ID KDM3A_RAT Reviewed; 1214 AA.
AC Q63679;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 27-MAR-2024, entry version 131.
DE RecName: Full=Lysine-specific demethylase 3A;
DE EC=1.14.11.65 {ECO:0000250|UniProtKB:Q9Y4C1};
DE AltName: Full=JmjC domain-containing histone demethylation protein 2A;
DE AltName: Full=Jumonji domain-containing protein 1A;
DE AltName: Full=Testis-specific gene A protein;
DE AltName: Full=Zinc finger protein TSGA;
DE AltName: Full=[histone H3]-dimethyl-L-lysine(9) demethylase 3A {ECO:0000305};
GN Name=Kdm3a; Synonyms=Jhdm2a, Jmjd1a, Tsga;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Testis;
RX PubMed=1793593; DOI=10.1002/mrd.1080300302;
RA Hoog C., Schalling M., Brundell E., Daneholt B.;
RT "Analysis of a murine male germ cell-specific transcript that encodes a
RT putative zinc finger protein.";
RL Mol. Reprod. Dev. 30:173-181(1991).
CC -!- FUNCTION: Histone demethylase that specifically demethylates 'Lys-9' of
CC histone H3, thereby playing a central role in histone code.
CC Preferentially demethylates mono- and dimethylated H3 'Lys-9' residue,
CC with a preference for dimethylated residue, while it has weak or no
CC activity on trimethylated H3 'Lys-9'. Demethylation of Lys residue
CC generates formaldehyde and succinate. Involved in hormone-dependent
CC transcriptional activation, by participating in recruitment to
CC androgen-receptor target genes, resulting in H3 'Lys-9' demethylation
CC and transcriptional activation. Involved in spermatogenesis by
CC regulating expression of target genes such as PRM1 and TNP1 which are
CC required for packaging and condensation of sperm chromatin. Directly
CC regulates expression of PPARA and UCP1 and is involved in obesity
CC resistance (By similarity). {ECO:0000250}.
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:0000250|UniProtKB:Q9Y4C1};
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: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.
CC Note=Nuclear in round spermatids. When spermatids start to elongate,
CC localizes to the cytoplasm where it forms distinct foci which disappear
CC in mature spermatozoa (By similarity). {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Testis specific. Expressed only in male germ cells.
CC -!- DEVELOPMENTAL STAGE: Reaches a maximum during the meiotic and the
CC postmeiotic stages of germ cell development.
CC -!- DOMAIN: The JmjC domain and the C6-type zinc-finger are required for
CC the demethylation activity. {ECO:0000250}.
CC -!- DOMAIN: Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs are known to mediate the
CC association with nuclear receptors. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the JHDM2 histone demethylase family.
CC {ECO:0000305}.
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DR EMBL; X59993; CAA42610.1; -; mRNA.
DR PIR; S28499; S28499.
DR RefSeq; NP_786940.1; NM_175764.2.
DR AlphaFoldDB; Q63679; -.
DR SMR; Q63679; -.
DR BioGRID; 260178; 1.
DR STRING; 10116.ENSRNOP00000072073; -.
DR PhosphoSitePlus; Q63679; -.
DR PaxDb; 10116-ENSRNOP00000041218; -.
DR GeneID; 312440; -.
DR KEGG; rno:312440; -.
DR UCSC; RGD:708351; rat.
DR AGR; RGD:708351; -.
DR CTD; 55818; -.
DR RGD; 708351; Kdm3a.
DR eggNOG; KOG1356; Eukaryota.
DR InParanoid; Q63679; -.
DR OrthoDB; 3473445at2759; -.
DR Reactome; R-RNO-3214842; HDMs demethylate histones.
DR PRO; PR:Q63679; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0000785; C:chromatin; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0000118; C:histone deacetylase complex; IBA:GO_Central.
DR GO; GO:0001673; C:male germ cell nucleus; ISO:RGD.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0003682; F:chromatin binding; ISO:RGD.
DR GO; GO:0031490; F:chromatin DNA binding; IBA:GO_Central.
DR GO; GO:0032454; F:histone H3K9 demethylase activity; ISO:RGD.
DR GO; GO:0140683; F:histone H3K9me/H3K9me2 demethylase activity; ISO:RGD.
DR GO; GO:0005506; F:iron ion binding; ISO:RGD.
DR GO; GO:0050681; F:nuclear androgen receptor binding; ISO:RGD.
DR GO; GO:0003712; F:transcription coregulator activity; ISO:RGD.
DR GO; GO:0030521; P:androgen receptor signaling pathway; ISO:RGD.
DR GO; GO:1990830; P:cellular response to leukemia inhibitory factor; ISO:RGD.
DR GO; GO:0046293; P:formaldehyde biosynthetic process; ISO:RGD.
DR GO; GO:0009755; P:hormone-mediated signaling pathway; ISO:RGD.
DR GO; GO:0008584; P:male gonad development; IEP:RGD.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:YuBioLab.
DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; ISO:RGD.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:RGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0010468; P:regulation of gene expression; ISO:RGD.
DR GO; GO:2000736; P:regulation of stem cell differentiation; ISO:RGD.
