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Gene Review

LXN  -  latexin

Homo sapiens

Synonyms: ECI, Endogenous carboxypeptidase inhibitor, Latexin, Protein MUM, TCI, ...
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Disease relevance of LXN

  • Three of the genes, QPCT, CYP1B1, and LXN, are densely methylated in >95% of uncultured melanoma tumor samples [1].
  • An eosinophil cytotoxicity inhibitor (ECI) was purified from serum of a human subject with severe allergic dermatitis [2].
  • Serum antibodies to adenovirus (ADN), cytomegalovirus (CMV), herpes simplex virus (HSV), influenza (INF), para-influenza (PAR), mumps (MUM), coxsackie B4 (Cox B4) and B5 (Cox B5) viruses were measured from 584 individuals belonging to 21 Indiana Amish families [3].
  • Recombinant TCI expressed in Escherichia coli is fully functional and inhibits carboxypeptidases of the A/B subfamily with equilibrium dissociation constants in the nanomolar range [4].
  • Production of human T cell colony-inducing activity (TCI) by malignant cells from patients with lymphocytic and myeloid leukemia [5].

Psychiatry related information on LXN

  • CONCLUSION: TCI prediction of personality disorder is susceptible to state effects of depression [6].
  • They show that the ECI is a useful instrument in measuring the impact of caring for people with severe mental health problems [7].
  • Information on the relationship between anorexia nervosa (AN) and personality disorders (PDs) and dimensions of temperament and character (measured by the Temperament and Character Inventory [TCI; Cloninger, Przybeck Svrakic, & Wetzel, 1994]) is limited [8].

High impact information on LXN

  • Latexin is a newly discovered regulator of hematopoietic stem cells [9].
  • Apparently free C3 beta chain was detected in certain human biological fluids associated with inflammation; the presence of C3 beta chain correlated with ECI activity [2].
  • Thus, ECI did not act by preventing the initial interaction of TNF with eosinophils or by interfering with the binding of TNF to its receptor on L929 cells [10].
  • Rat TCII-B12 has an affinity constant that is less than one-fifth that of human TCII-B12; human TCI-B12, bovine TCII-B12, hog intrinsic factor-B12 (IF-B12), and human IF-B12 do not bind to the membranes [11].
  • Glipizide (10-100 muM) AND TOLBUTAMIDE (400 MUM) inhibited the stimulatory effect of glucose, dbcAMP, and theophylline on [3H]leucine incorporation into IRI [12].

Chemical compound and disease context of LXN


Biological context of LXN

  • The comparison between the deduced amino acid sequences of LXN and latexins of rat and mouse revealed high sequence identity (84.2 and 84.7%, respectively) [15].
  • The cDNA (LXN) contains an open reading frame encoding 222 amino acids [15].
  • In addition, the LXN gene contains at least 6 exons and spans 5.9 kb according to the genomic sequence of the clone RP11-79M21 and the gap sequence cloned in this paper [15].
  • It is noteworthy that the tissue distribution of human LXN differs greatly to that of its homologue in the model animal, rat latexin [15].
  • Major differences in the loop segments shaping the border of the funnel-like access to the protease active site impede complex formation with latexin [16].

Anatomical context of LXN

  • Northern blot analysis showed that LXN was expressed as a transcript of 1.3 kb in 15 out of 16 tissues examined, except in peripheral blood leukocyte [15].
  • In the neocortex, a specific subpopulation of neurons in layers V and VI expresses latexin [17].
  • Genomic organization and regulatory elements of the rat latexin gene, which is expressed in a cell type-specific manner in both central and peripheral nervous systems [17].
  • To assess promoter activity, the luciferase reporter gene fused to the 5'-flanking region (6.4 kb) of the latexin gene was transiently transfected into several cell lines [17].
  • The results suggest that ECI is a component of a feedback mechanism that suppresses functions of cytokine-activated eosinophils in inflammation [10].

