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Protein

Lysine-specific demethylase 2A

Gene

Kdm2a

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-36' of histone H3, thereby playing a central role in histone code. Preferentially demethylates dimethylated H3 'Lys-36' residue while it has weak or no activity for mono- and tri-methylated H3 'Lys-36'. May also recognize and bind to some phosphorylated proteins and promote their ubiquitination and degradation. Required to maintain the heterochromatic state. Associates with centromeres and represses transcription of small non-coding RNAs that are encoded by the clusters of satellite repeats at the centromere. Required to sustain centromeric integrity and genomic stability, particularly during mitosis (By similarity).By similarity

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
Binding sitei209SubstrateBy similarity1
Metal bindingi212Iron; catalyticPROSITE-ProRule annotation1
Metal bindingi214Iron; catalyticPROSITE-ProRule annotation1
Binding sitei229SubstrateBy similarity1
Metal bindingi284Iron; catalyticPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri564 – 610CXXC-typePROSITE-ProRule annotationAdd BLAST47
Zinc fingeri617 – 678PHD-typePROSITE-ProRule annotationAdd BLAST62

GO - Molecular functioni

GO - Biological processi

  • double-strand break repair via nonhomologous end joining Source: MGI
  • heart looping Source: MGI
  • histone H3-K36 demethylation Source: MGI
  • in utero embryonic development Source: MGI
  • multicellular organism growth Source: MGI
  • negative regulation of apoptotic process Source: MGI
  • negative regulation of gene expression Source: MGI
  • neural tube closure Source: MGI
  • neuroepithelial cell differentiation Source: MGI
  • neuron differentiation Source: MGI
  • positive regulation of gene expression Source: MGI
  • positive regulation of histone ubiquitination Source: MGI
  • regulation of transcription, DNA-templated Source: UniProtKB-KW
  • transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Chromatin regulator, Dioxygenase, Oxidoreductase, Repressor

Keywords - Biological processi

Transcription, Transcription regulation, Ubl conjugation pathway

Keywords - Ligandi

DNA-binding, Iron, Metal-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
Lysine-specific demethylase 2A (EC:1.14.11.27)
Alternative name(s):
F-box and leucine-rich repeat protein 11
F-box/LRR-repeat protein 11
JmjC domain-containing histone demethylation protein 1A
[Histone-H3]-lysine-36 demethylase 1A
Gene namesi
Name:Kdm2a
Synonyms:Fbxl11, Jhdm1a, Kiaa1004
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:1354736. Kdm2a.

Subcellular locationi

  • Nucleusnucleoplasm By similarity

  • Note: Punctate expression throughout the nucleoplasm and enriched in the perinucleolar region. Specifically nucleates at CpG islands where it's presence results in chromatin depleted in H3K36me2 (By similarity).By similarity

GO - Cellular componenti

  • nuclear chromatin Source: MGI
  • nucleolus Source: MGI
  • nucleoplasm Source: UniProtKB-SubCell
  • nucleus Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001198561 – 1161Lysine-specific demethylase 2AAdd BLAST1161

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei28PhosphoserineCombined sources1
Modified residuei390PhosphoserineBy similarity1
Modified residuei394PhosphoserineBy similarity1
Modified residuei444PhosphoserineCombined sources1
Modified residuei550PhosphothreonineCombined sources1
Modified residuei558PhosphoserineBy similarity1
Modified residuei632PhosphothreonineCombined sources1
Modified residuei692PhosphoserineCombined sources1
Modified residuei713PhosphothreonineCombined sources1
Modified residuei718PhosphoserineCombined sources1
Modified residuei731PhosphoserineCombined sources1
Modified residuei825PhosphoserineBy similarity1
Modified residuei868PhosphoserineBy similarity1
Modified residuei882PhosphoserineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiP59997.
MaxQBiP59997.
PaxDbiP59997.
PeptideAtlasiP59997.
PRIDEiP59997.

PTM databases

iPTMnetiP59997.
PhosphoSitePlusiP59997.

Expressioni

Gene expression databases

CleanExiMM_FBXL11.

Interactioni

Subunit structurei

Part of a SCF (SKP1-cullin-F-box) protein ligase complex. Interacts with CBX5/HP1A; the interaction promotes CBX5 localization to chromatin (By similarity).By similarity

Protein-protein interaction databases

DIPiDIP-46352N.
IntActiP59997. 1 interactor.
STRINGi10090.ENSMUSP00000047683.

