Taxonomic distribution of proteins containing KRAP_IP3R_bind domains

The tree below includes only several representative species and genera. The complete taxonomic breakdown of all proteins containing KRAP_IP3R_bind domains can be accessed here. Click the counts or percentage values to display the corresponding proteins.

Determination of the critical region of KRAS-induced actin-interacting proteinfor the interaction with inositol 1,4,5-trisphosphate receptor.

Fujimoto T, Machida T, Tsunoda T, Doi K, Ota T, Kuroki M, Shirasawa S
Biochem Biophys Res Commun. 2011; 408: 282-6

KRAS-induced actin-interacting protein (KRAP) was originally characterized as afilamentous-actin-interacting protein. We have recently found that KRAP is anassociated molecule with inositol 1,4,5-trisphosphate receptor (IP(3)R) and iscritical for the proper subcellular localization and function of IP(3)R. However,the molecular mechanisms underlying the regulation of IP(3)R by KRAP remainelusive. In this report, to determine the critical region of KRAP protein for theregulation of IP(3)R, we generate several mutants of KRAP and examine theassociation with IP(3)R using coimmunoprecipitation and confocal imaging assays. Coimmunoprecipitations using the deletion mutants reveal that amino-acid residues1-218 but not 1-199 of KRAP interact with IP(3)R, indicating that the 19-lengthamino-acid residues (200-218) are essential for the association with IP(3)R. Thiscritical region is highly conserved between human and mouse KRAP. Within thecritical region, substitutions of two phenylalanine residues (Phe202/Phe203) inmouse KRAP to alanines result in failure of the association with IP(3)R,suggesting that the two consecutive phenylalanine residues are indispensable for the association. Moreover, the KRAP-knockdown stable HeLa cells exhibit theinappropriate subcellular localization of IP(3)R, in which exogenous expressionof full-length of KRAP properly restores the subcellular localization of IP(3)R, but not the 1-218 or 1-236 mutant, indicating that the residual carboxyl-terminalregion is also required for the proper subcellular localization of KRAP-IP(3)Rcomplex. All these results provide insight into the understandings for themolecular mechanisms underlying the regulation of IP(3)R, and would reveal apotent strategy for the drug development targeting on IP(3)R.

Deregulated expression of KRAP, a novel gene encoding actin-interacting protein, in human colon cancer cells.

Inokuchi J, Komiya M, Baba I, Naito S, Sasazuki T, Shirasawa S
J Hum Genet. 2004; 49: 46-52

We have identified a novel gene, designated KRAP (Ki- ras-inducedactin-interacting protein), encoding a protein of 1,259 amino acids withcoiled-coil regions and transmembrane regions, from the cDNA library of humancolon cancer HCT116 cells, as one of the genes upregulated by activated Ki- ras. While KRAP was rarely expressed in normal colon epithelium, deregulatedconstitutive KRAP expression was observed in some other colon cancer cells. Innormal tissues, KRAP was strongly expressed in pancreas and testis. Anti-KRAPpolyclonal antibodies detected endogenous KRAP as the molecular size of Mr180,000, and immunofluorescence microscopy and cytochalasin E treatment revealed that KRAP was clearly associated with the actin filaments. Furthermore, KRAP was localized as a membrane-bound form with extracellular regions. These resultstogether suggested KRAP might be involved in the regulation of filamentous actin and signals from the outside of the cells.