ID KDM8_HUMAN Reviewed; 416 AA. AC Q8N371; B4DLU9; Q6VAK5; Q9H8B1; DT 26-JUN-2007, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2002, sequence version 1. DT 27-MAR-2024, entry version 146. DE RecName: Full=Bifunctional peptidase and arginyl-hydroxylase JMJD5 {ECO:0000305|PubMed:28847961, ECO:0000305|PubMed:29459673, ECO:0000305|PubMed:29563586}; DE EC=1.14.11.73 {ECO:0000269|PubMed:29563586}; DE EC=3.4.-.- {ECO:0000269|PubMed:28847961, ECO:0000269|PubMed:29459673}; DE AltName: Full=JmjC domain-containing protein 5 {ECO:0000303|PubMed:28982940}; DE AltName: Full=Jumonji C domain-containing protein 5 {ECO:0000303|PubMed:28982940}; DE AltName: Full=L-arginine (3R)-hydroxylase KDM8 {ECO:0000305|PubMed:29563586}; GN Name=KDM8 {ECO:0000303|PubMed:20457893, ECO:0000303|PubMed:29563586, GN ECO:0000312|HGNC:HGNC:25840}; GN Synonyms=JMJD5 {ECO:0000303|PubMed:28847961, GN ECO:0000303|PubMed:28982940, ECO:0000303|PubMed:29563586}; 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 [LARGE SCALE MRNA] (ISOFORMS 1 AND 3). RC TISSUE=Brain, and Thyroid; 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 [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RA Li H., Yu R., Zheng G., Zhou G., Ke R., Shen C., Zhong G., Lin L., Yang S.; RL Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15616553; DOI=10.1038/nature03187; RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M., RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., RA Myers R.M., Rubin E.M., Pennacchio L.A.; RT "The sequence and analysis of duplication-rich human chromosome 16."; RL Nature 432:988-994(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Lung; 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 [5] RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, MUTAGENESIS OF HIS-321, RP AND CAUTION. RX PubMed=20457893; DOI=10.1073/pnas.1000401107; RA Hsia D.A., Tepper C.G., Pochampalli M.R., Hsia E.Y., Izumiya C., RA Huerta S.B., Wright M.E., Chen H.W., Kung H.J., Izumiya Y.; RT "KDM8, a H3K36me2 histone demethylase that acts in the cyclin A1 coding RT region to regulate cancer cell proliferation."; RL Proc. Natl. Acad. Sci. U.S.A. 107:9671-9676(2010). RN [6] RP FUNCTION, COFACTOR, IDENTIFICATION IN A COMPLEX WITH RCCD1, INTERACTION RP WITH RCCD1, SUBCELLULAR LOCATION, IDENTIFICATION BY MASS SPECTROMETRY, AND RP CAUTION. RX PubMed=24981860; DOI=10.1016/j.celrep.2014.05.050; RA Marcon E., Ni Z., Pu S., Turinsky A.L., Trimble S.S., Olsen J.B., RA Silverman-Gavrila R., Silverman-Gavrila L., Phanse S., Guo H., Zhong G., RA Guo X., Young P., Bailey S., Roudeva D., Zhao D., Hewel J., Li J., RA Graeslund S., Paduch M., Kossiakoff A.A., Lupien M., Emili A., Wodak S.J., RA Greenblatt J.; RT "Human-chromatin-related protein interactions identify a demethylase RT complex required for chromosome segregation."; RL Cell Rep. 8:297-310(2014). RN [7] RP FUNCTION, AND TISSUE SPECIFICITY. RX PubMed=24740926; DOI=10.1002/stem.1724; RA Zhu H., Hu S., Baker J.; RT "JMJD5 regulates cell cycle and pluripotency in human embryonic stem RT cells."; RL Stem Cells 32:2098-2110(2014). RN [8] RP FUNCTION, AND INTERACTION WITH RCCD1. RX PubMed=28455245; DOI=10.1016/j.canlet.2017.04.021; RA Wu J., He Z., Yang X.M., Li K.L., Wang D.L., Sun F.L.; RT "RCCD1 depletion attenuates TGF-beta-induced EMT and cell migration by RT stabilizing cytoskeletal microtubules in NSCLC cells."; RL Cancer Lett. 400:18-29(2017). RN [9] RP