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Gene Review

PROC  -  protein C (inactivator of coagulation...

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Disease relevance of PROC

  • In analogy with the ribonucleotide reductase system of Escherichia coli this protein was called glutaredoxin [Holmgren, A. (1976) Proc. Natl. Acad. Sci. USA 73, 2275-2279] [1].
  • We recently have shown that binding of foot-and-mouth disease virus (FMDV) to cells in culture requires an arginine-glycine-aspartic acid (RGD) sequence in the G-H loop of the capsid protein VP1 (P. W. Mason, E. Rieder, and B. Baxt, Proc. Natl. Acad. Sci. USA 91:1932-1936, 1994) [2].
  • (1) Removal of a carboxyl at residue 132 of subunit I of Rhodobacter sphaeroides cytochrome c oxidase significantly inhibits electron transfer and makes proton pumping undetectable [Fetter et al. (1995) Proc. Natl. Acad. Sci. USA 92, 1604-1608] [3].
  • The molecular weight of in vitro translated type IV adenylyl cyclase was 110,000, similar to that for type IV adenylyl cyclase produced in the baculovirus system [B. Gao and A. G. Gilman, (1991) Proc. Natl. Acad. Sci. USA 88, 10178-10182] [4].
  • (1999, Proc. Natl. Acad. Sci. USA 2645-2650) to inhibit endothelial cell proliferation and angiogenesis, both in vivo and in vitro, and to inhibit metastasis of a wide variety of tumors in vivo [5].

High impact information on PROC

  • Ascorbic acid in soluble extracts of neural tissue can account for the increase in surface acetylcholine receptors (AChR's) seen on L5 myogenic cells treated with crude brain extract (Knaack, D., and T. R. Podleski, 1985, Proc. Natl. Acad. Sci. USA., 82:575-579) [6].
  • An 11S protein composed of six polypeptide chains was previously purified from a salt extract of dog pancreas microsomal membranes and shown to be required for translocation of nascent secretory protein across the microsomal membrane (Wistar and Blobel 1980 Proc. Natl. Acad. Sci. U. S. A. 77:7112-7116) [7].
  • We previously proposed that the GTP complex of this protein regulates the cyclic GMP phosphodiesterase and that it may be the first amplified intermediate in visual excitation [Fung, B. K.-K. & Stryer, L. (1980) Proc. Natl. Acad. Sci. USA 77, 2500-2504] [8].
  • It has been shown previously that serotonin stimulates the production of prostacyclin by bovine aortic smooth muscle cells in culture, via 5-HT2 receptors (Coughlin SR, Moskowitz MA, Antoniades HN, Levine L. Proc Natl Acad Sci USA 1981;78:7134-7138) [9].
  • p36, a major in vivo substrate of protein-tyrosine kinases, is shown to be phosphorylated at serine 25, a site very close to the major site of tyrosine phosphorylation by pp60v-src, tyrosine 23 (J. R. Glenney, Jr., and B. F. Tack, Proc. Natl. Acad. Sci. USA 82:7884-7888, 1985) [10].

Biological context of PROC

  • The SAS statistical procedure PROC MIXED, with an autoregressive covariance structure, was used to quantify the effect of CM and several other control variables (herd, calving season, parity, month of lactation, J-5 vaccination status, and other diseases) on weekly milk yield [11].
  • The catalytic subunit of the branched-chain alpha-keto acid dehydrogenase (BCKDH) phosphatase (Damuni, Z., Merryfield, M.L., Humphreys, J.S., and Reed, L.J., (1984) Proc. Natl. Acad. Sci. U.S.A. 81, 4335-4338) has been purified over 50,000-fold from extracts of bovine kidney mitochondria [12].
  • Bovine brain kinesin binds ADP tightly and contains a stoichiometric amount of ADP at its active site when isolated in the presence of free Mg2+ (Hackney, D. D. (1988) Proc. Natl. Acad. Sci. U.S.A. 85, 6314-6318) [13].
  • We also showed that the enzyme displays sigmoidal kinetics toward phosphatidic acid substrates in Triton X-100 mixed micelle assay system (Higgs, H.N., and Glomset J.A. (1994) Proc. Natl. Acad. Sci. U.S.A. 91, 9574-9578) [14].
  • The amino acid sequence of UP1 (Williams, K. R., Stone, K. L., LoPresti, M. B., Merrill, B. M., and Planck, S. R. (1985) Proc. Natl. Acad. Sci. U. S. A. 82, 5666-5670) reveals that UP1 contains 195 amino acids, including one dimethylarginine residue near its COOH terminus [15].

