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Steven G. Clarke, Ph.D.
Director, Molecular Biology Institute
Professor, Chemistry and Biochemistry
Biochemistry, Molecular Biology
Member, Brain Research Institute
Graduate Program in Biochemistry and Molecular Biology
Professor, Chemistry and Biochemistry
Biochemistry, Molecular Biology
Member, Brain Research Institute
Graduate Program in Biochemistry and Molecular Biology
Awards and Honors:Princeton University Visiting Fellow, Princeton University American Chemical Society American Chemical Society/Ralph F. Hirschmann Award in Peptide Chemistry Alfred P. Sloan Research Fellowship in Chemistry Alfred P. Sloan Research Fellowship in Chemistry Harvard NSF Predoctoral Fellow NIH MERIT Award Pomona College Wilson Prize in Chemistry UCLA Academic Senate Distinguished Teaching Award, including the Eby Award for the Art of Teaching UCLA Academic Senate Distinguished Teaching Award, including the Eby Award for the Art of Teaching Miller Research Fellow, UC Berkeley Miller Research Fellow, UC Berkeley Joseph F. Foster Memorial Lecturer, Purdue University
PhoneLab Number: (310) 825-3137 & 825-8121Work Phone Number: (310) 825-8754
AddressLaboratory Address: Paul Boyer Hall 628, 637 & 638 Work Address: Paul Boyer Hall 640
BiographyProfessor Clarke received his B.A. degree from Pomona College in 1970 and his Ph.D. degree from Harvard University in 1976. After a two-year postdoctoral appointment as a Miller Fellow at the University of California at Berkeley, he joined the UCLA faculty in 1978. Professor Steven Clarke's 2009 UCLA Faculty Research Lecture on Nov. 3rd"Aging & Rejuvenation: Chemistry and Biology at Work" UCTV, Webcast, YouTube Professor Clarke accepts graduate students through the Biochemistry and Molecular Biology (BMB) Graduate Program and the UCLA ACCESS Ph.D. Program.
Mackay Kennen B, Tu Yiping, Young Stephen G, Clarke Steven G Circumventing Embryonic Lethality with Lcmt1 Deficiency: Generation of Hypomorphic Lcmt1 Mice with Reduced Protein Phosphatase 2A Methyltransferase Expression and Defects in Insulin Signaling PloS one, 2013; 8(6): e65967.
Patananan Alexander N, Palmer Jonathan M, Garvey Graeme S, Keller Nancy P, Clarke Steven G A novel automethylation reaction in the Aspergillus nidulans LaeA protein generates S-methylmethionine The Journal of biological chemistry, 2013; 288(20): 14032-45.
Clarke Steven G Protein methylation at the surface and buried deep: thinking outside the histone box Trends in biochemical sciences, 2013; 38(5): 243-52.
Urzica Eugen I, Casero David, Yamasaki Hiroaki, Hsieh Scott I, Adler Lital N, Karpowicz Steven J, Blaby-Haas Crysten E, Clarke Steven G, Loo Joseph A, Pellegrini Matteo, Merchant Sabeeha S Systems and trans-system level analysis identifies conserved iron deficiency responses in the plant lineage The Plant cell, 2012; 24(10): 3921-48.
Young Brian D, Weiss David I, Zurita-Lopez Cecilia I, Webb Kristofor J, Clarke Steven G, McBride Anne E Identification of methylated proteins in the yeast small ribosomal subunit: a role for SPOUT methyltransferases in protein arginine methylation Biochemistry, 2012; 51(25): 5091-104.
Urzica Eugen I, Adler Lital N, Page M Dudley, Linster Carole L, Arbing Mark A, Casero David, Pellegrini Matteo, Merchant Sabeeha S, Clarke Steven G Impact of oxidative stress on ascorbate biosynthesis in Chlamydomonas via regulation of the VTC2 gene encoding a GDP-L-galactose phosphorylase The Journal of biological chemistry, 2012; 287(17): 14234-45.
Castro Paola V, Khare Shilpi, Young Brian D, Clarke Steven G Caenorhabditis elegans battling starvation stress: low levels of ethanol prolong lifespan in L1 larvae PloS one, 2012; 7(1): e29984.
