LSD1_CAEEL
ID LSD1_CAEEL Reviewed; 770 AA.
AC Q9XWP6;
DT 29-AUG-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=Probable lysine-specific histone demethylase 1;
DE EC=1.-.-.-;
DE AltName: Full=P110b homolog;
DE AltName: Full=Suppressor of presenilin 5;
GN Name=spr-5 {ECO:0000312|WormBase:Y40B1B.6};
GN ORFNames=Y40B1B.6 {ECO:0000312|WormBase:Y40B1B.6};
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 [MRNA], FUNCTION, DEVELOPMENTAL STAGE, INTERACTION WITH
RP SPR-1, AND DISRUPTION PHENOTYPE.
RX PubMed=12411496; DOI=10.1093/emboj/cdf561;
RA Eimer S., Lakowski B., Donhauser R., Baumeister R.;
RT "Loss of spr-5 bypasses the requirement for the C.elegans presenilin sel-12
RT by derepressing hop-1.";
RL EMBO J. 21:5787-5796(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND MUTAGENESIS OF ALA-665.
RX PubMed=12381669; DOI=10.1101/gad.1022402;
RA Jarriault S., Greenwald I.;
RT "Suppressors of the egg-laying defective phenotype of sel-12 presenilin
RT mutants implicate the CoREST corepressor complex in LIN-12/Notch signaling
RT in C. elegans.";
RL Genes Dev. 16:2713-2728(2002).
RN [3]
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 [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=24685137; DOI=10.1016/j.celrep.2014.02.044;
RA Greer E.L., Beese-Sims S.E., Brookes E., Spadafora R., Zhu Y.,
RA Rothbart S.B., Aristizabal-Corrales D., Chen S., Badeaux A.I., Jin Q.,
RA Wang W., Strahl B.D., Colaiacovo M.P., Shi Y.;
RT "A histone methylation network regulates transgenerational epigenetic
RT memory in C. elegans.";
RL Cell Rep. 7:113-126(2014).
RN [5] {ECO:0000305}
RP INTERACTION WITH HPL-1.
RX PubMed=26476455; DOI=10.1093/nar/gkv1063;
RA Vandamme J., Sidoli S., Mariani L., Friis C., Christensen J., Helin K.,
RA Jensen O.N., Salcini A.E.;
RT "H3K23me2 is a new heterochromatic mark in Caenorhabditis elegans.";
RL Nucleic Acids Res. 43:9694-9710(2015).
CC -!- FUNCTION: Probable histone demethylase that specifically demethylates
CC 'Lys-4' of histone H3, a specific tag for epigenetic transcriptional
CC activation, thereby acting as a corepressor. Acts by oxidizing the
CC substrate by FAD to generate the corresponding imine that is
CC subsequently hydrolyzed. Demethylates both mono- and di-methylated
CC 'Lys-4' of histone H3 (By similarity). Participates in the
CC transcriptional repression of the presenilin protein hop-1
CC (PubMed:12411496). May act via the formation of a multiprotein complex
CC that remodel or modify the chromatin (PubMed:12381669). Together with
CC met-2, set-17 and set-26, required for transgenerational fertility
CC (PubMed:24685137). {ECO:0000250|UniProtKB:O60341,
CC ECO:0000269|PubMed:12381669, ECO:0000269|PubMed:12411496,
CC ECO:0000269|PubMed:24685137}.
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000250};
CC -!- SUBUNIT: Probably part of a large repressor complex (PubMed:12411496).
CC Interacts with CoREST protein spr-1 (PubMed:12411496). Interacts with
CC chromobox protein homolog hpl-1 (PubMed:26476455).
CC {ECO:0000269|PubMed:12411496, ECO:0000269|PubMed:26476455,
CC ECO:0000303|PubMed:12411496}.
CC -!- INTERACTION:
CC Q9XWP6; Q9XVK6: wve-1; NbExp=2; IntAct=EBI-312097, EBI-312105;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC -!- DEVELOPMENTAL STAGE: Expressed throughout the development. Expressed in
CC embryos, L1, L2, L3 and L4 larval stages and in adults.
CC {ECO:0000269|PubMed:12411496}.
CC -!- DISRUPTION PHENOTYPE: Progressive loss of fertility and accumulation of
CC histone H3 'Lys-4' dimethylation (H3K4me2) over generations
CC (PubMed:24685137). Suppression of sel-12 mutant phenotypes, possibly by
CC up-regulating hop-1 expression (PubMed:12411496).
CC {ECO:0000269|PubMed:12411496, ECO:0000269|PubMed:24685137}.
CC -!- SIMILARITY: Belongs to the flavin monoamine oxidase family.
CC {ECO:0000305}.
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DR EMBL; AY152852; AAN62580.1; -; mRNA.
DR EMBL; BX284601; CAA21604.1; -; Genomic_DNA.
DR PIR; T26783; T26783.
DR RefSeq; NP_493366.1; NM_060965.3.
DR AlphaFoldDB; Q9XWP6; -.
DR SMR; Q9XWP6; -.
DR BioGRID; 38609; 11.
DR DIP; DIP-24825N; -.
DR IntAct; Q9XWP6; 3.
DR STRING; 6239.Y40B1B.6; -.
