Alternative titles; symbols
HGNC Approved Gene Symbol: CPD
Cytogenetic location: 17q11.2 Genomic coordinates (GRCh38): 17:30,378,927-30,469,989 (from NCBI)
The metallocarboxypeptidase family of enzymes is divided into 2 subfamilies, the pancreatic carboxypeptidase subfamily (e.g., CPA1; 114850) and the regulatory B-type carboxypeptidase subfamily (e.g., CPN1; 603103), based on sequence similarities. In membrane fractions of mammalian cells, McGwire et al. (1997) identified a novel regulatory B-type carboxypeptidase that they designated carboxypeptidase D, or CPD. CPD is homologous to duck gp180, a hepatitis B virus-binding protein.
By searching databases to identify human homologs of gp180, Tan et al. (1997) isolated cDNAs encoding CPD. The predicted 1,377-amino acid protein contains a signal sequence, 3 tandem carboxypeptidase homology domains, and a C-terminal putative transmembrane domain. The 3 carboxypeptidase domains have sequence similarity to the regulatory B-type carboxypeptidase family. Overall, the amino acid sequences of CPD and gp180 are 75% identical. Northern blot analysis revealed CPD expression as multiple mRNAs in pancreas, placenta, heart, and skeletal muscle.
By screening human hepatoblastoma cell and mouse liver cDNA libraries for homologs of duck gp180, Ishikawa et al. (1998) isolated full-length cDNAs encoding CPD. The predicted 1,380-amino acid human protein shares 91% identity with mouse Cpd, and both contain 3 carboxypeptidase domains (A, B, and C), 15 potential N-linked glycosylation sites, a transmembrane domain, and a conserved cytoplasmic tail. Northern blot analysis detected a 5.5-kb transcript in all human tissues examined, and 8.0- and 10.0-kb transcripts were also present in heart, skeletal muscle, and pancreas.
Ishikawa et al. (1998) found that expression of human CPD in embryonic kidney cells significantly increased carboxypeptidase activity.
By mutation analysis, Eng et al. (1998) mapped carboxypeptidase activity to domains A and B of duck gp180. They mapped binding of duck hepatitis B virus preS protein to domain C.
Breiner et al. (1998) and Tong et al. (1999) independently showed that duck Cpd bound duck hepatitis B virus, but they found that it did not render mammalian cells permissive for productive infection. Breiner et al. (1998) suggested that a coreceptor may be necessary for entry into cells, and Tong et al. (1999) suggested that other factors may be necessary for postentry events.
Campbell et al. (1999) found that gp180 expressed on intestinal epithelial cells associated with CD1D (188410) on the cell surface and activated T-lymphocyte FYN (137025) in a CD1D-dependent manner.
Campbell et al. (2002) determined that carbohydrate on gp180 interacted with CD8 (see 186910)-positive T cells, but not CD4 (186940)-positive T cells, at a site distinct from that bound by class I MHC molecules. The gp180-CD8 interaction led to LCK (153390) activation.
By analysis of somatic cell hybrid panels, Riley et al. (1998) mapped the CPD gene to the centromeric region 17p11.1-q11.2. Using FISH, Ishikawa et al. (1998) mapped the CPD gene to chromosome 17q11.2.
Breiner, K. M., Urban, S., Schaller, H. Carboxypeptidase D (gp180), a Golgi-resident protein, functions in the attachment and entry of avian hepatitis B viruses. J. Virol. 72: 8098-8104, 1998. [PubMed: 9733850] [Full Text: https://doi.org/10.1128/JVI.72.10.8098-8104.1998]
Campbell, N. A., Kim, H. S., Blumberg, R. S., Mayer, L. The nonclassical class I molecule CD1d associates with the novel CD8 ligand gp180 on intestinal epithelial cells. J. Biol. Chem. 274: 26259-26265, 1999. [PubMed: 10473580] [Full Text: https://doi.org/10.1074/jbc.274.37.26259]
Campbell, N. A., Park, M. S., Toy, L. S., Yio, X. Y., Devine, L., Kavathas, P., Mayer, L. A non-class I MHC intestinal epithelial surface glycoprotein, gp180, binds to CD8. Clin. Immun. 102: 267-274, 2002. [PubMed: 11890713] [Full Text: https://doi.org/10.1006/clim.2001.5170]
Eng, F. J., Novikova, E. G., Kuroki, K., Ganem, D., Fricker, L. D. gp180, a protein that binds duck hepatitis B virus particles, has metallocarboxypeptidase D-like enzymatic activity. J. Biol. Chem. 273: 8382-8388, 1998. [PubMed: 9525948] [Full Text: https://doi.org/10.1074/jbc.273.14.8382]
Ishikawa, T., Murakami, K., Kido, Y., Ohnishi, S., Yazaki, Y., Harada, F., Kuroki, K. Cloning, functional expression, and chromosomal localization of the human and mouse gp180-carboxypeptidase D-like enzyme. Gene 215: 361-370, 1998. [PubMed: 9714835] [Full Text: https://doi.org/10.1016/s0378-1119(98)00270-4]
McGwire, G. B., Tan, F., Michel, B., Rehli, M., Skidgel, R. A. Identification of a membrane-bound carboxypeptidase as the mammalian homolog of duck gp180, a hepatitis B virus-binding protein. Life Sci. 60: 715-724, 1997. [PubMed: 9064476] [Full Text: https://doi.org/10.1016/s0024-3205(96)00642-x]
Riley, D. A., Tan, F., Miletich, D. J., Skidgel, R. A. Chromosomal localization of the genes for human carboxypeptidase D (CPD) and the active 50-kilodalton subunit of human carboxypeptidase N (CPN1). Genomics 50: 105-108, 1998. [PubMed: 9628828] [Full Text: https://doi.org/10.1006/geno.1998.5295]
Tan, F., Rehli, M., Krause, S. W., Skidgel, R. A. Sequence of human carboxypeptidase D reveals it to be a member of the regulatory carboxypeptidase family with three tandem active site domains. Biochem. J. 327: 81-87, 1997. [PubMed: 9355738] [Full Text: https://doi.org/10.1042/bj3270081]
Tong, S., Li, J., Wands, J. R. Carboxypeptidase D is an avian hepatitis B virus receptor. J. Virol. 73: 8696-8702, 1999. [PubMed: 10482623] [Full Text: https://doi.org/10.1128/JVI.73.10.8696-8702.1999]