FUNCTION, COFACTOR, SUBUNIT, INTERACTION WITH H3C1, SUBCELLULAR LOCATION, RP INDUCTION, MUTAGENESIS OF 321-HIS--ASP-323; 335-ARG-LYS-336 AND RP 398-TRP--HIS-400, AND CAUTION. RX PubMed=28982940; DOI=10.15252/embr.201743892; RA Shen J., Xiang X., Chen L., Wang H., Wu L., Sun Y., Ma L., Gu X., Liu H., RA Wang L., Yu Y.N., Shao J., Huang C., Chin Y.E.; RT "JMJD5 cleaves monomethylated histone H3 N-tail under DNA damaging RT stress."; RL EMBO Rep. 18:E201743892-E201743892(2017). RN [10] RP FUNCTION, AND MUTAGENESIS OF HIS-321; ASP-323 AND HIS-400. RX PubMed=28847961; DOI=10.1073/pnas.1706831114; RA Liu H., Wang C., Lee S., Deng Y., Wither M., Oh S., Ning F., Dege C., RA Zhang Q., Liu X., Johnson A.M., Zang J., Chen Z., Janknecht R., Hansen K., RA Marrack P., Li C.Y., Kappler J.W., Hagman J., Zhang G.; RT "Clipping of arginine-methylated histone tails by JMJD5 and JMJD7."; RL Proc. Natl. Acad. Sci. U.S.A. 114:E7717-E7726(2017). RN [11] RP FUNCTION, AND MUTAGENESIS OF HIS-321. RX PubMed=30500822; DOI=10.1371/journal.pbio.2006145; RA Saran A.R., Kalinowska D., Oh S., Janknecht R., DiTacchio L.; RT "JMJD5 links CRY1 function and proteasomal degradation."; RL PLoS Biol. 16:E2006145-E2006145(2018). RN [12] RP X-RAY CRYSTALLOGRAPHY (1.12 ANGSTROMS) OF 183-416 IN COMPLEX WITH RP 2-OXOGLUTARIC ACID, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, RP MUTAGENESIS OF GLU-238; TYR-243; GLN-275; TRP-310; HIS-321; LEU-356; RP TRP-414 AND 1-MET--LYS-182, FUNCTION, AND COFACTOR. RX PubMed=29563586; DOI=10.1038/s41467-018-03410-w; RA Wilkins S.E., Islam S., Gannon J.M., Markolovic S., Hopkinson R.J., Ge W., RA Schofield C.J., Chowdhury R.; RT "JMJD5 is a human L-arginyl C-3 hydroxylase."; RL Nat. Commun. 9:1180-1180(2018). RN [13] RP X-RAY CRYSTALLOGRAPHY (2.02 ANGSTROMS) OF 183-416 IN COMPLEX WITH RP 2-OXOGLUTARIC ACID; N(OMEGA)-METHYL-L-ARGININE AND SYMMETRICAL RP N(OMEGA),N'(OMEGA)-DIMETHYL-L-ARGININE, MUTAGENESIS OF GLN-275 AND LYS-336, RP AND FUNCTION. RX PubMed=29459673; DOI=10.1038/s41598-018-21432-8; RA Liu H., Wang C., Lee S., Ning F., Wang Y., Zhang Q., Chen Z., Zang J., RA Nix J., Dai S., Marrack P., Hagman J., Kappler J., Zhang G.; RT "Specific Recognition of Arginine Methylated Histone Tails by JMJD5 and RT JMJD7."; RL Sci. Rep. 8:3275-3275(2018). RN [14] RP X-RAY CRYSTALLOGRAPHY (1.05 ANGSTROMS) OF 183-416 IN COMPLEX WITH RP 2-OXOGLUTARATE AND COBALT, FUNCTION, AND CAUTION. RX PubMed=22851697; DOI=10.1128/mcb.00513-12; RA Del Rizzo P.A., Krishnan S., Trievel R.C.; RT "Crystal structure and functional analysis of JMJD5 indicate an alternate RT specificity and function."; RL Mol. Cell. Biol. 32:4044-4052(2012). RN [15] RP X-RAY CRYSTALLOGRAPHY (2.81 ANGSTROMS) OF 176-416 IN COMPLEX WITH RP N-OXALGLYCINE AND NICKEL, SUBUNIT, COFACTOR, AND CAUTION. RX PubMed=24100311; DOI=10.1107/s0907444913016600; RA Wang H., Zhou X., Wu M., Wang C., Zhang X., Tao Y., Chen N., Zang J.; RT "Structure of the JmjC-domain-containing protein JMJD5."; RL Acta Crystallogr. D 69:1911-1920(2013). CC -!