64626PathwayApoptotic DNA Fragmentation and Tissue HomeostasisApoptotic endonucleases degrade chromosomal DNA during programmed cell death. ICAD and CAD exist in the nucleus in normal cells and is a major endonuclease in apoptosis. Its activation is normally caspase dependent. EndoG resides in mitochondria in normal cells and travels to the nucleus, where it fragments chromosomal DNA upon activation of apoptosis. Once released from the mitochondrial intermembrane space, EndoG activity is caspase independent.ProteinPW064764CenterPathwayVisualizationContext6504013001798#000099PathwayVisualization6451064626Apoptotic DNA Fragmentation and Tissue HomeostasisApoptotic endonucleases degrade chromosomal DNA during programmed cell death. ICAD and CAD exist in the nucleus in normal cells and is a major endonuclease in apoptosis. Its activation is normally caspase dependent. EndoG resides in mitochondria in normal cells and travels to the nucleus, where it fragments chromosomal DNA upon activation of apoptosis. Once released from the mitochondrial intermembrane space, EndoG activity is caspase independent.Protein122989611849972Zhang J, Xu M: Apoptotic DNA fragmentation and tissue homeostasis. Trends Cell Biol. 2002 Feb;12(2):84-9.64626Pathway229924https://cgap.nci.nih.gov/Pathways/BioCarta/h_DNAfragmentPathway64626Pathway1CellCL:00000002Platelet CL:00002331Homo sapiens9606EukaryoteHuman18Saccharomyces cerevisiae4932EukaryoteYeast4Arabidopsis thaliana3702EukaryoteThale cress12Mus musculus10090EukaryoteMouse3Escherichia coli562Prokaryote5Bos taurus9913EukaryoteCattle17Rattus norvegicus10116EukaryoteRat10Drosophila melanogaster7227EukaryoteFruit fly6Caenorhabditis elegans6239EukaryoteRoundworm49Bathymodiolus platifrons220390EukaryoteDeep sea mussel23Pseudomonas aeruginosa287Prokaryote5CytoplasmGO:00057371CytosolGO:00058292MitochondrionGO:00057397Endoplasmic Reticulum MembraneGO:000578935ChloroplastGO:00095073Mitochondrial MatrixGO:000575911Extracellular SpaceGO:00056154PeroxisomeGO:000577712Mitochondrial Inner MembraneGO:000574313Endoplasmic ReticulumGO:000578310Cell MembraneGO:000588631Periplasmic SpaceGO:000562015NucleusGO:000563428StomachBTO:0001307155261LiverBTO:00007597292Endothelium BTO:00003938Blood VesselBTO:0001102741111HeartBTO:000056273108511PW_BS0000082111PW_BS0000023211PW_BS0000037028511PW_BS000070101711PW_BS0000101632181PW_BS0001631601181PW_BS000160151141PW_BS0001512253541PW_BS0000241122121PW_BS0001121321121PW_BS0001321115121PW_BS000111943PW_BS000094122551PW_BS000122407251PW_BS000115124151PW_BS0001241355171PW_BS0001351192171PW_BS0001191181171PW_BS0001182975101PW_BS0000244812101PW_BS0001152991101PW_BS000024205561PW_BS000024388161PW_BS000112206261PW_BS0000244311PW_BS00000416212PW_BS00001615111PW_BS0000155181PW_BS000051682512PW_BS00006829111PW_BS000029117131PW_BS000117103331PW_BS0001031203171PW_BS0001201333121PW_BS00013316611PW_BS0001661985181PW_BS000024226441PW_BS0000242905491PW_BS0000241141112PW_BS0001143361121PW_BS00002811PW_BS000001406351PW_BS000115409115PW_BS000115429151PW_BS0001151371117PW_BS0001374641171PW_BS0001154793101PW_BS0001154831110PW_BS000115501361PW_BS000115208116PW_BS000024171211PW_BS00001749711PW_BS000049711PW_BS000007181311PW_BS00001814101PW_BS000014311511PW_BS000031107313PW_BS000107101531PW_BS00010110813PW_BS0001081151012PW_BS00011565111PW_BS000065315123PW_BS0000243183123PW_BS000024253541PW_BS00002427151PW_BS000027801111PW_BS00008049PW_B0000491257558ProteinComplex112614ProteinComplex18032481051HydrogenHMDB0001362Hydrogen is a colorless, odorless, nonmetallic, tasteless, highly flammable diatomic gas with the molecular formula H2. With an atomic weight of 1.00794, hydrogen is the lightest element. Besides the common H1 isotope, hydrogen exists as the stable isotope Deuterium and the unstable, radioactive isotope Tritium. Hydrogen is the most abundant of the chemical elements, constituting roughly 75% of the universe's elemental mass. Hydrogen can form compounds with most elements and is present in water and most organic compounds. It plays a particularly important role in acid-base chemistry, in which many reactions involve the exchange of protons between soluble molecules. Oxidation of hydrogen, in the sense of removing its