Caspase-8

NameCaspase-8
Synonyms
  • 3.4.22.61
  • Apoptotic cysteine protease
  • Apoptotic protease Mch-5
  • CAP4
  • CASP-8
  • FADD-homologous ICE/ced-3-like protease
  • FADD-like ICE
  • FLICE
  • ICE-like apoptotic protease 5
  • MACH
  • MCH5
  • MORT1-associated ced-3 homolog
Gene NameCASP8
OrganismHuman
Amino acid sequence
>lcl|BSEQ0006731|Caspase-8
MDFSRNLYDIGEQLDSEDLASLKFLSLDYIPQRKQEPIKDALMLFQRLQEKRMLEESNLS
FLKELLFRINRLDLLITYLNTRKEEMERELQTPGRAQISAYRVMLYQISEEVSRSELRSF
KFLLQEEISKCKLDDDMNLLDIFIEMEKRVILGEGKLDILKRVCAQINKSLLKIINDYEE
FSKERSSSLEGSPDEFSNGEELCGVMTISDSPREQDSESQTLDKVYQMKSKPRGYCLIIN
NHNFAKAREKVPKLHSIRDRNGTHLDAGALTTTFEELHFEIKPHDDCTVEQIYEILKIYQ
LMDHSNMDCFICCILSHGDKGIIYGTDGQEAPIYELTSQFTGLKCPSLAGKPKVFFIQAC
QGDNYQKGIPVETDSEEQPYLEMDLSSPQTRYIPDEADFLLGMATVNNCVSYRNPAEGTW
YIQSLCQSLRERCPRGDDILTILTEVNYEVSNKDDKKNMGKQMPQPTFTLRKKLVFPSD
Number of residues479
Molecular Weight55390.53
Theoretical pI4.73
GO Classification
Functions
  • peptidase activity
  • cysteine-type endopeptidase activity involved in apoptotic signaling pathway
  • cysteine-type endopeptidase activity
  • cysteine-type peptidase activity
  • ubiquitin protein ligase binding
  • scaffold protein binding
  • cysteine-type endopeptidase activity involved in apoptotic process
  • death effector domain binding
Processes
  • apoptotic process
  • MyD88-independent toll-like receptor signaling pathway
  • syncytiotrophoblast cell differentiation involved in labyrinthine layer development
  • T cell activation
  • activation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway
  • death-inducing signaling complex assembly
  • toll-like receptor 3 signaling pathway
  • TRAIL-activated apoptotic signaling pathway
  • activation of cysteine-type endopeptidase activity involved in apoptotic process
  • programmed necrotic cell death
  • heart development
  • toll-like receptor 4 signaling pathway
  • intrinsic apoptotic signaling pathway
  • regulation of extrinsic apoptotic signaling pathway via death domain receptors
  • negative regulation of cysteine-type endopeptidase activity involved in apoptotic process
  • toll-like receptor signaling pathway
  • positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway
  • regulation of necrotic cell death
  • stimulatory C-type lectin receptor signaling pathway
  • TRIF-dependent toll-like receptor signaling pathway
  • proteolysis
  • response to cobalt ion
  • positive regulation of proteolysis
  • cell surface receptor signaling pathway
  • extrinsic apoptotic signaling pathway
  • response to antibiotic
  • macrophage differentiation
  • hepatocyte apoptotic process
  • cellular component disassembly involved in execution phase of apoptosis
  • programmed cell death
  • response to cold
  • viral process
  • execution phase of apoptosis
  • neural tube formation
