Microphthalmia-associated transcription factor (MITF) is a basic helix-loop-helix leucine zipper

Leucine zipper

A leucine zipper, aka leucine scissors, is a common three-dimensional structural motif in proteins. These motifs are usually found as part of a DNA-binding domain in various transcription factors, and are therefore involved in regulating gene expression...

 transcription factor

Transcription factor

In molecular biology and genetics, a transcription factor is a protein that binds to specific DNA sequences, thereby controlling the flow of genetic information from DNA to mRNA...

 involved in melanocyte

Melanocyte

-External links: - "Eye: fovea, RPE" - "Integument: pigmented skin"...

 and osteoclast

Osteoclast

An osteoclast is a type of bone cell that removes bone tissue by removing its mineralized matrix and breaking up the organic bone . This process is known as bone resorption. Osteoclasts were discovered by Kolliker in 1873...

 development.

Clinical significance

It can be associated with Tietz syndrome

Tietz syndrome

Tietz syndrome, also called Tietz albinism-deafness syndrome or albinism and deafness of Tietz, is an autosomal dominant congenital disorder characterized by deafness and leucism. It is caused by a mutation in the microphthalmia-associated transcription factor gene...

 and Waardenburg syndrome

Waardenburg syndrome

Waardenburg syndrome Waardenburg syndrome Waardenburg syndrome (also Waardenburg­ Shah Syndrome, Waardenburg-Klein syndrome, Mende's syndrome II, Van der Hoeve-Halbertsma-Waardenburg syndrome, Ptosis-Epicanthus syndrome, Van der Hoeve-Halbertsma-Gualdi syndrome, Waardenburg type Pierpont,[5] Van...

 type IIa.

Target genes

MITF recognizes E-box (CAYRTG) and M-box (TCAYRTG or CAYRTGA) sequences in the promoter regions of target genes. Known target genes (confirmed by at least two independent sources) of this transcription factor include,

ACP5 Tartrate resistant acid phosphatase Tartrate-resistant acid phosphatase or acid phosphatase 5, tartrate resistant is a glycosylated monomeric metalloenzyme expressed in mammals. It has a molecular weight of approximately 35kDa, a basic isoelectric point , and optimal activity in acidic conditions. TRAP is synthesized as latent...	BCL2 Bcl-2 Bcl-2 is the founding member of the Bcl-2 family of apoptosis regulator proteins encoded by the BCL2 gene. Bcl-2 derives its name from B-cell lymphoma 2, as it is the second member of a range of proteins initially described in chromosomal translocations involving chromosomes 14 and 18 in...	BEST1	BIRC7 BIRC7 Baculoviral IAP repeat-containing protein 7 is a protein that in humans is encoded by the BIRC7 gene.-Further reading:...
CDK2 Cyclin-dependent kinase 2 Cyclin-dependent kinase 2 also known as cell division protein kinase 2 is an enzyme that in humans is encoded by the CDK2 gene.-Function:...	CLCN7 CLCN7 Chloride channel 7, also known as CLCN7, is a human gene. In melanocytic cells this gene is regulated by the Microphthalmia-associated transcription factor.-External Links:*...	DCT Dopachrome tautomerase Dopachrome tautomerase , also known as DCT, is a human gene. Its expression is regulated by the microphthalmia-associated transcription factor .-Further reading:...	EDNRB Endothelin receptor type B Endothelin receptor type B, also known as ETB is a protein that in humans is encoded by the EDNRB gene.- Function :Endothelin receptor type B is a G protein-coupled receptor which activates a phosphatidylinositol-calcium second messenger system. Its ligand, endothelin, consists of a family of three...
GPNMB GPNMB Transmembrane glycoprotein NMB is a protein that in humans is encoded by the GPNMB gene. The mouse and rat orthologues of GPNMB are known as DC-HIL and Osteoactivin , respectively. Two transcript variants encoding 560 and 572 amino acid isoforms have been characterized for this gene in humans...	GPR143 GPR143 G-protein coupled receptor 143 is a protein that in humans is encoded by the GPR143 gene.Ocular albinism type 1 protein is a conserved integral membrane protein with seven transmembrane domains...	MC1R Melanocortin 1 receptor The melanocortin 1 receptor , also known as melanocyte-stimulating hormone receptor , melanin-activating peptide receptor, or melanotropin receptor, is a G protein-coupled receptor which binds to a class of pituitary peptide hormones known as the melanocortins, of which include adrenocorticotropic...	MLANA MLANA Melan-A, also known as MLANA, is a human gene. Its expression is regulated by the Microphthalmia-associated transcription factor.-Further reading:...
OSTM1 OSTM1 Osteopetrosis-associated transmembrane protein 1 is a protein that in humans is encoded by the OSTM1 gene.-Further reading:...	RAB27A RAB27A Ras-related protein Rab-27A is a protein that in humans is encoded by the RAB27A gene.-Interactions:RAB27A has been shown to interact with EXPH5, SYTL1, MYO5A, RPH3AL and SYTL2.-Further reading:...	SILV SILV Melanocyte protein Pmel 17 is a protein that in humans is encoded by the SILV gene. Its gene product may be referred to as silver, ME20, gp100 or Pmel17 and is a 100 kDa type I transmembrane protein...	SLC45A2 SLC45A2 Membrane-associated transporter protein also known as solute carrier family 45 member 2 or melanoma antigen AIM1 is a protein that in humans is encoded by the SLC45A2 gene.-Function:...
TBX2 TBX2 T-box transcription factor TBX2 is a protein that in humans is encoded by the TBX2 gene.-Further reading:...	TRPM1 TRPM1 Transient receptor potential cation channel subfamily M member 1 is a protein that in humans is encoded by the TRPM1 gene.- Function :The protein encoded by this gene is similar to the transient receptor potential calcium channel family members...	TYR Tyrosinase Tyrosinase also known as monophenol monooxygenase is an enzyme that catalyses the oxidation of phenols and is widespread in plants and animals...	TYRP1 TYRP1 Tyrosinase-related protein 1, also known as TYRP1, is an enzyme which in humans is encoded by the TYRP1 gene- Function :Tyrp1 is a melanocyte-specific gene product involved in melanin synthesis. Mouse Tyrp1 possesses dihydroxyindole carboxylic acid oxidase activity, The function in human...