electron, formally gives H+, containing no electrons and a nucleus which is usually composed of one proton. That is why H+ is often called a proton. This species is central to discussion of acids. Under the Bronsted-Lowry theory, acids are proton donors, while bases are proton acceptors. A bare proton H+ cannot exist in solution because of its strong tendency to attach itself to atoms or molecules with electrons. However, the term 'proton' is used loosely to refer to positively charged or cationic hydrogen, denoted H+. H2 is a product of some types of anaerobic metabolism and is produced by several microorganisms, usually via reactions catalyzed by iron- or nickel-containing enzymes called hydrogenases. These enzymes catalyze the reversible redox reaction between H2 and its component two protons and two electrons. Creation of hydrogen gas occurs in the transfer of reducing equivalents produced during pyruvate fermentation to water.1333-74-0C002825883867318276ALPHA-GLUCOSE-16-BISPHOSPHATE762[H][H]H2InChI=1S/H2/h1HUFHFLCQGNIYNRP-UHFFFAOYSA-N2.01592.015650064000FDB016247Dihydrogen;Hydrogen;Hydrogen cation;Hydrogen gas;Hydrogen ion;Hydronium;Proton;E 949;E-949;E949;H2;Molecular hydrogenPW_C001051H2175682388226963314670495210703316370451601277415113270225785941127860313278772111113163941214481221220324071220371241240061351245861191245911181260732971261824811261882991275292051280053881283232061005Zinc (II) ionHMDB0001303Zinc is an essential element, necessary for sustaining all life.Physiologically, it exists as an ion in the body. It is estimated that 3000 of the hundreds of thousands of proteins in the human body contain zinc prosthetic groups. In addition, there are over a dozen types of cells in the human body that secrete zinc ions, and the roles of these secreted zinc signals in medicine and health are now being actively studied. Intriguingly, brain cells in the mammalian forebrain are one type of cell that secretes zinc, along with its other neuronal messenger substances. Cells in the salivary gland, prostate, immune system and intestine are other types that secrete zinc. Obtaining a sufficient zinc intake during pregnancy and in young children is a problem, especially among those who cannot afford a good and varied diet. Brain development is stunted by zinc deficiency in utero and in youth. Zinc is an activator of certain enzymes, such as carbonic anhydrase. Carbonic anhydrase is important in the transport of carbon dioxide in vertebrate blood. Even though zinc is an essential requirement for a healthy body, too much zinc can be harmful. Excessive absorption of zinc can also suppress copper and iron absorption. The free zinc ion in solution is highly toxic to plants, invertebrates, and even vertebrate fish. The Free Ion Activity Model (FIAM) is well-established in the literature, and shows that just micromolar amounts of the free ion kills some organisms.23713-49-7C000383205129105ZN%2b229723DB01593[Zn++]ZnInChI=1S/Zn/q+2PTFCDOFLOPIGGS-UHFFFAOYSA-Nzinc(2+) ion65.40963.9291465780zinc(2+) ion22FDB003729Zinc;Zinc ion;Dietary zinc;Zinc cation;Zinc, ion (zn2+);Zn(ii);Zn(2+);Zn2+PW_C001005Zinc132384118827116529152957513044683120293147705410117542510354341185459120556013255851335598135744916611787198124662261272429013321151769672257740111177580114779293368040011200201241200354061200601221204414091212574291230751371238274641253982991254134791254382971256854831269383881269535011269762051271802089795ZincHMDB0015532Zinc is an essential element, necessary for sustaining all life. It is a trace element in the diet, forming an essential part of many enzymes, and playing an important role in protein synthesis and in cell division. Physiologically, it exists as an ion in the body. It is estimated that 3000 of the hundreds of thousands of proteins in the human body contain zinc prosthetic groups. In addition, there are over a dozen cell types in the human body that secrete zinc ions, and the roles of these secreted zinc signals in medicine and health are now being actively studied. Intriguingly, brain cells in the mammalian forebrain are one type of cell that secretes zinc, along with its other neuronal messenger substances. Cells in the salivary