BioPAX pathway converted from "HDMs demethylate histones" in the Reactome database.HDMs demethylate histonesHDMs demethylate histonesThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>KDM1A, KDM1B demethylate MeK5-histone H3KDM1A, KDM1B demethylate MeK5-histone H3This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Converted from EntitySet in ReactomeReactome DB_ID: 106135511nucleoplasmGO0005654MeK5-histone H3 [nucleoplasm]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityReactomehttp://www.reactome.orgReactome DB_ID: 294781formaldehyde [ChEBI:16842]formaldehydeChEBI16842Converted from EntitySet in ReactomeReactome DB_ID: 106135531Histone H3 [nucleoplasm]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityPHYSIOL-LEFT-TO-RIGHTACTIVATIONConverted from EntitySet in ReactomeReactome DB_ID: 10613560KDM1A,KDM1B [nucleoplasm]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityamx-1 [nucleoplasm]amx-2 [nucleoplasm]Caenorhabditis elegansNCBI Taxonomy6239UniProtQ21988UniProtQ9XXU5GO0032452GO molecular functionReactome Database ID Release 7510613561Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10613561Reactome Database ID Release 7510613563Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10613563ReactomeR-CEL-32149121Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-3214912.1Histone demethylases (HDMs) belong to two groups with distinct catalytic mechanisms. KDM1A and KDM1B (formerly known as Lysine Specific Demethylases 1 and 2), belong to the flavin adenine dinucleotide (FAD)-dependent amino oxidase family, releasing formaldehyde. The reaction mechanism requires a protonatable lysine epsilon-amino group, not available in trimethylated lysines (Shi et al. 2004). KDM1A and subsequently KDM1B were shown to catalyse demethylation of monomethyl and dimethyl, but not trimethyl, histone H3 at lysine 5 (H3K4) in vitro (Shi et al. 2004, Ciccone et al. 2009).<br>Subsequently KDM1A was found to be much more proficient at catalysing demethylation of H3K4 when part of a multiprotein complex (Lee et al. 2005) and shown to catalyse demethylation of histone H3 at lysine 10 (H3K9) in vivo when associated with the androgen receptor (Metzger et al. 2007), suggesting that its substrate specificity is modulated by interacting proteins. KDM1A is a subunit of several complexes, including CtBP, Co-REST, NRD and BRAF35 (Lan et al. 2008). It is also able to catalyse demethylation of a number of non-histone proteins (Nicholson & Chen 2009).16079794Pubmed2005An essential role for CoREST in nucleosomal histone 3 lysine 4 demethylationLee, MGWynder, CCooch, NShiekhattar, RNature 437:432-515620353Pubmed2004Histone demethylation mediated by the nuclear amine oxidase homolog LSD1Shi, YujiangLan, FeiMatson, CaitlinMulligan, PeterWhetstine, Johnathan RCole, Philip ACasero, Robert AShi, YangCell 119:941-5317851108Pubmed2007LSD1 and the chemistry of histone demethylationCulhane, Jeffrey CCole, Philip ACurr Opin Chem Biol 11:561-819727073Pubmed2009KDM1B is a histone H3K4 demethylase required to establish maternal genomic imprintsCiccone, David NSu, HuiHevi, SarahGay, FrédériqueLei, HongBajko, JeffreyXu, GuoliangLi, EnChen, TaipingNature 461:415-816362057Pubmed2006Histone demethylation by a family of JmjC domain-containing proteinsTsukada, Yu-ichiFang, JiaErdjument-Bromage, HWarren, Maria EBorchers, Christoph HTempst, PZhang, YiNature 439:811-619395867Pubmed2009LSD1 demethylates histone and non-histone proteinsNicholson, Thomas BChen, TaipingEpigenetics 4:129-3216079795Pubmed2005LSD1 demethylates repressive histone marks to promote androgen-receptor-dependent transcriptionMetzger, EricWissmann, MelanieYin, NaMüller, Judith MSchneider, RobertPeters, Antoine H F MGünther, ThomasBuettner, RSchüle, RolandNature 437:436-918440794Pubmed2008Mechanisms involved in the regulation of histone lysine demethylasesLan, FeiNottke, Amanda ClairShi, YangCurr. Opin. Cell Biol. 20:316-25inferred by electronic annotationIEAGOIEAKDM1A, KDM1B demethylate Me2K5-histone H3KDM1A, KDM1B demethylate Me2K5-histone H3This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Converted from EntitySet in ReactomeReactome DB_ID: 106167351Me2K5-histone H3 [nucleoplasm]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityConverted from EntitySet in ReactomeReactome DB_ID: 106135511Reactome DB_ID: 294781PHYSIOL-LEFT-TO-RIGHTACTIVATIONConverted from EntitySet in ReactomeReactome DB_ID: 10613560Reactome Database ID Release 7510621358Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10621358ReactomeR-CEL-56611231Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-5661123.1Histone demethylases (HDMs) belong to two groups with distinct catalytic mechanisms. KDM1A and KDM1B (formerly known as Lysine Specific Demethylases 1 and 2), belong to the flavin adenine dinucleotide (FAD)-dependent amino oxidase family, releasing formaldehyde. The reaction mechanism requires a protonatable lysine epsilon-amino group, not available in trimethylated lysines (Shi et al. 2004). KDM1A and subsequently KDM1B were shown to catalyse demethylation of monomethyl and dimethyl, but not trimethyl, histone H3 at lysine 5 (H3K4) in vitro (Shi et al. 2004, Ciccone et al. 2009).