KDM4E_HUMAN
ID KDM4E_HUMAN Reviewed; 506 AA.
AC B2RXH2;
DT 13-JUL-2010, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-2008, sequence version 1.
DT 03-AUG-2022, entry version 94.
DE RecName: Full=Lysine-specific demethylase 4E;
DE EC=1.14.11.66 {ECO:0000305|PubMed:21914792};
DE AltName: Full=KDM4D-like protein;
DE AltName: Full=Lysine-specific demethylase 4D-like;
DE AltName: Full=[histone H3]-trimethyl-L-lysine(9) demethylase 4E {ECO:0000305};
GN Name=KDM4E; Synonyms=KDM4DL;
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 GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [3]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 1-336 IN COMPLEX WITH OXOGLUTARATE
RP AND NICKEL ION, COFACTOR, FUNCTION, AND SUBSTRATE SPECIFICITY.
RX PubMed=21914792; DOI=10.1074/jbc.m111.283689;
RA Hillringhaus L., Yue W.W., Rose N.R., Ng S.S., Gileadi C., Loenarz C.,
RA Bello S.H., Bray J.E., Schofield C.J., Oppermann U.;
RT "Structural and evolutionary basis for the dual substrate selectivity of
RT human KDM4 histone demethylase family.";
RL J. Biol. Chem. 286:41616-41625(2011).
CC -!- FUNCTION: Histone demethylase that specifically demethylates 'Lys-9' of
CC histone H3, thereby playing a central role in histone code.
CC {ECO:0000269|PubMed:21914792}.
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:21914792};
CC -!- COFACTOR:
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC Evidence={ECO:0000269|PubMed:21914792};
CC Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000269|PubMed:21914792};
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00537}.
CC -!- SIMILARITY: Belongs to the JHDM3 histone demethylase family.
CC {ECO:0000305}.
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DR EMBL; AP002383; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC157851; AAI57852.1; -; mRNA.
DR EMBL; BC157889; AAI57890.1; -; mRNA.
DR EMBL; BC171916; AAI71916.1; -; mRNA.
DR CCDS; CCDS44713.1; -.
DR RefSeq; NP_001155102.1; NM_001161630.1.
DR PDB; 2W2I; X-ray; 2.10 A; A/B/C=1-336.
DR PDBsum; 2W2I; -.
DR AlphaFoldDB; B2RXH2; -.
DR SMR; B2RXH2; -.
DR STRING; 9606.ENSP00000397239; -.
DR BindingDB; B2RXH2; -.
DR ChEMBL; CHEMBL1293226; -.
DR DrugCentral; B2RXH2; -.
DR GuidetoPHARMACOLOGY; 2679; -.
DR iPTMnet; B2RXH2; -.
DR PhosphoSitePlus; B2RXH2; -.
DR BioMuta; KDM4E; -.
DR MassIVE; B2RXH2; -.
DR MaxQB; B2RXH2; -.
DR PaxDb; B2RXH2; -.
DR PeptideAtlas; B2RXH2; -.
DR PRIDE; B2RXH2; -.
DR Antibodypedia; 65787; 35 antibodies from 12 providers.
DR DNASU; 390245; -.
DR Ensembl; ENST00000450979.2; ENSP00000397239.2; ENSG00000235268.2.
DR GeneID; 390245; -.
DR KEGG; hsa:390245; -.
DR MANE-Select; ENST00000450979.2; ENSP00000397239.2; NM_001161630.1; NP_001155102.1.
DR UCSC; uc010ruf.1; human.
DR CTD; 390245; -.
DR GeneCards; KDM4E; -.
DR HGNC; HGNC:37098; KDM4E.
DR HPA; ENSG00000235268; Not detected.
DR MIM; 616581; gene.
DR neXtProt; NX_B2RXH2; -.
DR OpenTargets; ENSG00000235268; -.
DR PharmGKB; PA165543440; -.
DR VEuPathDB; HostDB:ENSG00000235268; -.
DR eggNOG; KOG0958; Eukaryota.
DR GeneTree; ENSGT00940000165078; -.
DR HOGENOM; CLU_001442_6_1_1; -.
DR InParanoid; B2RXH2; -.
DR OMA; NWRDDIV; -.
DR OrthoDB; 1186832at2759; -.
DR PhylomeDB; B2RXH2; -.
DR TreeFam; TF106449; -.
DR BioCyc; MetaCyc:MON66-43206; -.
DR BRENDA; 1.14.11.66; 2681.
DR BRENDA; 1.14.11.B19; 2681.
DR PathwayCommons; B2RXH2; -.
DR BioGRID-ORCS; 390245; 10 hits in 1069 CRISPR screens.
DR EvolutionaryTrace; B2RXH2; -.
DR GenomeRNAi; 390245; -.
DR Pharos; B2RXH2; Tchem.
DR PRO; PR:B2RXH2; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; B2RXH2; protein.
DR Bgee; ENSG00000235268; Expressed in placenta and 14 other tissues.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0032452; F:histone demethylase activity; IBA:GO_Central.
DR GO; GO:0032454; F:histone H3-methyl-lysine-9 demethylase activity; IDA:UniProtKB.
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:0033169; P:histone H3-K9 demethylation; IDA:UniProtKB.
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 3D-structure; Chromatin regulator; Dioxygenase; Iron; Metal-binding;
KW Nucleus; Oxidoreductase; Reference proteome; Transcription;
KW Transcription regulation; Zinc.
