  
    O75030 P23760 PAX3    HPRD  PubMed  
    O75030 P26367 PAX6    HPRD  PubMed  
    O75030 Q9Y6X2 PIAS3    HPRD  PubMed  
    O75030 Q15418 RPS6KA1    HPRD  PubMed  
    O75030 P17947 SPI1    HPRD  PubMed  
    O75030 P63165 SUMO1    HPRD  PubMed  
    O75030 P19532 TFE3    HPRD  PubMed  
    O75030 P19484 TFEB    HPRD  PubMed  
    O75030 Transcription factor EC TFEC    HPRD  PubMed  
    O75030 P63279 UBE2I    HPRD  PubMed  
    NT_029419.10 CDK2    BIND  PubMed MITF interacts with the CDK2 promoter. 
    NC_000006.9 CDKN1A    BIND  PubMed An unspecified isoform of Mitf interacts with the p21 promoter. 
    BioGRID:110432 BioGRID:108636 FOS    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:110432 BioGRID:119354 LEF1    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex; Two-hybrid 
    BioGRID:110432 BioGRID:110310 MARK3    BioGRID  PubMed Two-hybrid 
    BioGRID:110432 BioGRID:117133 PATZ1    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex; Two-hybrid 
    BioGRID:110432 BioGRID:111114 PAX6    BioGRID  PubMed Reconstituted Complex 
    BioGRID:110432 BioGRID:114124 PIAS1    BioGRID  PubMed Reconstituted Complex 
    BioGRID:110432 BioGRID:114523 PIAS2    BioGRID  PubMed Reconstituted Complex 
    BioGRID:110432 BioGRID:115673 PIAS3    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex; Two-hybrid 
    BioGRID:110432 BioGRID:115508 PSMD14    BioGRID  PubMed Affinity Capture-Western; Two-hybrid 
    NP_000312.1 RB1    BIND  PubMed An unspecified isoform of Mitf interacts with Rb. 
    BioGRID:110432 BioGRID:112566 SPI1    BioGRID  PubMed Reconstituted Complex 
    BioGRID:110432 BioGRID:113188 SUMO1    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:110432 BioGRID:112888 TFE3    BioGRID  PubMed Affinity Capture-Western; Phenotypic Enhancement 
    BioGRID:110432 BioGRID:116478 TFEC    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:110432 BioGRID:113177 UBE2I    BioGRID  PubMed Reconstituted Complex; Two-hybrid 
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    General gene information

    Markers

    Genotypes

    Homology

    Pathways from BioSystems

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    DNA binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription IDA
    Inferred from Direct Assay
    more info
    		  
    protein binding IPI
    Inferred from Physical Interaction
    more info
    		  
    Process Evidence Code Pubs
    melanocyte differentiation NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    multicellular organismal development IEA
    Inferred from Electronic Annotation
    more info
    		  
    positive regulation of transcription from RNA polymerase II promoter IDA
    Inferred from Direct Assay
    more info
    		  
    positive regulation of transcription, DNA-dependent IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    positive regulation of transcription, DNA-dependent NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    protein complex assembly IDA
    Inferred from Direct Assay
    more info
    		  
    regulation of transcription, DNA-dependent IEA
    Inferred from Electronic Annotation
    more info
    		  
    regulation of transcription, DNA-dependent NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    nucleus NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    protein complex IDA
    Inferred from Direct Assay
    more info
    		  
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    General protein information

    Preferred Names
    microphthalmia-associated transcription factor
    Names
    microphthalmia-associated transcription factor
    class E basic helix-loop-helix protein 32
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    NCBI Reference Sequences (RefSeq)

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_011631.1 RefSeqGene

      Range
      4954..233856
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_000248.3 → NP_000239.1  microphthalmia-associated transcription factor isoform 4

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) differs in the 5' UTR, the 5' coding region and uses an alternate, in-frame splice site in the 3' coding region, compared to variant 1. The resulting isoform (4), also known as isoform MITF-M, has a distinct N-terminus and is shorter than isoform 1.
      Source sequence(s)
      AC104449, AL117653, AW242257, BQ219650, Z29678
      Consensus CDS
      CCDS2913.1
      UniProtKB/Swiss-Prot
      O75030
      Related
      ENSP00000377880, OTTHUMP00000195139, ENST00000394351, OTTHUMT00000313944
      Conserved Domains (2) summary
      cd00083
      Location:202 – 262
      Blast Score: 158
      HLH; Helix-loop-helix domain, found in specific DNA- binding proteins that act as transcription factors; 60-100 amino acids long. A DNA-binding basic region is followed by two alpha-helices separated by a variable loop region; HLH forms homo- and heterodimers, ...
      pfam11851
      Location:290 – 402
      Blast Score: 331
      DUF3371; Domain of unknown function (DUF3371)