- FUNCTION: Bifunctional enzyme that acts both as an endopeptidase and 2- CC oxoglutarate-dependent monooxygenase (PubMed:28847961, PubMed:29459673, CC PubMed:28982940, PubMed:29563586). Endopeptidase that cleaves histones CC N-terminal tails at the carboxyl side of methylated arginine or lysine CC residues, to generate 'tailless nucleosomes', which may trigger CC transcription elongation (PubMed:28847961, PubMed:29459673, CC PubMed:28982940). Preferentially recognizes and cleaves monomethylated CC and dimethylated arginine residues of histones H2, H3 and H4. After CC initial cleavage, continues to digest histones tails via its CC aminopeptidase activity (PubMed:28847961, PubMed:29459673). Upon DNA CC damage, cleaves the N-terminal tail of histone H3 at monomethylated CC lysine residues, preferably at monomethylated 'Lys-9' (H3K9me1). The CC histone variant H3F3A is the major target for cleavage CC (PubMed:28982940). Additionally, acts as a Fe(2+) and 2-oxoglutarate- CC dependent monooxygenase, catalyzing (R)-stereospecific hydroxylation at CC C-3 of 'Arg-137' of RPS6 and 'Arg-141' of RCCD1, but the biological CC significance of this activity remains to be established CC (PubMed:29563586). Regulates mitosis through different mechanisms: CC Plays a role in transcriptional repression of satellite repeats, CC possibly by regulating H3K36 methylation levels in centromeric regions CC together with RCCD1. Possibly together with RCCD1, is involved in CC proper mitotic spindle organization and chromosome segregation CC (PubMed:24981860). Negatively regulates cell cycle repressor CC CDKN1A/p21, which controls G1/S phase transition (PubMed:24740926). CC Required for G2/M phase cell cycle progression. Regulates expression of CC CCNA1/cyclin-A1, leading to cancer cell proliferation CC (PubMed:20457893). Also, plays a role in regulating alpha-tubulin CC acetylation and cytoskeletal microtubule stability involved in CC epithelial to mesenchymal transition (PubMed:28455245). Regulates the CC circadian gene expression in the liver (By similarity). Represses the CC transcriptional activator activity of the CLOCK-BMAL1 heterodimer in a CC catalytically-independent manner (PubMed:30500822). Negatively CC regulates the protein stability and function of CRY1; required for CC AMPK-FBXL3-induced CRY1 degradation (PubMed:30500822). CC {ECO:0000250|UniProtKB:Q9CXT6, ECO:0000269|PubMed:20457893, CC ECO:0000269|PubMed:24740926, ECO:0000269|PubMed:24981860, CC ECO:0000269|PubMed:28455245, ECO:0000269|PubMed:28847961, CC ECO:0000269|PubMed:28982940, ECO:0000269|PubMed:29459673, CC ECO:0000269|PubMed:29563586, ECO:0000269|PubMed:30500822}. CC -!- CATALYTIC ACTIVITY: CC Reaction=2-oxoglutarate + L-arginyl-[protein] + O2 = (3R)-3-hydroxy-L- CC arginyl-[protein] + CO2 + succinate; Xref=Rhea:RHEA:56744, Rhea:RHEA- CC COMP:10532, Rhea:RHEA-COMP:14712, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:16526, ChEBI:CHEBI:16810, ChEBI:CHEBI:29965, CC ChEBI:CHEBI:30031, ChEBI:CHEBI:78294; EC=1.14.11.73; CC Evidence={ECO:0000269|PubMed:29563586}; CC -!- COFACTOR: CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033; CC Evidence={ECO:0000269|PubMed:24981860, ECO:0000269|PubMed:28982940, CC ECO:0000269|PubMed:29563586}; CC Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000305|PubMed:24100311}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=60.4 uM for Arg-137 of RPS6 {ECO:0000269|PubMed:29563586}; CC Note=KM>300 uM for Arg-141 of RCCD1. {ECO:0000269|PubMed:29563586}; CC -!- SUBUNIT: Can form homodimers (via JmjC domain) (PubMed:24100311, CC PubMed:28982940). Found in a complex with RCCD1 (PubMed:24981860). CC Interacts (via N-terminus) with RCCD1 (via N-terminus); this CC interaction stimulates H3K36me3 and H3K36me2 demethylation CC (PubMed:28455245, PubMed:24981860). Interacts (via JmjC domain) with CC H3C1 (PubMed:28982940). Interacts with FBXL3 and PSMD2 (By similarity). CC Interacts with CRY1 in a FBXL3-dependent manner (By similarity). CC {ECO:0000250|UniProtKB:Q9CXT6, ECO:0000269|PubMed:24100311, CC ECO:0000269|PubMed:24981860, ECO:0000269|PubMed:28455245, CC ECO:0000269|PubMed:28982940}. CC -!