ID G3SBH6_GORGO Unreviewed; 872 AA.
AC G3SBH6;
DT 16-NOV-2011, integrated into UniProtKB/TrEMBL.
DT 28-FEB-2018, sequence version 2.
DT 24-JAN-2024, entry version 68.
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:ENSGGOP00000025452.2};
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:ENSGGOP00000025452.2, ECO:0000313|Proteomes:UP000001519};
RN [1] {ECO:0000313|Ensembl:ENSGGOP00000025452.2, 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:ENSGGOP00000025452.2, 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:ENSGGOP00000025452.2}
RP IDENTIFICATION.
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 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_018868010.1; XM_019012465.1.
DR AlphaFoldDB; G3SBH6; -.
DR Ensembl; ENSGGOT00000031610.2; ENSGGOP00000025452.2; ENSGGOG00000003664.3.
DR GeneID; 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: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:UP000001519};
KW Repressor {ECO:0000256|PIRNR:PIRNR038051};
KW Transcription {ECO:0000256|PIRNR:PIRNR038051};
KW Transcription regulation {ECO:0000256|PIRNR:PIRNR038051}.
FT DOMAIN 194..293
FT /note="SWIRM"
FT /evidence="ECO:0000259|PROSITE:PS50934"
FT REGION 1..193
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 454..488
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 301..329
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000256|PIRSR:PIRSR038051-1"
FT BINDING 330
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000256|PIRSR:PIRSR038051-1"
FT BINDING 336
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000256|PIRSR:PIRSR038051-1"
FT BINDING 352..353
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000256|PIRSR:PIRSR038051-1"
FT BINDING 821
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000256|PIRSR:PIRSR038051-1"
FT BINDING 830..831
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000256|PIRSR:PIRSR038051-1"
SQ SEQUENCE 872 AA; 94681 MW; 1883AC704F969701 CRC64;
MLSGKKAAAA AAAAAAAAAG TEAGPGTAGG SENGSEVAAQ PAGLSGPAEV GPGAVGERTP
RKKEPPRASP PGGLAEPPGS AGPQAGPTVV PGSATPMETG IAETPEGRRT SRRKRAKVEY
REMDESLANL SEDEYYSEEE RNAKAEKEKK LPPPPPQAPP EEENESEPEE PSGQAGGLQD
DSSGGYGDGQ ASGVEGAAFQ 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
//