KDM8_RAT
ID KDM8_RAT Reviewed; 414 AA.
AC Q497B8;
DT 26-JUN-2007, integrated into UniProtKB/Swiss-Prot.
DT 13-SEP-2005, sequence version 1.
DT 03-AUG-2022, entry version 82.
DE RecName: Full=Bifunctional peptidase and arginyl-hydroxylase JMJD5 {ECO:0000250|UniProtKB:Q8N371};
DE EC=1.14.11.73 {ECO:0000250|UniProtKB:Q8N371};
DE EC=3.4.-.- {ECO:0000250|UniProtKB:Q8N371};
DE AltName: Full=JmjC domain-containing protein 5 {ECO:0000250|UniProtKB:Q8N371};
DE AltName: Full=Jumonji C domain-containing protein 5 {ECO:0000250|UniProtKB:Q8N371};
DE AltName: Full=L-arginine (3R)-hydroxylase KDM8 {ECO:0000250|UniProtKB:Q8N371};
GN Name=Kdm8; Synonyms=Jmjd5;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Prostate;
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).
CC -!- FUNCTION: Bifunctional enzyme that acts both as an endopeptidase and 2-
CC oxoglutarate-dependent monooxygenase. Endopeptidase that cleaves
CC histones N-terminal tails at the carboxyl side of methylated arginine
CC or lysine residues, to generate 'tailless nucleosomes', which may
CC trigger transcription elongation. Preferentially recognizes and cleaves
CC monomethylated and dimethylated arginine residues of histones H2, H3
CC and H4. After initial cleavage, continues to digest histones tails via
CC its aminopeptidase activity. Upon DNA damage, cleaves the N-terminal
CC tail of histone H3 at monomethylated lysine residues, preferably at
CC monomethylated 'Lys-9' (H3K9me1). The histone variant H3F3A is the
CC major target for cleavage. Additionnally, acts as Fe(2+) and 2-
CC oxoglutarate-dependent monooxygenase, catalyzing (R)-stereospecific
CC hydroxylation at C-3 of 'Arg-137' of RPS6 and 'Arg-141' of RCCD1, but
CC the biological significance of this activity remains to be established.
CC Regulates mitosis through different mechanisms: Plays a role in
CC transcriptional repression of satellite repeats, possibly by regulating
CC H3K36 methylation levels in centromeric regions together with RCCD1.
CC Possibly together with RCCD1, is involved in proper mitotic spindle
CC organization and chromosome segregation. Negatively regulates cell
CC cycle repressor CDKN1A/p21, which controls G1/S phase transition.
CC Required for G2/M phase cell cycle progression. Regulates expression of
CC CCNA1/cyclin-A1, leading to cancer cell proliferation. Also, plays a
CC role in regulating alpha-tubulin acetylation and cytoskeletal
CC microtubule stability involved in epithelial to mesenchymal transition
CC (By similarity). Regulates the circadian gene expression in the liver
CC (By similarity). Represses the transcriptional activator activity of
CC the CLOCK-ARNTL/BMAL1 heterodimer in a catalytically-independent manner
CC (By similarity). Negatively regulates the protein stability and
CC function of CRY1; required for AMPK-FBXL3-induced CRY1 degradation (By
CC similarity). {ECO:0000250|UniProtKB:Q8N371,
CC ECO:0000250|UniProtKB:Q9CXT6}.
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:0000250|UniProtKB:Q8N371};
CC -!- COFACTOR:
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC Evidence={ECO:0000250|UniProtKB:Q8N371};
CC Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000250|UniProtKB:Q8N371};
CC -!- SUBUNIT: Can form homodimers (via JmjC domain). Found in a complex with
CC RCCD1. Interacts (via N-terminus) with RCCD1 (via N-terminus); this
CC interaction stimulates H3K36me3 and H3K36me2 demethylation. Interacts
CC (via JmjC domain) with H3C1 (By similarity). Interacts with FBXL3 and
CC PSMD2 (By similarity). Interacts with CRY1 in a FBXL3-dependent manner
CC (By similarity). {ECO:0000250|UniProtKB:Q8N371}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q8N371}.
CC Chromosome {ECO:0000250|UniProtKB:Q8N371}. Note=Colocalizes with
CC trimethylated 'Lys-9' of histone H3 (H3K9me3).
CC {ECO:0000250|UniProtKB:Q8N371}.
CC -!- CAUTION: The demethylase activity of JMJD5 is controversial.