- INTERACTION: CC Q8N371; A6NED2: RCCD1; NbExp=2; IntAct=EBI-750326, EBI-21552314; CC Q8N371-3; Q96D03: DDIT4L; NbExp=3; IntAct=EBI-12161375, EBI-742054; CC Q8N371-3; Q8IY31-3: IFT20; NbExp=3; IntAct=EBI-12161375, EBI-9091197; CC Q8N371-3; Q9ULR0: ISY1; NbExp=5; IntAct=EBI-12161375, EBI-2557660; CC Q8N371-3; Q6FHY5: MEOX2; NbExp=6; IntAct=EBI-12161375, EBI-16439278; CC Q8N371-3; Q8TB37: NUBPL; NbExp=3; IntAct=EBI-12161375, EBI-12852610; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:20457893, CC ECO:0000269|PubMed:28982940}. Chromosome {ECO:0000269|PubMed:24981860}. CC Note=Colocalizes with trimethylated 'Lys-9' of histone H3 (H3K9me3). CC {ECO:0000269|PubMed:24981860}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q8N371-1; Sequence=Displayed; CC Name=2; CC IsoId=Q8N371-2; Sequence=VSP_026370; CC Name=3; CC IsoId=Q8N371-3; Sequence=VSP_039893; CC -!- TISSUE SPECIFICITY: Weakly expressed in most cells. Highly expressed in CC breast cancer cells (PubMed:20457893). Expressed in embryonic stem CC cells (PubMed:24740926). {ECO:0000269|PubMed:20457893, CC ECO:0000269|PubMed:24740926}. CC -!- INDUCTION: Up-regulated upon starvation, DNA replication stress, UV CC treatment and by camptothecin and etoposide treatment. CC {ECO:0000269|PubMed:28982940}. CC -!- CAUTION: The demethylase activity of JMJD5 is controversial. CC Demethylase activity toward H3K36me2 was observed in vivo and in vitro CC (PubMed:20457893). In addition, demethylase activity toward H3K36me3 CC when in a complex with RCCD1 has been observed (PubMed:24981860). In CC contrast, in other studies, JMJD5 was shown not to display any CC demethylase activity toward methylated H3K36 nor toward other CC methyllysines in the N-terminal tails of H3 and H4 in vitro CC (PubMed:28982940, PubMed:22851697, PubMed:24100311). CC {ECO:0000269|PubMed:20457893, ECO:0000269|PubMed:22851697, CC ECO:0000269|PubMed:24100311, ECO:0000269|PubMed:24981860, CC ECO:0000269|PubMed:28982940}. 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; AK023860; BAB14706.1; -; mRNA. DR EMBL; AK297166; BAG59661.1; -; mRNA. DR EMBL; AY345239; AAQ23080.1; -; mRNA. DR EMBL; AC092725; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC106739; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC109449; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC027911; AAH27911.1; -; mRNA. DR CCDS; CCDS10627.1; -. [Q8N371-1] DR CCDS; CCDS45448.1; -. [Q8N371-3] DR RefSeq; NP_001138820.1; NM_001145348.1. [Q8N371-3] DR RefSeq; NP_079049.2; NM_024773.2. [Q8N371-1] DR PDB; 3UYJ; X-ray; 2.35 A; A/B=173-416. DR PDB; 4AAP; X-ray; 2.60 A; A/B=180-416. DR PDB; 4GAZ; X-ray; 2.81 A; A/B=176-416. DR PDB; 4GJY; X-ray; 1.25 A; A=183-416. DR PDB; 4GJZ; X-ray; 1.05 A; A=183-416. DR PDB; 4QU1; X-ray; 1.57 A; A=183-416. DR PDB; 5FBJ; X-ray; 2.42 A; A=183-416. DR PDB; 6AVS; X-ray; 2.02 A; A=183-416. DR PDB; 6AX3; X-ray; 2.25 A; A=184-416. DR PDB; 6F4M; X-ray; 1.71 A; A=183-416. DR PDB; 6F4N; X-ray; 2.54 A; A/B=153-416. DR PDB; 6F4O; X-ray; 1.28 A; A=183-416. DR PDB; 6F4P; X-ray; 1.45 A; A=183-416. DR PDB; 6F4Q; X-ray; 1.12 A; A=183-416. DR PDB; 6F4R; X-ray; 1.30 