UniProtKB/Swiss-Prot P06213: Variant p.Met1180Ile

Insulin receptor
Gene: INSR
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Variant information Variant position:

1180 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

LB/B 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 Isoleucine (I) at position 1180 (M1180I, p.Met1180Ile). 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 a patient with insulin resistance. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs121913157 [ dbSNP | Ensembl ]

Sequence information Variant position:

1180 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

1382 The length of the canonical sequence.
Location on the sequence:

LAARNCMVAHDFTVKIGDFG M TRDIYETDYYRKGGKGLLPV 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                         LAARNCMVAHDFTVKIGDFGMTRDIYETDYYRKGGKGLLPV

Mouse                         LAARNCMVAHDFTVKIGDFGMTRDIYETDYYRKGGKGLLPV

Rat                           LAARNCMVAHDFTVKIGDFGMTRDIYETDYYRKGGKGLLPV

Xenopus laevis                LAARNCMVADDYAVKIGDFGMTRDIYETDYYRKGGKGLLPV

Caenorhabditis elegans        LAARNCMINRDETVKIGDFGMARDLFYHDYYKPSGKRMMPV

Drosophila                    LAARNCMVADDLTVKIGDFGMTRDIYETDYYRKGTKGLLPV

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	763 – 1382	Insulin receptor subunit beta
Topological domain	980 – 1382	Cytoplasmic
Domain	1023 – 1298	Protein kinase
Binding site	1177 – 1177
Modified residue	1185 – 1185	Phosphotyrosine; by autocatalysis
Modified residue	1189 – 1189	Phosphotyrosine; by autocatalysis
Modified residue	1190 – 1190	Phosphotyrosine; by autocatalysis
Mutagenesis	1163 – 1163	R -> Q. Loss of kinase activity.
Mutagenesis	1189 – 1189	Y -> F. Reduced interaction with GRB7.
Mutagenesis	1190 – 1190	Y -> F. Strongly reduced interaction with GRB7.

Literature citations
A mutation in the tyrosine kinase domain of the insulin receptor associated with insulin resistance in an obese woman.
Cama A.; de la Luz Sierra M.; Ottini L.; Kadowaki T.; Gorden P.; Imperato-Mcginley J.; Taylor S.I.;
J. Clin. Endocrinol. Metab. 73:894-901(1991)
Cited for: VARIANT INS RESISTANCE ILE-1180;

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.