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UniProtKB/Swiss-Prot Q8NBK3: Variant p.Cys336Arg

Formylglycine-generating enzyme
Gene: SUMF1
Variant information

Variant position:  336
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 Cysteine (C) to Arginine (R) at position 336 (C336R, p.Cys336Arg).
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 polar (C) to large size and basic (R)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -3
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 MSD; loss of activity.
Any additional useful information about the variant.

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



Sequence information

Variant position:  336
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  374
The length of the canonical sequence.

Location on the sequence:   LNPKGPPSGKDRVKKGGSYM  C HRSYCYRYRCAARSQNTPDS
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                         LNPKGPPSGKDRVKKGGSYMCHRSYCYRYRCAARSQNTPDS

Mouse                         FNPKGPTSGKDRVKKGGSYMCHKSYCYRYRCAARSQNTPDS

Bovine                        INPKGPPSGKDRVKKGGSYMCHKSYCYRYRCAARSQNTPDS

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.

TypePositionsDescription
Chain 34 – 374 Formylglycine-generating enzyme
Metal binding 336 – 336 Copper(2+); catalytic
Metal binding 341 – 341 Copper(2+); catalytic
Disulfide bond 218 – 365
Disulfide bond 235 – 346
Alternative sequence 319 – 338 Missing. In isoform 5.
Mutagenesis 333 – 333 S -> A. Loss of activity.
Mutagenesis 333 – 333 S -> T. Reduces activity by 99%.
Mutagenesis 336 – 336 C -> S. Loss of activity.
Mutagenesis 337 – 337 H -> A. Reduces activity 5-fold.
Mutagenesis 340 – 340 Y -> F. No effect.
Mutagenesis 341 – 341 C -> S. Loss of activity.


Literature citations

Multiple sulfatase deficiency is caused by mutations in the gene encoding the Homo sapiens C-alpha-formyglycine-generating enzyme.
Dierks T.; Schmidt B.; Borissenko L.V.; Peng J.; Preusser A.; Mariappan M.; von Figura K.;
Cell 113:435-444(2003)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1); VARIANTS MSD VAL-279; ARG-336; GLN-349 AND TRP-349; VARIANT ASN-63;

The multiple sulfatase deficiency gene encodes an essential and limiting factor for the activity of sulfatases.
Cosma M.P.; Pepe S.; Annunziata I.; Newbold R.F.; Grompe M.; Parenti G.; Ballabio A.;
Cell 113:445-456(2003)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1); VARIANTS MSD PRO-155; TYR-218; ARG-336; CYS-345; PRO-348; GLN-349 AND TRP-349; FUNCTION;

Molecular and functional analysis of SUMF1 mutations in multiple sulfatase deficiency.
Cosma M.P.; Pepe S.; Parenti G.; Settembre C.; Annunziata I.; Wade-Martins R.; Domenico C.D.; Natale P.D.; Mankad A.; Cox B.; Uziel G.; Mancini G.M.; Zammarchi E.; Donati M.A.; Kleijer W.J.; Filocamo M.; Carrozzo R.; Carella M.; Ballabio A.;
Hum. Mutat. 23:576-581(2004)
Cited for: VARIANTS MSD PHE-20; PRO-177; TRP-224; ILE-259 AND LEU-266; CHARACTERIZATION OF VARIANTS MSD PHE-20; PRO-155; PRO-177; TYR-218; TRP-224; ILE-259; LEU-266; VAL-279; ARG-336; CYS-345; PRO-348; TRP-349 AND GLN-349;

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.