Zurita-Lopez Cecilia I, Sandberg Troy, Kelly Ryan, Clarke Steven G Human protein arginine methyltransferase 7 (PRMT7) is a type III enzyme forming Ï‰-NG-monomethylated arginine residues The Journal of biological chemistry, 2012; 287(11): 7859-70.
MacKay Kennen B, Lowenson Jonathan D, Clarke Steven G Wortmannin reduces insulin signaling and death in seizure-prone Pcmt1-/- mice PloS one, 2012; 7(10): e46719.
Adler Lital N, Gomez Tara A, Clarke Steven G, Linster Carole L A novel GDP-D-glucose phosphorylase involved in quality control of the nucleoside diphosphate sugar pool in Caenorhabditis elegans and mammals The Journal of biological chemistry, 2011; 286(24): 21511-23.
Webb Kristofor J, Al-Hadid Qais, Zurita-Lopez Cecilia I, Young Brian D, Lipson Rebecca S, Clarke Steven G The ribosomal l1 protuberance in yeast is methylated on a lysine residue catalyzed by a seven-beta-strand methyltransferase The Journal of biological chemistry, 2011; 286(21): 18405-13.
Khare Shilpi, Linster Carole L, Clarke Steven G The interplay between protein L-isoaspartyl methyltransferase activity and insulin-like signaling to extend lifespan in Caenorhabditis elegans PloS one, 2011; 6(6): e20850.
Petrossian Tanya C, Clarke Steven G Uncovering the human methyltransferasome Molecular & cellular proteomics : MCP, 2011; 10(1): M110.000976.
Webb Kristofor J, Zurita-Lopez Cecilia I, Al-Hadid Qais, Laganowsky Arthur, Young Brian D, Lipson Rebecca S, Souda Puneet, Faull Kym F, Whitelegge Julian P, Clarke Steven G A novel 3-methylhistidine modification of yeast ribosomal protein Rpl3 is dependent upon the YIL110W methyltransferase The Journal of biological chemistry, 2010; 285(48): 37598-606.
Chen Tingsu, Nayak Nihar, Majee Susmita Maitra, Lowenson Jonathan, Schäfermeyer Kim R, Eliopoulos Alyssa C, Lloyd Taylor D, Dinkins Randy, Perry Sharyn E, Forsthoefel Nancy R, Clarke Steven G, Vernon Daniel M, Zhou Zhaohui Sunny, Rejtar Tomas, Downie A Bruce Substrates of the Arabidopsis thaliana protein isoaspartyl methyltransferase 1 identified using phage display and biopanning The Journal of biological chemistry, 2010; 285(48): 37281-92.
Lipson Rebecca S, Webb Kristofor J, Clarke Steven G Two novel methyltransferases acting upon eukaryotic elongation factor 1A in Saccharomyces cerevisiae Archives of biochemistry and biophysics, 2010; 500(2): 137-43.
Vinci Chris R, Clarke Steven G Homocysteine methyltransferases Mht1 and Sam4 prevent the accumulation of age-damaged (R,S)-AdoMet in the yeast Saccharomyces cerevisiae The Journal of biological chemistry, 2010; 285(27): 20526-31.
Webb Kristofor J, Lipson Rebecca S, Al-Hadid Qais, Whitelegge Julian P, Clarke Steven G Identification of protein N-terminal methyltransferases in yeast and humans Biochemistry, 2010; 49(25): 5225-35.
Fisk John C, Zurita-Lopez Cecilia, Sayegh Joyce, Tomasello Danielle L, Clarke Steven G, Read Laurie K TbPRMT6 is a type I protein arginine methyltransferase that contributes to cytokinesis in Trypanosoma brucei Eukaryotic cell, 2010; 9(6): 866-77.
Vinci Chris R, Clarke Steven G Yeast, plants, worms, and flies use a methyltransferase to metabolize age-damaged (R,S)-AdoMet, but what do mammals do? Rejuvenation research, 2010; 13(2-3): 362-4.
Lipson Rebecca S, Webb Kristofor J, Clarke Steven G Rmt1 catalyzes zinc-finger independent arginine methylation of the small ribosomal protein Rps2 in Saccharomyces cerevisiae Biochemical and biophysical research communications, 2009; .
