KDM4_CAEEL
ID KDM4_CAEEL Reviewed; 922 AA.
AC Q9U297;
DT 16-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 04-DEC-2007, sequence version 2.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=Lysine-specific demethylase 4;
DE EC=1.14.11.66 {ECO:0000305|PubMed:16603238};
DE EC=1.14.11.69 {ECO:0000305|PubMed:16603238};
DE AltName: Full=JmjC domain-containing histone demethylation protein 2;
DE Short=ceJMJD2;
DE AltName: Full=[histone H3]-trimethyl-L-lysine(36) demethylase 4 {ECO:0000305};
DE AltName: Full=[histone H3]-trimethyl-L-lysine(9) demethylase 4 {ECO:0000305};
GN Name=jmjd-2; ORFNames=Y48B6A.11;
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=16603238; DOI=10.1016/j.cell.2006.03.028;
RA Whetstine J.R., Nottke A., Lan F., Huarte M., Smolikov S., Chen Z.,
RA Spooner E., Li E., Zhang G., Colaiacovo M., Shi Y.;
RT "Reversal of histone lysine trimethylation by the JMJD2 family of histone
RT demethylases.";
RL Cell 125:467-481(2006).
RN [3]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=22212395; DOI=10.1111/j.1474-9726.2011.00785.x;
RA Ni Z., Ebata A., Alipanahiramandi E., Lee S.S.;
RT "Two SET domain containing genes link epigenetic changes and aging in
RT Caenorhabditis elegans.";
RL Aging Cell 11:315-325(2012).
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=24685137; DOI=10.1016/j.celrep.2014.02.044;
RA Greer E.L., Beese-Sims S.E., Brookes E., Spadafora R., Zhu Y.,
RA Rothbart S.B., Aristizabal-Corrales D., Chen S., Badeaux A.I., Jin Q.,
RA Wang W., Strahl B.D., Colaiacovo M.P., Shi Y.;
RT "A histone methylation network regulates transgenerational epigenetic
RT memory in C. elegans.";
RL Cell Rep. 7:113-126(2014).
CC -!- FUNCTION: Histone demethylase that specifically demethylates 'Lys-9'
CC and 'Lys-36' residues of histone H3, thereby playing a central role in
CC histone code (PubMed:16603238, PubMed:24685137). Demethylation of Lys
CC residue generates formaldehyde and succinate. Involved in the negative
CC regulation of lifespan in a germline-dependent fashion
CC (PubMed:22212395). {ECO:0000269|PubMed:16603238,
CC ECO:0000269|PubMed:22212395, ECO:0000269|PubMed:24685137}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 2-oxoglutarate + N(6),N(6),N(6)-trimethyl-L-lysyl(9)-
CC [histone H3] + 2 O2 = 2 CO2 + 2 formaldehyde + N(6)-methyl-L-
CC lysyl(9)-[histone H3] + 2 succinate; Xref=Rhea:RHEA:60200, Rhea:RHEA-
CC COMP:15538, Rhea:RHEA-COMP:15542, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:16810, ChEBI:CHEBI:16842,
CC ChEBI:CHEBI:30031, ChEBI:CHEBI:61929, ChEBI:CHEBI:61961;
CC EC=1.14.11.66; Evidence={ECO:0000305|PubMed:16603238};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 2-oxoglutarate + N(6),N(6),N(6)-trimethyl-L-lysyl(36)-
CC [histone H3] + 2 O2 = 2 CO2 + 2 formaldehyde + N(6)-methyl-L-
CC lysyl(36)-[histone H3] + 2 succinate; Xref=Rhea:RHEA:60236,
CC Rhea:RHEA-COMP:9786, Rhea:RHEA-COMP:15536, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:16810, ChEBI:CHEBI:16842,
CC ChEBI:CHEBI:30031, ChEBI:CHEBI:61929, ChEBI:CHEBI:61961;
CC EC=1.14.11.69; Evidence={ECO:0000305|PubMed:16603238};
CC -!- COFACTOR:
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033; Evidence={ECO:0000250};
CC Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000250};
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00537}.
CC -!- DISRUPTION PHENOTYPE: Increased H3 'Lys-9' and 'Lys-36' trimethylation
CC levels on meiotic chromosomes leading to trigger p53-dependent germline
CC apoptosis (PubMed:16603238). In spr-5 null mutants, suppresses the
CC progressive sterility over generations which is seen in spr-5 mutants
CC (PubMed:24685137). RNAi-mediated knockdown results in extended lifespan
CC (PubMed:22212395). {ECO:0000269|PubMed:16603238,
CC ECO:0000269|PubMed:22212395, ECO:0000269|PubMed:24685137}.
CC -!- SIMILARITY: Belongs to the JHDM3 histone demethylase family.
CC {ECO:0000305}.
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DR EMBL; AL110490; CAB54451.2; -; Genomic_DNA.
DR PIR; T27007; T27007.
DR RefSeq; NP_496969.2; NM_064568.3.
DR AlphaFoldDB; Q9U297; -.
DR SMR; Q9U297; -.
DR BioGRID; 40361; 1.
DR DIP; DIP-26971N; -.
DR STRING; 6239.Y48B6A.11; -.
DR iPTMnet; Q9U297; -.
DR EPD; Q9U297; -.
DR PaxDb; Q9U297; -.
DR PeptideAtlas; Q9U297; -.
DR EnsemblMetazoa; Y48B6A.11.1; Y48B6A.11.1; WBGene00012982.
DR GeneID; 175080; -.
DR KEGG; cel:CELE_Y48B6A.11; -.
DR UCSC; Y48B6A.11; c. elegans.
