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Protein

JmjC domain-containing protein 5

Gene

KDM8

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

Functioni

Histone demethylase required for G2/M phase cell cycle progression (PubMed:20457893). Specifically demethylates dimethylated 'Lys-36' (H3K36me2) of histone H3, an epigenetic repressive mark, thereby acting as a transcription activator (PubMed:20457893). Regulates expression of CCNA1 (cyclin-A1), leading to regulate cancer cell proliferation (PubMed:20457893). In a complex with coregulator RCCD1, is also able to demethylate trimethylated 'Lys-36' (H3K36me3) of histone H3 (PubMed:24981860). Plays a role in transcriptional repression of satellite repeats, possibly by regulating H3K36 methylation levels in centromeric regions together with RCCD1 (PubMed:24981860). Possibly together with RCCD1, involved in proper mitotic spindle organization and chromosome segregation (PubMed:24981860). Plays a role in regulating alpha-tubulin acetylation and cytoskeletal microtubule stability (PubMed:28455245). Might function as a protein hydroxylase (PubMed:22851697, PubMed:24100311). Under stress conditions that cause a DNA damage response, acts as a histone protease by cleaving the N-terminal tail of histone H3 at the carboxyl side of monomethyl-lysine (Kme1) residues, preferably at monomethylated 'Lys-9' (H3K9me1) (PubMed:28982940). The histone variant H3F3A is the major target for cleavage (PubMed:28982940).2 Publications4 Publications

Caution

The demethylase activity of JMJD5 is controversial. Demethylase activity towards H3K36me2 was observed in vivo and in vitro (PubMed:20457893). In addition, demethylase activity towards H3K36me3 when in a complex with RCCD1 has been observed (PubMed:24981860). In contrast, in other studies, JMJD5 was shown not to display any demethylase activity toward methylated H3K36 nor toward other methyllysines in the N-terminal tails of H3 and H4 in vitro (PubMed:24100311, PubMed:22851697, PubMed:28982940). It has been suggested that JMJD5 might function as a protein hydroxylase instead (PubMed:22851697, PubMed:24100311).2 Publications5 Publications

Catalytic activityi

Protein N6,N6-dimethyl-L-lysine + 2 2-oxoglutarate + 2 O2 = protein L-lysine + 2 succinate + 2 formaldehyde + 2 CO2.

Cofactori

Fe2+2 PublicationsNote: Binds 1 Fe2+ ion per subunit.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei2722-oxoglutarateCombined sources1 Publication1 Publication1
Binding sitei3182-oxoglutarateCombined sources1 Publication1 Publication1
Metal bindingi321Iron; catalyticPROSITE-ProRule annotationCombined sources2 Publications1
Metal bindingi323Iron; catalyticPROSITE-ProRule annotationCombined sources2 Publications1
Binding sitei3272-oxoglutarateCombined sources1 Publication1 Publication1
Binding sitei3362-oxoglutarateCombined sources1 Publication1 Publication1
Metal bindingi400Iron; catalyticPROSITE-ProRule annotationCombined sources2 Publications1
Binding sitei4142-oxoglutarateCombined sources1 Publication1

GO - Molecular functioni

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

Keywordsi

Molecular functionChromatin regulator, Dioxygenase, Hydrolase, Oxidoreductase, Protease
Biological processCell cycle, Transcription, Transcription regulation
LigandIron, Metal-binding

Enzyme and pathway databases

BRENDAi1.14.11.27 2681
ReactomeiR-HSA-3214842 HDMs demethylate histones

Names & Taxonomyi

Protein namesi
Recommended name:
JmjC domain-containing protein 5Curated (EC:1.14.11.27, EC:3.4.-.-)
Alternative name(s):
Jumonji domain-containing protein 5
Lysine-specific demethylase 8
Gene namesi
Name:KDM8
Synonyms:JMJD5
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

EuPathDBiHostDB:ENSG00000155666.11
HGNCiHGNC:25840 KDM8
MIMi611917 gene
neXtProtiNX_Q8N371

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Chromosome, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi321 – 323HQD → AQA: Fails to cleave HIST1H3A. 1 Publication3
Mutagenesisi321H → A: Loss of H3K36me2 demethylase activity. 1 Publication1
Mutagenesisi335 – 336RK → AA: Loss of interaction with HIST1H3A. Fails to cleave HIST1H3A. 1 Publication2
Mutagenesisi398 – 400YWH → AAA: Fails to cleave HIST1H3A. 1 Publication3

Organism-specific databases

DisGeNETi79831
OpenTargetsiENSG00000155666
PharmGKBiPA143485510

Polymorphism and mutation databases

BioMutaiKDM8
DMDMi74728780

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002920101 – 416JmjC domain-containing protein 5Add BLAST416

