Expasy logo

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q16595: Variant p.Arg165Cys

Frataxin, mitochondrial
Gene: FXN
Feedback?
Variant information Variant position: help 165 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help 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: help From Arginine (R) to Cysteine (C) at position 165 (R165C, p.Arg165Cys). 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: help Change from large size and basic (R) to medium size and polar (C) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -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: help In FRDA; mild form; decreases affinity for the SDAU complex by 40-fold; decreases the level of covalent incorporation of sulfur into both NFS1 and ISCU. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 165 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 210 The length of the canonical sequence.
Location on the sequence: help INKQTPNKQIWLSSPSSGPK R YDWTGKNWVYSHDGVSLHEL 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences. 
Human                         INKQTPNKQIWLSSPSSGPKRYDW----TGKNWVYSHDGVSLHEL

Mouse                         INKQTPNKQIWLSSPSSGPKRYDW----TGKNWVYSHDGVS

Rat                           INKQTPLLYLWFSGPCSGPKRYDW----TGKNWVYSHDGVS

Bovine                        INKQTPNKQIWLSSPSSGPKRYDW----TGRNWVYSHDGVS

Caenorhabditis elegans        INKQSPNKQIWLSSPMSGPKRYDL---EEEGKWTYAHDGEQ

Drosophila                    INRQTPNKQIWLSSPTSGPKRYDFVGTVAAGRWIYKHSGQS

Slime mold                    INKQTPNRQIWWSSPLSGPKRFDY--DSVEKRWVDNRDGTP

Baker's yeast                 INKQPPNKQIWLASPLSGPNRFDL----LNGEWVSLRNGTK

Fission yeast                 INKQPPAHQIWLSSPVSGPKHYEY--SLKSKTWCSTRDEGT
Sequence annotation in neighborhood: help 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 42 – 210 Frataxin intermediate form
Chain 56 – 210 Frataxin(56-210)
Chain 78 – 210 Frataxin(78-210)
Chain 81 – 210 Extramitochondrial frataxin
Chain 81 – 210 Frataxin mature form
Alternative sequence 161 – 210 SGPKRYDWTGKNWVYSHDGVSLHELLAAELTKALKTKLDLSSLAYSGKDA -> RLTWLLWLFHP. In isoform 2.
Alternative sequence 161 – 210 SGPKRYDWTGKNWVYSHDGVSLHELLAAELTKALKTKLDLSSLAYSGKDA -> RYVVDLSVMTGLGKTGCTPTTACPSMSCWPQSSLKP. In isoform 3.
Mutagenesis 146 – 146 N -> A. Does not affect interaction with the core iron-sulfur cluster assembly complex. Does not affect mitochondrial localization. Does not affect proteolytic processing.
Mutagenesis 173 – 173 W -> G. Loss of interaction with the core iron-sulfur cluster assembly complex. Does not affect mitochondrial localization. Does not affect proteolytic processing.
Beta strand 164 – 168



Literature citations
Human frataxin activates Fe-S cluster biosynthesis by facilitating sulfur transfer chemistry.
Bridwell-Rabb J.; Fox N.G.; Tsai C.L.; Winn A.M.; Barondeau D.P.;
Biochemistry 53:4904-4913(2014)
Cited for: VARIANTS FRDA PHE-154; ARG-155 AND CYS-165; CHARACTERIZATION OF VARIANTS FRDA PHE-154; ARG-155 AND CYS-165; FUNCTION; Structure of the human frataxin-bound iron-sulfur cluster assembly complex provides insight into its activation mechanism.
Fox N.G.; Yu X.; Feng X.; Bailey H.J.; Martelli A.; Nabhan J.F.; Strain-Damerell C.; Bulawa C.; Yue W.W.; Han S.;
Nat. Commun. 10:2210-2210(2019)
Cited for: STRUCTURE BY ELECTRON MICROSCOPY (3.20 ANGSTROMS) OF 81-210 IN COMPLEX WITH ISCU; LYRM4 AND FNS1; SUBUNIT; VARIANTS FRDA ARG-155 AND CYS-165; CHARACTERIZATION OF VARIANTS FRDA ARG-155 AND CYS-165; INTERACTION WITH ISCU; The correlation of clinical phenotype in Friedreich ataxia with the site of point mutations in the FRDA gene.
Forrest S.M.; Knight M.; Delatycki M.B.; Paris D.; Williamson R.; King J.; Yeung L.; Nassif N.; Nicholson G.A.;
Neurogenetics 1:253-257(1998)
Cited for: VARIANTS FRDA VAL-130; CYS-165 AND PHE-182;
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.