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Gene Review

CPM  -  carboxypeptidase M

Homo sapiens

Synonyms: Carboxypeptidase M
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Disease relevance of CPM


Psychiatry related information on CPM

  • Ninety-six children and adolescents with spinal muscular atrophy I-III, aged 6.0-18.11 years, 45 non-affected siblings and 59 healthy, matched controls were examined with one- (CPM/SPM), as well as multi-dimensional intelligence tests (Kaufman-ABC; Wechsler tests) [5].
  • The patients showed a significant memory deficit, both in Recognition Memory for Words (RMW) and Recognition Memory for Faces (RMF), even when the scores were corrected for verbal intelligence score (WAIS Vocabulary) or a measure of visuoperceptual ability (Raven's Coloured Progressive Matrices, CPM) [6].
  • It was observed that CPM caused little or no pain and elicited excellent patient compliance [7].

High impact information on CPM

  • This CPM induction was specifically enhanced by CD19 or CD40 ligation [8].
  • CD40 + BCR stimulation of resting B cells with CD40 ligand-transfected fibroblastic cells in the presence of cross-linked anti-BCR monoclonal antibodies resulted in the coexpression of CD38, CD95, and CPM [8].
  • In the present study, we report that the platelet-derived alpha-chemokine platelet factor 4 (PF4) induces the differentiation of monocytes into macrophages, as is evident from morphological changes as well as from the up-regulation of differentiation markers (carboxypeptidase M/MAX1 and CD71) [9].
  • RA suppressed the expression of the maturation-associated antigen carboxypeptidase M (CPM)/MAX.1 at both the protein and mRNA levels and modulated the lipopolysaccharide-stimulated cytokine secretion of MO/MAC [10].
  • Thus, the hydrolysis of hemoglobin by CPM and CPN demonstrated the contribution of the alpha-Arg141 residue to sustaining the tetrameric structure of hemoglobin and its normal oxygen affinity and vasoactivity [11].

Chemical compound and disease context of CPM

  • Case>We describe here a case of CPM that occurred in a young patient after correction of hyponatremia, its treatment by intravenous thyrotropin-releasing hormone, and its outcome [12].
  • As determined by MICs, the resistance to tested antibiotics in E. coli O157 isolates was found to AMS (90.9%), CLZ (81.8%), CRX (63.6%), CXT (72.7%), CPM (72.7%), TET (81.8%), SAM (59.1%), COT (9.1%), COL (63.61%), AZT (9%) and GEN (4.5%) [13].

Biological context of CPM

  • This locus, however, does not appear to correspond to the PTPRR or CPM, although a contribution of mutations in regulatory regions cannot be excluded at this time [14].
  • Modelling of the C-terminal part of the natural substrate Arg(6)-Met-enkephalin into the active site shows that the S1' pocket of CPM is particularly well designed to accommodate P1'-Arg residues, in agreement with the preference of CPM for cleaving C-terminal Arg [15].
  • Both forms had lower molecular masses (50 kDa) than native placental CPM (62 kDa), indicating minimal glycosylation [16].
  • The identity of the basic carboxypeptidase activity with CPM was shown by similarities in subcellular localization, membrane attachment, substrate hydrolysis, inhibition by a specific basic carboxypeptidase inhibitor, and cross-reaction with anti-human CPM antiserum [17].
  • Physical map location of the human carboxypeptidase M gene (CPM) distal to D12S375 and proximal to D12S8 at chromosome 12q15 [18].

Anatomical context of CPM


Associations of CPM with chemical compounds

  • Of interest, CPM displayed a largely overlapping distribution with the CD10 and CD13 peptidases, with which it shares common substrates (enkephalins, bradykinin) [20].
  • Carboxypeptidase M (CPM), an extracellular glycosylphosphatidyl-inositol(GPI)-anchored membrane glycoprotein belonging to the CPN/E subfamily of "regulatory" metallo-carboxypeptidases, specifically removes C-terminal basic residues from peptides and proteins [15].
  • Consistent with results obtained in placenta and cultured kidney cells, CPM in the brain appears to be membrane-bound via a phosphatidylinositol glycan anchor [17].
  • The released CPM contained ethanolamine, indicating liberation by a phospholipase [21].
  • This was demonstrated by [3H)ethanolamine labeling of Madin Darby canine kidney (MDCK) cells which resulted in labeling of the membrane anchor of CPM as shown by immunoprecipitation, polyacrylamide gel electrophoresis and autoradiography [22].

Enzymatic interactions of CPM

  • CPM was also found in soluble form in biological fluids such as urine and amniotic fluid where it is the primary enzyme that hydrolyzes epidermal growth factor (EGF), producing des-Arg53-EGF [22].

