Variant position: 997 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:
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 LFLRKRQ-PDGPLGPLYASSN PEYLSASDVFPCSVYVPDEWE
Mouse LFLRKRQ-PDGPMGPLYASSN PEYLSASDVFPSSVYVPDEW
Rat LFLRKRQ-PDGPMGPLYASSN PEYLSASDVFPSSVYVPDEW
Xenopus laevis CVVQKKKDAEGPAGPLYTSSN PEYLSASE-----VYIPDEW
Caenorhabditis elegans YYIQVRYGKKVKALSDFMQLN PEYCVDN------KYNADDW
Drosophila CYLHKRKVPSNDL-HMNTEVN PFYASM-------QYIPDDW
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
763 – 1382 Insulin receptor subunit beta
980 – 1382 Cytoplasmic
999 – 999 Important for interaction with IRS1, SHC1 and STAT5B
992 – 992 Phosphotyrosine; by autocatalysis
999 – 999 Phosphotyrosine; by autocatalysis
1011 – 1011 Phosphotyrosine; by autocatalysis
991 – 991 L -> A. Reduces interaction with IRS1 but has no effect on interaction with SHC1.
992 – 992 Y -> A. Reduces interaction with IRS1 but has no effect on interaction with SHC1.
996 – 997 NP -> AA. Abolishes interaction with IRS1. Severely disrupts, but does not abolish interaction with SHC1.
996 – 996 N -> A. Abolishes interaction with IRS1 and significantly reduces interaction with SHC1. Has no effect on interaction with PIK3R1.
997 – 997 P -> A. Abolishes interaction with IRS1 and significantly reduces interaction with SHC1. Has no effect on interaction with PIK3R1.
998 – 998 E -> A. Does not affect interaction with IRS1, SHC1 or PIK3R1.
999 – 999 Y -> E. Abolishes interaction with IRS1 and SHC1.
999 – 999 Y -> F. Has no effect on insulin-stimulated autophosphorylation, but inhibits the biological activity of the receptor. Abolishes interaction with IRS1 and almost completely prevents interaction with SHC1. Has no effect on interaction with PIK3R1. Abolishes interaction with STAT5B.
1000 – 1000 L -> AR. Severely reduces interaction with SHC1. Has no effect on interaction with IRS1.
1002 – 1002 A -> D. Reduces interaction with IRS1 but has no effect on interaction with SHC1.
1011 – 1011 Y -> A. Increases kinase activity.
Genotype-phenotype correlation in inherited severe insulin resistance.
Longo N.; Wang Y.; Smith S.A.; Langley S.D.; DiMeglio L.A.; Giannella-Neto D.;
Hum. Mol. Genet. 11:1465-1475(2002)
Cited for: CHARACTERIZATION OF VARIANTS LEPRCH PRO-113; VAL-119; ASN-308 DEL; THR-925 AND TRP-926; VARIANTS RMS THR-997; THR-1143; TRP-1158 AND TRP-1201;
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.