NameReceptor-interacting serine/threonine-protein kinase 2
Synonyms
  • 2.7.11.1
  • CARD-containing IL-1 beta ICE-kinase
  • CARD-containing interleukin-1 beta-converting enzyme-associated kinase
  • CARDIAK
  • Receptor-interacting protein 2
  • RICK
  • RIP-2
  • RIP-like-interacting CLARP kinase
  • RIP2
  • Tyrosine-protein kinase RIPK2
Gene NameRIPK2
OrganismHuman
Amino acid sequence
>lcl|BSEQ0009618|Receptor-interacting serine/threonine-protein kinase 2
MNGEAICSALPTIPYHKLADLRYLSRGASGTVSSARHADWRVQVAVKHLHIHTPLLDSER
KDVLREAEILHKARFSYILPILGICNEPEFLGIVTEYMPNGSLNELLHRKTEYPDVAWPL
RFRILHEIALGVNYLHNMTPPLLHHDLKTQNILLDNEFHVKIADFGLSKWRMMSLSQSRS
SKSAPEGGTIIYMPPENYEPGQKSRASIKHDIYSYAVITWEVLSRKQPFEDVTNPLQIMY
SVSQGHRPVINEESLPYDIPHRARMISLIESGWAQNPDERPSFLKCLIELEPVLRTFEEI
TFLEAVIQLKKTKLQSVSSAIHLCDKKKMELSLNIPVNHGPQEESCGSSQLHENSGSPET
SRSLPAPQDNDFLSRKAQDCYFMKLHHCPGNHSWDSTISGSQRAAFCDHKTTPCSSAIIN
PLSTAGNSERLQPGIAQQWIQSKREDIVNQMTEACLNQSLDALLSRDLIMKEDYELVSTK
PTRTSKVRQLLDTTDIQGEEFAKVIVQKLKDNKQMGLQPYPEILVVSRSPSLNLLQNKSM
Number of residues540
Molecular Weight61194.345
Theoretical pINot Available
GO Classification
Functions
  • signal transducer activity
  • CARD domain binding
  • LIM domain binding
  • ATP binding
  • protein serine/threonine kinase activity
  • receptor binding
  • non-membrane spanning protein tyrosine kinase activity
  • protein homodimerization activity
Processes
  • positive regulation of interferon-gamma production
  • positive regulation of interferon-beta production
  • innate immune response
  • response to exogenous dsRNA
  • T cell receptor signaling pathway
  • positive regulation of cytokine-mediated signaling pathway
  • positive regulation of apoptotic process
  • stress-activated MAPK cascade
  • toll-like receptor 10 signaling pathway
  • I-kappaB kinase/NF-kappaB signaling
  • cellular response to muramyl dipeptide
  • positive regulation of peptidyl-tyrosine phosphorylation
  • toll-like receptor 2 signaling pathway
  • positive regulation of protein ubiquitination
  • nucleotide-binding oligomerization domain containing 2 signaling pathway
  • apoptotic process
  • toll-like receptor 3 signaling pathway
  • positive regulation of JNK cascade
  • positive regulation of interferon-alpha production
  • negative regulation of apoptotic process
  • toll-like receptor 4 signaling pathway
  • adaptive immune response
  • neurotrophin TRK receptor signaling pathway
  • positive regulation of peptidyl-serine phosphorylation
  • toll-like receptor 5 signaling pathway
  • signal transduction
  • positive regulation of interleukin-2 production
  • positive regulation of transcription from RNA polymerase II promoter
  • toll-like receptor 9 signaling pathway
  • positive regulation of T-helper 1 cell differentiation
  • nucleotide-binding oligomerization domain containing 1 signaling pathway
  • positive regulation of interleukin-6 production
