Home  |  Contact

UniProtKB/Swiss-Prot O75030: Variant p.Glu425Lys

Microphthalmia-associated transcription factor
Gene: MITF
Variant information

Variant position:  425
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  LP/P [Disclaimer]
The variants are classified into three categories: LP/P, LB/B and US.
  • LP/P: likely pathogenic or pathogenic.
  • LB/B: likely benign or benign.
  • US: uncertain significance

Residue change:  From Glutamate (E) to Lysine (K) at position 425 (E425K, p.Glu425Lys).
Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.

Physico-chemical properties:  Change from medium size and acidic (E) to large size and basic (K)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  1
The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:
  • Lowest score: -4 (low probability of substitution).
  • Highest score: 11 (high probability of substitution).
More information can be found on the following page

Variant description:  In CMM8; associated with disease susceptibility; also associated with pheochromocytomas and paragangliomas susceptibility; results in impaired sumoylation.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.

Sequence information

Variant position:  425
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  526
The length of the canonical sequence.

The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.

Residue conservation: 
The multiple alignment of the region surrounding the variant against various orthologous sequences.




Sequence annotation in neighborhood:  
The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:
  • Type: the type of sequence feature.
  • Positions: endpoints of the sequence feature.
  • Description: contains additional information about the feature.

Chain 1 – 526 Microphthalmia-associated transcription factor
Region 401 – 431 DNA binding regulation
Modified residue 405 – 405 Phosphoserine; by GSK3
Modified residue 414 – 414 Phosphoserine
Cross 423 – 423 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)
Mutagenesis 405 – 405 S -> AP. Loss of phosphorylation and function.
Mutagenesis 423 – 423 K -> R. Loss of sumoylation; when associated with R-289.

Literature citations

The MITF, p.E318K Variant, as a Risk Factor for Pheochromocytoma and Paraganglioma.
Castro-Vega L.J.; Kiando S.R.; Burnichon N.; Buffet A.; Amar L.; Simian C.; Berdelou A.; Galan P.; Schlumberger M.; Bouatia-Naji N.; Favier J.; Bressac-de Paillerets B.; Gimenez-Roqueplo A.P.;
J. Clin. Endocrinol. Metab. 101:4764-4768(2016)

A SUMOylation-defective MITF germline mutation predisposes to melanoma and renal carcinoma.
Bertolotto C.; Lesueur F.; Giuliano S.; Strub T.; de Lichy M.; Bille K.; Dessen P.; d'Hayer B.; Mohamdi H.; Remenieras A.; Maubec E.; de la Fouchardiere A.; Molinie V.; Vabres P.; Dalle S.; Poulalhon N.; Martin-Denavit T.; Thomas L.; Andry-Benzaquen P.; Dupin N.; Boitier F.; Rossi A.; Perrot J.L.; Labeille B.; Robert C.; Escudier B.; Caron O.; Brugieres L.; Saule S.; Gardie B.; Gad S.; Richard S.; Couturier J.; Teh B.T.; Ghiorzo P.; Pastorino L.; Puig S.; Badenas C.; Olsson H.; Ingvar C.; Rouleau E.; Lidereau R.; Bahadoran P.; Vielh P.; Corda E.; Blanche H.; Zelenika D.; Galan P.; Aubin F.; Bachollet B.; Becuwe C.; Berthet P.; Bignon Y.J.; Bonadona V.; Bonafe J.L.; Bonnet-Dupeyron M.N.; Cambazard F.; Chevrant-Breton J.; Coupier I.; Dalac S.; Demange L.; d'Incan M.; Dugast C.; Faivre L.; Vincent-Fetita L.; Gauthier-Villars M.; Gilbert B.; Grange F.; Grob J.J.; Humbert P.; Janin N.; Joly P.; Kerob D.; Lasset C.; Leroux D.; Levang J.; Limacher J.M.; Livideanu C.; Longy M.; Lortholary A.; Stoppa-Lyonnet D.; Mansard S.; Mansuy L.; Marrou K.; Mateus C.; Maugard C.; Meyer N.; Nogues C.; Souteyrand P.; Venat-Bouvet L.; Zattara H.; Chaudru V.; Lenoir G.M.; Lathrop M.; Davidson I.; Avril M.F.; Demenais F.; Ballotti R.; Bressac-de Paillerets B.;
Nature 480:94-98(2011)

A novel recurrent mutation in MITF predisposes to familial and sporadic melanoma.
Yokoyama S.; Woods S.L.; Boyle G.M.; Aoude L.G.; MacGregor S.; Zismann V.; Gartside M.; Cust A.E.; Haq R.; Harland M.; Taylor J.C.; Duffy D.L.; Holohan K.; Dutton-Regester K.; Palmer J.M.; Bonazzi V.; Stark M.S.; Symmons J.; Law M.H.; Schmidt C.; Lanagan C.; O'Connor L.; Holland E.A.; Schmid H.; Maskiell J.A.; Jetann J.; Ferguson M.; Jenkins M.A.; Kefford R.F.; Giles G.G.; Armstrong B.K.; Aitken J.F.; Hopper J.L.; Whiteman D.C.; Pharoah P.D.; Easton D.F.; Dunning A.M.; Newton-Bishop J.A.; Montgomery G.W.; Martin N.G.; Mann G.J.; Bishop D.T.; Tsao H.; Trent J.M.; Fisher D.E.; Hayward N.K.; Brown K.M.;
Nature 480:99-103(2011)

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.