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Gene Review

Uhmk1  -  U2AF homology motif (UHM) kinase 1

Mus musculus

Synonyms: 4732477C12Rik, 4930500M09Rik, AA673513, AI449218, AU021979, ...
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Disease relevance of Uhmk1

  • E. coli MntH had a similar inhibition profile, except that Kis were three- to 10-fold higher [1].
  • This study investigated whether the anti-inflammatory effect of interleukin-10 (IL-10) when expressed by a recombinant adenoviral vector can prevent the onset of glomerulosclerosis in FGS/Kist mice (an animal model with naturally occurring renal failure initiated by FSGS) [2].
  • For herpes simplex virus type 1- and 2-encoded thymidine kinases, the Kis were 0.6 and 0.74 microM, respectively [3].
  • Except for the epistatic interaction effect of Ptnu4 and Ptnu5, all alleles derived from FGS/Kist were responsible for the high proteinuria [4].
  • The interaction of the 5'-triphosphate of CS-92 with HIV-1 reverse transcriptase indicated competitive inhibition (the inhibition constant, Kis, was 0.0093 microM) with a 30-fold greater affinity for CS-92-TP than for ddCTP [5].

High impact information on Uhmk1

  • The Kis for l-methionine-S-sulfoximine (MSOX), a highly potent ATP-dependent inactivator of GS, were considerably different such that the values are 0.067 and 0.124 mm for the short and long forms, respectively [6].
  • We present here the first identification of a serine/threonine kinase that possesses an RNP-type RNA recognition motif: KIS [7].
  • Altogether, these results suggest the implication of KIS in the control of trafficking and/or splicing of RNAs probably through phosphorylation of associated factors [7].
  • 5-Iodotubercidin, a non-competitive inhibitor (Kis = 9 nM, Ku = 20 nM) of adenosine kinase, prevented the above effects of c9Ado on lymphocyte function, c9ATP formation, and ATP levels [8].
  • We performed a genome-wide scan for quantitative trait loci (QTLs) affecting proteinuria in a population of 356 backcross progeny derived from a cross between FGS/Kist and the standard normal strain, C57BL/6J [4].

Chemical compound and disease context of Uhmk1

  • Non-competitive inhibition by PGI2-F or PGI2-Me of [3H]PGE2 binding to the cells, with apparent Kis of 1.29 microM and 1.13 microM, respectively, indicates the presence of different receptors for PGE2 and for PGI2-F or PGI2-Me in mastocytoma P-815 cells [9].

Biological context of Uhmk1

  • Furthermore, KIS gene expression increases dramatically during brain development [10].
  • Another function of KIS has recently been unravelled--it negatively regulates the cdk inhibitor p27Kip1 and thus promotes cell cycle progression through G1 [10].
  • All analogs with an intact or 3,4-dihydrogenated pyrido ring inhibited the enzyme competitively with apparent Kis at the micromolar range, but complete hydrogenation of the pyrido moiety abolished the inhibition [11].
  • KIS is designed for biology/pharmaceutical scientists to make learning and applying tracer kinetics fun and easy [12].

Anatomical context of Uhmk1

  • Interestingly, within the adult rat brain, KIS mRNA is enriched in several areas including the substantia nigra compacta and nuclei of the brain stem [10].

Associations of Uhmk1 with chemical compounds

  • The most effective inhibitor was N-acetyl-beta-D-glucopyranosylamine, which has Kis of 51 microM (muscle GPa), 30 microM (muscle GPb), 2.7 mM (liver GPa) and 4 mM (liver GPb) [13].
  • The organoselenium compound Ebselen was found to be a competitive inhibitor of human thioredoxin reductase (Ki 2.8 microM), while a number of organotellurium compounds were found to be noncompetitive inhibitors (Kis 2.3 to 35.2 microM) [14].
  • Pirfenidone suppressed the development of glomerulosclerosis in the FGS/Kist mouse [15].

Analytical, diagnostic and therapeutic context of Uhmk1

  • Quantitative RT-PCR reveals a ubiquitous but preferentially neural expression of the KIS gene in rat and human [10].
  • Immunofluorescence and biochemical analyses indicate that KIS overexpressed in HEK293 fibroblastic cells is partly targetted to the nucleus [7].
  • These results demonstrate that IL-10 effectively prevents the development of glomerulosclerosis in FGS/Kist mice, and IL-10 gene therapy may be of use for the treatment of renal failure [2].


