ID JMJD6_HUMAN Reviewed; 403 AA. AC Q6NYC1; B3KMN8; B4DGX1; Q86VY0; Q8IUM5; Q9Y4E2; DT 07-JUN-2005, integrated into UniProtKB/Swiss-Prot. DT 05-JUL-2004, sequence version 1. DT 27-MAR-2024, entry version 173. DE RecName: Full=Bifunctional arginine demethylase and lysyl-hydroxylase JMJD6 {ECO:0000305}; DE EC=1.14.11.- {ECO:0000269|PubMed:17947579, ECO:0000269|PubMed:19574390, ECO:0000269|PubMed:20684070, ECO:0000269|PubMed:22189873}; DE AltName: Full=Histone arginine demethylase JMJD6; DE AltName: Full=JmjC domain-containing protein 6; DE AltName: Full=Jumonji domain-containing protein 6; DE AltName: Full=Lysyl-hydroxylase JMJD6; DE AltName: Full=Peptide-lysine 5-dioxygenase JMJD6; DE AltName: Full=Phosphatidylserine receptor; DE Short=Protein PTDSR; GN Name=JMJD6 {ECO:0000312|HGNC:HGNC:19355}; GN Synonyms=KIAA0585, PSR {ECO:0000303|PubMed:14729065}, PTDSR; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RC TISSUE=Stomach cancer; RA Izawa M., Takahashi M.; RT "Identification of an alternative form of phosphatidylserine receptor."; RL Submitted (OCT-2001) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND TISSUE SPECIFICITY. RC TISSUE=Brain; RX PubMed=9628581; DOI=10.1093/dnares/5.1.31; RA Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N., RA Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. IX. The RT complete sequences of 100 new cDNA clones from brain which can code for RT large proteins in vitro."; RL DNA Res. 5:31-39(1998). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3). RC TISSUE=Brain, and Embryo; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16625196; DOI=10.1038/nature04689; RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.; RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the RT human lineage."; RL Nature 440:1045-1049(2006). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Skin, and Uterus; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP SUBCELLULAR LOCATION, AND NUCLEAR LOCALIZATION SIGNALS. RX PubMed=14729065; DOI=10.1016/j.yexcr.2003.09.023; RA Cui P., Qin B., Liu N., Pan G., Pei D.; RT "Nuclear localization of the phosphatidylserine receptor protein via RT multiple nuclear localization signals."; RL Exp. Cell Res. 293:154-163(2004). RN [8] RP TISSUE SPECIFICITY, AND INDUCTION. RX PubMed=15072554; DOI=10.1677/jme.0.0320497; RA Cao W.M., Murao K., Imachi H., Hiramine C., Abe H., Yu X., Dobashi H., RA Wong N.C.W., Takahara J., Ishida T.; RT "Phosphatidylserine receptor cooperates with high-density lipoprotein RT receptor in recognition of apoptotic cells by thymic nurse cells."; RL J. Mol. Endocrinol. 32:497-505(2004). RN [9] RP TISSUE SPECIFICITY, AND POSSIBLE FUNCTION. RX PubMed=15622002; DOI=10.1097/01.sla.0000149304.89456.5a; RA Koeninger J., Balaz P., Wagner M., Shi X., Cima I., Zimmermann A., RA di Sebastiano P., Buechler M.W., Friess H.; RT "Phosphatidylserine receptor in chronic pancreatitis: evidence for a RT macrophage independent role."; RL Ann. Surg. 241:144-151(2005). RN [10] RP FUNCTION AS HISTONE DEMETHYLASE, MUTAGENESIS OF HIS-187; ASP-189 AND RP HIS-273, AND CATALYTIC ACTIVITY. RX PubMed=17947579; DOI=10.1126/science.1145801; RA Chang B., Chen Y., Zhao Y., Bruick R.K.; RT "JMJD6 is a histone arginine demethylase."; RL Science 318:444-447(2007). RN [11] RP FUNCTION AS LYSYL-HYDROXYLASE, COFACTOR, INTERACTION WITH LUC7L2; LUC7L3 RP AND U2AF2, MUTAGENESIS OF HIS-187 AND ASP-189, AND CATALYTIC ACTIVITY. RX PubMed=19574390; DOI=10.1126/science.1175865; RA Webby C.J., Wolf A., Gromak N., Dreger M., Kramer H., Kessler B., RA Nielsen M.L., Schmitz C., Butler D.S., Yates J.R. III, Delahunty C.M., RA Hahn P., Lengeling A., Mann