  • response to lipopolysaccharide
  • response to tumor necrosis factor
  • angiogenesis
  • positive regulation of macrophage differentiation
  • tumor necrosis factor-mediated signaling pathway
  • nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway
  • negative regulation of necroptotic process
  • cellular response to organic cyclic compound
  • activation of cysteine-type endopeptidase activity
  • nucleotide-binding oligomerization domain containing signaling pathway
  • necroptotic process
  • positive regulation of I-kappaB kinase/NF-kappaB signaling
  • regulation of tumor necrosis factor-mediated signaling pathway
  • natural killer cell activation
  • protein heterooligomerization
  • innate immune response
  • negative regulation of I-kappaB kinase/NF-kappaB signaling
  • response to ethanol
  • proteolysis involved in cellular protein catabolic process
  • cellular response to mechanical stimulus
  • response to estradiol
  • B cell activation
  • regulation of thymocyte apoptotic process
  • apoptotic signaling pathway
  • positive regulation of extrinsic apoptotic signaling pathway
Components
  • cytoplasm
  • mitochondrion
  • cytoskeleton
  • membrane raft
  • neuron projection
  • microtubule organizing center
  • death-inducing signaling complex
  • mitochondrial outer membrane
  • ripoptosome
  • cell body
  • cytosol
  • CD95 death-inducing signaling complex
  • nucleoplasm
  • Noc1p-Noc2p complex
General FunctionUbiquitin protein ligase binding
Specific FunctionMost upstream protease of the activation cascade of caspases responsible for the TNFRSF6/FAS mediated and TNFRSF1A induced cell death. Binding to the adapter molecule FADD recruits it to either receptor. The resulting aggregate called death-inducing signaling complex (DISC) performs CASP8 proteolytic activation. The active dimeric enzyme is then liberated from the DISC and free to activate downstream apoptotic proteases. Proteolytic fragments of the N-terminal propeptide (termed CAP3, CAP5 and CAP6) are likely retained in the DISC. Cleaves and activates CASP3, CASP4, CASP6, CASP7, CASP9 and CASP10. May participate in the GZMB apoptotic pathways. Cleaves ADPRT. Hydrolyzes the small-molecule substrate, Ac-Asp-Glu-Val-Asp-|-AMC. Likely target for the cowpox virus CRMA death inhibitory protein. Isoform 5, isoform 6, isoform 7 and isoform 8 lack the catalytic site and may interfere with the pro-apoptotic activity of the complex.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein IDNot Available
UniProtKB IDQ14790
UniProtKB Entry NameCASP8_HUMAN
Cellular LocationCytoplasm
Gene sequence
>lcl|BSEQ0019424|Caspase-8 (CASP8)
ATGGACTTCAGCAGAAATCTTTATGATATTGGGGAACAACTGGACAGTGAAGATCTGGCC
TCCCTCAAGTTCCTGAGCCTGGACTACATTCCGCAAAGGAAGCAAGAACCCATCAAGGAT
GCCTTGATGTTATTCCAGAGACTCCAGGAAAAGAGAATGTTGGAGGAAAGCAATCTGTCC
