Alternative titles; symbols
HGNC Approved Gene Symbol: ACAP2
Cytogenetic location: 3q29 Genomic coordinates (GRCh38): 3:195,274,745-195,443,020 (from NCBI)
By sequencing clones obtained from a size-fractionated myeloid cell line cDNA library, Nomura et al. (1994) cloned a partial cDNA encoding CENTB2, which they designated KIAA0041. The 3-prime untranslated region of the CENTB2 mRNA contains an Alu repeat. CENTB2 shares 52% sequence identity with CENTB1 (607763) and about 28% identity with ankyrin (see 106410). Northern blot analysis revealed ubiquitous expression, with highest levels detected in peripheral blood leukocytes, followed by placenta, kidney, spleen, and ovary. Lowest levels were detected in brain.
Using the partial KIAA0041 sequence as probe, Jackson et al. (2000) obtained a full-length cDNA encoding CENTB2, which they designated ACAP2, from a lymphocyte cDNA library. The deduced 778-amino acid protein contains 2 N-terminal coiled-coil regions, a pleckstrin homology (PH) domain, an ARF-GAP domain (see ARF6; 600464), and C-terminal ankyrin repeats. ACAP2 shares significant similarity with CENTB1, which the authors called ACAP1, and 95% identity with mouse Acap2. It also shares similarity with ASAP1 (605953) and PAP (603817) in the ARF-GAP domain and in the overall domain structure. Jackson et al. (2000) also identified homologous sequences in C. elegans, A. thaliana, and D. melanogaster. By PCR, they detected ACAP2 mRNA expressed at similar levels in all tissues examined. Western blot analysis detected ACAP2 expression in all cell lines examined.
By Northern blot analysis, Dowler et al. (2000) detected expression of a 4.5-kb Centb2 transcript in all mouse tissues tested.
Jackson et al. (2000) determined that ACAP1 and ACAP2 were recruited to platelet-derived growth factor (PDGF; see 173430)-induced dorsal membrane ruffles in NIH 3T3 mouse fibroblasts, and overexpression inhibited ruffle formation. In vitro, ACAP1 and ACAP2 preferred ARF6 as substrate rather than ARF1 (103180) or ARF5 (103188), and the GAP activity of both ACAPs was dependent upon phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). Mutation of a highly conserved arginine in both ACAPs resulted in lack of ARF-GAP activity. Overexpression in HeLa cells of either ACAP blocked the formation of ARF6-dependent protrusions. Both ACAPs were also recruited to peripheral, tubular membranes, where activation of ARF6 occurs and allows membrane recycling back to the plasma membrane.
Dowler et al. (2000) determined that the isolated PH domain of mouse Centb2 exhibited moderate affinity for PtdIns(3,5)P2, but it did not bind any other phosphoinositides tested, including PtdIns(4,5)P2.
By PCR of a human/rodent hybrid panel, Nomura et al. (1994) mapped the CENTB2 gene to chromosome 3.
Dowler, S., Currie, R. A., Campbell, D. G., Deak, M., Kular, G., Downes, C. P., Alessi, D. R. Identification of pleckstrin-homology-domain-containing proteins with novel phosphoinositide-binding specificities. Biochem. J. 351: 19-31, 2000. [PubMed: 11001876] [Full Text: https://doi.org/10.1042/0264-6021:3510019]
Jackson, T. R., Brown, F. D., Nie, Z., Miura, K., Foroni, L., Sun, J., Hsu, V. W., Donaldson, J. G., Randazzo, P. A. ACAPs are Arf6 GTPase-activating proteins that function in the cell periphery. J. Cell Biol. 151: 627-638, 2000. [PubMed: 11062263] [Full Text: https://doi.org/10.1083/jcb.151.3.627]
Nomura, N., Nagase, T., Miyajima, N., Sazuka, T., Tanaka, A., Sato, S., Seki, N., Kawarabayasi, Y., Ishikawa, K., Tabata, S. Prediction of the coding sequences of unidentified human genes. II. The coding sequences of 40 new genes (KIAA0041-KIAA0080) deduced by analysis of cDNA clones from human cell line KG-1. DNA Res. 1: 223-229, 1994. [PubMed: 7584044] [Full Text: https://doi.org/10.1093/dnares/1.5.223]