UniProtKB/Swiss-Prot Q03393: Variant p.Arg16Cys

6-pyruvoyl tetrahydrobiopterin synthase
Gene: PTS
Chromosomal location: 11q22.3-q23.3
Variant information

Variant position:  16
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
  • Polymorphism: No disease-association has been reported.
  • Unclassified: Variants have been found in patients but disease-association remains unclear.

Residue change:  From Arginine (R) to Cysteine (C) at position 16 (R16C, p.Arg16Cys).
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 (C)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -3
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; severe decrease in activity; diminishes phosphorylation by PKG.
Any additional useful information about the variant.



Sequence information

Variant position:  16
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:   MSTEGGGRRCQAQVS  R RISFSASHRLYSKFLSDEEN
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                         MSTEGGGRRCQAQVSRRISFSASHRLYSKFLSDEEN

Mouse                         MSAAGDLRR-RARLSRLVSFSASHRLHSPSLSDEEN

Rat                           MNAAVGLRR-RARLSRLVSFSASHRLHSPSLSAEEN

Caenorhabditis elegans        -----MFRMPIVTMERVDSFSAAHRLHSEKLSDAEN

Drosophila                    -----MSQQPVAFLTRRETFSACHRLHSPQLSDAEN

Slime mold                    -----MSR--TVILTRREVFSSSHRLYSDKLSLEEN

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.

TypePositionsDescription
Chain 1 – 145 6-pyruvoyl tetrahydrobiopterin synthase
Metal binding 24 – 24 Zinc
Modified residue 19 – 19 Phosphoserine; by PKG
Mutagenesis 19 – 19 S -> A. Decrease in activity; abolishes phosphorylation by PKG.
Beta strand 11 – 24


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;

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.