ID   HAIR_RAT                Reviewed;        1181 AA.
AC   P97609;
DT   15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT   15-JUL-1998, sequence version 2.
DT   08-NOV-2023, entry version 118.
DE   RecName: Full=Lysine-specific demethylase hairless;
DE            EC=1.14.11.65 {ECO:0000250|UniProtKB:O43593};
DE   AltName: Full=[histone H3]-dimethyl-L-lysine(9) demethylase hairless {ECO:0000305};
GN   Name=Hr;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=Sprague-Dawley;
RX   PubMed=8987811; DOI=10.1523/jneurosci.16-24-07832.1996;
RA   Thompson C.C.;
RT   "Thyroid hormone-responsive genes in developing cerebellum include a novel
RT   synaptotagmin and a hairless homolog.";
RL   J. Neurosci. 16:7832-7840(1996).
RN   [2]
RP   DOMAIN, AND MUTAGENESIS OF 563-LEU-LEU-564 AND 756-LEU-LEU-756.
RX   PubMed=14570920; DOI=10.1074/jbc.m308152200;
RA   Moraitis A.N., Giguere V.;
RT   "The co-repressor hairless protects RORalpha orphan nuclear receptor from
RT   proteasome-mediated degradation.";
RL   J. Biol. Chem. 278:52511-52518(2003).
CC   -!- FUNCTION: Histone demethylase that specifically demethylates both
CC       mono- and dimethylated 'Lys-9' of histone H3. May act as a
CC       transcription regulator controlling hair biology (via targeting of
CC       collagens), neural activity, and cell cycle.
CC       {ECO:0000250|UniProtKB:O43593}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=2 2-oxoglutarate + N(6),N(6)-dimethyl-L-lysyl(9)-[histone H3]
CC         + 2 O2 = 2 CO2 + 2 formaldehyde + L-lysyl(9)-[histone H3] + 2
CC         succinate; Xref=Rhea:RHEA:60188, Rhea:RHEA-COMP:15541, Rhea:RHEA-
CC         COMP:15546, ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810,
CC         ChEBI:CHEBI:16842, ChEBI:CHEBI:29969, ChEBI:CHEBI:30031,
CC         ChEBI:CHEBI:61976; EC=1.14.11.65;
CC         Evidence={ECO:0000250|UniProtKB:O43593};
CC   -!- COFACTOR:
CC       Name=Fe(2+); Xref=ChEBI:CHEBI:29033; Evidence={ECO:0000250};
CC       Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000250};
CC   -!- SUBCELLULAR LOCATION: Nucleus.
CC   -!- DOMAIN: Contains two Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs. The LXXLL
CC       motifs are essential for the association with nuclear receptors
CC       (PubMed:14570920). {ECO:0000269|PubMed:14570920}.
CC   -!- DOMAIN: The JmjC domain and the C6-type zinc-finger are required for
CC       the demethylation activity. {ECO:0000250}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAC53018.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR   EMBL; U71293; AAC53018.1; ALT_INIT; mRNA.
DR   AlphaFoldDB; P97609; -.
DR   SMR; P97609; -.
DR   STRING; 10116.ENSRNOP00000015716; -.
DR   CarbonylDB; P97609; -.
DR   iPTMnet; P97609; -.
DR   PhosphoSitePlus; P97609; -.
DR   PaxDb; 10116-ENSRNOP00000015716; -.
DR   UCSC; RGD:620634; rat.
DR   AGR; RGD:620634; -.
DR   RGD; 620634; Hr.
DR   eggNOG; KOG1356; Eukaryota.
DR   InParanoid; P97609; -.
DR   PhylomeDB; P97609; -.
DR   PRO; PR:P97609; -.
DR   Proteomes; UP000002494; Unplaced.
DR   GO; GO:0000785; C:chromatin; IBA:GO_Central.
DR   GO; GO:0000118; C:histone deacetylase complex; IDA:RGD.
DR   GO; GO:0016604; C:nuclear body; ISO:RGD.
DR   GO; GO:0031490; F:chromatin DNA binding; IBA:GO_Central.
DR   GO; GO:0042826; F:histone deacetylase binding; IDA:RGD.
DR   GO; GO:0032454; F:histone H3K9 demethylase activity; IBA:GO_Central.
DR   GO; GO:0140683; F:histone H3K9me/H3K9me2 demethylase activity; IEA:UniProtKB-EC.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0046966; F:nuclear thyroid hormone receptor binding; IPI:RGD.
DR   GO; GO:0042809; F:nuclear vitamin D receptor binding; IPI:RGD.
DR   GO; GO:0044877; F:protein-containing complex binding; IDA:RGD.
DR   GO; GO:0003712; F:transcription coregulator activity; IBA:GO_Central.
DR   GO; GO:0003714; F:transcription corepressor activity; IDA:RGD.
DR   GO; GO:0045892; P:negative regulation of DNA-templated transcription; ISO:RGD.
DR   GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR   Gene3D; 2.60.120.650; Cupin; 1.
DR   InterPro; IPR045109; JHDM2-like.
DR   InterPro; IPR003347; JmjC_dom.
DR   PANTHER; PTHR12549; JMJC DOMAIN-CONTAINING HISTONE DEMETHYLATION PROTEIN; 1.