gland, prostate, immune system, and intestine are other types that secrete zinc. Obtaining a sufficient zinc intake during pregnancy and in young children is a problem, especially among those who cannot afford a good and varied diet. Zinc deficiency is associated with anemia, short stature, hypogonadism, impaired wound healing, and geophagia. Brain development is stunted by zinc deficiency in utero and in youth. Zinc is an activator of certain enzymes, such as carbonic anhydrase. Carbonic anhydrase is important in the transport of carbon dioxide in vertebrate blood. Even though zinc is an essential requirement for a healthy body, too much zinc can be harmful. Excessive absorption of zinc can also suppress copper and iron absorption. The free zinc ion in solution is highly toxic to plants, invertebrates, and even vertebrate fish. The Free Ion Activity Model (FIAM) is well-established in the literature and shows that just micromolar amounts of the free ion kill some organisms.7440-66-6239942736322430DB01593[Zn]ZnInChI=1S/ZnHCHKCACWOHOZIP-UHFFFAOYSA-Nzinc(2+) ion65.40963.9291465780zinc(2+) ion2230zn;Cinc;Zincum;Zink;Zn;Zn(ii);Zn2+PW_C009795Zinc57817112190432137172154493610294083744691845431449993166891076690101669910870201601175811512229151126336542397315423993187703025378023132783281127881111112011912412089812212230840712285211812346913512486011912548629912647448112702338812731720512804320614367Endonuclease G, mitochondrialQ14249
Cleaves DNA at double-stranded (DG)n.(DC)n and at single-stranded (DC)n tracts. In addition to deoxyribonuclease activities, also has ribonuclease (RNase) and RNase H activities. Capable of generating the RNA primers required by DNA polymerase gamma to initiate replication of mitochondrial DNA (By similarity).
ENDOG13.1.30.-80187380197880198272335CAD proteinP27708
This protein is a "fusion" protein encoding four enzymatic activities of the pyrimidine pathway (GATase, CPSase, ATCase and DHOase).
HMDBP03298CAD2p22-p21BC06551016.3.5.5; 2.1.3.2; 3.5.2.39182703214364DNA topoisomerase 2-alphaP11388
Control of topological states of DNA by transient breakage and subsequent rejoining of DNA strands. Topoisomerase II makes double-strand breaks. Essential during mitosis and meiosis for proper segregation of daughter chromosomes. May play a role in regulating the period length of ARNTL/BMAL1 transcriptional oscillation (By similarity).
TOP2A15.99.1.3801742780175814365High mobility group protein B1P09429
Multifunctional redox sensitive protein with various roles in different cellular compartments. In the nucleus is one of the major chromatin-associated non-histone proteins and acts as a DNA chaperone involved in replication, transcription, chromatin remodeling, V(D)J recombination, DNA repair and genome stability. Proposed to be an universal biosensor for nucleic acids. Promotes host inflammatory response to sterile and infectious signals and is involved in the coordination and integration of innate and adaptive immune responses. In the cytoplasm functions as sensor and/or chaperone for immunogenic nucleic acids implicating the activation of TLR9-mediated immune responses, and mediates autophagy. Acts as danger associated molecular pattern (DAMP) molecule that amplifies immune responses during tissue injury (PubMed:27362237). Released to the extracellular environment can bind DNA, nucleosomes, IL-1 beta, CXCL12, AGER isoform 2/sRAGE, lipopolysaccharide (LPS) and lipoteichoic acid (LTA), and activates cells through engagement of multiple surface receptors. In the extracellular compartment fully reduced HMGB1 (released by necrosis) acts as a chemokine, disulfide HMGB1 (actively secreted) as a cytokine, and sulfonyl HMGB1 (released from apoptotic cells) promotes immunological tolerance (PubMed:23519706, PubMed:23446148, PubMed:23994764, PubMed:25048472). Has proangiogdenic activity (By similarity). May be involved in platelet activation (By similarity). Binds to phosphatidylserine and phosphatidylethanolamide (By similarity). Bound to RAGE mediates signaling for neuronal outgrowth (By similarity). May play a role in accumulation of expanded polyglutamine (polyQ) proteins such as huntingtin (HTT) or TBP (PubMed:23303669, PubMed:25549101).
