ID F6ZUK1_XENTR Unreviewed; 833 AA.
AC F6ZUK1;
DT 27-JUL-2011, integrated into UniProtKB/TrEMBL.
DT 02-JUN-2021, sequence version 4.
DT 27-MAR-2024, entry version 80.
DE RecName: Full=Lysine-specific histone demethylase {ECO:0000256|PIRNR:PIRNR038051};
DE EC=1.14.99.66 {ECO:0000256|PIRNR:PIRNR038051};
GN Name=kdm1a {ECO:0000313|Ensembl:ENSXETP00000007985,
GN ECO:0000313|RefSeq:XP_002936640.1,
GN ECO:0000313|Xenbase:XB-GENE-5816927};
OS Xenopus tropicalis (Western clawed frog) (Silurana tropicalis).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Silurana.
OX NCBI_TaxID=8364 {ECO:0000313|Ensembl:ENSXETP00000007985};
RN [1] {ECO:0000313|Ensembl:ENSXETP00000007985}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Nigerian {ECO:0000313|Ensembl:ENSXETP00000007985};
RX PubMed=20431018; DOI=10.1126/science.1183670;
RA Hellsten U., Harland R.M., Gilchrist M.J., Hendrix D., Jurka J.,
RA Kapitonov V., Ovcharenko I., Putnam N.H., Shu S., Taher L., Blitz I.L.,
RA Blumberg B., Dichmann D.S., Dubchak I., Amaya E., Detter J.C., Fletcher R.,
RA Gerhard D.S., Goodstein D., Graves T., Grigoriev I.V., Grimwood J.,
RA Kawashima T., Lindquist E., Lucas S.M., Mead P.E., Mitros T., Ogino H.,
RA Ohta Y., Poliakov A.V., Pollet N., Robert J., Salamov A., Sater A.K.,
RA Schmutz J., Terry A., Vize P.D., Warren W.C., Wells D., Wills A.,
RA Wilson R.K., Zimmerman L.B., Zorn A.M., Grainger R., Grammer T.,
RA Khokha M.K., Richardson P.M., Rokhsar D.S.;
RT "The genome of the Western clawed frog Xenopus tropicalis.";
RL Science 328:633-636(2010).
RN [2] {ECO:0000313|Ensembl:ENSXETP00000007985}
RP IDENTIFICATION.
RG Ensembl;
RL Submitted (JUN-2011) to UniProtKB.
RN [3] {ECO:0000313|RefSeq:XP_002936640.1}
RP IDENTIFICATION.
RC STRAIN=Nigerian {ECO:0000313|RefSeq:XP_002936640.1};
RC TISSUE=Liver and blood {ECO:0000313|RefSeq:XP_002936640.1};
RG RefSeq;
RL Submitted (NOV-2023) to UniProtKB.
CC -!- FUNCTION: Histone demethylase that can demethylate both 'Lys-4'
CC (H3K4me) and 'Lys-9' (H3K9me) of histone H3, thereby acting as a
CC coactivator or a corepressor, depending on the context. Acts by
CC oxidizing the substrate by FAD to generate the corresponding imine that
CC is subsequently hydrolyzed. Acts as a corepressor by mediating
CC demethylation of H3K4me, a specific tag for epigenetic transcriptional
CC activation. Demethylates both mono- (H3K4me1) and di-methylated
CC (H3K4me2) H3K4me. May play a role in the repression of neuronal genes.
CC Alone, it is unable to demethylate H3K4me on nucleosomes and requires
CC the presence of RCOR1/CoREST to achieve such activity.
CC {ECO:0000256|PIRNR:PIRNR038051}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 A + 2 H2O + N(6),N(6)-dimethyl-L-lysyl(4)-[histone H3] = 2
CC AH2 + 2 formaldehyde + L-lysyl(4)-[histone H3]; Xref=Rhea:RHEA:60244,
CC Rhea:RHEA-COMP:15540, Rhea:RHEA-COMP:15547, ChEBI:CHEBI:13193,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:16842, ChEBI:CHEBI:17499,
CC ChEBI:CHEBI:29969, ChEBI:CHEBI:61976; EC=1.14.99.66;
CC Evidence={ECO:0000256|PIRNR:PIRNR038051};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000256|ARBA:ARBA00001974,
CC ECO:0000256|PIRNR:PIRNR038051, ECO:0000256|PIRSR:PIRSR038051-1};
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000256|PIRNR:PIRNR038051}.
CC -!- DOMAIN: The SWIRM domain may act as an anchor site for a histone tail.
CC {ECO:0000256|PIRNR:PIRNR038051}.
CC -!- SIMILARITY: Belongs to the flavin monoamine oxidase family.
CC {ECO:0000256|ARBA:ARBA00005995, ECO:0000256|PIRNR:PIRNR038051}.
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DR RefSeq; XP_002936640.1; XM_002936594.5.
DR Ensembl; ENSXETT00000007985; ENSXETP00000007985; ENSXETG00000003698.
DR GeneID; 100216250; -.
DR KEGG; xtr:100216250; -.
DR AGR; Xenbase:XB-GENE-5816927; -.
DR AGR; Xenbase:XB-GENE-5839769; -.
DR CTD; 23028; -.
DR Xenbase; XB-GENE-5816927; kdm1a.
DR eggNOG; KOG0029; Eukaryota.
DR eggNOG; KOG0685; Eukaryota.
DR HOGENOM; CLU_004498_5_1_1; -.
DR OMA; SSRGEMF; -.
DR OrthoDB; 2911539at2759; -.
DR TreeFam; TF312972; -.
DR Reactome; R-XTR-3214815; HDACs deacetylate histones.
DR Reactome; R-XTR-3214842; HDMs demethylate histones.
