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Protein

Lysine-specific demethylase 3A

Gene

Kdm3a

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Histone demethylase that specifically demethylates 'Lys-9' of histone H3, thereby playing a central role in histone code. Preferentially demethylates mono- and dimethylated H3 'Lys-9' residue, with a preference for dimethylated residue, while it has weak or no activity on trimethylated H3 'Lys-9'. Demethylation of Lys residue generates formaldehyde and succinate. Involved in hormone-dependent transcriptional activation, by participating in recruitment to androgen-receptor target genes, resulting in H3 'Lys-9' demethylation and transcriptional activation (By similarity). Involved in spermatogenesis by regulating expression of target genes such as PRM1 and TNP1 which are required for packaging and condensation of sperm chromatin (PubMed:17943087). Involved in obesity resistance through regulation of metabolic genes such as PPARA and UCP1.By similarity2 Publications

Cofactori

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi1122Iron; catalytic1
Metal bindingi1124Iron; catalytic1
Metal bindingi1251Iron; catalytic1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri662 – 687C6-typeSequence analysisAdd BLAST26

GO - Molecular functioni

GO - Biological processi

  • androgen receptor signaling pathway Source: MGI
  • cellular response to leukemia inhibitory factor Source: MGI
  • formaldehyde biosynthetic process Source: MGI
  • histone H3-K9 demethylation Source: MGI
  • histone H3-K9 dimethylation Source: MGI
  • hormone-mediated signaling pathway Source: MGI
  • negative regulation of histone H3-K9 methylation Source: MGI
  • positive regulation of transcription, DNA-templated Source: MGI
  • positive regulation of transcription from RNA polymerase II promoter Source: MGI
  • regulation of gene expression Source: MGI
  • regulation of stem cell differentiation Source: MGI
  • regulation of stem cell population maintenance Source: MGI
  • spermatid nucleus elongation Source: MGI
  • spermatogenesis Source: MGI
  • transcription, DNA-templated Source: UniProtKB-KW

Keywordsi

Molecular functionActivator, Chromatin regulator, Dioxygenase, Oxidoreductase
Biological processDifferentiation, Spermatogenesis, Transcription, Transcription regulation
LigandIron, Metal-binding, Zinc

Enzyme and pathway databases

BRENDAi1.14.11.B1. 3474.
ReactomeiR-MMU-3214842. HDMs demethylate histones.

Names & Taxonomyi

Protein namesi
Recommended name:
Lysine-specific demethylase 3A (EC:1.14.11.-)
Alternative name(s):
JmjC domain-containing histone demethylation protein 2A
Jumonji domain-containing protein 1A
Gene namesi
Name:Kdm3a
Synonyms:Jhdm2a, Jmjd1a, Kiaa0742
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 6

Organism-specific databases

MGIiMGI:98847. Kdm3a.

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

Cytoplasm, Nucleus

Pathology & Biotechi

Disruption phenotypei

Spermatogenesis defects and adult obesity.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000842861 – 1323Lysine-specific demethylase 3AAdd BLAST1323

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei264PhosphoserineBy similarity1
Modified residuei325PhosphoserineBy similarity1
Modified residuei446PhosphoserineBy similarity1
Modified residuei895N6-acetyllysineBy similarity1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ6PCM1.
PaxDbiQ6PCM1.
PeptideAtlasiQ6PCM1.
PRIDEiQ6PCM1.

PTM databases

iPTMnetiQ6PCM1.
PhosphoSitePlusiQ6PCM1.

Expressioni

Tissue specificityi

Highly expressed in testis (at protein level). Also expressed at high levels in tissues responsive to sympathetic nerve activity such as brown adipose tissue and skeletal muscle.1 Publication

Developmental stagei

Expression increases significantly during spermatogenesis with a 70-fold increase from day 7 testis to day 30 testis. First detected in the late pachytene stage, increases in diplotene and secondary spermatocytes and reaches its highest levels in round spermatids.1 Publication

Inductioni

By beta-adrenergic stimulation (at protein level).1 Publication

Gene expression databases

BgeeiENSMUSG00000053470.
CleanExiMM_JMJD1A.
ExpressionAtlasiQ6PCM1. baseline and differential.
GenevisibleiQ6PCM1. MM.

