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Chemical Compound Review

serine     (2S)-2-amino-3-hydroxy- propanoic acid

Synonyms: Serinum, Polyserine, Serene, Serina, L-serine, ...
 
 
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Disease relevance of L-serine

  • We identified three serine residues (S19, S33, and S35) on Chk2 that became phosphorylated in vivo rapidly and exclusively in response to ionizing radiation (IR)-induced DNA double-strand breaks in an ATM- and Nbs1-dependent but ataxia telangiectasia- and Rad3-related-independent manner [1].
  • We constructed, by site-directed mutagenesis, a mutant pullulanase gene in which the cysteine residue in a pentapeptide sequence, Leu16-Leu-Ser-Gly-Cys20 within the NH2-terminal region of pullulanase from Klebsiella aerogenes, is replaced by serine (Ser20) [2].
  • Monitoring of patients for the presence of new HIV-1 wild types with D, S, or N residues at position 215 may be warranted in order to estimate the threat to long-term efficacy of regimens including nucleoside analogues [3].
  • These data are the first to demonstrate tumor-specific expression of Ser/Thr kinase receptors mRNAs and their splice variants in human pituitary adenomas [4].
  • The polyserine tract of herpes simplex virus ICP4 is required for normal viral gene expression and growth in murine trigeminal ganglia [5].
 

Psychiatry related information on L-serine

 

High impact information on L-serine

 

Chemical compound and disease context of L-serine

 

Biological context of L-serine

  • An anti-Plk1 antibody depletes the M-phase extracts of the kinase activity toward S147 and/or S133 [10].
  • These data are consistent with a model in which splicing enhancers function by increasing the local concentration of SR proteins in the vicinity of the nearby intron through RNA looping [16].
  • Previously, we showed that SRrp86 could regulate alternative splicing by both positively and negatively modulating the activity of other SR proteins and that the unique EK domain could inhibit both constitutive and alternative splicing [17].
  • These findings underscore the critical roles of S19, S33, and S35 and argue that these phosphoresidues may serve to fine-tune the ATM-dependent response of Chk2 to increasing amounts of DNA damage [1].
  • The results presented here, in conjunction with previous studies, reveal a remarkably broad spectrum of RNA sequences capable of binding specific SR proteins and/or functioning as SR-specific splicing enhancers [18].
 

Anatomical context of L-serine

  • To examine the involvement of interchromatin granule clusters (IGCs) in transcription and pre-mRNA splicing in mammalian cell nuclei, the serine-arginine (SR) protein kinase cdc2-like kinase (Clk)/STY was used as a tool to manipulate IGC integrity in vivo [19].
  • We have recently identified a splicing "coactivator," SRm160/300, which contains SRm160 (the SR nuclear matrix protein of 160 kDa) and a 300-kDa nuclear matrix antigen [20].
  • Ras is required to recruit Raf-1 to the plasma membrane, which is where S338 phosphorylation occurs [21].
  • SLY1 was recently identified as an X-chromosomal SH3 protein that is serine phosphorylated (Ser27) upon B-and T-cell receptor engagement [22].
  • Moreover, MAPKs phosphorylate tau in vitro at Ser/Thr Proline sites, generating a multiply phosphorylated tau protein that is similar to the hyperphosphorylated tau found in Alzheimer neurofibrillary tangles (NFTs) [23].
 

Associations of L-serine with other chemical compounds

  • Although poly-serine and proline tracts exist near the CAG repeats, these polyserine or proline tracts did not show any polymorphisms, which is in strong contrast to the high heterogeneity in the length of the CAG repeat [24].
  • Compared to the wild-type form, Chk2 with alanine substitutions at S19, S33, and S35 (Chk2(S3A)) showed impaired dimerization, defective auto- and trans-phosphorylation activities, and reduced ability to promote degradation of Hdmx, a phosphorylation target of Chk2 and regulator of p53 activity [1].
  • Similarly, a Baka GPIIb cDNA expressing an isoleucine at amino acid 843 (IIe843) was modified to express the Bakb form containing a serine at the same position (Ser843) [25].
  • Moreover, using sucrose density gradient analysis, we provide evidence that the import receptor Mtr10p, but not the SR protein kinase Sky1p, is involved in the timely regulated release of Npl3p from polysome-associated mRNAs [26].
  • The phospho-CREB (P-CREB) phosphatase activity present in nuclear extracts coelutes with protein Ser/Thr phosphatase type 2A (PP2A) on Mono Q, amino-hexyl Sepharose, and heparin agarose columns and was chromatographically resolved from nuclear protein Ser/Thr-phosphatase type 1 (PP1) [27].
 

