ID KDM7A_MOUSE Reviewed; 940 AA.
AC Q3UWM4; A6H6E5; Q3UWN8; Q6ZPJ5; Q8C969; Q8C9E0; Q91VX8;
DT 07-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 07-MAR-2006, sequence version 2.
DT 27-MAR-2024, entry version 129.
DE RecName: Full=Lysine-specific demethylase 7A;
DE AltName: Full=JmjC domain-containing histone demethylation protein 1D;
DE AltName: Full=Lysine-specific demethylase 7;
DE AltName: Full=[histone H3]-dimethyl-L-lysine9 demethylase 7A;
DE EC=1.14.11.65 {ECO:0000269|PubMed:20194436};
GN Name=Kdm7a; Synonyms=Jhdm1d, Kdm7, Kiaa1718;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Cerebellum, Egg, and Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, and Mammary tumor;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 508-940.
RC TISSUE=Embryonic tail;
RX PubMed=14621295; DOI=10.1093/dnares/10.4.167;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA Saga Y., Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: III.
RT The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 10:167-180(2003).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND MUTAGENESIS OF 39-TYR--ALA-86;
RP 230-PHE--LYS-386 AND HIS-282.
RX PubMed=20194436; DOI=10.1101/gad.1864410;
RA Tsukada Y., Ishitani T., Nakayama K.I.;
RT "KDM7 is a dual demethylase for histone H3 Lys 9 and Lys 27 and functions
RT in brain development.";
RL Genes Dev. 24:432-437(2010).
CC -!- FUNCTION: Histone demethylase required for brain development.
CC Specifically demethylates dimethylated 'Lys-9', 'Lys-27' and 'Lys-36'
CC (H3K9me2, H3K27me2, H3K36me2, respectively) of histone H3 and
CC monomethylated histone H4 'Lys-20' residue (H4K20Me1), thereby playing
CC a central role in histone code. Specifically binds trimethylated 'Lys-
CC 4' of histone H3 (H3K4me3), affecting histone demethylase specificity:
CC in presence of H3K4me3, it has no demethylase activity toward H3K9me2,
CC while it has high activity toward H3K27me2. Demethylates H3K9me2 in
CC absence of H3K4me3. Has activity toward H4K20Me1 only when nucleosome
CC is used as a substrate and when not histone octamer is used as
CC substrate. {ECO:0000250|UniProtKB:Q6ZMT4, ECO:0000269|PubMed:20194436}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 2-oxoglutarate + N(6),N(6)-dimethyl-L-lysyl(9)-[histone H3]
CC + 2 O2 = 2 CO2 + 2 formaldehyde + L-lysyl(9)-[histone H3] + 2
CC succinate; Xref=Rhea:RHEA:60188, Rhea:RHEA-COMP:15541, Rhea:RHEA-
CC COMP:15546, ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810,
CC ChEBI:CHEBI:16842, ChEBI:CHEBI:29969, ChEBI:CHEBI:30031,
CC ChEBI:CHEBI:61976; EC=1.14.11.65;
CC Evidence={ECO:0000269|PubMed:20194436};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60189;
CC Evidence={ECO:0000305|PubMed:20194436};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 2-oxoglutarate + N(6),N(6)-dimethyl-L-lysyl(27)-[histone H3]
CC + 2 O2 = 2 CO2 + 2 formaldehyde + L-lysyl(27)-[histone H3] + 2
CC succinate; Xref=Rhea:RHEA:67800, Rhea:RHEA-COMP:15539, Rhea:RHEA-
CC COMP:15548, ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810,
CC ChEBI:CHEBI:16842, ChEBI:CHEBI:29969, ChEBI:CHEBI:30031,
CC ChEBI:CHEBI:61976; Evidence={ECO:0000250|UniProtKB:Q6ZMT4};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67801;
CC Evidence={ECO:0000250|UniProtKB:Q6ZMT4};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + N(6),N(6)-dimethyl-L-lysyl(36)-[histone H3] +
CC O2 = CO2 + formaldehyde + N(6)-methyl-L-lysyl(36)-[histone H3] +
CC succinate; Xref=Rhea:RHEA:21788, Rhea:RHEA-COMP:9786, Rhea:RHEA-
CC COMP:9787, ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810,
CC ChEBI:CHEBI:16842, ChEBI:CHEBI:30031, ChEBI:CHEBI:61929,
CC ChEBI:CHEBI:61976; Evidence={ECO:0000269|PubMed:20194436};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21789;
CC Evidence={ECO:0000305|PubMed:20194436};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + N(6)-methyl-L-lysyl(20)-[histone H4] + O2 =
CC CO2 + formaldehyde + L-lysyl(20)-[histone H4] + succinate;
CC Xref=Rhea:RHEA:67804, Rhea:RHEA-COMP:15554, Rhea:RHEA-COMP:15555,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810,
CC ChEBI:CHEBI:16842, ChEBI:CHEBI:29969, ChEBI:CHEBI:30031,
CC ChEBI:CHEBI:61929; Evidence={ECO:0000250|UniProtKB:Q6ZMT4};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67805;
CC Evidence={ECO:0000250|UniProtKB:Q6ZMT4};
CC -!- COFACTOR:
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC Evidence={ECO:0000269|PubMed:20194436};
CC Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000250|UniProtKB:Q6ZMT4};
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}.
