This family includes the N-terminus of the actin-interacting protein sperm-specific antigen 2, or KRAP (Ki-ras-induced actin-interacting protein) (PUBMED:14673706). This region is found to be the residues that interact with inositol 1,4,5-trisphosphate receptor (IP3R). KRAP was first localized as a membrane-bound form with extracellular regions suggesting it might be involved in the regulation of filamentous actin and signals from the outside of the cells (PUBMED:14673706). It has now been shown to be critical for the proper subcellular localization and function of IP3R. Inositol 1,4,5-trisphosphate receptor functions as the Ca2+ release channel on specialized endoplasmic reticulum membranes, so the subcellular localisation of IP3R is crucial for its proper function (PUBMED:21501587).
This domain entry includes the N terminus of the actin-interacting protein sperm-specific antigen 2 (SSFA2), also known as Ki-ras-induced actin-interacting protein (KRAP) [ (PUBMED:14673706) ]. In this region are found the residues that interact with inositol 1,4,5-trisphosphate receptor (IP3R, also known as ITPR). SSFA2 was first localised as a membrane-bound form with extracellular regions suggesting it might be involved in the regulation of filamentous actin and signals from the outside of the cells [ (PUBMED:14673706) ]. It has now been shown to be critical for the proper subcellular localisation and function of IP3R. Inositol 1,4,5-trisphosphate receptor functions as the Ca2+ release channel on specialised endoplasmic reticulum membranes, so the subcellular localisation of IP3R is crucial for its proper function [ (PUBMED:21501587) ].
This entry also recognises a domain in Tespa1 and in uncharacterized coiled-coil protein CCDC129. Tespa1 (thymocyte-expressed positive selection-associated protein 1) is required for the development and maturation of T-cells [ (PUBMED:22561606) ]. Tespa1 shows sequence homology to SSFA2 and physically associates with IP3R in T and B lymphocytes [ (PUBMED:23650607) ].
There are 1163 KRAP_IP3R_bind domains in 1162 proteins in SMART's nrdb database.
Click on the following links for more information.
Evolution (species in which this domain is found)
Taxonomic distribution of proteins containing KRAP_IP3R_bind domain.
This tree includes only several representative species. The complete taxonomic breakdown of all proteins with KRAP_IP3R_bind domain is also avaliable.
Click on the protein counts, or double click on taxonomic names to display all proteins containing KRAP_IP3R_bind domain in the selected taxonomic class.
Literature (relevant references for this domain)
Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.
Determination of the critical region of KRAS-induced actin-interacting proteinfor the interaction with inositol 1,4,5-trisphosphate receptor.
Biochem Biophys Res Commun. 2011; 408: 282-6
Display abstract
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.
J Hum Genet. 2004; 49: 46-52
Display abstract
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.
Links (links to other resources describing this domain)