Interactioni

GO - Molecular functioni

Protein-protein interaction databases

BioGridi222501. 1 interactor.
IntActiQ6PCM1. 1 interactor.
STRINGi10090.ENSMUSP00000065716.

Structurei

3D structure databases

ProteinModelPortaliQ6PCM1.
SMRiQ6PCM1.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1060 – 1283JmjCAdd BLAST224

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi885 – 889LXXLL motif5

Domaini

The JmjC domain and the C6-type zinc-finger are required for the demethylation activity.By similarity
Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs are known to mediate the association with nuclear receptors.By similarity

Sequence similaritiesi

Belongs to the JHDM2 histone demethylase family.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri662 – 687C6-typeSequence analysisAdd BLAST26

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG1356. Eukaryota.
ENOG410XTAA. LUCA.
GeneTreeiENSGT00530000063039.
InParanoidiQ6PCM1.
KOiK15601.
OMAiNVFRECW.
OrthoDBiEOG091G00RB.
PhylomeDBiQ6PCM1.
TreeFamiTF324723.

Family and domain databases

InterProiView protein in InterPro
IPR003347. JmjC_dom.
PfamiView protein in Pfam
PF02373. JmjC. 1 hit.
SMARTiView protein in SMART
SM00558. JmjC. 1 hit.
PROSITEiView protein in PROSITE
PS51184. JMJC. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: Q6PCM1-1) [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
MVLTLGESWP VLVGKRFLSL SAAEGNEGGQ DNWDLERVAE WPWLSGTIRA
60 70 80 90 100
VSHTDVTKKD LKVCVEFDGE SWRKRRWIDV YSLQRKAFLV EHNLVLAERK
110 120 130 140 150
SPEVPEQVIQ WPAIMYKSLL DKAGLGAITS VRFLGDQQSV FVSKDLLKPI
160 170 180 190 200
QDVNSLRLSL TDNQTVSKEF QALIVKHLDE SHLLQGDKNL VGSEVKIYSL
210 220 230 240 250
DPSTQWFSAT VVHGNPSSKT LQVNCEEIPA LKIVDPALIH VEVVHDNFVT
260 270 280 290 300
CGNSTRTGAV KRKSSENNGS SVSKQAKSCS EASPSMCPVQ SVPTTVFKEI
310 320 330 340 350
LLGCTAATPS SKDPRQQNTP QAANSPPNIG AKLPQGCHKQ NLPEELSSCL
360 370 380 390 400
NTKPEVPRTK PDVCKEGLLS SKSSQVGAGD LKILSEPKGS CIQPKTNTDQ
410 420 430 440 450
ESRLESAPQP VTGLPKECLP AKTSSKAELD IATTPELQKH LEHAASTSDD
460 470 480 490 500
LSDKPEVKAG VTSLNSCAEK KVEPSHLGSQ SQNLKETSVK VDNESCCTRS
510 520 530 540 550
SNKTQTPPAR KSVLTDPDKV RKLQQSGEAF VQDDSCVNIV AQLPKCRECR
560 570 580 590 600
LDSLRKDKDQ QKDSPVFCRF FHFRRLQFNK HGVLRVEGFL TPNKYDSEAI
610 620 630 640 650
GLWLPLTKNV VGTDLDTAKY ILANIGDHFC QMVISEKEAM STIEPHRQVA
660 670 680 690 700
WKRAVKGVRE MCDVCDTTIF NLHWVCPRCG FGVCVDCYRM KRKNCQQGAA
710 720 730 740 750
YKTFSWIRCV KSQIHEPENL MPTQIIPGKA LYDVGDIVHS VRAKWGIKAN
760 770 780 790 800
CPCSNRQFKL FSKPALKEDL KQTSLSGEKP TLGTMVQQSS PVLEPVAVCG
810 820 830 840 850
EAASKPASSV KPTCPTSTSP LNWLADLTSG NVNKENKEKQ LTMPILKNEI
860 870 880 890 900
KCLPPLPPLN KPSTVLHTFN STILTPVSNN NSGFLRNLLN SSTAKTENGL
910 920 930 940 950
KNTPKILDDI FASLVQNKTS SDSSKRPQGL TIKPSILGFD TPHYWLCDNR
960 970 980 990 1000
LLCLQDPNNK SNWNVFRECW KQGQPVMVSG VHHKLNTELW KPESFRKEFG
1010 1020 1030 1040 1050
EQEVDLVNCR TNEIITGATV GDFWDGFEDV PNRLKNDKEK EPMVLKLKDW
1060 1070 1080 1090 1100
PPGEDFRDMM PSRFDDLMAN IPLPEYTRRD GKLNLASRLP NYFVRPDLGP
1110 1120 1130 1140 1150
KMYNAYGLIT PEDRKYGTTN LHLDVSDAAN VMVYVGIPKG QCEQEEEVLR
1160 1170 1180 1190 1200
TIQDGDSDEL TIKRFIEGKE KPGALWHIYA AKDTEKIREF LKKVSEEQGQ
1210 1220 1230 1240 1250
DNPADHDPIH DQSWYLDRSL RKRLYQEYGV QGWAIVQFLG DVVFIPAGAP
1260 1270 1280 1290 1300
HQVHNLYSCI KVAEDFVSPE HVKHCFWLTQ EFRYLSQTHT NHEDKLQVKN
1310 1320
VIYHAVKDAV AMLKASESSL GKP
Length:1,323
Mass (Da):147,847
Last modified:July 5, 2004 - v1
Checksum:i6D9C4A7779076AED
GO
Isoform 2 (identifier: Q6PCM1-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-492: Missing.
     493-507: NESCCTRSSNKTQTP → MFWGDWKNIMEGAPA