TTCCTGAAGGAGCTGCTCTTCCGAATTAATAGACTGGATTTGCTGATTACCTACCTAAAC
ACTAGAAAGGAGGAGATGGAAAGGGAACTTCAGACACCAGGCAGGGCTCAAATTTCTGCC
TACAGGGTCATGCTCTATCAGATTTCAGAAGAAGTGAGCAGATCAGAATTGAGGTCTTTT
AAGTTTCTTTTGCAAGAGGAAATCTCCAAATGCAAACTGGATGATGACATGAACCTGCTG
GATATTTTCATAGAGATGGAGAAGAGGGTCATCCTGGGAGAAGGAAAGTTGGACATCCTG
AAAAGAGTCTGTGCCCAAATCAACAAGAGCCTGCTGAAGATAATCAACGACTATGAAGAA
TTCAGCAAAGGGGAGGAGTTGTGTGGGGTAATGACAATCTCGGACTCTCCAAGAGAACAG
GATAGTGAATCACAGACTTTGGACAAAGTTTACCAAATGAAAAGCAAACCTCGGGGATAC
TGTCTGATCATCAACAATCACAATTTTGCAAAAGCACGGGAGAAAGTGCCCAAACTTCAC
AGCATTAGGGACAGGAATGGAACACACTTGGATGCAGGGGCTTTGACCACGACCTTTGAA
GAGCTTCATTTTGAGATCAAGCCCCACGATGACTGCACAGTAGAGCAAATCTATGAGATT
TTGAAAATCTACCAACTCATGGACCACAGTAACATGGACTGCTTCATCTGCTGTATCCTC
TCCCATGGAGACAAGGGCATCATCTATGGCACTGATGGACAGGAGGCCCCCATCTATGAG
CTGACATCTCAGTTCACTGGTTTGAAGTGCCCTTCCCTTGCTGGAAAACCCAAAGTGTTT
TTTATTCAGGCTTGTCAGGGGGATAACTACCAGAAAGGTATACCTGTTGAGACTGATTCA
GAGGAGCAACCCTATTTAGAAATGGATTTATCATCACCTCAAACGAGATATATCCCGGAT
GAGGCTGACTTTCTGCTGGGGATGGCCACTGTGAATAACTGTGTTTCCTACCGAAACCCT
GCAGAGGGAACCTGGTACATCCAGTCACTTTGCCAGAGCCTGAGAGAGCGATGTCCTCGA
GGCGATGATATTCTCACCATCCTGACTGAAGTGAACTATGAAGTAAGCAACAAGGATGAC
AAGAAAAACATGGGGAAACAGATGCCTCAGCCTACTTTCACACTAAGAAAAAAACTTGTC
TTCCCTTCTGATTGA
GenBank Gene IDAC007256
GeneCard IDNot Available
GenAtlas IDCASP8
HGNC IDHGNC:1509
Chromosome Location2
LocusNot Available
References
  1. Boldin MP, Goncharov TM, Goltsev YV, Wallach D: Involvement of MACH, a novel MORT1/FADD-interacting protease, in Fas/APO-1- and TNF receptor-induced cell death. Cell. 1996 Jun 14;85(6):803-15. 8681376
  2. Muzio M, Chinnaiyan AM, Kischkel FC, O'Rourke K, Shevchenko A, Ni J, Scaffidi C, Bretz JD, Zhang M, Gentz R, Mann M, Krammer PH, Peter ME, Dixit VM: FLICE, a novel FADD-homologous ICE/CED-3-like protease, is recruited to the CD95 (Fas/APO-1) death--inducing signaling complex. Cell. 1996 Jun 14;85(6):817-27. 8681377
  3. Fernandes-Alnemri T, Armstrong RC, Krebs J, Srinivasula SM, Wang L, Bullrich F, Fritz LC, Trapani JA, Tomaselli KJ, Litwack G, Alnemri ES: In vitro activation of CPP32 and Mch3 by Mch4, a novel human apoptotic cysteine protease containing two FADD-like domains. Proc Natl Acad Sci U S A. 1996 Jul 23;93(15):7464-9. 8755496
  4. Srinivasula SM, Ahmad M, Ottilie S, Bullrich F, Banks S, Wang Y, Fernandes-Alnemri T, Croce CM, Litwack G, Tomaselli KJ, Armstrong RC, Alnemri ES: FLAME-1, a novel FADD-like anti-apoptotic molecule that regulates Fas/TNFR1-induced apoptosis. J Biol Chem. 1997 Jul 25;272(30):18542-5. 9228018
  5. Grenet J, Teitz T, Wei T, Valentine V, Kidd VJ: Structure and chromosome localization of the human CASP8 gene. Gene. 1999 Jan 21;226(2):225-32. 9931493