Regulatory relationships of CPM

  • We found the known macrophage differentiation marker Carboxypeptidase M to be suppressed while CD14, HLA-DR, and CD16 were up-regulated [23].
  • A monoclonal antibody to the C-terminal beta-sheet domain of CPM reduced the B1R response to B2R agonists without inhibiting CPM [24].

Other interactions of CPM

  • However, if cells are activated by the lectins PWM or ConA or by double-stranded RNA (polyinosinic-polycytidylic acid, pI:C), normal MAC maturation is suppressed: MO stay small and do not acquire MAC maturation-associated surface molecules like carboxypeptidase M (CPM, determined by antibody MAX.1) or CD84 (determined by antibody MAX.3) [25].
  • In this study, purified carboxypeptidase M efficiently released the COOH-terminal arginine residue from EGF with a Km = 56 microM, kcat = 388 min-1, and kcat/Km = 6.9 microM-1 min-1 [26].
  • Although CPM belongs to the same metallocarboxypeptidase subfamily as CPE, their intron/exon structures differ significantly [27].
  • CPM as detected by MAX [28].
  • Three Thr residues at the distal TT edge of CPN1 are O-linked to N-acetyl glucosamine sugars; equivalent sites in the membrane-anchored CPM are occupied by basic residues probably involved in membrane interaction [29].

