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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q9Y4W6: Variant p.Tyr616Cys

Mitochondrial inner membrane m-AAA protease component AFG3L2
Gene: AFG3L2
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Variant information Variant position: help 616 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 Tyrosine (Y) to Cysteine (C) at position 616 (Y616C, p.Tyr616Cys). 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 aromatic (Y) to medium size and polar (C) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -2 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 SPAX5 and SCA28; hypomorphic mutation; impaired oligomerization with itself and SPG7; increased ATPase and proteolytic activities. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 616 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 797 The length of the canonical sequence.
Location on the sequence: help IIPRGKGLGYAQYLPKEQYL Y TKEQLLDRMCMTLGGRVSEE 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                         IIPRGKGLGYAQYLPKEQYLYTKEQLLDRMCMTLGGRVSEE

Mouse                         IIPRGKGLGYAQYLPKEQYLYTKEQLLDRMCMTLGGRVSEE

Bovine                        IIPRGKGLGYAQYLPREQYLYTREQLLDRMCMTLGGRVSEE
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 67 – 797 Mitochondrial inner membrane m-AAA protease component AFG3L2
Topological domain 272 – 797 Mitochondrial matrix



Literature citations
Unique structural features of the mitochondrial AAA+ protease AFG3L2 reveal the molecular basis for activity in health and disease.
Puchades C.; Ding B.; Song A.; Wiseman R.L.; Lander G.C.; Glynn S.E.;
Mol. Cell 75:1073-1085(2019)
Cited for: STRUCTURE BY ELECTRON MICROSCOPY (3.00 ANGSTROMS) OF 272-797 IN COMPLEX WITH ZINC; ADP AND PEPTIDE SUBSTRATE; FUNCTION; CATALYTIC ACTIVITY; COFACTOR; SUBUNIT; SUBCELLULAR LOCATION; MUTAGENESIS OF PHE-289; LEU-299; MET-380; PHE-421; GLU-575 AND TRP-779; CHARACTERIZATION OF VARIANTS SCA28 THR-432; CYS-616; ARG-666 AND THR-688; CHARACTERIZATION OF VARIANT THR-572; Whole-exome sequencing identifies homozygous AFG3L2 mutations in a spastic ataxia-neuropathy syndrome linked to mitochondrial m-AAA proteases.
Pierson T.M.; Adams D.; Bonn F.; Martinelli P.; Cherukuri P.F.; Teer J.K.; Hansen N.F.; Cruz P.; Mullikin J.C.; Blakesley R.W.; Golas G.; Kwan J.; Sandler A.; Fuentes Fajardo K.; Markello T.; Tifft C.; Blackstone C.; Rugarli E.I.; Langer T.; Gahl W.A.; Toro C.;
PLoS Genet. 7:E1002325-E1002325(2011)
Cited for: VARIANT SPAX5 CYS-616; CHARACTERIZATION OF VARIANT SPAX5 CYS-616; Spinocerebellar ataxia type 28-phenotypic and molecular characterization of a family with heterozygous and compound-heterozygous mutations in AFG3L2.
Tunc S.; Dulovic-Mahlow M.; Baumann H.; Baaske M.K.; Jahn M.; Junker J.; Muenchau A.; Brueggemann N.; Lohmann K.;
Cerebellum 18:817-822(2019)
Cited for: VARIANTS SCA28 CYS-616 AND MET-723;
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.