CC -!- DOMAIN: The PHD-type zinc finger mediates the binding to H3K4me3.
CC Binding to H3K4me3 prevents its access to H3K9me2.
CC {ECO:0000250|UniProtKB:Q6ZMT4}.
CC -!- DOMAIN: The linker region is a critical determinant of demethylase
CC specificity. It prevents the active site of JmjC to reach the target
CC H3K9me2 when the PHD-type zinc finger binds to H3K4me3, while it favors
CC selectivity toward H3K27me2. {ECO:0000250|UniProtKB:Q6ZMT4}.
CC -!- SIMILARITY: Belongs to the JHDM1 histone demethylase family. JHDM1D
CC subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAI45849.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAE22876.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK042327; BAC31226.2; -; mRNA.
DR EMBL; AK042834; BAC31377.1; -; mRNA.
DR EMBL; AK136209; BAE22876.1; ALT_INIT; mRNA.
DR EMBL; AK136238; BAE22890.1; -; mRNA.
DR EMBL; BC007161; AAH07161.1; -; mRNA.
DR EMBL; BC145848; AAI45849.1; ALT_INIT; mRNA.
DR EMBL; AK129429; BAC98239.1; -; mRNA.
DR CCDS; CCDS51753.1; -.
DR RefSeq; NP_001028602.2; NM_001033430.4.
DR AlphaFoldDB; Q3UWM4; -.
DR SMR; Q3UWM4; -.
DR STRING; 10090.ENSMUSP00000002305; -.
DR ChEMBL; CHEMBL3038497; -.
DR iPTMnet; Q3UWM4; -.
DR PhosphoSitePlus; Q3UWM4; -.
DR EPD; Q3UWM4; -.
DR MaxQB; Q3UWM4; -.
DR PaxDb; 10090-ENSMUSP00000002305; -.
DR PeptideAtlas; Q3UWM4; -.
DR ProteomicsDB; 264993; -.
DR Antibodypedia; 2004; 141 antibodies from 20 providers.
DR Ensembl; ENSMUST00000002305.9; ENSMUSP00000002305.9; ENSMUSG00000042599.9.
DR GeneID; 338523; -.
DR KEGG; mmu:338523; -.
DR UCSC; uc009bli.2; mouse.
DR AGR; MGI:2443388; -.
DR MGI; MGI:2443388; Kdm7a.
DR VEuPathDB; HostDB:ENSMUSG00000042599; -.
DR eggNOG; KOG1633; Eukaryota.
DR eggNOG; KOG1634; Eukaryota.
DR GeneTree; ENSGT00940000158039; -.
DR HOGENOM; CLU_003540_2_1_1; -.
DR InParanoid; Q3UWM4; -.
DR OMA; PWEEDIT; -.
DR OrthoDB; 2784357at2759; -.
DR PhylomeDB; Q3UWM4; -.
DR TreeFam; TF106480; -.
DR Reactome; R-MMU-3214842; HDMs demethylate histones.
DR BioGRID-ORCS; 338523; 2 hits in 79 CRISPR screens.
DR ChiTaRS; Kdm7a; mouse.
DR PRO; PR:Q3UWM4; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; Q3UWM4; Protein.
DR Bgee; ENSMUSG00000042599; Expressed in blood and 228 other cell types or tissues.
DR Genevisible; Q3UWM4; MM.
DR GO; GO:0005730; C:nucleolus; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0016706; F:2-oxoglutarate-dependent dioxygenase activity; ISS:UniProtKB.
DR GO; GO:0032452; F:histone demethylase activity; IBA:GO_Central.
DR GO; GO:0071558; F:histone H3K27me2/H3K27me3 demethylase activity; IMP:UniProtKB.
DR GO; GO:0051864; F:histone H3K36 demethylase activity; ISS:UniProtKB.
DR GO; GO:0032454; F:histone H3K9 demethylase activity; IMP:UniProtKB.
DR GO; GO:0140683; F:histone H3K9me/H3K9me2 demethylase activity; IEA:RHEA.
DR GO; GO:0035575; F:histone H4K20 demethylase activity; ISS:UniProtKB.
DR GO; GO:0005506; F:iron ion binding; ISS:UniProtKB.
DR GO; GO:0035064; F:methylated histone binding; ISS:UniProtKB.
DR GO; GO:0003712; F:transcription coregulator activity; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR GO; GO:0030901; P:midbrain development; ISS:UniProtKB.
DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IMP:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR CDD; cd15640; PHD_KDM7; 1.
DR Gene3D; 1.20.58.1360; -; 1.
DR Gene3D; 2.60.120.650; Cupin; 1.
DR Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 1.