Associations of LXN with chemical compounds

  • Deoxygenation reduced the HCO3- flux from 1.24 plus or minus 0.1 mum/h/8 cm2 (SEM) to 0.50 plus or minus 0.1 muM/h with glucose (2 times 10-3 M) AND FROM 1.32 PLUS OR MINUS TO 0.47 PLUS OR MINUS 0.1 MUM/h without glucose [18].
  • It has been observed that guanyl-5'-yl imidodiphosphate (Gpp(NH)p) (S0.5 = 10 MUM) significantly increased and Ca2+ (S0.5 = 0.5 MM) significantly decreased only the Vmax without affecting the Hill coefficient or S0.5 for ATP [19].
  • ECI, one of three isoforms of cysteine protease inhibitor found in chum salmon eggs was purified to homogeneity, and its complete amino acid sequence was determined [20].
  • Data base searches revealed that ovocalyxin-32 has limited identity (32%) to two unrelated proteins: latexin, a carboxypeptidase inhibitor expressed in the rat cerebral cortex and mast cells, and a skin protein, which is encoded by a retinoic acid receptor-responsive gene, TIG1 [21].
  • The full-length TCI cDNA contains an open reading frame coding for a precursor protein of 97 amino acid residues that consists of a predicted signal peptide of 22 residues and of mature TCI, a 75-residue cysteine-rich protein (12 Cys) [4].

Physical interactions of LXN

  • Such an inhibitory mode is evocative of the recently reported structure of the human inhibitor latexin in its complex with hCPA4 [22].

Other interactions of LXN


Analytical, diagnostic and therapeutic context of LXN

  • This suggests that ECI in serum can be stabilized in an inactive or partially active form and that HPLC removes the stabilizing component [10].
  • METHODS AND RESULTS: Immunological studies were performed in NYHA class IV patients awaiting cardiac transplantation who received either a TCI Heartmate left ventricular assist device (LVAD) or medical management [23].
  • METHODS AND RESULTS: To separate the effects of cardiopulmonary bypass (CPB), eight patients undergoing coronary revascularization (CABG) were compared with seven LVAD (TCI HeartMate) recipients intraoperatively and 2 hours postoperatively [24].
  • Structural analyses by circular dichroism and nuclear magnetic resonance indicate that TCI is a protein strongly constrained by disulfide bonds, unusually stable over a wide pH range and highly resistant to denaturing conditions [4].
  • The transcutaneous index (TCI = PtcO2/arterial oxygen tension [PaO2]) is known to depend both on age and on cardiac index but is assumed to be independent of other physiologic variables [25].


