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Q8N371

- KDM8_HUMAN

UniProt

Q8N371 - KDM8_HUMAN

Protein

Lysine-specific demethylase 8

Gene

KDM8

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 85 (01 Oct 2014)
      Sequence version 1 (01 Oct 2002)
      Previous versions | rss
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    Functioni

    Histone demethylase required for G2/M phase cell cycle progression. Specifically demethylates dimethylated 'Lys-36' (H3K36me2) of histone H3, an epigenetic repressive mark, thereby acting as a transcription activator. Regulates expression of CCNA1 (cyclin-A1), leading to regulate cancer cell proliferation.1 Publication

    Catalytic activityi

    Protein N6,N(6)-dimethyl-L-lysine + 2-oxoglutarate + O2 = protein N(6)-methyl-L-lysine + succinate + formaldehyde + CO2.
    Protein N(6)-methyl-L-lysine + 2-oxoglutarate + O2 = protein L-lysine + succinate + formaldehyde + CO2.

    Cofactori

    Binds 1 Fe2+ ion per subunit.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi321 – 3211Iron; catalyticCurated
    Metal bindingi323 – 3231Iron; catalyticPROSITE-ProRule annotation
    Metal bindingi400 – 4001Iron; catalyticPROSITE-ProRule annotation

    GO - Molecular functioni

    1. chromatin binding Source: UniProtKB
    2. histone demethylase activity (H3-K36 specific) Source: UniProtKB
    3. metal ion binding Source: UniProtKB-KW

    GO - Biological processi

    1. G2/M transition of mitotic cell cycle Source: UniProtKB
    2. histone H3-K36 demethylation Source: UniProtKB
    3. positive regulation of transcription, DNA-templated Source: UniProtKB
    4. transcription, DNA-templated Source: UniProtKB-KW

    Keywords - Molecular functioni

    Chromatin regulator, Dioxygenase, Oxidoreductase

    Keywords - Biological processi

    Cell cycle, Transcription, Transcription regulation

    Keywords - Ligandi

    Iron, Metal-binding

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Lysine-specific demethylase 8 (EC:1.14.11.27)
    Alternative name(s):
    JmjC domain-containing protein 5
    Jumonji domain-containing protein 5
    Gene namesi
    Name:KDM8
    Synonyms:JMJD5
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 16

    Organism-specific databases

    HGNCiHGNC:25840. KDM8.

    Subcellular locationi

    Nucleus 1 Publication

    GO - Cellular componenti

    1. nucleus Source: UniProtKB

    Keywords - Cellular componenti

    Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi321 – 3211H → A: Loss of activity. 1 Publication

    Organism-specific databases

    PharmGKBiPA143485510.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 416416Lysine-specific demethylase 8PRO_0000292010Add
    BLAST

    Proteomic databases

    MaxQBiQ8N371.
    PaxDbiQ8N371.
    PRIDEiQ8N371.

    PTM databases

    PhosphoSiteiQ8N371.

    Expressioni

    Tissue specificityi

    Weakly expressed in most cells. Highly expressed in breast cancer cells.1 Publication

    Gene expression databases

    ArrayExpressiQ8N371.
    BgeeiQ8N371.
    CleanExiHS_JMJD5.
    GenevestigatoriQ8N371.

    Organism-specific databases

    HPAiHPA026545.

    Interactioni

    Protein-protein interaction databases

    BioGridi122923. 2 interactions.
    IntActiQ8N371. 1 interaction.
    STRINGi9606.ENSP00000398410.

    Structurei

    Secondary structure

    1
    416
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi178 – 1803
    Beta strandi181 – 1833
    Beta strandi186 – 1894
    Helixi192 – 1987
    Turni199 – 2035
    Beta strandi206 – 2127
    Helixi216 – 2205
    Helixi223 – 2308
    Beta strandi233 – 2397
    Helixi245 – 2473
    Beta strandi249 – 2546
    Helixi255 – 2628
    Beta strandi271 – 2766
    Helixi278 – 2814
    Helixi283 – 2864
    Helixi293 – 2975
    Beta strandi298 – 3003
    Helixi302 – 3043
    Beta strandi306 – 3127
    Beta strandi317 – 3215
    Beta strandi324 – 33411
    Beta strandi336 – 3416
    Helixi343 – 3486
    Turni355 – 3595
    Beta strandi360 – 3634
    Turni370 – 3723
    Helixi374 – 3785
    Beta strandi382 – 3865
    Beta strandi391 – 3944
    Beta strandi399 – 41517

