Prediction of the structure of human Janus kinase 2 (JAK2) comprising JAK homology domains 1 through 7.
A theoretical model of human Janus kinase 2 (JAK2) comprising all seven Janus homology domains is presented. The model was generated by application of homology modelling approaches. The three-dimensional structure contains, starting from the N-terminus, FERM (4.1, ezrin, radixin, moesin), SH2 (Src homology region 2), tyrosine kinase-like, and tyrosine kinase domains. The predicted inter-domain orientation in JAK2 is discussed and the currently existing mutational data for Janus kinases are evaluated. Structural details of the SH2 and the FERM domains are presented. The predictions indicate that the SH2 domain is not fully functional. A number of hydrophobic amino acids of the FERM domain that are predicted to be involved in the constitutive association with the cytokine receptors are highlighted. The model gives new insights into the structure-function relationship of this important protein, and areas that could be investigated by mutation studies are highlighted.
Giordanetto
Fabrizio
F
Department of Chemistry, Queen Mary and Westfield College,University of London, Mile End Road, London E1 4NS, UK.
Kroemer
Romano T
RT
D000595:Amino Acid Sequence; D003198:Computer Simulation; D006801:Humans; D053614:Janus Kinase 2; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D015202:Protein Engineering; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D017386:Sequence Homology, Amino Acid; D055672:Static Electricity
D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; D053614:Janus Kinase 2