HMGB118017627801771480181814366High mobility group protein B2P26583
Multifunctional protein with various roles in different cellular compartments. May act in a redox sensitive manner. In the nucleus is an abundant chromatin-associated non-histone protein involved in transcription, chromatin remodeling and V(D)J recombination and probably other processes. Binds DNA with a preference to non-canonical DNA structures such as single-stranded DNA. Can bent DNA and enhance DNA flexibility by looping thus providing a mechanism to promote activities on various gene promoters by enhancing transcription factor binding and/or bringing distant regulatory sequences into close proximity (PubMed:7797075, PubMed:11909973, PubMed:19522541, PubMed:18413230, PubMed:19965638, PubMed:20123072). Involved in V(D)J recombination by acting as a cofactor of the RAG complex: acts by stimulating cleavage and RAG protein binding at the 23 bp spacer of conserved recombination signal sequences (RSS) (By similarity). Proposed to be involved in the innate immune response to nucleic acids by acting as a promiscuous immunogenic DNA/RNA sensor which cooperates with subsequent discriminative sensing by specific pattern recognition receptors (By similarity). In the extracellular compartment acts as a chemokine. Promotes proliferation and migration of endothelial cells implicating AGER/RAGE (PubMed:19811285). Has antimicrobial activity in gastrointestinal epithelial tissues (PubMed:23877675). Involved in inflammatory response to antigenic stimulus coupled with proinflammatory activity (By similarity). Involved in modulation of neurogenesis probably by regulation of neural stem proliferation (By similarity). Involved in articular cartilage surface maintenance implicating LEF1 and the Wnt/beta-catenin pathway (By similarity).
HMGB21801782780182814363DNA fragmentation factor subunit alphaO00273
Inhibitor of the caspase-activated DNase (DFF40).
DFFA18017085802Caspase-7P55210Involved in the activation cascade of caspases responsible for apoptosis execution. Cleaves and activates sterol regulatory element binding proteins (SREBPs). Proteolytically cleaves poly(ADP-ribose) polymerase (PARP) at a '216-Asp-|-Gly-217' bond. Overexpression promotes programmed cell death.CASP713.4.22.60465428018582069Granzyme BP10144This enzyme is necessary for target cell lysis in cell- mediated immune responses. It cleaves after Asp. Seems to be linked to an activation cascade of caspases (aspartate-specific cysteine proteases) responsible for apoptosis execution. Cleaves caspase-3, -7, -9 and 10 to give rise to active enzymes mediating apoptosisHMDBP02728GZMB14q11.2M2887913.4.21.79801868854778014460Caspase-3P4257418032887558ICAD1PW_P007558154351436380171814CAD protein1PW_P000014152335611100568887561Endonuclease G, mitochondrial1PW_P00756115441143677559CAD-Topo II-HMG 1-HMG 2-H11PW_P00755915436233515437143641543814365154391436679210511097Caspase-71PW_P001097125858021456979517560Granzyme B1PW_P0075601544020698017987534Caspase-31PW_P00753415410144601110821PW_R110821Right403192491Boundfalse40319375581ProteinComplexfalse1156PW_T001156Active139475611ProteinComplex38Right1157PW_T001157139575611ProteinComplex827Right417ActivationPW_I00041783349Bound18347559ProteinComplex1424ActivationPW_I0004248471097ProteinComplex184849Bound1425ActivationPW_I0004258497560ProteinComplex185049Bound1422ActivationPW_I0004228437534ProteinComplex184449Bound143549864510682482917216582368348291821658251588603100589true1110-841regular100251588602105189false68568210regular100251588608979589true430610regular100255948131436382false7703398subunitregular15070594814233582false7704018subunitregular150705943781436732false12023548subunitregular150705943791436782false12025298subunitregular1507059438014367272false12027148subunitregular15070594809233582false7257028subunitregular150705948101436482false7307478subunitregular150705948111436582false5956978subunitregular150705948121436682false5957