LSDA_DROME
ID LSDA_DROME Reviewed; 890 AA.
AC Q9VW97; Q0E8C9;
DT 07-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=Possible lysine-specific histone demethylase 1;
DE EC=1.-.-.-;
GN Name=Su(var)3-3; Synonyms=Hdm, LSD1; ORFNames=CG17149;
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Embryo;
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [4]
RP FUNCTION, AND INTERACTION WITH COREST.
RX PubMed=15306652; DOI=10.1523/jneurosci.0238-04.2004;
RA Dallman J.E., Allopenna J., Bassett A., Travers A., Mandel G.;
RT "A conserved role but different partners for the transcriptional
RT corepressor CoREST in fly and mammalian nervous system formation.";
RL J. Neurosci. 24:7186-7193(2004).
RN [5]
RP FUNCTION, SUBUNIT, AND SUBCELLULAR LOCATION.
RX PubMed=17434130; DOI=10.1016/j.molcel.2007.02.025;
RA Rudolph T., Yonezawa M., Lein S., Heidrich K., Kubicek S., Schafer C.,
RA Phalke S., Walther M., Schmidt A., Jenuwein T., Reuter G.;
RT "Heterochromatin formation in Drosophila is initiated through active
RT removal of H3K4 methylation by the LSD1 homolog SU(VAR)3-3.";
RL Mol. Cell 26:103-115(2007).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-24; SER-27 AND SER-866, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Embryo;
RX PubMed=18327897; DOI=10.1021/pr700696a;
RA Zhai B., Villen J., Beausoleil S.A., Mintseris J., Gygi S.P.;
RT "Phosphoproteome analysis of Drosophila melanogaster embryos.";
RL J. Proteome Res. 7:1675-1682(2008).
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. Required for
CC heterochromatic gene silencing. Acts by oxidizing the substrate by FAD
CC to generate the corresponding imine that is subsequently hydrolyzed.
CC Demethylates both mono- and tri-methylated 'Lys-4' of histone H3. May
CC also demethylate 'Lys-9' of histone H3, Plays a role in the repression
CC of neuronal genes. {ECO:0000269|PubMed:15306652,
CC ECO:0000269|PubMed:17434130}.
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000250};
CC -!- SUBUNIT: Component of a complex that contains at least HDAC1/Rpd3,
CC CoRest and Su(var)3-3/Hdm. {ECO:0000269|PubMed:17434130}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:17434130}. Chromosome
CC {ECO:0000269|PubMed:17434130}. Note=In early cleavage, protein displays
CC a uniform nuclear distribution. At metaphase, protein is detected at
CC the chromosome periphery, and between the chromosomes during anaphase.
CC A rather uniform interphase chromatin association is detected until
CC syncytial blastoderm. When cellular blastoderm is formed (cycle 14),
CC protein is preferably associated with pericentric heterochromatin
CC situated at the apical pole of blastoderm nuclei. Later in development,
CC protein is only found over euchromatin. In the germline precursor pole
CC cells, protein remains uniformly distributed within the nucleus.
CC -!- SIMILARITY: Belongs to the flavin monoamine oxidase family.
CC {ECO:0000305}.
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DR EMBL; AE014296; AAF49052.1; -; Genomic_DNA.
DR EMBL; AY094837; AAM11190.1; -; mRNA.
DR RefSeq; NP_649194.1; NM_140937.3.
DR RefSeq; NP_730497.1; NM_168835.2.
DR AlphaFoldDB; Q9VW97; -.
DR SMR; Q9VW97; -.
DR BioGRID; 65482; 19.
DR IntAct; Q9VW97; 3.
DR STRING; 7227.FBpp0074594; -.
DR iPTMnet; Q9VW97; -.
DR PaxDb; Q9VW97; -.
DR EnsemblMetazoa; FBtr0074825; FBpp0074594; FBgn0260397.
DR EnsemblMetazoa; FBtr0074826; FBpp0074595; FBgn0260397.
DR GeneID; 40217; -.
DR KEGG; dme:Dmel_CG17149; -.
DR CTD; 40217; -.
DR FlyBase; FBgn0260397; Su(var)3-3.
DR VEuPathDB; VectorBase:FBgn0260397; -.
DR eggNOG; KOG0029; Eukaryota.
DR GeneTree; ENSGT00940000157193; -.
DR HOGENOM; CLU_004498_5_1_1; -.
DR InParanoid; Q9VW97; -.
DR OMA; SSRGEMF; -.
DR OrthoDB; 1034142at2759; -.
