MITF melanocyte inducing transcription factor [Homo sapiens (human)] - Gene

Summary

Official Symbol: MITFprovided by HGNC
Official Full Name: melanocyte inducing transcription factorprovided by HGNC
Primary source: HGNC:HGNC:7105
See related: Ensembl:ENSG00000187098 MIM:156845; AllianceGenome:HGNC:7105
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; CMM8; WS2A; COMMAD; MITF-A; bHLHe32
Summary: The protein encoded by this gene is a transcription factor that contains both basic helix-loop-helix and leucine zipper structural features. The encoded protein regulates melanocyte development and is 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. [provided by RefSeq, Aug 2017]
Expression: Broad expression in endometrium (RPKM 9.9), heart (RPKM 3.9) and 19 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 3p13

Exon count:: 17

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	3	NC_000003.12 (69739464..69968332)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	3	NC_060927.1 (69776362..70005284)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	3	NC_000003.11 (69788615..70017483)

Chromosome 3 - NC_000003.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Novel mechanisms of MITF regulation identified in a mouse suppressor screen.
Title: Novel mechanisms of MITF regulation identified in a mouse suppressor screen.
UVB-induced TRPS1 regulates MITF transcription activity to promote skin pigmentation.
Title: UVB-induced TRPS1 regulates MITF transcription activity to promote skin pigmentation.
Waardenburg syndrome type 2A in a large Iranian family with a novel MITF gene mutation.
Title: Waardenburg syndrome type 2A in a large Iranian family with a novel MITF gene mutation.
MITF regulates the subcellular location of HIF1alpha through SUMOylation to promote the invasion and metastasis of daughter cells derived from polyploid giant cancer cells.
Title: MITF regulates the subcellular location of HIF1α through SUMOylation to promote the invasion and metastasis of daughter cells derived from polyploid giant cancer cells.
Emerging roles of MITF as a crucial regulator of immunity.
Title: Emerging roles of MITF as a crucial regulator of immunity.
Modeling of pigmentation disorders associated with MITF mutation in Waardenburg syndrome revealed an impaired melanogenesis pathway in iPS-derived melanocytes.
Title: Modeling of pigmentation disorders associated with MITF mutation in Waardenburg syndrome revealed an impaired melanogenesis pathway in iPS-derived melanocytes.
Ataxia Telangiectasia Mutated Signaling Delays Skin Pigmentation upon UV Exposure by Mediating MITF Function toward DNA Repair Mode.
Title: Ataxia Telangiectasia Mutated Signaling Delays Skin Pigmentation upon UV Exposure by Mediating MITF Function toward DNA Repair Mode.
GREB1 isoform 4 is specifically transcribed by MITF and required for melanoma proliferation.
Title: GREB1 isoform 4 is specifically transcribed by MITF and required for melanoma proliferation.
Acetylation reprograms MITF target selectivity and residence time.
Title: Acetylation reprograms MITF target selectivity and residence time.
Integrative analyses of RNA-seq and ChIP-seq Reveal MITF as a Target Gene of TFPI-2 in MDA231 Cells.
Title: Integrative analyses of RNA-seq and ChIP-seq Reveal MITF as a Target Gene of TFPI-2 in MDA231 Cells.

Submit: New GeneRIF Correction See all GeneRIFs (307)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Coloboma, osteopetrosis, microphthalmia, macrocephaly, albinism, and deafness MedGen: C4310625 OMIM: 617306 GeneReviews: Not available	not available
Melanoma, cutaneous malignant, susceptibility to, 8 MedGen: C3152204 OMIM: 614456 GeneReviews: Not available	not available
Tietz syndrome MedGen: C0391816 OMIM: 103500 GeneReviews: Not available	not available
Waardenburg syndrome type 2A MedGen: C1860339 OMIM: 193510 GeneReviews: Not available	not available

Copy number response

Description
Copy number response Triplosensitivity No evidence available (Last evaluated 2021-04-13) ClinGen Genome Curation Page Haploinsufficency Sufficient evidence for dosage pathogenicity (Last evaluated 2021-04-13) ClinGen Genome Curation PagePubMed

EBI GWAS Catalog

Description
Genome wide association study (GWAS) of Chagas cardiomyopathy in Trypanosoma cruzi seropositive subjects. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

