Members

 Gbeta proteins
 protein kinases
 ankyrin
 kinesin
 gelsolin
 neurogranin
 neuromodulin
 Bruton tyrosin kinase (BTK)

Function

 HIKE regions have been demonstrated to bind both proteins and lipids, and to regulate the interaction of Gbeta, neuromodulin and the BTK PH domain with downstream effectors and the cell membrane.

Pathology

 Several HIKE mutations in protein kinases lead to constitutive activation and cellular transformation, e.g. in MEN-2B, acute myeloid and mast cell leukemias, hereditary papillary renal carcinomas and multiple myeloma.
 Kinase-inactivating HIKE mutations cause Hirschsprung's disease, piebaldism, insulin resistance and developmental dysplasias.
 HIKE mutations in the PH domain of BTK lead to X-linked agammaglobulinemia, and different forms of amyloidosis are caused by mutations of HIKE-bearing molecules, for example gelsolin, Ret and Trop-2.

References

 Ciccarelli FD, Acciarito A, Alberti S. Large and diverse numbers of human diseases with HIKE mutations. Hum Mol Genet. 2000 Apr 12;9(6):1001-7. PMID: #10767324#