M., Proudfoot N.J., Schofield C.J., RA Boettger A.; RT "Jmjd6 catalyses lysyl-hydroxylation of U2AF65, a protein associated with RT RNA splicing."; RL Science 325:90-93(2009). RN [12] RP SUBCELLULAR LOCATION, RNA-BINDING, AND FUNCTION. RX PubMed=21060799; DOI=10.1371/journal.pone.0013769; RA Hahn P., Wegener I., Burrells A., Bose J., Wolf A., Erck C., Butler D., RA Schofield C.J., Bottger A., Lengeling A.; RT "Analysis of Jmjd6 cellular localization and testing for its involvement in RT histone demethylation."; RL PLoS ONE 5:E13769-E13769(2010). RN [13] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [14] RP INTERACTION WITH BRD4. RX PubMed=21555454; DOI=10.1128/mcb.01341-10; RA Rahman S., Sowa M.E., Ottinger M., Smith J.A., Shi Y., Harper J.W., RA Howley P.M.; RT "The Brd4 extraterminal domain confers transcription activation independent RT of pTEFb by recruiting multiple proteins, including NSD3."; RL Mol. Cell. Biol. 31:2641-2652(2011). RN [15] RP FUNCTION, MUTAGENESIS OF HIS-187, CATALYTIC ACTIVITY, COFACTOR, AND RP SUBUNIT. RX PubMed=22189873; DOI=10.1002/jcb.24035; RA Han G., Li J., Wang Y., Li X., Mao H., Liu Y., Chen C.D.; RT "The hydroxylation activity of Jmjd6 is required for its homo- RT oligomerization."; RL J. Cell. Biochem. 113:1663-1670(2012). RN [16] RP FUNCTION, INTERACTION WITH BRD4; CDK9 AND CCNT1, CATALYTIC ACTIVITY, RP MUTAGENESIS OF HIS-187, AND SUBUNIT. RX PubMed=24360279; DOI=10.1016/j.cell.2013.10.056; RA Liu W., Ma Q., Wong K., Li W., Ohgi K., Zhang J., Aggarwal A., RA Rosenfeld M.G.; RT "Brd4 and JMJD6-associated anti-pause enhancers in regulation of RT transcriptional pause release."; RL Cell 155:1581-1595(2013). RN [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-38, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [18] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=24498420; DOI=10.1371/journal.pone.0087982; RA Poulard C., Rambaud J., Hussein N., Corbo L., Le Romancer M.; RT "JMJD6 regulates ERalpha methylation on arginine."; RL PLoS ONE 9:E87982-E87982(2014). RN [19] RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 1-335 IN COMPLEX WITH NICKEL RP IONS, FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF TYR-131; RP LYS-204; GLU-231; THR-285 AND ASN-287, AND CATALYTIC ACTIVITY. RX PubMed=20684070; RA Mantri M., Krojer T., Bagg E.A., Webby C.J., Butler D.S., Kochan G., RA Kavanagh K.L., Oppermann U., McDonough M.A., Schofield C.J.; RT "Crystal structure of the 2-oxoglutarate- and Fe(II)-dependent lysyl RT hydroxylase JMJD6."; RL J. Mol. Biol. 401:211-222(2010). RN [20] RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 1-334 IN COMPLEX WITH IRON IONS RP AND 2-OXOGLUTARATE, POSSIBLE FUNCTION, AND RNA-BINDING. RX PubMed=20679243; DOI=10.1073/pnas.1008832107; RA Hong X., Zang J., White J., Wang C., Pan C.H., Zhao R., Murphy R.C., RA Dai S., Henson P., Kappler J.W., Hagman J., Zhang G.; RT "Interaction of JMJD6 with single-stranded RNA."; RL Proc. Natl. Acad. Sci. U.S.A. 107:14568-14572(2010). RN [21] {ECO:0007744|PDB:6BNH} RP STRUCTURE BY NMR OF 84-96 IN COMPLEX WITH BRD4, INTERACTION WITH BRD4, RP SSRNA-BINDING, AND MUTAGENESIS OF TRP-85; LEU-90; LYS-91 AND ARG-95. RX PubMed=29176719; DOI=10.1038/s41598-017-16588-8; RA Konuma T., Yu D., Zhao C., Ju Y., Sharma R., Ren C., Zhang Q., Zhou M.M., RA Zeng L.; RT "Structural Mechanism of the Oxygenase JMJD6 Recognition by the RT Extraterminal (ET) Domain of BRD4."; RL Sci. Rep. 7:16272-16272(2017). CC -!