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Protein

Microphthalmia-associated transcription factor

Gene

Mitf

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at transcript leveli

Functioni

Transcription factor that regulates the expression of genes with essential roles in cell differentiation, proliferation and survival. Binds to M-boxes (5'-TCATGTG-3') and symmetrical DNA sequences (E-boxes) (5'-CACGTG-3') found in the promoters of target genes, such as BCL2 and tyrosinase (TYR). Plays an important role in melanocyte development by regulating the expression of tyrosinase (TYR) and tyrosinase-related protein 1 (TYRP1). Plays a critical role in the differentiation of various cell types, such as neural crest-derived melanocytes, mast cells, osteoclasts and optic cup-derived retinal pigment epithelium.By similarity

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionActivator, Developmental protein, DNA-binding
Biological processTranscription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-RNO-3232118. SUMOylation of transcription factors.

Names & Taxonomyi

Protein namesi
Recommended name:
Microphthalmia-associated transcription factor
Gene namesi
Name:Mitf
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componentsi: Chromosome 4, Unplaced

Organism-specific databases

RGDi3092. Mitf.

Subcellular locationi

  • Nucleus By similarity

GO - Cellular componenti

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

Osteopetrotic rat of unknown genetic defect microphthalmia-blanc (mib) has been described whose skeletal sclerosis improves dramatically with age and that is associated with pigmentation defects. Mib at the homozygous state shows absence of skin and fur pigmentation, small eyes, and defects of incisor tooth eruption.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001272781 – 526Microphthalmia-associated transcription factorAdd BLAST526

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei180Phosphoserine; by MAPKBy similarity1
Cross-linki289Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Modified residuei405Phosphoserine; by GSK3By similarity1
Modified residuei414PhosphoserineBy similarity1
Cross-linki423Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Modified residuei491PhosphoserineBy similarity1
Modified residuei516Phosphoserine; by RPS6KA1By similarity1

Post-translational modificationi

Phosphorylation at Ser-405 significantly enhances the ability to bind the tyrosinase promoter. Phosphorylated at Ser-180 and Ser-516 following KIT signaling, trigerring a short live activation: Phosphorylation at Ser-180 and Ser-516 by MAPK and RPS6KA1, respectively, activate the transcription factor activity but also promote ubiquitination and subsequent degradation by the proteasome.By similarity
Ubiquitinated following phosphorylation at Ser-180, leading to subsequent degradation by the proteasome. Deubiquitinated by USP13, preventing its degradation.By similarity

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiO88368.

PTM databases

iPTMnetiF1LQV3.
PhosphoSitePlusiF1LQV3.

Expressioni

Gene expression databases

BgeeiENSRNOG00000008658.
ExpressionAtlasiO88368. baseline and differential.

Interactioni

Subunit structurei

Homodimer or heterodimer; dimerization is mediated via the coiled coil region. Efficient DNA binding requires dimerization with another bHLH protein. Binds DNA in the form of homodimer or heterodimer with either TFE3, TFEB or TFEC. Identified in a complex with HINT1 and CTNNB1 (By similarity). Interacts with KARS (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000044350.

Structurei

3D structure databases

ProteinModelPortaliO88368.
SMRiO88368.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini311 – 364bHLHPROSITE-ProRule annotationAdd BLAST54

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni374 – 395Leucine-zipperCuratedAdd BLAST22

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili355 – 401Sequence analysisAdd BLAST47

Domaini

The leucine zipper region is part of a larger coiled coil.By similarity

Sequence similaritiesi

Belongs to the MiT/TFE family.Curated

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiKOG1318. Eukaryota.
ENOG4110SME. LUCA.
GeneTreeiENSGT00390000004402.
HOGENOMiHOG000231368.
InParanoidiO88368.
KOiK09455.
OMAiDLYTLHP.
OrthoDBiEOG091G0QCO.
TreeFamiTF317174.

Family and domain databases

CDDicd00083. HLH. 1 hit.
Gene3Di4.10.280.10. 1 hit.
InterProiView protein in InterPro
IPR011598. bHLH_dom.
IPR030532. MITF.
PANTHERiPTHR12565:SF258. PTHR12565:SF258. 1 hit.
PfamiView protein in Pfam
PF00010. HLH. 1 hit.
SMARTiView protein in SMART
SM00353. HLH. 1 hit.
SUPFAMiSSF47459. SSF47459. 1 hit.
PROSITEiView protein in PROSITE
PS50888. BHLH. 1 hit.

Sequencei

Sequence statusi: Complete.

O88368-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MQSESGIVAD FEVGEEFHEE PKTYYELKSQ PLKSSSSAEH SGASKPPLSS
60 70 80 90 100
STMTSRILLR QQLMREQMQE QERREQQQKL QAAQFMQQRV AVSQTPAINV
110 120 130 140 150
SVPTTLPSAT QVPMEVLKVQ THLENPTKYH IQQAQRHQVK QYLSTTLANK
160 170 180 190 200
HAGQVLSPPC PNQPGDHAMP PVPGSSAPNS PMAMLTLNSN CEKEAFYKFE
210 220 230 240 250
EQSRAESECP GMNTHSRASC MQMDDVIDDI ISLESSYNEE ILGLMDPALQ
260 270 280 290 300
MANTLPVSGN LIDLYSNQGL PPPGLTISNS CPANLPNIKR ELTACIFPTE
310 320 330 340 350
SEARALAKER QKKDNHNLIE RRRRFNINDR IKELGTLIPK SNDPDMRWNK
360 370 380 390 400
GTILKASVDY IRKLQREQQR AKDLENRQKK LEHANRHLLL RVQELEMQAR
410 420 430 440 450
AHGLSLIPST GLCSPDLVNR IIKQEPVLEN CSQELVQHQA DLTCTTTLDL
460 470 480 490 500
TDGTISFTNN LGTMPESSPA YSIPRKMASN LEDILMDDAL SPVGVTDPLL
510 520
SSVSPGASKT SSRRSSMSAE ETEHAC
Length:526
Mass (Da):58,585
Last modified:July 5, 2017 - v2
Checksum:iDC08692AEEE4CF59
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AABR07061507 Genomic DNA. No translation available.
AABR07061508 Genomic DNA. No translation available.
AABR07061509 Genomic DNA. No translation available.
AABR07061510 Genomic DNA. No translation available.
AABR07061511 Genomic DNA. No translation available.
AF029886 mRNA. Translation: AAC26170.1.
RefSeqiNP_001178018.1. NM_001191089.2.
UniGeneiRn.31427.

Genome annotation databases

EnsembliENSRNOT00000051121; ENSRNOP00000044350; ENSRNOG00000008658.
GeneIDi25094.
KEGGirno:25094.
UCSCiRGD:3092. rat.

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.

Entry informationi

Entry nameiMITF_RAT
AccessioniPrimary (citable) accession number: O88368
Secondary accession number(s): F1LQV3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: July 5, 2017
Last modified: July 5, 2017
This is version 117 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families