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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P50336: Variant p.Arg59Trp

Protoporphyrinogen oxidase
Gene: PPOX
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Variant information Variant position: help 59 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help 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: help From Arginine (R) to Tryptophan (W) at position 59 (R59W, p.Arg59Trp). 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: help Change from large size and basic (R) to large size and aromatic (W) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -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: help In VP; strongly decreases enzyme activity; does not affect mitochondrial protein targeting and localization; more resistant to thermal denaturation than wild-type enzyme. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 59 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 477 The length of the canonical sequence.
Location on the sequence: help LGGWIRSVRGPNGAIFELGP R GIRPAGALGARTLLLVSELG 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences.
Human                         LGGWIRSVR------GPNGAIFELGPRGIRPAGALGARTLLLVSELG

Mouse                         LGGWIRSIR------GSDGAIFELGPRGIRPAGALGARTLL

Bovine                        LGGWIRSVR------GPDGAIFELGPRGIRPAGALGARTLL

Slime mold                    VGGNIQT-RIIQGKNKDEKIIVEEGPRSLRALGR-GLNTLE

Baker's yeast                 TGGWIYSCN--TRDMSGNPIMLEKGPRTLRGVSDGTVLIMD

Fission yeast                 LGGWLQSVKIPCADSPTGTVLFEQGPRTLRPAGVAGLANLD

Sequence annotation in neighborhood: help 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 – 477 Protoporphyrinogen oxidase
Binding site 42 – 42
Binding site 57 – 60
Mutagenesis 59 – 59 R -> G. Decreases enzyme activity by 75%.
Mutagenesis 59 – 59 R -> Q. Decreases enzyme activity by 90%. Strongly decreases affinity for protoporphyrinogen-IX.
Mutagenesis 74 – 74 L -> P. Abolishes enzyme activity. Impairs protein folding and/or stability.
Beta strand 59 – 61



Literature citations
Structural insight into human variegate porphyria disease.
Qin X.; Tan Y.; Wang L.; Wang Z.; Wang B.; Wen X.; Yang G.; Xi Z.; Shen Y.;
FASEB J. 25:653-664(2011)
Cited for: X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) IN COMPLEX WITH FAD AND ACIFLUORFEN; CATALYTIC ACTIVITY; FUNCTION; SUBUNIT; CHARACTERIZATION OF VARIANTS VP ASP-11; THR-12; PHE-15; PRO-20; PRO-38; ALA-40; GLU-40; TRP-59; PRO-73; GLY-84; PRO-85; PRO-106; PRO-138; ASP-139; VAL-143; CYS-152; PRO-154; MET-158; HIS-168; VAL-178; VAL-205; CYS-217; GLY-224; ARG-232; ASP-282; ASN-283; PRO-295; ARG-330; ALA-332; GLY-335; CYS-348; ALA-349; PRO-350; ARG-358; ASP-397; PHE-401; PRO-433; PRO-444; ARG-448; PRO-450 AND ARG-453; MUTAGENESIS OF LEU-74; ARG-97; LEU-166; GLY-169; SER-284; VAL-290; PHE-331; LEU-334; VAL-347 AND MET-368; Quantitative structural insight into human variegate porphyria disease.
Wang B.; Wen X.; Qin X.; Wang Z.; Tan Y.; Shen Y.; Xi Z.;
J. Biol. Chem. 288:11731-11740(2013)
Cited for: X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF MUTANTS GLY-59 AND GLN-59 IN COMPLEXES WITH FAD AND ACIFLUORFEN; FUNCTION; CATALYTIC ACTIVITY; MUTAGENESIS OF ARG-59; ARG-97; LEU-166; GLY-169; PHE-331; LEU-334; VAL-347 AND MET-368; CHARACTERIZATION OF VARIANTS VP TRP-59; HIS-168; ARG-330; GLY-335; ALA-349; PHE-401 AND ARG-453; Identification of three mutations and associated haplotypes in the protoporphyrinogen oxidase gene in South African families with variegate porphyria.
Warnich L.; Kotze M.J.; Groenewald I.M.; Groenewald J.Z.; van Brakel M.G.; van Heerden C.J.; de Villiers J.N.; van de Ven W.J.; Schoenmakers E.F.; Taketani S.; Retief A.E.;
Hum. Mol. Genet. 5:981-984(1996)
Cited for: VARIANTS VP PRO-20; TRP-59 AND CYS-168; A R59W mutation in human protoporphyrinogen oxidase results in decreased enzyme activity and is prevalent in South Africans with variegate porphyria.
Meissner P.N.; Dailey T.A.; Hift R.J.; Ziman M.; Corrigall A.V.; Roberts A.G.; Meissner D.M.; Kirsch R.E.; Dailey H.A.;
Nat. Genet. 13:95-97(1996)
Cited for: VARIANTS VP TRP-59 AND CYS-168; Homozygous variegate porphyria in South Africa: genotypic analysis in two cases.
Corrigall A.V.; Hift R.J.; Davids L.M.; Hancock V.; Meissner D.; Kirsch R.E.; Meissner P.N.;
Mol. Genet. Metab. 69:323-330(2000)
Cited for: VARIANTS VP TRP-59; PRO-138 AND CYS-348; Variegate porphyria in Western Australian Aboriginal patients.
Rossi E.; Chin C.Y.; Beilby J.P.; Waso H.F.; Warnich L.;
Intern. Med. J. 32:445-450(2002)
Cited for: VARIANTS VP TRP-59; CYS-217 AND SER-236; Kinetic and physical characterisation of recombinant wild-type and mutant human protoporphyrinogen oxidases.
Maneli M.H.; Corrigall A.V.; Klump H.H.; Davids L.M.; Kirsch R.E.; Meissner P.N.;
Biochim. Biophys. Acta 1650:10-21(2003)
Cited for: CHARACTERIZATION OF VARIANTS VP PRO-20; TRP-59; CYS-168 AND CYS-348; Mitochondrial targeting of human protoporphyrinogen oxidase.
Davids L.M.; Corrigall A.V.; Meissner P.N.;
Cell Biol. Int. 30:416-426(2006)
Cited for: CHARACTERIZATION OF VARIANTS VP PRO-20; TRP-59 AND CYS-168;
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.