UniProtKB/SwissProt variant VAR

Variant information

Variant position:

134

The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:

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:

From Methionine (M) to Leucine (L) at position 134 (M134L, p.Met134Leu).

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:

Similar physico-chemical property. Both residues are medium size and hydrophobic.

The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:

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:

In prostate cancer; no effect on protein phosphatase activity; reduced phosphatase activity towards Ins(1,3,4,5)P3 but retains PtdIns(3,4,5)P3 phosphatase activity.

Any additional useful information about the variant.

Sequence information

Variant position:

134

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:

EDDNHVAAIHCKAGKGRTGV M ICAYLLHRGKFLKAQEALDF

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                         EDDNHVAAIHCKAGKGRTGVMICAYLLHRGKFLKAQEALDF

Mouse                         EDDNHVAAIHCKAGKGRTGVMICAYLLHRGKFLKAQEALDF

Rat                           EDDNHVAAIHCKAGKGRTGVMICAYLLHRGKFLKAQEALDF

Xenopus laevis                ENEN-VAAIHCKAGKGRTGVMICAYLLHRGKFPRAQEALDF

Caenorhabditis elegans        ADDKHVIAVHCKAGKGRTGVMICALLIYINFYPSPRQILDY

Slime mold                    EDSKNIAVIHCKAGKGRTGLMICCWLMYCGMWKNTEDSLRF

Fission yeast                 TQPLLTLVVHCKAGKGRTGTVICSYLVAFGG-LTAKQSLEL

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	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.
Helix	129 – 141

Literature citations

PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer.
Li J.; Yen C.; Liaw D.; Podsypanina K.; Bose S.; Wang S.I.; Puc J.; Miliaresis C.; Rodgers L.; McCombie R.; Bigner S.H.; Giovanella B.C.; Ittmann M.; Tycko B.; Hibshoosh H.; Wigler M.H.; Parsons R.;
Science 275:1943-1947(1997)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1); VARIANTS GLIOBLASTOMA ARG-129 AND PROSTATE CANCER LEU-134;

P-TEN, the tumor suppressor from human chromosome 10q23, is a dual-specificity phosphatase.
Myers M.P.; Stolarov J.P.; Eng C.; Li J.; Wang S.I.; Wigler M.H.; Parsons R.; Tonks N.K.;
Proc. Natl. Acad. Sci. U.S.A. 94:9052-9057(1997)
Cited for: FUNCTION; CATALYTIC ACTIVITY; CHARACTERIZATION OF VARIANTS GLIOMA TRP-57; ENDOMETRIAL CANCER TYR-123; GLIOBLASTOMA ARG-129; CWS1 ARG-129; PROSTATE CANCER LEU-134; GLIOBLASTOMA ARG-165; BREAST CANCER PRO-167 AND BZ ARG-170;

Functional evaluation of PTEN missense mutations using in vitro phosphoinositide phosphatase assay.
Han S.-Y.; Kato H.; Kato S.; Suzuki T.; Shibata H.; Ishii S.; Shiiba K.; Matsuno S.; Kanamaru R.; Ishioka C.;
Cancer Res. 60:3147-3151(2000)
Cited for: CHARACTERIZATION OF VARIANTS ASN-10; CYS-16; GLU-20; SER-27; ARG-61; HIS-68; ARG-112; PRO-121; ARG-129; GLY-130; ILE-133; LEU-134; ARG-165; ASN-170; CYS-173; HIS-173; PRO-173; ASN-174; PHE-227; CYS-251; GLN-345; GLY-369 AND ILE-401; CHARACTERIZATION OF VARIANTS CWS1 TYR-71; TYR-93; PHE-105; TYR-107; PRO-112; ARG-124; GLU-129; LEU-130; GLN-130; TYR-136; CYS-155; ARG-170; GLU-289; GLY-331; VAL-341; ASN-342; GLU-343 AND LEU-347;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P60484: Variant p.Met134Leu