<br>Subsequently KDM1A was found to be much more proficient at catalysing demethylation of H3K4 when part of a multiprotein complex (Lee et al. 2005) and shown to catalyse demethylation of histone H3 at lysine 10 (H3K9) in vivo when associated with the androgen receptor (Metzger et al. 2007), suggesting that its substrate specificity is modulated by interacting proteins. KDM1A is a subunit of several complexes, including CtBP, Co-REST, NRD and BRAF35 (Lan et al. 2008). It is also able to catalyse demethylation of a number of non-histone proteins (Nicholson & Chen 2009).inferred by electronic annotationIEAGOIEAKDM2A, KDM2B, KDM4A demethylate MeK37-histone H3KDM2A, KDM2B, KDM4A demethylate MeK37-histone H3This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Converted from EntitySet in ReactomeReactome DB_ID: 106166881MeK37-histone H3 [nucleoplasm]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityReactome DB_ID: 11367112-oxoglutarate(2-) [ChEBI:16810]2-oxoglutarate(2-)2-ketoglutaratealpha-ketoglutarate2-oxopentanedioic acid, ion(2-)2-oxoglutarateChEBI16810Reactome DB_ID: 1136851dioxygen [ChEBI:15379]dioxygenChEBI15379Reactome DB_ID: 294781Reactome DB_ID: 1599421carbon dioxide [ChEBI:16526]carbon dioxideChEBI16526Converted from EntitySet in ReactomeReactome DB_ID: 106135531Reactome DB_ID: 1599391succinate(2-) [ChEBI:30031]succinate(2-)succinate(-)OOC-CH2-CH2-COO(-)butanedioic acid, ion(2-)butanedioateChEBI30031PHYSIOL-LEFT-TO-RIGHTACTIVATIONConverted from EntitySet in ReactomeReactome DB_ID: 10616702KDM2A, KDM2B, KDM4A [nucleoplasm]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityjmjd-2 [nucleoplasm]jhdm-1 [nucleoplasm]UniProtQ9U297UniProtQ95Q98Reactome Database ID Release 7510616703Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10616703Reactome Database ID Release 7510616705Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10616705ReactomeR-CEL-47221331Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-4722133.1All characterised lysine demethylases other than KDM1A belong to the jumonji C-domain (JmjC) containing family, members of the Cupin superfamily of mononuclear Fe (II)-dependent oxygenases. They require 2-oxoglutarate (2-OG) and molecular oxygen as co-substrates, producing succinate and carbon dioxide. This hydroxylation-based mechanism does not require a protonatable lysine epsilon-amine group and consequently JmjC-containing demethylases are able to demethylate tri-, di- and monomethylated lyines. <br><br>The first reported JmjC-containing demethylases were KDM2A and KDM2B (JHDM1A/B, FBXL11/10). These demethylate lysine-37 of histone H3 when mono- or di-methylated (H3K36Me1/2) (Tsukada et al. 2006). KDM4A (JHDM3A) can demethylate mono-, di and trimethylated lysine-37 of histone H3 (Klose et al. 2006).16732292Pubmed2006The transcriptional repressor JHDM3A demethylates trimethyl histone H3 lysine 9 and lysine 36Klose, Robert JYamane, KenichiBae, YangjinZhang, DianzhengErdjument-Bromage, HTempst, PWong, JieminZhang, YiNature 442:312-6inferred by electronic annotationIEAGOIEAKDM2A, KDM2B, KDM4A demethylate Me2K37-histone H3KDM2A, KDM2B, KDM4A demethylate Me2K37-histone H3This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Converted from EntitySet in ReactomeReactome DB_ID: 106208191Me2K37-histone H3 [nucleoplasm]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityReactome DB_ID: 1136711Reactome DB_ID: 1136851Reactome DB_ID: 294781Reactome DB_ID: 1599421Converted from EntitySet in ReactomeReactome DB_ID: 106166881Reactome DB_ID: 1599391PHYSIOL-LEFT-TO-RIGHTACTIVATIONConverted from EntitySet in ReactomeReactome DB_ID: 10616702Reactome Database ID Release 7510621336Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10621336ReactomeR-CEL-56611141Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-5661114.1All characterised lysine demethylases other than KDM1A belong to the jumonji C-domain (JmjC) containing family, members of the Cupin superfamily of mononuclear Fe (II)-dependent oxygenases. They require 2-oxoglutarate (2-OG) and molecular oxygen as co-substrates, producing succinate and carbon dioxide. This hydroxylation-based mechanism does not require a protonatable lysine epsilon-amine group and consequently JmjC-containing demethylases are able to demethylate tri-, di- and monomethylated lysines. <br><br>The first reported JmjC-containing demethylases were KDM2A and KDM2B (JHDM1A/B, FBXL11/10). These demethylate lysine-37 of histone H3 when mono- or di-methylated (H3K36Me1/2) (Tsukada et al. 2006). KDM4A (JHDM3A) can demethylate mono-, di and trimethylated lysine-37 of histone H3 (Klose et al. 2006).<br><br>KDM8 was initially thought to demethylate dimethylated lysine-37 of histone H3 (Hsia et al. 2010) but later work indicates that, consistent with its closer structural similarity to JmjC hydroxylases, the enzyme lacks histone demethylase activity and rather hydroxylates arginine residues of proteins RPS6 and RCCD1 (Wilkins et al. 2018).29563586Pubmed2018JMJD5 is a human arginyl C-3 hydroxylaseWilkins, Sarah EIslam, Md SaifulGannon, Joan MMarkolovic, SuzanaHopkinson, Richard JGe, WeiSchofield, Christopher JChowdhury, RasheduzzamanNat Commun 9:118020457893Pubmed2010KDM8, a H3K36me2 histone demethylase that acts in the cyclin A1 coding region to regulate cancer cell proliferationHsia, Datsun ATepper, Clifford GPochampalli, Mamata RHsia, Elaine Y CIzumiya, ChieHuerta, Steve BWright, Michael EChen, Hong-WuKung, Hsing-JienIzumiya, YoshihiroProc. Natl. Acad. Sci. U.S.A. 107:9671-6inferred by electronic annotationIEAGOIEAKDM3A, KDM3B, KDM7A, PHF2:ARID5B, PHF8 demethylate MeK10-histone H3KDM3A, KDM3B, KDM7A, PHF2:ARID5B, PHF8 demethylate MeK10-histone H3This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Converted from EntitySet in ReactomeReactome DB_ID: 106167091MeK10-histone H3 [nucleoplasm]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityReactome DB_ID: 1136711Reactome DB_ID: 1136851Reactome DB_ID: 294781Reactome DB_ID: 1599421Converted from EntitySet in ReactomeReactome DB_ID: 106135531Reactome DB_ID: 1599391PHYSIOL-LEFT-TO-RIGHTACTIVATIONConverted from EntitySet in ReactomeReactome DB_ID: 10616722KDM3A,KDM3B,KDM7A,PHF2:ARID5B,PHF8 [nucleoplasm]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityjmjd-1.1 [nucleoplasm]jmjd-1.2 [nucleoplasm]jmjd-1.2 [nucleoplasm]UniProtQ20367UniProtQ9GYI0Reactome Database ID Release 7510616723Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10616723Reactome Database ID Release 7510616725Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10616725ReactomeR-CEL-47242841Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-4724284.1All characterized lysine demethylases other than KDM1A belong to the jumonjiC domain (JmjC) containing family.The JmjC KDMs are members of the Cupin superfamily of mononuclear Fe (II) dependent oxygenases, which are characterized by the presence of a double-stranded beta-helix core fold. The JmjC KDMs require 2 oxoglutarate (2 OG) and molecular oxygen as co substrates, producing, along with formaldehyde, succinate and carbon dioxide. This hydroxylation based mechanism does not require a protonatable lysine epsilon-amine group and consequently JmjC containing demethylases are able to catalyse demethylateion of tri , di and monomethylated lysines. KDM3A (JHDM2A), KDM3B (JHDM2B), KDM7A (JHDM1D), PHF8 (JHDM1E) and PHF2 when complexed with ARID5B (Wen et al. 2010, Baba et al. 2011) are specific for mono or di-methylated lysine-10 on histone H3 (H3K9Me1/2) (Yamane et al. 2006, Kim et al. 2012, Horton et al. 2010, Huang et al. 2010, Loenarz et al. 2008, Feng et al. 2010, Fortschegger et al. 2010, Qi et al. 2010).16603237Pubmed2006JHDM2A, a JmjC-containing H3K9 demethylase, facilitates transcription activation by androgen receptorYamane, KenichiToumazou, CharalambosTsukada, Yu-ichiErdjument-Bromage, HTempst, PWong, JieminZhang, YiCell 125:483-9519843542Pubmed2010PHF8, a gene associated with cleft lip/palate and mental retardation, encodes for an Nepsilon-dimethyl lysine demethylaseLoenarz, ChristophGe, WeiColeman, Mathew LRose, Nathan RCooper, Christopher D OKlose, Robert JRatcliffe, Peter JSchofield, Christopher JHum. Mol. Genet. 19:217-2220129925Pubmed2010Recognition of histone H3K4 trimethylation by the plant homeodomain of PHF2 modulates histone demethylationWen, HongLi, JingzhiSong, TanjingLu, MingKan, Pu-YehLee, Min GyuSha, BingdongShi, XiaobingJ. Biol. Chem. 285:9322-620023638Pubmed2010Enzymatic and structural insights for substrate specificity of a family of jumonji histone lysine demethylasesHorton, John RUpadhyay, Anup KQi, Hank HZhang, XingShi, YangCheng, XiaodongNat. Struct. Mol. Biol. 17:38-4320208542Pubmed2010PHF8 activates transcription of rRNA genes through H3K4me3 binding and H3K9me1/2 demethylationFeng, WeijunYonezawa, MasatoYe, JingJenuwein, ThomasGrummt, IngridNat. Struct. Mol. Biol. 17:445-5020622853Pubmed2010Histone H4K20/H3K9 demethylase PHF8 regulates zebrafish brain and craniofacial developmentQi, Hank HSarkissian, MadathiaHu, Gang-QingWang, ZhibinBhattacharjee, ArindamGordon, D BenjaminGonzales, MichelleLan, FeiOngusaha, Pat PHuarte, MaiteYaghi, Nasser KLim, HuijunGarcia, Benjamin ABrizuela, LeonardoZhao, KejiRoberts, Thomas MShi, YangNature 466:503-720622854Pubmed2010PHF8 mediates histone H4 lysine 20 demethylation events involved in cell cycle progressionLiu, WTanasa, BTyurina, OVZhou, TYGassmann, RLiu, WTOhgi, KABenner, CGarcia-Bassets, IAggarwal, AKDesai, ADorrestein, PCGlass, CKRosenfeld, MGNature 466:508-1220084082Pubmed2010Dual-specificity histone demethylase KIAA1718 (KDM7A) regulates neural differentiation through FGF4Huang, ChengyangXiang, YangWang, YanruLi, XiaXu, LongyongZhu, ZiqiZhang, TingZhu, QingqingZhang, KejingJing, NaiheChen, Charlie DeguiCell Res. 20:154-6520346720Pubmed2010A functional link between the histone demethylase PHF8 and the transcription factor ZNF711 in X-linked mental retardationKleine-Kohlbrecher, DanielaChristensen, JesperVandamme, JulienAbarrategui, IratxeBak, MadsTommerup, NielsShi, XiaobingGozani, OrRappsilber, JuriSalcini, Anna ElisabettaHelin, KristianMol. Cell 38:165-7822615488Pubmed2012KDM3B is the H3K9 demethylase involved in transcriptional activation of lmo2 in leukemiaKim, Ji-YoungKim, Kee-BeomEom, Gwang HyeonChoe, NakwonKee, Hae JinSon, Hye-JuOh, Si-TaekKim, Dong-WookPak, Jhang HoBaek, Hee JoKook, HoonHahn, YoonsooKook, HyunChakravarti, DebabrataSeo, Sang-BeomMol. Cell. Biol. 32:2917-3320421419Pubmed2010PHF8 targets histone methylation and RNA polymerase II to activate transcriptionFortschegger, Klausde Graaf, PetraOutchkourov, Nikolay Svan Schaik, Frederik M ATimmers, H T MarcShiekhattar, RaminMol. Cell. Biol. 30:3286-9821532585Pubmed2011PKA-dependent regulation of the histone lysine demethylase complex PHF2-ARID5BBaba, AtsushiOhtake, FumiakiOkuno, YosukeYokota, KenichiOkada, MaikoImai, YuukiNi, MinMeyer, Clifford AIgarashi, KatsuhideKanno, JunBrown, MylesKato, ShigeakiNat. Cell Biol. 13:668-75inferred by electronic annotationIEAGOIEAKDM3A, KDM3B, KDM7A, PHF2:ARID5B, PHF8 demethylate Me2K10-histone H3KDM3A, KDM3B, KDM7A, PHF2:ARID5B, PHF8 demethylate Me2K10-histone H3This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Converted from EntitySet in ReactomeReactome DB_ID: 106167071Me2K10-histone H3 [nucleoplasm]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityReactome DB_ID: 1136711Reactome DB_ID: 1136851Converted from EntitySet in ReactomeReactome DB_ID: 106167091Reactome DB_ID: 294781Reactome DB_ID: 1599421Reactome DB_ID: 1599391PHYSIOL-LEFT-TO-RIGHTACTIVATIONConverted from EntitySet in ReactomeReactome DB_ID: 10616722Reactome Database ID Release 7510621338Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10621338ReactomeR-CEL-56611151Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-5661115.1All characterized lysine demethylases other than KDM1A belong to the jumonjiC domain (JmjC) containing family.The JmjC KDMs are members of the Cupin superfamily of mononuclear Fe (II) dependent