Petrossian Tanya, Clarke Steven Bioinformatic Identification of Novel Methyltransferases Epigenomics, 2009; 1(1): 163-175.
Khare Shilpi, Gomez Tara, Linster Carole L, Clarke Steven G Defective responses to oxidative stress in protein l-isoaspartyl repair-deficient Caenorhabditis elegans Mechanisms of ageing and development, 2009; 130(10): 670-80.
Lakowski Ted M, Zurita-Lopez Cecilia, Clarke Steven G, Frankel Adam Approaches to measuring the activities of protein arginine N-methyltransferases Analytical biochemistry, 2009; .
Petrossian, T. C., and Clarke, S. G. Bioinformatic Identification of Novel Methyltransferases Epigenomics, 2009; 1: 163-175.
Fisk John C, Sayegh Joyce, Zurita-Lopez Cecilia, Menon Sarita, Presnyak Vladimir, Clarke Steven G, Read Laurie K A type III protein arginine methyltransferase from the protozoan parasite Trypanosoma brucei The Journal of biological chemistry, 2009; 284(17): 11590-600.
Petrossian Laurie K, Clarke Laurie K Multiple motif scanning to identify methyltransferases from the yeast proteome Molecular & cellular proteomics : MCP, 2009; 284(17): .
Bedford Mark T, Clarke Steven G Protein arginine methylation in mammals: who, what, and why Molecular cell, 2009; 33(1): 1-13.
Webb Kristofor J, Laganowsky Arthur, Whitelegge Julian P, Clarke Steven G Identification of two SET domain proteins required for methylation of lysine residues in yeast ribosomal protein Rpl42ab The Journal of biological chemistry, 2008; 283(51): 35561-8.
Gomez Tara A, Banfield Kelley L, Clarke Steven G The protein L-isoaspartyl-O-methyltransferase functions in the Caenorhabditis elegans stress response Mechanisms of ageing and development, 2008; 129(12): 752-8.
Linster Carole L, Clarke Steven G L-Ascorbate biosynthesis in higher plants: the role of VTC2 Trends in plant science, 2008; 13(11): 567-73.
Sayegh Joyce, Clarke Steven G Hsl7 is a substrate-specific type II protein arginine methyltransferase in yeast Biochem. Biophys. Res. Commun, 2008; 372(4): 811-5.
Banfield Kelley L, Gomez Tara A, Lee Wendy, Clarke Steven, Larsen Pamela L Protein-repair and hormone-signaling pathways specify dauer and adult longevity and dauer development in Caenorhabditis elegans The journals of gerontology. Series A, Biological sciences and medical sciences, 2008; 63(8): 798-808.
Linster Carole L, Adler Lital N, Webb Kristofor, Christensen Kathryn C, Brenner Charles, Clarke Steven G A second GDP-L-galactose phosphorylase in arabidopsis en route to vitamin C. Covalent intermediate and substrate requirements for the conserved reaction J. Biol. Chem, 2008; 283(27): 18483-92.
Alfaro Joshua F, Gillies Laura A, Sun He G, Dai Shujia, Zang Tianzhu, Klaene Joshua J, Kim Byung Ju, Lowenson Jonathan D, Clarke Steven G, Karger Barry L, Zhou Zhaohui Sunny Chemo-enzymatic detection of protein isoaspartate using protein isoaspartate methyltransferase and hydrazine trapping Anal. Chem, 2008; 80(10): 3882-9.
Dumlao Darren S, Hertz Nicholas, Clarke Steven Secreted 3-isopropylmalate methyl ester signals invasive growth during amino acid starvation in Saccharomyces cerevisiae Biochemistry, 2008; 47(2): 698-709.
Sayegh Joyce, Webb Kristofor, Cheng Donghang, Bedford Mark T, Clarke Steven G Regulation of protein arginine methyltransferase 8 (PRMT8) activity by its N-terminal domain J. Biol. Chem, 2007; 282(50): 36444-53.
Lipson Rebecca S, Clarke Steven G S-adenosylmethionine-dependent protein methylation in mammalian cytosol via tyrphostin modification by catechol-O-methyltransferase J. Biol. Chem, 2007; 282(42): 31094-102.