Proteomic databases

EPDiQ8N371
MaxQBiQ8N371
PaxDbiQ8N371
PeptideAtlasiQ8N371
PRIDEiQ8N371
ProteomicsDBi71772
71773 [Q8N371-2]
71774 [Q8N371-3]

PTM databases

iPTMnetiQ8N371
PhosphoSitePlusiQ8N371

Expressioni

Tissue specificityi

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

Inductioni

Up-regulated upon starvation, DNA replication stress, UV treatment and by camptothecin and etoposide treatment.1 Publication

Gene expression databases

BgeeiENSG00000155666 Expressed in 152 organ(s), highest expression level in right lobe of liver
CleanExiHS_JMJD5
ExpressionAtlasiQ8N371 baseline and differential
GenevisibleiQ8N371 HS

Organism-specific databases

HPAiHPA026545

Interactioni

Subunit structurei

Can form homodimers (via JmjC domain) (PubMed:24100311, PubMed:28982940). Found in a complex with RCCD1 (PubMed:24981860). Interacts (via N-terminus) with RCCD1 (via N-terminus); this interaction stimulates H3K36me3 and H3K36me2 demethylation (PubMed:24981860, PubMed:28455245). Interacts (via JmjC domain) with HIST1H3A (PubMed:28982940).4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
MEOX2Q6FHY55EBI-12161375,EBI-16439278

Protein-protein interaction databases

BioGridi122923, 10 interactors
IntActiQ8N371, 6 interactors
STRINGi9606.ENSP00000398410

Structurei

Secondary structure

1416
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ8N371
SMRiQ8N371
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

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

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 110Interaction with RCCD11 PublicationAdd BLAST110

Phylogenomic databases

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

Family and domain databases

InterProiView protein in InterPro
IPR003347 JmjC_dom
SMARTiView protein in SMART
SM00558 JmjC, 1 hit
PROSITEiView protein in PROSITE
PS51184 JMJC, 1 hit

Sequences (3+)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 3 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H3BR76H3BR76_HUMAN
JmjC domain-containing protein 5
KDM8
163Annotation score:
H3BPT5H3BPT5_HUMAN
JmjC domain-containing protein 5
KDM8
90Annotation score:
H3BM39H3BM39_HUMAN
JmjC domain-containing protein 5
KDM8
120Annotation score:

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 dbSNP:rs34445573Ensembl.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

Similar proteinsi

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[»]
5FBJX-ray2.42A183-416[»]
6AVSX-ray2.02A183-416[»]
6AX3X-ray2.25A184-416[»]
6F4MX-ray1.71A183-416[»]
6F4NX-ray2.54A/B153-416[»]
6F4OX-ray1.28A183-416[»]
6F4PX-ray1.45A183-416[»]
6F4QX-ray1.12A183-416[»]
6F4RX-ray1.30A183-416[»]
6F4SX-ray1.46A183-416[»]
6F4TX-ray1.22A183-416[»]
ProteinModelPortaliQ8N371
SMRiQ8N371
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi122923, 10 interactors
IntActiQ8N371, 6 interactors
STRINGi9606.ENSP00000398410

PTM databases

iPTMnetiQ8N371
PhosphoSitePlusiQ8N371

Polymorphism and mutation databases

BioMutaiKDM8
DMDMi74728780

Proteomic databases

EPDiQ8N371
MaxQBiQ8N371
PaxDbiQ8N371
PeptideAtlasiQ8N371
PRIDEiQ8N371
ProteomicsDBi71772
71773 [Q8N371-2]
71774 [Q8N371-3]

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
DisGeNETi79831
EuPathDBiHostDB:ENSG00000155666.11
GeneCardsiKDM8
H-InvDBiHIX0012910
HIX0173203
HGNCiHGNC:25840 KDM8
HPAiHPA026545
MIMi611917 gene
neXtProtiNX_Q8N371
OpenTargetsiENSG00000155666
PharmGKBiPA143485510
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BRENDAi1.14.11.27 2681
ReactomeiR-HSA-3214842 HDMs demethylate histones

Miscellaneous databases

ChiTaRSiKDM8 human
GenomeRNAii79831
PROiPR:Q8N371
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000155666 Expressed in 152 organ(s), highest expression level in right lobe of liver
CleanExiHS_JMJD5
ExpressionAtlasiQ8N371 baseline and differential
GenevisibleiQ8N371 HS

Family and domain databases

InterProiView protein in InterPro
IPR003347 JmjC_dom
SMARTiView protein in SMART
SM00558 JmjC, 1 hit
PROSITEiView protein in PROSITE
PS51184 JMJC, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiKDM8_HUMAN
AccessioniPrimary (citable) accession number: Q8N371
Secondary accession number(s): B4DLU9, Q6VAK5, Q9H8B1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 26, 2007
Last sequence update: October 1, 2002
Last modified: November 7, 2018
This is version 116 of the entry and version 1 of the sequence. See 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
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Main funding by: National Institutes of Health

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