ID A0A286XX86_CAVPO Unreviewed; 865 AA.
AC A0A286XX86;
DT 22-NOV-2017, integrated into UniProtKB/TrEMBL.
DT 22-NOV-2017, sequence version 1.
DT 27-MAR-2024, entry version 34.
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:ENSCPOP00000030158.1};
OS Cavia porcellus (Guinea pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Hystricomorpha; Caviidae;
OC Cavia.
OX NCBI_TaxID=10141 {ECO:0000313|Ensembl:ENSCPOP00000030158.1, ECO:0000313|Proteomes:UP000005447};
RN [1] {ECO:0000313|Proteomes:UP000005447}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=2N {ECO:0000313|Proteomes:UP000005447};
RX PubMed=21993624; DOI=10.1038/nature10530;
RA Lindblad-Toh K., Garber M., Zuk O., Lin M.F., Parker B.J., Washietl S.,
RA Kheradpour P., Ernst J., Jordan G., Mauceli E., Ward L.D., Lowe C.B.,
RA Holloway A.K., Clamp M., Gnerre S., Alfoldi J., Beal K., Chang J.,
RA Clawson H., Cuff J., Di Palma F., Fitzgerald S., Flicek P., Guttman M.,
RA Hubisz M.J., Jaffe D.B., Jungreis I., Kent W.J., Kostka D., Lara M.,
RA Martins A.L., Massingham T., Moltke I., Raney B.J., Rasmussen M.D.,
RA Robinson J., Stark A., Vilella A.J., Wen J., Xie X., Zody M.C., Baldwin J.,
RA Bloom T., Chin C.W., Heiman D., Nicol R., Nusbaum C., Young S.,
RA Wilkinson J., Worley K.C., Kovar C.L., Muzny D.M., Gibbs R.A., Cree A.,
RA Dihn H.H., Fowler G., Jhangiani S., Joshi V., Lee S., Lewis L.R.,
RA Nazareth L.V., Okwuonu G., Santibanez J., Warren W.C., Mardis E.R.,
RA Weinstock G.M., Wilson R.K., Delehaunty K., Dooling D., Fronik C.,
RA Fulton L., Fulton B., Graves T., Minx P., Sodergren E., Birney E.,
RA Margulies E.H., Herrero J., Green E.D., Haussler D., Siepel A., Goldman N.,
RA Pollard K.S., Pedersen J.S., Lander E.S., Kellis M.;
RT "A high-resolution map of human evolutionary constraint using 29 mammals.";
RL Nature 478:476-482(2011).
RN [2] {ECO:0000313|Ensembl:ENSCPOP00000030158.1}
RP IDENTIFICATION.
RC STRAIN=2N {ECO:0000313|Ensembl:ENSCPOP00000030158.1};
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; AAKN02028686; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR AlphaFoldDB; A0A286XX86; -.
DR STRING; 10141.ENSCPOP00000030158; -.
DR Ensembl; ENSCPOT00000040562.1; ENSCPOP00000030158.1; ENSCPOG00000010744.4.
DR VEuPathDB; HostDB:ENSCPOG00000010744; -.
DR eggNOG; KOG0029; Eukaryota.
DR eggNOG; KOG0685; Eukaryota.
DR GeneTree; ENSGT00940000157193; -.
DR InParanoid; A0A286XX86; -.
DR OMA; SSRGEMF; -.
DR Proteomes; UP000005447; Unassembled WGS sequence.
DR Bgee; ENSCPOG00000010744; Expressed in ovary and 13 other cell types or tissues.
DR GO; GO:0000785; C:chromatin; IEA:Ensembl.
DR GO; GO:0000781; C:chromosome, telomeric region; IEA:Ensembl.
DR GO; GO:1990391; C:DNA repair complex; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0003682; F:chromatin binding; IEA:Ensembl.
DR GO; GO:0019899; F:enzyme binding; IEA:Ensembl.
DR GO; GO:0140682; F:FAD-dependent H3K4me/H3K4me3 demethylase activity; IEA:Ensembl.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IEA:UniProtKB-UniRule.
DR GO; GO:0032454; F:histone H3K9 demethylase activity; IEA:Ensembl.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0043426; F:MRF binding; IEA:Ensembl.
DR GO; GO:0050681; F:nuclear androgen receptor binding; IEA:Ensembl.