oxygenases, which are characterized by the presence of a double-stranded beta-helix core fold. The JmjC KDMs require 2 oxoglutarate (2 OG) and molecular oxygen as co substrates, producing, along with formaldehyde, succinate and carbon dioxide. This hydroxylation based mechanism does not require a protonatable lysine epsilon-amine group and consequently JmjC containing demethylases are able to catalyse demethylateion of tri , di and monomethylated lysines. KDM3A (JHDM2A), KDM3B (JHDM2B), KDM7A (JHDM1D), PHF8 (JHDM1E) and PHF2 when complexed with ARID5B (Wen et al. 2010, Baba et al. 2011) are specific for mono or di-methylated lysine-10 on histone H3 (H3K9Me1/2) (Yamane et al. 2006, Kim et al. 2012, Horton et al. 2010, Huang et al. 2010, Loenarz et al. 2008, Feng et al. 2010, Fortschegger et al. 2010, Qi et al. 2010).inferred by electronic annotationIEAGOIEAKDM4A, KDM4B, KDM4C, KDM4D demethylate Me2K10-histone H3KDM4A, KDM4B, KDM4C, KDM4D demethylate Me2K10-histone H3This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Converted from EntitySet in ReactomeReactome DB_ID: 106167071Reactome DB_ID: 1136711Reactome DB_ID: 1136851Converted from EntitySet in ReactomeReactome DB_ID: 106167091Reactome DB_ID: 294781Reactome DB_ID: 1599421Reactome DB_ID: 1599391PHYSIOL-LEFT-TO-RIGHTACTIVATIONReactome DB_ID: 10616700UniProt:Q9U297jmjd-2Chain Coordinates1EQUAL1064EQUALReactome Database ID Release 7510616712Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10616712Reactome Database ID Release 7510616714Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10616714ReactomeR-CEL-47242791Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-4724279.1All characterized lysine demethylases other than KDM1A belong to the jumonjiC domain (JmjC) containing family.The JmjC KDMs are members of the Cupin superfamily of mononuclear Fe (II) dependent oxygenases, which are characterized by the presence of a double-stranded beta-helix core fold. The JmjC KDMs require 2 oxoglutarate (2 OG) and molecular oxygen as co substrates, producing, along with formaldehyde, succinate and carbon dioxide. This hydroxylation based mechanism does not require a protonatable lysine e amine group and consequently JmjC containing demethylases are able to demethylate tri , di and monomethylated lysines.<br>KDM4A-D (JMJD2A-D/JHDM3A-D) catalyse the demethylation of di- or tri-methylated histone H3 at lysine-10 (H3K9Me2/3) (Cloos et al. 2006, Fodor et al. 2006, Whetstine et al. 2007), with a strong preference for Me3 (Whetstine et al. 2007). MINA, a bifunctional histone lysine demethylase and ribosomal histidine hydroxylase, demethylates trimethylated lysine-10 of histone H3 (Lu et al. 2009). KDM4A (JHDM3A) can also demethylate lysine-37 of histone H3 (H3K36Me2/3) (Klose et al. 2006).19502796Pubmed2009Lung cancer-associated JmjC domain protein mdig suppresses formation of tri-methyl lysine 9 of histone H3Lu, YongjuChang, QingshanZhang, YadongBeezhold, KevinRojanasakul, YonZhao, HongwenCastranova, VinceShi, XianglinChen, FCell Cycle 8:2101-916732293Pubmed2006The putative oncogene GASC1 demethylates tri- and dimethylated lysine 9 on histone H3Cloos, Paul A CChristensen, JesperAgger, KarlMaiolica, AlessioRappsilber, JuriAntal, TorbenHansen, Klaus HHelin, KristianNature 442:307-1116603238Pubmed2006Reversal of histone lysine trimethylation by the JMJD2 family of histone demethylasesWhetstine, Johnathan RNottke, AmandaLan, FeiHuarte, MaiteSmolikov, SaritChen, ZhongzhouSpooner, ELi, EnZhang, GongyiColaiácovo, Monica PShi, YangCell 125:467-8116738407Pubmed2006Jmjd2b antagonizes H3K9 trimethylation at pericentric heterochromatin in mammalian cellsFodor, Barna DKubicek, StefanYonezawa, MasatoO'Sullivan, Roderick JSengupta, RoopshaPerez-Burgos, LauraOpravil, SusanneMechtler, KarlSchotta, GunnarJenuwein, ThomasGenes Dev. 20:1557-62inferred by electronic annotationIEAGOIEAKDM4A, KDM4B, KDM4C, KDM4D, MINA demethylate Me3K10-histone H3KDM4A, KDM4B, KDM4C, KDM4D, MINA demethylate Me3K10-histone H3This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Reactome DB_ID: 1136711Reactome DB_ID: 1136851Converted from EntitySet in ReactomeReactome DB_ID: 106168341Me3K10-histone H3 [nucleoplasm]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityReactome DB_ID: 294781Reactome DB_ID: 1599421Converted from EntitySet in ReactomeReactome DB_ID: 106167071Reactome DB_ID: 1599391PHYSIOL-LEFT-TO-RIGHTACTIVATIONReactome DB_ID: 106167001EQUAL1064EQUALReactome Database ID Release 7510621352Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10621352ReactomeR-CEL-56611201Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-5661120.1All characterized lysine demethylases other than KDM1A belong to the jumonjiC domain (JmjC) containing family.The JmjC KDMs are members of the Cupin superfamily of mononuclear Fe (II) dependent oxygenases, which are characterized by the presence of a double-stranded beta-helix core fold. The JmjC KDMs require 2 oxoglutarate (2 OG) and molecular oxygen as co substrates, producing, along with formaldehyde, succinate and carbon dioxide. This hydroxylation based mechanism does not require a protonatable lysine e amine group and consequently JmjC containing demethylases are able to demethylate tri , di and monomethylated lysines.