  • toll-like receptor signaling pathway
  • response to interleukin-1
  • positive regulation of immature T cell proliferation
  • response to interleukin-12
  • positive regulation of tumor necrosis factor production
  • toll-like receptor TLR1
  • positive regulation of interleukin-12 production
  • response to interleukin-18
  • lipopolysaccharide-mediated signaling pathway
  • toll-like receptor TLR6
  • positive regulation of I-kappaB kinase/NF-kappaB signaling
  • T cell proliferation
  • positive regulation of ERK1 and ERK2 cascade
  • TRIF-dependent toll-like receptor signaling pathway
  • inflammatory response
  • positive regulation of NF-kappaB transcription factor activity
  • activation of MAPK activity
  • nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway
  • defense response to Gram-positive bacterium
  • JNK cascade
  • nucleotide-binding oligomerization domain containing signaling pathway
  • MyD88-dependent toll-like receptor signaling pathway
  • positive regulation of chemokine production
  • cellular response to lipoteichoic acid
  • MyD88-independent toll-like receptor signaling pathway
  • positive regulation of alpha-beta T cell proliferation
  • cellular response to peptidoglycan
  • positive regulation of peptidyl-threonine phosphorylation
Components
  • cytoplasm
  • protein complex
  • cytoskeleton
  • vesicle
  • cytosol
General FunctionSignal transducer activity
Specific FunctionSerine/threonine/tyrosine kinase that plays an essential role in modulation of innate and adaptive immune responses. Upon stimulation by bacterial peptidoglycans, NOD1 and NOD2 are activated, oligomerize and recruit RIPK2 through CARD-CARD domains. Contributes to the tyrosine phosphorylation of the guanine exchange factor ARHGEF2 through Src tyrosine kinase leading to NF-kappaB activation by NOD2. Once recruited, RIPK2 autophosphorylates and undergoes 'Lys-63'-linked polyubiquitination by E3 ubiquitin ligases XIAP, BIRC2 and BIRC3. The polyubiquitinated protein mediates the recruitment of MAP3K7/TAK1 to IKBKG/NEMO and induces 'Lys-63'-linked polyubiquitination of IKBKG/NEMO and subsequent activation of IKBKB/IKKB. In turn, NF-kappa-B is released from NF-kappa-B inhibitors and translocates into the nucleus where it activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis. Plays also a role during engagement of the T-cell receptor (TCR) in promoting BCL10 phosphorylation and subsequent NF-kappa-B activation.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein IDNot Available
UniProtKB IDO43353
UniProtKB Entry NameRIPK2_HUMAN
Cellular LocationCytoplasm
Gene sequence
>lcl|BSEQ0017792|Receptor-interacting serine/threonine-protein kinase 2 (RIPK2)
ATGAACGGGGAGGCCATCTGCAGCGCCCTGCCCACCATTCCCTACCACAAACTCGCCGAC
CTGCGCTACCTGAGCCGCGGCGCCTCTGGCACTGTGTCGTCCGCCCGCCACGCAGACTGG
CGCGTCCAGGTGGCCGTGAAGCACCTGCACATCCACACTCCGCTGCTCGACAGTGAAAGA