A; A=183-416. DR PDB; 6F4S; X-ray; 1.46 A; A=183-416. DR PDB; 6F4T; X-ray; 1.22 A; A=183-416. DR PDB; 6I9L; X-ray; 1.53 A; A=183-416. DR PDB; 6I9M; X-ray; 1.65 A; A=183-416. DR PDB; 6I9N; X-ray; 1.36 A; A=183-416. DR PDB; 7DYT; X-ray; 1.62 A; A=183-416. DR PDB; 7DYU; X-ray; 1.72 A; A=183-416. DR PDB; 7DYV; X-ray; 1.92 A; A=183-416. DR PDB; 7DYW; X-ray; 2.13 A; A=183-416. DR PDB; 7DYX; X-ray; 2.27 A; A=183-416. DR PDB; 7UQ3; X-ray; 1.49 A; A=183-416. DR PDBsum; 3UYJ; -. DR PDBsum; 4AAP; -. DR PDBsum; 4GAZ; -. DR PDBsum; 4GJY; -. DR PDBsum; 4GJZ; -. DR PDBsum; 4QU1; -. DR PDBsum; 5FBJ; -. DR PDBsum; 6AVS; -. DR PDBsum; 6AX3; -. DR PDBsum; 6F4M; -. DR PDBsum; 6F4N; -. DR PDBsum; 6F4O; -. DR PDBsum; 6F4P; -. DR PDBsum; 6F4Q; -. DR PDBsum; 6F4R; -. DR PDBsum; 6F4S; -. DR PDBsum; 6F4T; -. DR PDBsum; 6I9L; -. DR PDBsum; 6I9M; -. DR PDBsum; 6I9N; -. DR PDBsum; 7DYT; -. DR PDBsum; 7DYU; -. DR PDBsum; 7DYV; -. DR PDBsum; 7DYW; -. DR PDBsum; 7DYX; -. DR PDBsum; 7UQ3; -. DR AlphaFoldDB; Q8N371; -. DR SMR; Q8N371; -. DR BioGRID; 122923; 49. DR CORUM; Q8N371; -. DR IntAct; Q8N371; 14. DR MINT; Q8N371; -. DR STRING; 9606.ENSP00000398410; -. DR ChEMBL; CHEMBL4523396; -. DR iPTMnet; Q8N371; -. DR PhosphoSitePlus; Q8N371; -. DR BioMuta; KDM8; -. DR DMDM; 74728780; -. DR EPD; Q8N371; -. DR jPOST; Q8N371; -. DR MassIVE; Q8N371; -. DR MaxQB; Q8N371; -. DR PaxDb; 9606-ENSP00000398410; -. DR PeptideAtlas; Q8N371; -. DR ProteomicsDB; 71772; -. [Q8N371-1] DR ProteomicsDB; 71773; -. [Q8N371-2] DR ProteomicsDB; 71774; -. [Q8N371-3] DR Pumba; Q8N371; -. DR ABCD; Q8N371; 1 sequenced antibody. DR Antibodypedia; 12808; 334 antibodies from 32 providers. DR DNASU; 79831; -. DR Ensembl; ENST00000286096.9; ENSP00000286096.5; ENSG00000155666.12. [Q8N371-1] DR Ensembl; ENST00000441782.6; ENSP00000398410.2; ENSG00000155666.12. [Q8N371-3] DR Ensembl; ENST00000568965.1; ENSP00000456901.1; ENSG00000155666.12. [Q8N371-2] DR GeneID; 79831; -. DR KEGG; hsa:79831; -. DR MANE-Select; ENST00000286096.9; ENSP00000286096.5; NM_024773.3; NP_079049.2. DR UCSC; uc002doh.3; human. [Q8N371-1] DR AGR; HGNC:25840; -. DR CTD; 79831; -. DR DisGeNET; 79831; -. DR GeneCards; KDM8; -. DR HGNC; HGNC:25840; KDM8. DR HPA; ENSG00000155666; Tissue enriched (liver). DR MIM; 611917; gene. DR neXtProt; NX_Q8N371; -. DR OpenTargets; ENSG00000155666; -. DR PharmGKB; PA143485510; -. DR VEuPathDB; HostDB:ENSG00000155666; -. DR eggNOG; KOG2132; Eukaryota. DR GeneTree; ENSGT00940000158074; -. DR HOGENOM; CLU_016785_0_3_1; -. DR InParanoid; Q8N371; -. DR OrthoDB; 11696at2759; -. DR PhylomeDB; Q8N371; -. DR TreeFam; TF315056; -. DR BioCyc; MetaCyc:ENSG00000155666-MONOMER; -. DR BRENDA; 1.14.11.27; 2681. DR BRENDA; 1.14.11.73; 2681. DR PathwayCommons; Q8N371; -. DR Reactome; R-HSA-9629569; Protein hydroxylation. DR SABIO-RK; Q8N371; -. DR SignaLink; Q8N371; -. DR BioGRID-ORCS; 79831; 392 hits in 1196 CRISPR screens. DR ChiTaRS; KDM8; human. DR GenomeRNAi; 79831; -. DR Pharos; Q8N371; Tbio. DR PRO; PR:Q8N371; -. DR Proteomes; UP000005640; Chromosome 16. DR RNAct; Q8N371; Protein. DR Bgee; ENSG00000155666; Expressed in right lobe of liver and 110 other cell types or tissues. DR ExpressionAtlas; Q8N371; baseline and differential. DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0004177; F:aminopeptidase activity; IDA:UniProtKB. DR GO; GO:0003682; F:chromatin binding; IDA:UniProtKB. DR GO; GO:0004175; F:endopeptidase activity; IDA:UniProtKB. DR GO; GO:0051864; F:histone H3K36 demethylase activity; IDA:UniProtKB. