ID   KDM8_HUMAN              Reviewed;         416 AA.
AC   Q8N371; B4DLU9; Q6VAK5; Q9H8B1;
DT   26-JUN-2007, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2002, sequence version 1.
DT   25-JAN-2012, entry version 61.
DE   RecName: Full=Lysine-specific demethylase 8;
DE            EC=1.14.11.27;
DE   AltName: Full=JmjC domain-containing protein 5;
DE   AltName: Full=Jumonji domain-containing protein 5;
GN   Name=JMJD5; Synonyms=KDM8;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC   TISSUE=Brain, and Thyroid;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA   Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA   Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA   Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA   Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA   Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA   Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA   Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA   Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA   Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA   Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA   Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA   Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA   Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA   Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA   Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA   Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA   Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA   Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA   Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RA   Li H., Yu R., Zheng G., Zhou G., Ke R., Shen C., Zhong G., Lin L.,
RA   Yang S.;
RL   Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15616553; DOI=10.1038/nature03187;
RA   Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X.,
RA   Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A.,
RA   Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J.,
RA   Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L.,
RA   Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A.,
RA   Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D.,
RA   Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J.,
RA   Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA   Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I.,
RA   Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W.,
RA   Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A.,
RA   Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S.,
RA   Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA   Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA   Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L.,
RA   Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A.,
RA   Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L.,
RA   Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N.,
RA   Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M.,
RA   Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L.,
RA   Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D.,
RA   Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P.,
RA   Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M.,
RA   Rubin E.M., Pennacchio L.A.;
RT   "The sequence and analysis of duplication-rich human chromosome 16.";
RL   Nature 432:988-994(2004).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Lung;
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
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [5]
RP   FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND MUTAGENESIS OF
RP   HIS-321.
RX   PubMed=20457893; DOI=10.1073/pnas.1000401107;
RA   Hsia D.A., Tepper C.G., Pochampalli M.R., Hsia E.Y., Izumiya C.,
RA   Huerta S.B., Wright M.E., Chen H.W., Kung H.J., Izumiya Y.;
RT   "KDM8, a H3K36me2 histone demethylase that acts in the cyclin A1
RT   coding region to regulate cancer cell proliferation.";
RL   Proc. Natl. Acad. Sci. U.S.A. 107:9671-9676(2010).
CC   -!- FUNCTION: Histone demethylase required for G2/M phase cell cycle
CC       progression. Specifically demethylates dimethylated 'Lys-36'
CC       (H3K36me2) of histone H3, an epigenetic repressive mark, thereby
CC       acting as a transcription activator. Regulates expression of CCNA1
CC       (cyclin-A1), leading to regulate cancer cell proliferation.
CC   -!- CATALYTIC ACTIVITY: Protein N(6),N(6)-dimethyl-L-lysine + 2-
CC       oxoglutarate + O(2) = protein N(6)-methyl-L-lysine + succinate +
CC       formaldehyde + CO(2).
CC   -!- CATALYTIC ACTIVITY: Protein N(6)-methyl-L-lysine + 2-oxoglutarate
CC       + O(2) = protein L-lysine + succinate + formaldehyde + CO(2).
CC   -!- COFACTOR: Binds 1 Fe(2+) ion per subunit (By similarity).
CC   -!- SUBCELLULAR LOCATION: Nucleus.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1;
CC         IsoId=Q8N371-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q8N371-2; Sequence=VSP_026370;
CC         Note=No experimental confirmation available;
CC       Name=3;
CC         IsoId=Q8N371-3; Sequence=VSP_039893;
CC         Note=No experimental confirmation available;
CC   -!- TISSUE SPECIFICITY: Weakly expressed in most cells. Highly
CC       expressed in breast cancer cells.
CC   -!- SIMILARITY: Contains 1 JmjC domain.
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DR   EMBL; AK023860; BAB14706.1; -; mRNA.
DR   EMBL; AK297166; BAG59661.1; -; mRNA.
DR   EMBL; AY345239; AAQ23080.1; -; mRNA.
DR   EMBL; AC092725; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC106739; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC109449; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC027911; AAH27911.1; -; mRNA.
DR   IPI; IPI00296340; -.
DR   IPI; IPI00435577; -.
DR   IPI; IPI00922284; -.
DR   RefSeq; NP_001138820.1; NM_001145348.1.
DR   RefSeq; NP_079049.2; NM_024773.2.
DR   UniGene; Hs.145717; -.
DR   HSSP; Q9NWT6; 1MZF.
DR   ProteinModelPortal; Q8N371; -.
DR   SMR; Q8N371; 181-416.
DR   IntAct; Q8N371; 1.
DR   STRING; Q8N371; -.
