ID G3TYK0_LOXAF Unreviewed; 814 AA.
AC G3TYK0;
DT 16-NOV-2011, integrated into UniProtKB/TrEMBL.
DT 16-NOV-2011, sequence version 1.
DT 24-JAN-2024, entry version 63.
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:ENSLAFP00000020658.1};
OS Loxodonta africana (African elephant).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Afrotheria; Proboscidea; Elephantidae; Loxodonta.
OX NCBI_TaxID=9785 {ECO:0000313|Ensembl:ENSLAFP00000020658.1, ECO:0000313|Proteomes:UP000007646};
RN [1] {ECO:0000313|Ensembl:ENSLAFP00000020658.1, ECO:0000313|Proteomes:UP000007646}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Isolate ISIS603380 {ECO:0000313|Ensembl:ENSLAFP00000020658.1,
RC ECO:0000313|Proteomes:UP000007646};
RA Di Palma F., Heiman D., Young S., Johnson J., Lander E.S., Lindblad-Toh K.;
RT "The Genome Sequence of Loxodonta africana (African elephant).";
RL Submitted (JUN-2009) to the EMBL/GenBank/DDBJ databases.
RN [2] {ECO:0000313|Ensembl:ENSLAFP00000020658.1}
RP IDENTIFICATION.
RC STRAIN=Isolate ISIS603380 {ECO:0000313|Ensembl:ENSLAFP00000020658.1};
RG Ensembl;
RL Submitted (JUL-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|PIRNR:PIRNR038051,
CC ECO:0000256|PIRSR:PIRSR038051-1};
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000256|ARBA:ARBA00004123,
CC 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|PIRNR:PIRNR038051}.
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DR AlphaFoldDB; G3TYK0; -.
DR Ensembl; ENSLAFT00000036581.1; ENSLAFP00000020658.1; ENSLAFG00000007981.3.
DR GeneTree; ENSGT00940000157193; -.
DR HOGENOM; CLU_004498_5_1_1; -.
DR Proteomes; UP000007646; Unassembled WGS sequence.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0140682; F:FAD-dependent H3K4me/H3K4me3 demethylase activity; IEA:RHEA.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IEA:UniProtKB-UniRule.
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|ARBA:ARBA00023002,
KW ECO:0000256|PIRNR:PIRNR038051};
KW Reference proteome {ECO:0000313|Proteomes:UP000007646};
KW Repressor {ECO:0000256|PIRNR:PIRNR038051};
KW Transcription {ECO:0000256|PIRNR:PIRNR038051};
KW Transcription regulation {ECO:0000256|PIRNR:PIRNR038051}.
FT DOMAIN 136..235
FT /note="SWIRM"
FT /evidence="ECO:0000259|PROSITE:PS50934"
FT REGION 1..138
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 396..430
FT /evidence="ECO:0000256|SAM:Coils"
FT COMPBIAS 67..113
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 243..271
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000256|PIRSR:PIRSR038051-1"
FT BINDING 272
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000256|PIRSR:PIRSR038051-1"
FT BINDING 278
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000256|PIRSR:PIRSR038051-1"
FT BINDING 294..295
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000256|PIRSR:PIRSR038051-1"
FT BINDING 763
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000256|PIRSR:PIRSR038051-1"
FT BINDING 772..773
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000256|PIRSR:PIRSR038051-1"
SQ SEQUENCE 814 AA; 89573 MW; C28BB0EA4BA07EB5 CRC64;
TGSAALSAVG GQATRDVVGT EAGSGAAGGT ENGSEGERTP RKKEPQAGPT VVPGSATPME
TGIAETPEGR RTSRRKRAKV EYREMDESLA NLSEDEYYSE EERNAKAEKE KKLPPPPPQA
PPEEENESEP EEPSGVEGAA FQSRLPHDRM TSQEAACFPD IISGPQQTQK VFLFIRNRTL
QLWLDNPKIQ LTFEAALQQL EAPCNGDTVL VHRVHSYLER HGLINFGIYK RIKPLPTKKT
GKVIIIGSGV SGLAAARQLQ SFGMDVTLLE ARDRVGGRVA TFRKGNYVAD LGAMVVTGLG
GNPMAVVSKQ VNMELAKIKQ KCPLYEANGQ AVPKEKDEMV EQEFNRLLEA TSYLSHQLDF
NVLNNKPVSL GQALEVVIQL QEKHVKDEQI EHWKKIVKTQ EELKELLNKM VNLKEKIKEL
HQQYKEASEV KPPRDITAEF LVKSKHRDLT ALCKEYDELA ETQGKLEEKL QELEANPPSD
VYLSSRDRQI LDWHFANLEF ANATPLSTLS LKHWDQDDDF EFTGSHLTVR NGYSCVPVAL
AEGLDIKLNT AVRQVRYTAS GCEVIAVNTR STSQTFIYKC DAVLCTLPLG VLKQQPPAVQ
FVPPLPEWKT SAVQRMGFGN LNKVVLCFDR VFWDPSVNLF GHVGSTTASR GELFLFWNLY
KAPILLALVA GEAAGIMENI SDDVIVGRCL AILKGIFGSS AVPQPKETVV SRWRADPWAR
GSYSYVAAGS SGNDYDLMAQ PITPGPSIPG APQPIPRLFF AGEHTIRNYP ATVHGALLSG
LREAGRIADQ FLGAMYTLPR QATPGVPAQQ SPSM
//