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Gene Review

Klkb1  -  kallikrein B, plasma 1

Mus musculus

Synonyms: APS, Fletcher factor, Kal-3, Kal3, Kininogenin, ...
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Disease relevance of Klkb1

  • These results may have important implications for the design of new treatment strategies aimed at preventing recurrent thrombosis in patients with APS [1].
  • Phylogenetic analysis of APS reductase amplicons obtained from the stomach, middle small intestine, and cecum of neonatal mice revealed that Desulfotomaculum spp. may be a predominant SRB group in the neonatal mouse intestine [2].
  • The monoclonal antibody (mAb) SV5-Pk is used widely in a variety of procedures to detect recombinant proteins tagged with the Pk tag, a 14 amino acid sequence derived from the P and V proteins of the paramyxovirus Simian Virus 5 [3].
  • The rat chondrosarcoma ATP sulfurylase and APS kinase activities, in fact, reside in a single bifunctional cytoplasmic protein, which has now been cloned and expressed [4].
  • In the tumor pathology, the incidence of hepatocellular carcinoma was significantly decreased in the males in the 10% APS treated group [5].

High impact information on Klkb1

  • Incorporation of 35SO42- into adenosine 5'-phosphosulfate (APS), 3'-phosphoadenosine 5'-phosphosulfate (PAPS), and chondroitin sulfate was simultaneously assessed with extracts prepared from epiphyseal cartilage of neonatal normal or homozygous brachymorphic mice [6].
  • Specific assays for ATP sulfurylase (sulfate adenylyltransferase; ATP:sulfate adenylyltransferase, EC and APS kinase (adenylylsulfate kinase; ATP:adenylylsulfate 3'-phosphotransferase, EC showed that the sulfurylase enzyme activity is reduced to approximately 1/2 and the kinase to approxomately 1/14 in brachymorphic mice [6].
  • Radioactivity measured in APS, PAPS, and chondroitin sulfate of extracts from brachymorphic cartilage was approximately 300%, 9%, and 13% of the normal levels, respectively [6].
  • APS I is caused by mutations in the AIRE gene (autoimmune regulator), expressed in cells of the thymus and spleen, suggesting a role in central and peripheral tolerance [7].
  • Autoimmune polyendocrine syndrome type I (APS I) is an inherited recessive disorder with a progressive immunological destruction of many tissues including the adrenal cortex, the parathyroid glands, and the gonads [7].

Chemical compound and disease context of Klkb1


Biological context of Klkb1

  • We report the genetic map location of Kal3, bringing to 4 the number of genes with homologues on human 4q31-35 placed on the genetic map of mouse chromosome 8 [9].
  • APS-facilitated phosphorylation occurred on tyrosines 371, 700, and 774 in the Cbl protein [10].
  • Murine adenosine 3'-phosphate 5'-phosphosulfate (PAPS) synthetase consists of a COOH-terminal ATP-sulfurylase domain covalently linked through a nonhomologous intervening sequence to an NH2-terminal adenosine 5'-phosphosulfate (APS) kinase domain forming a bifunctional fused protein [11].
  • A Cbl mutant incapable of dimerization failed to interact with APS and to undergo tyrosine phosphorylation in response to insulin, indicating an essential role of Cbl dimerization in these processes [12].
  • Lastly, isotope dilution and enrichment experiments show directly that the APS binding sites of the mutant enzymes are more accessible to free APS than are those of the normal enzymes [13].

Anatomical context of Klkb1

  • APS facilitates c-Cbl tyrosine phosphorylation and GLUT4 translocation in response to insulin in 3T3-L1 adipocytes [10].
  • APS colocalized with filamentous actin (F-actin) accumulated during the capping of BCRs in APS-transgenic B cells [14].
  • While experiments using cultured cell lines have demonstrated that APS is phosphorylated in response to various stimuli, its in vivo functions remain unclear [14].
  • Moreover, the translocation of GLUT4 from intracellular vesicles to the plasma membrane was also inhibited by overexpression of the APS/Y(618)F mutant [10].
  • Immunologically, APS(-/-) mice showed normal development and distribution of lymphocytes and myeloid cells, except for increased numbers of B-1 cells in the peritoneal cavity [14].

Associations of Klkb1 with chemical compounds


Other interactions of Klkb1


Analytical, diagnostic and therapeutic context of Klkb1

  • Reverse transcriptase PCR analysis demonstrated APS reductase mRNA expression in all intestinal segments of 30-day-old mice, including the stomach [2].
  • All the SV5-Pk mAbs can detect Pk tagged recombinant proteins in a variety of immunological procedures, including ELISA and immunofluorescence [3].
  • Light and dark field autoradiography of semithin sections prepared 6 h after a treatment with APS showed that the incorporation of H3-leucine into the cells of the convoluted tubules of the kidney was increased in mice [8].
  • The survival rates at the end of the dosing period were 73.3% (male) and 78.3% (female) in the control group, and 86.7-95.0% (male) and 86.7-91.7% (female) in the APS treated groups [5].


