ID G1M8R7_AILME Unreviewed; 868 AA.
AC G1M8R7;
DT 19-OCT-2011, integrated into UniProtKB/TrEMBL.
DT 02-JUN-2021, sequence version 2.
DT 24-JAN-2024, entry version 74.
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:ENSAMEP00000015737.2};
OS Ailuropoda melanoleuca (Giant panda).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Ursidae; Ailuropoda.
OX NCBI_TaxID=9646 {ECO:0000313|Ensembl:ENSAMEP00000015737.2, ECO:0000313|Proteomes:UP000008912};
RN [1] {ECO:0000313|Ensembl:ENSAMEP00000015737.2, ECO:0000313|Proteomes:UP000008912}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=20010809; DOI=10.1038/nature08696;
RA Li R., Fan W., Tian G., Zhu H., He L., Cai J., Huang Q., Cai Q., Li B.,
RA Bai Y., Zhang Z., Zhang Y., Wang W., Li J., Wei F., Li H., Jian M., Li J.,
RA Zhang Z., Nielsen R., Li D., Gu W., Yang Z., Xuan Z., Ryder O.A.,
RA Leung F.C., Zhou Y., Cao J., Sun X., Fu Y., Fang X., Guo X., Wang B.,
RA Hou R., Shen F., Mu B., Ni P., Lin R., Qian W., Wang G., Yu C., Nie W.,
RA Wang J., Wu Z., Liang H., Min J., Wu Q., Cheng S., Ruan J., Wang M.,
RA Shi Z., Wen M., Liu B., Ren X., Zheng H., Dong D., Cook K., Shan G.,
RA Zhang H., Kosiol C., Xie X., Lu Z., Zheng H., Li Y., Steiner C.C.,
RA Lam T.T., Lin S., Zhang Q., Li G., Tian J., Gong T., Liu H., Zhang D.,
RA Fang L., Ye C., Zhang J., Hu W., Xu A., Ren Y., Zhang G., Bruford M.W.,
RA Li Q., Ma L., Guo Y., An N., Hu Y., Zheng Y., Shi Y., Li Z., Liu Q.,
RA Chen Y., Zhao J., Qu N., Zhao S., Tian F., Wang X., Wang H., Xu L., Liu X.,
RA Vinar T., Wang Y., Lam T.W., Yiu S.M., Liu S., Zhang H., Li D., Huang Y.,
RA Wang X., Yang G., Jiang Z., Wang J., Qin N., Li L., Li J., Bolund L.,
RA Kristiansen K., Wong G.K., Olson M., Zhang X., Li S., Yang H., Wang J.,
RA Wang J.;
RT "The sequence and de novo assembly of the giant panda genome.";
RL Nature 463:311-317(2010).
RN [2] {ECO:0000313|Ensembl:ENSAMEP00000015737.2}
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 AlphaFoldDB; G1M8R7; -.
DR STRING; 9646.ENSAMEP00000015737; -.
DR Ensembl; ENSAMET00000016391.2; ENSAMEP00000015737.2; ENSAMEG00000014887.2.
DR eggNOG; KOG0029; Eukaryota.
DR eggNOG; KOG0685; Eukaryota.
DR GeneTree; ENSGT00940000157193; -.
DR HOGENOM; CLU_004498_5_1_1; -.
DR TreeFam; TF312972; -.
DR Proteomes; UP000008912; 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:UP000008912};
KW Repressor {ECO:0000256|PIRNR:PIRNR038051};
KW Transcription {ECO:0000256|PIRNR:PIRNR038051};
KW Transcription regulation {ECO:0000256|PIRNR:PIRNR038051}.
FT DOMAIN 190..289
FT /note="SWIRM"
FT /evidence="ECO:0000259|PROSITE:PS50934"
FT REGION 1..189
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 450..484
FT /evidence="ECO:0000256|SAM:Coils"
FT COMPBIAS 101..147
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 297..325
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000256|PIRSR:PIRSR038051-1"
FT BINDING 326
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000256|PIRSR:PIRSR038051-1"
FT BINDING 332
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000256|PIRSR:PIRSR038051-1"
FT BINDING 348..349
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000256|PIRSR:PIRSR038051-1"
FT BINDING 817
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000256|PIRSR:PIRSR038051-1"
FT BINDING 826..827
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000256|PIRSR:PIRSR038051-1"
SQ SEQUENCE 868 AA; 94223 MW; CE6A75BB87B1E521 CRC64;
MLSGKKAAAA AAAAAAAAAG TEAGPGAAGG AENGSEVAAP PAGLSGPAEA GPGVAGERTP
RKKEPPRASP PGGLAEPPGS AGPTVVPGSA TPMETGIAET PEGRRTSRRK RAKVEYREMD
ESLANLSEDE YYSEEERNAK AEKEKKLPPP PPQAPPEEEN ESEPEEPSGQ AGGLQDDSSG
GYGDGQASGV EGAAFQSRLP HDRMTSQEAA CFPDIISGPQ QTQKVFLFIR NRTLQLWLDN
PKIQLTFEAT LQQLEAPYNS DTVLVHRVHS YLERHGLINF GIYKRIKPLP TKKTGKVIII
GSGVSGLAAA RQLQSFGMDV TLLEARDRVG GRVATFRKGN YVADLGAMVV TGLGGNPMAV
VSKQVNMELA KIKQKCPLYE ANGQAVPKEK DEMVEQEFNR LLEATSYLSH QLDFNVLNNK
PVSLGQALEV VIQLQEKHVK DEQIEHWKKI VKTQEELKEL LNKMVNLKEK IKELHQQYKE
ASEVKPPRDI TAEFLVKSKH RDLTALCKEY DELAETQGKL EEKLQELEAN PPSDVYLSSR
DRQILDWHFA NLEFANATPL STLSLKHWDQ DDDFEFTGSH LTVRNGYSCV PVALAEGLDI
KLNTAVRQVR YTASGCEVIA VNTRSTSQTF IYKCDAVLCT LPLGVLKQQP PAVQFVPPLP
EWKTSAVQRM GFGNLNKVVL CFDRVFWDPS VNLFGHVGST TASRGELFLF WNLYKAPILL
ALVAGEAAGI MENISDDVIV GRCLAILKGI FGSSAVPQPK ETVVSRWRAD PWARGSYSYV
AAGSSGNDYD LMAQPITPGP SIPGAPQPIP RLFFAGEHTI RNYPATVHGA LLSGLREAGR
IADQFLGAMY TLPRQATPGV PAQQSPSM
//