Anatomical context of PROC

  • Mitotic inhibition results, at least in part, from stabilization of growing and shortening dynamics, specifically at the plus ends of microtubules, by the binding of very few Taxol molecules to the microtubule surface (M. A. Jordan et al., Proc. Natl. Acad. Sci. USA, 90: 9552-9556, 1993; W. B. Derry et al., Biochemistry, 34: 2203-2211, 1995) [16].
  • In previous work ( Papazian , D., H. Rahamimoff , and S. M. Goldin (1979) Proc. Natl. Acad. Sci. U. S. A. 76: 3708-3712), an ATP-dependent calcium transport activity derived from rat brain synaptosomes was reconstituted into artificial lipid vesicles and substantially purified by transport-specific fractionation [17].
  • Coated vesicles were isolated from rat liver by a modification of the procedure described by Nandi et al. for bovine brain (Proc. Natl. Acad. Sci. U.S.A. 1982; 79:5881-5885) [18].
  • Cultured bovine aortic endothelial cells are associated with an unusually stable fibrinolytic inhibitor (Loskutoff, D.J., van Mourik, J.A., Erickson, L.A., and Lawrence, D. (1983) Proc. Natl. Acad. Sci. U.S.A. 80, 2956-2960) [19].
  • The ATP-dependent proton pump which was previously identified in clathrin-coated vesicles isolated from calf brain (Forgac, M., Cantley, L., Wiedenmann, B., Altstiel, L., and Branton, D. (1983) Proc. Natl. Acad. Sci. U.S.A. 80, 1300-1303) is further characterized [20].

Associations of PROC with chemical compounds

  • Thus, in cultured animal cells, this alkaloid causes an increase in the surface content of high mannose glycoproteins and a decrease in the amount of complex type glycoproteins (Elbein, A. D., Solf, R., Dorling, P. R., and Vosbeck, K. (1982) Proc. Natl. Acad. Sci. U. S. A., 78, 7393-7397) [21].
  • Cysteine residues 110 and 187 are essential for the formation of the correct bovine rhodopsin structure (Karnik, S. S., Sakmar, T. P., Chen, H.-B., and Khorana, H. G. (1988) Proc. Natl. Acad. Sci. U. S. A. 85, 8459-8463) [22].
  • This peptide has been shown to contain the vitamin K-dependent modification required for Ca2+ binding (Nelsestuen, G. L., and Suttie, J. W. (1973) Proc. Natl. Acad. Sci. U. S. A. 70, 3366-3370) and the modified amino acid, gamma-carboxyglutamic acid (Nelsestuen, G. L., Zytkovicz, T., and Howard, J. B. (1974) J. Biol. Chem. 249, 6347-6350) [23].
  • The conformation of the dephosphorylated 10 S monomer is highly unusual in that the 1500 A long myosin tail is folded into approximately equal thirds (Onishi, H., and Wakabayashi, T. (1982) J. Biochem. (Tokyo) 92, 871-879; Trybus, K. M., Huiatt, T. W., and Lowey, S. (1982) Proc. Natl. Acad. Sci. U. S. A. 79, 6151-6155) [24].
  • The DnaK mutant T199A which lacks the threonine residue that is essential for ATP hydrolysis and autophosphorylation activity (McCarty, J. S., and Walker, G. C. (1991) Proc. Natl. Acad. Sci. U. S. A. 88, 9513-9517) shows nearly identical properties to the wild type in the presence or absence of nucleotides [25].

Analytical, diagnostic and therapeutic context of PROC

  • Immunological data revealed that the 42- and 43-kDa proteins were related to alpha-subunits of the Gq class recently purified from brain (Pang, I.-H., and Sternweis, P. C. (1990) J. Biol. Chem. 265, 18707-18712) and identified by molecular cloning (Strathmann, M., and Simon, M. I. (1990) Proc. Natl. Acad. Sci. U. S. A. 87, 9113-9117) [26].
  • This work broadens the scope and improves the time resolution of spin-probe oximetry, a technique in which small nitroxide spin probes detect oxygen consumption via change in their relaxation properties [Froncisz, W., Lai, C.-S., & Hyde, J. S. (1985) Proc. Natl. Acad. Sci. U.S.A. 82, 411-415] [27].


