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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)DescriptionActionsGraphical viewLength
Metal bindingi321Iron; catalyticCurated1
Metal bindingi323Iron; catalyticPROSITE-ProRule annotation1
Metal bindingi400Iron; catalyticPROSITE-ProRule annotation1

GO - Molecular functioni

  • chromatin binding Source: UniProtKB
  • histone demethylase activity (H3-K36 specific) Source: UniProtKB
  • metal ion binding Source: UniProtKB-KW

GO - Biological processi

  • G2/M transition of mitotic cell cycle Source: UniProtKB
  • histone H3-K36 demethylation Source: UniProtKB
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • 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

Enzyme and pathway databases

BioCyciZFISH:ENSG00000155666-MONOMER.
BRENDAi1.14.11.27. 2681.
ReactomeiR-HSA-3214842. HDMs demethylate histones.

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
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

HGNCiHGNC:25840. KDM8.

Subcellular locationi

GO - Cellular componenti

  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi321H → A: Loss of activity. 1 Publication1

Organism-specific databases

OpenTargetsiENSG00000155666.
PharmGKBiPA143485510.

Polymorphism and mutation databases

BioMutaiKDM8.
DMDMi74728780.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002920101 – 416Lysine-specific demethylase 8Add BLAST416

Proteomic databases

EPDiQ8N371.
MaxQBiQ8N371.
PaxDbiQ8N371.
PeptideAtlasiQ8N371.
PRIDEiQ8N371.

PTM databases

iPTMnetiQ8N371.
PhosphoSitePlusiQ8N371.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSG00000155666.
CleanExiHS_JMJD5.
ExpressionAtlasiQ8N371. baseline and differential.
GenevisibleiQ8N371. HS.

Organism-specific databases

HPAiHPA026545.

Interactioni

Protein-protein interaction databases

BioGridi122923. 5 interactors.
IntActiQ8N371. 2 interactors.
STRINGi9606.ENSP00000398410.

Structurei

Secondary structure

1416
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi178 – 180Combined sources3
Beta strandi181 – 183Combined sources3
Beta strandi186 – 189Combined sources4
Helixi192 – 198Combined sources7
Turni199 – 203Combined sources5
Beta strandi206 – 212Combined sources7
Helixi216 – 220Combined sources5
Helixi223 – 230Combined sources8
Beta strandi233 – 239Combined sources7
Beta strandi245 – 247Combined sources3
Beta strandi249 – 254Combined sources6
Helixi255 – 262Combined sources8
Beta strandi271 – 276Combined sources6
Helixi278 – 281Combined sources4
Helixi283 – 286Combined sources4
Helixi293 – 297Combined sources5
Beta strandi298 – 300Combined sources3
Helixi302 – 304Combined sources3
Beta strandi306 – 312Combined sources7
Beta strandi317 – 321Combined sources5
Beta strandi324 – 334Combined sources11
Beta strandi336 – 341Combined sources6
Helixi343 – 348Combined sources6
Turni355 – 359Combined sources5
Beta strandi360 – 363Combined sources4
Turni370 – 372Combined sources3
Helixi374 – 378Combined sources5
Beta strandi382 – 386Combined sources5
Beta strandi391 – 394Combined sources4
Beta strandi399 – 415Combined sources17

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
4QU1X-ray1.57A183-416[»]
ProteinModelPortaliQ8N371.
SMRiQ8N371.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini271 – 416JmjCPROSITE-ProRule annotationAdd BLAST146

Sequence similaritiesi

Contains 1 JmjC domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG2132. Eukaryota.
ENOG410XQDR. LUCA.
GeneTreeiENSGT00530000062914.
HOGENOMiHOG000264453.
HOVERGENiHBG105493.
InParanoidiQ8N371.
KOiK10277.
OMAiPHSKEDL.
OrthoDBiEOG091G069K.
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. AlignAdd to basket

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)DescriptionActionsGraphical viewLength
Sequence conflicti73D → G in BAB14706 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_032928302E → D.Corresponds to variant rs34445573dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0398931M → MSREKCSPGEGAEEGRGSEA SGLKASAGHGTEPAGGGPM in isoform 3. 1 Publication1
Alternative sequenceiVSP_026370167 – 362Missing in isoform 2. 1 PublicationAdd BLAST196

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.3. human. [Q8N371-1]

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
PDB 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[»]
4QU1X-ray1.57A183-416[»]
ProteinModelPortaliQ8N371.
SMRiQ8N371.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi122923. 5 interactors.
IntActiQ8N371. 2 interactors.
STRINGi9606.ENSP00000398410.

PTM databases

iPTMnetiQ8N371.
PhosphoSitePlusiQ8N371.

Polymorphism and mutation databases

BioMutaiKDM8.
DMDMi74728780.

Proteomic databases

EPDiQ8N371.
MaxQBiQ8N371.
PaxDbiQ8N371.
PeptideAtlasiQ8N371.
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.3. human. [Q8N371-1]

Organism-specific databases

CTDi79831.
GeneCardsiKDM8.
H-InvDBHIX0012910.
HIX0173203.
HGNCiHGNC:25840. KDM8.
HPAiHPA026545.
MIMi611917. gene.
neXtProtiNX_Q8N371.
OpenTargetsiENSG00000155666.
PharmGKBiPA143485510.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2132. Eukaryota.
ENOG410XQDR. LUCA.
GeneTreeiENSGT00530000062914.
HOGENOMiHOG000264453.
HOVERGENiHBG105493.
InParanoidiQ8N371.
KOiK10277.
OMAiPHSKEDL.
OrthoDBiEOG091G069K.
PhylomeDBiQ8N371.
TreeFamiTF315056.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000155666-MONOMER.
BRENDAi1.14.11.27. 2681.
ReactomeiR-HSA-3214842. HDMs demethylate histones.

Miscellaneous databases

GenomeRNAii79831.
PROiQ8N371.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000155666.
CleanExiHS_JMJD5.
ExpressionAtlasiQ8N371. baseline and differential.
GenevisibleiQ8N371. HS.

Family and domain databases

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

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: November 30, 2016
This is version 102 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

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 one 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.