KDM4A_PONAB
ID KDM4A_PONAB Reviewed; 1064 AA.
AC Q5RD88;
DT 22-NOV-2005, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 98.
DE RecName: Full=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=JmjC domain-containing histone demethylation protein 3A;
DE AltName: Full=Jumonji domain-containing protein 2A;
DE AltName: Full=[histone H3]-trimethyl-L-lysine(36) demethylase 4A {ECO:0000305};
DE AltName: Full=[histone H3]-trimethyl-L-lysine(9) demethylase 4A {ECO:0000305};
GN Name=KDM4A; Synonyms=JHDM3A, JMJD2A;
OS Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
RG The German cDNA consortium;
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
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 (By similarity). Does not demethylate histone H3 'Lys-4',
CC H3 'Lys-27' nor H4 'Lys-20'. Demethylates trimethylated H3 'Lys-9' and
CC H3 'Lys-36' residue, while it has no activity on mono- and dimethylated
CC residues. Demethylation of Lys residue generates formaldehyde and
CC succinate. Participates in transcriptional repression of ASCL2 and E2F-
CC responsive promoters via the recruitment of histone deacetylases and
CC NCOR1, respectively (By similarity). {ECO:0000250|UniProtKB:O75164,
CC ECO:0000250|UniProtKB:Q8BW72}.
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;
CC Evidence={ECO:0000250|UniProtKB:O75164};
CC Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000250|UniProtKB:O75164};
CC -!- SUBUNIT: Interacts with histone deacetylase proteins HDAC1, HDAC2 and
CC HDAC3. Interacts with RB and NCOR1 (By similarity).
CC {ECO:0000250|UniProtKB:O75164}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00537}.
CC -!- DOMAIN: The 2 Tudor domains recognize and bind methylated histone H3
CC 'Lys-4' residue (H3K4me). Double Tudor domain has an interdigitated
CC structure and the unusual fold is required for its ability to bind
CC methylated histone tails. Trimethylated H3 'Lys-4' (H3K4me3) is bound
CC in a cage of 3 aromatic residues, 2 of which are from the Tudor domain
CC 2, while the binding specificity is determined by side-chain
CC interactions involving residues from the Tudor domain 1. The Tudor
CC domains are also able to bind trimethylated histone H3 'Lys-9'
CC (H3K9me3), di- and trimethylated H4 'Lys-20' (H4K20me2 and H4K20me3).
CC Has high affinity for H4K20me2, blocking recruitment of proteins such
CC as TP53BP1 (By similarity). {ECO:0000250|UniProtKB:O75164}.
CC -!- PTM: Ubiquitinated by RNF8 and RNF168, leading to its degradation (By
CC similarity). Degradation promotes accessibility of H4K20me2 mark for
CC DNA repair protein TP53BP1, which is then recruited (By similarity).
CC {ECO:0000250|UniProtKB:O75164, ECO:0000250|UniProtKB:Q8BW72}.
CC -!- SIMILARITY: Belongs to the JHDM3 histone demethylase family.
CC {ECO:0000305}.
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DR EMBL; CR858028; CAH90269.1; -; mRNA.
DR RefSeq; NP_001125120.1; NM_001131648.1.
DR AlphaFoldDB; Q5RD88; -.
DR SMR; Q5RD88; -.
DR STRING; 9601.ENSPPYP00000001670; -.
DR PRIDE; Q5RD88; -.
DR GeneID; 100172003; -.
DR KEGG; pon:100172003; -.
DR CTD; 9682; -.
DR eggNOG; KOG0958; Eukaryota.
DR InParanoid; Q5RD88; -.
DR Proteomes; UP000001595; Unplaced.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
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:0035064; F:methylated histone binding; ISS:UniProtKB.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0070076; P:histone lysine demethylation; IEA:UniProt.
DR CDD; cd04508; TUDOR; 2.
DR Gene3D; 3.30.40.10; -; 2.
DR InterPro; IPR034732; EPHD.
DR InterPro; IPR003347; JmjC_dom.
DR InterPro; IPR003349; JmjN.
DR InterPro; IPR040477; KDM4_Tudor_2.
DR InterPro; IPR002999; Tudor.
DR InterPro; IPR011011; Znf_FYVE_PHD.
DR InterPro; IPR001965; Znf_PHD.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR Pfam; PF02373; JmjC; 1.
DR Pfam; PF02375; JmjN; 1.
DR Pfam; PF18104; Tudor_2; 2.
DR SMART; SM00558; JmjC; 1.
DR SMART; SM00545; JmjN; 1.
DR SMART; SM00249; PHD; 2.
DR SMART; SM00333; TUDOR; 2.
DR SUPFAM; SSF57903; SSF57903; 1.
DR PROSITE; PS51805; EPHD; 1.
