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Protein

Lysine-specific demethylase 4A

Gene

Kdm4a

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Histone demethylase that specifically demethylates 'Lys-9' and 'Lys-36' residues of histone H3, thereby playing a central role in histone code (PubMed:24953653). Does not demethylate histone H3 'Lys-4', H3 'Lys-27' nor H4 'Lys-20'. Demethylates trimethylated H3 'Lys-9' and H3 'Lys-36' residue, while it has no activity on mono- and dimethylated residues. Demethylation of Lys residue generates formaldehyde and succinate. Participates in transcriptional repression of ASCL2 and E2F-responsive promoters via the recruitment of histone deacetylases and NCOR1, respectively (By similarity).By similarity1 Publication

Cofactori

Fe2+By similarityNote: Binds 1 Fe2+ ion per subunit.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei1322-oxoglutarateBy similarity1
Metal bindingi188Iron; catalyticPROSITE-ProRule annotation1
Metal bindingi190Iron; catalyticPROSITE-ProRule annotation1
Binding sitei1982-oxoglutarateBy similarity1
Binding sitei2062-oxoglutarateBy similarity1
Metal bindingi234ZincBy similarity1
Metal bindingi240Zinc; via tele nitrogenBy similarity1
Binding sitei2412-oxoglutarateBy similarity1
Metal bindingi276Iron; catalyticPROSITE-ProRule annotation1
Metal bindingi306ZincBy similarity1
Metal bindingi308ZincBy similarity1
Binding sitei945Histone H3K4me3By similarity1
Binding sitei967Histone H3K4me3By similarity1
Binding sitei973Histone H3K4me3By similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri709 – 767PHD-type 1Add BLAST59
Zinc fingeri772 – 805C2HC pre-PHD-typePROSITE-ProRule annotationAdd BLAST34
Zinc fingeri828 – 885PHD-type 2PROSITE-ProRule annotationAdd BLAST58

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionChromatin regulator, Dioxygenase, Oxidoreductase
Biological processTranscription, Transcription regulation
LigandIron, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-MMU-3214842 HDMs demethylate histones
R-MMU-5693565 Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks

Names & Taxonomyi

Protein namesi
Recommended name:
Lysine-specific demethylase 4A (EC:1.14.11.-)
Alternative name(s):
JmjC domain-containing histone demethylation protein 3A
Jumonji domain-containing protein 2A
Gene namesi
Name:Kdm4a
Synonyms:Jhdm3a, Jmjd2, Jmjd2a, Kiaa0677
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 4

Organism-specific databases

MGIiMGI:2446210 Kdm4a

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

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00001831732 – 1064Lysine-specific demethylase 4AAdd BLAST1063

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineBy similarity1
Modified residuei523PhosphoserineBy similarity1

Post-translational modificationi

Ubiquitinated by RNF8 and RNF168, leading to its degradation (PubMed:24953653). Degradation promotes accessibility of H4K20me2 mark for DNA repair protein TP53BP1, which is then recruited (By similarity).By similarity1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ8BW72
PaxDbiQ8BW72
PeptideAtlasiQ8BW72
PRIDEiQ8BW72

PTM databases

iPTMnetiQ8BW72
PhosphoSitePlusiQ8BW72

Expressioni

Tissue specificityi

Widely expressed.1 Publication

Gene expression databases

BgeeiENSMUSG00000033326
CleanExiMM_JMJD2A
ExpressionAtlasiQ8BW72 baseline and differential
GenevisibleiQ8BW72 MM

Interactioni

Subunit structurei

Interacts with histone deacetylase proteins HDAC1, HDAC2 and HDAC3. Interacts with RB and NCOR1 (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

BioGridi230999, 4 interactors
IntActiQ8BW72, 1 interactor
STRINGi10090.ENSMUSP00000095524

Structurei

3D structure databases

ProteinModelPortaliQ8BW72
SMRiQ8BW72
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini14 – 56JmjNPROSITE-ProRule annotationAdd BLAST43
Domaini142 – 308JmjCPROSITE-ProRule annotationAdd BLAST167
Domaini897 – 954Tudor 1Add BLAST58
Domaini955 – 1011Tudor 2Add BLAST57