Gene context of L-serine

  • Therefore, S122 phosphorylation may provide a mechanism whereby the properties of TAL1 polypeptides can be modulated by extracellular stimuli [28].
  • The N-terminal region plays a crucial role in interaction of annexin 1 with other proteins and membranes, and therefore, phosphorylation of annexin 1 at Ser5 by TRPM7 kinase may modulate function of annexin 1 [29].
  • Functional phosphorylation of Bcl2 at Ser70 is proposed to be a dynamic process regulated by the sequential action of an agonist-activated Bcl2 kinase and PP2A [30].
  • Receptor interacting protein-2 (RIP2) contains an N-terminal domain with homology to Ser/Thr kinases and a C-terminal caspase activation and recruitment domain (CARD), a homophilic interaction motif that mediates the recruitment of caspase death proteases [31].
  • Our results suggest that the polyserine (S) domain is most likely the site of phosphorylation in ERD14 responsible for the activation of calcium binding [32].
 

Analytical, diagnostic and therapeutic context of L-serine

References

  1. DNA damage-induced cell cycle regulation and function of novel chk2 phosphoresidues. Buscemi, G., Carlessi, L., Zannini, L., Lisanti, S., Fontanella, E., Canevari, S., Delia, D. Mol. Cell. Biol. (2006) [Pubmed]
  2. Biosynthesis and secretion of pullulanase, a lipoprotein from Klebsiella aerogenes. Murooka, Y., Ikeda, R. J. Biol. Chem. (1989) [Pubmed]
  3. Establishment of new transmissible and drug-sensitive human immunodeficiency virus type 1 wild types due to transmission of nucleoside analogue-resistant virus. de Ronde, A., van Dooren, M., van Der Hoek, L., Bouwhuis, D., de Rooij, E., van Gemen, B., de Boer, R., Goudsmit, J. J. Virol. (2001) [Pubmed]
  4. Tumor-specific expression and alternate splicing of messenger ribonucleic acid encoding activin/transforming growth factor-beta receptors in human pituitary adenomas. Alexander, J.M., Bikkal, H.A., Zervas, N.T., Laws, E.R., Klibanski, A. J. Clin. Endocrinol. Metab. (1996) [Pubmed]
  5. The polyserine tract of herpes simplex virus ICP4 is required for normal viral gene expression and growth in murine trigeminal ganglia. Bates, P.A., DeLuca, N.A. J. Virol. (1998) [Pubmed]
  6. Allelic association analysis of the 5-HT2C receptor gene in bipolar affective disorder. Gutiérrez, B., Fañanás, L., Arranz, M.J., Vallès, V., Guillamat, R., van Os, J., Collier, D. Neurosci. Lett. (1996) [Pubmed]
  7. Behavior-related alterations of striatal neurochemistry in a mouse model of stereotyped movement disorder. Presti, M.F., Watson, C.J., Kennedy, R.T., Yang, M., Lewis, M.H. Pharmacol. Biochem. Behav. (2004) [Pubmed]
  8. Polyalanine and polyserine frameshift products in Huntington's disease. Davies, J.E., Rubinsztein, D.C. J. Med. Genet. (2006) [Pubmed]
  9. Adaptation of a DNA replication checkpoint response depends upon inactivation of Claspin by the Polo-like kinase. Yoo, H.Y., Kumagai, A., Shevchenko, A., Shevchenko, A., Dunphy, W.G. Cell (2004) [Pubmed]
  10. Polo-like kinase 1 phosphorylates cyclin B1 and targets it to the nucleus during prophase. Toyoshima-Morimoto, F., Taniguchi, E., Shinya, N., Iwamatsu, A., Nishida, E. Nature (2001) [Pubmed]
  11. Nuclear import of the Drosophila Rel protein Dorsal is regulated by phosphorylation. Drier, E.A., Huang, L.H., Steward, R. Genes Dev. (1999) [Pubmed]
  12. Association of phosphorylated serine/arginine (SR) splicing factors with the U1-small ribonucleoprotein (snRNP) autoantigen complex accompanies apoptotic cell death. Utz, P.J., Hottelet, M., van Venrooij, W.J., Anderson, P. J. Exp. Med. (1998) [Pubmed]
  13. Both viral transcription and replication are reduced when the rabies virus nucleoprotein is not phosphorylated. Wu, X., Gong, X., Foley, H.D., Schnell, M.J., Fu, Z.F. J. Virol. (2002) [Pubmed]
  14. Intracerebral microdialysis of extracellular amino acids in the human epileptic focus. Ronne-Engström, E., Hillered, L., Flink, R., Spännare, B., Ungerstedt, U., Carlson, H. J. Cereb. Blood Flow Metab. (1992) [Pubmed]
  15. The role of cysteine residues in structure and enzyme activity of a maize beta-glucosidase. Rotrekl, V., Nejedlá, E., Kucera, I., Abdallah, F., Palme, K., Brzobohatý, B. Eur. J. Biochem. (1999) [Pubmed]