DR GO; GO:2000036; P:regulation of stem cell population maintenance; ISO:RGD.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0001666; P:response to hypoxia; IEP:RGD.
DR GO; GO:0007290; P:spermatid nucleus elongation; ISO:RGD.
DR GO; GO:0007283; P:spermatogenesis; ISO:RGD.
DR Gene3D; 2.60.120.650; Cupin; 1.
DR InterPro; IPR045109; JHDM2-like.
DR InterPro; IPR003347; JmjC_dom.
DR PANTHER; PTHR12549; JMJC DOMAIN-CONTAINING HISTONE DEMETHYLATION PROTEIN; 1.
DR PANTHER; PTHR12549:SF7; LYSINE-SPECIFIC DEMETHYLASE 3A; 1.
DR Pfam; PF02373; JmjC; 1.
DR SMART; SM00558; JmjC; 1.
DR SUPFAM; SSF51197; Clavaminate synthase-like; 1.
DR PROSITE; PS51184; JMJC; 1.
PE 2: Evidence at transcript level;
KW Acetylation; Activator; Chromatin regulator; Cytoplasm; Differentiation;
KW Dioxygenase; Iron; Metal-binding; Nucleus; Oxidoreductase; Phosphoprotein;
KW Reference proteome; Spermatogenesis; Transcription;
KW Transcription regulation; Zinc; Zinc-finger.
FT CHAIN 1..1214
FT /note="Lysine-specific demethylase 3A"
FT /id="PRO_0000084287"
FT DOMAIN 944..1167
FT /note="JmjC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00538"
FT ZN_FING 546..571
FT /note="C6-type"
FT /evidence="ECO:0000255"
FT REGION 194..215
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 271..293
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 310..398
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 769..773
FT /note="LXXLL motif"
FT COMPBIAS 194..212
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 274..293
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 317..333
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 352..370
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 1006
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00538"
FT BINDING 1008
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00538"
FT BINDING 1135
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00538"
FT MOD_RES 150
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4C1"
FT MOD_RES 209
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4C1"
FT MOD_RES 330
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4C1"
FT MOD_RES 779
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4C1"
SQ SEQUENCE 1214 AA; 135404 MW; 8E6B52220760EA6E CRC64;
MYKSLLDKAG LGSITSVRFL GDQQSVFVSK DLLKPIQDVN SLRLSLTDNQ TVSKEFQALI
VKHLDESHLL QGDKNLVGSE VRIYSLDPST QWFSATVVHG NPSSKTLQVN CEEIPALKIV
DPALIHVEVV HDNFVTCGNS TRIGAVKRKS SENNGSSVSK QAKSCSEVSP SMCPVQSVPT
TVCKEILLGC TAATPSSNRQ QNTPQAANSP PNIGAKLPQG CHKQSLPEEI SSCLNTKSEV
LRTKPDVCKA GLLSSKSSQV GAGDLKILSE PKGSCIQPKT NTDQESRLES TPQPVTGLTK
ECLVTKTSSK AELDNATAPE LQKRLEHTAS TPDGLSDKPE VEAGVTRLNS CSEKKVGPSD
LGSQSQNLKE TSVKVDHDSC CTRSSNKTQT PPARKSVLTD PDKLKKLQQS GEAFVQDDSC
VNIVAQLPKC RECRLDSLRK DKDQQKDSPV FCRFFHFRRL QFNKHGVLRV EGFLTPNKYD
SEAIGLWLPL TKNVVGTDLD TAKYILANIG DHFCQMVISE KEAMSTIEPH RQVAWKRAVK
GVREMCDVCD TTIFNLHWVC PRCGFGVCVD CYRLKRKNCQ QGAAYKTFSW IRCVKSQIHE
PENLMPTQII PGKALYDVGD IVHSVRAKWG IKANCPCSNR QFKLFSKPAL KEDLKQASLS
GEKPSLGTMV QQSSPVLEPA AVCGEAPSKP ASNVKPICPA NTSPLNWLAD LTSGNVNKEN
KEKQLTMPIL KNEIKCLPPL PPLNKSSTVL HTFNSTILTP VSNNNSGFLR NLLNSSTGKT
ENGLKNTPKI LDDIFASLVQ NKTSSDLSKR PQGLTIKPSI LGFDTPHYWL CDNRLLCLQD
PNNKSNWNVF RECWKQGQPV MVSGVHHKLN TELWKPESFR KEFGEQEVDL VNCRTNEIIT
GATVGDFWDG FEDVPNRLKN EKEKEPMVLK LKDWPPGEDF RDMMPSRFDD LMANIPLPEY
TRRDGKLNLA SRLPNYFVRP DLGPKMYNAY GLITPEDRKY GTTNLHLDVS DAANVMVYVG
IPKGQCEQEE EVLRTIQDGD SDELTIKRFI EGKEKPGALW HIYAAKDTEK IREFLKKVSE
EQGQENPADH DPIHDQSWYL DRSLRKRLYQ EYGVQGWAIV QFLGDVVFIP AGAPHQVHNL
YSCIKVAEDF VSPEHVKHCF WLTQEFRHLS QTHTNHEDKL QVKNVIYHAV KDAVAMLKAV
NPVWANVNSS AHWR
//
