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Gene Review

STK19  -  serine/threonine kinase 19

Homo sapiens

Synonyms: D6S60, D6S60E, G11, HLA-RP1, Protein G11, ...
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Disease relevance of STK19

  • The human SKI2W is located between the RD and RP1 genes in the class III region of the major histocompatibility complex (MHC) on chromosome 6, a genomic region associated with many malignant, genetic and autoimmune diseases [1].
  • The methodology makes use of the unique sequence of the G11 gene upstream of C4A and the sequence of a 6.4 kb retrotransposon, the human endogenous retrovirus HERV-K(C4), which is present in intron 9 of C4A but absent in the case of the deletion [2].
  • The G11 gene products of 41.5 and 30 kDa were expressed in insect cells using the baculovirus system and transiently in the mammalian cell line COS-7 [3].
  • Competitive ELISA indicated that the antiserum reacted with this peptide but that it showed minimal ability to recognize peptides which represent the equivalent regions of the pertussis toxin-insensitive G-proteins, Gq + G11, G12, G15 + G16, GL1 (also called G14) as Gz, and well as other G-proteins [4].
  • Pneumonectomy 1 (RP1) was a group of N0, intralobar N1, and skip metastasis involvement (N0-N2) [5].

High impact information on STK19

  • In membranes from these cells, stimulation of PI-PLC by BK is mediated by Gq and/or G11, two homologous, pertussis toxin-insensitive G proteins [6].
  • In membranes of human thyroid gland, we immunologically identified alpha subunits of the G proteins Gs short, Gs long, Gi1, Gi2, Gi3, G(o) (Go2 and another form of Go, presumably Go1), Gq, G11, G12, and G13 [7].
  • These studies indicate that gonadotrophin-releasing hormone receptor agonist-mediated down-regulation of Gq alpha/G11 alpha is a reflection of enhanced proteolysis of the activated G proteins [8].
  • Characterisation of the novel gene G11 lying adjacent to the complement C4A gene in the human major histocompatibility complex [9].
  • Characterisation of cDNA and genomic clones corresponding to the novel gene G11 has revealed that the gene spans approximately 9.1 kb of DNA and is split into 7 exons [9].

Chemical compound and disease context of STK19


Biological context of STK19

  • The RP1 gene contains nine exons [14].
  • The DNA sequence between human RD and RP1 was determined and the exon-intron structure of SKI2W elucidated [15].
  • The duplicated module contains an intact C4 gene as well as Cyp21 and Stk19 pseudogenes [16].
  • Several new members of the pancreatic lipase family have been reported recently, and amino acid sequence comparison reveals that this family can now be divided into three subgroups: (1) "classical" pancreatic lipases, (2) related proteins 1 (RP1), and (3) related proteins 2 (RP2) (Giller, T., et al. (1992) J. Biol. Chem. 267(23), 16509-16516) [17].
  • In one proband with the RP1 mutation, paternity was established by analyzing 24 short tandem repeat polymorphisms [18].

Anatomical context of STK19

  • The approximately 1.4 kb G11 mRNA, which is expressed in a number of different cell types including monocytes, hepatocytes, epithelial cells, T and B lymphocytes, encodes protein products of 254 or 258 amino acids due to differential use of two splice sites lying 12 bp apart at the end of exon 3 [9].
  • Immunofluorescence staining of transfected COS-7 cells transiently expressing G11 revealed that this novel Ser/Thr protein kinase is localized predominantly in the nucleus [3].
  • An enriched population of normal human promyelocytes and myelocytes was obtained from bone marrow using the monoclonal antibody WEM G11 and the fluorescence-activated cell sorter (FACS) [19].
  • This antibody 11.2 G11 does not react with B cells, lyses 50 to 60% of peripheral blood T cells, and precipitates a single chain protein with an apparent m.w. of 57,000 [20].
  • Two monoclonal IgG antibodies E11 and G11, which react with parathyroid and kidney tubule cells, are in the present communication demonstrated to immunostain the surface of cytotrophoblast cells in human placenta [21].

Associations of STK19 with chemical compounds

  • Members of SVA are also present in the complement C2 gene located about 20 kilobases upstream of RP1 in the HLA and in the cytochrome CYP1A1 gene [14].
  • RP1 (HGMW-approved symbol D6S60E) is located 611 bp upstream of C4 [15].
  • The G11 gene located in the major histocompatibility complex encodes a novel nuclear serine/threonine protein kinase [3].
  • The C5a chemoattractant factor receptor, when expressed in COS-7 cells, can stimulate phosphoinositide-specific phospholipase C activity through the activation of the G16 isoform of the heterotrimeric G protein, but not through the G11 isoform [22].
  • The internal loop adopts a unique fold with the purine ring of AMP intercalated between A10 and G11 in the complex [23].