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni597 – 638Interaction with NCOR1By similarityAdd BLAST42

Domaini

The 2 Tudor domains recognize and bind methylated histone H3 'Lys-4' residue (H3K4me). Double Tudor domain has an interdigitated structure and the unusual fold is required for its ability to bind methylated histone tails. Trimethylated H3 'Lys-4' (H3K4me3) is bound in a cage of 3 aromatic residues, 2 of which are from the Tudor domain 2, while the binding specificity is determined by side-chain interactions involving residues from the Tudor domain 1. The Tudor domains are also able to bind trimethylated histone H3 'Lys-9' (H3K9me3), di- and trimethylated H4 'Lys-20' (H4K20me2 and H4K20me3). Has high affinity for H4K20me2, blocking recruitment of proteins such as TP53BP1 (By similarity).By similarity

Sequence similaritiesi

Belongs to the JHDM3 histone demethylase family.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri709 – 767PHD-type 1Add BLAST59
Zinc fingeri772 – 805C2HC pre-PHD-typePROSITE-ProRule annotationAdd BLAST34
Zinc fingeri828 – 885PHD-type 2PROSITE-ProRule annotationAdd BLAST58

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiENOG410IT40 Eukaryota
COG5141 LUCA
GeneTreeiENSGT00530000063342
HOVERGENiHBG080483
InParanoidiQ8BW72
KOiK06709
OMAiCRAQGQT
OrthoDBiEOG091G01FR
TreeFamiTF106449

Family and domain databases

Gene3Di3.30.40.10, 2 hits
InterProiView protein in InterPro
IPR034732 EPHD
IPR003347 JmjC_dom
IPR003349 JmjN
IPR002999 Tudor
IPR011011 Znf_FYVE_PHD
IPR001965 Znf_PHD
IPR013083 Znf_RING/FYVE/PHD
PfamiView protein in Pfam
PF02373 JmjC, 1 hit
PF02375 JmjN, 1 hit
SMARTiView protein in SMART
SM00558 JmjC, 1 hit
SM00545 JmjN, 1 hit
SM00249 PHD, 2 hits
SM00333 TUDOR, 2 hits
SUPFAMiSSF57903 SSF57903, 1 hit
PROSITEiView protein in PROSITE
PS51805 EPHD, 1 hit
PS51184 JMJC, 1 hit
PS51183 JMJN, 1 hit

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8BW72-1) [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
MASESETLNP SARIMTFYPT MEEFRNFSRY IAYIESQGAH RAGLAKVVPP
60 70 80 90 100
KEWKPRTSYD DIDDLVIPAP IQQLVTGQSG LFTQYNIQKK AMTVREFRKI
110 120 130 140 150
ANSDKYCTPR YSEFEELERK YWKNLTFNPP IYGADVNGTL YEQHVDEWNI
160 170 180 190 200
GRLKTILDLV EKESGITIEG VNTPYLYFGM WKTSFAWHTE DMDLYSINYL
210 220 230 240 250
HFGEPKSWYS VPPEHGKRLE RLAKGFFPGS AQSCEAFLRH KMTLISPLML
260 270 280 290 300
KKYGIPFDKV TQEAGEFMIT FPYGYHAGFN HGFNCAESTN FATRRWIEYG
310 320 330 340 350
KQAVLCSCRK DMVKISMDVF VRRFQPERYK LWKAGKDSMV IDHTLPTPEA
360 370 380 390 400
AEFLKDSGGL TPRAGSEECP EEDVEAADQG EEGDVKRSLA KHRIGTKRHR
410 420 430 440 450
VCLEIPQEVS QSELFPKEEL SSGQYEMTEC PATLAPVRPT HSSVRQVEDS
460 470 480 490 500
LPFPDYSDPT EVKFEELKNV KLEEEDEEDE PEAAALDLSV NPASVGGRLV
510 520 530 540 550
FSGSKKKSSS SLGSTSSQDS VSSDSETAES VSCQGQEKTG VLTVHSYARG
560 570 580 590 600
DGKAATGEPS VKKKRSAPRS ISEQELAEVA DEYMLSLEEN KKTKGRRQPL
610 620 630 640 650
SKLPRHHPLV LQECGSDDET SEQLTPEEEA EETEAWAKPL SQLWQNRPPN
660 670 680 690 700
FEAEKEFNEI MAQQAPHCAV CMIFQTYHQV EFGAFSQSCG DASEPAAQTQ
710 720 730 740 750
RTKPLIPEMC FTTTGCSTDI NLSTPYLEED GTSMLVSCKK CSVRVHASCY
760 770 780 790 800
GVPPAKASEE WMCSRCSANA LEEDCCLCSL RGGALQRAND DRWVHVSCAV
810 820 830 840 850
AILEARFVNI AERSPVDVSK IPLPRFKLKC VFCKKRRKRN AGCCVQCSHG
860 870 880 890 900
RCPTAFHVSC AQAAGVMMQP DDWPFVVFIT CFRHKIPNLE RAKGALLSIT
910 920 930 940 950
AGQKVISKHK NGRFYQCEVV RLTTETFYEV NFDDGSFSDN LYPEDIVSQD
960 970 980 990 1000
CLQLGPPAEG EVVQVRWTDG QVYGAKFVAS HPIQMYQVEF EDGSQLVVKR
1010 1020 1030 1040 1050
DDVYTLDEEL PKRVKSRLSV ASDMRFNEIF TEKEVKQEKK RQRVINSRYR
1060
EDYIEPALYR AIME
Length:1,064
Mass (Da):120,334
Last modified:July 27, 2011 - v3
Checksum:i92FB3E363FDF9E7D
GO
Isoform 2 (identifier: Q8BW72-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     948-1033: SQDCLQLGPP...MRFNEIFTEK → MSESGFWQHF...ISDQIISNSI
     1034-1064: Missing.