  6. Hadano S, Yanagisawa Y, Skaug J, Fichter K, Nasir J, Martindale D, Koop BF, Scherer SW, Nicholson DW, Rouleau GA, Ikeda J, Hayden MR: Cloning and characterization of three novel genes, ALS2CR1, ALS2CR2, and ALS2CR3, in the juvenile amyotrophic lateral sclerosis (ALS2) critical region at chromosome 2q33-q34: candidate genes for ALS2. Genomics. 2001 Jan 15;71(2):200-13. 11161814
  7. Himeji D, Horiuchi T, Tsukamoto H, Hayashi K, Watanabe T, Harada M: Characterization of caspase-8L: a novel isoform of caspase-8 that behaves as an inhibitor of the caspase cascade. Blood. 2002 Jun 1;99(11):4070-8. 12010809
  8. Breckenridge DG, Nguyen M, Kuppig S, Reth M, Shore GC: The procaspase-8 isoform, procaspase-8L, recruited to the BAP31 complex at the endoplasmic reticulum. Proc Natl Acad Sci U S A. 2002 Apr 2;99(7):4331-6. Epub 2002 Mar 26. 11917123
  9. Hillier LW, Graves TA, Fulton RS, Fulton LA, Pepin KH, Minx P, Wagner-McPherson C, Layman D, Wylie K, Sekhon M, Becker MC, Fewell GA, Delehaunty KD, Miner TL, Nash WE, Kremitzki C, Oddy L, Du H, Sun H, Bradshaw-Cordum H, Ali J, Carter J, Cordes M, Harris A, Isak A, van Brunt A, Nguyen C, Du F, Courtney L, Kalicki J, Ozersky P, Abbott S, Armstrong J, Belter EA, Caruso L, Cedroni M, Cotton M, Davidson T, Desai A, Elliott G, Erb T, Fronick C, Gaige T, Haakenson W, Haglund K, Holmes A, Harkins R, Kim K, Kruchowski SS, Strong CM, Grewal N, Goyea E, Hou S, Levy A, Martinka S, Mead K, McLellan MD, Meyer R, Randall-Maher J, Tomlinson C, Dauphin-Kohlberg S, Kozlowicz-Reilly A, Shah N, Swearengen-Shahid S, Snider J, Strong JT, Thompson J, Yoakum M, Leonard S, Pearman C, Trani L, Radionenko M, Waligorski JE, Wang C, Rock SM, Tin-Wollam AM, Maupin R, Latreille P, Wendl MC, Yang SP, Pohl C, Wallis JW, Spieth J, Bieri TA, Berkowicz N, Nelson JO, Osborne J, Ding L, Meyer R, Sabo A, Shotland Y, Sinha P, Wohldmann PE, Cook LL, Hickenbotham MT, Eldred J, Williams D, Jones TA, She X, Ciccarelli FD, Izaurralde E, Taylor J, Schmutz J, Myers RM, Cox DR, Huang X, McPherson JD, Mardis ER, Clifton SW, Warren WC, Chinwalla AT, Eddy SR, Marra MA, Ovcharenko I, Furey TS, Miller W, Eichler EE, Bork P, Suyama M, Torrents D, Waterston RH, Wilson RK: Generation and annotation of the DNA sequences of human chromosomes 2 and 4. Nature. 2005 Apr 7;434(7034):724-31. 15815621
  10. 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
  11. Srinivasula SM, Ahmad M, Fernandes-Alnemri T, Litwack G, Alnemri ES: Molecular ordering of the Fas-apoptotic pathway: the Fas/APO-1 protease Mch5 is a CrmA-inhibitable protease that activates multiple Ced-3/ICE-like cysteine proteases. Proc Natl Acad Sci U S A. 1996 Dec 10;93(25):14486-91. 8962078
  12. Muzio M, Salvesen GS, Dixit VM: FLICE induced apoptosis in a cell-free system. Cleavage of caspase zymogens. J Biol Chem. 1997 Jan 31;272(5):2952-6. 9006941