<br>KDM4A-D (JMJD2A-D/JHDM3A-D) catalyse the demethylation of di- or tri-methylated histone H3 at lysine-10 (H3K9Me2/3) (Cloos et al. 2006, Fodor et al. 2006, Whetstine et al. 2007), with a strong preference for Me3 (Whetstine et al. 2007). MINA, a bifunctional histone lysine demethylase and ribosomal histidine hydroxylase, demethylates trimethylated lysine-10 of histone H3 (Lu et al. 2009). KDM4A (JHDM3A) can also demethylate lysine-37 of histone H3 (H3K36Me2/3) (Klose et al. 2006).inferred by electronic annotationIEAGOIEAKDM5A-D demethylate Me2K5-histone H3KDM5A-D demethylate Me2K5-histone H3This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Converted from EntitySet in ReactomeReactome DB_ID: 106167351Reactome DB_ID: 1136711Reactome DB_ID: 1136851Converted from EntitySet in ReactomeReactome DB_ID: 106135511Reactome DB_ID: 294781Reactome DB_ID: 1599421Reactome DB_ID: 1599391PHYSIOL-LEFT-TO-RIGHTACTIVATIONReactome DB_ID: 10616740UniProt:Q23541rbr-2UniProtQ235411EQUAL1690EQUALReactome Database ID Release 7510616747Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10616747Reactome Database ID Release 7510616749Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10616749ReactomeR-CEL-47541811Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-4754181.1All characterized lysine demethylases other than KDM1A belong to the jumonjiC domain (JmjC) containing family.The JmjC KDMs are members of the Cupin superfamily of mononuclear Fe (II) dependent oxygenases, which are characterized by the presence of a double-stranded beta-helix core fold. The JmjC KDMs require 2 oxoglutarate (2 OG) and molecular oxygen as co substrates, producing, along with formaldehyde, succinate and carbon dioxide. This hydroxylation based mechanism does not require a protonatable lysine epsilon-amine group and consequently JmjC containing demethylases are able to demethylate tri , di and monomethylated lysines. KDM5A-D (JARID1A-D) catalyse the demethylation of di- or tri-methylated lysine-5 of histone H3 (H3K4Me2/3) (Christensen et al. 2007, Klose et al. 2007, Lee et al. 2007, Secombe et al. 2007, Seward et al. 2007, Iwase et al. 2007).17351631Pubmed2007The trithorax-group protein Lid is a histone H3 trimethyl-Lys4 demethylaseLee, NaraZhang, JunyuKlose, Robert JErdjument-Bromage, HTempst, PJones, Richard SZhang, YiNat. Struct. Mol. Biol. 14:341-317310255Pubmed2007Demethylation of trimethylated histone H3 Lys4 in vivo by JARID1 JmjC proteinsSeward, David JCubberley, GabrielleKim, SoojinSchonewald, MattZhang, LianTripet, BrianBentley, David LNat. Struct. Mol. Biol. 14:240-217311883Pubmed2007The Trithorax group protein Lid is a trimethyl histone H3K4 demethylase required for dMyc-induced cell growthSecombe, JulieLi, LCarlos, LeniEisenman, Robert NGenes Dev. 21:537-5117320163Pubmed2007The retinoblastoma binding protein RBP2 is an H3K4 demethylaseKlose, Robert JYan, QinTothova, ZuzanaYamane, KenichiErdjument-Bromage, HTempst, PGilliland, D GaryZhang, YiKaelin, William GCell 128:889-90017320161Pubmed2007RBP2 belongs to a family of demethylases, specific for tri-and dimethylated lysine 4 on histone 3Christensen, JesperAgger, KarlCloos, Paul A CPasini, DiegoRose, SimonSennels, LauRappsilber, JuriHansen, Klaus HSalcini, Anna ElisabettaHelin, KristianCell 128:1063-7617320160Pubmed2007The X-linked mental retardation gene SMCX/JARID1C defines a family of histone H3 lysine 4 demethylasesIwase, ShigekiLan, FeiBayliss, Peterde la Torre-Ubieta, LuisHuarte, MaiteQi, Hank HWhetstine, Johnathan RBonni, AzadRoberts, Thomas MShi, YangCell 128:1077-88inferred by electronic annotationIEAGOIEAKDM5A-D demethylate Me3K5-histone H3KDM5A-D demethylate Me3K5-histone H3This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Converted from EntitySet in ReactomeReactome DB_ID: 106178811Me3K5-histone H3 [nucleoplasm]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityReactome DB_ID: 1136711Reactome DB_ID: 1136851Reactome DB_ID: 294781Reactome DB_ID: 1599421Converted from EntitySet in ReactomeReactome DB_ID: 106167351Reactome DB_ID: 1599391PHYSIOL-LEFT-TO-RIGHTACTIVATIONReactome DB_ID: 106167401EQUAL1690EQUALReactome Database ID Release 7510621340Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10621340ReactomeR-CEL-56611161Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-5661116.1All characterized lysine demethylases other than KDM1A belong to the jumonjiC domain (JmjC) containing family.The JmjC KDMs are members of the Cupin superfamily of mononuclear Fe (II) dependent oxygenases, which are characterized by the presence of a double-stranded beta-helix core fold. The JmjC KDMs require 2 oxoglutarate (2 OG) and molecular oxygen as co substrates, producing, along with formaldehyde, succinate and carbon dioxide. This hydroxylation based mechanism does not require a protonatable lysine epsilon-amine group and consequently JmjC containing demethylases are able to demethylate tri , di and monomethylated lysines. KDM5A-D (JARID1A-D) catalyse the demethylation of di- or tri-methylated lysine-5 of histone H3 (H3K4Me2/3) (Christensen et al. 2007, Klose et al. 2007, Lee et al. 2007, Secombe et al. 2007, Seward et al. 2007, Iwase et al. 2007).inferred by electronic annotationIEAGOIEAKDM6A, KDM6B, KDM7A demethylate Me2K28-histone H3KDM6A, KDM6B, KDM7A demethylate Me2K28-histone H3This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Converted from EntitySet in ReactomeReactome DB_ID: 106167571Me2K28-histone H3 [nucleoplasm]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityReactome DB_ID: 1136711Reactome DB_ID: 1136851Reactome DB_ID: 294781Reactome DB_ID: 1599421Converted from EntitySet in ReactomeReactome DB_ID: 106167651MeK28-histone H3 [nucleoplasm]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityReactome DB_ID: 1599391PHYSIOL-LEFT-TO-RIGHTACTIVATIONConverted from EntitySet in ReactomeReactome DB_ID: 10616779KDM6A,KDM6B,KDM6C,KDM7A [nucleoplasm]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityjmjd-3.1 [nucleoplasm]jmjd-1.1 [nucleoplasm]jmjd-3.1 [nucleoplasm]jmjd-3.1 [nucleoplasm]jmjd-1.2 [nucleoplasm]jmjd-3.2 [nucleoplasm]jmjd-3.2 [nucleoplasm]jmjd-3.2 [nucleoplasm]UniProtQ95QK3UniProtQ19760Reactome Database ID Release 