DR Reactome; R-XTR-5625886; Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3.
DR Reactome; R-XTR-9018519; Estrogen-dependent gene expression.
DR Reactome; R-XTR-983231; Factors involved in megakaryocyte development and platelet production.
DR Proteomes; UP000008143; Chromosome 2.
DR Bgee; ENSXETG00000003698; Expressed in 2-cell stage embryo and 12 other cell types or tissues.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0140682; F:FAD-dependent H3K4me/H3K4me3 demethylase activity; IEA:UniProt.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IEA:UniProtKB-UniRule.
DR GO; GO:0010558; P:negative regulation of macromolecule biosynthetic process; IEA:UniProt.
DR GO; GO:0006355; P:regulation of DNA-templated transcription; IEA:InterPro.
DR Gene3D; 3.90.660.10; -; 1.
DR Gene3D; 1.10.287.80; ATP synthase, gamma subunit, helix hairpin domain; 1.
DR Gene3D; 3.50.50.60; FAD/NAD(P)-binding domain; 2.
DR Gene3D; 1.10.10.10; Winged helix-like DNA-binding domain superfamily/Winged helix DNA-binding domain; 1.
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 PANTHER; PTHR10742; FLAVIN MONOAMINE OXIDASE; 1.
DR PANTHER; PTHR10742:SF386; LYSINE-SPECIFIC HISTONE DEMETHYLASE 1A; 1.
DR Pfam; PF01593; Amino_oxidase; 1.
DR Pfam; PF04433; SWIRM; 1.
DR PIRSF; PIRSF038051; Histone_Lys-demethylase; 1.
DR SUPFAM; SSF54373; FAD-linked reductases, C-terminal domain; 1.
DR SUPFAM; SSF51905; FAD/NAD(P)-binding domain; 1.
DR SUPFAM; SSF46689; Homeodomain-like; 1.
DR PROSITE; PS50934; SWIRM; 1.
PE 3: Inferred from homology;
KW Chromatin regulator {ECO:0000256|PIRNR:PIRNR038051};
KW Coiled coil {ECO:0000256|SAM:Coils};
KW FAD {ECO:0000256|ARBA:ARBA00022827, ECO:0000256|PIRNR:PIRNR038051};
KW Flavoprotein {ECO:0000256|ARBA:ARBA00022630,
KW ECO:0000256|PIRNR:PIRNR038051}; Nucleus {ECO:0000256|PIRNR:PIRNR038051};
KW Oxidoreductase {ECO:0000256|PIRNR:PIRNR038051};
KW Reference proteome {ECO:0000313|Proteomes:UP000008143};
KW Repressor {ECO:0000256|PIRNR:PIRNR038051};
KW Transcription {ECO:0000256|PIRNR:PIRNR038051};
KW Transcription regulation {ECO:0000256|PIRNR:PIRNR038051}.
FT DOMAIN 158..257
FT /note="SWIRM"
FT /evidence="ECO:0000259|PROSITE:PS50934"
FT REGION 1..160
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 418..498
FT /evidence="ECO:0000256|SAM:Coils"
FT COMPBIAS 1..46
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 89..135
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 265..293
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000256|PIRSR:PIRSR038051-1"
FT BINDING 294
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000256|PIRSR:PIRSR038051-1"
FT BINDING 300
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000256|PIRSR:PIRSR038051-1"
FT BINDING 316..317
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000256|PIRSR:PIRSR038051-1"
FT BINDING 785
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000256|PIRSR:PIRSR038051-1"
FT BINDING 794..795
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000256|PIRSR:PIRSR038051-1"
SQ SEQUENCE 833 AA; 91555 MW; 8E94373C4B4A0329 CRC64;
MLTTKKSESS GGGDNGSDPQ PPASSSSSSS SSSSSSSSSS SGIMASPDTA AGLERTPRKK
ERASPGAEHG ASTAPGIMAG AEGGQPETPE GRRTSRRKRA KVEYREMDES LANLSEDEYY
SEEERNARAE KEKKVPPPPP QAPPEEENDS EPEEPSGVEG AAFQSRLPHD RMTSQEAACF
PDIISGPQQT QKVFLYIRNR TLQSWLDNPK VQLTFENTLQ QLEAPYNSDS VLVHRIHCYL
ERHGLINFGV YKRLKPLPTK KTGKVIIIGS GVSGLAAARQ LQSFGMDVTV LEARDRVGGR
VATFRKGNYV ADLGAMVVTG LGGNPMAVIS KQVNMELAKI KQKCPLYEAN GQGVPKEKDE
MVEQEFNRLL EATSYLSHQL DFNILNNKPV SLGQALEVVI QLQEKHVKDE QIEHWKKIVK
TQDELKELLN KMVNVKEKIK ELHQQYKEAS EVKPPRDITA EFLVKSKHRD LTALCKEYDQ
LAETQVKLEE KLQELEANPP SDVYLSSRDR QILDWHFANL EFANATPLST LSLKHWDQDD
DFEFTGSHLT VRNGYSCVPV ALAEGLDIKL NTAVRQVRYT ASGCEVIAVN TRSTSQTFIY
KCDAVLCTLP LGVLKQQPPA VQFVPPLPEW KTSAVQRMGF GNLNKVVLCF DRVFWDSSVN
LFGHVGSTTA SRGELFLFWN LYKAPILLAL VAGEAAGIME NISDDVIVGR CLAILKGIFG
SSAVPQPKET VVSRWRADPW ARGSYSYVAA GSSGNDYDLM AQPITPGPAI PGAPQPIPRL
FFAGEHTIRN YPATVHGALL SGLREAGRIA DQFLGVMYNL PRQATPGVPA PTL
//