- FUNCTION: Dioxygenase that can both act as a arginine demethylase and a CC lysyl-hydroxylase (PubMed:24498420, PubMed:17947579, PubMed:20684070, CC PubMed:21060799, PubMed:22189873). Acts as a lysyl-hydroxylase that CC catalyzes 5-hydroxylation on specific lysine residues of target CC proteins such as U2AF2/U2AF65 and LUC7L2. Regulates RNA splicing by CC mediating 5-hydroxylation of U2AF2/U2AF65, affecting the pre-mRNA CC splicing activity of U2AF2/U2AF65 (PubMed:19574390). Hydroxylates its CC own N-terminus, which is required for homooligomerization CC (PubMed:22189873). Plays a role in the regulation of nucleolar liquid- CC liquid phase separation (LLPS) by post-translationally modifying LIAT1 CC at its lysine-rich domain which inhibits LIAT1 nucleolar targeting (By CC similarity). In addition to peptidyl-lysine 5-dioxygenase activity, may CC act as an RNA hydroxylase, as suggested by its ability to bind single CC strand RNA (PubMed:20679243, PubMed:29176719). Also acts as an arginine CC demethylase which preferentially demethylates asymmetric dimethylation CC (PubMed:17947579, PubMed:24498420, PubMed:24360279). Demethylates CC histone H3 at 'Arg-2' (H3R2me) and histone H4 at 'Arg-3' (H4R3me), CC including mono-, symmetric di- and asymmetric dimethylated forms, CC thereby playing a role in histone code (PubMed:17947579, CC PubMed:24360279). However, histone arginine demethylation may not CC constitute the primary activity in vivo (PubMed:17947579, CC PubMed:21060799, PubMed:22189873). In collaboration with BRD4, CC interacts with the positive transcription elongation factor b (P-TEFb) CC complex in its active form to regulate polymerase II promoter-proximal CC pause release for transcriptional activation of a large cohort of CC genes. On distal enhancers, so called anti-pause enhancers, CC demethylates both histone H4R3me2 and the methyl cap of 7SKsnRNA CC leading to the dismissal of the 7SKsnRNA:HEXIM1 inhibitor complex. CC After removal of repressive marks, the complex BRD4:JMJD6 attract and CC retain the P-TEFb complex on chromatin, leading to its activation, CC promoter-proximal polymerase II pause release, and transcriptional CC activation (PubMed:24360279). Demethylates other arginine methylated- CC proteins such as ESR1 (PubMed:24498420). Has no histone lysine CC demethylase activity (PubMed:21060799). Required for differentiation of CC multiple organs during embryogenesis. Acts as a key regulator of CC hematopoietic differentiation: required for angiogenic sprouting by CC regulating the pre-mRNA splicing activity of U2AF2/U2AF65 (By CC similarity). Seems to be necessary for the regulation of macrophage CC cytokine responses (PubMed:15622002). {ECO:0000250|UniProtKB:Q9ERI5, CC ECO:0000269|PubMed:15622002, ECO:0000269|PubMed:17947579, CC ECO:0000269|PubMed:19574390, ECO:0000269|PubMed:20679243, CC ECO:0000269|PubMed:20684070, ECO:0000269|PubMed:21060799, CC ECO:0000269|PubMed:22189873, ECO:0000269|PubMed:24360279, CC ECO:0000269|PubMed:24498420, ECO:0000269|PubMed:29176719}. CC -!- CATALYTIC ACTIVITY: CC Reaction=2-oxoglutarate + L-lysyl-[protein] + O2 = (5S)-5-hydroxy-L- CC lysyl-[protein] + CO2 + succinate; Xref=Rhea:RHEA:58360, Rhea:RHEA- CC COMP:9752, Rhea:RHEA-COMP:15144, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:16526, ChEBI:CHEBI:16810, ChEBI:CHEBI:29969, CC ChEBI:CHEBI:30031, ChEBI:CHEBI:141843; CC Evidence={ECO:0000269|PubMed:19574390, ECO:0000269|PubMed:20684070, CC ECO:0000269|PubMed:22189873}; CC -!- CATALYTIC ACTIVITY: CC Reaction=2 2-oxoglutarate + N(omega),N(omega)'-dimethyl-L-arginyl- CC [protein] + 2 O2 = 2 CO2 + 2 formaldehyde + L-arginyl-[protein] + 2 CC succinate; Xref=Rhea:RHEA:58348, Rhea:RHEA-COMP:10532, Rhea:RHEA- CC COMP:11992, ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810, CC ChEBI:CHEBI:16842, ChEBI:CHEBI:29965, ChEBI:CHEBI:30031, CC ChEBI:CHEBI:88221; Evidence={ECO:0000269|PubMed:17947579, CC ECO:0000269|PubMed:24360279}; CC -!