7510616780Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10616780Reactome Database ID Release 7510616782Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10616782ReactomeR-CEL-47541871Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-4754187.1All characterized lysine demethylases other than KDM1A belong to the jumonjiC domain (JmjC) containing family.The JmjC KDMs are members of the Cupin superfamily of mononuclear Fe (II) dependent oxygenases, which are characterized by the presence of a double-stranded beta-helix core fold. The JmjC KDMs require 2 oxoglutarate (2 OG) and molecular oxygen as co substrates, producing, along with formaldehyde, succinate and carbon dioxide. This hydroxylation based mechanism does not require a protonatable lysine e amine group and consequently JmjC containing demethylases are able to demethylate tri , di and monomethylated lysines.<br>KDM6A (UTX), KDM6B (JMJD3), KDM6C (UTY) and KDM7A (JHDM1D) catalyse the demethylation of di or tri-methylated lysine-28 of histone H3 (H3K27Me2/3) (Agger et al. 2007, Cho et al. 2007, De Santra et al. 2007, Hong et al. 2007, Lan et al. 2007, Lee et al. 2007, Horton et al. 2010, Huang et al. 2010, Walport et al. 2014).17825402Pubmed2007The histone H3 lysine-27 demethylase Jmjd3 links inflammation to inhibition of polycomb-mediated gene silencingDe Santa, FrancescaTotaro, Maria GraziaProsperini, ElenaNotarbartolo, SamueleTesta, GiuseppeNatoli, GioacchinoCell 130:1083-9417500065Pubmed2007PTIP associates with MLL3- and MLL4-containing histone H3 lysine 4 methyltransferase complexCho, Young-WookHong, TeresaHong, SunhwaGuo, HongYu, HongKim, DoyeobGuszczynski, TadDressler, Gregory RCopeland, Terry DKalkum, MarkusGe, KaiJ. Biol. Chem. 282:20395-40624798337Pubmed2014Human UTY(KDM6C) is a male-specific Nϵ-methyl lysyl demethylaseWalport, Louise JHopkinson, Richard JVollmar, MelanieMadden, Sarah KGileadi, CarinaOppermann, USchofield, Christopher JJohansson, CatrineJ. Biol. Chem. 289:18302-1317713478Pubmed2007UTX and JMJD3 are histone H3K27 demethylases involved in HOX gene regulation and developmentAgger, KarlCloos, Paul A CChristensen, JesperPasini, DiegoRose, SimonRappsilber, JuriIssaeva, IrinaCanaani, EliSalcini, Anna ElisabettaHelin, KristianNature 449:731-417851529Pubmed2007A histone H3 lysine 27 demethylase regulates animal posterior developmentLan, FeiBayliss, Peter ERinn, John LWhetstine, Johnathan RWang, Jordon KChen, ShuzhenIwase, ShigekiAlpatov, RomanIssaeva, IrinaCanaani, EliRoberts, Thomas MChang, HYShi, YangNature 449:689-9417761849Pubmed2007Demethylation of H3K27 regulates polycomb recruitment and H2A ubiquitinationLee, Min GyuVilla, RaffaellaTrojer, PatrickNorman, JessicaYan, Kai-PingReinberg, DannyDi Croce, LucianoShiekhattar, RaminScience 318:447-50inferred by electronic annotationIEAGOIEAKDM6A, KDM6B, KDM7A demethylate Me3K28-histone H3KDM6A, KDM6B, KDM7A demethylate Me3K28-histone H3This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Converted from EntitySet in ReactomeReactome DB_ID: 106208741Me3K28-histone H3 [nucleoplasm]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityReactome DB_ID: 1136711Reactome DB_ID: 1136851Reactome DB_ID: 294781Reactome DB_ID: 1599421Converted from EntitySet in ReactomeReactome DB_ID: 106167571Reactome DB_ID: 1599391PHYSIOL-LEFT-TO-RIGHTACTIVATIONConverted from EntitySet in ReactomeReactome DB_ID: 10616779Reactome Database ID Release 7510621354Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10621354ReactomeR-CEL-56611211Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-5661121.1All characterized lysine demethylases other than KDM1A belong to the jumonjiC domain (JmjC) containing family.The JmjC KDMs are members of the Cupin superfamily of mononuclear Fe (II) dependent oxygenases, which are characterized by the presence of a double-stranded beta-helix core fold. The JmjC KDMs require 2 oxoglutarate (2 OG) and molecular oxygen as co substrates, producing, along with formaldehyde, succinate and carbon dioxide. This hydroxylation based mechanism does not require a protonatable lysine e amine group and consequently JmjC containing demethylases are able to demethylate tri , di and monomethylated lysines.<br>KDM6A (UTX), KDM6B (JMJD3), KDM6C (UTY) and KDM7A (JHDM1D) catalyse the demethylation of di or tri-methylated lysine-28 of histone H3 (H3K27Me2/3) (Agger et al. 2007, Cho et al. 2007, De Santra et al. 2007, Hong et al. 2007, Lan et al. 2007, Lee et al. 2007, Horton et al. 2010, Huang et al. 2010, Walport et al. 2014).inferred by electronic annotationIEAGOIEAJMJD6 demethylates MeR3-histone H3JMJD6 demethylates MeR3-histone H3This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Converted from EntitySet in ReactomeReactome DB_ID: 106138471MeR3-histone H3 [nucleoplasm]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityReactome DB_ID: 1136711Reactome DB_ID: 1136851Reactome DB_ID: 294781Reactome DB_ID: 1599421Converted from EntitySet in ReactomeReactome DB_ID: 106135531Reactome DB_ID: 1599391PHYSIOL-LEFT-TO-RIGHTACTIVATIONReactome DB_ID: 10616730UniProt:Q9GYI4psr-1UniProtQ9GYI41EQUAL403EQUALReactome Database ID Release 7510616731Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10616731Reactome Database ID Release 7510616733Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10616733ReactomeR-CEL-47541761Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-4754176.1JMJD6 catalyses demethylation of mono- or di-methylated arginine-3 of histone H3 (H3R2Me1/2) and arginine-4 of histone H4 (H4R3Me1/2) (Chang et al. 2007). Non-histone substrates of JMJD6 arginine demethylation have also been reported (Poulard et al. 2014, Lawrence et al. 2014). Subsequent to its characterization as an arginine demethylase, JMJD6 was