UniProtKB/Swiss-Prot P60484: Variant p.Ala126Gly

Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN
Gene: PTEN
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Variant information Variant position:

126 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

US 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 Alanine (A) to Glycine (G) at position 126 (A126G, p.Ala126Gly). 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 small size and hydrophobic (A) to glycine (G) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

0 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 a patient with prostate cancer; reduced phosphatase activity towards PtdIns(3,4,5); shifts its activity from phosphatidylinositol phosphate 3-phosphatase to phosphatidylinositol phosphate 5-phosphatase; disrupts PI3K/ATK signaling; reduced cell migration. Any additional useful information about the variant.

Sequence information Variant position:

126 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

403 The length of the canonical sequence.
Location on the sequence:

EDLDQWLSEDDNHVAAIHCK A GKGRTGVMICAYLLHRGKFL 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                         EDLDQWLSEDDNHVAAIHCKAGKGRTGVMICAYLLHRGKFL

                              EDLDQWLSEDDNHVAAIHCKAGKGRTGVMICAYLLHRGKFL

Mouse                         EDLDQWLSEDDNHVAAIHCKAGKGRTGVMICAYLLHRGKFL

Rat                           EDLDQWLSEDDNHVAAIHCKAGKGRTGVMICAYLLHRGKFL

Xenopus laevis                EDLDQLLSENEN-VAAIHCKAGKGRTGVMICAYLLHRGKFP

Caenorhabditis elegans        REAKEWLEADDKHVIAVHCKAGKGRTGVMICALLIYINFYP

Slime mold                    RDVDAWMKEDSKNIAVIHCKAGKGRTGLMICCWLMYCGMWK

Fission yeast                 MNMDALFQTQPLLTLVVHCKAGKGRTGTVICSYLVAFGG-L

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	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.
Beta strand	125 – 128

Literature citations
Discovery and functional characterization of a neomorphic PTEN mutation.
Costa H.A.; Leitner M.G.; Sos M.L.; Mavrantoni A.; Rychkova A.; Johnson J.R.; Newton B.W.; Yee M.C.; De La Vega F.M.; Ford J.M.; Krogan N.J.; Shokat K.M.; Oliver D.; Halaszovich C.R.; Bustamante C.D.;
Proc. Natl. Acad. Sci. U.S.A. 112:13976-13981(2015)
Cited for: VARIANT PROSTATE CANCER GLY-126; CHARACTERIZATION OF VARIANT GLY-126; MUTAGENESIS OF ALA-126; FUNCTION;

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.