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    3UYJX-ray2.35A/B173-416[»]
    4AAPX-ray2.60A/B180-416[»]
    4GAZX-ray2.81A/B176-416[»]
    4GJYX-ray1.25A183-416[»]
    4GJZX-ray1.05A183-416[»]
    ProteinModelPortaliQ8N371.
    SMRiQ8N371. Positions 180-416.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini271 – 416146JmjCPROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Contains 1 JmjC domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiNOG71927.
    HOGENOMiHOG000264453.
    HOVERGENiHBG105493.
    InParanoidiQ8N371.
    OMAiVYSYGCL.
    OrthoDBiEOG7KWSJQ.
    PhylomeDBiQ8N371.
    TreeFamiTF315056.

    Family and domain databases

    InterProiIPR003347. JmjC_dom.
    [Graphical view]
    SMARTiSM00558. JmjC. 1 hit.
    [Graphical view]
    PROSITEiPS51184. JMJC. 1 hit.
    [Graphical view]

    Sequences (3)i

    Sequence statusi: Complete.

    This entry describes 3 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q8N371-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MAGDTHCPAE PLAREGTLWE ALRALLPHSK EDLKLDLGEK VERSVVTLLQ    50
    RATELFYEGR RDECLQSSEV ILDYSWEKLN TGTWQDVDKD WRRVYAIGCL 100
    LKALCLCQAP EDANTVAAAL RVCDMGLLMG AAILGDILLK VAAILQTHLP 150
    GKRPARGSLP EQPCTKKARA DHGLIPDVKL EKTVPRLHRP SLQHFREQFL 200
    VPGRPVILKG VADHWPCMQK WSLEYIQEIA GCRTVPVEVG SRYTDEEWSQ 250
    TLMTVNEFIS KYIVNEPRDV GYLAQHQLFD QIPELKQDIS IPDYCSLGDG 300
    EEEEITINAW FGPQGTISPL HQDPQQNFLV QVMGRKYIRL YSPQESGALY 350
    PHDTHLLHNT SQVDVENPDL EKFPKFAKAP FLSCILSPGE ILFIPVKYWH 400
    YVRALDLSFS VSFWWS 416
    Length:416
    Mass (Da):47,270
    Last modified:October 1, 2002 - v1
    Checksum:i18CE6D01E00ED5A4
    GO
    Isoform 2 (identifier: Q8N371-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         167-362: Missing.

    Note: No experimental confirmation available.

    Show »
    Length:220
    Mass (Da):24,686
    Checksum:i3B9B54CCB843C8CD
    GO
    Isoform 3 (identifier: Q8N371-3) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-1: M → MSREKCSPGEGAEEGRGSEASGLKASAGHGTEPAGGGPM

    Note: No experimental confirmation available.

    Show »
    Length:454
    Mass (Da):50,852
    Checksum:iB7F33C98121DC9F1
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti73 – 731D → G in BAB14706. (PubMed:14702039)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti302 – 3021E → D.
    Corresponds to variant rs34445573 [ dbSNP | Ensembl ].
    VAR_032928

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 11M → MSREKCSPGEGAEEGRGSEA SGLKASAGHGTEPAGGGPM in isoform 3. 1 PublicationVSP_039893
    Alternative sequencei167 – 362196Missing in isoform 2. 1 PublicationVSP_026370Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AK023860 mRNA. Translation: BAB14706.1.
    AK297166 mRNA. Translation: BAG59661.1.
    AY345239 mRNA. Translation: AAQ23080.1.
    AC092725 Genomic DNA. No translation available.
    AC106739 Genomic DNA. No translation available.
    AC109449 Genomic DNA. No translation available.
    BC027911 mRNA. Translation: AAH27911.1.
    CCDSiCCDS10627.1. [Q8N371-1]
    CCDS45448.1. [Q8N371-3]
    RefSeqiNP_001138820.1. NM_001145348.1. [Q8N371-3]
    NP_079049.2. NM_024773.2. [Q8N371-1]
    UniGeneiHs.145717.