  1. Epigenetic silencing of novel tumor suppressors in malignant melanoma. Muthusamy, V., Duraisamy, S., Bradbury, C.M., Hobbs, C., Curley, D.P., Nelson, B., Bosenberg, M. Cancer Res. (2006) [Pubmed]
  2. Identification of C3 beta chain as the human serum eosinophil cytotoxicity inhibitor. Minkoff, M.S., Wong, W.W., Silberstein, D.S. J. Exp. Med. (1991) [Pubmed]
  3. Studies of viral antibody responses among Amish families. Hsia, S., Howell, D.N., Amos, D.B., Woodbury, M.A. J. Immunol. (1977) [Pubmed]
  4. A carboxypeptidase inhibitor from the tick Rhipicephalus bursa: isolation, cDNA cloning, recombinant expression, and characterization. Arolas, J.L., Lorenzo, J., Rovira, A., Castellà, J., Aviles, F.X., Sommerhoff, C.P. J. Biol. Chem. (2005) [Pubmed]
  5. Production of human T cell colony-inducing activity (TCI) by malignant cells from patients with lymphocytic and myeloid leukemia. Douer, D., Sachs, L. J. Immunol. (1979) [Pubmed]
  6. Personality disorder scores improve with effective pharmacotherapy of depression. Black, K.J., Sheline, Y.I. Journal of affective disorders. (1997) [Pubmed]
  7. Carers and community mental health services. Schneider, J., Carpenter, J., Wooff, D., Brandon, T., McNiven, F. Social psychiatry and psychiatric epidemiology. (2001) [Pubmed]
  8. Personality disorders and personality dimensions in anorexia nervosa. Karwautz, A., Troop, N.A., Rabe-Hesketh, S., Collier, D.A., Treasure, J.L. J. Personal. Disord. (2003) [Pubmed]
  9. Latexin is a newly discovered regulator of hematopoietic stem cells. de Haan, G. Nat. Genet. (2007) [Pubmed]
  10. A serum factor that suppresses the cytotoxic function of cytokine-stimulated human eosinophils. Silberstein, D.S., Minkoff, M.S., Creasey, A.A., David, J.R. J. Exp. Med. (1990) [Pubmed]
  11. A saturable high affinity binding site for transcobalamin II-vitamin B12 complexes in human placental membrane preparations. Friedman, P.A., Shia, M.A., Wallace, J.K. J. Clin. Invest. (1977) [Pubmed]
  12. Biosynthesis of proinsulin and insulin in newborn rat pancreas. Interaction of glucose, cyclic AMP, somatostatin, and sulfonylureas on the (3H) leucine incorporation into immunoreactive insulin. Garcia, S.D., Jarrousse, C., Rosselin, G. J. Clin. Invest. (1976) [Pubmed]
  13. Close relationship of tissue plasminogen activator-plasminogen activator inhibitor-1 complex with multiple organ dysfunction syndrome investigated by means of the artificial pancreas. Hoshino, M., Haraguchi, Y., Hirasawa, H., Sakai, M., Saegusa, H., Hayashi, K., Horita, N., Ohsawa, H. Critical care (London, England) (2001) [Pubmed]
  14. Polyribosome size analysis. Measurement of number-average polyribosome sizes. Fioretti, W.C., Davis, D.F., Ledford, B.E. Biochim. Biophys. Acta (1979) [Pubmed]
  15. Cloning, tissue expression pattern and genomic organization of latexin, a human homologue of rat carboxypeptidase A inhibitor. Liu, Q., Yu, L., Gao, J., Fu, Q., Zhang, J., Zhang, P., Chen, J., Zhao, S. Mol. Biol. Rep. (2000) [Pubmed]
  16. Structure of human carboxypeptidase A4 with its endogenous protein inhibitor, latexin. Pallarès, I., Bonet, R., García-Castellanos, R., Ventura, S., Avilés, F.X., Vendrell, J., Gomis-Rüth, F.X. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  17. Genomic organization and regulatory elements of the rat latexin gene, which is expressed in a cell type-specific manner in both central and peripheral nervous systems. Miyasaka, N., Hatanaka, Y., Jin, M., Arimatsu, Y. Brain Res. Mol. Brain Res. (1999) [Pubmed]
  18. Energy dependence of urinary bicarbonate secretion in turtle bladder. Oliver, J.A., Himmelstein, S., Steinmetz, P.R. J. Clin. Invest. (1975) [Pubmed]
  19. Mechanism of regulation of adenylate cyclase activity in human polymorphonuclear leukocytes by calcium, guanosyl nucleotides, and positive effectors. Stolc, V. J. Biol. Chem. (1977) [Pubmed]
  20. A novel cysteine protease inhibitor of the egg of chum salmon, containing a cysteine-rich thyroglobulin-like motif. Yamashita, M., Konagaya, S. J. Biol. Chem. (1996) [Pubmed]
  21. Ovocalyxin-32, a novel chicken eggshell matrix protein. isolation, amino acid sequencing, cloning, and immunocytochemical localization. Gautron, J., Hincke, M.T., Mann, K., Panheleux, M., Bain, M., McKee, M.D., Solomon, S.E., Nys, Y. J. Biol. Chem. (2001) [Pubmed]
  22. Detailed molecular comparison between the inhibition mode of A/B-type carboxypeptidases in the zymogen state and by the endogenous inhibitor latexin. García-Castellanos, R., Bonet-Figueredo, R., Pallarés, I., Ventura, S., Avilés, F.X., Vendrell, J., Gomis-Rütha, F.X. Cell. Mol. Life Sci. (2005) [Pubmed]
  23. Quantitative changes in T-cell populations after left ventricular assist device implantation: relationship to T-cell apoptosis and soluble CD95. Ankersmit, H.J., Edwards, N.M., Schuster, M., John, R., Kocher, A., Rose, E.A., Oz, M., Itescu, S. Circulation (1999) [Pubmed]
  24. Increased activation of the coagulation and fibrinolytic systems leads to hemorrhagic complications during left ventricular assist implantation. Livingston, E.R., Fisher, C.A., Bibidakis, E.J., Pathak, A.S., Todd, B.A., Furukawa, S., McClurken, J.B., Addonizio, V.P., Jeevanandam, V. Circulation (1996) [Pubmed]
  25. Hyperventilation reduces transcutaneous oxygen tension and skin blood flow. Barker, S.J., Hyatt, J., Clarke, C., Tremper, K.K. Anesthesiology (1991) [Pubmed]
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