KDM5_CAEEL
ID KDM5_CAEEL Reviewed; 1477 AA.
AC Q23541;
DT 26-JUN-2007, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 2.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=Lysine-specific demethylase rbr-2;
DE AltName: Full=Histone demethylase rbr-2;
DE EC=1.14.11.67 {ECO:0000269|PubMed:17320161};
DE AltName: Full=Jumonji/ARID domain-containing protein rbr-2;
DE AltName: Full=[histone H3]-trimethyl-L-lysine(4) demethylase rbr-2 {ECO:0000305};
GN Name=rbr-2; ORFNames=ZK593.4;
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2]
RP FUNCTION AS HISTONE DEMETHYLASE, AND CATALYTIC ACTIVITY.
RX PubMed=17320161; DOI=10.1016/j.cell.2007.02.003;
RA Christensen J., Agger K., Cloos P.A.C., Pasini D., Rose S., Sennels L.,
RA Rappsilber J., Hansen K.H., Salcini A.E., Helin K.;
RT "RBP2 belongs to a family of demethylases, specific for tri-and
RT dimethylated lysine 4 on histone 3.";
RL Cell 128:1063-1076(2007).
RN [3]
RP FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX PubMed=20555324; DOI=10.1038/nature09195;
RA Greer E.L., Maures T.J., Hauswirth A.G., Green E.M., Leeman D.S.,
RA Maro G.S., Han S., Banko M.R., Gozani O., Brunet A.;
RT "Members of the H3K4 trimethylation complex regulate lifespan in a
RT germline-dependent manner in C. elegans.";
RL Nature 466:383-387(2010).
RN [4]
RP FUNCTION.
RX PubMed=22012258; DOI=10.1038/nature10572;
RA Greer E.L., Maures T.J., Ucar D., Hauswirth A.G., Mancini E., Lim J.P.,
RA Benayoun B.A., Shi Y., Brunet A.;
RT "Transgenerational epigenetic inheritance of longevity in Caenorhabditis
RT elegans.";
RL Nature 479:365-371(2011).
RN [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=22212395; DOI=10.1111/j.1474-9726.2011.00785.x;
RA Ni Z., Ebata A., Alipanahiramandi E., Lee S.S.;
RT "Two SET domain containing genes link epigenetic changes and aging in
RT Caenorhabditis elegans.";
RL Aging Cell 11:315-325(2012).
CC -!- FUNCTION: Histone demethylase that specifically demethylates 'Lys-4' of
CC histone H3, thereby playing a central role in histone code
CC (PubMed:17320161). Does not demethylate histone H3 'Lys-9', H3 'Lys-
CC 27', H3 'Lys-36', H3 'Lys-79' or H4 'Lys-20' (PubMed:17320161).
CC Demethylates trimethylated and dimethylated but not monomethylated H3
CC 'Lys-4' (PubMed:17320161). Required for normal longevity of the soma in
CC a germline-dependent manner (PubMed:20555324, PubMed:22212395).
CC Implicated in the epigenetic inheritance of lifespan over several
CC generations (PubMed:22012258). Involved in larval development and vulva
CC formation (PubMed:17320161). {ECO:0000269|PubMed:17320161,
CC ECO:0000269|PubMed:20555324, ECO:0000269|PubMed:22012258,
CC ECO:0000269|PubMed:22212395}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3 2-oxoglutarate + N(6),N(6),N(6)-trimethyl-L-lysyl(4)-
CC [histone H3] + 3 O2 = 3 CO2 + 3 formaldehyde + L-lysyl(4)-[histone
CC H3] + 3 succinate; Xref=Rhea:RHEA:60208, Rhea:RHEA-COMP:15537,
CC Rhea:RHEA-COMP:15547, ChEBI:CHEBI:15379, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:16810, ChEBI:CHEBI:16842, ChEBI:CHEBI:29969,
CC ChEBI:CHEBI:30031, ChEBI:CHEBI:61961; EC=1.14.11.67;
CC Evidence={ECO:0000269|PubMed:17320161};
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:PRU00355,
CC ECO:0000255|PROSITE-ProRule:PRU00537, ECO:0000269|PubMed:20555324}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown decreases lifespan in
CC wild type worms with an intact germline (PubMed:20555324). Results in
CC extended lifespan when egg production is inhibited by the addition of
CC floxuridine (FUDR) or in a glp-1 mutant background which lacks a
CC germline (PubMed:22212395, PubMed:20555324).