DR PROSITE; PS51184; JMJC; 1.
DR PROSITE; PS51183; JMJN; 1.
PE 2: Evidence at transcript level;
KW Acetylation; Chromatin regulator; Dioxygenase; Iron; Metal-binding;
KW Nucleus; Oxidoreductase; Phosphoprotein; Reference proteome; Repeat;
KW Transcription; Transcription regulation; Ubl conjugation; Zinc;
KW Zinc-finger.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:O75164"
FT CHAIN 2..1064
FT /note="Lysine-specific demethylase 4A"
FT /id="PRO_0000183174"
FT DOMAIN 14..56
FT /note="JmjN"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00537"
FT DOMAIN 142..308
FT /note="JmjC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00538"
FT DOMAIN 897..954
FT /note="Tudor 1"
FT DOMAIN 955..1011
FT /note="Tudor 2"
FT ZN_FING 709..767
FT /note="PHD-type 1"
FT ZN_FING 772..805
FT /note="C2HC pre-PHD-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01146"
FT ZN_FING 828..885
FT /note="PHD-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01146"
FT REGION 358..384
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 501..537
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 597..638
FT /note="Interaction with NCOR1"
FT /evidence="ECO:0000250"
FT REGION 616..642
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 503..537
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 132
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:O75164"
FT BINDING 188
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00538"
FT BINDING 190
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00538"
FT BINDING 198
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:O75164"
FT BINDING 206
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:O75164"
FT BINDING 234
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:O75164"
FT BINDING 240
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:O75164"
FT BINDING 241
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:B2RXH2"
FT BINDING 276
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00538"
FT BINDING 306
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:O75164"
FT BINDING 308
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:O75164"
FT SITE 945
FT /note="Histone H3K4me3 binding"
FT /evidence="ECO:0000250"
FT SITE 967
FT /note="Histone H3K4me3 binding"
FT /evidence="ECO:0000250"
FT SITE 973
FT /note="Histone H3K4me3 binding"
FT /evidence="ECO:0000250"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:O75164"
FT MOD_RES 523
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O75164"
SQ SEQUENCE 1064 AA; 120712 MW; 09FB21D779D1ED05 CRC64;
MASESETLNP SARIMTFYPT MEEFRNFSRY IAYIESQGAH RAGLAKVVPP KEWKPRASYD
DIDDLVIPAP IQQLVTGQSG LFTQYNIQKK AMTVREFRKI ANSDKYCTPR YSEFEELERK
YWKNLTFNPP IYGADVNGTL YEKHVDEWNI GRLRTILDLV EKESGITIEG VNTPYLYFGM
WKTSFAWHTE DMDLYSINYL HFGEPKSWYS VPPEHGKRLE RLAKGFFPGS AQSCEAFLRH
KMTLISPLML KKYGIPFDKV TQEAGEFMIT FPYGYHAGFN HGFNCAESTN FATRRWIEYG
KQAVLCSCRK DMVKISMDVF VRKFQPERYK LWKAGKDNTV IDHTLPTPEA AEFLKESELP
PRAGNEEECP EDDMEGVEDG EEGDLKTSLA KHRIGTKRHR VCLEIPQEVS QSELFPKEDL
SSEQYEMTEC PAALAPVRPT HSSVRQVEDG LTFPDYSDST EVKFEELKNV KLEEEDEEEE
QEAAALDLSV NPASVGGRLV FSGSKKKSSS SLGSGSSRDS VSSDSETSEP LSCRAQGQTG
VLTVHSYAKG DGRVTVGEPC MRKKGSTARS FSERELAEVA DEYMFSLEEN KKSKGRRQPL
SKLPRHHPLV LQECVSDDET SEQLTPEEEA EETEAWAKPL SQLWQNRPPN FEAEKEFNET
MAQQAPHCAV CMIFQTYHQV EFGGFNQNCG NASDLAPQKQ RTKPLIPEMC FTSTGCGTDI
NLSTPYLEED GTSILVSCKK CSVRVHASCY GVPPAKASED WMCSRCSANA LEEDCCLCSL
RGGALQRAND DRWVHVSCAV AILEARFVNI AERSPVDVSK IPLPRFKLKC IFCKKRRKRT
AGCCVQCSHG RCPTAFHVSC AQAAGVMMQP DDWPFVVFIT CFRHKIPNLE RAKGALQSIT
AGQKVISKHK NGRFYQCEVV RLTTETFYEV NFDDGSFSDN LYPEDIVSQD CLQFGPPAEG
EVVQVRWTDG QVYGAKFVAS HPIQMYQVEF EDGSQLVVKR DDVYTLDEEL PKRVKSRLSV
ASDMRFNEIF TEKEVKQEKK RQRVINSRYR EDYIESALYR AIME