Structurei

Secondary structure

11161
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi40 – 45Combined sources6
Helixi59 – 61Combined sources3
Helixi64 – 70Combined sources7
Beta strandi76 – 80Combined sources5
Turni82 – 84Combined sources3
Helixi95 – 102Combined sources8
Beta strandi107 – 112Combined sources6
Turni113 – 116Combined sources4
Beta strandi117 – 122Combined sources6
Helixi123 – 131Combined sources9
Helixi134 – 136Combined sources3
Beta strandi141 – 147Combined sources7
Helixi154 – 156Combined sources3
Helixi161 – 166Combined sources6
Helixi168 – 172Combined sources5
Helixi175 – 180Combined sources6
Helixi188 – 190Combined sources3
Beta strandi199 – 203Combined sources5
Beta strandi208 – 212Combined sources5
Helixi215 – 217Combined sources3
Beta strandi219 – 227Combined sources9
Beta strandi229 – 234Combined sources6
Helixi238 – 250Combined sources13
Turni253 – 255Combined sources3
Helixi258 – 260Combined sources3
Beta strandi261 – 263Combined sources3
Beta strandi266 – 270Combined sources5
Beta strandi275 – 278Combined sources4
Beta strandi283 – 287Combined sources5
Beta strandi292 – 299Combined sources8
Helixi305 – 317Combined sources13
Helixi322 – 324Combined sources3
Helixi329 – 345Combined sources17
Helixi352 – 362Combined sources11
Helixi455 – 469Combined sources15
Helixi473 – 476Combined sources4
Helixi485 – 499Combined sources15
Turni504 – 507Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4QWNX-ray2.10A/C36-364[»]
B/D450-517[»]
4QX7X-ray2.34A/C36-364[»]
B/D450-517[»]
4QX8X-ray1.65A/C36-364[»]
B/D450-517[»]
4QXBX-ray1.60A/C36-364[»]
B/D450-517[»]
4QXCX-ray1.75A/C36-364[»]
B/D450-517[»]
4QXHX-ray2.20A/C36-364[»]
B/D450-517[»]
4TN7X-ray2.20A/C36-364[»]
B/D450-517[»]
ProteinModelPortaliP59997.
SMRiP59997.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini148 – 316JmjCPROSITE-ProRule annotationAdd BLAST169
Domaini888 – 935F-boxAdd BLAST48
Repeati960 – 981LRR 1Add BLAST22
Repeati983 – 1009LRR 2Add BLAST27
Repeati1047 – 1072LRR 3Add BLAST26
Repeati1073 – 1102LRR 4Add BLAST30
Repeati1103 – 1127LRR 5Add BLAST25
Repeati1128 – 1155LRR 6Add BLAST28

Domaini

The JmjC domain mediates demethylation activity and is required for satellite silencing.By similarity
The CXXC zinc finger preferentially recognizes nonmethylated CpG DNA, and binding is blocked when the CpG DNA is methylated.By similarity

Sequence similaritiesi

Belongs to the JHDM1 histone demethylase family.Curated
Contains 1 CXXC-type zinc finger.PROSITE-ProRule annotation
Contains 1 F-box domain.Curated
Contains 1 JmjC domain.PROSITE-ProRule annotation
Contains 6 LRR (leucine-rich) repeats.Curated
Contains 1 PHD-type zinc finger.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri564 – 610CXXC-typePROSITE-ProRule annotationAdd BLAST47
Zinc fingeri617 – 678PHD-typePROSITE-ProRule annotationAdd BLAST62