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0035064; F:methylated histone binding; IDA:UniProtKB. DR GO; GO:0002039; F:p53 binding; IEA:Ensembl. DR GO; GO:0106157; F:peptidyl-arginine 3-dioxygenase activity; IDA:UniProtKB. DR GO; GO:0032922; P:circadian regulation of gene expression; ISS:UniProtKB. DR GO; GO:0048144; P:fibroblast proliferation; IEA:Ensembl. DR GO; GO:0000086; P:G2/M transition of mitotic cell cycle; IMP:UniProtKB. DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; IMP:UniProtKB. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IMP:UniProtKB. DR GO; GO:0031648; P:protein destabilization; IMP:UniProtKB. DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW. DR GO; GO:1901796; P:regulation of signal transduction by p53 class mediator; IEA:Ensembl. DR Gene3D; 2.60.120.650; Cupin; 1. DR InterPro; IPR041667; Cupin_8. DR InterPro; IPR003347; JmjC_dom. DR PANTHER; PTHR12461:SF97; BIFUNCTIONAL PEPTIDASE AND (3S)-LYSYL HYDROXYLASE JMJD7-RELATED; 1. DR PANTHER; PTHR12461; HYPOXIA-INDUCIBLE FACTOR 1 ALPHA INHIBITOR-RELATED; 1. DR Pfam; PF13621; Cupin_8; 1. DR SMART; SM00558; JmjC; 1. DR SUPFAM; SSF51197; Clavaminate synthase-like; 1. DR PROSITE; PS51184; JMJC; 1. DR Genevisible; Q8N371; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Aminopeptidase; Biological rhythms; KW Cell cycle; Chromatin regulator; Chromosome; Dioxygenase; Hydrolase; Iron; KW Metal-binding; Nucleus; Oxidoreductase; Protease; Reference proteome; KW Transcription; Transcription regulation. FT CHAIN 1..416 FT /note="Bifunctional peptidase and arginyl-hydroxylase FT JMJD5" FT /id="PRO_0000292010" FT DOMAIN 271..416 FT /note="JmjC" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00538" FT REGION 1..110 FT /note="Interaction with RCCD1" FT /evidence="ECO:0000269|PubMed:24981860" FT BINDING 238 FT /ligand="a protein" FT /ligand_id="ChEBI:CHEBI:16541" FT /ligand_part="N(omega)-methyl-L-arginine residue" FT /ligand_part_id="ChEBI:CHEBI:65280" FT /evidence="ECO:0000269|PubMed:29459673" FT BINDING 272 FT /ligand="2-oxoglutarate" FT /ligand_id="ChEBI:CHEBI:16810" FT /evidence="ECO:0000269|PubMed:22851697, FT ECO:0000269|PubMed:29459673, ECO:0000269|PubMed:29563586, FT ECO:0000305|PubMed:24100311, ECO:0007744|PDB:3UYJ, FT ECO:0007744|PDB:4GJZ, ECO:0007744|PDB:4QU1, FT ECO:0007744|PDB:5FBJ" FT BINDING 275 FT /ligand="a protein" FT /ligand_id="ChEBI:CHEBI:16541" FT /ligand_part="N(omega),N(omega)'-dimethyl-L-arginine FT residue" FT /ligand_part_id="ChEBI:CHEBI:88221" FT /evidence="ECO:0000269|PubMed:29459673" FT BINDING 275 FT /ligand="a protein" FT /ligand_id="ChEBI:CHEBI:16541" FT /ligand_part="N(omega)-methyl-L-arginine residue" FT /ligand_part_id="ChEBI:CHEBI:65280" FT /evidence="ECO:0000269|PubMed:29459673" FT BINDING 318 FT /ligand="2-oxoglutarate" FT /ligand_id="ChEBI:CHEBI:16810" FT /evidence="ECO:0000269|PubMed:22851697, FT ECO:0000269|PubMed:29459673, ECO:0000269|PubMed:29563586, FT ECO:0000305|PubMed:24100311, ECO:0007744|PDB:3UYJ, FT ECO:0007744|PDB:4GJZ, ECO:0007744|PDB:4QU1, FT ECO:0007744|PDB:5FBJ" FT BINDING 318 FT /ligand="a protein" FT /ligand_id="ChEBI:CHEBI:16541" FT /ligand_part="N(omega),N(omega)'-dimethyl-L-arginine FT residue" FT /ligand_part_id="ChEBI:CHEBI:88221" FT /evidence="ECO:0000269|PubMed:29459673" FT BINDING 318 FT /ligand="a protein" FT /ligand_id="ChEBI:CHEBI:16541" FT /ligand_part="N(omega)-methyl-L-arginine residue" FT /ligand_part_id="ChEBI:CHEBI:65280" FT /evidence="ECO:0000269|PubMed:29459673" FT BINDING 321 FT /ligand="2-oxoglutarate" FT /ligand_id="ChEBI:CHEBI:16810" FT /evidence="ECO:0000269|PubMed:29563586" FT BINDING 321 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /ligand_note="catalytic" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00538, FT ECO:0000305|PubMed:22851697, ECO:0000305|PubMed:24100311, FT ECO:0007744|PDB:4GJY, ECO:0007744|PDB:4GJZ" FT BINDING 323 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /ligand_note="catalytic" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00538, FT ECO:0000305|PubMed:22851697, ECO:0000305|PubMed:24100311, FT ECO:0007744|PDB:4GJY, ECO:0007744|PDB:4GJZ" FT BINDING 327 FT /ligand="2-oxoglutarate" FT /ligand_id="ChEBI:CHEBI:16810" FT /evidence="ECO:0000269|PubMed:22851697, FT ECO:0000269|PubMed:29459673, ECO:0000269|PubMed:29563586, FT ECO:0000305|PubMed:24100311, ECO:0007744|PDB:3UYJ, FT ECO:0007744|PDB:4GJZ, ECO:0007744|PDB:4QU1, FT ECO:0007744|PDB:5FBJ" FT BINDING 336 FT /ligand="2-oxoglutarate" FT /ligand_id="ChEBI:CHEBI:16810" FT /evidence="ECO:0000269|PubMed:22851697, FT ECO:0000269|PubMed:29459673, ECO:0000269|PubMed:29563586, FT ECO:0000305|PubMed:24100311, ECO:0007744|PDB:3UYJ, FT ECO:0007744|PDB:4GJZ, ECO:0007744|PDB:4QU1, FT ECO:0007744|PDB:5FBJ" FT BINDING 400 FT /ligand="2-oxoglutarate" FT /ligand_id="ChEBI:CHEBI:16810" FT /evidence="ECO:0000269|PubMed:29563586" FT BINDING 400 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /ligand_note="catalytic" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00538, FT ECO:0000305|PubMed:22851697, ECO:0000305|PubMed:24100311, FT ECO:0007744|PDB:4GJY, ECO:0007744|PDB:4GJZ" FT BINDING 414 FT /ligand="2-oxoglutarate" FT /ligand_id="ChEBI:CHEBI:16810" FT /evidence="ECO:0000269|PubMed:22851697, FT ECO:0000269|PubMed:29459673, ECO:0000269|PubMed:29563586, FT ECO:0007744|PDB:3UYJ, ECO:0007744|PDB:4GJZ" FT VAR_SEQ 1 FT /note="M -> MSREKCSPGEGAEEGRGSEASGLKASAGHGTEPAGGGPM (in FT isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_039893" FT VAR_SEQ 167..362 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|Ref.2" FT /id="VSP_026370" FT VARIANT 302 FT /note="E -> D (in dbSNP:rs34445573)" FT /id="VAR_032928" FT MUTAGEN 1..182 FT /note="Missing: No effect on L-arginyl 3-hydroxylase FT activity toward RPS6." FT /evidence="ECO:0000269|PubMed:29563586" FT MUTAGEN 238 FT /note="E->A: Loss of L-arginyl 3-hydroxylase activity FT toward RPS6." FT /evidence="ECO:0000269|PubMed:29563586" FT MUTAGEN 243 FT /note="Y->A: Loss of L-arginyl 3-hydroxylase activity FT toward RPS6." FT /evidence="ECO:0000269|PubMed:29563586" FT MUTAGEN 275 FT /note="Q->A: Loss of L-arginyl 3-hydroxylase activity FT toward RPS6. Loss of peptidase activity toward methylated FT histones." FT /evidence="ECO:0000269|PubMed:29459673, FT ECO:0000269|PubMed:29563586" FT MUTAGEN 310 FT /note="W->A: Loss of L-arginyl 3-hydroxylase activity FT toward RPS6." FT /evidence="ECO:0000269|PubMed:29563586" FT MUTAGEN 321..323 FT /note="HQD->AQA: Fails to cleave H3C1." FT /evidence="ECO:0000269|PubMed:28982940" FT MUTAGEN 321 FT /note="H->A: Loss of H3K36me2 demethylase activity." FT /evidence="ECO:0000269|PubMed:20457893" FT MUTAGEN 321 FT /note="H->A: Loss of L-arginyl 3-hydroxylase activity FT toward RPS6. Loss of peptidase activity toward methylated FT histones; when associated