Reviewed, UniProtKB/Swiss-Prot P59997 (KDM2A_MOUSE)

Names and origin

Protein names

Recommended name:
    Lysine-specific demethylase 2A
    EC=1.14.11.27
Alternative name(s):
    JmjC domain-containing histone demethylation protein 1A
    [Histone-H3]-lysine-36 demethylase 1A
    F-box and leucine-rich repeat protein 11
    F-box/LRR-repeat protein 11

Gene names

Name:	Kdm2a
Synonyms:	Fbxl11, Jhdm1a, Kiaa1004

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	1161 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	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.
Catalytic activity	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.
Cofactor	Binds 1 Fe2+ ion per subunit By similarity.
Subunit structure	Part of a SCF (SKP1-cullin-F-box) protein ligase complex. Interacts with CBX5/HP1A; the interaction promotes CBX5 localization to chromatin By similarity.
Subcellular location	Nucleus › nucleoplasm By similarity. Note: Punctate expression throughout the nucleoplasm and enriched in the perinucleolar region By similarity.
Domain	The JmjC domain mediates demethylation activity and is required for satellite silencing By similarity.
Post-translational modification	Phosphorylated upon DNA damage, probably by ATM or ATR. Ref.4 Ref.5
Sequence similarities	Belongs to the JHDM1 histone demethylase family. Contains 1 CXXC-type zinc finger. Contains 1 F-box domain. Contains 1 JmjC domain. Contains 3 LRR (leucine-rich) repeats. Contains 1 PHD-type zinc finger.
Sequence caution	The sequence BC076576 differs from that shown. Reason: Frameshift at position 834.

Ontologies

Keywords
Biological process	Transcription Transcription regulation Ubl conjugation pathway
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Domain	Leucine-rich repeat Repeat Zinc-finger
Ligand	DNA-binding Iron Metal-binding Zinc
Molecular function	Chromatin regulator Dioxygenase Oxidoreductase Repressor
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	chromatin modification Inferred from electronic annotation. Source: UniProtKB-KW modification-dependent protein catabolic process Inferred from electronic annotation. Source: UniProtKB-KW oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW regulation of transcription Inferred from electronic annotation. Source: UniProtKB-KW transcription Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	nucleoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	DNA binding Inferred from electronic annotation. Source: UniProtKB-KW histone demethylase activity (H3-K36 specific) Inferred from electronic annotation. Source: EC iron ion binding Inferred from electronic annotation. Source: UniProtKB-KW oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen Inferred from electronic annotation. Source: UniProtKB-KW protein binding Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P59997-1)

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.

Isoform 2 (identifier: P59997-2)

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

Note: No experimental confirmation available.

Isoform 3 (identifier: P59997-3)

