UniProtKB/Swiss-Prot P60484: Variant p.Thr348Ile

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

348 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 Threonine (T) to Isoleucine (I) at position 348 (T348I, p.Thr348Ile). 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 medium size and polar (T) to medium size and hydrophobic (I) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

-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:

In endometrial hyperplasia; reduced phosphatase activity towards PtdIns(3,4,5)P3; mildly reduced tumor suppressor activity; reduced ability to inactivate AKT/PKB. Any additional useful information about the variant.

Sequence information Variant position:

348 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:

ANKDKANRYFSPNFKVKLYF T KTVEEPSNPEASSSTSVTPD 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                         ANKDKANRY------------------FSPN--------------------------------------------------------------FKVKLY------------------------------FTKTVEEPS----NPEASSS-------TSVTPD

                              ANKDKANRY------------------FSPN----------

Mouse                         ANKDKANRY------------------FSPN----------

Rat                           ANKDKANRY------------------FSPN----------

Xenopus laevis                ANKDKANRL------------------FSPN----------

Caenorhabditis elegans        PEEESCEHKTVESIAGFEPLEHLFHESYHPNTAGNMLRQDY

Slime mold                    NNNNNLNSSNSNNA-------------TTTT----------

Fission yeast                 ---ERKGQF------------------YFPS----------

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	190 – 350	C2 tensin-type
Region	338 – 348	Required for interaction with NOP53
Modified residue	336 – 336	Phosphotyrosine; by FRK
Modified residue	366 – 366	Phosphothreonine; by GSK3-beta and PLK3
Alternative sequence	191 – 403	Missing. In isoform 3.
Mutagenesis	336 – 336	Y -> F. Significantly lower phosphatase activity, reduced protein stability and decreased growth-inhibitory effect.
Mutagenesis	366 – 366	T -> A. Decreased stability.
Beta strand	342 – 349

Literature citations
The tumor-suppressor activity of PTEN is regulated by its carboxyl-terminal region.
Georgescu M.-M.; Kirsch K.H.; Akagi T.; Shishido T.; Hanafusa H.;
Proc. Natl. Acad. Sci. U.S.A. 96:10182-10187(1999)
Cited for: FUNCTION; DOMAIN; CHARACTERIZATION OF VARIANTS THR-319 DEL; GLN-345 AND ILE-348; Mutation of the PTEN tumor suppressor gene in endometrial hyperplasias.
Maxwell G.L.; Risinger J.I.; Gumbs C.; Shaw H.; Bentley R.C.; Barrett J.C.; Berchuck A.; Futreal P.A.;
Cancer Res. 58:2500-2503(1998)
Cited for: VARIANTS ENDOMETRIAL HYPERPLASIA ARG-36; LEU-130; CYS-173; ALA-191 AND ILE-348;

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.