    2. NM_001184967.1 → NP_001171896.1  microphthalmia-associated transcription factor isoform 7

      Status: REVIEWED

      Description
      Transcript Variant: This variant (7) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at a downstream start codon, compared to variant 1. The encoded isoform (7) is shorter than isoform 1.
      Source sequence(s)
      AC104449, AK296129, AL110195, AL117653, AW242257
      Consensus CDS
      CCDS54607.1
      UniProtKB/TrEMBL
      B4DJL2
      UniProtKB/TrEMBL
      E9PFN0
      UniProtKB/Swiss-Prot
      O75030
      Related
      ENSP00000418845, OTTHUMP00000213867, ENST00000472437, OTTHUMT00000352921
      Conserved Domains (2) summary
      cd00083
      Location:251 – 311
      Blast Score: 159
      HLH; Helix-loop-helix domain, found in specific DNA- binding proteins that act as transcription factors; 60-100 amino acids long. A DNA-binding basic region is followed by two alpha-helices separated by a variable loop region; HLH forms homo- and heterodimers, ...
      pfam11851
      Location:339 – 451
      Blast Score: 325
      DUF3371; Domain of unknown function (DUF3371)

    3. NM_001184968.1 → NP_001171897.1  microphthalmia-associated transcription factor isoform 8

      Status: REVIEWED

      Description
      Transcript Variant: This variant (8) has multiple differences, compared to variant 1. These differences result in a distinct 5' UTR and cause translation initiation at an alternate start codon, compared to variant 1. The encoded protein (isoform 8) is shorter than isoform 1 and has unique N- and C-termini.
      Source sequence(s)
      BC012503, BQ219650

    4. NM_006722.2 → NP_006713.1  microphthalmia-associated transcription factor isoform 3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) differs in the 5' UTR and the 5' coding region, compared to variant 1. The resulting isoform (3), also known as isoform MITF-C, has a distinct N-terminus and is shorter than isoform 1.
      Source sequence(s)
      AB006988, AC104449, AL110195, AL117653, AW242257
      UniProtKB/Swiss-Prot
      O75030
      UniProtKB/TrEMBL
      Q8WYR3
      Related
      ENSP00000327867, ENST00000328528
      Conserved Domains (2) summary
      cd00083
      Location:302 – 362
      Blast Score: 158
      HLH; Helix-loop-helix domain, found in specific DNA- binding proteins that act as transcription factors; 60-100 amino acids long. A DNA-binding basic region is followed by two alpha-helices separated by a variable loop region; HLH forms homo- and heterodimers, ...
      pfam11851
      Location:390 – 502
      Blast Score: 327
      DUF3371; Domain of unknown function (DUF3371)

    5. NM_198158.2 → NP_937801.1  microphthalmia-associated transcription factor isoform 5

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) differs in the 5' UTR and the 5' coding region, compared to variant 1. The resulting isoform (5), has a distinct N-terminus and is shorter than isoform 1.
      Source sequence(s)
      AC104449, AL117653, AW242257, BC026961, BQ219650
      Consensus CDS
      CCDS43107.1
      UniProtKB/Swiss-Prot
      O75030
      Related
      ENSP00000324246, OTTHUMP00000195140, ENST00000314557, OTTHUMT00000313945
      Conserved Domains (2) summary
      cd00083
      Location:196 – 256
      Blast Score: 156
      HLH; Helix-loop-helix domain, found in specific DNA- binding proteins that act as transcription factors; 60-100 amino acids long. A DNA-binding basic region is followed by two alpha-helices separated by a variable loop region; HLH forms homo- and heterodimers, ...
      pfam11851
      Location:284 – 396
      Blast Score: 329
      DUF3371; Domain of unknown function (DUF3371)

    6. NM_198159.2 → NP_937802.1  microphthalmia-associated transcription factor isoform 1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript, and encodes the longest isoform (1), also known as isoform MITF-A.
      Source sequence(s)
      AC104449, AL110195, AL117653, AW242257, DA058963
      Consensus CDS
      CCDS43106.1
      UniProtKB/Swiss-Prot
      O75030
      Related
      ENSP00000295600, OTTHUMP00000195123, ENST00000352241, OTTHUMT00000313920
      Conserved Domains (2) summary
      cd00083
      Location:303 – 363
      Blast Score: 160
      HLH; Helix-loop-helix domain, found in specific DNA- binding proteins that act as transcription factors; 60-100 amino acids long. A DNA-binding basic region is followed by two alpha-helices separated by a variable loop region; HLH forms homo- and heterodimers, ...
      pfam11851
      Location:391 – 503
      Blast Score: 323
      DUF3371; Domain of unknown function (DUF3371)

