ID   HAIR_MOUSE              Reviewed;        1182 AA.
AC   Q61645; Q80Y47;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   15-AUG-2003, sequence version 2.
DT   24-JAN-2024, entry version 148.
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   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=BALB/cJ; TISSUE=Skin;
RX   PubMed=8052649; DOI=10.1073/pnas.91.16.7717;
RA   Cachon-Gonzalez M.B., Fenner S., Coffin J.M., Moran C., Best S.,
RA   Stoye J.P.;
RT   "Structure and expression of the hairless gene of mice.";
RL   Proc. Natl. Acad. Sci. U.S.A. 91:7717-7721(1994).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Retina;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
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   -!- TISSUE SPECIFICITY: Expressed predominantly in brain, hair follicles
CC       and interfollicular epidermis. No expression in dermis.
CC   -!- DOMAIN: Contains two Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs. The LXXLL
CC       motifs are essential for the association with nuclear receptors (By
CC       similarity). {ECO:0000250}.
CC   -!- DOMAIN: The JmjC domain and the C6-type zinc-finger are required for
CC       the demethylation activity. {ECO:0000250}.
CC   -!- DISEASE: Note=Defects in Hr are the cause of a number of pleiotropic
CC       effects including structural abnormalities of epithelial cells in the
CC       hair follicles, hair loss towards the end of the first hair growth
CC       cycle, and the failure of subsequent hair growth cycles. Older mice
CC       carrying a hr mutation have been reported to possess altered ratios of
CC       T-cell-dependent B-cell responses. Mice homozygous for hr mutation are
CC       uniquely sensitive to UV and chemically induced skin tumors.
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DR   EMBL; Z32675; CAA83587.1; -; mRNA.
DR   EMBL; BC049182; AAH49182.1; -; mRNA.
DR   CCDS; CCDS27257.1; -.
DR   PIR; I48378; I48378.
DR   RefSeq; NP_068677.2; NM_021877.3.
DR   RefSeq; XP_011243268.1; XM_011244966.1.
DR   AlphaFoldDB; Q61645; -.
DR   SMR; Q61645; -.
DR   BioGRID; 200415; 3.
DR   IntAct; Q61645; 3.
DR   STRING; 10090.ENSMUSP00000124816; -.
DR   iPTMnet; Q61645; -.
DR   PhosphoSitePlus; Q61645; -.
DR   PaxDb; 10090-ENSMUSP00000022691; -.
DR   ProteomicsDB; 269763; -.
DR   Antibodypedia; 9297; 227 antibodies from 27 providers.
DR   DNASU; 15460; -.
DR   Ensembl; ENSMUST00000022691.14; ENSMUSP00000022691.8; ENSMUSG00000022096.15.
DR   Ensembl; ENSMUST00000161069.8; ENSMUSP00000124816.2; ENSMUSG00000022096.15.
DR   GeneID; 15460; -.
DR   KEGG; mmu:15460; -.
DR   UCSC; uc007uoj.2; mouse.
DR   AGR; MGI:96223; -.
DR   CTD; 55806; -.
DR   MGI; MGI:96223; Hr.
DR   VEuPathDB; HostDB:ENSMUSG00000022096; -.
DR   eggNOG; KOG1356; Eukaryota.
DR   GeneTree; ENSGT00940000161687; -.
DR   InParanoid; Q61645; -.
DR   OrthoDB; 3473445at2759; -.
DR   PhylomeDB; Q61645; -.
DR   TreeFam; TF324723; -.
DR   BioGRID-ORCS; 15460; 3 hits in 80 CRISPR screens.
DR   ChiTaRS; Hr; mouse.
DR   PRO; PR:Q61645; -.
DR   Proteomes; UP000000589; Chromosome 14.
DR   RNAct; Q61645; Protein.
DR   Bgee; ENSMUSG00000022096; Expressed in lip and 141 other cell types or tissues.
DR   ExpressionAtlas; Q61645; baseline and differential.
DR   GO; GO:0000785; C:chromatin; IBA:GO_Central.
DR   GO; GO:0000118; C:histone deacetylase complex; ISO:MGI.
DR   GO; GO:0016604; C:nuclear body; IDA:MGI.
DR   GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR   GO; GO:0031490; F:chromatin DNA binding; IBA:GO_Central.
DR   GO; GO:0042826; F:histone deacetylase binding; ISO:MGI.
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; ISO:MGI.
DR   GO; GO:0042809; F:nuclear vitamin D receptor binding; ISO:MGI.
DR   GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR   GO; GO:0003712; F:transcription coregulator activity; IBA:GO_Central.
