HGNC Approved Gene Symbol: DOC2B
Cytogenetic location: 17p13.3 Genomic coordinates (GRCh38) : 17:142,789-181,650 (from NCBI)
Sakaguchi et al. (1995) isolated a DOC2-beta cDNA by screening a human colorectal adenocarcinoma cell line cDNA library with a fragment showing homology to the conserved C2-like domains of rabphilin-3A (RPH3A; 612159) and DOC2A (604567). The DOC2B nucleotide sequence predicts a 412-amino acid protein with relative mass 45,946. The DOC2-beta protein has 61% sequence identity with DOC2-alpha and contains two C2-like domains. Northern blot analysis of human tissues detected a 5.5-kb DOC2-beta transcript in all tissues examined, with highest levels of expression in brain and kidney.
Groffen et al. (2010) found that DOC2 proteins act as calcium sensors to trigger spontaneous release from synaptic vesicles. Although DOC2 proteins are cytosolic, they function analogously to synaptotagmin-1 (185605) but with a higher calcium sensitivity. DOC2 proteins bound to SNARE complexes in competition with synaptotagmin-1. Thus, Groffen et al. (2010) concluded that different classes of multiple C2 domain-containing molecules trigger synchronous versus spontaneous fusion, which suggests a general mechanism for synaptic vesicle fusion triggered by the combined actions of SNARES and multiple C2 domain-containing proteins.
In mouse, Groffen et al. (2010) found that Doc2b mRNA expression is abundant in Purkinje cells of the cerebellum.
Groffen et al. (2010) generated Doc2b-null mice. They were viable and fertile without gross abnormalities. Double knockouts of Doc2a and Doc2b were also viable, fertile, and indistinguishable from wildtype with regard to gross anatomy. However, double-knockout mice exhibited reduction in the spontaneous release frequency from synapses to half that of controls.
Groffen, A. J., Martens, S., Arazola, R. D., Cornelisse, L. N., Lozovaya, N., de Jong, A. P. H., Goriounova, N. A., Habets, R. L. P., Takai, Y., Borst, J. G., Brose, N., McMahon, H. T., Verhage, M. Doc2b is a high-affinity Ca(2+) sensor for spontaneous neurotransmitter release. Science 327: 1614-1618, 2010. Note: Erratum: Science 328: 690 only, 2010. [PubMed: 20150444] [Full Text: https://doi.org/10.1126/science.1183765]
Sakaguchi, G., Orita, S., Maeda, M., Igarashi, H., Takai, Y. Molecular cloning of an isoform of DOC2 having two C2-like domains. Biochem. Biophys. Res. Commun. 217: 1053-1061, 1995. [PubMed: 8554557] [Full Text: https://doi.org/10.1006/bbrc.1995.2876]