reported to be a lysine hydroxylase (Webby et al 2009).24498420Pubmed2014JMJD6 regulates ER? methylation on argininePoulard, CoralieRambaud, JulietteHussein, NaderCorbo, LauraLe Romancer, MurielPLoS ONE 9:e8798217947579Pubmed2007JMJD6 is a histone arginine demethylaseChang, BingshengChen, YZhao, YingmingBruick, Richard KScience 318:444-719574390Pubmed2009Jmjd6 catalyses lysyl-hydroxylation of U2AF65, a protein associated with RNA splicingWebby, Celia JWolf, AlexanderGromak, NataliaDreger, MathiasKramer, HolgerKessler, BenediktNielsen, Michael LSchmitz, CorinnaButler, Danica SYates, John RDelahunty, Claire MHahn, PhillipLengeling, AndreasMann, MatthiasProudfoot, Nicholas JSchofield, Christopher JBöttger, AngelikaScience 325:90-324606677Pubmed2014Redistribution of demethylated RNA helicase A during foot-and-mouth disease virus infection: role of Jumonji C-domain containing protein 6 in RHA demethylationLawrence, PaulConderino, Joseph SRieder, ElizabethVirology 452:1-11inferred by electronic annotationIEAGOIEAJMJD6 demethylates Me2R3-histone H3JMJD6 demethylates Me2R3-histone H3This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Converted from EntitySet in ReactomeReactome DB_ID: 106175701Me2aR3-histone H3 [nucleoplasm]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityReactome DB_ID: 1136711Reactome DB_ID: 1136851Reactome DB_ID: 294781Converted from EntitySet in ReactomeReactome DB_ID: 106138472Reactome DB_ID: 1599421Reactome DB_ID: 1599391PHYSIOL-LEFT-TO-RIGHTACTIVATIONReactome DB_ID: 106167301EQUAL403EQUALReactome Database ID Release 7510621356Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10621356ReactomeR-CEL-56611221Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-5661122.1JMJD6 catalyses demethylation of mono- or di-methylated arginine-3 of histone H3 (H3R2Me1/2) and arginine-4 of histone H4 (H4R3Me1/2) (Chang et al. 2007). Non-histone substrates of JMJD6 arginine demethylation have also been reported (Poulard et al. 2014, Lawrence et al. 2014). Subsequent to its characterization as an arginine demethylase, JMJD6 was reported to be a lysine hydroxylase (Webby et al 2009).inferred by electronic annotationIEAGOIEAJMJD6 demethylates Me2sR4-HIST1H4JMJD6 demethylates Me2sR4-HIST1H4This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Reactome DB_ID: 106175771UniProt:P62784his-56UniProtP62784symmetric dimethyl-L-arginine at 4 (in Homo sapiens)4EQUALsymmetric dimethyl-L-arginine2EQUAL103EQUALReactome DB_ID: 1136711Reactome DB_ID: 1136851Reactome DB_ID: 294781Reactome DB_ID: 1599421Reactome DB_ID: 106175131omega-N-methyl-L-arginine at 4 (in Homo sapiens)4EQUALomega-N-methyl-L-arginine2EQUAL103EQUALReactome DB_ID: 1599391PHYSIOL-LEFT-TO-RIGHTACTIVATIONReactome DB_ID: 106167301EQUAL403EQUALReactome Database ID Release 7510621362Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10621362ReactomeR-CEL-56611251Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-5661125.1JMJD6 catalyses demethylation of mono- or di-methylated arginine-3 of histone H3 (H3R2Me1/2) and arginine-4 of histone H4 (H4R3Me1/2) (Chang et al. 2007). Non-histone substrates of JMJD6 arginine demethylation have also been reported (Poulard et al. 2014, Lawrence et al. 2014). Subsequent to its characterization as an arginine demethylase, JMJD6 was reported to be a lysine hydroxylase (Webby et al 2009).inferred by electronic annotationIEAGOIEAJMJD6 demethylates MeR4-HIST1H4JMJD6 demethylates MeR4-HIST1H4This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Reactome DB_ID: 106175131omega-N-methyl-L-arginine at 4 (in Homo sapiens)4EQUAL2EQUAL103EQUALReactome DB_ID: 1136711Reactome DB_ID: 1136851Reactome DB_ID: 294781Reactome DB_ID: 1599421Reactome DB_ID: 1057531412EQUAL103EQUALReactome DB_ID: 1599391PHYSIOL-LEFT-TO-RIGHTACTIVATIONReactome DB_ID: 106167301EQUAL403EQUALReactome Database ID Release 7510621360Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10621360ReactomeR-CEL-56611241Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-5661124.1JMJD6 catalyses demethylation of mono- or di-methylated arginine-3 of histone H3 (H3R2Me1/2) and arginine-4 of histone H4 (H4R3Me1/2) (Chang et al. 2007). Non-histone substrates of JMJD6 arginine demethylation have also been reported (Poulard et al. 2014, Lawrence et al. 2014). Subsequent to its characterization as an arginine demethylase, JMJD6 was reported to be a lysine hydroxylase (Webby et al 2009).inferred by electronic annotationIEAGOIEAPHF8 demethylates MeK21-histone H4PHF8 demethylates MeK21-histone H4This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Reactome DB_ID: 106109231N6-methyl-L-lysine at 21 (in Homo sapiens)21EQUALN6-methyl-L-lysine [MOD:00085]2EQUAL103EQUALReactome DB_ID: 1136711Reactome DB_ID: 1136851Reactome DB_ID: 294781Reactome DB_ID: 1599421Reactome DB_ID: 1057531412EQUAL103EQUALReactome DB_ID: 1599391PHYSIOL-LEFT-TO-RIGHTACTIVATIONReactome DB_ID: 10610929UniProt:Q9GYI0jmjd-1.21EQUAL1060EQUALReactome Database ID Release 7510619045Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10619045Reactome Database ID Release 7510619047Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10619047ReactomeR-CEL-54231171Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-5423117.1PHF8 (JHDM1E) catalyses demethylation of mono-methylated lysine-21 of histone H4 (H4K20Me1) (Qi et al. 2010, Liu et al. 2010).inferred by electronic annotationIEAGOIEAReactome Database ID Release 7510643256Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10643256ReactomeR-CEL-32148421Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-3214842.1Histone lysine demethylases (KDMs) are able to reverse N-methylations of histones and probably other proteins. To date KDMs have been demonstrated to catalyse