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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P23458: Variant p.Ser703Ile

Tyrosine-protein kinase JAK1
Gene: JAK1
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Variant information Variant position: help 703 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 Serine (S) to Isoleucine (I) at position 703 (S703I, p.Ser703Ile). 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 polar (S) to medium size and hydrophobic (I) 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 AIIDE; increased activation of protein kinase activity; constitutive gain of function through the transactivation of associated JAK kinases; increased receptor signaling pathway via JAK-STAT. Any additional useful information about the variant.


Sequence information Variant position: help 703 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 1154 The length of the canonical sequence.
Location on the sequence: help SDVLTTPWKFKVAKQLASAL S YLEDKDLVHGNVCTKNLLLA 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                         SDVLTTPWKFKVAKQLASALSYLEDKDLVHGNVCTKNLLLA

Mouse                         SDALTTPWKFKVAKQLASALSYLEDKDLVHGNVCTKNLLLA

Zebrafish                     TTPLSTAWKFQVAKQLASALSYLEDKKMVHGYVCSKNILVA
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 1 – 1154 Tyrosine-protein kinase JAK1
Domain 583 – 855 Protein kinase 1
Helix 688 – 707



Literature citations
Complex Autoinflammatory Syndrome Unveils Fundamental Principles of JAK1 Kinase Transcriptional and Biochemical Function.
Gruber C.N.; Calis J.J.A.; Buta S.; Evrony G.; Martin J.C.; Uhl S.A.; Caron R.; Jarchin L.; Dunkin D.; Phelps R.; Webb B.D.; Saland J.M.; Merad M.; Orange J.S.; Mace E.M.; Rosenberg B.R.; Gelb B.D.; Bogunovic D.;
Immunity 53:e11672-e11684(2020)
Cited for: VARIANT AIIDE ILE-703; CHARACTERIZATION OF VARIANT AIIDE ILE-703; FUNCTION; MUTAGENESIS OF LYS-908; ATP-BINDING;
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.