    Genome annotation databases

    EnsembliENST00000286096; ENSP00000286096; ENSG00000155666. [Q8N371-1]
    ENST00000441782; ENSP00000398410; ENSG00000155666. [Q8N371-3]
    ENST00000568965; ENSP00000456901; ENSG00000155666. [Q8N371-2]
    GeneIDi79831.
    KEGGihsa:79831.
    UCSCiuc002doh.2. human. [Q8N371-1]
    uc010bxw.2. human. [Q8N371-2]
    uc010vcn.1. human. [Q8N371-3]

    Polymorphism databases

    DMDMi74728780.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AK023860 mRNA. Translation: BAB14706.1 .
    AK297166 mRNA. Translation: BAG59661.1 .
    AY345239 mRNA. Translation: AAQ23080.1 .
    AC092725 Genomic DNA. No translation available.
    AC106739 Genomic DNA. No translation available.
    AC109449 Genomic DNA. No translation available.
    BC027911 mRNA. Translation: AAH27911.1 .
    CCDSi CCDS10627.1. [Q8N371-1 ]
    CCDS45448.1. [Q8N371-3 ]
    RefSeqi NP_001138820.1. NM_001145348.1. [Q8N371-3 ]
    NP_079049.2. NM_024773.2. [Q8N371-1 ]
    UniGenei Hs.145717.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    3UYJ X-ray 2.35 A/B 173-416 [» ]
    4AAP X-ray 2.60 A/B 180-416 [» ]
    4GAZ X-ray 2.81 A/B 176-416 [» ]
    4GJY X-ray 1.25 A 183-416 [» ]
    4GJZ X-ray 1.05 A 183-416 [» ]
    ProteinModelPortali Q8N371.
    SMRi Q8N371. Positions 180-416.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 122923. 2 interactions.
    IntActi Q8N371. 1 interaction.
    STRINGi 9606.ENSP00000398410.

    PTM databases

    PhosphoSitei Q8N371.

    Polymorphism databases

    DMDMi 74728780.

    Proteomic databases

    MaxQBi Q8N371.
    PaxDbi Q8N371.
    PRIDEi Q8N371.

    Protocols and materials databases

    DNASUi 79831.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000286096 ; ENSP00000286096 ; ENSG00000155666 . [Q8N371-1 ]
    ENST00000441782 ; ENSP00000398410 ; ENSG00000155666 . [Q8N371-3 ]
    ENST00000568965 ; ENSP00000456901 ; ENSG00000155666 . [Q8N371-2 ]
    GeneIDi 79831.
    KEGGi hsa:79831.
    UCSCi uc002doh.2. human. [Q8N371-1 ]
    uc010bxw.2. human. [Q8N371-2 ]
    uc010vcn.1. human. [Q8N371-3 ]

    Organism-specific databases

    CTDi 79831.
    GeneCardsi GC16P027214.
    H-InvDB HIX0012910.
    HIX0173203.
    HGNCi HGNC:25840. KDM8.
    HPAi HPA026545.
    MIMi 611917. gene.
    neXtProti NX_Q8N371.
    PharmGKBi PA143485510.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG71927.
    HOGENOMi HOG000264453.
    HOVERGENi HBG105493.
    InParanoidi Q8N371.
    OMAi VYSYGCL.
    OrthoDBi EOG7KWSJQ.
    PhylomeDBi Q8N371.
    TreeFami TF315056.

    Miscellaneous databases

    GenomeRNAii 79831.
    NextBioi 69473.
    PROi Q8N371.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q8N371.
    Bgeei Q8N371.
    CleanExi HS_JMJD5.
    Genevestigatori Q8N371.

    Family and domain databases

    InterProi IPR003347. JmjC_dom.
    [Graphical view ]
    SMARTi SM00558. JmjC. 1 hit.
    [Graphical view ]
    PROSITEi PS51184. JMJC. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
      Tissue: Brain and Thyroid.
    2. Li H., Yu R., Zheng G., Zhou G., Ke R., Shen C., Zhong G., Lin L., Yang S.
      Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
    3. "The sequence and analysis of duplication-rich human chromosome 16."
      Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J.
      , Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., Rubin E.M., Pennacchio L.A.
      Nature 432:988-994(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
      Tissue: Lung.
    5. "KDM8, a H3K36me2 histone demethylase that acts in the cyclin A1 coding region to regulate cancer cell proliferation."
      Hsia D.A., Tepper C.G., Pochampalli M.R., Hsia E.Y., Izumiya C., Huerta S.B., Wright M.E., Chen H.W., Kung H.J., Izumiya Y.
      Proc. Natl. Acad. Sci. U.S.A. 107:9671-9676(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, MUTAGENESIS OF HIS-321.

    Entry informationi

    Entry nameiKDM8_HUMAN
    AccessioniPrimary (citable) accession number: Q8N371
    Secondary accession number(s): B4DLU9, Q6VAK5, Q9H8B1
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: June 26, 2007
    Last sequence update: October 1, 2002
    Last modified: October 1, 2014
    This is version 85 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 16
      Human chromosome 16: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3