UniProtKB/SwissProt variant VAR

Variant information

Variant position:

279

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 Valine (V) to Phenylalanine (F) at position 279 (V279F, p.Val279Phe).

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 hydrophobic (V) to large size and aromatic (F)

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:

In PAFAD; loss of function; risk factor for coronary arthery disease and stroke.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs76863441 [ dbSNP | Ensembl ]

Sequence information

Variant position:

279

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

Protein sequence length:

441

The length of the canonical sequence.

Location on the sequence:

KDSIDREKIAVIGHSFGGAT V IQTLSEDQRFRCGIALDAWM

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                         KDSIDREKIAVIGHSFGGATVIQTLSEDQRFRCGIALDAWM

                              KDSIDRDKIAVIGHSFGGATVLQALSEDQRFRCGIALDAWM

Mouse                         KDAIDETKIALMGHSFGGATVLQALSEDQRFRCGVALDPWM

Bovine                        KDSIDRDKIAIIGHSFGGATVIQTLSEDQRFRCGIALDAWM

Chicken                       KDSVDTSRIAVMGHSFGGATVIESLSKEIRFRCGIALDAWM

Caenorhabditis elegans        KNKLVMSSASVIGHSFGGATSLASSAYTTDFQKAIVFDGWM

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	22 – 441	Platelet-activating factor acetylhydrolase
Active site	273 – 273	Nucleophile
Active site	296 – 296	Charge relay system
Mutagenesis	273 – 273	S -> A. Loss of activity.
Mutagenesis	286 – 286	D -> A. Almost no activity.
Mutagenesis	286 – 286	D -> N. Diminishes activity.
Mutagenesis	296 – 296	D -> A. Loss of activity.
Mutagenesis	296 – 296	D -> N. Loss of activity.
Helix	274 – 285

Literature citations

Release of free F2-isoprostanes from esterified phospholipids is catalyzed by intracellular and plasma platelet-activating factor acetylhydrolases.
Stafforini D.M.; Sheller J.R.; Blackwell T.S.; Sapirstein A.; Yull F.E.; McIntyre T.M.; Bonventre J.V.; Prescott S.M.; Roberts L.J. II;
J. Biol. Chem. 281:4616-4623(2006)
Cited for: FUNCTION; CATALYTIC ACTIVITY; BIOPHYSICOCHEMICAL PROPERTIES; VARIANT PHE-279;

Platelet-activating factor acetylhydrolase deficiency. A missense mutation near the active site of an anti-inflammatory phospholipase.
Stafforini D.M.; Satoh K.; Atkinson D.L.; Tjoelker L.W.; Eberhardt C.; Yoshida H.; Imaizumi T.; Takamatsu S.; Zimmerman G.A.; McIntyre T.M.; Gray P.W.; Prescott S.M.;
J. Clin. Invest. 97:2784-2791(1996)
Cited for: VARIANT PAFAD PHE-279; FUNCTION; CATALYTIC ACTIVITY;

A mutation in plasma platelet-activating factor acetylhydrolase (Val279-->Phe) is a genetic risk factor for stroke.
Hiramoto M.; Yoshida H.; Imaizumi T.; Yoshimizu N.; Satoh K.;
Stroke 28:2417-2420(1997)
Cited for: VARIANT PAFAD PHE-279;

Identification of the G994--> T missense in exon 9 of the plasma platelet-activating factor acetylhydrolase gene as an independent risk factor for coronary artery disease in Japanese men.
Yamada Y.; Ichihara S.; Fujimura T.; Yokota M.;
Metabolism 47:177-181(1998)
Cited for: VARIANT PAFAD PHE-279;

A mutation in plasma platelet-activating factor acetylhydrolase (Val279Phe) is a genetic risk factor for cerebral hemorrhage but not for hypertension.
Yoshida H.; Imaizumi T.; Fujimoto K.; Itaya H.; Hiramoto M.; Yoshimizu N.; Fukushi K.; Satoh K.;
Thromb. Haemost. 80:372-375(1998)
Cited for: VARIANT PAFAD PHE-279;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q13093: Variant p.Val279Phe