Note: No experimental confirmation available.
Show »
Length:1,033
Mass (Da):115,963
Checksum:iA0485D01A1AEDF4D
GO

Sequence cautioni

The sequence BAC97997 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti339M → T in BAC97997 (PubMed:14621295).Curated1
Sequence conflicti339M → T in BAE26217 (PubMed:16141072).Curated1
Sequence conflicti339M → T in AAH28866 (PubMed:15489334).Curated1
Sequence conflicti1007D → G in BAE26776 (PubMed:16141072).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_016144948 – 1033SQDCL…IFTEK → MSESGFWQHFGSSGTSSCYC RLDDCGLFACPWSVSKQKEP LFPGSLSRKSGHAGALSFPE EFRGVSVPCSPLKYAYISDQ IISNSI in isoform 2. 1 PublicationAdd BLAST86
Alternative sequenceiVSP_0161451034 – 1064Missing in isoform 2. 1 PublicationAdd BLAST31

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK129187 mRNA Translation: BAC97997.1 Different initiation.
AK054095 mRNA Translation: BAC35653.1
AK136085 mRNA Translation: BAE22812.1
AK145066 mRNA Translation: BAE26217.1
AK145947 mRNA Translation: BAE26776.1
AL626764 Genomic DNA No translation available.
BC028866 mRNA Translation: AAH28866.1
CCDSiCCDS51282.1 [Q8BW72-1]
RefSeqiNP_001155295.1, NM_001161823.1 [Q8BW72-1]
NP_759014.2, NM_172382.2
XP_006503073.1, XM_006503010.2 [Q8BW72-1]
UniGeneiMm.234234

Genome annotation databases

EnsembliENSMUST00000097911; ENSMUSP00000095524; ENSMUSG00000033326 [Q8BW72-1]
ENSMUST00000106403; ENSMUSP00000102011; ENSMUSG00000033326 [Q8BW72-1]
ENSMUST00000106406; ENSMUSP00000102014; ENSMUSG00000033326 [Q8BW72-1]
GeneIDi230674
KEGGimmu:230674
UCSCiuc008ujn.2 mouse [Q8BW72-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiKDM4A_MOUSE
AccessioniPrimary (citable) accession number: Q8BW72
Secondary accession number(s): A2A8L8
, Q3UKM5, Q3UM81, Q3UWV2, Q6ZQ72, Q8K137
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 16, 2004
Last sequence update: July 27, 2011
Last modified: May 23, 2018
This is version 133 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

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