Physical interactions of STK19


Other interactions of STK19

  • Four ubiquitously expressed genes, RD (D6S45)-SKI2W (SKIV2L)-DOM3Z-RP1 (D6S60E), are present between complement component genes factor B and C4 in the class III region of the HLA [15].
  • In addition, characterization of the 13-kb intergenic gap separating the RD (D6545) and G11 (D6S60E) genes has revealed the presence of a gene encoding a 1246-amino-acid polypeptide that shows significant sequence similarity to the yeast anti-viral Ski2p gene product [25].
  • Two of these mAbs (RP1/12 and RP2/19) selectively recognized mouse 300-19 pre-B cells that had been transfected with CD45 cDNA that contained exon C, suggesting that epitopes recognized by these mAbs are dependent on the expression of exon C [26].

Analytical, diagnostic and therapeutic context of STK19

  • Sequence analysis of a 1.5 kb segment of DNA flanking the C4B gene has revealed that 914 bp of the 3' end of the G11 gene also lies 611 bp from the transcriptional start site of the C4B gene.(ABSTRACT TRUNCATED AT 250 WORDS)[9]
  • It was found that after immunoprecipitation of the G11 polypeptides from recombinant baculovirus-infected insect cell lysates or transfected COS-7 cell lysates the immunoprecipitates contained a Mn2+-dependent protein kinase activity that phosphorylated alpha-casein at Ser/Thr residues and histone at Ser residues [3].
  • Deletion of the 2'-hydroxyl group at each of four sites (A10, G11, A24, and C25) was found to result in severe inhibition of cleavage activity (kcat/KM decreased by 100- to 1000-fold), although KM measurements and mobility-shift assays showed that substrate binding was not affected [27].
  • Isothermal titration calorimetry and fluorescence spectroscopy show that the thermodynamics of the binding of the APP-RP1 molecule to Abl-SH3 is comparable to that of the shorter RP1 peptide [28].
  • PCR amplification of reverse-transcribed K562 RNA followed by DNA sequencing showed that these cells express messages for both Gq alpha and G11 alpha [29].