Pasternack Deborah A, Sayegh Joyce, Clarke Steven, Read Laurie K Evolutionarily divergent type II protein arginine methyltransferase in Trypanosoma brucei Eukaryotic Cell, 2007; 6(9): 1665-81.
Clarke Steven Gerard HIV protease inhibitors and nuclear lamin processing: getting the right bells and whistles Proc. Natl. Acad. Sci. U.S.A, 2007; 104(35): 13857-8.
Zou Yan, Webb Kristofor, Perna Avi D, Zhang Qingchun, Clarke Steven, Wang Yinsheng A mass spectrometric study on the in vitro methylation of HMGA1a and HMGA1b proteins by PRMTs: methylation specificity, the effect of binding to AT-rich duplex DNA, and the effect of C-terminal phosphorylation Biochemistry, 2007; 46(26): 7896-906.
Gomez Tara A, Clarke Steven G Autophagy and insulin/TOR signaling in Caenorhabditis elegans pcm-1 protein repair mutants Autophagy, 2007; 3(4): 357-9.
McBride Anne E, Zurita-Lopez Cecilia, Regis Anthony, Blum Emily, Conboy Ana, Elf Shannon, Clarke Steven Protein arginine methylation in Candida albicans: role in nuclear transport Eukaryotic Cell, 2007; 6(7): 1119-29.
Chen Hui, Xia Meng, Lin Mark, Yang Heping, Kuhlenkamp John, Li Tony, Sodir Nicole M, Chen Yong-Heng, Josef-Lenz Heinz, Laird Peter W, Clarke Steven, Mato JosM, Lu Shelly C Role of methionine adenosyltransferase 2A and S-adenosylmethionine in mitogen-induced growth of human colon cancer cells Gastroenterology, 2007; 133(1): 207-18.
Linster Carole L, Gomez Tara A, Christensen Kathryn C, Adler Lital N, Young Brian D, Brenner Charles, Clarke Steven G Arabidopsis VTC2 encodes a GDP-L-galactose phosphorylase, the last unknown enzyme in the Smirnoff-Wheeler pathway to ascorbic acid in plants J. Biol. Chem, 2007; 282(26): 18879-85.
Porras-Yakushi Tanya R, Whitelegge Julian P, Clarke Steven Yeast ribosomal/cytochrome c SET domain methyltransferase subfamily: identification of Rpl23ab methylation sites and recognition motifs J. Biol. Chem, 2007; 282(17): 12368-76.
Vinci Chris R, Clarke Steven G Recognition of age-damaged (R,S)-adenosyl-L-methionine by two methyltransferases in the yeast Saccharomyces cerevisiae J. Biol. Chem, 2007; 282(12): 8604-12.
Gomez Tara A, Banfield Kelley L, Trogler Dorothy M, Clarke Steven G The L-isoaspartyl-O-methyltransferase in Caenorhabditis elegans larval longevity and autophagy Developmental biology, 2007; 303(2): 493-500.
Villa Sarah T, Xu Qilong, Downie A Bruce, Clarke Steven G Arabidopsis Protein Repair L-Isoaspartyl Methyltransferases: Predominant Activities at Lethal Temperatures Physiologia plantarum, 2006; 128(4): 581-592.
Porras-Yakushi Tanya R, Whitelegge Julian P, Clarke Steven A novel SET domain methyltransferase in yeast: Rkm2-dependent trimethylation of ribosomal protein L12ab at lysine 10 The Journal of biological chemistry, 2006; 281(47): 35835-45.
Yang Mei-Ling, Doyle Hester A, Gee Renelle J, Lowenson Jonathan D, Clarke Steven, Lawson Brian R, Aswad Dana W, Mamula Mark J Intracellular protein modification associated with altered T cell functions in autoimmunity Journal of immunology (Baltimore, Md. : 1950), 2006; 177(7): 4541-9.
Vigneswara Vasanthy, Lowenson Jonathan D, Powell Claire D, Thakur Matthew, Bailey Kevin, Clarke Steven, Ray David E, Carter Wayne G Proteomic identification of novel substrates of a protein isoaspartyl methyltransferase repair enzyme The Journal of biological chemistry, 2006; 281(43): 32619-29.