DR CTD; 175080; -.
DR WormBase; Y48B6A.11; CE41181; WBGene00012982; jmjd-2.
DR eggNOG; KOG0958; Eukaryota.
DR GeneTree; ENSGT00940000154930; -.
DR HOGENOM; CLU_001442_0_1_1; -.
DR InParanoid; Q9U297; -.
DR OMA; AQQPPYC; -.
DR OrthoDB; 1186832at2759; -.
DR PhylomeDB; Q9U297; -.
DR BRENDA; 1.14.11.69; 1045.
DR Reactome; R-CEL-3214842; HDMs demethylate histones.
DR PRO; PR:Q9U297; -.
DR Proteomes; UP000001940; Chromosome II.
DR Bgee; WBGene00012982; Expressed in embryo and 4 other tissues.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0032452; F:histone demethylase activity; IBA:GO_Central.
DR GO; GO:0051864; F:histone H3-methyl-lysine-36 demethylase activity; IDA:WormBase.
DR GO; GO:0032454; F:histone H3-methyl-lysine-9 demethylase activity; IDA:WormBase.
DR GO; GO:0140681; F:histone H3-tri/dimethyl-lysine-36 demethylase activity; IEA:UniProtKB-EC.
DR GO; GO:0140684; F:histone H3-tri/dimethyl-lysine-9 demethylase activity; IEA:UniProtKB-EC.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006338; P:chromatin remodeling; IBA:GO_Central.
DR GO; GO:0016577; P:histone demethylation; IMP:UniProtKB.
DR GO; GO:0070544; P:histone H3-K36 demethylation; IDA:WormBase.
DR GO; GO:0033169; P:histone H3-K9 demethylation; IDA:WormBase.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR InterPro; IPR034732; EPHD.
DR InterPro; IPR003347; JmjC_dom.
DR InterPro; IPR003349; JmjN.
DR Pfam; PF02373; JmjC; 1.
DR Pfam; PF02375; JmjN; 1.
DR SMART; SM00558; JmjC; 1.
DR SMART; SM00545; JmjN; 1.
DR PROSITE; PS51805; EPHD; 1.
DR PROSITE; PS51184; JMJC; 1.
DR PROSITE; PS51183; JMJN; 1.
PE 3: Inferred from homology;
KW Chromatin regulator; Dioxygenase; Iron; Metal-binding; Nucleus;
KW Oxidoreductase; Reference proteome; Transcription;
KW Transcription regulation; Zinc; Zinc-finger.
FT CHAIN 1..922
FT /note="Lysine-specific demethylase 4"
FT /id="PRO_0000234378"
FT DOMAIN 87..130
FT /note="JmjN"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00537"
FT DOMAIN 223..388
FT /note="JmjC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00538"
FT ZN_FING 639..675
FT /note="C2HC pre-PHD-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01146"
FT ZN_FING 723..783
FT /note="PHD-type; degenerate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01146"
FT REGION 1..21
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 42..61
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 435..475
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..19
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 454..475
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 213
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:B2RXH2"
FT BINDING 265
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00538"
FT BINDING 267
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00538"
FT BINDING 275
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:B2RXH2"
FT BINDING 283
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:B2RXH2"
FT BINDING 314
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 320
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 321
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:B2RXH2"
FT BINDING 356
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00538"
FT BINDING 386
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 388
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
SQ SEQUENCE 922 AA; 105659 MW; 3C1CA2456A69E5A1 CRC64;
MASAATTTHF PSSRIPSEPC ASSGPLFPDD VLFTTEASSA SSSSCHVEND SRPLSPTMFT
DGRTPVNISA KHLKDHPLHE PTGTSEVLTF YPTMREFKNF SQYIKKIEQN GGHLKAGIAK
IVAPEGWTPR PTRKDFSDVD DYEITQPARE TIEATEKPGA YFKRNVTCRR KMPVREFRTL
ANSAQYRNPR PDLKGSEIEK HYFDNILHGE PIYGADTEGS FYDAQVEEWN MNRLGTILED
TNYEIKGVNT VYLYFGMYKT TFPWHAEDMD LYSINFLHFG APKYWFAISS EHADRFERFM
SQQFSYQNEY APQCKAFLRH KTYLVTPELL RQAGIPYATM VQRPNEFIIT FPRGYHMGFN
LGYNLAESTN FASQRWIDYG KDAVLCDCNK DSVKIDMTHF MAKYRPDEYT TWWTYWYGGG
RELWIPKKKK EVPKKRRQSL ADASKIAKRA RLGASSTATD SDGSSGSSGS EEATEGSSFM
RALPAGYTVH NWQLRPDYDE LLRKYKKETK LLRSDTRIDF YQEREFNHAR RAEWPHCAVC
QYFQPPHMNA INHTVPNSSR RLIPKWCFSK TDTKKHEDHH EPPPPLDRLL TCSNCHVTVH
SHCCSGGGGG GGDDDDVTSS GEPWRCPRCR NRTDVEIRTT SCQLCELRGG ALIPCQIGTD
STWAHVACAL FNRRAIFDCP NRPGACFVEP SPRQQSETPR MPPRRLSEEY RAELGDLYEN
SRWECVVCHR TDEGLAPCVL CIEEQATTSL PTLAHVTCAR RVGFVCEVRD YPRGVVMICH
KHEHSYLVNK TTQQQAYTNV KVGDFVFVED VVEPPQKLFT RGAIVRADKK ETVVVDFLDN
SCSRDNHVED IISCECLFCE NGDHQYGARV KVVWDDKQVY DAYFRGKGQM IEYTVRLEDG
REVRHPRNRL KTKRELNAYL KK
