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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P06213: Variant p.Ala1075Asp

Insulin receptor
Gene: INSR
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Variant information Variant position: help 1075 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help 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: help From Alanine (A) to Aspartate (D) at position 1075 (A1075D, p.Ala1075Asp). 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: help Change from small size and hydrophobic (A) to medium size and acidic (D) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -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: help In IRAN type A. Any additional useful information about the variant.


Sequence information Variant position: help 1075 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 1382 The length of the canonical sequence.
Location on the sequence: help AVKTVNESASLRERIEFLNE A SVMKGFTCHHVVRLLGVVSK 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences. 
Human                         AVKTVNESASLRERIEFLNEASVMKGFTCHHVVRLLGVVSK

Mouse                         AVKTVNESASLRERIEFLNEASVMKGFTCHHVVRLLGVVSK

Rat                           AVKTVNESASLRERIEFLNEASVMKGFTCHHVVRLLGVVSK

Xenopus laevis                AVKTVNESASLRERIEFLNEASVMKAFNCHHVVRLLGVVSK

Caenorhabditis elegans        AIKINVDDPASTENLNYLMEANIMKNFKTNFIVKLYGVIST

Drosophila                    AIKTVNENATDRERTNFLSEASVMKEFDTYHVVRLLGVCSR
Sequence annotation in neighborhood: help 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 763 – 1382 Insulin receptor subunit beta
Topological domain 980 – 1382 Cytoplasmic
Domain 1023 – 1298 Protein kinase
Binding site 1057 – 1057
Modified residue 1083 – 1083 S-nitrosocysteine
Mutagenesis 1057 – 1057 K -> A. Abolishes the kinase activity and abolishes interaction with IRS1, SHC1, GRB7 and PIK3R1.
Mutagenesis 1057 – 1057 K -> MR. Abolishes the kinase activity.
Mutagenesis 1083 – 1083 C -> A. Reduced S-nitrosylation by BLVRB, leading to increased receptor tyrosine kinase activity.
Helix 1065 – 1078



Literature citations
Ala1048-->Asp mutation in the kinase domain of insulin receptor causes defective kinase activity and insulin resistance.
Haruta T.; Takata Y.; Iwanishi M.; Maegawa H.; Imamura T.; Egawa K.; Itazu T.; Kobayashi M.;
Diabetes 42:1837-1844(1993)
Cited for: VARIANT IRAN TYPE A ASP-1075;
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.