Expasy logo

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P60484: Variant p.Cys124Ser

Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN
Gene: PTEN
Feedback?
Variant information Variant position: help 124 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 Cysteine (C) to Serine (S) at position 124 (C124S, p.Cys124Ser). 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 polar (C) to small size and polar (S) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -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: help In CWS1; phosphatase-dead protein with neither lipid nor protein phosphatase activity. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 124 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 403 The length of the canonical sequence.
Location on the sequence: help FCEDLDQWLSEDDNHVAAIH C KAGKGRTGVMICAYLLHRGK 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                         FCEDLDQWLSEDDNHVAAIHCKAGKGRTGVMICAYLLHRGK

                              FCEDLDQWLSEDDNHVAAIHCKAGKGRTGVMICAYLLHRGK

Mouse                         FCEDLDQWLSEDDNHVAAIHCKAGKGRTGVMICAYLLHRGK

Rat                           FCEDLDQWLSEDDNHVAAIHCKAGKGRTGVMICAYLLHRGK

Xenopus laevis                FCEDLDQLLSENEN-VAAIHCKAGKGRTGVMICAYLLHRGK

Caenorhabditis elegans        FCREAKEWLEADDKHVIAVHCKAGKGRTGVMICALLIYINF

Slime mold                    FCRDVDAWMKEDSKNIAVIHCKAGKGRTGLMICCWLMYCGM

Fission yeast                 IVMNMDALFQTQPLLTLVVHCKAGKGRTGTVICSYLVAFGG
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 2 – 403 Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN
Domain 14 – 185 Phosphatase tensin-type
Active site 124 – 124 Phosphocysteine intermediate
Mutagenesis 124 – 124 C -> A. Loss of protein phosphatase activity. Unable to inhibit focal adhesion formation.
Mutagenesis 124 – 124 C -> S. Loss of phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity.
Mutagenesis 125 – 125 K -> M. Reduced phosphatase activity towards PtdIns(3,4,5)P3, PtdIns(3,4)P2 and PtdIns(3)P.
Mutagenesis 126 – 126 A -> P. Does not reduce phosphatase activity towards PtdIns(3,4,5)P3 and PtdIns(3,4)P2.
Mutagenesis 126 – 126 A -> S. Does not reduce phosphatase activity towards PtdIns(3,4,5)P3 and PtdIns(3,4)P2.
Mutagenesis 126 – 126 A -> V. Does not reduce phosphatase activity towards PtdIns(3,4,5)P3 and PtdIns(3,4)P2.
Mutagenesis 128 – 128 K -> M. 85% reduction in phosphatase activity towards PtdIns(3,4,5)P3.
Mutagenesis 128 – 128 K -> R. Does not reduce phosphatase activity towards PtdIns(3,4,5)P3.
Mutagenesis 130 – 130 R -> M. Does not affect the ability to inhibit AKT/PKB activation.



Literature citations
The lipid phosphatase activity of PTEN is critical for its tumor suppressor function.
Myers M.P.; Pass I.; Batty I.H.; Van der Kaay J.; Stolarov J.P.; Hemmings B.A.; Wigler M.H.; Downes C.P.; Tonks N.K.;
Proc. Natl. Acad. Sci. U.S.A. 95:13513-13518(1998)
Cited for: FUNCTION; CATALYTIC ACTIVITY; MUTAGENESIS OF ARG-130; CHARACTERIZATION OF VARIANTS CWS1 SER-124 AND CWS1 GLU-129; PTEN coordinates G1 arrest by down-regulating cyclin D1 via its protein phosphatase activity and up-regulating p27 via its lipid phosphatase activity in a breast cancer model.
Weng L.-P.; Brown J.L.; Eng C.;
Hum. Mol. Genet. 10:599-604(2001)
Cited for: CHARACTERIZATION OF VARIANTS CWS1 SER-124 AND GLU-129;
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.