- CATALYTIC ACTIVITY: CC Reaction=2-oxoglutarate + N(omega),N(omega)'-dimethyl-L-arginyl- CC [protein] + O2 = CO2 + formaldehyde + N(omega)-methyl-L-arginyl- CC [protein] + succinate; Xref=Rhea:RHEA:58472, Rhea:RHEA-COMP:11990, CC Rhea:RHEA-COMP:11992, ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, CC ChEBI:CHEBI:16810, ChEBI:CHEBI:16842, ChEBI:CHEBI:30031, CC ChEBI:CHEBI:65280, ChEBI:CHEBI:88221; CC Evidence={ECO:0000269|PubMed:17947579, ECO:0000269|PubMed:24360279}; CC -!- CATALYTIC ACTIVITY: CC Reaction=2-oxoglutarate + a 5'-end methyltriphosphate-guanosine- CC ribonucleotide-snRNA + O2 = a 5'-end triphospho-guanosine- CC ribonucleotide-snRNA + CO2 + formaldehyde + H(+) + succinate; CC Xref=Rhea:RHEA:58784, Rhea:RHEA-COMP:15220, Rhea:RHEA-COMP:15221, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, CC ChEBI:CHEBI:16810, ChEBI:CHEBI:16842, ChEBI:CHEBI:30031, CC ChEBI:CHEBI:138278, ChEBI:CHEBI:142789; CC Evidence={ECO:0000269|PubMed:24360279}; CC -!- COFACTOR: CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033; CC Evidence={ECO:0000269|PubMed:19574390, ECO:0000269|PubMed:22189873}; CC Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000269|PubMed:19574390}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=39 uM for 2-oxoglutarate {ECO:0000269|PubMed:20684070}; CC -!- SUBUNIT: Homooligomerizes; requires lysyl-hydroxylase activity CC (PubMed:22189873, PubMed:24360279). Interacts with LUC7L2, LUC7L3 and CC U2AF2/U2AF65 (PubMed:19574390). Interacts with CDK9 and CCNT1; the CC interaction is direct with CDK9 and associates the P-TEFb complex when CC active (PubMed:24360279). Interacts (via JmjC and N-terminal domains) CC with BRD4 (via NET domain); the interaction is stronger in presence of CC ssRNA and recruits JMJD6 on distal enhancers (PubMed:21555454, CC PubMed:24360279, PubMed:29176719). {ECO:0000269|PubMed:19574390, CC ECO:0000269|PubMed:21555454, ECO:0000269|PubMed:22189873, CC ECO:0000269|PubMed:24360279, ECO:0000269|PubMed:29176719}. CC -!- INTERACTION: CC Q6NYC1; O60885: BRD4; NbExp=10; IntAct=EBI-8464037, EBI-723869; CC Q6NYC1; Q86X55: CARM1; NbExp=2; IntAct=EBI-8464037, EBI-2339854; CC Q6NYC1; P50750: CDK9; NbExp=5; IntAct=EBI-8464037, EBI-1383449; CC Q6NYC1; P03372: ESR1; NbExp=8; IntAct=EBI-8464037, EBI-78473; CC Q6NYC1; Q96NE9: FRMD6; NbExp=3; IntAct=EBI-8464037, EBI-741729; CC Q6NYC1; Q6NYC1: JMJD6; NbExp=3; IntAct=EBI-8464037, EBI-8464037; CC Q6NYC1; Q9GZZ1: NAA50; NbExp=6; IntAct=EBI-8464037, EBI-1052523; CC Q6NYC1; Q8NAV1: PRPF38A; NbExp=2; IntAct=EBI-8464037, EBI-715374; CC Q6NYC1; P04637: TP53; NbExp=7; IntAct=EBI-8464037, EBI-366083; CC Q6NYC1; Q01081: U2AF1; NbExp=2; IntAct=EBI-8464037, EBI-632461; CC Q6NYC1; Q9NP64: ZCCHC17; NbExp=2; IntAct=EBI-8464037, EBI-746345; CC -!- SUBCELLULAR LOCATION: Nucleus, nucleoplasm CC {ECO:0000269|PubMed:14729065, ECO:0000269|PubMed:21060799}. Nucleus, CC nucleolus {ECO:0000269|PubMed:21060799}. Cytoplasm CC {ECO:0000269|PubMed:21060799, ECO:0000269|PubMed:24498420}. Note=Mainly CC found throughout the nucleoplasm outside of regions containing CC heterochromatic DNA, with some localization in nucleolus. During CC mitosis, excluded from the nucleus and reappears in the telophase of CC the cell cycle. {ECO:0000269|PubMed:21060799}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; Synonyms=Alpha; CC IsoId=Q6NYC1-1; Sequence=Displayed; CC Name=2; Synonyms=Beta; CC IsoId=Q6NYC1-2; Sequence=VSP_014022, VSP_014023; CC Name=3; CC IsoId=Q6NYC1-3; Sequence=VSP_014023; CC -!