DR InterPro; IPR041070; JHD.
DR InterPro; IPR003347; JmjC_dom.
DR InterPro; IPR019786; Zinc_finger_PHD-type_CS.
DR InterPro; IPR011011; Znf_FYVE_PHD.
DR InterPro; IPR001965; Znf_PHD.
DR InterPro; IPR019787; Znf_PHD-finger.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR PANTHER; PTHR23123:SF15; LYSINE-SPECIFIC DEMETHYLASE 7A; 1.
DR PANTHER; PTHR23123; PHD/F-BOX CONTAINING PROTEIN; 1.
DR Pfam; PF17811; JHD; 1.
DR Pfam; PF02373; JmjC; 1.
DR Pfam; PF00628; PHD; 1.
DR SMART; SM00558; JmjC; 1.
DR SMART; SM00249; PHD; 1.
DR SUPFAM; SSF51197; Clavaminate synthase-like; 1.
DR SUPFAM; SSF57903; FYVE/PHD zinc finger; 1.
DR PROSITE; PS51184; JMJC; 1.
DR PROSITE; PS01359; ZF_PHD_1; 1.
DR PROSITE; PS50016; ZF_PHD_2; 1.
PE 1: Evidence at protein level;
KW Chromatin regulator; Dioxygenase; Iron; Metal-binding; Neurogenesis;
KW Nucleus; Oxidoreductase; Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation; Zinc; Zinc-finger.
FT CHAIN 1..940
FT /note="Lysine-specific demethylase 7A"
FT /id="PRO_0000226772"
FT DOMAIN 230..386
FT /note="JmjC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00538"
FT ZN_FING 37..88
FT /note="PHD-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00146"
FT REGION 97..114
FT /note="Linker"
FT /evidence="ECO:0000250"
FT REGION 483..509
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 599..670
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 710..729
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 818..854
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 876..920
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 599..615
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 616..650
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 823..838
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 839..854
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 279
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 282
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00538"
FT BINDING 284
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00538"
FT BINDING 299
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 354
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00538"
FT MOD_RES 604
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6ZMT4"
FT MUTAGEN 39..86
FT /note="Missing: Has no effect on enzymatic activity."
FT /evidence="ECO:0000269|PubMed:20194436"
FT MUTAGEN 230..386
FT /note="Missing: Abolishes enzymatic activity."
FT /evidence="ECO:0000269|PubMed:20194436"
FT MUTAGEN 282
FT /note="H->A: Abolishes enzymatic activity."
FT /evidence="ECO:0000269|PubMed:20194436"
FT CONFLICT 372
FT /note="N -> D (in Ref. 1; BAE22890)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 940 AA; 106075 MW; B14FC1F85C7A5AFE CRC64;
MAGAAAAVAA GAAAGAAAAA GSVSAPGRAS APPPPPPVYC VCRQPYDVNR FMIECDVCKD
WFHGSCVGVE EHHAVDIDLY HCPDCAALHG SSLMKKRRNW HRHDYTEVDD GSKPVQAGTR
AFVKELRSRV FPSADEIIVK MHGSQLTQRY LEKHGFDVPI MVPKLDDLGL RLPSPAFSVM
DVERYVGGDK VIDVIDVARQ ADSKMTLHNY VKYFMNPDRP KVLNVISLEF SDTKMSELVE
VPDIARKLSW VENYWPDDSV FPKPFVQKYC LMGVQDSYTD FHIDFGGTSV WYHVLWGEKI
FYLIKPTNEN LALYESWSSS VTQSEVFFGD KVDKCYKCVV KQGHTLFVPT GWIHAVLTSQ
DCMAFGGNFL HNLNIGMQLR CYEMEKRLKT PDLFKFPFFE AICWFVAKSL LETLKELKED
GFQPQSYLVQ GVKALHTALK LWMKKELVSE HAFEIPDNVR PGHLIKELSK VIRAIEEENG
KPVKSQGIPS VCPVSRPSNE ASPPYHSRRK MRKLRDHNVR TPSNLDILEL HTREVLKRLE
MCPWEEDLLS SKLNGKFNKH LQPSSTVPEW RAKDNDLRLL LTNGRIIKDE RQLFADRSLY
TADSENEEDK KPTQNANMKT EQSSGREEAE SQGSPKPLNR IFTSVRSELR SRPSEYSDGS
DSEDSGPDCT ALKINFATED SESSGDEKKH EITSHFKEES DIVRNLLQKS QKPSRQEIPV
KRECPTSTST EEEAIQGMLS MAGLHYSSCL QRQIQSTDCS GEKNSLQDPS SCHGSNPEFR
QLYRCNKPVE FGYHAKTEDQ DLMTSSWNKQ FDRTSRFNAQ DLSRSQKHIK KESSSEINQK
AQSRHCVDSN SSSIQNGKYT LNPSLVSCQI SNGSLSPERP IGETSFSMPL HPTKRPASNP
PPISNQATKG KRPKKGMATA KQRLGKILKL NRNGHARFFV
//
