Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Gene Review:

Cpd - carboxypeptidase D

Mus musculus

Eng, F.J., Mayanil, C.S., Singh, U., Fricker, L.D., Varlamov, O., et al.

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Disease relevance of Cpd

Based on their sizes, prosthetic groups, and locations in virions, these proteins were designated gp180/E2, gp90/E2, pp54/N, gp26.5/E1, gp25.5/E1, p24/E1, p22/X, and p14.5/Y [1].

High impact information on Cpd

After ligand-induced receptor patching and/or capping, the amount of gp 180 in the membrane-associated cytoskeleton fraction increases in direct proportion to the percentage of patched/capped cells [2].
The purposes of this study were to examine the Cys residues of the transmembrane domain of metallocarboxypeptidase D (CPD) that could be a target for palmitoylation and to clarify the function of this modification [3].
Cdc25A inhibitor Cpd 5, a vitamin K analog, inhibited Cdc25A activity in the Cdc25A-EGFR immunocomplex and consequently caused prolonged EGFR tyrosine phosphorylation [4].
A second major finding of the present study is that a soluble truncated form of CPD is secreted mainly via the constitutive pathway in AtT-20 cells, indicating that the lumenal domain does not contain signals for the sorting of CPD to mature secretory granules [5].
To investigate the regions of the gp180 tail involved with TGN retention and intracellular trafficking, gp180 and various deletion and point mutations were expressed in the AtT-20 mouse pituitary corticotroph cell line [6].

Biological context of Cpd

Concordant deregulation of Cpe and Cpd in abnormal placentas of interspecies hybrids before the onset of IHPD phenotype and recapitulation of some phenotypes of IHPD hyperplastic placentas in Cpe mutant placentas suggests that these two genes are causally involved in IHPD and may function as speciation genes in the genus Mus [7].
Northern blotting revealed a ubiquitous tissue distribution of human gp180 mRNA with several transcript species [8].
The carboxypeptidase D gene was further localized to the centromeric region 17p11.1-q11.1/11.2 by use of a regional mapping panel derived from somatic cell hybrids containing different portions of chromosome 17 [9].

Anatomical context of Cpd

Our lectin overlays on Western blots showed that (1) the synaptic vesicle glycoproteins, gp80-100, gp47 and gp44, and (2) the synaptic membrane glycoproteins, gp180, gp72, gp70 and gp34, show temporal regulation of expression of carbohydrate moieties [10].

Associations of Cpd with chemical compounds

Taken together, these data suggest that CPE is completely inactive in the Cpefat/Cpefat mice, and that all of the CPE-like activity is due to other carboxypeptidases such as carboxypeptidase D. Levels of Leu-enkephalin in Cpefat/Cpefat mouse brain are approximately 5-fold lower than those in control brain [11].
In the presence of 2-mercaptoethanol, three major glycopolypeptides, gp180, gp69, gp25 (as a group of similar species) and one major non-glycosylated polypeptide p58 were detected [12].

Regulatory relationships of Cpd

Anti neural cell adhesion molecule (N-CAM) antibody cross-reacted with gp180 [10].
Protein phosphatase 2A binds to the cytoplasmic tail of carboxypeptidase D and regulates post-trans-Golgi network trafficking [13].

Other interactions of Cpd

Sequences within the cytoplasmic domain of gp180/carboxypeptidase D mediate localization to the trans-Golgi network [6].

Analytical, diagnostic and therapeutic context of Cpd

Fluorescence in-situ hybridization reveals that the gene encoding human gp180 is located in region 17q11.2 [8].
Microinjection of the CPD tail into AtT-20 cells inhibits the transition of CPD from endosomal compartments to the TGN [13].

References

Viral protein synthesis in mouse hepatitis virus strain A59-infected cells: effect of tunicamycin. Rottier, P.J., Horzinek, M.C., van der Zeijst, B.A. J. Virol. (1981)
A T-lymphoma transmembrane glycoprotein (gp180) is linked to the cytoskeletal protein, fodrin. Bourguignon, L.Y., Suchard, S.J., Nagpal, M.L., Glenney, J.R. J. Cell Biol. (1985)
Palmitoylation of carboxypeptidase D. Implications for intracellular trafficking. Kalinina, E.V., Fricker, L.D. J. Biol. Chem. (2003)
Identification of epidermal growth factor receptor as a target of Cdc25A protein phosphatase. Wang, Z., Wang, M., Lazo, J.S., Carr, B.I. J. Biol. Chem. (2002)
Localization of metallocarboxypeptidase D in AtT-20 cells. Potential role in prohormone processing. Varlamov, O., Eng, F.J., Novikova, E.G., Fricker, L.D. J. Biol. Chem. (1999)
Sequences within the cytoplasmic domain of gp180/carboxypeptidase D mediate localization to the trans-Golgi network. Eng, F.J., Varlamov, O., Fricker, L.D. Mol. Biol. Cell (1999)
Carboxypeptidase E in the mouse placenta. Singh, U., Yu, Y., Kalinina, E., Konno, T., Sun, T., Ohta, H., Wakayama, T., Soares, M.J., Hemberger, M., Fundele, R.H. Differentiation (2006)
Cloning, functional expression, and chromosomal localization of the human and mouse gp180-carboxypeptidase D-like enzyme. Ishikawa, T., Murakami, K., Kido, Y., Ohnishi, S., Yazaki, Y., Harada, F., Kuroki, K. Gene (1998)
Chromosomal localization of the genes for human carboxypeptidase D (CPD) and the active 50-kilodalton subunit of human carboxypeptidase N (CPN1). Riley, D.A., Tan, F., Miletich, D.J., Skidgel, R.A. Genomics (1998)
Synaptic vesicle and synaptic membrane glycoproteins during pre- and postnatal development of mouse cerebral cortex, cerebellum and spinal cord. Mayanil, C.S., Knepper, P.A. Dev. Neurosci. (1993)
Carboxypeptidase E activity is deficient in mice with the fat mutation. Effect on peptide processing. Fricker, L.D., Berman, Y.L., Leiter, E.H., Devi, L.A. J. Biol. Chem. (1996)
Structural polypeptides of the murine coronavirus DVIM. Sugiyama, K., Ishikawa, R., Fukuhara, N. Arch. Virol. (1986)
Protein phosphatase 2A binds to the cytoplasmic tail of carboxypeptidase D and regulates post-trans-Golgi network trafficking. Varlamov, O., Kalinina, E., Che, F.Y., Fricker, L.D. J. Cell. Sci. (2001)