Additional genes identified by a microarray study (which confirmed the above targets) include the following,

MBP Myelin basic protein Myelin basic protein is a protein believed to be important in the process of myelination of nerves in the central nervous system .MBP was initially sequenced in 1971 after isolation from myelin membranes...	TNFRSF14 TNFRSF14 Tumor necrosis factor receptor superfamily member 14 is a protein that in humans is encoded by the TNFRSF14 gene. It is also known as "herpesvirus entry mediator" .-Interactions:...	IRF4 IRF4 Interferon regulatory factor 4 is a protein that in humans is encoded by the IRF4 gene, also known as MUM1. In melanocytic cells the IRF4 gene may be regulated by MITF.-Interactions:IRF4 has been shown to interact with STAT6, NFATC2, BCL6 and SPI1....	RBM35A
PLA1A Phospholipase A1 Phospholipase A1 is a phospholipase enzyme which removes the 1-acyl. Phospholipase A1 is a component of snake venom, but it also serves in normal metabolism to produce fatty acids from phospholipids. In melanocytic cells the Phospholipase A1 gene may be regulated by MITF.-External links:*...	APOLD1	KCNN2 KCNN2 Potassium intermediate/small conductance calcium-activated channel, subfamily N, member 2, also known as KCNN2, is a protein which in humans is encoded by the KCNN2 gene...	INPP4B
CAPN3 CAPN3 Calpain-3 is a protein that in humans is encoded by the CAPN3 gene.-External links:* The MEROPS online database for peptidases and their inhibitors: ** LOVD mutation database:...	LGALS3 LGALS3 Galectin-3 is a protein that in humans is encoded by the LGALS3 gene. In melanocytic cells LGALS3 gene expression may be regulated by MITF.-Interactions:LGALS3 has been shown to interact with LGALS3BP.-Further reading:...	GREB1	FRMD4B
SLC1A4 SLC1A4 Neutral amino acid transporter A is a protein that in humans is encoded by the SLC1A4 gene.In melanocytic cells SLC1A4 gene expression may be regulated by MITF.-Further reading:...	TBC1D16	GMPR GMP reductase GMP reductase is an enzyme that converts GMP to IMP. In melanocytic cells, GMP reductase gene expression may be regulated by MITF.-External links:...	ASAH1 ASAH1 Acid ceramidase is an enzyme that in humans is encoded by the ASAH1 gene.-Further reading:...
MICAL1 MICAL1 NEDD9-interacting protein with calponin homology and LIM domains is a protein that in humans is encoded by the MICAL1 gene.-Interactions:MICAL1 has been shown to interact with NEDD9 and RAB1A.-Further reading:...	TMC6 TMC6 Transmembrane channel-like protein 6 is a protein that in humans is encoded by the TMC6 gene. In vivo, TMC6 and its homolog TMC8, interact and form a complex with the zinc transporter 1 and localize mostly to the endoplasmic reticulum, but also to the nuclear membrane and Golgi...	ITPKB ITPKB Inositol-trisphosphate 3-kinase B is an enzyme that in humans is encoded by the ITPKB gene.. Itpkb regulates immune cell function and is required for T and B cell development. -Further reading:...	SLC7A8 SLC7A8 Large neutral amino acids transporter small subunit 2 is a protein that in humans is encoded by the SLC7A8 gene.-Further reading:...

Interactions

MITF has been shown to interact

Protein-protein interaction

Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...

 with PATZ1

PATZ1

POZ-, AT hook-, and zinc finger-containing protein 1 is a protein that in humans is encoded by the PATZ1 gene.-Interactions:PATZ1 has been shown to interact with RNF4, Microphthalmia-associated transcription factor and Androgen receptor....

, PIAS3

PIAS3

E3 SUMO-protein ligase PIAS3 is an enzyme that in humans is encoded by the PIAS3 gene.-Interactions:PIAS3 has been shown to interact with GFI1, RELA, Mothers against decapentaplegic homolog 3, Microphthalmia-associated transcription factor, HMGA2 and Mothers against decapentaplegic homolog...

, TFE3

TFE3

Transcription factor E3 is a protein that in humans is encoded by the TFE3 gene.-Interactions:TFE3 has been shown to interact with E2F3, Mothers against decapentaplegic homolog 3 and Microphthalmia-associated transcription factor.-Further reading:...

, UBE2I

UBE2I

SUMO-conjugating enzyme UBC9 is a protein that in humans is encoded by the UBE2I gene.-Interactions:UBE2I has been shown to interact with WT1, TOP1, RAD51, Activating transcription factor 2, PIAS1, SALL1, FHIT, RANBP2, Protein inhibitor of activated STAT2, DNMT3A, DNMT3B, Small ubiquitin-related...

 and LEF1

Lymphoid enhancer-binding factor 1

Lymphoid enhancer-binding factor 1 is a protein that in humans is encoded by the LEF1 gene.- Function :Lymphoid enhancer-binding factor-1 is a 48-kD nuclear protein that is expressed in pre-B and T cells. It binds to a functionally important site in the T-cell receptor-alpha enhancer and confers...

.

External links