CC {ECO:0000269|PubMed:20555324, ECO:0000269|PubMed:22212395}.
CC -!- SIMILARITY: Belongs to the JARID1 histone demethylase family.
CC {ECO:0000305}.
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DR EMBL; Z69385; CAA93426.2; -; Genomic_DNA.
DR PIR; T27924; T27924.
DR RefSeq; NP_502032.2; NM_069631.6.
DR AlphaFoldDB; Q23541; -.
DR SMR; Q23541; -.
DR BioGRID; 43086; 31.
DR IntAct; Q23541; 26.
DR STRING; 6239.ZK593.4; -.
DR EPD; Q23541; -.
DR PaxDb; Q23541; -.
DR PeptideAtlas; Q23541; -.
DR PRIDE; Q23541; -.
DR EnsemblMetazoa; ZK593.4a.1; ZK593.4a.1; WBGene00004319.
DR GeneID; 177985; -.
DR KEGG; cel:CELE_ZK593.4; -.
DR UCSC; ZK593.4; c. elegans.
DR CTD; 177985; -.
DR WormBase; ZK593.4a; CE35704; WBGene00004319; rbr-2.
DR eggNOG; KOG1246; Eukaryota.
DR GeneTree; ENSGT00940000168915; -.
DR InParanoid; Q23541; -.
DR OMA; DGISYME; -.
DR OrthoDB; 664180at2759; -.
DR PhylomeDB; Q23541; -.
DR BRENDA; 1.14.11.67; 1045.
DR Reactome; R-CEL-3214842; HDMs demethylate histones.
DR SignaLink; Q23541; -.
DR PRO; PR:Q23541; -.
DR Proteomes; UP000001940; Chromosome IV.
DR Bgee; WBGene00004319; Expressed in germ line (C elegans) and 4 other tissues.
DR ExpressionAtlas; Q23541; baseline and differential.
DR GO; GO:0005634; C:nucleus; IDA:WormBase.
DR GO; GO:0003677; F:DNA binding; IEA:InterPro.
DR GO; GO:0032452; F:histone demethylase activity; IBA:GO_Central.
DR GO; GO:0034647; F:histone H3-tri/di/monomethyl-lysine-4 demethylase activity; IDA:WormBase.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006338; P:chromatin remodeling; IBA:GO_Central.
DR GO; GO:0008340; P:determination of adult lifespan; IMP:WormBase.
DR GO; GO:0034720; P:histone H3-K4 demethylation; IDA:WormBase.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; ISS:WormBase.
DR GO; GO:0040028; P:regulation of vulval development; IMP:WormBase.
DR Gene3D; 1.10.150.60; -; 1.
DR Gene3D; 3.30.40.10; -; 3.
DR InterPro; IPR001606; ARID_dom.
DR InterPro; IPR036431; ARID_dom_sf.
DR InterPro; IPR003347; JmjC_dom.
DR InterPro; IPR003349; JmjN.
DR InterPro; IPR013637; Lys_sp_deMease-like_dom.
DR InterPro; IPR004198; Znf_C5HC2.
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 Pfam; PF01388; ARID; 1.
DR Pfam; PF02373; JmjC; 1.
DR Pfam; PF02375; JmjN; 1.
DR Pfam; PF00628; PHD; 1.
DR Pfam; PF08429; PLU-1; 1.
DR Pfam; PF02928; zf-C5HC2; 1.
DR SMART; SM00501; BRIGHT; 1.
DR SMART; SM00558; JmjC; 1.
DR SMART; SM00545; JmjN; 1.
DR SMART; SM00249; PHD; 3.
DR SUPFAM; SSF46774; SSF46774; 1.
DR SUPFAM; SSF57903; SSF57903; 3.
DR PROSITE; PS51011; ARID; 1.
DR PROSITE; PS51184; JMJC; 1.
DR PROSITE; PS51183; JMJN; 1.
DR PROSITE; PS01359; ZF_PHD_1; 1.
DR PROSITE; PS50016; ZF_PHD_2; 1.
PE 1: Evidence at protein level;
KW Chromatin regulator; Coiled coil; Dioxygenase; Iron; Metal-binding;
KW Nucleus; Oxidoreductase; Reference proteome; Repeat; Transcription;
KW Transcription regulation; Zinc; Zinc-finger.