demethylation of N-epsilon methylated lysine residues. Biochemically there are two distinct groups of N-epsilon methylated lysine demethylases with different catalytic mechanisms, both of which result in methyl group oxidation to produce formaldhyde. KDM1A, formerly known as Lysine Specific Demethylase 1 (LSD1), belongs to the flavin adenine dinucleotide (FAD)-dependent amino oxidase family. The KDM1A reaction mechanism requires a protonatable lysine epsilon-amine group, not available in trimethylated lysines, which consequently are not KDM1 substrates. Other KDMs belong to the Jumonji C (JmjC) -domain containing family. These are members of the Cupin superfamily of mononuclear Fe (II)-dependent oxygenases, which are characterised by the presence of a double-stranded beta-helix core fold. They require 2-oxoglutarate (2OG) and molecular oxygen as co-substrates, producing, in addition to formaldehyde, succinate and carbon dioxide. This hydroxylation-based mechanism does not require a protonatable lysine epsilon-amine group and consequently JmjC-containing demethylases are able to demethylate tri-, di- and monomethylated lysines.<br>The coordinates of post-translational modifications represented and described here follow UniProt standard practice whereby coordinates refer to the translated protein before any further processing. Histone literature typically refers to coordinates of the protein after the initiating methionine has been removed. Therefore the coordinates of post-translated residues in the Reactome database and described here are frequently +1 when compared with the literature.<br>In general, methylation at histone H3 lysine-5 (H3K4) and lysine-37 (H3K36), including di- and trimethylation at these sites, has been linked to actively transcribed genes (reviewed in Martin & Zhang 2005). In contrast, lysine-10 (H3K9) promoter methylation is considered a repressive mark for euchromatic genes and is also one of the landmark modifications associated with heterochromatin (Peters et al. 2002).<br>The first reported JmjC-containing demethylases were KDM2A/B (JHDM1A/B, FBXL11/10). These catalyse demethylation of histone H3 lysine-37 when mono- or di-methylated (H3K36Me1/2) (Tsukada et al. 2006). They were found to contain a JmjC catalytic domain, previously implicated in chromatin-dependent functions (Clissold & Ponting 2001). Subsequently, many other JmjC enzymes have been identified and discovered to have lysine demethylase activities with distinct methylation site and state specificities. <br>KDM3A/B (JHDM2A/B) are specific for mono or di-methylated lysine-10 on histone H3 (H3K9Me1/2) (Yamane et al. 2006, Kim et al. 2012). KDM4A-C (JMJD2A-C/JHDM3A-C) catalyse demethylation of di- or tri-methylated histone H3 at lysine-10 (H3K9Me2/3) (Cloos et al. 2006, Fodor et al. 2006), with a strong preference for Me3 (Whetstine et al. 2007). KDM4D (JMJD2D) also catalyses demethylation of H3K9Me2/3 (Whetstine et al. 2007). KDM4A-C (JHDM3A-C) can also catalyse demethylation of lysine-37 of histone H3 (H3K36Me2/3) (Klose et al. 2006). KDM5A-D (JARID1A-D) catalyses demethylation of di- or tri-methylated lysine-5 of histone H3 (H3K4Me2/3) (Christensen et al. 2007, Klose et al. 2007, Lee et al. 2007, Secombe et al. 2007, Seward et al. 2007, Iwase et al. 2007). KDM6A and KDM6B (UTX/JMJD3) catalyse demethylation of di- or tri-methylated lysine-28 of histone H3 (H3K27Me2/3) (Agger et al. 2007, Cho et al. 2007, De Santra et al. 2007, Lan et al. 2007, Lee et al. 2007).<br><br>KDM7A (KIAA1718/JHDM1D) catalyses demethylation of mono- or di-methylated lysine-10 of histone H3 (H3K9Me1/2) and mono- and di-methylated lysine-28 of histone H3 (H3K27Me1/2) (Horton et al. 2010, Huang et al. 2010). PHF8 (JHDM1E) catalyses demethylation of mono- or di-methylated lysine-10 of histone H3 (H3K9Me1/2) and mono-methylated lysine-21 of histone H4 (H4K20Me1) (Loenarz et al. 2010, Horton et al. 2010, Feng et al. 2010, Kleine-Kohlbrecher et al. 2010, Fortschegger et al. 2010, Qi et al. 2010, Liu et al. 2010). PHF2 (JHDM1E) catalyses demethylation of mono- or di-methylated lysine-10 of histone H3 (H3K9Me1/2) (Wen et al, 2010, Baba et al. 2011). JMJD6 was initially characterized as an arginine demethylase that catalyses demethylation of mono or di methylated arginine 3 of histone H3 (H3R2Me1/2) and arginine 4 of histone H4 (H4R3Me1/2) (Chang et al. 2007) although it was subsequently also characterized as a lysine hydroxylase (Webby et al. 2009). N.B. The coordinates of post-translational modifications represented and described here follow UniProt standard practice whereby coordinates refer to the translated protein before any further processing. Histone literature typically refers to coordinates of the protein after the initiating methionine has been removed. Therefore the coordinates of post-translated residues in the Reactome database and described here are frequently +1 when compared with the literature. 11740497Pubmed2002Histone H3 lysine 9 methylation is an epigenetic imprint of facultative heterochromatinPeters, Antoine H F MMermoud, Jacqueline EO'Carroll, DónalPagani, MichaelaSchweizer, DieterBrockdorff, NeilJenuwein, ThomasNat. Genet. 30:77-8011165500Pubmed2001JmjC: cupin metalloenzyme-like domains in jumonji, hairless and phospholipase A2betaClissold, P MPonting, C PTrends Biochem. Sci. 26:7-916261189Pubmed2005The diverse functions of histone lysine methylationMartin, CyrusZhang, YiNat. Rev. Mol. Cell Biol. 6:838-4923142576Pubmed2012Role of the jelly-roll fold in substrate binding by 2-oxoglutarate oxygenasesAik, WeiShenMcDonough, MAThalhammer, ArminChowdhury, RasheduzzamanSchofield, Christopher JCurr. Opin. Struct. Biol. 22:691-700inferred by electronic annotationIEAGOIEA