  16. A systematic analysis of the factors that determine the strength of pre-mRNA splicing enhancers. Graveley, B.R., Hertel, K.J., Maniatis, T. EMBO J. (1998) [Pubmed]
  17. Regulation of alternative splicing by SRrp86 and its interacting proteins. Li, J., Hawkins, I.C., Harvey, C.D., Jennings, J.L., Link, A.J., Patton, J.G. Mol. Cell. Biol. (2003) [Pubmed]
  18. Selection and characterization of pre-mRNA splicing enhancers: identification of novel SR protein-specific enhancer sequences. Schaal, T.D., Maniatis, T. Mol. Cell. Biol. (1999) [Pubmed]
  19. Disassembly of interchromatin granule clusters alters the coordination of transcription and pre-mRNA splicing. Sacco-Bubulya, P., Spector, D.L. J. Cell Biol. (2002) [Pubmed]
  20. The SRm160/300 splicing coactivator is required for exon-enhancer function. Eldridge, A.G., Li, Y., Sharp, P.A., Blencowe, B.J. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  21. S338 phosphorylation of Raf-1 is independent of phosphatidylinositol 3-kinase and Pak3. Chiloeches, A., Mason, C.S., Marais, R. Mol. Cell. Biol. (2001) [Pubmed]
  22. Impaired immune responses and prolonged allograft survival in Sly1 mutant mice. Beer, S., Scheikl, T., Reis, B., Hüser, N., Pfeffer, K., Holzmann, B. Mol. Cell. Biol. (2005) [Pubmed]
  23. Extracellular signal regulated kinases. Localization of protein and mRNA in the human hippocampal formation in Alzheimer's disease. Hyman, B.T., Elvhage, T.E., Reiter, J. Am. J. Pathol. (1994) [Pubmed]
  24. Molecular cloning of a full-length cDNA for dentatorubral-pallidoluysian atrophy and regional expressions of the expanded alleles in the CNS. Onodera, O., Oyake, M., Takano, H., Ikeuchi, T., Igarashi, S., Tsuji, S. Am. J. Hum. Genet. (1995) [Pubmed]
  25. Effect of single amino acid substitutions on the formation of the PlA and Bak alloantigenic epitopes. Goldberger, A., Kolodziej, M., Poncz, M., Bennett, J.S., Newman, P.J. Blood (1991) [Pubmed]
  26. Yeast shuttling SR proteins Npl3p, Gbp2p, and Hrb1p are part of the translating mRNPs, and Npl3p can function as a translational repressor. Windgassen, M., Sturm, D., Cajigas, I.J., González, C.I., Seedorf, M., Bastians, H., Krebber, H. Mol. Cell. Biol. (2004) [Pubmed]
  27. Nuclear protein phosphatase 2A dephosphorylates protein kinase A-phosphorylated CREB and regulates CREB transcriptional stimulation. Wadzinski, B.E., Wheat, W.H., Jaspers, S., Peruski, L.F., Lickteig, R.L., Johnson, G.L., Klemm, D.J. Mol. Cell. Biol. (1993) [Pubmed]
  28. Phosphorylation of the TAL1 oncoprotein by the extracellular-signal-regulated protein kinase ERK1. Cheng, J.T., Cobb, M.H., Baer, R. Mol. Cell. Biol. (1993) [Pubmed]
  29. Phosphorylation of annexin I by TRPM7 channel-kinase. Dorovkov, M.V., Ryazanov, A.G. J. Biol. Chem. (2004) [Pubmed]
  30. Reversible phosphorylation of Bcl2 following interleukin 3 or bryostatin 1 is mediated by direct interaction with protein phosphatase 2A. Deng, X., Ito, T., Carr, B., Mumby, M., May, W.S. J. Biol. Chem. (1998) [Pubmed]
  31. RIP2 is a novel NF-kappaB-activating and cell death-inducing kinase. McCarthy, J.V., Ni, J., Dixit, V.M. J. Biol. Chem. (1998) [Pubmed]
  32. Ion binding properties of the dehydrin ERD14 are dependent upon phosphorylation. Alsheikh, M.K., Heyen, B.J., Randall, S.K. J. Biol. Chem. (2003) [Pubmed]
  33. Human IFN-alpha protein engineering: the amino acid residues at positions 86 and 90 are important for antiproliferative activity. Hu, R., Bekisz, J., Schmeisser, H., McPhie, P., Zoon, K. J. Immunol. (2001) [Pubmed]
  34. Blue-light- and phosphorylation-dependent binding of a 14-3-3 protein to phototropins in stomatal guard cells of broad bean. Kinoshita, T., Emi, T., Tominaga, M., Sakamoto, K., Shigenaga, A., Doi, M., Shimazaki, K. Plant Physiol. (2003) [Pubmed]
  35. Activation of the Epstein-Barr virus transcription factor BZLF1 by 12-O-tetradecanoylphorbol-13-acetate-induced phosphorylation. Baumann, M., Mischak, H., Dammeier, S., Kolch, W., Gires, O., Pich, D., Zeidler, R., Delecluse, H.J., Hammerschmidt, W. J. Virol. (1998) [Pubmed]
  36. The protein kinase activity of the large subunit of herpes simplex virus type 2 ribonucleotide reductase (ICP10) fused to the extracellular domain of the epidermal growth factor receptor is ligand-inducible. Smith, C.C., Luo, J.H., Aurelian, L. Virology (1996) [Pubmed]
 
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