- TISSUE SPECIFICITY: Highly expressed in the heart, skeletal muscle and CC kidney. Expressed at moderate or low level in brain, placenta, lung, CC liver, pancreas, spleen, thymus, prostate, testis and ovary. Up- CC regulated in many patients with chronic pancreatitis. Expressed in CC nursing thymic epithelial cells. {ECO:0000269|PubMed:15072554, CC ECO:0000269|PubMed:15622002, ECO:0000269|PubMed:9628581}. CC -!- INDUCTION: Up-regulated upon cytokine treatment, but not upon TNF CC treatment. {ECO:0000269|PubMed:15072554}. CC -!- DOMAIN: The nuclear localization signal motifs are necessary and CC sufficient to target it into the nucleus. CC {ECO:0000269|PubMed:14729065}. CC -!- PTM: Hydroxylates its own N-terminus; hydroxylation is required for CC homooligomerization. {ECO:0000269|PubMed:22189873}. CC -!- SIMILARITY: Belongs to the JMJD6 family. {ECO:0000305}. CC -!- CAUTION: Was initially thought to constitute the phosphatidylserine CC receptor, a receptor that mediates recognition of phosphatidylserine, a CC specific marker only present at the surface of apoptotic cells. CC Phosphatidylserine receptor probably participates in apoptotic cell CC phagocytosis. This protein was identified using phage display CC expressing mAb 217, an antibody that specifically recognizes CC phosphatidylserine receptor. However, its nuclear localization and the CC fact that mAb 217 antibody still recognizes the phosphatidylserine CC receptor in mice lacking JMJD6, strongly suggest that it does not CC constitute the receptor for phosphatidylserine and is not involved in CC apoptotic cell removal. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH47003.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC Sequence=BAA25511.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AB073711; BAC16755.1; -; mRNA. DR EMBL; AB011157; BAA25511.1; ALT_INIT; mRNA. DR EMBL; AK021780; BAG51050.1; -; mRNA. DR EMBL; AK294816; BAG57932.1; -; mRNA. DR EMBL; AC005837; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471099; EAW89434.1; -; Genomic_DNA. DR EMBL; BC047003; AAH47003.1; ALT_INIT; mRNA. DR EMBL; BC066654; AAH66654.1; -; mRNA. DR CCDS; CCDS42383.1; -. [Q6NYC1-3] DR CCDS; CCDS42384.1; -. [Q6NYC1-1] DR RefSeq; NP_001074930.1; NM_001081461.1. [Q6NYC1-3] DR RefSeq; NP_055982.2; NM_015167.2. [Q6NYC1-1] DR PDB; 3K2O; X-ray; 1.75 A; A/B=2-335. DR PDB; 3LD8; X-ray; 2.70 A; A=1-334. DR PDB; 3LDB; X-ray; 2.70 A; A=1-334. DR PDB; 6BNH; NMR; -; B=84-96. DR PDB; 6GDY; X-ray; 2.04 A; A/B=1-343. DR PDB; 6MEV; X-ray; 2.60 A; A/B/C/D/E/F/G/H=1-341. DR PDBsum; 3K2O; -. DR PDBsum; 3LD8; -. DR PDBsum; 3LDB; -. DR PDBsum; 6BNH; -. DR PDBsum; 6GDY; -. DR PDBsum; 6MEV; -. DR AlphaFoldDB; Q6NYC1; -. DR SMR; Q6NYC1; -. DR BioGRID; 116817; 200. DR DIP; DIP-60686N; -. DR IntAct; Q6NYC1; 144. DR MINT; Q6NYC1; -. DR STRING; 9606.ENSP00000394085; -. DR BindingDB; Q6NYC1; -. DR ChEMBL; CHEMBL4523345; -. DR GlyGen; Q6NYC1; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q6NYC1; -. DR PhosphoSitePlus; Q6NYC1; -. DR BioMuta; JMJD6; -. DR DMDM; 67461014; -. DR EPD; Q6NYC1; -. DR jPOST; Q6NYC1; -. DR MassIVE; Q6NYC1; -. DR MaxQB; Q6NYC1; -. DR PaxDb; 9606-ENSP00000394085; -. DR PeptideAtlas; Q6NYC1; -. DR ProteomicsDB; 66781; -. [Q6NYC1-1] DR ProteomicsDB; 66782; -. [Q6NYC1-2] DR ProteomicsDB; 66783; -. [Q6NYC1-3] DR Pumba; Q6NYC1; -. DR ABCD; Q6NYC1; 4 sequenced antibodies. DR Antibodypedia; 3874; 490 antibodies from 41 providers. DR DNASU; 23210; -. DR Ensembl; ENST00000397625.9; ENSP00000380750.4; ENSG00000070495.15. [Q6NYC1-1] DR Ensembl; ENST00000445478.6; ENSP00000394085.2; ENSG00000070495.15. [Q6NYC1-3] DR GeneID; 23210; -. DR KEGG; hsa:23210; -. DR MANE-Select; ENST00000397625.9; ENSP00000380750.4; NM_015167.3; NP_055982.2. DR