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Protein

Lysine-specific demethylase 8

Gene

KDM8

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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

Fe2+By similarityNote: 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
Complete GO annotation...

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
Complete GO annotation...

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

BgeeiQ8N371.
CleanExiHS_JMJD5.
ExpressionAtlasiQ8N371. baseline and differential.
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 – 1803Combined sources
Beta strandi181 – 1833Combined sources
Beta strandi186 – 1894Combined sources
Helixi192 – 1987Combined sources
Turni199 – 2035Combined sources
Beta strandi206 – 2127Combined sources
Helixi216 – 2205Combined sources
Helixi223 – 2308Combined sources
Beta strandi233 – 2397Combined sources
Helixi245 – 2473Combined sources
Beta strandi249 – 2546Combined sources
Helixi255 – 2628Combined sources
Beta strandi271 – 2766Combined sources
Helixi278 – 2814Combined sources
Helixi283 – 2864Combined sources
Helixi293 – 2975Combined sources
Beta strandi298 – 3003Combined sources
Helixi302 – 3043Combined sources
Beta strandi306 – 3127Combined sources
Beta strandi317 – 3215Combined sources
Beta strandi324 – 33411Combined sources
Beta strandi336 – 3416Combined sources
Helixi343 – 3486Combined sources
Turni355 – 3595Combined sources
Beta strandi360 – 3634Combined sources
Turni370 – 3723Combined sources
Helixi374 – 3785Combined sources
Beta strandi382 – 3865Combined sources
Beta strandi391 – 3944Combined sources
Beta strandi399 – 41517Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
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.
GeneTreeiENSGT00530000062914.
HOGENOMiHOG000264453.
HOVERGENiHBG105493.
InParanoidiQ8N371.
OMAiYSPQESG.
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

        10         20         30         40         50
MAGDTHCPAE PLAREGTLWE ALRALLPHSK EDLKLDLGEK VERSVVTLLQ
60 70 80 90 100
RATELFYEGR RDECLQSSEV ILDYSWEKLN TGTWQDVDKD WRRVYAIGCL
110 120 130 140 150
LKALCLCQAP EDANTVAAAL RVCDMGLLMG AAILGDILLK VAAILQTHLP
160 170 180 190 200
GKRPARGSLP EQPCTKKARA DHGLIPDVKL EKTVPRLHRP SLQHFREQFL
210 220 230 240 250
VPGRPVILKG VADHWPCMQK WSLEYIQEIA GCRTVPVEVG SRYTDEEWSQ
260 270 280 290 300
TLMTVNEFIS KYIVNEPRDV GYLAQHQLFD QIPELKQDIS IPDYCSLGDG
310 320 330 340 350
EEEEITINAW FGPQGTISPL HQDPQQNFLV QVMGRKYIRL YSPQESGALY
360 370 380 390 400
PHDTHLLHNT SQVDVENPDL EKFPKFAKAP FLSCILSPGE ILFIPVKYWH
410
YVRALDLSFS VSFWWS
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:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
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...

Protein-protein interaction databases

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

PTM databases

PhosphoSiteiQ8N371.

Polymorphism databases

DMDMi74728780.

Proteomic databases

MaxQBiQ8N371.
PaxDbiQ8N371.
PRIDEiQ8N371.

Protocols and materials databases

DNASUi79831.
Structural Biology KnowledgebaseSearch...

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]

Organism-specific databases

CTDi79831.
GeneCardsiGC16P027214.
H-InvDBHIX0012910.
HIX0173203.
HGNCiHGNC:25840. KDM8.
HPAiHPA026545.
MIMi611917. gene.
neXtProtiNX_Q8N371.
PharmGKBiPA143485510.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG71927.
GeneTreeiENSGT00530000062914.
HOGENOMiHOG000264453.
HOVERGENiHBG105493.
InParanoidiQ8N371.
OMAiYSPQESG.
OrthoDBiEOG7KWSJQ.
PhylomeDBiQ8N371.
TreeFamiTF315056.

Miscellaneous databases

GenomeRNAii79831.
NextBioi69473.
PROiQ8N371.
SOURCEiSearch...

Gene expression databases

BgeeiQ8N371.
CleanExiHS_JMJD5.
ExpressionAtlasiQ8N371. baseline and differential.
GenevestigatoriQ8N371.

Family and domain databases

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

Publicationsi

« Hide 'large scale' publications
  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: January 7, 2015
This is version 88 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.