DR EPD; Q9XWP6; -.
DR PaxDb; Q9XWP6; -.
DR PeptideAtlas; Q9XWP6; -.
DR EnsemblMetazoa; Y40B1B.6.1; Y40B1B.6.1; WBGene00005010.
DR EnsemblMetazoa; Y40B1B.6.2; Y40B1B.6.2; WBGene00005010.
DR GeneID; 173214; -.
DR KEGG; cel:CELE_Y40B1B.6; -.
DR UCSC; Y40B1B.6.1; c. elegans.
DR CTD; 173214; -.
DR WormBase; Y40B1B.6; CE20240; WBGene00005010; spr-5.
DR eggNOG; KOG0029; Eukaryota.
DR GeneTree; ENSGT00940000172632; -.
DR HOGENOM; CLU_004498_5_1_1; -.
DR InParanoid; Q9XWP6; -.
DR OMA; SSRGEMF; -.
DR OrthoDB; 1034142at2759; -.
DR PhylomeDB; Q9XWP6; -.
DR BRENDA; 1.14.99.66; 1045.
DR SignaLink; Q9XWP6; -.
DR PRO; PR:Q9XWP6; -.
DR Proteomes; UP000001940; Chromosome I.
DR Bgee; WBGene00005010; Expressed in embryo and 4 other tissues.
DR GO; GO:0005737; C:cytoplasm; IDA:WormBase.
DR GO; GO:0005634; C:nucleus; IDA:WormBase.
DR GO; GO:0003682; F:chromatin binding; IBA:GO_Central.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IBA:GO_Central.
DR GO; GO:0140682; F:histone H3-di/monomethyl-lysine-4 FAD-dependent demethylase activity; IMP:WormBase.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0034720; P:histone H3-K4 demethylation; IMP:WormBase.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0040029; P:regulation of gene expression, epigenetic; IMP:WormBase.
DR Gene3D; 1.10.10.10; -; 1.
DR Gene3D; 3.50.50.60; -; 2.
DR InterPro; IPR002937; Amino_oxidase.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR InterPro; IPR017366; Hist_Lys-spec_deMease.
DR InterPro; IPR009057; Homeobox-like_sf.
DR InterPro; IPR007526; SWIRM.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR Pfam; PF01593; Amino_oxidase; 1.
DR Pfam; PF04433; SWIRM; 1.
DR PIRSF; PIRSF038051; Histone_Lys-demethylase; 1.
DR SUPFAM; SSF46689; SSF46689; 1.
DR SUPFAM; SSF51905; SSF51905; 1.
DR PROSITE; PS50934; SWIRM; 1.
PE 1: Evidence at protein level;
KW Chromatin regulator; FAD; Flavoprotein; Nucleus; Oxidoreductase;
KW Reference proteome; Repressor; Transcription; Transcription regulation.
FT CHAIN 1..770
FT /note="Probable lysine-specific histone demethylase 1"
FT /id="PRO_0000099883"
FT DOMAIN 28..126
FT /note="SWIRM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00247"
FT REGION 1..21
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 718..739
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 137..165
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000255"
FT MUTAGEN 665
FT /note="A->T: In ar197; results in suppression of Sel-12
FT mutant phenotypes."
FT /evidence="ECO:0000269|PubMed:12381669"
SQ SEQUENCE 770 AA; 86345 MW; A7FEB1427B7A2FE4 CRC64;
MSSDTGSEYL DEEIRGDELG PSIDDNALAA AASAARLPFD RPTDHELAFF PELWEHKTAV
EVFLLLRNST LATWQYNPLK ECTALDVRNN VFPPFNSDLD LIQNIVHYLS RHGLINFGRY
VRSTKISRFL VRDRRSVIVI GAGAAGISAA TQLESFGFDV IVLEARNCIG GRIHSFKSKS
GEIMETGGDT LRKIEDSPMA TLLHQVNFEE HGVFDFTSVF VEGRPLNEEK IHLFLDHYKS
AHGALNYQAH QCEHRDDQGS FISRQQAYEN LLSMCERGTL IKYYNFCKSL ETVARAREHH
FNQMKQLRMT ALMAENQLKK MEEEGNLEQD PVLRRSLKRD IATSLEKFEE VADAFETADN
HWQRLNEHPQ AKQYMHPGSE FATFNFMLGF EEYLVGAQLE KVQFSCDSMQ NKENGVAARL
TEGIAELLTQ LSEKRKLDIR LKHRVLDIDY SGFEHVLLKV QRENGDIEEM KAAFVVSTLP
IGVLKKTIIA DERAPTFTPS LPDKKVEAIR NIGCGSVNKC ILEFDRVFWT ANGGRNQFVT
VSPNIKTRGS MNIWSSVPGS KVLCTYIVGE EAMLELPDDV IIQNAMINLQ KAFGNNCPRA
PISAHITRWH DDELAFGSGA FMSLRTETTS FDDVMEPLKT SDGMSRVYFA GEHTCSSYTS
TIQGAWMSGA RAAADISNDH IGIGFVDISG TRGQRGDEEE ELLIEVDIDG KIPEKDENEA
VADIPNAPNA PNAQKPEEIP KIAEEIELVA EAEKAEKAEV QLEPLVPTVE