DR GO; GO:0030374; F:nuclear receptor coactivator activity; IEA:Ensembl.
DR GO; GO:0002039; F:p53 binding; IEA:Ensembl.
DR GO; GO:0061752; F:telomeric repeat-containing RNA binding; IEA:Ensembl.
DR GO; GO:0071480; P:cellular response to gamma radiation; IEA:Ensembl.
DR GO; GO:0034644; P:cellular response to UV; IEA:Ensembl.
DR GO; GO:0140861; P:DNA repair-dependent chromatin remodeling; IEA:Ensembl.
DR GO; GO:0043518; P:negative regulation of DNA damage response, signal transduction by p53 class mediator; IEA:Ensembl.
DR GO; GO:1902166; P:negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; IEA:Ensembl.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0002052; P:positive regulation of neuroblast proliferation; IEA:Ensembl.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0090308; P:regulation of DNA methylation-dependent heterochromatin formation; IEA:Ensembl.
DR GO; GO:0010569; P:regulation of double-strand break repair via homologous recombination; IEA:Ensembl.
DR GO; GO:0032880; P:regulation of protein localization; IEA:Ensembl.
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:UP000005447};
KW Repressor {ECO:0000256|PIRNR:PIRNR038051};
KW Transcription {ECO:0000256|PIRNR:PIRNR038051};
KW Transcription regulation {ECO:0000256|PIRNR:PIRNR038051}.
FT DOMAIN 187..286
FT /note="SWIRM"
FT /evidence="ECO:0000259|PROSITE:PS50934"
FT REGION 1..186
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 447..481
FT /evidence="ECO:0000256|SAM:Coils"
FT COMPBIAS 110..144
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 294..322
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000256|PIRSR:PIRSR038051-1"
FT BINDING 323
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000256|PIRSR:PIRSR038051-1"
FT BINDING 329
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000256|PIRSR:PIRSR038051-1"
FT BINDING 345..346
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000256|PIRSR:PIRSR038051-1"
FT BINDING 814
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000256|PIRSR:PIRSR038051-1"
FT BINDING 823..824
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000256|PIRSR:PIRSR038051-1"
SQ SEQUENCE 865 AA; 94621 MW; FE4ACA92EE9AB8B7 CRC64;
AAAAGPGGRP GRTPGPGGGR AGPEKRLRRV APPPAGLFGP PSEGRAPERP GKRSPRKKRA
SAGPPLLAAW PSPQGSAGPQ AGPTVVPRVC DPHGDGNIRD SGRATDQPAQ VEYREMDESL
ANLSEDEYYS EEERNAKAEK EKKLPPPPPQ APPEEENESE PEEPSGQAGG LQDDSSGGYG
DGQASGVEGA AFQSRLPHDR MTSQEAACFP DIISGPQQTQ KVFLFIRNRT LQLWLDNPKI
QLTFEATLQQ LEAPYNSDTV LVHRVHSYLE RHGLINFGIY KRIKPLPTKK TGKVIIIGSG
VSGLAAARQL QSFGMDVTLL EARDRVGGRV ATFRKGNYVA DLGAMVVTGL GGNPMAVVSK
QVNMELAKIK QKCPLYEANG QAVPKEKDEM VEQEFNRLLE ATSYLSHQLD FNVLNNKPVS
LGQALEVVIQ LQEKHVKDEQ IEHWKKIVKT QEELKELLNK MVNLKEKIKE LHQQYKEASE
VKPPRDITAE FLVKSKHRDL TALCKEYDEL AETQGKLEEK LQELEANPPS DVYLSSRDRQ
ILDWHFANLE FANATPLSTL SLKHWDQDDD FEFTGSHLTV RNGYSCVPVA LAEGLDIKLN
TAVRQVRYTA SGCEVIAVNT RSTSQTFIYK CDAVLCTLPL GVLKQQPPAV QFVPPLPEWK
TSAVQRMGFG NLNKVVLCFD RVFWDPSVNL FGHVGSTTAS RGELFLFWNL YKAPILLALV
AGEAAGIMEN ISDDVIVGRC LAILKGIFGS SAVPQPKETV VSRWRADPWA RGSYSYVAAG
SSGNDYDLMA QPITPGPSIP GAPQPIPRLF FAGEHTIRNY PATVHGALLS GLREAGRIAD
QFLGAMYTLP RQATPGVPAQ QSPSM
//
