UniProtKB/Swiss-Prot O75030: Variant p.Glu425Lys

Microphthalmia-associated transcription factor
Gene: MITF
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Variant information Variant position:

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

LB/B 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:

Risk factor for CMM8; risk factor for pheochromocytomas and paragangliomas; results in impaired sumoylation. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs149617956 [ dbSNP | Ensembl ]

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.
Location on the sequence:

SLIPSTGLCSPDLVNRIIKQ E PVLENCSQDLLQHHADLTCT 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.

Human                         SLIPSTGLCSPDLVNRIIKQEPVLENCSQDLLQHHADLTCT

Mouse                         SLIPSTGLCSPDLVNRIIKQEPVLENCSQELVQHQADLTCT

Rat                           SLIPSTGLCSPDLVNRIIKQEPVLENCSQELVQHQADLTCT

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.

Type	Positions	Description
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)
Cited for: INVOLVEMENT IN DISEASE; VARIANT LYS-425; 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)
Cited for: INVOLVEMENT IN CMM8; VARIANT CMM8 LYS-425; 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)
Cited for: INVOLVEMENT IN CMM8; VARIANT CMM8 LYS-425; CHARACTERIZATION OF VARIANT CMM8 LYS-425;

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.