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The human HERC3 gene maps1 to chromosome 4q21 by fluorescence in situ hybridization

The human HERC3 gene (GenBank accession number D25215) was isolated during a random search for human cDNAs larger than 2 kb (Nomura et al., 1994). The protein product predicted for the HERC3 gene reveals at least two significant homology domains. First, an N-terminal domain with homology to the Regulator of Chromosome Condensation (RCC1), a protein that acts as a guanine exchange factor for the small GTPase Ran (Koepp and Silver, 1996). The second outstanding region of the putative HERC3 protein is a C-terminal domain known as HECT (Homologous to E6-AP carboxy-terminus), which is found in a number of E3 ubiquitin-protein ligases including the E6-AP ubiquitin ligase (Schwarz et al., 1998). Genes whose predicted protein products contain this combination of one or more RCC1 like domains (RLDs) and a HECT domain have recently received an HGNC-approved nomenclature: HERC, for HECT domain and RCC1 domain protein. At present, only three human genes belong to the HERC family: HERC1/P532, HERC2/rjs/jdf2 and HERC3/ D25215 (Fig. 1a). The HERC1/P532 gene was isolated during a gene transfer assay aimed at the identification of novel oncogenes from human tumor DNA. Subsequent analysis showed