UCSC; uc002jsn.2; human. [Q6NYC1-1] DR AGR; HGNC:19355; -. DR CTD; 23210; -. DR DisGeNET; 23210; -. DR GeneCards; JMJD6; -. DR HGNC; HGNC:19355; JMJD6. DR HPA; ENSG00000070495; Tissue enhanced (bone). DR MIM; 604914; gene. DR neXtProt; NX_Q6NYC1; -. DR OpenTargets; ENSG00000070495; -. DR PharmGKB; PA162392513; -. DR VEuPathDB; HostDB:ENSG00000070495; -. DR eggNOG; KOG2130; Eukaryota. DR GeneTree; ENSGT00940000156867; -. DR HOGENOM; CLU_016785_8_0_1; -. DR InParanoid; Q6NYC1; -. DR OMA; NAWVAMR; -. DR OrthoDB; 120564at2759; -. DR PhylomeDB; Q6NYC1; -. DR TreeFam; TF314988; -. DR BRENDA; 1.14.11.4; 2681. DR PathwayCommons; Q6NYC1; -. DR Reactome; R-HSA-3214842; HDMs demethylate histones. DR Reactome; R-HSA-9629569; Protein hydroxylation. DR SABIO-RK; Q6NYC1; -. DR SignaLink; Q6NYC1; -. DR SIGNOR; Q6NYC1; -. DR BioGRID-ORCS; 23210; 283 hits in 1185 CRISPR screens. DR ChiTaRS; JMJD6; human. DR EvolutionaryTrace; Q6NYC1; -. DR GeneWiki; JMJD6; -. DR GenomeRNAi; 23210; -. DR Pharos; Q6NYC1; Tchem. DR PRO; PR:Q6NYC1; -. DR Proteomes; UP000005640; Chromosome 17. DR RNAct; Q6NYC1; Protein. DR Bgee; ENSG00000070495; Expressed in saphenous vein and 211 other cell types or tissues. DR ExpressionAtlas; Q6NYC1; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IEA:Ensembl. DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IEA:Ensembl. DR GO; GO:1990904; C:ribonucleoprotein complex; IEA:Ensembl. DR GO; GO:0032452; F:histone demethylase activity; IDA:UniProtKB. DR GO; GO:0033746; F:histone H3R2 demethylase activity; IDA:UniProtKB. DR GO; GO:0033749; F:histone H4R3 demethylase activity; IDA:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IDA:BHF-UCL. DR GO; GO:0005506; F:iron ion binding; IDA:UniProtKB. DR GO; GO:0035515; F:oxidative RNA demethylase activity; IMP:UniProtKB. DR GO; GO:0106140; F:P-TEFb complex binding; IDA:UniProtKB. DR GO; GO:0070815; F:peptidyl-lysine 5-dioxygenase activity; IDA:UniProtKB. DR GO; GO:0140457; F:protein demethylase activity; IDA:UniProtKB. DR GO; GO:0003723; F:RNA binding; TAS:UniProtKB. DR GO; GO:0038023; F:signaling receptor activity; IEA:Ensembl. DR GO; GO:0003727; F:single-stranded RNA binding; IDA:UniProtKB. DR GO; GO:0140537; F:transcription regulator activator activity; IMP:UniProtKB. DR GO; GO:0007166; P:cell surface receptor signaling pathway; IEA:Ensembl. DR GO; GO:0006338; P:chromatin remodeling; IDA:BHF-UCL. DR GO; GO:0048821; P:erythrocyte development; IEA:Ensembl. DR GO; GO:0007507; P:heart development; IEA:Ensembl. DR GO; GO:0001822; P:kidney development; IEA:Ensembl. DR GO; GO:0030324; P:lung development; IEA:Ensembl. DR GO; GO:0042116; P:macrophage activation; IEA:Ensembl. DR GO; GO:0006397; P:mRNA processing; IEA:UniProtKB-KW. DR GO; GO:0032463; P:negative regulation of protein homooligomerization; ISS:UniProt. DR GO; GO:0140694; P:non-membrane-bounded organelle assembly; ISS:UniProt. DR GO; GO:0035513; P:oxidative RNA demethylation; IDA:UniProtKB. DR GO; GO:0018395; P:peptidyl-lysine hydroxylation to 5-hydroxy-L-lysine; IDA:UniProtKB. DR GO; GO:0006909; P:phagocytosis; IBA:GO_Central. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IMP:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB. DR GO; GO:0051260; P:protein homooligomerization; IDA:UniProtKB. DR GO; GO:0043654; P:recognition of apoptotic cell; IEA:Ensembl. DR GO; GO:0048024; P:regulation of mRNA splicing, via spliceosome; IMP:UniProtKB. DR GO; GO:0060041; P:retina development in camera-type eye; IEA:Ensembl. DR GO; GO:0008380; P:RNA splicing; IEA:UniProtKB-KW. DR GO; GO:0002040; P:sprouting angiogenesis; ISS:UniProtKB. DR GO; GO:0033077; P:T cell differentiation in thymus; IEA:Ensembl. DR Gene3D; 1.20.1280.270; -; 1. DR Gene3D; 2.60.120.650; Cupin; 1. DR InterPro; IPR003347; JmjC_dom. DR PANTHER; PTHR12480; ARGININE DEMETHYLASE AND LYSYL-HYDROXYLASE JMJD; 1. DR PANTHER; PTHR12480:SF32; BIFUNCTIONAL ARGININE DEMETHYLASE AND LYSYL-HYDROXYLASE JMJD6; 1. DR Pfam; PF02373; JmjC; 1. DR SMART; SM00558; JmjC; 1. DR SUPFAM; SSF51197; Clavaminate synthase-like; 1. DR PROSITE; PS51184; JMJC; 1. DR Genevisible; Q6NYC1; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Chromatin regulator; Cytoplasm; KW Developmental protein; Differentiation; Dioxygenase; Iron; Metal-binding; KW mRNA processing; mRNA splicing; Nucleus; Oxidoreductase; Phosphoprotein; KW Reference proteome; RNA-binding; Transcription; Transcription regulation. FT CHAIN 1..403 FT /note="Bifunctional arginine demethylase and lysyl- FT hydroxylase JMJD6" FT /id="PRO_0000129369" FT DOMAIN 141..305 FT /note="JmjC" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00538" FT REGION 336..403 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 6..10 FT /note="Nuclear localization signal 1" FT /evidence="ECO:0000269|PubMed:14729065" FT MOTIF 91..95 FT /note="Nuclear localization signal 2" FT /evidence="ECO:0000269|PubMed:14729065" FT MOTIF 141..145 FT /note="Nuclear localization signal 3" FT /evidence="ECO:0000269|PubMed:14729065" FT MOTIF 167..170 FT /note="Nuclear localization signal 4" FT /evidence="ECO:0000269|PubMed:14729065" FT MOTIF 373..378 FT /note="Nuclear localization signal 5" FT /evidence="ECO:0000269|PubMed:14729065" FT COMPBIAS 336..360 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 184 FT /ligand="substrate" FT /evidence="ECO:0000250" FT BINDING 187 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:20679243" FT BINDING 189 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:20679243" FT BINDING 197 FT /ligand="2-oxoglutarate" FT /ligand_id="ChEBI:CHEBI:16810" FT /evidence="ECO:0000269|PubMed:20679243" FT BINDING 204 FT /ligand="substrate" FT /evidence="ECO:0000250" FT BINDING 273 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:20679243" FT BINDING 285 FT /ligand="2-oxoglutarate" FT /ligand_id="ChEBI:CHEBI:16810" FT /evidence="ECO:0000269|PubMed:20679243" FT MOD_RES 38 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT VAR_SEQ 361..402 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|Ref.1" FT /id="VSP_014022" FT VAR_SEQ 403 FT /note="R -> RIRDTCGGRAHP (in isoform 2 and isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:9628581, ECO:0000303|Ref.1" FT /id="VSP_014023" FT MUTAGEN 85 FT /note="W->A: Decreases interaction with the NET domain of FT BRD4." FT /evidence="ECO:0000269|PubMed:29176719" FT MUTAGEN 90 FT /note="L->A: Nearly abolishes the interaction with the NET FT domain of BRD4." FT /evidence="ECO:0000269|PubMed:29176719" FT MUTAGEN 91 FT /note="K->A: Nearly abolishes the interaction with the NET FT domain of BRD4." FT /evidence="ECO:0000269|PubMed:29176719" FT MUTAGEN 95 FT /note="R->A: Nearly abolishes the interaction with the NET FT domain of BRD4." FT /evidence="ECO:0000269|PubMed:29176719" FT MUTAGEN 131 FT /note="Y->F: Abolishes 2-oxoglutarate-binding and enzyme FT activity." FT /evidence="ECO:0000269|PubMed:20684070" FT MUTAGEN 187 FT /note="H->A: Loss of histone arginine demethylase and FT lysyl-hydroxylase activities. Abolishes FT homooligomerisation. Loss of arginine demethylase and a FT lysyl-hydroxylase activities; when associated with A-189 FT and A-273." FT /evidence="ECO:0000269|PubMed:17947579, FT ECO:0000269|PubMed:19574390, ECO:0000269|PubMed:22189873, FT ECO:0000269|PubMed:24360279" FT MUTAGEN 189 FT /note="D->A: Loss of