DR   DMDM; 74728780; -.
DR   PRIDE; Q8N371; -.
DR   Ensembl; ENST00000286096; ENSP00000286096; ENSG00000155666.
DR   Ensembl; ENST00000441782; ENSP00000398410; ENSG00000155666.
DR   GeneID; 79831; -.
DR   KEGG; hsa:79831; -.
DR   UCSC; uc002doh.1; human.
DR   UCSC; uc010bxw.1; human.
DR   CTD; 79831; -.
DR   GeneCards; GC16P027123; -.
DR   HGNC; HGNC:25840; JMJD5.
DR   HPA; HPA026545; -.
DR   neXtProt; NX_Q8N371; -.
DR   PharmGKB; PA143485510; -.
DR   eggNOG; prNOG05246; -.
DR   GeneTree; ENSGT00530000062914; -.
DR   HOVERGEN; HBG105493; -.
DR   InParanoid; Q8N371; -.
DR   OMA; VYSYGCL; -.
DR   OrthoDB; EOG4894MV; -.
DR   PhylomeDB; Q8N371; -.
DR   NextBio; 69473; -.
DR   ArrayExpress; Q8N371; -.
DR   Bgee; Q8N371; -.
DR   CleanEx; HS_JMJD5; -.
DR   Genevestigator; Q8N371; -.
DR   GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR   GO; GO:0003682; F:chromatin binding; IDA:UniProtKB.
DR   GO; GO:0051864; F:histone demethylase activity (H3-K36 specific); IDA:UniProtKB.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0016702; F:oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen; IEA:UniProtKB-KW.
DR   GO; GO:0000086; P:G2/M transition of mitotic cell cycle; IMP:UniProtKB.
DR   GO; GO:0045893; P:positive regulation of transcription, DNA-dependent; IMP:UniProtKB.
DR   GO; GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
DR   InterPro; IPR022777; Cupin_JmjC.
DR   InterPro; IPR003347; TF_JmjC_AAH.
DR   Pfam; PF08007; Cupin_4; 1.
DR   SMART; SM00558; JmjC; 1.
DR   PROSITE; PS51184; JMJC; 1.
PE   1: Evidence at protein level;
KW   Alternative splicing; Cell cycle; Chromatin regulator;
KW   Complete proteome; Dioxygenase; Iron; Metal-binding; Nucleus;
KW   Oxidoreductase; Polymorphism; Reference proteome; Transcription;
KW   Transcription regulation.
FT   CHAIN         1    416       Lysine-specific demethylase 8.
FT                                /FTId=PRO_0000292010.
FT   DOMAIN      271    416       JmjC.
FT   METAL       321    321       Iron; catalytic (Probable).
FT   METAL       323    323       Iron; catalytic (By similarity).
FT   METAL       400    400       Iron; catalytic (By similarity).
FT   VAR_SEQ       1      1       M -> MSREKCSPGEGAEEGRGSEASGLKASAGHGTEPAGG
FT                                GPM (in isoform 3).
FT                                /FTId=VSP_039893.
FT   VAR_SEQ     167    362       Missing (in isoform 2).
FT                                /FTId=VSP_026370.
FT   VARIANT     302    302       E -> D (in dbSNP:rs34445573).
FT                                /FTId=VAR_032928.
FT   MUTAGEN     321    321       H->A: Loss of activity.
FT   CONFLICT     73     73       D -> G (in Ref. 1; BAB14706).
SQ   SEQUENCE   416 AA;  47270 MW;  18CE6D01E00ED5A4 CRC64;
     MAGDTHCPAE PLAREGTLWE ALRALLPHSK EDLKLDLGEK VERSVVTLLQ RATELFYEGR
     RDECLQSSEV ILDYSWEKLN TGTWQDVDKD WRRVYAIGCL LKALCLCQAP EDANTVAAAL
     RVCDMGLLMG AAILGDILLK VAAILQTHLP GKRPARGSLP EQPCTKKARA DHGLIPDVKL
     EKTVPRLHRP SLQHFREQFL VPGRPVILKG VADHWPCMQK WSLEYIQEIA GCRTVPVEVG
     SRYTDEEWSQ TLMTVNEFIS KYIVNEPRDV GYLAQHQLFD QIPELKQDIS IPDYCSLGDG
     EEEEITINAW FGPQGTISPL HQDPQQNFLV QVMGRKYIRL YSPQESGALY PHDTHLLHNT
     SQVDVENPDL EKFPKFAKAP FLSCILSPGE ILFIPVKYWH YVRALDLSFS VSFWWS
//