Comparative analysis of apoptosis and inflammation genes of mice and humans.
Apoptosis (programmed cell death) plays important roles in many facets of normal mammalian physiology. Host-pathogen interactions have provided evolutionary pressure for apoptosis as a defense mechanism against viruses and microbes, sometimes linking apoptosis mechanisms with inflammatory responses through NFkappaB induction. Proteins involved in apoptosis and NFkappaB induction commonly contain evolutionarily conserved domains that can serve as signatures for identification by bioinformatics methods. Using a combination of public (NCBI) and private (RIKEN) databases, we compared the repertoire of apoptosis and NFkappaB-inducing genes in humans and mice from cDNA/EST/genomic data, focusing on the following domain families: (1) Caspase proteases; (2) Caspase recruitment domains (CARD); (3) Death Domains (DD); (4) Death Effector Domains (DED); (5) BIR domains of Inhibitor of Apoptosis Proteins (IAPs); (6) Bcl-2 homology (BH) domains of Bcl-2 family proteins; (7) Tumor Necrosis Factor (TNF)-family ligands; (8) TNF receptors (TNFR); (9) TIR domains; (10) PAAD (PYRIN; PYD, DAPIN); (11) nucleotide-binding NACHT domains; (12) TRAFs; (13) Hsp70-binding BAG domains; (14) endonuclease-associated CIDE domains; and (15) miscellaneous additional proteins. After excluding redundancy due to alternative splice forms, sequencing errors, and other considerations, we identified cDNAs derived from a total of 227 human genes among these domain families. Orthologous murine genes were found for 219 (96%); in addition, several unique murine genes were found, which appear not to have human orthologs. This mismatch may be due to the still fragmentary information about the mouse genome or genuine differences between mouse and human repertoires of apoptotic genes. With this caveat, we discuss similarities and differences in human and murine genes from these domain families.
Reed
John C
JC
The Burnham Institute, La Jolla, California 92037, USA. jreed@burnham.org
Doctor
Kutbuddin
K
Rojas
Ana
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Zapata
Juan M
JM
Stehlik
Christian
C
Fiorentino
Loredana
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Damiano
Jason
J
Roth
Wilfried
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Matsuzawa
Shu-Ichi
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Newman
Ruchi
R
Takayama
Shinichi
S
Marusawa
Hiroyuki
H
Xu
Famming
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Salvesen
Guy
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Godzik
Adam
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D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins; D053468:CARD Signaling Adaptor Proteins; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology; D020169:Caspases / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D053938:DNA Fragmentation / Q000235:genetics / Q000502:physiology; D030541:Databases, Genetic / Q000706:statistics & numerical data; D051528:Guanylate Kinases; D006801:Humans; D051550:I-kappa B Kinase; D020672:I-kappa B Proteins / Q000235:genetics / Q000502:physiology; D007249:Inflammation / Q000201:enzymology / Q000235:genetics; D051034:Inhibitor of Apoptosis Proteins; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology; D008565:Membrane Proteins; D051379:Mice; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000235:genetics / Q000502:physiology; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000737:chemistry / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology; D018124:Receptors, Tumor Necrosis Factor / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D012689:Sequence Homology, Nucleic Acid; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha / Q000737:chemistry / Q000235:genetics / Q000502:physiology
D051017:Apoptosis Regulatory Proteins; D053468:CARD Signaling Adaptor Proteins; C472088:CIDEC protein, human; C496467:Card11 protein, mouse; D002352:Carrier Proteins; C112510:Cidea protein, mouse; D020672:I-kappa B Proteins; D051034:Inhibitor of Apoptosis Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011506:Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011956:Receptors, Cell Surface; D018124:Receptors, Tumor Necrosis Factor; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D017346:Protein Serine-Threonine Kinases; C496559:CHUK protein, human; C496564:Chuk protein, mouse; D051550:I-kappa B Kinase; C496560:IKBKB protein, human; C496565:IKBKE protein, human; C496562:Ikbkb protein, mouse; C496566:Ikbke protein, mouse; D051528:Guanylate Kinases; D020169:Caspases