Mitf (e-PCR), detects polymorphism
- UniSTS:143873

RH28674 (e-PCR)
- UniSTS:92187

D3S3964 (e-PCR)
- UniSTS:80449

D3S2825E (e-PCR)
- UniSTS:150861

GDB:363545 (e-PCR)
- UniSTS:156771

MITF_7830 (e-PCR)
- UniSTS:466336

SHGC-81156 (e-PCR)
- UniSTS:103340

SHGC-77109 (e-PCR)
- UniSTS:4786

RH119999 (e-PCR)
- UniSTS:133323

STS-N33393 (e-PCR)
- UniSTS:32973

SHGC-84185 (e-PCR)
- UniSTS:104681

RH77689 (e-PCR)
- UniSTS:44285

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables DNA-binding transcription activator activity, RNA polymerase II-specific	IDA Inferred from Direct Assay more info	PubMed
enables DNA-binding transcription activator activity, RNA polymerase II-specific	IMP Inferred from Mutant Phenotype more info	PubMed
enables DNA-binding transcription factor activity, RNA polymerase II-specific	IBA Inferred from Biological aspect of Ancestor more info
enables DNA-binding transcription factor activity, RNA polymerase II-specific	ISA Inferred from Sequence Alignment more info
enables DNA-binding transcription repressor activity, RNA polymerase II-specific	NAS Non-traceable Author Statement more info	PubMed
enables E-box binding	IDA Inferred from Direct Assay more info	PubMed
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA Inferred from Biological aspect of Ancestor more info
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables chromatin binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein dimerization activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in Wnt signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in bone remodeling	IEA Inferred from Electronic Annotation more info
involved_in camera-type eye development	IEA Inferred from Electronic Annotation more info
involved_in cell fate commitment	IEA Inferred from Electronic Annotation more info
involved_in melanocyte apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in melanocyte differentiation	IBA Inferred from Biological aspect of Ancestor more info
involved_in melanocyte differentiation	NAS Non-traceable Author Statement more info	PubMed
involved_in negative regulation of apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of cell migration	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of transcription by RNA polymerase II	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in osteoclast differentiation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of DNA-templated transcription	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of DNA-templated transcription	NAS Non-traceable Author Statement more info	PubMed
involved_in positive regulation of DNA-templated transcription initiation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of gene expression	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of gene expression	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein-containing complex assembly	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of DNA-templated transcription	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of DNA-templated transcription	NAS Non-traceable Author Statement more info	PubMed
involved_in regulation of RNA biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of cell population proliferation	IEA Inferred from Electronic Annotation more info
involved_in regulation of osteoclast differentiation	IEA Inferred from Electronic Annotation more info
involved_in regulation of transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
located_in chromatin	ISA Inferred from Sequence Alignment more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info
located_in lysosomal membrane	IDA Inferred from Direct Assay more info	PubMed
located_in nucleoplasm	TAS Traceable Author Statement more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
is_active_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in nucleus	NAS Non-traceable Author Statement more info	PubMed
part_of protein-containing complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: microphthalmia-associated transcription factor

Names: class E basic helix-loop-helix protein 32; melanogenesis associated transcription factor; microphtalmia-associated transcription factor

NCBI Reference Sequences (RefSeq)

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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

NG_011631.1 RefSeqGene

Range

4954..233856

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_776

mRNA and Protein(s)

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

See identical proteins and their annotated locations for NP_000239.1

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/TrEMBL

A0A0H3W5T2

Related

ENSP00000377880.3, ENST00000394351.9

Conserved Domains (3) summary

cd00083
Location:202 → 262

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 → 403

DUF3371; Domain of unknown function (DUF3371)

pfam15951
Location:11 → 87

MITF_TFEB_C_3_N; MITF/TFEB/TFEC/TFE3 N-terminus
NM_001184967.2 → 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)

AC104445, AC104449, AK296129, AL110195, AL117653, AW242257

Consensus CDS

CCDS54607.1

UniProtKB/TrEMBL

A0A0H3W5T2

Related

ENSP00000418845.1, ENST00000472437.5

Conserved Domains (3) summary

cd00083
Location:251 → 311

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 → 458

DUF3371; Domain of unknown function (DUF3371)

pfam15951
Location:4 → 142

MITF_TFEB_C_3_N; MITF/TFEB/TFEC/TFE3 N-terminus
NM_001184968.2 → NP_001171897.1 microphthalmia-associated transcription factor isoform 8

See identical proteins and their annotated locations for NP_001171897.1

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)

AC104449, BC012503, BQ219650

Consensus CDS

CCDS74962.1

UniProtKB/TrEMBL

A0A087WXU1, E9PKJ8

Related

ENSP00000481286.1, ENST00000394348.2

Conserved Domains (1) summary

pfam15951
Location:11 → 88

MITF_TFEB_C_3_N; MITF/TFEB/TFEC/TFE3 N-terminus
NM_001354604.2 → NP_001341533.1 microphthalmia-associated transcription factor isoform 9

Status: REVIEWED

Source sequence(s)

AC099326, AC104445, AC104449

Consensus CDS

CCDS87108.1

UniProtKB/Swiss-Prot

B4DJL2, D3K197, E9PFN0, O75030, Q14841, Q9P2V0, Q9P2V1, Q9P2V2, Q9P2Y8

UniProtKB/TrEMBL

A8K5K3

Related

ENSP00000295600.8, ENST00000352241.9

Conserved Domains (3) summary

cd00083
Location:309 → 369

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:397 → 516

DUF3371; Domain of unknown function (DUF3371)

pfam15951
Location:56 → 194

MITF_TFEB_C_3_N; MITF/TFEB/TFEC/TFE3 N-terminus
NM_001354605.2 → NP_001341534.1 microphthalmia-associated transcription factor isoform 10

