Q8N371 (KDM8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	JMJD5
Synonyms:	KDM8

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	416 AA.
Sequence status	Complete.
Protein existence	Evidence 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.

Ontologies

Keywords
Biological process	Cell cycle Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	Iron Metal-binding
Molecular function	Chromatin regulator Dioxygenase Oxidoreductase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	G2/M transition of mitotic cell cycle Inferred from mutant phenotype Ref.5. Source: UniProtKB positive regulation of transcription, DNA-dependent Inferred from mutant phenotype Ref.5. Source: UniProtKB transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	nucleus Inferred from direct assay Ref.5. Source: UniProtKB
Molecular function	chromatin binding Inferred from direct assay Ref.5. Source: UniProtKB histone demethylase activity (H3-K36 specific) Inferred from direct assay Ref.5. Source: UniProtKB metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 416	416	Lysine-specific demethylase 8		PRO_0000292010
Regions
	Domain	271 – 416	146	JmjC
Sites
	Metal binding	321	1	Iron; catalytic Probable
	Metal binding	323	1	Iron; catalytic By similarity
	Metal binding	400	1	Iron; catalytic By similarity
Natural variations
	Alternative sequence	1	1	M → MSREKCSPGEGAEEGRGSEA SGLKASAGHGTEPAGGGPM in isoform 3.		VSP_039893
	Alternative sequence	167 – 362	196	Missing in isoform 2.		VSP_026370
	Natural variant	302	1	E → D. Corresponds to variant rs34445573 [ dbSNP | Ensembl ].		VAR_032928
Experimental info
	Mutagenesis	321	1	H → A: Loss of activity. Ref.5
	Sequence conflict	73	1	D → G in BAB14706. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 1, 2002. Version 1. Checksum: 18CE6D01E00ED5A4	FASTA	416	47,270
	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
	Isoform 2 [UniParc]. Checksum: 3B9B54CCB843C8CD	FASTA	220	24,686
	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 EQPCTKVDVE NPDLEKFPKF 190 200 210 220 AKAPFLSCIL SPGEILFIPV KYWHYVRALD LSFSVSFWWS
	Isoform 3 [UniParc]. Checksum: B7F33C98121DC9F1	FASTA	454	50,852
	10 20 30 40 50 60 MSREKCSPGE GAEEGRGSEA SGLKASAGHG TEPAGGGPMA GDTHCPAEPL AREGTLWEAL 70 80 90 100 110 120 RALLPHSKED LKLDLGEKVE RSVVTLLQRA TELFYEGRRD ECLQSSEVIL DYSWEKLNTG 130 140 150 160 170 180 TWQDVDKDWR RVYAIGCLLK ALCLCQAPED ANTVAAALRV CDMGLLMGAA ILGDILLKVA 190 200 210 220 230 240 AILQTHLPGK RPARGSLPEQ PCTKKARADH GLIPDVKLEK TVPRLHRPSL QHFREQFLVP 250 260 270 280 290 300 GRPVILKGVA DHWPCMQKWS LEYIQEIAGC RTVPVEVGSR YTDEEWSQTL MTVNEFISKY 310 320 330 340 350 360 IVNEPRDVGY LAQHQLFDQI PELKQDISIP DYCSLGDGEE EEITINAWFG PQGTISPLHQ 370 380 390 400 410 420 DPQQNFLVQV MGRKYIRLYS PQESGALYPH DTHLLHNTSQ VDVENPDLEK FPKFAKAPFL 430 440 450 SCILSPGEIL FIPVKYWHYV RALDLSFSVS FWWS

References

	« Hide 'large scale' referencesShow '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. , 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: 14702039] [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: 15616553] [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: 15489334] [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: 20457893] [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.
IPI	IPI00296340. IPI00435577. IPI00922284.
RefSeq	NP_001138820.1. NM_001145348.1. NP_079049.2. NM_024773.2.
UniGene	Hs.145717.
3D structure databases
HSSP	HSSP built from PDB template 1MZF based on UniProtKB Q9NWT6.
ProteinModelPortal	Q8N371.
SMR	Q8N371. Positions 181-416.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q8N371. 1 interaction.
STRING	Q8N371.
Polymorphism databases
DMDM	74728780.
Proteomic databases
PRIDE	Q8N371.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000286096; ENSP00000286096; ENSG00000155666. ENST00000441782; ENSP00000398410; ENSG00000155666.
GeneID	79831.
KEGG	hsa:79831.
UCSC	uc002doh.1. human. uc010bxw.1. human.
Organism-specific databases
CTD	79831.
GeneCards	GC16P027123.
HGNC	HGNC:25840. JMJD5.
HPA	HPA026545.
neXtProt	NX_Q8N371.
PharmGKB	PA143485510.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG05246.
GeneTree	ENSGT00530000062914.
HOVERGEN	HBG105493.
InParanoid	Q8N371.
OMA	VYSYGCL.
OrthoDB	EOG4894MV.
PhylomeDB	Q8N371.
Gene expression databases
ArrayExpress	Q8N371.
Bgee	Q8N371.
CleanEx	HS_JMJD5.
Genevestigator	Q8N371.
Family and domain databases
InterPro	IPR022777. Cupin_JmjC. IPR003347. TF_JmjC_AAH. [Graphical view]
Pfam	PF08007. Cupin_4. 1 hit. [Graphical view]
SMART	SM00558. JmjC. 1 hit. [Graphical view]
PROSITE	PS51184. JMJC. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	69473.

Entry information

Entry name

KDM8_HUMAN

Accession

Primary (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:	January 25, 2012
This is version 61 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.