  1. Inhibition of the thrombogenic and inflammatory properties of antiphospholipid antibodies by fluvastatin in an in vivo animal model. Ferrara, D.E., Liu, X., Espinola, R.G., Meroni, P.L., Abukhalaf, I., Harris, E.N., Pierangeli, S.S. Arthritis Rheum. (2003) [Pubmed]
  2. Molecular ecological analysis of the succession and diversity of sulfate-reducing bacteria in the mouse gastrointestinal tract. Deplancke, B., Hristova, K.R., Oakley, H.A., McCracken, V.J., Aminov, R., Mackie, R.I., Gaskins, H.R. Appl. Environ. Microbiol. (2000) [Pubmed]
  3. Fine mapping of the binding sites of monoclonal antibodies raised against the Pk tag. Dunn, C., O'Dowd, A., Randall, R.E. J. Immunol. Methods (1999) [Pubmed]
  4. Sulfate activation and transport in mammals: system components and mechanisms. Schwartz, N.B., Lyle, S., Ozeran, J.D., Li, H., Deyrup, A., Ng, K., Westley, J. Chem. Biol. Interact. (1998) [Pubmed]
  5. Chronic toxicity and tumorigenicity study of aluminum potassium sulfate in B6C3F1 mice. Oneda, S., Takasaki, T., Kuriwaki, K., Ohi, Y., Umekita, Y., Hatanaka, S., Fujiyoshi, T., Yoshida, A., Yoshida, H. In Vivo (1994) [Pubmed]
  6. Defect in 3'-phosphoadenosine 5'-phosphosulfate formation in brachymorphic mice. Sugahara, K., Schwartz, N.B. Proc. Natl. Acad. Sci. U.S.A. (1979) [Pubmed]
  7. Aire-deficient mice develop hematopoetic irregularities and marginal zone B-cell lymphoma. Hässler, S., Ramsey, C., Karlsson, M.C., Larsson, D., Herrmann, B., Rozell, B., Backheden, M., Peltonen, L., Kämpe, O., Winqvist, O. Blood (2006) [Pubmed]
  8. Incorporation of H3-leucine in the mouse kidney in thrombocytopenia. Attempt to demonstrate thrombopoietin production. Krizsa, F., Cserháti, I., Halász, N., Joó, F. Acta Haematol. (1977) [Pubmed]
  9. Mouse myodystrophy (myd) mutation: refined mapping in an interval flanked by homology with distal human 4q. Mathews, K.D., Mills, K.A., Bailey, H.L., Schelper, R.L., Murray, J.C. Muscle Nerve (1995) [Pubmed]
  10. APS facilitates c-Cbl tyrosine phosphorylation and GLUT4 translocation in response to insulin in 3T3-L1 adipocytes. Liu, J., Kimura, A., Baumann, C.A., Saltiel, A.R. Mol. Cell. Biol. (2002) [Pubmed]
  11. Activity and stability of recombinant bifunctional rearranged and monofunctional domains of ATP-sulfurylase and adenosine 5'-phosphosulfate kinase. Deyrup, A.T., Krishnan, S., Singh, B., Schwartz, N.B. J. Biol. Chem. (1999) [Pubmed]
  12. The roles of Cbl-b and c-Cbl in insulin-stimulated glucose transport. Liu, J., DeYoung, S.M., Hwang, J.B., O'Leary, E.E., Saltiel, A.R. J. Biol. Chem. (2003) [Pubmed]
  13. Sulfate-activating enzymes in normal and brachymorphic mice: evidence for a channeling defect. Lyle, S., Stanczak, J.D., Westley, J., Schwartz, N.B. Biochemistry (1995) [Pubmed]
  14. Increased numbers of B-1 cells and enhanced responses against TI-2 antigen in mice lacking APS, an adaptor molecule containing PH and SH2 domains. Iseki, M., Kubo, C., Kwon, S.M., Yamaguchi, A., Kataoka, Y., Yoshida, N., Takatsu, K., Takaki, S. Mol. Cell. Biol. (2004) [Pubmed]
  15. Increased insulin sensitivity and hypoinsulinemia in APS knockout mice. Minami, A., Iseki, M., Kishi, K., Wang, M., Ogura, M., Furukawa, N., Hayashi, S., Yamada, M., Obata, T., Takeshita, Y., Nakaya, Y., Bando, Y., Izumi, K., Moodie, S.A., Kajiura, F., Matsumoto, M., Takatsu, K., Takaki, S., Ebina, Y. Diabetes (2003) [Pubmed]
  16. Cross-talk between the two divergent insulin signaling pathways is revealed by the protein kinase B (Akt)-mediated phosphorylation of adapter protein APS on serine 588. Katsanakis, K.D., Pillay, T.S. J. Biol. Chem. (2005) [Pubmed]
  17. Deletion and site-directed mutagenesis of the ATP-binding motif (P-loop) in the bifunctional murine ATP-sulfurylase/adenosine 5'-phosphosulfate kinase enzyme. Deyrup, A.T., Krishnan, S., Cockburn, B.N., Schwartz, N.B. J. Biol. Chem. (1998) [Pubmed]
  18. Crystal structure of adenosine 5'-phosphosulfate kinase from Penicillium chrysogenum. MacRae, I.J., Segel, I.H., Fisher, A.J. Biochemistry (2000) [Pubmed]
  19. The Ant1 gene maps near Klk3 on proximal mouse chromosome 8. Mills, K.A., Ellison, J.W., Mathews, K.D. Mamm. Genome (1996) [Pubmed]
  20. Effects of a highly selective plasma kallikrein inhibitor on collagen-induced arthritis in mice. Fujimori, Y., Nakamura, T., Shimizu, K., Yamamuro, T., Wanaka, K., Okamoto, S., Katsuura, Y. Agents Actions (1993) [Pubmed]
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