AAGGATGTCTTAAGAGAAGCTGAAATTTTACACAAAGCTAGATTTAGTTACATTCTTCCA
ATTTTGGGAATTTGCAATGAGCCTGAATTTTTGGGAATAGTTACTGAATACATGCCAAAT
GGATCATTAAATGAACTCCTACATAGGAAAACTGAATATCCTGATGTTGCTTGGCCATTG
AGATTTCGCATCCTGCATGAAATTGCCCTTGGTGTAAATTACCTGCACAATATGACTCCT
CCTTTACTTCATCATGACTTGAAGACTCAGAATATCTTATTGGACAATGAATTTCATGTT
AAGATTGCAGATTTTGGTTTATCAAAGTGGCGCATGATGTCCCTCTCACAGTCACGAAGT
AGCAAATCTGCACCAGAAGGAGGGACAATTATCTATATGCCACCTGAAAACTATGAACCT
GGACAAAAATCAAGGGCCAGTATCAAGCACGATATATATAGCTATGCAGTTATCACATGG
GAAGTGTTATCCAGAAAACAGCCTTTTGAAGATGTCACCAATCCTTTGCAGATAATGTAT
AGTGTGTCACAAGGACATCGACCTGTTATTAATGAAGAAAGTTTGCCATATGATATACCT
CACCGAGCACGTATGATCTCTCTAATAGAAAGTGGATGGGCACAAAATCCAGATGAAAGA
CCATCTTTCTTAAAATGTTTAATAGAACTTGAACCAGTTTTGAGAACATTTGAAGAGATA
ACTTTTCTTGAAGCTGTTATTCAGCTAAAGAAAACAAAGTTACAGAGTGTTTCAAGTGCC
ATTCACCTATGTGACAAGAAGAAAATGGAATTATCTCTGAACATACCTGTAAATCATGGT
CCACAAGAGGAATCATGTGGATCCTCTCAGCTCCATGAAAATAGTGGTTCTCCTGAAACT
TCAAGGTCCCTGCCAGCTCCTCAAGACAATGATTTTTTATCTAGAAAAGCTCAAGACTGT
TATTTTATGAAGCTGCATCACTGTCCTGGAAATCACAGTTGGGATAGCACCATTTCTGGA
TCTCAAAGGGCTGCATTCTGTGATCACAAGACCACTCCATGCTCTTCAGCAATAATAAAT
CCACTCTCAACTGCAGGAAACTCAGAACGTCTGCAGCCTGGTATAGCCCAGCAGTGGATC
CAGAGCAAAAGGGAAGACATTGTGAACCAAATGACAGAAGCCTGCCTTAACCAGTCGCTA
GATGCCCTTCTGTCCAGGGACTTGATCATGAAAGAGGACTATGAACTTGTTAGTACCAAG
CCTACAAGGACCTCAAAAGTCAGACAATTACTAGACACTACTGACATCCAAGGAGAAGAA
TTTGCCAAAGTTATAGTACAAAAATTGAAAGATAACAAACAAATGGGTCTTCAGCCTTAC
CCGGAAATACTTGTGGTTTCTAGATCACCATCTTTAAATTTACTTCAAAATAAAAGCATG
TAA
GenBank Gene IDNot Available
GeneCard IDNot Available
GenAtlas IDNot Available
HGNC IDHGNC:10020
Chromosome Location8
LocusNot Available
References
  1. Inohara N, del Peso L, Koseki T, Chen S, Nunez G: RICK, a novel protein kinase containing a caspase recruitment domain, interacts with CLARP and regulates CD95-mediated apoptosis. J Biol Chem. 1998 May 15;273(20):12296-300. 9575181
  2. McCarthy JV, Ni J, Dixit VM: RIP2 is a novel NF-kappaB-activating and cell death-inducing kinase. J Biol Chem. 1998 Jul 3;273(27):16968-75. 9642260
  3. Thome M, Hofmann K, Burns K, Martinon F, Bodmer JL, Mattmann C, Tschopp J: Identification of CARDIAK, a RIP-like kinase that associates with caspase-1. Curr Biol. 1998 Jul 16;8(15):885-8. 9705938
  4. Clark HF, Gurney AL, Abaya E, Baker K, Baldwin D, Brush J, Chen J, Chow B, Chui C, Crowley C, Currell B, Deuel B, Dowd P, Eaton D, Foster J, Grimaldi C, Gu Q, Hass PE, Heldens S, Huang A, Kim HS, Klimowski L, Jin Y, Johnson S, Lee J, Lewis L, Liao D, Mark M, Robbie E, Sanchez C, Schoenfeld J, Seshagiri S, Simmons L, Singh J, Smith V, Stinson J, Vagts A, Vandlen R, Watanabe C, Wieand D, Woods K, Xie MH, Yansura D, Yi S, Yu G, Yuan J, Zhang M, Zhang Z, Goddard A, Wood WI, Godowski P, Gray A: The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment. Genome Res. 2003 Oct;13(10):2265-70. Epub 2003 Sep 15. 12975309
  5. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. 14702039