DR PhylomeDB; Q9VW97; -.
DR Reactome; R-DME-3214815; HDACs deacetylate histones.
DR Reactome; R-DME-5625886; Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3.
DR Reactome; R-DME-9018519; Estrogen-dependent gene expression.
DR Reactome; R-DME-983231; Factors involved in megakaryocyte development and platelet production.
DR SignaLink; Q9VW97; -.
DR BioGRID-ORCS; 40217; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 40217; -.
DR PRO; PR:Q9VW97; -.
DR Proteomes; UP000000803; Chromosome 3L.
DR Bgee; FBgn0260397; Expressed in egg cell and 23 other tissues.
DR ExpressionAtlas; Q9VW97; baseline and differential.
DR Genevisible; Q9VW97; DM.
DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0017053; C:transcription repressor complex; IPI:FlyBase.
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:FlyBase.
DR GO; GO:0032453; F:histone H3-methyl-lysine-4 demethylase activity; IMP:FlyBase.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0006325; P:chromatin organization; IMP:FlyBase.
DR GO; GO:0033696; P:heterochromatin boundary formation; IGI:FlyBase.
DR GO; GO:0070828; P:heterochromatin organization; IMP:FlyBase.
DR GO; GO:0034720; P:histone H3-K4 demethylation; IMP:UniProtKB.
DR GO; GO:0007474; P:imaginal disc-derived wing vein specification; IMP:FlyBase.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0048477; P:oogenesis; IMP:FlyBase.
DR GO; GO:0090309; P:positive regulation of DNA methylation-dependent heterochromatin assembly; IMP:FlyBase.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IBA:GO_Central.
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; Chromosome; Coiled coil; FAD; Flavoprotein; Nucleus;
KW Oxidoreductase; Phosphoprotein; Reference proteome; Repressor;
KW Transcription; Transcription regulation.
FT CHAIN 1..890
FT /note="Possible lysine-specific histone demethylase 1"
FT /id="PRO_0000226785"
FT DOMAIN 160..259
FT /note="SWIRM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00247"
FT REGION 1..164
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 860..890
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..17
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 52..81
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 82..142
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 861..890
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 267..295
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000255"
FT MOD_RES 24
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 27
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 866
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
SQ SEQUENCE 890 AA; 98389 MW; 47BB1CA7F7404827 CRC64;
MKPTQFGGSS SKMTEPIEYV TLISDDSDGE PTPKRNVNHP PSALSAPNPG QKQKHPDEDS
NDAPATSDER RTSRRNRPKV DYSNRPSGSG DTASNDKSGS ASMGPNNQQA ERRSQSQTRK
SEANATSSSV SGPSAGNSRP SQNGDSKDRD AGTPTVLSGQ EGAVFQSRLP FNKMTPNEEA
CFPDISRSGI LGHRVFLNIR NSLLHMWVDN PKIQLSFEIA LKNLPPPFDS EPSLVRRVHS
FLERHGFINF GIFKRLKPIP AKKLGKVIVI GAGISGLAVA HQLQQFGMDV IVLEARDRVG
GRISTFRKNS YIADVGAMVV TGVYGNPMTI LSKQIGMDLV PIQQTCPLYG PDGKPVPKEK
DDVIEREFNR LLESASYLSH RLDFNYAGDC PVSLGDALEW IISMQEMQVM HKRGQHMQEI
IATQTKIIEQ RRRLKTLRDT IGKLKNEHLA MINQRKPKGT DGDLKYCYQE FNIRNTQIKM
EETISTFHDL HAEEKQMLAK LHELEQNRPS DVYLSSRDRL ILDWHFANLE FANATRLNNL
SLKHWDQDDD FEFIGHHTTV RNGYSCVPVA LTENLDIRVN SAVKEIKYGT KGVEVVAENL
KTSNSQMTYK ADLVVCTLTL GVLKVAVAHK ESQQSNTVKF DPPLPDWKQQ AIKRLGFGNL
NKVVLCFDRI FWDPNANLFG HVGSTTASRG EMFLFWSISS SPVLLALVAG MAANLVESVT
DDIIIGRCMS VLKNIFGNTS VPQPKETVVT RWRSDPWARG SYSYVSVGSS GSDYDLLAAP
VIPPSSKDAE GLPRLFFAGE HTIRNYPATV HGAYLSGLRE AGRIADYYLG YPEGTPPDIG
YSVAEAANLV SVGNVVKLRD LSPNLSDSSP SSKKSEENSN SNTADSTELQ