DR   GO; GO:0003714; F:transcription corepressor activity; IDA:MGI.
DR   GO; GO:0045892; P:negative regulation of DNA-templated transcription; IDA:MGI.
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.
DR   Genevisible; Q61645; MM.
PE   2: Evidence at transcript level;
KW   DNA-binding; Iron; Metal-binding; Nucleus; Oxidoreductase;
KW   Reference proteome; Transcription; Transcription regulation; Zinc;
KW   Zinc-finger.
FT   CHAIN           1..1182
FT                   /note="Lysine-specific demethylase hairless"
FT                   /id="PRO_0000083891"
FT   DOMAIN          939..1150
FT                   /note="JmjC"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00538"
FT   ZN_FING         595..620
FT                   /note="C6-type"
FT   REGION          227..257
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          302..380
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          411..443
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          507..546
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          697..746
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           561..565
FT                   /note="LXXLL motif 1"
FT   MOTIF           753..757
FT                   /note="LXXLL motif 2"
FT   COMPBIAS        308..324
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        357..371
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         1000
FT                   /ligand="Fe cation"
FT                   /ligand_id="ChEBI:CHEBI:24875"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00538"
FT   BINDING         1002
FT                   /ligand="Fe cation"
FT                   /ligand_id="ChEBI:CHEBI:24875"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00538"
FT   BINDING         1118
FT                   /ligand="Fe cation"
FT                   /ligand_id="ChEBI:CHEBI:24875"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00538"
FT   CONFLICT        401
FT                   /note="P -> S (in Ref. 1; CAA83587)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   1182 AA;  127193 MW;  3AFABE96C6EB3241 CRC64;
     MESMPSFLKD TPAWEKTAPV NGIVGQEPGT SPQDGLRHGA LCLGEPAPFW RGVLSTPDSW
     LPPGFLQGPK DTLSLVEGEG PRNGERKGSW LGGKEGLRWK EAMLAHPLAF CGPACPPRYG
     PLIPEHSGGH PKSDPVAFRP LHCPFLLETK ILERAPFWVP TCLPPYLMSS LPPERPYDWP
     LAPNPWVYSG SQPKVPSAFG LGSKGFYHKD PNILRPAKEP LAESGMLGLA PGGHLQQACE
     SEGPSLHQRD GETGAGRQQN LCPVFLGYPD TVPRAPWPSC PPGLVHSLGN IWAGPGSNSL
     GYQLGPPATP RCPSPGPPTP PGGCCSSHLP AREGDLGPCR KCQDSPEGGS SGPGESSEER
     NKADSRACPP SHHTKLKKTW LTRHSEQFEC PGGCSGKEES PATGLRALKR AGSPEVQGAS
     RGPAPKRPSH PFPGTGRQGA RAWQETPETI IGSKAEAEQQ EEQRGPRDGR IRLQESRLVD
     TSCQHHLAGV TQCQSCVQAA GEVGVLTGHS QKSRRSPLEE KQLEEEDSSA TSEEGGGGPG
     PEASLNKGLA KHLLSGLGDR LCRLLRKERE ALAWAQREGQ GPAMTEDSPG IPHCCSRCHH
     GLFNTHWRCS HCSHRLCVAC GRIAGAGKNR EKTGSQEQHT DDCAQEAGHA ACSLILTQFV
     SSQALAELST VMHQVWAKFD IRGHCFCQVD ARVWAPGDGG QQKEPTEKTP PTPQPSCNGD
     SNRTKDIKEE TPDSTESPAE DGAGRSPLPC PSLCELLAST AVKLCLGHDR IHMAFAPVTP
     ALPSDDRITN ILDSIIAQVV ERKIQEKALG PGLRAGSGLR KGLSLPLSPV RTRLSPPGAL
     LWLQEPRPKH GFHLFQEHWR QGQPVLVSGI QKTLRLSLWG MEALGTLGGQ VQTLTALGPP
     QPTNLDSTAF WEGFSHPETR PKLDEGSVLL LHRTLGDKDA SRVQNLASSL PLPEYCAHQG
     KLNLASYLPL GLTLHPLEPQ LWAAYGVNSH RGHLGTKNLC VEVSDLISIL VHAEAQLPPW
     YRAQKDFLSG LDGEGLWSPG SQTSTVWHVF RAQDAQRIRR FLQMVCPAGA GTLEPGAPGS
     CYLDAGLRRR LREEWGVSCW TLLQAPGEAV LVPAGAPHQV QGLVSTISVT QHFLSPETSA
     LSAQLYHQGA SLPPDHRMLY AQMDRAVFQA VKAAVGALQE AK
//