  1. Human helicase gene SKI2W in the HLA class III region exhibits striking structural similarities to the yeast antiviral gene SKI2 and to the human gene KIAA0052: emergence of a new gene family. Dangel, A.W., Shen, L., Mendoza, A.R., Wu, L.C., Yu, C.Y. Nucleic Acids Res. (1995) [Pubmed]
  2. Long PCR detection of the C4A null allele in B8-C4AQ0-C4B1-DR3. Grant, S.F., Kristjánsdóttir, H., Steinsson, K., Blöndal, T., Yuryev, A., Stefansson, K., Gulcher, J.R. J. Immunol. Methods (2000) [Pubmed]
  3. The G11 gene located in the major histocompatibility complex encodes a novel nuclear serine/threonine protein kinase. Gomez-Escobar, N., Chou, C.F., Lin, W.W., Hsieh, S.L., Campbell, R.D. J. Biol. Chem. (1998) [Pubmed]
  4. Immunological identification of the alpha subunit of G13, a novel guanine nucleotide binding protein. Milligan, G., Mullaney, I., Mitchell, F.M. FEBS Lett. (1992) [Pubmed]
  5. Sleeve lobectomy versus pneumonectomy: tumor characteristics and comparative analysis of feasibility and results. Bagan, P., Berna, P., Pereira, J.C., Le Pimpec Barthes, F., Foucault, C., Dujon, A., Riquet, M. Ann. Thorac. Surg. (2005) [Pubmed]
  6. Bradykinin modulates potassium and calcium currents in neuroblastoma hybrid cells via different pertussis toxin-insensitive pathways. Wilk-Blaszczak, M.A., Gutowski, S., Sternweis, P.C., Belardetti, F. Neuron (1994) [Pubmed]
  7. The human thyrotropin receptor: a heptahelical receptor capable of stimulating members of all four G protein families. Laugwitz, K.L., Allgeier, A., Offermanns, S., Spicher, K., Van Sande, J., Dumont, J.E., Schultz, G. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  8. Gonadotrophin-releasing hormone receptor agonist-mediated down-regulation of Gq alpha/G11 alpha (pertussis toxin-insensitive) G proteins in alpha T3-1 gonadotroph cells reflects increased G protein turnover but not alterations in mRNA levels. Shah, B.H., MacEwan, D.J., Milligan, G. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  9. Characterisation of the novel gene G11 lying adjacent to the complement C4A gene in the human major histocompatibility complex. Sargent, C.A., Anderson, M.J., Hsieh, S.L., Kendall, E., Gomez-Escobar, N., Campbell, R.D. Hum. Mol. Genet. (1994) [Pubmed]
  10. NMR structure of the HIV-1 nucleocapsid protein bound to stem-loop SL2 of the psi-RNA packaging signal. Implications for genome recognition. Amarasinghe, G.K., De Guzman, R.N., Turner, R.B., Chancellor, K.J., Wu, Z.R., Summers, M.F. J. Mol. Biol. (2000) [Pubmed]
  11. Agonist-induced endocytosis of muscarinic cholinergic receptors: relationship to stimulated phosphoinositide turnover. Sorensen, S.D., McEwen, E.L., Linseman, D.A., Fisher, S.K. J. Neurochem. (1997) [Pubmed]
  12. A constitutively active mutant of the alpha 1B-adrenergic receptor can cause greater agonist-dependent down-regulation of the G-proteins G9 alpha and G11 alpha than the wild-type receptor. Lee, T.W., Wise, A., Cotecchia, S., Milligan, G. Biochem. J. (1996) [Pubmed]
  13. Adhesion of biodegradative anaerobic bacteria to solid surfaces. van Schie, P.M., Fletcher, M. Appl. Environ. Microbiol. (1999) [Pubmed]
  14. Structure and genetics of the partially duplicated gene RP located immediately upstream of the complement C4A and the C4B genes in the HLA class III region. Molecular cloning, exon-intron structure, composite retroposon, and breakpoint of gene duplication. Shen, L., Wu, L.C., Sanlioglu, S., Chen, R., Mendoza, A.R., Dangel, A.W., Carroll, M.C., Zipf, W.B., Yu, C.Y. J. Biol. Chem. (1994) [Pubmed]
  15. Four ubiquitously expressed genes, RD (D6S45)-SKI2W (SKIV2L)-DOM3Z-RP1 (D6S60E), are present between complement component genes factor B and C4 in the class III region of the HLA. Yang, Z., Shen, L., Dangel, A.W., Wu, L.C., Yu, C.Y. Genomics (1998) [Pubmed]
  16. The rat expresses two complement factor C4 proteins, but only one isotype is expressed in the liver. Roos, C., Dressel, R., Schmidt, B., Günther, E., Walter, L. J. Immunol. (2005) [Pubmed]
  17. Evidence for a pancreatic lipase subfamily with new kinetic properties. Thirstrup, K., Verger, R., Carrière, F. Biochemistry (1994) [Pubmed]
  18. De novo mutation in the RP1 gene (Arg677ter) associated with retinitis pigmentosa. Schwartz, S.B., Aleman, T.S., Cideciyan, A.V., Swaroop, A., Jacobson, S.G., Stone, E.M. Invest. Ophthalmol. Vis. Sci. (2003) [Pubmed]
  19. The clonal proliferation in vitro of enriched populations of human promyelocytes and myelocytes. Begley, C.G., Lopez, A.F., Vadas, M.A., Metcalf, D. Blood (1985) [Pubmed]
  20. Cytotoxic murine monoclonal antibody recognizing an ovine lymphocyte subpopulation similar to the human OKT4-positive set. Lalonde, G., Gershwin, L.J., Moore, P.F., Bernoco, D. J. Immunol. (1986) [Pubmed]
  21. 500-Kilodalton calcium sensor regulating cytoplasmic Ca2+ in cytotrophoblast cells of human placenta. Juhlin, C., Lundgren, S., Johansson, H., Lorentzen, J., Rask, L., Larsson, E., Rastad, J., Akerström, G., Klareskog, L. J. Biol. Chem. (1990) [Pubmed]
  22. Multiple regions of G alpha 16 contribute to the specificity of activation by the C5a receptor. Lee, C.H., Katz, A., Simon, M.I. Mol. Pharmacol. (1995) [Pubmed]
  23. RNA folding topology and intermolecular contacts in the AMP-RNA aptamer complex. Jiang, F., Fiala, R., Live, D., Kumar, R.A., Patel, D.J. Biochemistry (1996) [Pubmed]
  24. Chromosomal localization and promoter analysis of the adenomatous polyposis coli binding protein RP1. Wadle, A., Thiel, G., Mischo, A., Jung, V., Pfreundschuh, M., Renner, C. Oncogene (2001) [Pubmed]
  25. Localization of eight additional genes in the human major histocompatibility complex, including the gene encoding the casein kinase II beta subunit (CSNK2B). Albertella, M.R., Jones, H., Thomson, W., Olavesen, M.G., Campbell, R.D. Genomics (1996) [Pubmed]
  26. Human CD45RC specificity. A novel marker for T cells at different maturation and activation stages. Zapata, J.M., Pulido, R., Acevedo, A., Sánchez-Madrid, F., de Landázuri, M.O. J. Immunol. (1994) [Pubmed]
  27. Four ribose 2'-hydroxyl groups essential for catalytic function of the hairpin ribozyme. Chowrira, B.M., Berzal-Herranz, A., Keller, C.F., Burke, J.M. J. Biol. Chem. (1993) [Pubmed]
  28. A miniprotein scaffold used to assemble the polyproline II binding epitope recognized by SH3 domains. Cobos, E.S., Pisabarro, M.T., Vega, M.C., Lacroix, E., Serrano, L., Ruiz-Sanz, J., Martinez, J.C. J. Mol. Biol. (2004) [Pubmed]
  29. Ca2+ signalling in K562 human erythroleukaemia cells: effect of dimethyl sulphoxide and role of G-proteins in thrombin- and thromboxane A2-activated pathways. Thomas, C.P., Dunn, M.J., Mattera, R. Biochem. J. (1995) [Pubmed]
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