with A-323 and A-400. No effect FT on its regulatory function on the circadian clock or CRY1 FT stability." FT /evidence="ECO:0000269|PubMed:28847961, FT ECO:0000269|PubMed:29563586, ECO:0000269|PubMed:30500822" FT MUTAGEN 323 FT /note="D->A: Loss of peptidase activity toward methylated FT histones; when associated with A-321 and A-400." FT /evidence="ECO:0000269|PubMed:28847961" FT MUTAGEN 335..336 FT /note="RK->AA: Loss of interaction with H3C1. Fails to FT cleave H3C1." FT /evidence="ECO:0000269|PubMed:28982940" FT MUTAGEN 336 FT /note="K->E: Loss of peptidase activity toward methylated FT histones." FT /evidence="ECO:0000269|PubMed:29459673" FT MUTAGEN 356 FT /note="L->A: Reduces L-arginyl 3-hydroxylase activity FT toward RPS6 substrate." FT /evidence="ECO:0000269|PubMed:29563586" FT MUTAGEN 398..400 FT /note="YWH->AAA: Fails to cleave H3C1." FT /evidence="ECO:0000269|PubMed:28982940" FT MUTAGEN 400 FT /note="H->A: Loss of peptidase activity toward methylated FT histones; when associated with A-321 and A-323." FT /evidence="ECO:0000269|PubMed:28847961" FT MUTAGEN 414 FT /note="W->A: Reduces L-arginyl 3-hydroxylase activity FT toward RPS6." FT /evidence="ECO:0000269|PubMed:29563586" FT CONFLICT 73 FT /note="D -> G (in Ref. 1; BAB14706)" FT /evidence="ECO:0000305" FT HELIX 178..180 FT /evidence="ECO:0007829|PDB:3UYJ" FT STRAND 181..183 FT /evidence="ECO:0007829|PDB:4AAP" FT STRAND 186..189 FT /evidence="ECO:0007829|PDB:4GJZ" FT HELIX 192..198 FT /evidence="ECO:0007829|PDB:4GJZ" FT TURN 199..203 FT /evidence="ECO:0007829|PDB:4GJZ" FT STRAND 206..212 FT /evidence="ECO:0007829|PDB:4GJZ" FT HELIX 216..220 FT /evidence="ECO:0007829|PDB:4GJZ" FT HELIX 223..230 FT /evidence="ECO:0007829|PDB:4GJZ" FT STRAND 233..239 FT /evidence="ECO:0007829|PDB:4GJZ" FT STRAND 245..247 FT /evidence="ECO:0007829|PDB:6F4Q" FT STRAND 249..254 FT /evidence="ECO:0007829|PDB:4GJZ" FT HELIX 255..262 FT /evidence="ECO:0007829|PDB:4GJZ" FT STRAND 271..276 FT /evidence="ECO:0007829|PDB:4GJZ" FT HELIX 278..281 FT /evidence="ECO:0007829|PDB:4GJZ" FT HELIX 283..286 FT /evidence="ECO:0007829|PDB:4GJZ" FT HELIX 293..297 FT /evidence="ECO:0007829|PDB:4GJZ" FT STRAND 298..300 FT /evidence="ECO:0007829|PDB:4GJZ" FT HELIX 302..304 FT /evidence="ECO:0007829|PDB:4GJZ" FT STRAND 306..312 FT /evidence="ECO:0007829|PDB:4GJZ" FT STRAND 317..321 FT /evidence="ECO:0007829|PDB:4GJZ" FT STRAND 324..334 FT /evidence="ECO:0007829|PDB:4GJZ" FT STRAND 336..341 FT /evidence="ECO:0007829|PDB:4GJZ" FT HELIX 343..348 FT /evidence="ECO:0007829|PDB:4GJZ" FT TURN 355..359 FT /evidence="ECO:0007829|PDB:4GJZ" FT STRAND 360..363 FT /evidence="ECO:0007829|PDB:4GJZ" FT TURN 370..372 FT /evidence="ECO:0007829|PDB:4GJZ" FT HELIX 374..378 FT /evidence="ECO:0007829|PDB:4GJZ" FT STRAND 382..386 FT /evidence="ECO:0007829|PDB:4GJZ" FT STRAND 391..394 FT /evidence="ECO:0007829|PDB:4GJZ" FT STRAND 399..415 FT /evidence="ECO:0007829|PDB:4GJZ" SQ SEQUENCE 416 AA; 47270 MW; 18CE6D01E00ED5A4 CRC64; MAGDTHCPAE PLAREGTLWE ALRALLPHSK EDLKLDLGEK VERSVVTLLQ RATELFYEGR RDECLQSSEV ILDYSWEKLN TGTWQDVDKD WRRVYAIGCL LKALCLCQAP EDANTVAAAL RVCDMGLLMG AAILGDILLK VAAILQTHLP GKRPARGSLP EQPCTKKARA DHGLIPDVKL EKTVPRLHRP SLQHFREQFL VPGRPVILKG VADHWPCMQK WSLEYIQEIA GCRTVPVEVG SRYTDEEWSQ TLMTVNEFIS KYIVNEPRDV GYLAQHQLFD QIPELKQDIS IPDYCSLGDG EEEEITINAW FGPQGTISPL HQDPQQNFLV QVMGRKYIRL YSPQESGALY PHDTHLLHNT SQVDVENPDL EKFPKFAKAP FLSCILSPGE ILFIPVKYWH YVRALDLSFS VSFWWS //