Note: No experimental confirmation available.
Show »
Length:831
Mass (Da):94,415
Checksum:i63B683DCE461B7C1
GO

Sequence cautioni

The sequence BAC98014 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti144K → Q in ABC54567 (Ref. 4) Curated1
Sequence conflicti229P → L in ABC54567 (Ref. 4) Curated1
Sequence conflicti618A → T in ABC54567 (Ref. 4) Curated1
Sequence conflicti832V → F in AAH31200 (PubMed:15489334).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0182961 – 492Missing in isoform 2. 1 PublicationAdd BLAST492
Alternative sequenceiVSP_018297493 – 507NESCC…KTQTP → MFWGDWKNIMEGAPA in isoform 2. 1 PublicationAdd BLAST15

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK129204 mRNA. Translation: BAC98014.1. Different initiation.
BC026605 mRNA. Translation: AAH26605.1.
BC031158 mRNA. Translation: AAH31158.1.
BC031200 mRNA. Translation: AAH31200.1.
BC059264 mRNA. Translation: AAH59264.1.
AK144825 mRNA. Translation: BAE26085.1.
AK166797 mRNA. Translation: BAE39025.1.
DQ323991 mRNA. Translation: ABC54567.1.
CCDSiCCDS20233.1. [Q6PCM1-1]
RefSeqiNP_001033784.2. NM_001038695.3. [Q6PCM1-1]
NP_766589.1. NM_173001.3. [Q6PCM1-1]
XP_006505327.1. XM_006505264.3. [Q6PCM1-1]
UniGeneiMm.260479.

Genome annotation databases

EnsembliENSMUST00000065509; ENSMUSP00000065716; ENSMUSG00000053470. [Q6PCM1-1]
ENSMUST00000167220; ENSMUSP00000128789; ENSMUSG00000053470. [Q6PCM1-1]
ENSMUST00000207023; ENSMUSP00000145959; ENSMUSG00000053470. [Q6PCM1-1]
GeneIDi104263.
KEGGimmu:104263.
UCSCiuc009cgy.3. mouse. [Q6PCM1-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiKDM3A_MOUSE
AccessioniPrimary (citable) accession number: Q6PCM1
Secondary accession number(s): Q2MJQ6
, Q3TKW8, Q3UML3, Q6ZQ57, Q8K2J6, Q8K2K4, Q8R350
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 22, 2005
Last sequence update: July 5, 2004
Last modified: October 25, 2017
This is version 118 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families