Keywords - Domaini

Leucine-rich repeat, Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG1633. Eukaryota.
KOG1947. Eukaryota.
ENOG410XQXU. LUCA.
HOGENOMiHOG000007396.
InParanoidiP59997.
KOiK10276.
PhylomeDBiP59997.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
3.80.10.10. 1 hit.
InterProiIPR001810. F-box_dom.
IPR003347. JmjC_dom.
IPR032675. L_dom-like.
IPR006553. Leu-rich_rpt_Cys-con_subtyp.
IPR019786. Zinc_finger_PHD-type_CS.
IPR002857. Znf_CXXC.
IPR011011. Znf_FYVE_PHD.
IPR001965. Znf_PHD.
IPR019787. Znf_PHD-finger.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PfamiPF00646. F-box. 1 hit.
PF02373. JmjC. 1 hit.
PF16866. PHD_4. 1 hit.
PF02008. zf-CXXC. 1 hit.
[Graphical view]
SMARTiSM00558. JmjC. 1 hit.
SM00367. LRR_CC. 3 hits.
SM00249. PHD. 1 hit.
[Graphical view]
SUPFAMiSSF57903. SSF57903. 1 hit.
PROSITEiPS51184. JMJC. 1 hit.
PS51058. ZF_CXXC. 1 hit.
PS01359. ZF_PHD_1. 1 hit.
PS50016. ZF_PHD_2. 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: P59997-1) [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
MEPEEERIRY SQRLRGTMRR RYEDDGISDD EIEGKRTFDL EEKLQTNKYN
60 70 80 90 100
ANFVTFMEGK DFNVEYIQRG GLRDPLIFKN SDGLGIKMPD PDFTVNDVKM
110 120 130 140 150
CVGSRRMVDV MDVNTQKGIE MTMAQWTRYY ETPEEEREKL YNVISLEFSH
160 170 180 190 200
TRLENMVQWP STVDFIDWVD NMWPRHLKES QTESTNAILE MQYPKVQKYC
210 220 230 240 250
LISVRGCYTD FHVDFGGTSV WYHIHQGGKV FWLIPPTAHN LELYENWLLS
260 270 280 290 300
GKQGDIFLGD RVSDCQRIEL KQGYTFVIPS GWIHAVYTPT DTLVFGGNFL
310 320 330 340 350
HSFNIPMQLK IYSIEDRTRV PNKFRYPFYY EMCWYVLERY VYCITNRSHL
360 370 380 390 400
TKDFQKESLS MDMELNELES GNGDEEGVDR EARRMNNKRS VLTSPVANGV
410 420 430 440 450
NLDYDGLGKA CRSLPSLKKT LSGDSSSDST RGSHNGQVWD PQCSPKKDRQ
460 470 480 490 500
VHLTHFELEG LRCLVDKLES LPLHKKCVPT GIEDEDALIA DVKILLEELA
510 520 530 540 550
SSDPKLALTG VPIVQWPKRD KLKFPTRPKV RVPTIPITKP HTMKPAPRLT
560 570 580 590 600
PVRPAAASPI VSGARRRRVR CRKCKACVQG ECGVCHYCRD MKKFGGPGRM
610 620 630 640 650
KQSCVLRQCL APRLPHSVTC SLCGEVDQNE ETQDFEKKLM ECCICNEIVH
660 670 680 690 700
PGCLQMDGEG LLNEELPNCW ECPKCYQEDS SDKAQKRKIE ESDEEAVQAK
710 720 730 740 750
VLRPLRSCEE PLTPPPHSPT SMLQLIHDPV SPRGMVTRSS PGAGPSDHHS
760 770 780 790 800
ASRDERFKRR QLLRLQATER TMVREKENNP SGKKELSEVE KAKIRGSYLT
810 820 830 840 850
VTLQRPTKEL HGTSIVPKLQ AITASSANLR PNPRVLMQHC PARNPQHGDE
860 870 880 890 900
EGLGGEEEEE EEEEEDDSAE EGGAARLNGR GSWAQDGDES WMQREVWMSV
910 920 930 940 950
FRYLSRKELC ECMRVCKTWY KWCCDKRLWT KIDLSRCKAI VPQALSGIIK
960 970 980 990 1000
RQPVSLDLSW TNISKKQLTW LVNRLPGLKD LLLAGCSWSA VSALSTSSCP
1010 1020 1030 1040 1050
LLRTLDLRWA VGIKDPQIRD LLTPPTDKPG QDNRSKLRNM TDFRLAGLDI
1060 1070 1080 1090 1100
TDATLRLIIR HMPLLSRLDL SHCSHLTDQS SNLLTAVGSS TRYSLTELNM
1110 1120 1130 1140 1150
AGCNKLTDQT LFFLRRIANV TLIDLRGCKQ ITRKACEHFI SDLSINSLYC
1160
LSDEKLIQKI S
Length:1,161
Mass (Da):132,680
Last modified:March 7, 2006 - v2
Checksum:i210BD9F65BED0AE4
GO
Isoform 2 (identifier: P59997-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     494-494: I → S
     495-1161: Missing.

Note: No experimental confirmation available.
Show »
Length:494
Mass (Da):57,492
Checksum:i00BAE63E96EC5E44
GO
Isoform 3 (identifier: P59997-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     321-338: PNKFRYPFYYEMCWYVLE → SNVTIICVDVSPFKADVR
     339-1161: Missing.