CC Demethylase activity towards H3K36me2 was observed in vivo and in
CC vitro. In addition, demethylase activity towards H3K36me3 when in a
CC complex with RCCD1 has been observed. In contrast, in other studies,
CC JMJD5 was shown not to display any demethylase activity toward
CC methylated H3K36 nor toward other methyllysines in the N-terminal tails
CC of H3 and H4 in vitro. {ECO:0000250|UniProtKB:Q8N371}.
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DR EMBL; BC100627; AAI00628.1; -; mRNA.
DR RefSeq; NP_001032273.1; NM_001037196.1.
DR AlphaFoldDB; Q497B8; -.
DR SMR; Q497B8; -.
DR STRING; 10116.ENSRNOP00000020388; -.
DR PhosphoSitePlus; Q497B8; -.
DR PaxDb; Q497B8; -.
DR PRIDE; Q497B8; -.
DR GeneID; 308976; -.
DR KEGG; rno:308976; -.
DR UCSC; RGD:1304823; rat.
DR CTD; 79831; -.
DR RGD; 1304823; Kdm8.
DR eggNOG; KOG2132; Eukaryota.
DR InParanoid; Q497B8; -.
DR PhylomeDB; Q497B8; -.
DR PRO; PR:Q497B8; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0016706; F:2-oxoglutarate-dependent dioxygenase activity; IBA:GO_Central.
DR GO; GO:0004177; F:aminopeptidase activity; ISO:RGD.
DR GO; GO:0003682; F:chromatin binding; ISS:UniProtKB.
DR GO; GO:0004175; F:endopeptidase activity; ISO:RGD.
DR GO; GO:0051864; F:histone H3-methyl-lysine-36 demethylase activity; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0035064; F:methylated histone binding; ISO:RGD.
DR GO; GO:0106157; F:peptidyl-arginine 3-dioxygenase activity; ISS: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; ISS:UniProtKB.
DR GO; GO:0070544; P:histone H3-K36 demethylation; ISS:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0031648; P:protein destabilization; ISS: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 2: Evidence at transcript level;
KW Aminopeptidase; Biological rhythms; Cell cycle; Chromatin regulator;
KW Chromosome; Dioxygenase; Hydrolase; Iron; Metal-binding; Nucleus;
KW Oxidoreductase; Protease; Reference proteome; Transcription;
KW Transcription regulation.
FT CHAIN 1..414
FT /note="Bifunctional peptidase and arginyl-hydroxylase
FT JMJD5"
FT /id="PRO_0000292012"
FT DOMAIN 269..414
FT /note="JmjC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00538"
FT REGION 1..107
FT /note="Interaction with RCCD1"
FT /evidence="ECO:0000250|UniProtKB:Q8N371"
FT REGION 152..173
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 236
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:0000250|UniProtKB:Q8N371"
FT BINDING 270
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:Q8N371"
FT BINDING 273
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:0000250|UniProtKB:Q8N371"
FT BINDING 273
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:0000250|UniProtKB:Q8N371"
FT BINDING 316
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:Q8N371"
FT BINDING 316
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:0000250|UniProtKB:Q8N371"
FT BINDING 316
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:0000250|UniProtKB:Q8N371"
FT BINDING 319
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:Q8N371"
FT BINDING 319
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00538"
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 BINDING 325
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:Q8N371"
FT BINDING 334
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:Q8N371"
FT BINDING 398
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:Q8N371"
FT BINDING 398
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00538"
FT BINDING 412
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:Q8N371"
SQ SEQUENCE 414 AA; 47247 MW; 7E5C0DC9BB0EBEB1 CRC64;
MSEDTTEPLV GPSTLWKDLR ALLPDTEEEL KLDLSEKVDR SMATLLRQAL GLFYEGRWQK
CLQASEAVLD YSWEKLNTGP WRDVDKEWRR VYSFGCLLKT LCLCQAPQKA TAVAEALRVC
DMGLLMGAAI LGDILLKVAT VLQTHLLPRK QPACGPHQDQ PATKKAKHDA SSTPDVVLDR
EVPRLRCPPL QHFKKHFLVP GRPVILEGVA DHWPCMKKWS LQYIQEIAGC RTVPVEVGSR
YTDEDWSQTL MTVNEFIHKY ILSEAKDVGY LAQHQLFDQI PELKQDISIP DYCCLGNGEE
EEITINAWFG PQGTISPLHQ DPQQNFLVQV LGRKYIRLYS PQESEAVYPH ETHILHNTSQ
VDVENPDLEK FPKFTEAPFL SCILSPGDTL FIPAKYWHYV RSLDLSFSVS FWWS
