ID G3S4L3_GORGO Unreviewed; 852 AA.
AC G3S4L3;
DT 16-NOV-2011, integrated into UniProtKB/TrEMBL.
DT 28-FEB-2018, sequence version 2.
DT 27-MAR-2024, entry version 72.
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:ENSGGOP00000023016.2};
OS Gorilla gorilla gorilla (Western lowland gorilla).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Gorilla.
OX NCBI_TaxID=9595 {ECO:0000313|Ensembl:ENSGGOP00000023016.2, ECO:0000313|Proteomes:UP000001519};
RN [1] {ECO:0000313|Ensembl:ENSGGOP00000023016.2, ECO:0000313|Proteomes:UP000001519}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Scally A.;
RT "Insights into the evolution of the great apes provided by the gorilla
RT genome.";
RL Submitted (MAY-2011) to the EMBL/GenBank/DDBJ databases.
RN [2] {ECO:0000313|Ensembl:ENSGGOP00000023016.2, ECO:0000313|Proteomes:UP000001519}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=22398555; DOI=10.1038/nature10842;
RA Scally A., Dutheil J.Y., Hillier L.W., Jordan G.E., Goodhead I.,
RA Herrero J., Hobolth A., Lappalainen T., Mailund T., Marques-Bonet T.,
RA McCarthy S., Montgomery S.H., Schwalie P.C., Tang Y.A., Ward M.C., Xue Y.,
RA Yngvadottir B., Alkan C., Andersen L.N., Ayub Q., Ball E.V., Beal K.,
RA Bradley B.J., Chen Y., Clee C.M., Fitzgerald S., Graves T.A., Gu Y.,
RA Heath P., Heger A., Karakoc E., Kolb-Kokocinski A., Laird G.K., Lunter G.,
RA Meader S., Mort M., Mullikin J.C., Munch K., O'Connor T.D., Phillips A.D.,
RA Prado-Martinez J., Rogers A.S., Sajjadian S., Schmidt D., Shaw K.,
RA Simpson J.T., Stenson P.D., Turner D.J., Vigilant L., Vilella A.J.,
RA Whitener W., Zhu B., Cooper D.N., de Jong P., Dermitzakis E.T.,
RA Eichler E.E., Flicek P., Goldman N., Mundy N.I., Ning Z., Odom D.T.,
RA Ponting C.P., Quail M.A., Ryder O.A., Searle S.M., Warren W.C.,
RA Wilson R.K., Schierup M.H., Rogers J., Tyler-Smith C., Durbin R.;
RT "Insights into hominid evolution from the gorilla genome sequence.";
RL Nature 483:169-175(2012).
RN [3] {ECO:0000313|Ensembl:ENSGGOP00000023016.2}
RP IDENTIFICATION.
RG Ensembl;
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 EMBL; CABD030001594; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CABD030001595; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CABD030001596; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CABD030001597; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; XP_004024918.1; XM_004024869.2.
DR AlphaFoldDB; G3S4L3; -.
DR Ensembl; ENSGGOT00000024772.2; ENSGGOP00000023016.2; ENSGGOG00000003664.3.
DR GeneID; 101144258; -.
DR KEGG; ggo:101144258; -.
DR CTD; 23028; -.
DR GeneTree; ENSGT00940000157193; -.
DR OrthoDB; 5402444at2759; -.
DR Proteomes; UP000001519; Chromosome 1.
DR Bgee; ENSGGOG00000003664; Expressed in testis and 6 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:UP000001519};
KW Repressor {ECO:0000256|PIRNR:PIRNR038051};
KW Transcription {ECO:0000256|PIRNR:PIRNR038051};
KW Transcription regulation {ECO:0000256|PIRNR:PIRNR038051}.
FT DOMAIN 174..273
FT /note="SWIRM"
FT /evidence="ECO:0000259|PROSITE:PS50934"
FT REGION 1..176
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 434..468
FT /evidence="ECO:0000256|SAM:Coils"
FT COMPBIAS 105..151
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 281..309
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000256|PIRSR:PIRSR038051-1"
FT BINDING 310
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000256|PIRSR:PIRSR038051-1"
FT BINDING 316
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000256|PIRSR:PIRSR038051-1"
FT BINDING 332..333
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000256|PIRSR:PIRSR038051-1"
FT BINDING 801
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000256|PIRSR:PIRSR038051-1"
FT BINDING 810..811
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000256|PIRSR:PIRSR038051-1"
SQ SEQUENCE 852 AA; 92873 MW; 9A37E20CD54083D8 CRC64;
MLSGKKAAAA AAAAAAAAAG TEAGPGTAGG SENGSEVAAQ PAGLSGPAEV GPGAVGERTP
RKKEPPRASP PGGLAEPPGS AGPQAGPTVV PGSATPMETG IAETPEGRRT SRRKRAKVEY
REMDESLANL SEDEYYSEEE RNAKAEKEKK LPPPPPQAPP EEENESEPEE PSGVEGAAFQ
SRLPHDRMTS QEAACFPDII SGPQQTQKVF LFIRNRTLQL WLDNPKIQLT FEATLQQLEA
PYNSDTVLVH RVHSYLERHG LINFGIYKRI KPLPTKKTGK VIIIGSGVSG LAAARQLQSF
GMDVTLLEAR DRVGGRVATF RKGNYVADLG AMVVTGLGGN PMAVVSKQVN MELAKIKQKC
PLYEANGQAV PKEKDEMVEQ EFNRLLEATS YLSHQLDFNV LNNKPVSLGQ ALEVVIQLQE
KHVKDEQIEH WKKIVKTQEE LKELLNKMVN LKEKIKELHQ QYKEASEVKP PRDITAEFLV
KSKHRDLTAL CKEYDELAET QGKLEEKLQE LEANPPSDVY LSSRDRQILD WHFANLEFAN
ATPLSTLSLK HWDQDDDFEF TGSHLTVRNG YSCVPVALAE GLDIKLNTAV RQVRYTASGC
EVIAVNTRST SQTFIYKCDA VLCTLPLGVL KQQPPAVQFV PPLPEWKTSA VQRMGFGNLN
KVVLCFDRVF WDPSVNLFGH VGSTTASRGE LFLFWNLYKA PILLALVAGE AAGIMENISD
DVIVGRCLAI LKGIFGSSAV PQPKETVVSR WRADPWARGS YSYVAAGSSG NDYDLMAQPI
TPGPSIPGAP QPIPRLFFAG EHTIRNYPAT VHGALLSGLR EAGRIADQFL GAMYTLPRQA
TPGVPAQQSP SM
//
