Alternative titles; symbols
HGNC Approved Gene Symbol: ARAP1
Cytogenetic location: 11q13.4 Genomic coordinates (GRCh38): 11:72,685,069-72,752,408 (from NCBI)
By screening brain cDNAs for the potential to encode proteins that are at least 50 kD, Nagase et al. (1998) identified a partial cDNA encoding CENTD2, which they called KIAA0782. The deduced KIAA0782 protein shares 43% overall identity with the KIAA0580 protein (CENTD1; 606645) and was predicted to be involved in cell signaling/communication. RT-PCR analysis followed by ELISA detected expression of KIAA0782 in all tissues tested, with highest levels in ovary, followed by lung, liver, and kidney.
By searching sequence databases, followed by 5-prime RACE, Miura et al. (2002) obtained full-length cDNAs encoding CENTD2 and CENTD1, which they called ARAP1 and ARAP2, respectively. The 1,210-amino acid ARAP1 protein contains ARF-GAP (see 103180), RHO-GAP (see 602732), ankyrin repeat (see 605787), RAS (190020)-associating, and 5 pleckstrin (173570) homology (PH) domains. Northern blot analysis detected a 5.5-kb ARAP1 transcript in all tissues tested; an additional 7-kb transcript was present in heart and skeletal muscle.
Miura et al. (2002) examined ARAP1 as a possible link between phosphoinositide-, ARF-, and RHO-mediated cell signaling. In vitro, ARAP1 had RHO-GAP and phosphatidylinositol (3,4,5) trisphosphate (PIP3; see 171834)-dependent ARF-GAP activity. ARAP1 associated with the Golgi. The RHO-GAP activity mediated cell rounding and loss of stress fibers when ARAP1 was overexpressed. The ARF-GAP activity mediated changes in the Golgi apparatus and the formation of filopodia, the latter a consequence of increased cellular activity of CDC42 (116952). The ARF-GAP and RHO-GAP activities both contributed to inhibiting cell spreading. Thus, ARAP1 is a PIP3-dependent ARF-GAP that regulates ARF-, RHO-, and CDC42-dependent cell activities.
By radiation hybrid analysis, Nagase et al. (1998) mapped the KIAA0782 gene to chromosome 11.
Miura, K., Jacques, K. M., Stauffer, S., Kubosaki, A., Zhu, K., Hirsch, D. S., Resau, J., Zheng, Y., Randazzo, P. A. ARAP1: a point of convergence for Arf and Rho signaling. Molec. Cell 9: 109-119, 2002. [PubMed: 11804590] [Full Text: https://doi.org/10.1016/s1097-2765(02)00428-8]
Nagase, T., Ishikawa, K., Suyama, M., Kikuno, R., Miyajima, N., Tanaka, A., Kotani, H., Nomura, N., Ohara, O. Prediction of the coding sequences of unidentified human genes. XI. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. DNA Res. 5: 277-286, 1998. [PubMed: 9872452] [Full Text: https://doi.org/10.1093/dnares/5.5.277]