Miranda Tina Branscombe, Sayegh Joyce, Frankel Adam, Katz Jonathan E, Miranda Mark, Clarke Steven Yeast Hsl7 (histone synthetic lethal 7) catalyses the in vitro formation of omega-N(G)-monomethylarginine in calf thymus histone H2A The Biochemical journal, 2006; 395(3): 563-70.
Stetler April, Winograd Claudia, Sayegh Joyce, Cheever Anne, Patton Erin, Zhang Xing, Clarke Steven, Ceman Stephanie Identification and characterization of the methyl arginines in the fragile X mental retardation protein Fmrp Human molecular genetics, 2006; 15(1): 87-96.
Farrar Christine E, Huang Christine S, Clarke Steven G, Houser Carolyn R Increased cell proliferation and granule cell number in the dentate gyrus of protein repair-deficient mice The Journal of comparative neurology, 2005; 493(4): 524-37.
Porras-Yakushi Tanya R, Whitelegge Julian P, Miranda Tina Branscombe, Clarke Steven A novel SET domain methyltransferase modifies ribosomal protein Rpl23ab in yeast The Journal of biological chemistry, 2005; 280(41): 34590-8.
Miranda Tina Branscombe, Webb Kristofor J, Edberg Dale D, Reeves Raymond, Clarke Steven Protein arginine methyltransferase 6 specifically methylates the nonhistone chromatin protein HMGA1a Biochemical and biophysical research communications, 2005; 336(3): 831-5.
Farrar Christine E, Clarke Steven Diet-dependent survival of protein repair-deficient mice The Journal of nutritional biochemistry, 2005; 16(9): 554-61.
Lee Jaeho, Sayegh Joyce, Daniel Jeremy, Clarke Steven, Bedford Mark T PRMT8, a new membrane-bound tissue-specific member of the protein arginine methyltransferase family The Journal of biological chemistry, 2005; 280(38): 32890-6.
Kalhor Hamid R, Penjwini Mahmud, Clarke Steven A novel methyltransferase required for the formation of the hypermodified nucleoside wybutosine in eucaryotic tRNA Biochemical and biophysical research communications, 2005; 334(2): 433-40.
Farrar Christine, Houser Carolyn R, Clarke Steven Activation of the PI3K/Akt signal transduction pathway and increased levels of insulin receptor in protein repair-deficient mice Aging cell, 2005; 4(1): 1-12.
Miranda Tina Branscombe, Lowenson Jonathan D, Clarke Steven A new type of protein methylation activated by tyrphostin A25 and vanadate FEBS letters, 2004; 577(1-2): 181-6.
Singh Vinita, Miranda Tina Branscombe, Jiang Wei, Frankel Adam, Roemer Martha E, Robb Victoria A, Gutmann David H, Herschman Harvey R, Clarke Steven, Newsham Irene F DAL-1/4.1B tumor suppressor interacts with protein arginine N-methyltransferase 3 (PRMT3) and inhibits its ability to methylate substrates in vitro and in vivo Oncogene, 2004; 23(47): 7761-71.
Wang Yanming, Wysocka Joanna, Sayegh Joyce, Lee Young-Ho, Perlin Julie R, Leonelli Lauriebeth, Sonbuchner Lakshmi S, McDonald Charles H, Cook Richard G, Dou Yali, Roeder Robert G, Clarke Steven, Stallcup Michael R, Allis C David, Coonrod Scott A Human PAD4 regulates histone arginine methylation levels via demethylimination Science (New York, N.Y.), 2004; 306(5694): 279-83.
Miranda Tina Branscombe, Khusial Permanan, Cook Jeffry R, Lee Jin-Hyung, Gunderson Samuel I, Pestka Sidney, Zieve Gary W, Clarke Steven Spliceosome Sm proteins D1, D3, and B/B' are asymmetrically dimethylated at arginine residues in the nucleus Biochemical and biophysical research communications, 2004; 323(2): 382-7.
Xu Qilong, Belcastro Marisa P, Villa Sarah T, Dinkins Randy D, Clarke Steven G, Downie A Bruce A second protein L-isoaspartyl methyltransferase gene in Arabidopsis produces two transcripts whose products are sequestered in the nucleus Plant physiology, 2004; 136(1): 2652-64.