  13. Medema JP, Scaffidi C, Kischkel FC, Shevchenko A, Mann M, Krammer PH, Peter ME: FLICE is activated by association with the CD95 death-inducing signaling complex (DISC). EMBO J. 1997 May 15;16(10):2794-804. 9184224
  14. Horiuchi T, Himeji D, Tsukamoto H, Harashima S, Hashimura C, Hayashi K: Dominant expression of a novel splice variant of caspase-8 in human peripheral blood lymphocytes. Biochem Biophys Res Commun. 2000 Jun 16;272(3):877-81. 10860845
  15. Ng FW, Nguyen M, Kwan T, Branton PE, Nicholson DW, Cromlish JA, Shore GC: p28 Bap31, a Bcl-2/Bcl-XL- and procaspase-8-associated protein in the endoplasmic reticulum. J Cell Biol. 1997 Oct 20;139(2):327-38. 9334338
  16. Condorelli G, Vigliotta G, Cafieri A, Trencia A, Andalo P, Oriente F, Miele C, Caruso M, Formisano P, Beguinot F: PED/PEA-15: an anti-apoptotic molecule that regulates FAS/TNFR1-induced apoptosis. Oncogene. 1999 Aug 5;18(31):4409-15. 10442631
  17. Skaletskaya A, Bartle LM, Chittenden T, McCormick AL, Mocarski ES, Goldmacher VS: A cytomegalovirus-encoded inhibitor of apoptosis that suppresses caspase-8 activation. Proc Natl Acad Sci U S A. 2001 Jul 3;98(14):7829-34. Epub 2001 Jun 26. 11427719
  18. Hillman RT, Green RE, Brenner SE: An unappreciated role for RNA surveillance. Genome Biol. 2004;5(2):R8. Epub 2004 Feb 2. 14759258
  19. Jo DG, Jun JI, Chang JW, Hong YM, Song S, Cho DH, Shim SM, Lee HJ, Cho C, Kim DH, Jung YK: Calcium binding of ARC mediates regulation of caspase 8 and cell death. Mol Cell Biol. 2004 Nov;24(22):9763-70. 15509781
  20. McDonald ER 3rd, El-Deiry WS: Suppression of caspase-8- and -10-associated RING proteins results in sensitization to death ligands and inhibition of tumor cell growth. Proc Natl Acad Sci U S A. 2004 Apr 20;101(16):6170-5. Epub 2004 Apr 6. 15069192
  21. Rush J, Moritz A, Lee KA, Guo A, Goss VL, Spek EJ, Zhang H, Zha XM, Polakiewicz RD, Comb MJ: Immunoaffinity profiling of tyrosine phosphorylation in cancer cells. Nat Biotechnol. 2005 Jan;23(1):94-101. Epub 2004 Dec 12. 15592455
  22. Jun JI, Chung CW, Lee HJ, Pyo JO, Lee KN, Kim NS, Kim YS, Yoo HS, Lee TH, Kim E, Jung YK: Role of FLASH in caspase-8-mediated activation of NF-kappaB: dominant-negative function of FLASH mutant in NF-kappaB signaling pathway. Oncogene. 2005 Jan 20;24(4):688-96. 15592525
  23. Milovic-Holm K, Krieghoff E, Jensen K, Will H, Hofmann TG: FLASH links the CD95 signaling pathway to the cell nucleus and nuclear bodies. EMBO J. 2007 Jan 24;26(2):391-401. 17245429
  24. Matthess Y, Raab M, Sanhaji M, Lavrik IN, Strebhardt K: Cdk1/cyclin B1 controls Fas-mediated apoptosis by regulating caspase-8 activity. Mol Cell Biol. 2010 Dec;30(24):5726-40. doi: 10.1128/MCB.00731-10. Epub 2010 Oct 11. 20937773
  25. 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