  1. Glutathione-dependent hydrogen donor system for calf thymus ribonucleoside-diphosphate reductase. Luthman, M., Eriksson, S., Holmgren, A., Thelander, L. Proc. Natl. Acad. Sci. U.S.A. (1979) [Pubmed]
  2. Animal-derived antigenic variants of foot-and-mouth disease virus type A12 have low affinity for cells in culture. Rieder, E., Baxt, B., Mason, P.W. J. Virol. (1994) [Pubmed]
  3. Fatty acids stimulate activity and restore respiratory control in a proton channel mutant of cytochrome c oxidase. Fetter, J., Sharpe, M., Qian, J., Mills, D., Ferguson-Miller, S., Nicholls, P. FEBS Lett. (1996) [Pubmed]
  4. Cell-free synthesis of functional type IV adenylyl cyclase. Warner, D.R., Basi, N.S., Rebois, R.V. Anal. Biochem. (1995) [Pubmed]
  5. Troponin I inhibits capillary endothelial cell proliferation by interaction with the cell's bFGF receptor. Feldman, L., Rouleau, C. Microvasc. Res. (2002) [Pubmed]
  6. Selective effects of ascorbic acid on acetylcholine receptor number and distribution. Knaack, D., Shen, I., Salpeter, M.M., Podleski, T.R. J. Cell Biol. (1986) [Pubmed]
  7. Translocation of proteins across the endoplasmic reticulum. I. Signal recognition protein (SRP) binds to in-vitro-assembled polysomes synthesizing secretory protein. Walter, P., Ibrahimi, I., Blobel, G. J. Cell Biol. (1981) [Pubmed]
  8. Flow of information in the light-triggered cyclic nucleotide cascade of vision. Fung, B.K., Hurley, J.B., Stryer, L. Proc. Natl. Acad. Sci. U.S.A. (1981) [Pubmed]
  9. Stimulation of aortic smooth muscle prostacyclin by serotonin: role of distinct receptors in contractile and synthetic states. Demolle, D., Van Coevorden, A., Boeynaems, J.M. Circ. Res. (1989) [Pubmed]
  10. The protein-tyrosine kinase substrate p36 is also a substrate for protein kinase C in vitro and in vivo. Gould, K.L., Woodgett, J.R., Isacke, C.M., Hunter, T. Mol. Cell. Biol. (1986) [Pubmed]
  11. Effect of pathogen-specific clinical mastitis on milk yield in dairy cows. Gröhn, Y.T., Wilson, D.J., González, R.N., Hertl, J.A., Schulte, H., Bennett, G., Schukken, Y.H. J. Dairy Sci. (2004) [Pubmed]
  12. Purification and properties of the catalytic subunit of the branched-chain alpha-keto acid dehydrogenase phosphatase from bovine kidney mitochondria. Damuni, Z., Reed, L.J. J. Biol. Chem. (1987) [Pubmed]
  13. Nucleotide-free kinesin hydrolyzes ATP with burst kinetics. Hackney, D.D., Malik, A.S., Wright, K.W. J. Biol. Chem. (1989) [Pubmed]
  14. Purification and properties of a phosphatidic acid-preferring phospholipase A1 from bovine testis. Examination of the molecular basis of its activation. Higgs, H.N., Glomset, J.A. J. Biol. Chem. (1996) [Pubmed]
  15. High pressure liquid chromatography purification of UP1 and UP2, two related single-stranded nucleic acid-binding proteins from calf thymus. Merrill, B.M., LoPresti, M.B., Stone, K.L., Williams, K.R. J. Biol. Chem. (1986) [Pubmed]
  16. Low potency of taxol at microtubule minus ends: implications for its antimitotic and therapeutic mechanism. Derry, W.B., Wilson, L., Jordan, M.A. Cancer Res. (1998) [Pubmed]
  17. Purification and immunological characterization of a calcium pump from bovine brain synaptosomal vesicles. Chan, S.Y., Hess, E.J., Rahamimoff, H., Goldin, S.M. J. Neurosci. (1984) [Pubmed]
  18. Evidence for the presence of the asialoglycoprotein receptor in coated vesicles isolated from rat liver. Steer, C.J., Wall, D.A., Ashwell, G. Hepatology (1983) [Pubmed]
  19. Purification of an inhibitor of plasminogen activator (antiactivator) synthesized by endothelial cells. van Mourik, J.A., Lawrence, D.A., Loskutoff, D.J. J. Biol. Chem. (1984) [Pubmed]
  20. Characterization of the ATP-dependent proton pump of clathrin-coated vesicles. Forgac, M., Cantley, L. J. Biol. Chem. (1984) [Pubmed]
  21. Swainsonine prevents the processing of the oligosaccharide chains of influenza virus hemagglutinin. Elbein, A.D., Dorling, P.R., Vosbeck, K., Horisberger, M. J. Biol. Chem. (1982) [Pubmed]
  22. Assembly of functional rhodopsin requires a disulfide bond between cysteine residues 110 and 187. Karnik, S.S., Khorana, H.G. J. Biol. Chem. (1990) [Pubmed]
  23. Amino acid sequence of a vitamin K-dependent Ca2+-binding peptide from bovine prothrombin. Howard, J.B., Fausch, M.D. J. Biol. Chem. (1975) [Pubmed]
  24. Conformational states of smooth muscle myosin. Effects of light chain phosphorylation and ionic strength. Trybus, K.M., Lowey, S. J. Biol. Chem. (1984) [Pubmed]
  25. DnaK, hsp73, and their molten globules. Two different ways heat shock proteins respond to heat. Palleros, D.R., Reid, K.L., McCarty, J.S., Walker, G.C., Fink, A.L. J. Biol. Chem. (1992) [Pubmed]
  26. Purification and characterization of two G-proteins that activate the beta 1 isozyme of phosphoinositide-specific phospholipase C. Identification as members of the Gq class. Blank, J.L., Ross, A.H., Exton, J.H. J. Biol. Chem. (1991) [Pubmed]
  27. The method of time-resolved spin-probe oximetry: its application to oxygen consumption by cytochrome c oxidase. Jiang, J.J., Bank, J.F., Zhao, W.W., Scholes, C.P. Biochemistry (1992) [Pubmed]
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