478subunitregular15070594826580282false2404018subunitregular15070594827206982false2355198subunitregular150705948461446082false2402648subunitregular150705949041436382false7701568subunitregular15070482917755864510859347259481348291814645108593473594814820915886032165824Cofactor48259275616451035930735943784825937561645108593074594379482594756164510275930755943804829167559645108593468594809593469594810593470594811593471594812820815886022165821Cofactor4829301097645108593485594826821415886082165850Cofactor4829317560645108593486594827482938753464510859349359484648294175586451085934965949042164661M1555 49.5 C1555 79.5 1557 24.5 1557 54.5 83true182164662M1277 529 C1277 499 1277 454 1277 424 83false18trueM 25.946855044164835 13.26155629629604 L 11 12 L 17.380887721185843 25.575134323078345false2164663M1277 599 C1277 629 1277 684 1277 714 83false18trueM 1223.5 1140.0096189432334 L 1231 1153 L 1238.5 1140.0096189432334false2164664M1277 709.5 C1277 679.5 1278 478.5 1278 448.5 83true18trueM 25.946855044164835 50.76155629629604 L 11 49.5 L 17.380887721185843 63.075134323078345false2165821M225 102.5 L225 152.5 L275 102.5 z10true182165822M800 702 C800 560 800 501 800 471 C816 471 829 471 845 471 149false18trueM 126.94685504416483 221.26155629629605 L 112 220 L 118.38088772118584 233.57513432307834false2165823M875 -90.5 L875 -40.5 L925 -90.5 z10true182165824M1105 -88 L1105 -38 L1155 -88 z10true182165825M1015 -98 L1015 -48 L1065 -98 z10true182165826M813 397.5 C813 427.5 815 407 809 409 149true12165850M360 -38 L360 12 L410 -38 z10true182165851M315 411.5 C345 411.5 306.5 410.5 336.5 410.5 149false12165852M770 436 C714 438 420 436 390 436 149false18trueM 712.2855821868905 394.4588679894621 L 725 386.5 L 711.7502092292043 379.4684251742488false2165853M294 422.5 C324 422.5 292.5 427.5 315.5 401.5 149false12165854M770 436 C754 438 565 436.5 547 438.5 C545 473.5 546 511.5 546 560.5 C492 558.5 390 559.5 390 559.5 149false18trueM 819.9533746525511 552.2623489382979 L 834 547 L 822.4193594621314 537.4664400808158false2165866M1340.3333740234375 866.5 C1341.3333740234375 894.5 1344.3333740234375 950.5 1348.3333740234375 1007.5 218false18true2112.397775006424,1971.611518094107 2127.3333740234375,1973 2121.0680351181295,1959.371150877582false2165867M986 856.5 C1009 872.5 1232.3333740234375 1009.5 1256.3333740234375 1026.5 218false18true1677.3977750064241,2036.611518094107 1692.3333740234375,2038 1686.0680351181293,2024.371150877582false2165874M316 422.5 C346 422.5 316.5 423.5 346.5 423.5 149false12165875M770 436 C740 436 585 440.5 546 436.5 C546 400.5 545 349.5 546 300.5 C502 301.5 424 299 390 299 149false18trueM 25.946855044164835 166.26155629629605 L 11 165 L 17.380887721185843 178.57513432307834false2165892M845 226 C845 256 847 306 845 339 5false18trueM 25.946855044164835 77.26155629629604 L 11 76 L 17.380887721185843 89.57513432307834false2165893M845 339 C845 309 767 384.75 765 304.75 5true184888706451011082184044352165893Left106384829412165892Right22983115664510954825922164661Left964825932164662Right22984115764510974825932164663Left984825942164664Right16044176451084994352165826Left16364829162165822Right16124246451085034352165852Right16474829302165851Left16134256451085044352165854Right16484829312165853Left16194226451085094352165875Right16554829382165874Left63545216586663546216586710376411273190.60.60214902401038794566720.20.206543000176410388010026680.20.20654300017641038811918960.70.70214327267220359M125 188.5 C125 138.5 175 88.5 225 88.5 C633 88.5 1165 88.5 1573 88.5 C1623 88.5 1673 138.5 1673 188.5 C1673 457.5 1673 806.5 1673 1075.5 C1673 1125.5 1623 1175.5 1573 1175.5 C1165 1175.5 633 1175.5 225 1175.5 C175 1175.5 125 1125.5 125 1075.5 C125 806.5 125 457.5 125 188.5 1true60.00.0245376235Cytoplasm187124201.31.320015245377235Nucleus887614201.31.320015245385235DNA Degradation12681005201.01.020015245386235Cut460401200.80.820015408638235Mitochondria1135261201.31.32001510231033010034456321598109239#FFF9C941153460