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

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1161	1161	Lysine-specific demethylase 2A		PRO_0000119856
Regions
	Domain	148 – 316	169	JmjC
	Domain	888 – 935	48	F-box
	Repeat	999 – 1024	26	LRR 1
	Repeat	1062 – 1090	29	LRR 2
	Repeat	1094 – 1117	24	LRR 3
	Zinc finger	564 – 610	47	CXXC-type
	Zinc finger	617 – 678	62	PHD-type
Sites
	Metal binding	212	1	Iron; catalytic By similarity
	Metal binding	214	1	Iron; catalytic By similarity
	Metal binding	284	1	Iron; catalytic By similarity
	Binding site	209	1	Substrate By similarity
	Binding site	229	1	Substrate By similarity
Amino acid modifications
	Modified residue	28	1	Phosphoserine Ref.5
	Modified residue	390	1	Phosphoserine By similarity
	Modified residue	394	1	Phosphoserine By similarity
	Modified residue	534	1	Phosphothreonine By similarity
	Modified residue	550	1	Phosphothreonine By similarity
	Modified residue	558	1	Phosphoserine By similarity
	Modified residue	632	1	Phosphothreonine Ref.4
	Modified residue	692	1	Phosphoserine By similarity
	Modified residue	713	1	Phosphothreonine By similarity
	Modified residue	718	1	Phosphoserine By similarity
	Modified residue	720	1	Phosphothreonine By similarity
	Modified residue	721	1	Phosphoserine By similarity
	Modified residue	731	1	Phosphoserine By similarity
	Modified residue	739	1	Phosphoserine By similarity
	Modified residue	740	1	Phosphoserine By similarity
	Modified residue	868	1	Phosphoserine By similarity
Natural variations
	Alternative sequence	321 – 338	18	PNKFR…WYVLE → SNVTIICVDVSPFKADVR in isoform 3.		VSP_017471
	Alternative sequence	339 – 1161	823	Missing in isoform 3.		VSP_017472
	Alternative sequence	494	1	I → S in isoform 2.		VSP_017473
	Alternative sequence	495 – 1161	667	Missing in isoform 2.		VSP_017474
Experimental info
	Sequence conflict	159	1	W → R in BAE20506. Ref.1
	Sequence conflict	159	1	W → R in BC076576. Ref.2
	Sequence conflict	202	1	I → M in BAE20506. Ref.1
	Sequence conflict	202	1	I → M in BC076576. Ref.2
	Sequence conflict	913	1	M → I in AAH57051. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 7, 2006. Version 2. Checksum: 210BD9F65BED0AE4	FASTA	1,161	132,680
	10 20 30 40 50 60 MEPEEERIRY SQRLRGTMRR RYEDDGISDD EIEGKRTFDL EEKLQTNKYN ANFVTFMEGK 70 80 90 100 110 120 DFNVEYIQRG GLRDPLIFKN SDGLGIKMPD PDFTVNDVKM CVGSRRMVDV MDVNTQKGIE 130 140 150 160 170 180 MTMAQWTRYY ETPEEEREKL YNVISLEFSH TRLENMVQWP STVDFIDWVD NMWPRHLKES 190 200 210 220 230 240 QTESTNAILE MQYPKVQKYC LISVRGCYTD FHVDFGGTSV WYHIHQGGKV FWLIPPTAHN 250 260 270 280 290 300 LELYENWLLS GKQGDIFLGD RVSDCQRIEL KQGYTFVIPS GWIHAVYTPT DTLVFGGNFL 310 320 330 340 350 360 HSFNIPMQLK IYSIEDRTRV PNKFRYPFYY EMCWYVLERY VYCITNRSHL TKDFQKESLS 370 380 390 400 410 420 MDMELNELES GNGDEEGVDR EARRMNNKRS VLTSPVANGV NLDYDGLGKA CRSLPSLKKT 430 440 450 460 470 480 LSGDSSSDST RGSHNGQVWD PQCSPKKDRQ VHLTHFELEG LRCLVDKLES LPLHKKCVPT 490 500 510 520 530 540 GIEDEDALIA DVKILLEELA SSDPKLALTG VPIVQWPKRD KLKFPTRPKV RVPTIPITKP 550 560 570 580 590 600 HTMKPAPRLT PVRPAAASPI VSGARRRRVR CRKCKACVQG ECGVCHYCRD MKKFGGPGRM 610 620 630 640 650 660 KQSCVLRQCL APRLPHSVTC SLCGEVDQNE ETQDFEKKLM ECCICNEIVH PGCLQMDGEG 670 680 690 700 710 720 LLNEELPNCW ECPKCYQEDS SDKAQKRKIE ESDEEAVQAK VLRPLRSCEE PLTPPPHSPT 730 740 750 760 770 780 SMLQLIHDPV SPRGMVTRSS PGAGPSDHHS ASRDERFKRR QLLRLQATER TMVREKENNP 790 800 810 820 830 840 SGKKELSEVE KAKIRGSYLT VTLQRPTKEL HGTSIVPKLQ AITASSANLR PNPRVLMQHC 850 860 870 880 890 900 PARNPQHGDE EGLGGEEEEE EEEEEDDSAE EGGAARLNGR GSWAQDGDES WMQREVWMSV 910 920 930 940 950 960 FRYLSRKELC ECMRVCKTWY KWCCDKRLWT KIDLSRCKAI VPQALSGIIK RQPVSLDLSW 970 980 990 1000 1010 1020 TNISKKQLTW LVNRLPGLKD LLLAGCSWSA VSALSTSSCP LLRTLDLRWA VGIKDPQIRD 1030 1040 1050 1060 1070 1080 LLTPPTDKPG QDNRSKLRNM TDFRLAGLDI TDATLRLIIR HMPLLSRLDL SHCSHLTDQS 1090 1100 1110 1120 1130 1140 SNLLTAVGSS TRYSLTELNM AGCNKLTDQT LFFLRRIANV TLIDLRGCKQ ITRKACEHFI 1150 1160 SDLSINSLYC LSDEKLIQKI S
	Isoform 2. Checksum: 00BAE63E96EC5E44	FASTA	494	57,492
	10 20 30 40 50 60 MEPEEERIRY SQRLRGTMRR RYEDDGISDD EIEGKRTFDL EEKLQTNKYN ANFVTFMEGK 70 80 90 100 110 120 DFNVEYIQRG GLRDPLIFKN SDGLGIKMPD PDFTVNDVKM CVGSRRMVDV MDVNTQKGIE 130 140 150 160 170 180 MTMAQWTRYY ETPEEEREKL YNVISLEFSH TRLENMVQWP STVDFIDWVD NMWPRHLKES 190 200 210 220 230 240 QTESTNAILE MQYPKVQKYC LISVRGCYTD FHVDFGGTSV WYHIHQGGKV FWLIPPTAHN 250 260 270 280 290 300 LELYENWLLS GKQGDIFLGD RVSDCQRIEL KQGYTFVIPS GWIHAVYTPT DTLVFGGNFL 310 320 330 340 350 360 HSFNIPMQLK IYSIEDRTRV PNKFRYPFYY EMCWYVLERY VYCITNRSHL TKDFQKESLS 370 380 390 400 410 420 MDMELNELES GNGDEEGVDR EARRMNNKRS VLTSPVANGV NLDYDGLGKA CRSLPSLKKT 430 440 450 460 470 480 LSGDSSSDST RGSHNGQVWD PQCSPKKDRQ VHLTHFELEG LRCLVDKLES LPLHKKCVPT 490 GIEDEDALIA DVKS
	Isoform 3. Checksum: 73D648015209B855	FASTA	338	39,634
	10 20 30 40 50 60 MEPEEERIRY SQRLRGTMRR RYEDDGISDD EIEGKRTFDL EEKLQTNKYN ANFVTFMEGK 70 80 90 100 110 120 DFNVEYIQRG GLRDPLIFKN SDGLGIKMPD PDFTVNDVKM CVGSRRMVDV MDVNTQKGIE 130 140 150 160 170 180 MTMAQWTRYY ETPEEEREKL YNVISLEFSH TRLENMVQWP STVDFIDWVD NMWPRHLKES 190 200 210 220 230 240 QTESTNAILE MQYPKVQKYC LISVRGCYTD FHVDFGGTSV WYHIHQGGKV FWLIPPTAHN 250 260 270 280 290 300 LELYENWLLS GKQGDIFLGD RVSDCQRIEL KQGYTFVIPS GWIHAVYTPT DTLVFGGNFL 310 320 330 HSFNIPMQLK IYSIEDRTRV SNVTIICVDV SPFKADVR

