UniProtKB/Swiss-Prot Q05932: Variant p.Ser499Phe

Folylpolyglutamate synthase, mitochondrial
Gene: FPGS
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Variant information Variant position:

499 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

LB/B 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 Serine (S) to Phenylalanine (F) at position 499 (S499F, p.Ser499Phe). 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 small size and polar (S) to large size and aromatic (F) 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:

Expression reduced by 2.11-fold; Vmax with methotrexate as substrate is significantly reduced resulting in significantly decreased intrinsic clearance of methotrexate; apparent Vmax for glutamic acid is reduced 5-fold; reaction velocity at 100 nmol/L of pemetrexed is significantly reduced and folic acid dose-response curve is shifted to the right which corresponds to 4.28-fold increase in the EC(50) for folic acid; IC(50) of methotrexate is 1.64-fold higher and accumulation of a lower ratio of long-chain methotrexate polyglutamates to short-chain polyglutamates is detected; all results are for isoform 2 variant in comparison to the wild-type of it. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs200314440 [ dbSNP | Ensembl ]

Sequence information Variant position:

499 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

587 The length of the canonical sequence.
Location on the sequence:

EEQASPDLWSAPSPEPGGSA S LLLAPHPPHTCSASSLVFSC 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                         EEQASPDLWSAPSPEPGGSASLLLAPHPPHTCSASSLVFSC

Mouse                         EKQASSNLWSSCGPDPAGPGSLLLAPHPPQPTRTSSLVFSC

Bovine                        EEQVSPDPWSTPGQEQDGPASLLLAPHPPHTHSASSLVFSC

Caenorhabditis elegans        DQPESVT-------------------------EDQMKVFDC

Slime mold                    QSNQSSTATTTPIPDNA-------AVKQTTEIKESSTWEDF

Baker's yeast                 MQPDLQSVWT-------------------------------

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	43 – 587	Folylpolyglutamate synthase, mitochondrial

Literature citations
Identification and characterization of genetic variation in the folylpolyglutamate synthase gene.
Leil T.A.; Endo C.; Adjei A.A.; Dy G.K.; Salavaggione O.E.; Reid J.R.; Ames M.M.; Adjei A.A.;
Cancer Res. 67:8772-8782(2007)
Cited for: CATALYTIC ACTIVITY; BIOPHYSICOCHEMICAL PROPERTIES; VARIANTS LEU-13; CYS-466; VAL-489 AND PHE-499;

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.