FT CHAIN 1..506
FT /note="Lysine-specific demethylase 4E"
FT /id="PRO_0000395404"
FT DOMAIN 15..57
FT /note="JmjN"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00537"
FT DOMAIN 143..309
FT /note="JmjC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00538"
FT REGION 432..473
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 133
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000269|PubMed:21914792"
FT BINDING 189
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000305|PubMed:21914792"
FT BINDING 191
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000305|PubMed:21914792"
FT BINDING 199
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250"
FT BINDING 207
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000269|PubMed:21914792"
FT BINDING 235
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 241
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 242
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000269|PubMed:21914792"
FT BINDING 277
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000305|PubMed:21914792"
FT BINDING 307
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 309
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT VARIANT 26
FT /note="A -> T (in dbSNP:rs12798990)"
FT /id="VAR_063402"
FT VARIANT 42
FT /note="Q -> R (in dbSNP:rs2257265)"
FT /id="VAR_063403"
FT VARIANT 113
FT /note="Q -> R (in dbSNP:rs10752685)"
FT /id="VAR_063404"
FT VARIANT 258
FT /note="F -> S (in dbSNP:rs16921260)"
FT /id="VAR_063405"
FT STRAND 16..18
FT /evidence="ECO:0007829|PDB:2W2I"
FT HELIX 22..25
FT /evidence="ECO:0007829|PDB:2W2I"
FT HELIX 28..37
FT /evidence="ECO:0007829|PDB:2W2I"
FT HELIX 40..42
FT /evidence="ECO:0007829|PDB:2W2I"
FT STRAND 44..48
FT /evidence="ECO:0007829|PDB:2W2I"
FT STRAND 67..70
FT /evidence="ECO:0007829|PDB:2W2I"
FT STRAND 72..79
FT /evidence="ECO:0007829|PDB:2W2I"
FT STRAND 82..89
FT /evidence="ECO:0007829|PDB:2W2I"
FT HELIX 95..103
FT /evidence="ECO:0007829|PDB:2W2I"
FT TURN 105..107
FT /evidence="ECO:0007829|PDB:2W2I"
FT HELIX 115..124
FT /evidence="ECO:0007829|PDB:2W2I"
FT STRAND 127..129
FT /evidence="ECO:0007829|PDB:2W2I"
FT STRAND 132..138
FT /evidence="ECO:0007829|PDB:2W2I"
FT HELIX 157..159
FT /evidence="ECO:0007829|PDB:2W2I"
FT HELIX 160..165
FT /evidence="ECO:0007829|PDB:2W2I"
FT TURN 170..172
FT /evidence="ECO:0007829|PDB:2W2I"
FT STRAND 176..180
FT /evidence="ECO:0007829|PDB:2W2I"
FT STRAND 185..189
FT /evidence="ECO:0007829|PDB:2W2I"
FT HELIX 192..194
FT /evidence="ECO:0007829|PDB:2W2I"
FT STRAND 196..205
FT /evidence="ECO:0007829|PDB:2W2I"
FT STRAND 207..212
FT /evidence="ECO:0007829|PDB:2W2I"
FT HELIX 214..216
FT /evidence="ECO:0007829|PDB:2W2I"
FT HELIX 217..227
FT /evidence="ECO:0007829|PDB:2W2I"
FT TURN 229..231
FT /evidence="ECO:0007829|PDB:2W2I"
FT TURN 239..242
FT /evidence="ECO:0007829|PDB:2W2I"
FT STRAND 244..246
FT /evidence="ECO:0007829|PDB:2W2I"
FT HELIX 248..253
FT /evidence="ECO:0007829|PDB:2W2I"
FT STRAND 259..263
FT /evidence="ECO:0007829|PDB:2W2I"
FT STRAND 268..271
FT /evidence="ECO:0007829|PDB:2W2I"
FT STRAND 276..292
FT /evidence="ECO:0007829|PDB:2W2I"
FT HELIX 295..297
FT /evidence="ECO:0007829|PDB:2W2I"
FT HELIX 298..303
FT /evidence="ECO:0007829|PDB:2W2I"
FT HELIX 319..325
FT /evidence="ECO:0007829|PDB:2W2I"
FT HELIX 327..329
FT /evidence="ECO:0007829|PDB:2W2I"
FT HELIX 331..334
FT /evidence="ECO:0007829|PDB:2W2I"
SQ SEQUENCE 506 AA; 56804 MW; 546D69F3A159E68B CRC64;
MKSVHSSPQN TSHTIMTFYP TMEEFADFNT YVAYMESQGA HQAGLAKVIP PKEWKARQMY
DDIEDILIAT PLQQVTSGQG GVFTQYHKKK KAMRVGQYRR LANSKKYQTP PHQNFADLEQ
RYWKSHPGNP PIYGADISGS LFEESTKQWN LGHLGTILDL LEQECGVVIE GVNTPYLYFG
MWKTTFAWHT EDMDLYSINY LHFGEPKTWY VVPPEHGQHL ERLARELFPD ISRGCEAFLR
HKVALISPTV LKENGIPFNC MTQEAGEFMV TFPYGYHAGF NHGFNCAEAI NFATPRWIDY
GKMASQCSCG ESTVTFSMDP FVRIVQPESY ELWKHRQDLA IVEHTEPRVA ESQELSNWRD
DIVLRRAALG LRLLPNLTAQ CPTQPVSSGH CYNPKGCGTD AVPGSAFQSS AYHTQTQSLT
LGMSARVLLP STGSWGSGRG RGRGQGQGRG CSRGRGHGCC TRELGTEEPT VQPASKRRLL
MGTRSRAQGH RPQLPLANDL MTNLSL