  6. Nusbaum C, Mikkelsen TS, Zody MC, Asakawa S, Taudien S, Garber M, Kodira CD, Schueler MG, Shimizu A, Whittaker CA, Chang JL, Cuomo CA, Dewar K, FitzGerald MG, Yang X, Allen NR, Anderson S, Asakawa T, Blechschmidt K, Bloom T, Borowsky ML, Butler J, Cook A, Corum B, DeArellano K, DeCaprio D, Dooley KT, Dorris L 3rd, Engels R, Glockner G, Hafez N, Hagopian DS, Hall JL, Ishikawa SK, Jaffe DB, Kamat A, Kudoh J, Lehmann R, Lokitsang T, Macdonald P, Major JE, Matthews CD, Mauceli E, Menzel U, Mihalev AH, Minoshima S, Murayama Y, Naylor JW, Nicol R, Nguyen C, O'Leary SB, O'Neill K, Parker SC, Polley A, Raymond CK, Reichwald K, Rodriguez J, Sasaki T, Schilhabel M, Siddiqui R, Smith CL, Sneddon TP, Talamas JA, Tenzin P, Topham K, Venkataraman V, Wen G, Yamazaki S, Young SK, Zeng Q, Zimmer AR, Rosenthal A, Birren BW, Platzer M, Shimizu N, Lander ES: DNA sequence and analysis of human chromosome 8. Nature. 2006 Jan 19;439(7074):331-5. 16421571
  7. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334
  8. Ruefli-Brasse AA, Lee WP, Hurst S, Dixit VM: Rip2 participates in Bcl10 signaling and T-cell receptor-mediated NF-kappaB activation. J Biol Chem. 2004 Jan 9;279(2):1570-4. Epub 2003 Nov 24. 14638696
  9. Dorsch M, Wang A, Cheng H, Lu C, Bielecki A, Charron K, Clauser K, Ren H, Polakiewicz RD, Parsons T, Li P, Ocain T, Xu Y: Identification of a regulatory autophosphorylation site in the serine-threonine kinase RIP2. Cell Signal. 2006 Dec;18(12):2223-9. Epub 2006 May 22. 16824733
  10. Manon F, Favier A, Nunez G, Simorre JP, Cusack S: Solution structure of NOD1 CARD and mutational analysis of its interaction with the CARD of downstream kinase RICK. J Mol Biol. 2007 Jan 5;365(1):160-74. Epub 2006 Sep 29. 17054981
  11. Clark NM, Marinis JM, Cobb BA, Abbott DW: MEKK4 sequesters RIP2 to dictate NOD2 signal specificity. Curr Biol. 2008 Sep 23;18(18):1402-8. doi: 10.1016/j.cub.2008.07.084. Epub 2008 Sep 4. 18775659
  12. Hasegawa M, Fujimoto Y, Lucas PC, Nakano H, Fukase K, Nunez G, Inohara N: A critical role of RICK/RIP2 polyubiquitination in Nod-induced NF-kappaB activation. EMBO J. 2008 Jan 23;27(2):373-83. Epub 2007 Dec 13. 18079694
  13. Daub H, Olsen JV, Bairlein M, Gnad F, Oppermann FS, Korner R, Greff Z, Keri G, Stemmann O, Mann M: Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol Cell. 2008 Aug 8;31(3):438-48. doi: 10.1016/j.molcel.2008.07.007. 18691976
  14. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. 18669648
  15. Tao M, Scacheri PC, Marinis JM, Harhaj EW, Matesic LE, Abbott DW: ITCH K63-ubiquitinates the NOD2 binding protein, RIP2, to influence inflammatory signaling pathways. Curr Biol. 2009 Aug 11;19(15):1255-63. doi: 10.1016/j.cub.2009.06.038. Epub 2009 Jul 9. 19592251
  16. Bertrand MJ, Doiron K, Labbe K, Korneluk RG, Barker PA, Saleh M: Cellular inhibitors of apoptosis cIAP1 and cIAP2 are required for innate immunity signaling by the pattern recognition receptors NOD1 and NOD2. Immunity. 2009 Jun 19;30(6):789-801. doi: 10.1016/j.immuni.2009.04.011. Epub 2009 May 21. 19464198