Note: No experimental confirmation available.
Show »
Length:338
Mass (Da):39,634
Checksum:i73D648015209B855
GO

Sequence cautioni

The sequence BC076576 differs from that shown. Reason: Frameshift at position 834.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti159W → R in BAE20506 (PubMed:16141072).Curated1
Sequence conflicti159W → R in BC076576 (PubMed:15489334).Curated1
Sequence conflicti202I → M in BAE20506 (PubMed:16141072).Curated1
Sequence conflicti202I → M in BC076576 (PubMed:15489334).Curated1
Sequence conflicti913M → I in AAH57051 (PubMed:15489334).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_017471321 – 338PNKFR…WYVLE → SNVTIICVDVSPFKADVR in isoform 3. 1 PublicationAdd BLAST18
Alternative sequenceiVSP_017472339 – 1161Missing in isoform 3. 1 PublicationAdd BLAST823
Alternative sequenceiVSP_017473494I → S in isoform 2. 1 Publication1
Alternative sequenceiVSP_017474495 – 1161Missing in isoform 2. 1 PublicationAdd BLAST667

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK037157 mRNA. Translation: BAE20506.1.
AK141779 mRNA. Translation: BAE24832.1.
AK155866 mRNA. Translation: BAE33470.1.
BC057051 mRNA. Translation: AAH57051.1.
BC076576 mRNA. No translation available.
AK173084 mRNA. Translation: BAD32362.1.
CCDSiCCDS37886.1. [P59997-1]
RefSeqiNP_001001984.2. NM_001001984.2.
UniGeneiMm.31941.

Genome annotation databases

GeneIDi225876.
KEGGimmu:225876.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK037157 mRNA. Translation: BAE20506.1.
AK141779 mRNA. Translation: BAE24832.1.
AK155866 mRNA. Translation: BAE33470.1.
BC057051 mRNA. Translation: AAH57051.1.
BC076576 mRNA. No translation available.
AK173084 mRNA. Translation: BAD32362.1.
CCDSiCCDS37886.1. [P59997-1]
RefSeqiNP_001001984.2. NM_001001984.2.
UniGeneiMm.31941.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4QWNX-ray2.10A/C36-364[»]
B/D450-517[»]
4QX7X-ray2.34A/C36-364[»]
B/D450-517[»]
4QX8X-ray1.65A/C36-364[»]
B/D450-517[»]
4QXBX-ray1.60A/C36-364[»]
B/D450-517[»]
4QXCX-ray1.75A/C36-364[»]
B/D450-517[»]
4QXHX-ray2.20A/C36-364[»]
B/D450-517[»]
4TN7X-ray2.20A/C36-364[»]
B/D450-517[»]
ProteinModelPortaliP59997.
SMRiP59997.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-46352N.
IntActiP59997. 1 interactor.
STRINGi10090.ENSMUSP00000047683.

PTM databases

iPTMnetiP59997.
PhosphoSitePlusiP59997.

Proteomic databases

EPDiP59997.
MaxQBiP59997.
PaxDbiP59997.
PeptideAtlasiP59997.
PRIDEiP59997.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi225876.
KEGGimmu:225876.

Organism-specific databases

CTDi22992.
MGIiMGI:1354736. Kdm2a.
RougeiSearch...

Phylogenomic databases

eggNOGiKOG1633. Eukaryota.
KOG1947. Eukaryota.
ENOG410XQXU. LUCA.
HOGENOMiHOG000007396.
InParanoidiP59997.
KOiK10276.
PhylomeDBiP59997.

Miscellaneous databases

ChiTaRSiKdm2a. mouse.
PROiP59997.
SOURCEiSearch...

Gene expression databases

CleanExiMM_FBXL11.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
3.80.10.10. 1 hit.
InterProiIPR001810. F-box_dom.
IPR003347. JmjC_dom.
IPR032675. L_dom-like.
IPR006553. Leu-rich_rpt_Cys-con_subtyp.
IPR019786. Zinc_finger_PHD-type_CS.
IPR002857. Znf_CXXC.
IPR011011. Znf_FYVE_PHD.
IPR001965. Znf_PHD.
IPR019787. Znf_PHD-finger.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PfamiPF00646. F-box. 1 hit.
PF02373. JmjC. 1 hit.
PF16866. PHD_4. 1 hit.
PF02008. zf-CXXC. 1 hit.
[Graphical view]
SMARTiSM00558. JmjC. 1 hit.
SM00367. LRR_CC. 3 hits.
SM00249. PHD. 1 hit.
[Graphical view]
SUPFAMiSSF57903. SSF57903. 1 hit.
PROSITEiPS51184. JMJC. 1 hit.
PS51058. ZF_CXXC. 1 hit.
PS01359. ZF_PHD_1. 1 hit.
PS50016. ZF_PHD_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiKDM2A_MOUSE
AccessioniPrimary (citable) accession number: P59997
Secondary accession number(s): Q3U1M5
, Q3UR56, Q3V3Q1, Q69ZT4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 7, 2003
Last sequence update: March 7, 2006
Last modified: November 2, 2016
This is version 123 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. 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.