KDM8_HUMAN
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 03-AUG-2022, entry version 137.
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, ECO:0000303|PubMed:28982940,
GN 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). Additionnally, acts as 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-ARNTL/BMAL1 heterodimer
CC in a 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}.
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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 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 AlphaFoldDB; Q8N371; -.
DR SMR; Q8N371; -.
DR BioGRID; 122923; 48.
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; Q8N371; -.
DR PeptideAtlas; Q8N371; -.
DR PRIDE; Q8N371; -.
DR ProteomicsDB; 71772; -. [Q8N371-1]
DR ProteomicsDB; 71773; -. [Q8N371-2]
DR ProteomicsDB; 71774; -. [Q8N371-3]
DR ABCD; Q8N371; 1 sequenced antibody.
DR Antibodypedia; 12808; 311 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 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; 1385616at2759; -.
DR PhylomeDB; Q8N371; -.
DR TreeFam; TF315056; -.
DR BioCyc; MetaCyc:ENSG00000155666-MON; -.
DR BRENDA; 1.14.11.27; 2681.
DR BRENDA; 1.14.11.73; 2681.
DR PathwayCommons; Q8N371; -.
DR SignaLink; Q8N371; -.
DR BioGRID-ORCS; 79831; 379 hits in 1108 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 108 other tissues.
DR ExpressionAtlas; Q8N371; baseline and differential.
DR Genevisible; Q8N371; HS.
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:0016706; F:2-oxoglutarate-dependent dioxygenase activity; IBA:GO_Central.
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 H3-methyl-lysine-36 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:0106157; F:peptidyl-arginine 3-dioxygenase activity; IDA:UniProtKB.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0032922; P:circadian regulation of gene expression; ISS:UniProtKB.
DR GO; GO:0000086; P:G2/M transition of mitotic cell cycle; IMP:UniProtKB.
DR GO; GO:0070544; P:histone H3-K36 demethylation; IDA:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IMP:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IMP:UniProtKB.
DR GO; GO:0031648; P:protein destabilization; IMP:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR InterPro; IPR041667; Cupin_8.
DR InterPro; IPR003347; JmjC_dom.
DR Pfam; PF13621; Cupin_8; 1.
DR SMART; SM00558; JmjC; 1.
DR PROSITE; PS51184; JMJC; 1.
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
