JH1 is the kinase domain important for the enzymatic activity of the JAK and contains typical features of a tyrosine kinase such as conserved tyrosines necessary for JAK activation (e.g., Y1038/Y1039 in JAK1, Y1007/Y1008 in JAK2, Y980/Y981 in JAK3, and Y1054/Y1055 in Tyk2).

May 12, 2004 · Seven Jak homology (JH) domains have been identified, numbered from the carboxyl to the amino terminus (Figure 1). The JH1 domain at the carboxyl terminus has all the features of a typical eukaryotic tyrosine kinase domain.

Aug 21, 2024 · JH1 is approximately 275 amino acids in length and encodes a protein kinase that constitutes the catalytic domain responsible for phosphorylating substrate molecules.

The catalytically active kinase domain (JH1) is located at the carboxyl-terminus, and at its amino-terminal site, it is directly followed by the enzymatically inactive pseudokinase domain, a unique feature of Jaks among PTKs.

We used JAK-deficient cell-lines and structure-based mutagenesis to study the function of JAK1 and its pseudokinase domain (JH2) in cytokine signaling pathways that employ JAK1 with different JAK heterodimerization partner.

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JAK2 possesses a pseudokinase domain (JH2) and a tyrosine kinase domain (JH1). Through unknown mechanisms, JH2 regulates the catalytic activity of JH1, and hyperactivating mutations in the JH2 region of human JAK2 cause myeloproliferative neoplasms (MPNs).