  17. Oppermann FS, Gnad F, Olsen JV, Hornberger R, Greff Z, Keri G, Mann M, Daub H: Large-scale proteomics analysis of the human kinome. Mol Cell Proteomics. 2009 Jul;8(7):1751-64. doi: 10.1074/mcp.M800588-MCP200. Epub 2009 Apr 15. 19369195
  18. Tigno-Aranjuez JT, Asara JM, Abbott DW: Inhibition of RIP2's tyrosine kinase activity limits NOD2-driven cytokine responses. Genes Dev. 2010 Dec 1;24(23):2666-77. doi: 10.1101/gad.1964410. 21123652
  19. Olsen JV, Vermeulen M, Santamaria A, Kumar C, Miller ML, Jensen LJ, Gnad F, Cox J, Jensen TS, Nigg EA, Brunak S, Mann M: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal. 2010 Jan 12;3(104):ra3. doi: 10.1126/scisignal.2000475. 20068231
  20. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. 21269460
  21. Bertrand MJ, Lippens S, Staes A, Gilbert B, Roelandt R, De Medts J, Gevaert K, Declercq W, Vandenabeele P: cIAP1/2 are direct E3 ligases conjugating diverse types of ubiquitin chains to receptor interacting proteins kinases 1 to 4 (RIP1-4). PLoS One. 2011;6(9):e22356. doi: 10.1371/journal.pone.0022356. Epub 2011 Sep 12. 21931591
  22. Lautz K, Damm A, Menning M, Wenger J, Adam AC, Zigrino P, Kremmer E, Kufer TA: NLRP10 enhances Shigella-induced pro-inflammatory responses. Cell Microbiol. 2012 Oct;14(10):1568-83. doi: 10.1111/j.1462-5822.2012.01822.x. Epub 2012 Jun 21. 22672233
  23. Zhao Y, Alonso C, Ballester I, Song JH, Chang SY, Guleng B, Arihiro S, Murray PJ, Xavier R, Kobayashi KS, Reinecker HC: Control of NOD2 and Rip2-dependent innate immune activation by GEF-H1. Inflamm Bowel Dis. 2012 Apr;18(4):603-12. doi: 10.1002/ibd.21851. Epub 2011 Sep 1. 21887730
  24. Fiil BK, Damgaard RB, Wagner SA, Keusekotten K, Fritsch M, Bekker-Jensen S, Mailand N, Choudhary C, Komander D, Gyrd-Hansen M: OTULIN restricts Met1-linked ubiquitination to control innate immune signaling. Mol Cell. 2013 Jun 27;50(6):818-30. doi: 10.1016/j.molcel.2013.06.004. 23806334
  25. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. 24275569
  26. Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G, Davies H, Teague J, Butler A, Stevens C, Edkins S, O'Meara S, Vastrik I, Schmidt EE, Avis T, Barthorpe S, Bhamra G, Buck G, Choudhury B, Clements J, Cole J, Dicks E, Forbes S, Gray K, Halliday K, Harrison R, Hills K, Hinton J, Jenkinson A, Jones D, Menzies A, Mironenko T, Perry J, Raine K, Richardson D, Shepherd R, Small A, Tofts C, Varian J, Webb T, West S, Widaa S, Yates A, Cahill DP, Louis DN, Goldstraw P, Nicholson AG, Brasseur F, Looijenga L, Weber BL, Chiew YE, DeFazio A, Greaves MF, Green AR, Campbell P, Birney E, Easton DF, Chenevix-Trench G, Tan MH, Khoo SK, Teh BT, Yuen ST, Leung SY, Wooster R, Futreal PA, Stratton MR: Patterns of somatic mutation in human cancer genomes. Nature. 2007 Mar 8;446(7132):153-8. 17344846