FT CHAIN 1..1477
FT /note="Lysine-specific demethylase rbr-2"
FT /id="PRO_0000292420"
FT DOMAIN 56..97
FT /note="JmjN"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00537"
FT DOMAIN 121..218
FT /note="ARID"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00355"
FT DOMAIN 468..634
FT /note="JmjC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00538"
FT ZN_FING 319..371
FT /note="PHD-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00146"
FT ZN_FING 1203..1257
FT /note="PHD-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00146"
FT ZN_FING 1411..1466
FT /note="PHD-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00146"
FT REGION 1..37
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 222..314
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1375..1404
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 874..926
FT /evidence="ECO:0000255"
FT COMPBIAS 1..36
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 222..262
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 514
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00538"
FT BINDING 517
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00538"
FT BINDING 602
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00538"
SQ SEQUENCE 1477 AA; 170791 MW; E2539E727C6E72D7 CRC64;
MRARRQENSI STPSAPSTST SPRKKASIGN SRSKNHGSKM EMYDQFYKKF VRPPMAPIYY
PTEEEFSDPI EYVAKIRHEA EKFGVVKIVP PANFKPPFAI DKEAFTFRPR TQKLNEVEAI
VKEKHTFIDR LINFNRYSGL TFEFPVDRDG NIVDLYRLHR IVQNFGGCEE VNEDEKWRDV
AREYLPKEQM ARGVPSAFIN LIRSHYNLHI EPFNRNLKEK AMKNDDESDD EMEELKHKYQ
HHHGTMRTEI EVPNDKTTEG GEDECPVSMQ SGRRRSKNKK ASSSRKTLGT SSKKNSTRGR
KNKKKAEGDD DDDEDPMDQV FCVACNEGKD EDLLLLCDID GCNNGRHTYC CDPVLDEVPE
GEWRCPKCIE SEDAKIGLDW GFYDADTEYN LNSFTEFANK WKCDYFGVKD VSQVSCDAVE
RSFWKNVISH ENPVSVKYGA DLITSRVGSG FPRKEDKHTG PDLKLKQQYA SHAWNLNNMP
VLRESVLSHF NTGISGMMVP WVYVGMCFST FCWHTEDHWT YSVNYNHFGE RKIWYGVGGE
DAEKFEDALK KIAPGLTGRQ RDLFHHMTTA ANPHLLRSLG VPIHSVHQNA GEFVITFPRA
YHAGFNEGLN FAEAVNFAPI DWLSKGRECV ESYSNVRRYL VFSHDELLFK MVEAMDKLGI
SMSLATHEEL IRIYEKQKML RELLARLGVS NRQMQQVMFE KIPDEQRSCR FCKTTLFMCA
LVCNKHKKMT CVEHHDHLCN SCTTKDYRYQ YRFELDQLNN MCDELGKRTV NYNGWKEESD
EMLEEEGKPK LERIEEFIDS AKQNKYPQTD QVHKLITIRH TAKSAIEKAN QLLFKKVRTR
TKTRCQRADT RTDTEGVRSL IEQMQAMDCN LTVIIDKLEK WMEQVEMWRN RAKDAIYREQ
EYSKEEIEKI IEEGDEYDIK LEEIDELRKV IQMKDWSDRA RKVTTWKATP DMEKDIDFEY
KLRYASSDIL SLIRDSPRNP TDGTSKLVFE LQQMLRDANT LEVIANNFCE NPALDQLQSI
WQSLRETDWF YEKYINMVRY EIIHVAKIKS MIDAAIPVLS EFDLKTQLQK IVNVEITLSK
AAEISKAFET SKCLNGSEEH LGILDMISTM NAFTQRIAIL FKPNNAYHNL FEILSERDDL
TPLAEGQTIP LYFQGGAVHP SDEWHQMKEF ESLDQIVHHQ SSLREMQMRI FEKVKQANSA
RGLEACSCLG FNKSDDSEST LTCIMCDSEF HVRCCEWSPF LEKLPEGCFL CVRCLRGQRP
VIDDVTTALN GTPSGCLETH LVRNLIQKTR GITQNLMEAA NKRKSGESSD DICKIALFDW
LSCEILNPNG LPKARELISE FYMEYLQKQS SAALELKNRP VRSKPSVSLF DPKITAKRKR
PSVSHKETSK KSRKRQSQAS PSEYYEDESE FKSCQARACL KPYGDSVNWV MCEAGCKNWF
HVICLGFTLR EINDMHEYRC SSCLDHADSP TSSVSTD
