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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O43586: Variant p.Glu250Gln

Proline-serine-threonine phosphatase-interacting protein 1
Gene: PSTPIP1
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Variant information Variant position: help 250 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 Glutamate (E) to Glutamine (Q) at position 250 (E250Q, p.Glu250Gln). 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 medium size and acidic (E) to medium size and polar (Q) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help 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: help In PAPAS; severely reduced binding with PTPN12; markedly increased binding to MEFV; accentuates IL1B secretion; increased induction of MEFV in response to retroviral infection. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 250 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 416 The length of the canonical sequence.
Location on the sequence: help ALWVHSNQLSMQCVKDDELY E EVRLTLEGCSIDADIDSFIQ 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                         ALWVHSNQLSMQCVKDDELYEEVRLTLEGCSIDADIDSFIQ

Mouse                         ALWVHCNQLSMQCVKDDELYEEVRLTLEGCDVEGDINGFIQ
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 – 416 Proline-serine-threonine phosphatase-interacting protein 1
Domain 5 – 264 F-BAR
Mutagenesis 232 – 232 W -> A. Abolishes binding to MEFV. Cytoplasmic filaments are finer with fewer branches.
Mutagenesis 266 – 266 D -> N. No effect on filament formation.
Helix 167 – 257



Literature citations
Pyrin binds the PSTPIP1/CD2BP1 protein, defining familial Mediterranean fever and PAPA syndrome as disorders in the same pathway.
Shoham N.G.; Centola M.; Mansfield E.; Hull K.M.; Wood G.; Wise C.A.; Kastner D.L.;
Proc. Natl. Acad. Sci. U.S.A. 100:13501-13506(2003)
Cited for: INTERACTION WITH MEFV; TISSUE SPECIFICITY; CHARACTERIZATION OF VARIANTS PAPAS THR-230 AND GLN-250; MUTAGENESIS OF TRP-232 AND TYR-345; Pyrin activates the ASC pyroptosome in response to engagement by autoinflammatory PSTPIP1 mutants.
Yu J.W.; Fernandes-Alnemri T.; Datta P.; Wu J.; Juliana C.; Solorzano L.; McCormick M.; Zhang Z.; Alnemri E.S.;
Mol. Cell 28:214-227(2007)
Cited for: FUNCTION; SUBUNIT; INTERACTION WITH MEFV; CHARACTERIZATION OF VARIANTS THR-230 AND GLN-250; Pyrin Modulates the Intracellular Distribution of PSTPIP1.
Waite A.L.; Schaner P.; Richards N.; Balci-Peynircioglu B.; Masters S.L.; Brydges S.D.; Fox M.; Hong A.; Yilmaz E.; Kastner D.L.; Reinherz E.L.; Gumucio D.L.;
PLoS ONE 4:E6147-E6147(2009)
Cited for: FUNCTION; SUBUNIT; SUBCELLULAR LOCATION; CHARACTERIZATION OF VARIANTS THR-230 AND GLN-250; MUTAGENESIS OF TRP-232 AND ASP-266; Mutations in CD2BP1 disrupt binding to PTP PEST and are responsible for PAPA syndrome, an autoinflammatory disorder.
Wise C.A.; Gillum J.D.; Seidman C.E.; Lindor N.M.; Veile R.; Bashiardes S.; Lovett M.;
Hum. Mol. Genet. 11:961-969(2002)
Cited for: VARIANTS PAPAS THR-230 AND GLN-250; CHARACTERIZATION OF VARIANTS PAPAS THR-230 AND GLN-250; Brief report: genotype, phenotype, and clinical course in five patients with PAPA syndrome (pyogenic sterile arthritis, pyoderma gangrenosum, and acne).
Demidowich A.P.; Freeman A.F.; Kuhns D.B.; Aksentijevich I.; Gallin J.I.; Turner M.L.; Kastner D.L.; Holland S.M.;
Arthritis Rheum. 64:2022-2027(2012)
Cited for: VARIANTS PAPAS THR-230; GLN-250 AND LYS-250;
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.