UniProtKB/Swiss-Prot Q15831: Variant p.Val66Met

Serine/threonine-protein kinase STK11
Gene: STK11
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Variant information Variant position:

66 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 Valine (V) to Methionine (M) at position 66 (V66M, p.Val66Met). 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:

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 cervical carcinoma; somatic mutation. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs1599915144 [ dbSNP | Ensembl ]

Sequence information Variant position:

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

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

IGKYLMGDLLGEGSYGKVKE V LDSETLCRRAVKILKKKKLR 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                         IGKYLMGDLLGEGSYGKVKEVLDSETLCRRAVKILKKKKLR

Mouse                         IGKYLMGDLLGEGSYGKVKEVLDSETLCRRAVKILKKKKLR

Rat                           IGKYLMGDLLGEGSYGKVKEVLDSETLCRRAVKILKKKKLR

Chicken                       IGKYLMGDLLGEGSYGKVKEMLDSETLCRRAVKILKKKKLR

Xenopus laevis                VGKYLMGDLLGEGSYGKVKEMLDSDTLCRRAVKILKKKKLR

Slime mold                    VKHYILGEVLGEGAYGKVKDGMDSFTQKRVAVKILKRARLK

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	1 – 430	Serine/threonine-protein kinase STK11
Domain	49 – 309	Protein kinase
Region	45 – 90	Sufficient for interaction with SIRT1
Binding site	78 – 78
Modified residue	48 – 48	N6-acetyllysine
Mutagenesis	48 – 48	K -> Q. No effect on basal nucleocytoplasmic localization, but fails to translocate to the cytoplasm when coexpressed with SIRT1.
Mutagenesis	48 – 48	K -> R. Enhanced phosphorylation at Thr-336 and Ser-428, enhanced cytoplasmic localization and increased kinase activity.
Mutagenesis	74 – 74	R -> A. Impaired formation of a heterotrimeric complex with STRADA and CAB39; when associated with A-204.
Mutagenesis	78 – 78	K -> I. Loss of kinase activity, leading to greatly reduced autophosphorylation.
Mutagenesis	78 – 78	K -> M. Loss of kinase activity, leading to reduced autophosphorylation and acting as a dominant-negative mutant.
Beta strand	62 – 68

Literature citations
Structure of the LKB1-STRAD-MO25 complex reveals an allosteric mechanism of kinase activation.
Zeqiraj E.; Filippi B.M.; Deak M.; Alessi D.R.; van Aalten D.M.;
Science 326:1707-1711(2009)
Cited for: X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) OF 43-347 IN COMPLEX WITH STRADA AND CAB39; ACTIVITY REGULATION; CHARACTERIZATION OF VARIANTS SPORADIC CANCER MET-66; GLY-86; ARG-123; SER-157; ASP-163; PRO-170; SER-171; ARG-174; TYR-176; ASN-177; GLU-181; GLN-199; THR-205; PHE-216; VAL-223; PRO-230; PRO-232; ARG-245; PRO-250; HIS-272; TYR-277; GLN-285 AND SER-315; MUTAGENESIS OF ARG-74; ASP-194 AND PHE-204; Mutations in the STK11 gene characterize minimal deviation adenocarcinoma of the uterine cervix.
Kuragaki C.; Enomoto T.; Ueno Y.; Sun H.; Fujita M.; Nakashima R.; Ueda Y.; Wada H.; Murata Y.; Toki T.; Konishi I.; Fujii S.;
Lab. Invest. 83:35-45(2003)
Cited for: VARIANTS CERVICAL CANCER LYS-14; PRO-160 AND LEU-231; VARIANT CERVICAL CARCINOMA MET-66;

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.