Vitali Ryan, Clarke Steven Improved rotorod performance and hyperactivity in mice deficient in a protein repair methyltransferase Behavioural brain research, 2004; 153(1): 129-41.
Katz Jonathan E, Dumlao Darren S, Wasserman Jacob I, Lansdown Michael G, Jung Michael E, Faull Kym F, Clarke Steven 3-Isopropylmalate is the major endogenous substrate of the Saccharomyces cerevisiae trans-aconitate methyltransferase Biochemistry, 2004; 43(20): 5976-86.
Miranda Tina Branscombe, Miranda Mark, Frankel Adam, Clarke Steven PRMT7 is a member of the protein arginine methyltransferase family with a distinct substrate specificity The Journal of biological chemistry, 2004; 279(22): 22902-7.
Katz Jonathan E, Dumlao Darren S, Clarke Steven, Hau Jörg A new technique (COMSPARI) to facilitate the identification of minor compounds in complex mixtures by GC/MS and LC/MS: tools for the visualization of matched datasets Journal of the American Society for Mass Spectrometry, 2004; 15(4): 580-4.
Boulanger Marie-Chloé, Miranda Tina Branscombe, Clarke Steven, Di Fruscio Marco, Suter Beat, Lasko Paul, Richard Stéphane Characterization of the Drosophila protein arginine methyltransferases DART1 and DART4 The Biochemical journal, 2004; 379(Pt 2): 283-9.
Clarke Steven, Tamanoi Fuyuhiko Fighting cancer by disrupting C-terminal methylation of signaling proteins The Journal of clinical investigation, 2004; 113(4): 513-5.
Kalhor Hamid R, Clarke Steven Novel methyltransferase for modified uridine residues at the wobble position of tRNA Molecular and cellular biology, 2003; 23(24): 9283-92.
Katz Jonathan E, Dlaki? Mensur, Clarke Steven Automated identification of putative methyltransferases from genomic open reading frames Molecular & cellular proteomics : MCP, 2003; 2(8): 525-40.
Clarke Steven Aging as war between chemical and biochemical processes: protein methylation and the recognition of age-damaged proteins for repair Ageing research reviews, 2003; 2(3): 263-85.
Mura Cameron, Katz Jonathan E, Clarke Steven G, Eisenberg David Structure and function of an archaeal homolog of survival protein E (SurEalpha): an acid phosphatase with purine nucleotide specificity Journal of molecular biology, 2003; 326(5): 1559-75.
Farrar Christine, Clarke Steven Altered levels of S-adenosylmethionine and S-adenosylhomocysteine in the brains of L-isoaspartyl (D-Aspartyl) O-methyltransferase-deficient mice The Journal of biological chemistry, 2002; 277(31): 27856-63.
Clarke Steven D, Gasperikova Daniela, Nelson Carolanne, Lapillonne Alexandre, Heird William C Fatty acid regulation of gene expression: a genomic explanation for the benefits of the mediterranean diet Annals of the New York Academy of Sciences, 2002; 967(31): 283-98.
Ryttersgaard Carsten, Griffith Scott C, Sawaya Michael R, MacLaren Duncan C, Clarke Steven, Yeates Todd O Crystal structure of human L-isoaspartyl methyltransferase The Journal of biological chemistry, 2002; 277(12): 10642-6.
Clarke Steven The methylator meets the terminator Proceedings of the National Academy of Sciences of the United States of America, 2002; 99(3): 1104-6.
Frankel Adam, Yadav Neelu, Lee Jaeho, Branscombe Tina L, Clarke Steven, Bedford Mark T The novel human protein arginine N-methyltransferase PRMT6 is a nuclear enzyme displaying unique substrate specificity The Journal of biological chemistry, 2002; 277(5): 3537-43.
Thapar Nitika, Griffith Scott C, Yeates Todd O, Clarke Steven Protein repair methyltransferase from the hyperthermophilic archaeon Pyrococcus furiosus. Unusual methyl-accepting affinity for D-aspartyl and N-succinyl-containing peptides The Journal of biological chemistry, 2002; 277(2): 1058-65.