DR   PANTHER; PTHR12549:SF4; LYSINE-SPECIFIC DEMETHYLASE HAIRLESS; 1.
DR   Pfam; PF02373; JmjC; 1.
DR   SMART; SM00558; JmjC; 1.
DR   SUPFAM; SSF51197; Clavaminate synthase-like; 1.
DR   PROSITE; PS51184; JMJC; 1.
PE   1: Evidence at protein level;
KW   DNA-binding; Iron; Metal-binding; Nucleus; Oxidoreductase;
KW   Reference proteome; Transcription; Transcription regulation; Zinc;
KW   Zinc-finger.
FT   CHAIN           1..1181
FT                   /note="Lysine-specific demethylase hairless"
FT                   /id="PRO_0000083892"
FT   DOMAIN          938..1149
FT                   /note="JmjC"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00538"
FT   ZN_FING         594..619
FT                   /note="C6-type"
FT   REGION          311..378
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          413..472
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          509..543
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          696..745
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           560..564
FT                   /note="LXXLL motif 1"
FT   MOTIF           752..756
FT                   /note="LXXLL motif 2"
FT   COMPBIAS        311..326
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        346..360
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        443..460
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        514..529
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        706..720
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        721..739
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         999
FT                   /ligand="Fe cation"
FT                   /ligand_id="ChEBI:CHEBI:24875"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00538"
FT   BINDING         1001
FT                   /ligand="Fe cation"
FT                   /ligand_id="ChEBI:CHEBI:24875"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00538"
FT   BINDING         1117
FT                   /ligand="Fe cation"
FT                   /ligand_id="ChEBI:CHEBI:24875"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00538"
FT   MUTAGEN         563..564
FT                   /note="LL->AA: Decreases RORA protein stability. Strongly
FT                   decreases RORA protein stability; when associated with
FT                   752-L--A-756."
FT                   /evidence="ECO:0000269|PubMed:14570920"
FT   MUTAGEN         755..756
FT                   /note="LL->AA: Decreases RORA protein stability. Strongly
FT                   decreases RORA protein stability; when associated with
FT                   560-L--A-564."
SQ   SEQUENCE   1181 AA;  127307 MW;  834B7029CF8E88F0 CRC64;
     MESMPSFLKD TPAWEKTAPV NGIVGQEPGT SPQDGLHHGA LCLGEPVPFW RGVLSAPDSW
     LPPGFLQGPK DTLSVVEGEG SRNGERKANW LGSKEGLRWK EAMLAHPLAF CGPACPPRYG
     PLIPEHSSGH PKSDPVAFRP LHCPFLLETK ILERAPFWVP TCLPPYLMSS LPPERSYDWP
     LAPSPWVYSG SQPKVPSAFS LGSKGFYHKD PNILRPAKEP LAASESGMLG LAPGGHLQQA
     CDAEGPSLHQ RDGETGAGRQ QNLCPVFLGY PDTVPRTPWP SCPPGLVHTL GNVWAGPGSN
     SFGYQLGPPV TPRCPSPGPP TPPGGCCSSH LPAREGDPGP CRKCQDSPEG SSSGPGESSE
     ERNKAGSRAS PPSHHTKLKK TWLTRHSEQF ECPGGCPGKG ESPATGLRAL KRAGSPEVQG
     ARGPAPKRPS HTFPGTGRQG ARAWQETPET STGSKAEAQQ QEEQRGPRDG RIRLRESRLE
     DTSCQHHLAG VTQCPSCVQA AGEVEILTSH SQKSHKLPLE EKPLEEDSCA TSEEGGGSSP
     EASINKGLAK HLLSGLGDRL CRLLRKEREA LAWAQREGQG PAMTEDSPGI PHCCSRCHHG
     LFNTHWRCSH CSHRLCVACG RIAGAGKNRE KTGSREQRTD DCAQEAGHAA CSLILTQFVS
     SQALAELSTV MHQVWAKFDI RGHCFCQVDA RVWAPGDGGQ QKEPTEKTPP APQLSCNGDS
     NRTKDIKEET PDSTESPAED RAGRSPLPCP SLCELLASTA VKLCLGHERI HMAFAPVTPA
     LPSDDRITNI LDSIIAQVVE RKIQEKALGP GLRAGSGLRK GLSLPLSPVR TQLSPPGALL
     WLQEPRPKHG FRLFQEHWRQ GQPVLVSGIQ KTLRLSLWGM EALGTLGGQV QTLTALGPPQ
     PTSLDSTAFW KGFSHPEARP KLDEGSVLLL HRPLGDKDES RVENLASSLP LPEYCAHQGK
     LNLASYLPLG LTLHPLEPQL WAAYGVNSHR GHLGTKNLCV EVSDLISILV HAEAQLPPWY
     RAQKDFLSGL DGEGLWSPGS QTSTVWHVFR AQDAQRIRRF LQMVCPAGAG TLEPGAPGSC
     YLDSGLRRRL REEWGVSCWT LLQAPGEAVL VPAGAPHQVQ GLVSTISVTQ HFLSPETSAL
     SAQLCHQGAS LPPDHRMLYA QMDRAVFQAV KVAVGTLQEA K
//