UniProtKB/SwissProt variant VAR

Variant information

Variant position:

25

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 Arginine (R) to Glutamine (Q) at position 25 (R25Q, p.Arg25Gln).

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 large size and basic (R) to medium size and polar (Q)

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 HPABH4A; abolishes activity; no effect on phosphorylation by PKG.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs104894273 [ dbSNP | Ensembl ]

Sequence information

Variant position:

25

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

Protein sequence length:

145

The length of the canonical sequence.

Location on the sequence:

GGGRRCQAQVSRRISFSASH R LYSKFLSDEENLKLFGKCNN

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                         GGGRRCQAQVSRRISFSASHRLYSKFLSDEENLKLFGKCNN

Mouse                         GDLRR-RARLSRLVSFSASHRLHSPSLSDEENLRVFGKCNN

Rat                           VGLRR-RARLSRLVSFSASHRLHSPSLSAEENLKVFGKCNN

Caenorhabditis elegans        -MFRMPIVTMERVDSFSAAHRLHSEKLSDAENKETFGKCNN

Drosophila                    -MSQQPVAFLTRRETFSACHRLHSPQLSDAENLEVFGKCNN

Slime mold                    -MSR--TVILTRREVFSSSHRLYSDKLSLEENKKIYGKC--

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	1 – 145	6-pyruvoyl tetrahydrobiopterin synthase
Active site	43 – 43	Proton acceptor
Binding site	24 – 24
Modified residue	19 – 19	Phosphoserine; by PKG
Modified residue	28 – 28	Phosphoserine
Mutagenesis	19 – 19	S -> A. Decrease in activity; abolishes phosphorylation by PKG.

Literature citations

Serine 19 of human 6-pyruvoyltetrahydropterin synthase is phosphorylated by cGMP protein kinase II.
Scherer-Oppliger T.; Leimbacher W.; Blau N.; Thoeny B.;
J. Biol. Chem. 274:31341-31348(1999)
Cited for: CHARACTERIZATION OF VARIANTS HPABH4A CYS-16 AND GLN-25; KINETIC PARAMETERS; PHOSPHORYLATION AT SER-19; MUTAGENESIS OF SER-19;

Hyperphenylalaninemia due to defects in tetrahydrobiopterin metabolism: molecular characterization of mutations in 6-pyruvoyl-tetrahydropterin synthase.
Thoeny B.; Leimbacher W.; Blau N.; Harvie A.; Heizmann C.W.;
Am. J. Hum. Genet. 54:782-792(1994)
Cited for: VARIANTS HPABH4A CYS-16 AND GLN-25;

Structural and functional consequences of mutations in 6-pyruvoyltetrahydropterin synthase causing hyperphenylalaninemia in humans. Phosphorylation is a requirement for in vivo activity.
Oppliger T.; Thoeny B.; Nar H.; Buergisser D.; Huber R.; Heizmann C.W.; Blau N.;
J. Biol. Chem. 270:29498-29506(1995)
Cited for: CHARACTERIZATION OF VARIANTS HPABH4A CYS-16; GLN-25; VAL-57 DEL AND LEU-87;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q03393: Variant p.Arg25Gln