arginine demethylase and a FT lysyl-hydroxylase activities; when associated with A-187 FT and A-273." FT /evidence="ECO:0000269|PubMed:17947579, FT ECO:0000269|PubMed:19574390" FT MUTAGEN 204 FT /note="K->A: Impairs enzyme activity without affecting FT 2-oxoglutarate-binding." FT /evidence="ECO:0000269|PubMed:20684070" FT MUTAGEN 231 FT /note="E->A: Impairs both hydroxylation activity and FT 2-oxoglutarate turnover assays." FT /evidence="ECO:0000269|PubMed:20684070" FT MUTAGEN 273 FT /note="H->A: Loss of arginine demethylase and a FT lysyl-hydroxylase activities; when associated with A-187 FT and A-189." FT /evidence="ECO:0000269|PubMed:17947579" FT MUTAGEN 285 FT /note="T->A: Impairs enzyme activity and FT 2-oxoglutarate-binding." FT /evidence="ECO:0000269|PubMed:20684070" FT MUTAGEN 287 FT /note="N->A: Impairs enzyme activity." FT /evidence="ECO:0000269|PubMed:20684070" FT CONFLICT 136 FT /note="S -> G (in Ref. 3; BAG51050)" FT /evidence="ECO:0000305" FT HELIX 3..16 FT /evidence="ECO:0007829|PDB:3K2O" FT HELIX 23..27 FT /evidence="ECO:0007829|PDB:3K2O" FT HELIX 31..34 FT /evidence="ECO:0007829|PDB:3K2O" FT HELIX 39..41 FT /evidence="ECO:0007829|PDB:3K2O" FT STRAND 48..50 FT /evidence="ECO:0007829|PDB:3K2O" FT HELIX 51..53 FT /evidence="ECO:0007829|PDB:3K2O" FT HELIX 56..62 FT /evidence="ECO:0007829|PDB:3K2O" FT TURN 63..67 FT /evidence="ECO:0007829|PDB:3K2O" FT STRAND 70..74 FT /evidence="ECO:0007829|PDB:3K2O" FT TURN 75..78 FT /evidence="ECO:0007829|PDB:3K2O" FT HELIX 81..84 FT /evidence="ECO:0007829|PDB:3K2O" FT HELIX 87..93 FT /evidence="ECO:0007829|PDB:3K2O" FT TURN 94..96 FT /evidence="ECO:0007829|PDB:6GDY" FT STRAND 98..103 FT /evidence="ECO:0007829|PDB:3K2O" FT STRAND 109..113 FT /evidence="ECO:0007829|PDB:3K2O" FT HELIX 114..123 FT /evidence="ECO:0007829|PDB:3K2O" FT STRAND 132..135 FT /evidence="ECO:0007829|PDB:3K2O" FT HELIX 137..139 FT /evidence="ECO:0007829|PDB:3K2O" FT HELIX 143..149 FT /evidence="ECO:0007829|PDB:3K2O" FT HELIX 154..156 FT /evidence="ECO:0007829|PDB:3K2O" FT HELIX 160..164 FT /evidence="ECO:0007829|PDB:3K2O" FT TURN 166..168 FT /evidence="ECO:0007829|PDB:3K2O" FT STRAND 173..178 FT /evidence="ECO:0007829|PDB:3K2O" FT STRAND 183..187 FT /evidence="ECO:0007829|PDB:3K2O" FT HELIX 190..192 FT /evidence="ECO:0007829|PDB:3K2O" FT STRAND 194..202 FT /evidence="ECO:0007829|PDB:3K2O" FT STRAND 204..209 FT /evidence="ECO:0007829|PDB:3K2O" FT HELIX 215..218 FT /evidence="ECO:0007829|PDB:3K2O" FT HELIX 222..225 FT /evidence="ECO:0007829|PDB:3K2O" FT HELIX 226..228 FT /evidence="ECO:0007829|PDB:3K2O" FT HELIX 232..238 FT /evidence="ECO:0007829|PDB:3K2O" FT HELIX 240..244 FT /evidence="ECO:0007829|PDB:3K2O" FT HELIX 250..252 FT /evidence="ECO:0007829|PDB:3K2O" FT STRAND 255..259 FT /evidence="ECO:0007829|PDB:3K2O" FT STRAND 264..267 FT /evidence="ECO:0007829|PDB:3K2O" FT STRAND 272..279 FT /evidence="ECO:0007829|PDB:3K2O" FT STRAND 281..288 FT /evidence="ECO:0007829|PDB:3K2O" FT TURN 291..293 FT /evidence="ECO:0007829|PDB:3K2O" FT HELIX 294..304 FT /evidence="ECO:0007829|PDB:3K2O" FT HELIX 306..319 FT /evidence="ECO:0007829|PDB:3K2O" FT HELIX 321..333 FT /evidence="ECO:0007829|PDB:3K2O" SQ SEQUENCE 403 AA; 46462 MW; 9C9AADA98B24B035 CRC64; MNHKSKKRIR EAKRSARPEL KDSLDWTRHN YYESFSLSPA AVADNVERAD ALQLSVEEFV ERYERPYKPV VLLNAQEGWS AQEKWTLERL KRKYRNQKFK CGEDNDGYSV KMKMKYYIEY MESTRDDSPL YIFDSSYGEH PKRRKLLEDY KVPKFFTDDL FQYAGEKRRP PYRWFVMGPP RSGTGIHIDP LGTSAWNALV QGHKRWCLFP TSTPRELIKV TRDEGGNQQD EAITWFNVIY PRTQLPTWPP EFKPLEILQK PGETVFVPGG WWHVVLNLDT TIAITQNFAS STNFPVVWHK TVRGRPKLSR KWYRILKQEH PELAVLADSV DLQESTGIAS DSSSDSSSSS SSSSSDSDSE CESGSEGDGT VHRRKKRRTC SMVGNGDTTS QDDCVSKERS SSR //