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UniProtKB/Swiss-Prot P60484: Variant p.Ala121Gly

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

Variant position:  121
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 implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Alanine (A) to Glycine (G) at position 121 (A121G, p.Ala121Gly).
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

Involvement in disease:  Squamous cell carcinoma of the head and neck (HNSCC) [MIM:275355]: A non-melanoma skin cancer affecting the head and neck. The hallmark of cutaneous SCC is malignant transformation of normal epidermal keratinocytes. {ECO:0000269|PubMed:11801303}. Note=The disease is caused by mutations affecting the gene represented in this entry.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In HNSCC.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  121
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:   IKPFCEDLDQWLSEDDNHVA  A IHCKAGKGRTGVMICAYLLH
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                         IKPFCEDLDQWLSEDDNHVAAIHCKAGKGRTGVMICAYLLH

                              IKPFCEDLDQWLSEDDNHVAAIHCKAGKGRTGVMICAYLLH

Mouse                         IKPFCEDLDQWLSEDDNHVAAIHCKAGKGRTGVMICAYLLH

Xenopus laevis                IKPFCEDLDQLLSENEN-VAAIHCKAGKGRTGVMICAYLLH

Caenorhabditis elegans        MAPFCREAKEWLEADDKHVIAVHCKAGKGRTGVMICALLIY

Slime mold                    IDAFCRDVDAWMKEDSKNIAVIHCKAGKGRTGLMICCWLMY

Fission yeast                 LWAIVMNMDALFQTQPLLTLVVHCKAGKGRTGTVICSYLVA

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 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 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 118 – 123


Literature citations

Detection of new PTEN/MMAC1 mutations in head and neck squamous cell carcinomas with loss of chromosome 10.
Poetsch M.; Lorenz G.; Kleist B.;
Cancer Genet. Cytogenet. 132:20-24(2002)
Cited for: VARIANT HNSCC GLY-121;

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.