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Q8N371 (KDM8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 84. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Lysine-specific demethylase 8

EC=1.14.11.27
Alternative name(s):
JmjC domain-containing protein 5
Jumonji domain-containing protein 5
Gene names
Name:KDM8
Synonyms:JMJD5
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length416 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.5

Catalytic activity

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.

Cofactor

Binds 1 Fe2+ ion per subunit By similarity.

Subcellular location

Nucleus Ref.5.

Tissue specificity

Weakly expressed in most cells. Highly expressed in breast cancer cells. Ref.5

Sequence similarities

Contains 1 JmjC domain.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q8N371-1)

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.
Isoform 2 (identifier: Q8N371-2)

The sequence of this isoform differs from the canonical sequence as follows:
     167-362: Missing.
Note: No experimental confirmation available.
Isoform 3 (identifier: Q8N371-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MSREKCSPGEGAEEGRGSEASGLKASAGHGTEPAGGGPM
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 416416Lysine-specific demethylase 8
PRO_0000292010

Regions

Domain271 – 416146JmjC

Sites

Metal binding3211Iron; catalytic Probable
Metal binding3231Iron; catalytic By similarity
Metal binding4001Iron; catalytic By similarity

Natural variations

Alternative sequence11M → MSREKCSPGEGAEEGRGSEA SGLKASAGHGTEPAGGGPM in isoform 3.
VSP_039893
Alternative sequence167 – 362196Missing in isoform 2.
VSP_026370
Natural variant3021E → D.
Corresponds to variant rs34445573 [ dbSNP | Ensembl ].
VAR_032928

Experimental info

Mutagenesis3211H → A: Loss of activity. Ref.5
Sequence conflict731D → G in BAB14706. Ref.1

Secondary structure

........................................................ 416
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 1, 2002. Version 1.
Checksum: 18CE6D01E00ED5A4

FASTA41647,270
        10         20         30         40         50         60 
MAGDTHCPAE PLAREGTLWE ALRALLPHSK EDLKLDLGEK VERSVVTLLQ RATELFYEGR 

        70         80         90        100        110        120 
RDECLQSSEV ILDYSWEKLN TGTWQDVDKD WRRVYAIGCL LKALCLCQAP EDANTVAAAL 

       130        140        150        160        170        180 
RVCDMGLLMG AAILGDILLK VAAILQTHLP GKRPARGSLP EQPCTKKARA DHGLIPDVKL 

       190        200        210        220        230        240 
EKTVPRLHRP SLQHFREQFL VPGRPVILKG VADHWPCMQK WSLEYIQEIA GCRTVPVEVG 

       250        260        270        280        290        300 
SRYTDEEWSQ TLMTVNEFIS KYIVNEPRDV GYLAQHQLFD QIPELKQDIS IPDYCSLGDG 

       310        320        330        340        350        360 
EEEEITINAW FGPQGTISPL HQDPQQNFLV QVMGRKYIRL YSPQESGALY PHDTHLLHNT 

       370        380        390        400        410 
SQVDVENPDL EKFPKFAKAP FLSCILSPGE ILFIPVKYWH YVRALDLSFS VSFWWS 

« Hide

Isoform 2 [UniParc].

Checksum: 3B9B54CCB843C8CD
Show »

FASTA22024,686
Isoform 3 [UniParc].

Checksum: B7F33C98121DC9F1
Show »

FASTA45450,852

References

« Hide 'large scale' references
[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. expand/collapse author list , 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. expand/collapse author list , 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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS10627.1. [Q8N371-1]
CCDS45448.1. [Q8N371-3]
RefSeqNP_001138820.1. NM_001145348.1. [Q8N371-3]
NP_079049.2. NM_024773.2. [Q8N371-1]
UniGeneHs.145717.

3D structure databases

PDBe
RCSB-PDB
PDBj
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[»]
ProteinModelPortalQ8N371.
SMRQ8N371. Positions 180-416.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid122923. 2 interactions.
IntActQ8N371. 1 interaction.
STRING9606.ENSP00000398410.

PTM databases

PhosphoSiteQ8N371.

Polymorphism databases

DMDM74728780.

Proteomic databases

MaxQBQ8N371.
PaxDbQ8N371.
PRIDEQ8N371.

Protocols and materials databases

DNASU79831.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000286096; ENSP00000286096; ENSG00000155666. [Q8N371-1]
ENST00000380948; ENSP00000370335; ENSG00000155666. [Q8N371-2]
ENST00000441782; ENSP00000398410; ENSG00000155666. [Q8N371-3]
ENST00000568965; ENSP00000456901; ENSG00000155666. [Q8N371-2]
GeneID79831.
KEGGhsa:79831.
UCSCuc002doh.2. human. [Q8N371-1]
uc010bxw.2. human. [Q8N371-2]
uc010vcn.1. human. [Q8N371-3]

Organism-specific databases

CTD79831.
GeneCardsGC16P027214.
H-InvDBHIX0012910.
HIX0173203.
HGNCHGNC:25840. KDM8.
HPAHPA026545.
MIM611917. gene.
neXtProtNX_Q8N371.
PharmGKBPA143485510.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG71927.
HOGENOMHOG000264453.
HOVERGENHBG105493.
InParanoidQ8N371.
OMAVYSYGCL.
OrthoDBEOG7KWSJQ.
PhylomeDBQ8N371.
TreeFamTF315056.

Gene expression databases

ArrayExpressQ8N371.
BgeeQ8N371.
CleanExHS_JMJD5.
GenevestigatorQ8N371.

Family and domain databases

InterProIPR003347. JmjC_dom.
[Graphical view]
SMARTSM00558. JmjC. 1 hit.
[Graphical view]
PROSITEPS51184. JMJC. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi79831.
NextBio69473.
PROQ8N371.
SOURCESearch...

Entry information

Entry nameKDM8_HUMAN
AccessionPrimary (citable) accession number: Q8N371
Secondary accession number(s): B4DLU9, Q6VAK5, Q9H8B1
Entry history
Integrated into UniProtKB/Swiss-Prot: June 26, 2007
Last sequence update: October 1, 2002
Last modified: July 9, 2014
This is version 84 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 16

Human chromosome 16: entries, gene names and cross-references to MIM