    7. NM_198177.2 → NP_937820.1  microphthalmia-associated transcription factor isoform 2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR and the 5' coding region, compared to variant 1. The resulting isoform (2), also known as isoform MITF-H, has a distinct N-terminus and is shorter than isoform 1.
      Source sequence(s)
      AC104449, AK297858, AL110195, AL117653, AW242257, DC388606
      Consensus CDS
      CCDS46865.1
      UniProtKB/TrEMBL
      B4DNC7
      UniProtKB/Swiss-Prot
      O75030
      Related
      ENSP00000324443, OTTHUMP00000213868, ENST00000314589, OTTHUMT00000352922
      Conserved Domains (2) summary
      cd00083
      Location:287 – 347
      Blast Score: 159
      HLH; Helix-loop-helix domain, found in specific DNA- binding proteins that act as transcription factors; 60-100 amino acids long. A DNA-binding basic region is followed by two alpha-helices separated by a variable loop region; HLH forms homo- and heterodimers, ...
      pfam11851
      Location:375 – 487
      Blast Score: 325
      DUF3371; Domain of unknown function (DUF3371)

    8. NM_198178.2 → NP_937821.2  microphthalmia-associated transcription factor isoform 6

      Status: REVIEWED

      Description
      Transcript Variant: This variant (6) differs in the 5' UTR and the 5' coding region, and uses two alternate, in-frame splice sites in the coding region compared to variant 1. The resulting isoform (6), also known as isoform MITF-Mdel, has a distinct N-terminus and is shorter than isoform 1.
      Source sequence(s)
      AC104449, AL117653, AW242257, BQ219650, GU355676
      Consensus CDS
      CCDS46866.2
      UniProtKB/TrEMBL
      D3K197
      Related
      ENSP00000435909, OTTHUMP00000230787, ENST00000531774, OTTHUMT00000385879
      Conserved Domains (2) summary
      cd00083
      Location:140 – 200
      Blast Score: 151
      HLH; Helix-loop-helix domain, found in specific DNA- binding proteins that act as transcription factors; 60-100 amino acids long. A DNA-binding basic region is followed by two alpha-helices separated by a variable loop region; HLH forms homo- and heterodimers, ...
      pfam11851
      Location:228 – 340
      Blast Score: 337
      DUF3371; Domain of unknown function (DUF3371)

    RefSeqs of Annotated Genomes: Build 37.3

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh37.p5 Primary Assembly

    Genomic

    1. NC_000003.11 Reference GRCh37.p5 Primary Assembly

      Range
      69788586..70017488
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate HuRef

    Genomic

    1. AC_000135.1 Alternate HuRef

      Range
      69788411..70016737
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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    Related Sequences

    Nucleotide Protein
    Heading Accession and Version
    genomic AB009608.1 BAA95209.1
    genomic AB032357.1 BAA95206.1
    genomic AB032358.1 BAA95207.1
    genomic AB032359.1 BAA95208.1
    genomic AC099326.1 (76535..152771) None
    genomic AC104445.2 (169499..201217) None
    genomic AC104449.3 (61951..106193) None
    genomic AC124915.5 (107092..183747) None
    genomic AF034755.1 AAC39639.1
    genomic CH471055.1 EAW65479.1
      EAW65480.1
      EAW65481.1
      EAW65482.1
      EAW65483.1
      EAW65484.1
    genomic D82874.1 None
    mRNA AB006909.1 BAA32288.1
    mRNA AB006988.1 BAB83926.1
    mRNA AB006989.1 BAC16749.1
    mRNA AK291318.1 BAF84007.1
    mRNA AK296129.1 BAG58874.1
    mRNA AK297858.1 BAG60189.1
    mRNA AL110195.1 CAB53672.1
    mRNA AL117653.1 None
    mRNA AW242257.1 None
    mRNA BC011461.1 None
    mRNA BC012503.1 None
    mRNA BC026961.2 AAH26961.1
    mRNA BC065243.1 AAH65243.1
    mRNA BM800230.1 None
    mRNA BQ219650.1 None
    mRNA BU167035.1 None
    mRNA DA058963.1 None
    mRNA DC388606.1 None
    mRNA GU355676.1 ADB90411.1
    mRNA Z29678.1 CAA82775.1
    Protein Accession Links
    GenePept Link UniProtKB Link
    O75030.2 GenPept UniProtKB/Swiss-Prot:O75030
    Q8WYR3 GenPept UniProtKB/TrEMBL:Q8WYR3
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    Additional Links

    Additional Links

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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