  26. Blasche S, Mortl M, Steuber H, Siszler G, Nisa S, Schwarz F, Lavrik I, Gronewold TM, Maskos K, Donnenberg MS, Ullmann D, Uetz P, Kogl M: The E. coli effector protein NleF is a caspase inhibitor. PLoS One. 2013;8(3):e58937. doi: 10.1371/journal.pone.0058937. Epub 2013 Mar 14. 23516580
  27. Blanchard H, Kodandapani L, Mittl PR, Marco SD, Krebs JF, Wu JC, Tomaselli KJ, Grutter MG: The three-dimensional structure of caspase-8: an initiator enzyme in apoptosis. Structure. 1999 Sep 15;7(9):1125-33. 10508784
  28. Watt W, Koeplinger KA, Mildner AM, Heinrikson RL, Tomasselli AG, Watenpaugh KD: The atomic-resolution structure of human caspase-8, a key activator of apoptosis. Structure. 1999 Sep 15;7(9):1135-43. 10508785
  29. Chun HJ, Zheng L, Ahmad M, Wang J, Speirs CK, Siegel RM, Dale JK, Puck J, Davis J, Hall CG, Skoda-Smith S, Atkinson TP, Straus SE, Lenardo MJ: Pleiotropic defects in lymphocyte activation caused by caspase-8 mutations lead to human immunodeficiency. Nature. 2002 Sep 26;419(6905):395-9. 12353035
  30. MacPherson G, Healey CS, Teare MD, Balasubramanian SP, Reed MW, Pharoah PD, Ponder BA, Meuth M, Bhattacharyya NP, Cox A: Association of a common variant of the CASP8 gene with reduced risk of breast cancer. J Natl Cancer Inst. 2004 Dec 15;96(24):1866-9. 15601643
  31. Cox A, Dunning AM, Garcia-Closas M, Balasubramanian S, Reed MW, Pooley KA, Scollen S, Baynes C, Ponder BA, Chanock S, Lissowska J, Brinton L, Peplonska B, Southey MC, Hopper JL, McCredie MR, Giles GG, Fletcher O, Johnson N, dos Santos Silva I, Gibson L, Bojesen SE, Nordestgaard BG, Axelsson CK, Torres D, Hamann U, Justenhoven C, Brauch H, Chang-Claude J, Kropp S, Risch A, Wang-Gohrke S, Schurmann P, Bogdanova N, Dork T, Fagerholm R, Aaltonen K, Blomqvist C, Nevanlinna H, Seal S, Renwick A, Stratton MR, Rahman N, Sangrajrang S, Hughes D, Odefrey F, Brennan P, Spurdle AB, Chenevix-Trench G, Beesley J, Mannermaa A, Hartikainen J, Kataja V, Kosma VM, Couch FJ, Olson JE, Goode EL, Broeks A, Schmidt MK, Hogervorst FB, Van't Veer LJ, Kang D, Yoo KY, Noh DY, Ahn SH, Wedren S, Hall P, Low YL, Liu J, Milne RL, Ribas G, Gonzalez-Neira A, Benitez J, Sigurdson AJ, Stredrick DL, Alexander BH, Struewing JP, Pharoah PD, Easton DF: A common coding variant in CASP8 is associated with breast cancer risk. Nat Genet. 2007 Mar;39(3):352-8. Epub 2007 Feb 11. 17293864
  32. Sun T, Gao Y, Tan W, Ma S, Shi Y, Yao J, Guo Y, Yang M, Zhang X, Zhang Q, Zeng C, Lin D: A six-nucleotide insertion-deletion polymorphism in the CASP8 promoter is associated with susceptibility to multiple cancers. Nat Genet. 2007 May;39(5):605-13. Epub 2007 Apr 22. 17450141
  33. Li C, Zhao H, Hu Z, Liu Z, Wang LE, Gershenwald JE, Prieto VG, Lee JE, Duvic M, Grimm EA, Wei Q: Genetic variants and haplotypes of the caspase-8 and caspase-10 genes contribute to susceptibility to cutaneous melanoma. Hum Mutat. 2008 Dec;29(12):1443-51. doi: 10.1002/humu.20803. 18563783