  1. The NRAMP proteins of Salmonella typhimurium and Escherichia coli are selective manganese transporters involved in the response to reactive oxygen. Kehres, D.G., Zaharik, M.L., Finlay, B.B., Maguire, M.E. Mol. Microbiol. (2000) [Pubmed]
  2. Suppression of glomerulosclerosis by adenovirus-mediated IL-10 expression in the kidney. Choi, Y.K., Kim, Y.J., Park, H.S., Choi, K., Paik, S.G., Lee, Y.I., Park, J.G. Gene Ther. (2003) [Pubmed]
  3. Synthesis and biological effects of 2'-fluoro-5-ethyl-1-beta-D-arabinofuranosyluracil. Chou, T.C., Kong, X.B., Fanucchi, M.P., Cheng, Y.C., Takahashi, K., Watanabe, K.A., Fox, J.J. Antimicrob. Agents Chemother. (1987) [Pubmed]
  4. Quantitative trait loci for proteinuria in the focal glomerulosclerosis mouse model. Kim, E.H., Lee, C.H., Hyun, B.H., Suh, J.G., Oh, Y.S., Namikawa, T., Ishikawa, A. Mamm. Genome (2005) [Pubmed]
  5. Antiretroviral activity, biochemistry, and pharmacokinetics of 3'-azido-2',3'-dideoxy-5-methylcytidine. Schinazi, R.F., Chu, C.K., Eriksson, B.F., Sommadossi, J.P., Doshi, K.J., Boudinot, F.D., Oswald, B., McClure, H.M. Ann. N. Y. Acad. Sci. (1990) [Pubmed]
  6. N-terminal extension of canine glutamine synthetase created by splicing alters its enzymatic property. Shin, D., Park, C. J. Biol. Chem. (2004) [Pubmed]
  7. KIS is a protein kinase with an RNA recognition motif. Maucuer, A., Ozon, S., Manceau, V., Gavet, O., Lawler, S., Curmi, P., Sobel, A. J. Biol. Chem. (1997) [Pubmed]
  8. Inhibition of lymphocyte function by 9-deazaadenosine. Zimmerman, T.P., Deeprose, R.D., Wolberg, G., Stopford, C.R., Duncan, G.S., Miller, W.H., Miller, R.L., Lim, M.I., Ren, W.Y., Klein, R.S. Biochem. Pharmacol. (1983) [Pubmed]
  9. Effect of 7-fluoro prostacyclin, a stable prostacyclin analogue, on cAMP accumulation and prostaglandin binding in mastocytoma P-815 cells. Mizuno, Y., Ichikawa, A., Tomita, K. Prostaglandins (1983) [Pubmed]
  10. Quantitative RT-PCR reveals a ubiquitous but preferentially neural expression of the KIS gene in rat and human. Bièche, I., Manceau, V., Curmi, P.A., Laurendeau, I., Lachkar, S., Leroy, K., Vidaud, D., Sobel, A., Maucuer, A. Brain Res. Mol. Brain Res. (2003) [Pubmed]
  11. Contribution of pi-electrons to the inhibition of S-adenosyl-L-methionine decarboxylase by aromatic tricyclic compounds. Lapinjoki, S.P., Gynther, J. Biochem. Int. (1986) [Pubmed]
  12. An internet-based "kinetic imaging system" (KIS) for MicroPET. Huang, S.C., Truong, D., Wu, H.M., Chatziioannou, A.F., Shao, W., Wu, A.M., Phelps, M.E. Molecular imaging and biology : MIB : the official publication of the Academy of Molecular Imaging. (2005) [Pubmed]
  13. Effects of novel analogues of D-glucose on glycogen phosphorylase activities in crude extracts of liver and skeletal muscle. Board, M., Hadwen, M., Johnson, L.N. Eur. J. Biochem. (1995) [Pubmed]
  14. Diaryl chalcogenides as selective inhibitors of thioredoxin reductase and potential antitumor agents. Engman, L., Cotgreave, I., Angulo, M., Taylor, C.W., Paine-Murrieta, G.D., Powis, G. Anticancer Res. (1997) [Pubmed]
  15. Pirfenidone suppressed the development of glomerulosclerosis in the FGS/Kist mouse. Park, H.S., Bao, L., Kim, Y.J., Cho, I.H., Lee, C.H., Hyun, B.H., Margolin, S.B., Park, Y.H. J. Korean Med. Sci. (2003) [Pubmed]
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