Status: REVIEWED

Source sequence(s)

AC099326, AC104445, AC104449

UniProtKB/TrEMBL

A8K5K3

Conserved Domains (3) summary

cd00083
Location:308 → 368

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:396 → 515

DUF3371; Domain of unknown function (DUF3371)

pfam15951
Location:55 → 193

MITF_TFEB_C_3_N; MITF/TFEB/TFEC/TFE3 N-terminus
NM_001354606.2 → NP_001341535.1 microphthalmia-associated transcription factor isoform 11

Status: REVIEWED

Source sequence(s)

AC099326, AC104445, AC104449

UniProtKB/TrEMBL

A8K5K3

Conserved Domains (1) summary

cd18926
Location:293 → 396

bHLHzip_MITF; basic Helix-Loop-Helix-zipper (bHLHzip) domain found in microphthalmia-associated transcription factor (MITF) and similar proteins
NM_001354607.2 → NP_001341536.1 microphthalmia-associated transcription factor isoform 12

Status: REVIEWED

Source sequence(s)

AC099326, AC104445, AC104449, AC124915

Consensus CDS

CCDS93308.1

UniProtKB/TrEMBL

A0A8I5KSZ4, B4DNC7

Related

ENSP00000510225.1, ENST00000687384.1

Conserved Domains (3) summary

cd00083
Location:286 → 346

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:374 → 493

DUF3371; Domain of unknown function (DUF3371)

pfam15951
Location:39 → 177

MITF_TFEB_C_3_N; MITF/TFEB/TFEC/TFE3 N-terminus
NM_001354608.2 → NP_001341537.1 microphthalmia-associated transcription factor isoform 7

Status: REVIEWED

Description

Transcript Variant: This variant (13), as well as variant 7, encodes isoform 7.

Source sequence(s)

AC099326, AC104445, AC104449, AC124915

Consensus CDS

CCDS54607.1

UniProtKB/TrEMBL

A0A0H3W5T2

Conserved Domains (3) summary

cd00083
Location:251 → 311

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 → 458

DUF3371; Domain of unknown function (DUF3371)

pfam15951
Location:4 → 142

MITF_TFEB_C_3_N; MITF/TFEB/TFEC/TFE3 N-terminus
NM_006722.3 → NP_006713.1 microphthalmia-associated transcription factor isoform 3

See identical proteins and their annotated locations for NP_006713.1

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/TrEMBL

B4DNC7

Related

ENSP00000391803.3, ENST00000448226.9

Conserved Domains (3) summary

cd00083
Location:302 → 362

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 → 503

DUF3371; Domain of unknown function (DUF3371)

pfam15951
Location:55 → 193

MITF_TFEB_C_3_N; MITF/TFEB/TFEC/TFE3 N-terminus
NM_198158.3 → NP_937801.1 microphthalmia-associated transcription factor isoform 5

See identical proteins and their annotated locations for NP_937801.1

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/TrEMBL

A0A0H3W5T2

Related

ENSP00000324246.6, ENST00000314557.10

Conserved Domains (3) summary

cd00083
Location:196 → 256

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 → 403

DUF3371; Domain of unknown function (DUF3371)

pfam15951
Location:11 → 87

MITF_TFEB_C_3_N; MITF/TFEB/TFEC/TFE3 N-terminus
NM_198159.3 → NP_937802.1 microphthalmia-associated transcription factor isoform 1

See identical proteins and their annotated locations for NP_937802.1

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/TrEMBL

A8K5K3

Related

ENSP00000494105.1, ENST00000642352.1

Conserved Domains (3) summary

cd00083
Location:303 → 363

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 → 504

DUF3371; Domain of unknown function (DUF3371)

pfam15951
Location:56 → 194

MITF_TFEB_C_3_N; MITF/TFEB/TFEC/TFE3 N-terminus
NM_198177.3 → NP_937820.1 microphthalmia-associated transcription factor isoform 2

See identical proteins and their annotated locations for NP_937820.1

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

Related

ENSP00000324443.5, ENST00000314589.11

Conserved Domains (3) summary

cd00083
Location:287 → 347

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 → 488

DUF3371; Domain of unknown function (DUF3371)

pfam15951
Location:40 → 178

MITF_TFEB_C_3_N; MITF/TFEB/TFEC/TFE3 N-terminus
NM_198178.3 → NP_937821.2 microphthalmia-associated transcription factor isoform 6

See identical proteins and their annotated locations for NP_937821.2

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

A0A0H3W5T2

Related

ENSP00000435909.1, ENST00000531774.1

Conserved Domains (3) summary

cd00083
Location:140 → 200

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 → 341

DUF3371; Domain of unknown function (DUF3371)

pfam15951
Location:11 → 31

MITF_TFEB_C_3_N; MITF/TFEB/TFEC/TFE3 N-terminus