Analytical, diagnostic and therapeutic context of CPM


  1. Carboxypeptidase M activity is increased in bronchoalveolar lavage in human lung disease. Dragović, T., Schraufnagel, D.E., Becker, R.P., Sekosan, M., Votta-Velis, E.G., Erdös, E.G. Am. J. Respir. Crit. Care Med. (1995) [Pubmed]
  2. Central and extrapontine myelinolysis: then...and now. Kleinschmidt-Demasters, B.K., Rojiani, A.M., Filley, C.M. J. Neuropathol. Exp. Neurol. (2006) [Pubmed]
  3. Alterations of iodine-131 MIBG biodistribution in an anephric patient: comparison to normal and impaired renal function. Tobes, M.C., Fig, L.M., Carey, J., Geatti, O., Sisson, J.C., Shapiro, B. J. Nucl. Med. (1989) [Pubmed]
  4. Overlapping features of extrapontine myelinolysis and acquired chronic (non-Wilsonian) hepatocerebral degeneration. Kleinschmidt-Demasters, B.K., Filley, C.M., Rojiani, A.M. Acta Neuropathol. (2006) [Pubmed]
  5. Intelligence and cognitive function in children and adolescents with spinal muscular atrophy. von Gontard, A., Zerres, K., Backes, M., Laufersweiler-Plass, C., Wendland, C., Melchers, P., Lehmkuhl, G., Rudnik-Schöneborn, S. Neuromuscul. Disord. (2002) [Pubmed]
  6. Recognition memory for words and faces in primary degenerative dementia of the Alzheimer type and normal old age. Diesfeldt, H.F. Journal of clinical and experimental neuropsychology : official journal of the International Neuropsychological Society. (1990) [Pubmed]
  7. Continuous passive motion for prevention and rehabilitation of knee stiffness--(a clinical evaluation). Mullaji, A.B., Shahane, M.N. Journal of postgraduate medicine. (1989) [Pubmed]
  8. CD40 and B cell antigen receptor dual triggering of resting B lymphocytes turns on a partial germinal center phenotype. Galibert, L., Burdin, N., de Saint-Vis, B., Garrone, P., Van Kooten, C., Banchereau, J., Rousset, F. J. Exp. Med. (1996) [Pubmed]
  9. The CXC-chemokine platelet factor 4 promotes monocyte survival and induces monocyte differentiation into macrophages. Scheuerer, B., Ernst, M., Dürrbaum-Landmann, I., Fleischer, J., Grage-Griebenow, E., Brandt, E., Flad, H.D., Petersen, F. Blood (2000) [Pubmed]
  10. Retinoic acid inhibits monocyte to macrophage survival and differentiation. Kreutz, M., Fritsche, J., Ackermann, U., Krause, S.W., Andreesen, R. Blood (1998) [Pubmed]
  11. Removal of Arg141 from the alpha chain of human hemoglobin by carboxypeptidases N and M. Michel, B., Igić, R., Leray, V., Deddish, P.A., Erdös, E.G. Circ. Res. (1996) [Pubmed]
  12. Treatment of central pontine myelinolysis with thyrotropin-releasing hormone. Zein, E.M., Karaa, S.E., Rollot, F., Blanche, P., Chemaly, R.E. Presse médicale (Paris, France : 1983) (2006) [Pubmed]
  13. Occurrence of Escherichia coli O157 in raw material and food in Czech Republic. Lukásová, J., Abraham, B., Cupáková, S. J. Vet. Med. B Infect. Dis. Vet. Public Health (2004) [Pubmed]
  14. Type 2 diabetes locus on 12q15. Further mapping and mutation screening of two candidate genes. Bektas, A., Hughes, J.N., Warram, J.H., Krolewski, A.S., Doria, A. Diabetes (2001) [Pubmed]
  15. Crystal structure of human carboxypeptidase M, a membrane-bound enzyme that regulates peptide hormone activity. Reverter, D., Maskos, K., Tan, F., Skidgel, R.A., Bode, W. J. Mol. Biol. (2004) [Pubmed]
  16. Effect of mutation of two critical glutamic acid residues on the activity and stability of human carboxypeptidase M and characterization of its signal for glycosylphosphatidylinositol anchoring. Tan, F., Balsitis, S., Black, J.K., Blöchl, A., Mao, J.F., Becker, R.P., Schacht, D., Skidgel, R.A. Biochem. J. (2003) [Pubmed]
  17. Carboxypeptidase M in brain and peripheral nerves. Nagae, A., Deddish, P.A., Becker, R.P., Anderson, C.H., Abe, M., Tan, F., Skidgel, R.A., Erdös, E.G. J. Neurochem. (1992) [Pubmed]
  18. Physical map location of the human carboxypeptidase M gene (CPM) distal to D12S375 and proximal to D12S8 at chromosome 12q15. Kas, K., Schoenmakers, E.F., Van de Ven, W.J. Genomics (1995) [Pubmed]
  19. Kininase I-type carboxypeptidases enhance nitric oxide production in endothelial cells by generating bradykinin B1 receptor agonists. Sangsree, S., Brovkovych, V., Minshall, R.D., Skidgel, R.A. Am. J. Physiol. Heart Circ. Physiol. (2003) [Pubmed]
  20. Distribution of carboxypeptidase M on lymphoid and myeloid cells parallels the other zinc-dependent proteases CD10 and CD13. de Saint-Vis, B., Cupillard, L., Pandrau-Garcia, D., Ho, S., Renard, N., Grouard, G., Duvert, V., Thomas, X., Galizzi, J.P., Banchereau, J. Blood (1995) [Pubmed]
  21. Release of glycosylphosphatidylinositol-anchored carboxypeptidase M by phosphatidylinositol-specific phospholipase C upregulates enzyme synthesis. Li, X.Y., Skidgel, R.A. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  22. Membrane anchoring and release of carboxypeptidase M: implications for extracellular hydrolysis of peptide hormones. Skidgel, R.A., McGwire, G.B., Li, X.Y. Immunopharmacology (1996) [Pubmed]
  23. Identification of genes expressed in tumor-associated macrophages. Gottfried, E., Faust, S., Fritsche, J., Kunz-Schughart, L.A., Andreesen, R., Miyake, K., Kreutz, M. Immunobiology (2003) [Pubmed]
  24. Carboxypeptidase M and kinin B1 receptors interact to facilitate efficient b1 signaling from B2 agonists. Zhang, X., Tan, F., Zhang, Y., Skidgel, R.A. J. Biol. Chem. (2008) [Pubmed]
  25. Activation of lymphocytes inhibits human monocyte to macrophage differentiation. Krause, S.W., Zaiss, M., Kreutz, M., Andreesen, R. Immunobiology (2001) [Pubmed]
  26. Extracellular conversion of epidermal growth factor (EGF) to des-Arg53-EGF by carboxypeptidase M. McGwire, G.B., Skidgel, R.A. J. Biol. Chem. (1995) [Pubmed]
  27. Structure of the human carboxypeptidase M gene. Identification of a proximal GC-rich promoter and a unique distal promoter that consists of repetitive elements. Li, J., Rehli, M., Timblin, B., Tan, F., Krause, S.W., Skidgel, R.A. Gene (2002) [Pubmed]
  28. The membrane-bound ectopeptidase CPM as a marker of macrophage maturation in vitro and in vivo. Rehli, M., Krause, S.W., Andreesen, R. Adv. Exp. Med. Biol. (2000) [Pubmed]
  29. Crystal structure of the human carboxypeptidase N (kininase I) catalytic domain. Keil, C., Maskos, K., Than, M., Hoopes, J.T., Huber, R., Tan, F., Deddish, P.A., Erdös, E.G., Skidgel, R.A., Bode, W. J. Mol. Biol. (2007) [Pubmed]
  30. Molecular cloning and sequencing of the cDNA for human membrane-bound carboxypeptidase M. Comparison with carboxypeptidases A, B, H, and N. Tan, F., Chan, S.J., Steiner, D.F., Schilling, J.W., Skidgel, R.A. J. Biol. Chem. (1989) [Pubmed]
  31. High concentration of carboxypeptidase M in lungs: presence of the enzyme in alveolar type I cells. Nagae, A., Abe, M., Becker, R.P., Deddish, P.A., Skidgel, R.A., Erdös, E.G. Am. J. Respir. Cell Mol. Biol. (1993) [Pubmed]
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