KDM4A_DROME
ID KDM4A_DROME Reviewed; 495 AA.
AC Q9V333;
DT 16-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=Probable lysine-specific demethylase 4A;
DE EC=1.14.11.66 {ECO:0000250|UniProtKB:O75164};
DE EC=1.14.11.69 {ECO:0000250|UniProtKB:O75164};
DE AltName: Full=Probable JmjC domain-containing histone demethylation protein 3A;
DE AltName: Full=Probable [histone H3]-trimethyl-L-lysine(36) demethylase 4A {ECO:0000305};
DE AltName: Full=Probable [histone H3]-trimethyl-L-lysine(9) demethylase 4A {ECO:0000305};
GN Name=Kdm4A; ORFNames=CG15835;
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Embryo;
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-409, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
RC TISSUE=Embryo;
RX PubMed=18327897; DOI=10.1021/pr700696a;
RA Zhai B., Villen J., Beausoleil S.A., Mintseris J., Gygi S.P.;
RT "Phosphoproteome analysis of Drosophila melanogaster embryos.";
RL J. Proteome Res. 7:1675-1682(2008).
CC -!- FUNCTION: Probable histone demethylase that specifically demethylates
CC 'Lys-9' and 'Lys-36' residues of histone H3, thereby playing a central
CC role in histone code. Demethylation of Lys residue generates
CC formaldehyde and succinate (By similarity). {ECO:0000250}.
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:0000250|UniProtKB:O75164};
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:0000250|UniProtKB:O75164};
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 -!- SIMILARITY: Belongs to the JHDM3 histone demethylase family.
CC {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; AE013599; AAF59172.1; -; Genomic_DNA.
DR EMBL; AY058636; AAL13865.1; -; mRNA.
DR RefSeq; NP_610331.1; NM_136487.4.
DR AlphaFoldDB; Q9V333; -.
DR SMR; Q9V333; -.
DR BioGRID; 61608; 8.
DR IntAct; Q9V333; 1.
DR STRING; 7227.FBpp0087961; -.
DR iPTMnet; Q9V333; -.
DR PaxDb; Q9V333; -.
DR DNASU; 35744; -.
DR EnsemblMetazoa; FBtr0088886; FBpp0087961; FBgn0033233.
DR GeneID; 35744; -.
DR KEGG; dme:Dmel_CG15835; -.
DR UCSC; CG15835-RA; d. melanogaster.
DR CTD; 9682; -.
DR FlyBase; FBgn0033233; Kdm4A.
DR VEuPathDB; VectorBase:FBgn0033233; -.
DR eggNOG; KOG0958; Eukaryota.
DR GeneTree; ENSGT00940000154930; -.
DR InParanoid; Q9V333; -.
DR OrthoDB; 1186832at2759; -.
DR PhylomeDB; Q9V333; -.
DR BRENDA; 1.14.11.65; 1994.
DR BRENDA; 1.14.11.66; 1994.
DR BRENDA; 1.14.11.67; 1994.
DR BRENDA; 1.14.11.69; 1994.
DR BRENDA; 1.14.11.B19; 1994.
DR SignaLink; Q9V333; -.
DR BioGRID-ORCS; 35744; 0 hits in 3 CRISPR screens.
DR ChiTaRS; Kdm4A; fly.
DR GenomeRNAi; 35744; -.
DR PRO; PR:Q9V333; -.
DR Proteomes; UP000000803; Chromosome 2R.
DR Bgee; FBgn0033233; Expressed in egg cell and 27 other tissues.
DR ExpressionAtlas; Q9V333; baseline and differential.
DR Genevisible; Q9V333; DM.
DR GO; GO:0000792; C:heterochromatin; IDA:FlyBase.
DR GO; GO:0005634; C:nucleus; IDA:FlyBase.
DR GO; GO:0032452; F:histone demethylase activity; IBA:GO_Central.
DR GO; GO:0051864; F:histone H3-methyl-lysine-36 demethylase activity; IDA:FlyBase.
DR GO; GO:0032454; F:histone H3-methyl-lysine-9 demethylase activity; IMP:FlyBase.
DR GO; GO:0140681; F:histone H3-tri/dimethyl-lysine-36 demethylase activity; IEA:UniProtKB-EC.
DR GO; GO:0140760; F:histone H3-tri/dimethyl-lysine-56 demethylase activity; IMP:FlyBase.
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; ISS:UniProtKB.
DR GO; GO:0070544; P:histone H3-K36 demethylation; IMP:FlyBase.
DR GO; GO:0033169; P:histone H3-K9 demethylation; IMP:FlyBase.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:FlyBase.
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; PS51184; JMJC; 1.
DR PROSITE; PS51183; JMJN; 1.
PE 1: Evidence at protein level;
KW Chromatin regulator; Dioxygenase; Iron; Metal-binding; Nucleus;
KW Oxidoreductase; Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation; Zinc.
FT CHAIN 1..495
FT /note="Probable lysine-specific demethylase 4A"
FT /id="PRO_0000234379"
FT DOMAIN 18..60
FT /note="JmjN"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00537"
FT DOMAIN 149..315
FT /note="JmjC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00538"
FT BINDING 139
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:B2RXH2"
FT BINDING 195
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00538"
FT BINDING 197
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00538"
FT BINDING 205
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250"
FT BINDING 213
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:B2RXH2"
FT BINDING 241
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 247
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 248
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:B2RXH2"
FT BINDING 283
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00538"
FT BINDING 313
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 315
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT MOD_RES 409
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
SQ SEQUENCE 495 AA; 56990 MW; 75EF4AC188C834A9 CRC64;
MSTRSSFADE EQNKVPRIMT FRPSYEEFQN FSAYIEYIES RGAHLAGLAK IQPPAEWVPR
KSGYDIDNIN MTIPAPICQV VTGAHGVYQQ INIQQRRQMT LRQFMEKANS ELHQTPRHFD
YDDLERKYWK NITYISPLYA ADVKGSLSDE DLDVWNIGRL DTILNLVNTD YNIIIDGVNT
AYLYFGMWKS SFAWHTEDMD LYSINYLHFG APKTWYAIPP AYGRRLEKLA NETFSENYQE
CNAYLRHKMT MISPKVLRQH NIPYNKITQE AGEIMITFPF GYHAGFNHGF NGAESTNFAS
KRWIEYGKRA SICRCRSDMV KISMETFVRR FQPERYDNWL KGQDMGCHPE EPGKICAAAP
PTLNEYEKQE NLRAAKSEEE SPQKRGCSLA GNGCERNAES AEDVDDKASV SSYSSCRQLQ
PVVKLRKLPT IASVPEPSSA PKRYDFNTEA VVRVKRLWNE LPCPDRGANL LTNGVVKNTK
RMRFQTKVLT LDDED
