UniProtKB/SwissProt variant VAR

Variant information

Variant position:

493

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 Valine (V) at position 493 (E493V, p.Glu493Val).

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 medium size and hydrophobic (V)

The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:

-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:

In CMTX4; increases affinity for NADH and electron transfer activity; increases affinity for DNA, resulting in increased apoptosis; no effect on interaction with CHCHD4.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs281864468 [ dbSNP | Ensembl ]

Sequence information

Variant position:

493

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

Protein sequence length:

613

The length of the canonical sequence.

Location on the sequence:

AKPYWHQSMFWSDLGPDVGY E AIGLVDSSLPTVGVFAKATA

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                         AK--PYWHQSMFWSDLGPDVGYEAIGLVDSSLPTVGVFAKATA

Mouse                         AK--PYWHQSMFWSDLGPDVGYEAIGLVDSSLPTVGVFAKA

Rat                           AK--PYWHQSMFWSDLGPDVGYEAIGLVDSSLPTVGVFAKA

Drosophila                    KK--PYQHQSMFWSDLGPEIGYEGIGLVDSSLPTVGVFALP

Slime mold                    DTPAPYTYQPFFWSDLTPGVGFEAVGNTSSKLKTFSVWEKP

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	102 – 613	Apoptosis-inducing factor 1, mitochondrial
Binding site	483 – 483	FAD; via carbonyl oxygen
Binding site	483 – 483	NAD 1; via carbonyl oxygen
Binding site	493 – 493	NAD 2
Alternative sequence	44 – 613	Missing. In isoform 6.
Alternative sequence	325 – 613	Missing. In isoform 4.
Mutagenesis	477 – 477	W -> A. Disrupts dimerization; when associated with A-443--445-A.
Mutagenesis	480 – 480	S -> A. Allows dimerization in absence of NADH.
Mutagenesis	485 – 485	D -> A. Increases protein dimerization at lower NADH levels.
Beta strand	491 – 496

Literature citations

Interaction between AIF and CHCHD4 Regulates Respiratory Chain Biogenesis.
Hangen E.; Feraud O.; Lachkar S.; Mou H.; Doti N.; Fimia G.M.; Lam N.V.; Zhu C.; Godin I.; Muller K.; Chatzi A.; Nuebel E.; Ciccosanti F.; Flamant S.; Benit P.; Perfettini J.L.; Sauvat A.; Bennaceur-Griscelli A.; Ser-Le Roux K.; Gonin P.; Tokatlidis K.; Rustin P.; Piacentini M.; Ruvo M.; Blomgren K.; Kroemer G.; Modjtahedi N.;
Mol. Cell 58:1001-1014(2015)
Cited for: FUNCTION; INTERACTION WITH CHCHD4; SUBCELLULAR LOCATION; CHARACTERIZATION OF VARIANT COXPD6 GLU-308; CHARACTERIZATION OF VARIANT CMTX4 VAL-493;

Cowchock syndrome is associated with a mutation in apoptosis-inducing factor.
Rinaldi C.; Grunseich C.; Sevrioukova I.F.; Schindler A.; Horkayne-Szakaly I.; Lamperti C.; Landoure G.; Kennerson M.L.; Burnett B.G.; Boennemann C.; Biesecker L.G.; Ghezzi D.; Zeviani M.; Fischbeck K.H.;
Am. J. Hum. Genet. 91:1095-1102(2012)
Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 103-613 IN COMPLEX WITH FAD; FUNCTION; COFACTOR; BIOPHYSICOCHEMICAL PROPERTIES; DNA-BINDING; SUBUNIT; SUBCELLULAR LOCATION; TISSUE SPECIFICITY; VARIANT CMTX4 VAL-493; CHARACTERIZATION OF VARIANT CMTX4 VAL-493; CATALYTIC ACTIVITY;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O95831: Variant p.Glu493Val