References

[1]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 646-1161. Strain: C57BL/6J. Tissue: Skin.
[2]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Strain: C57BL/6. Tissue: Brain.
[3]	"Prediction of the coding sequences of mouse homologues of KIAA gene: IV. The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs identified by screening of terminal sequences of cDNA clones randomly sampled from size-fractionated libraries." Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S., Saga Y., Seino S., Nishimura M., Kaisho T., Hoshino K., Kitamura H., Nagase T., Ohara O., Koga H. DNA Res. 11:205-218(2004) [PubMed: 15368895] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 453-1161. Tissue: Thymus.
[4]	"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed: 17525332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-632, MASS SPECTROMETRY.
[5]	"Solid tumor proteome and phosphoproteome analysis by high resolution mass spectrometry." Zanivan S., Gnad F., Wickstroem S.A., Geiger T., Macek B., Cox J., Faessler R., Mann M. J. Proteome Res. 7:5314-5326(2008) [PubMed: 18973353] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-28, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	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.
IPI	IPI00453782. IPI00742275. IPI00742336.
RefSeq	NP_001001984.2.
UniGene	Mm.31941
3D structure databases
SMR	P59997. Positions 36-364, 450-517.
ModBase	Search...
Protein-protein interaction databases
STRING	P59997.
PTM databases
PhosphoSite	P59997.
Proteomic databases
PRIDE	P59997.
Genome annotation databases
Ensembl	ENSMUST00000047898; ENSMUSP00000047683; ENSMUSG00000054611; Mus musculus. [Genome view] ENSMUST00000075856; ENSMUSP00000076698; ENSMUSG00000054611; Mus musculus. [Genome view] ENSMUST00000116571; ENSMUSP00000112270; ENSMUSG00000054611; Mus musculus. [Genome view]
GeneID	225876.
KEGG	mmu:225876.
UCSC	uc008fzw.1. mouse. uc008fzy.1. mouse.
Organism-specific databases
MGI	MGI:1354736. Kdm2a.
Rouge	Search...
Phylogenomic databases
HOGENOM	P59997.
HOVERGEN	P59997.
Enzyme and pathway databases
BRENDA	1.14.11.27. 244.
Gene expression databases
ArrayExpress	P59997.
Bgee	P59997.
CleanEx	MM_FBXL11.
Genevestigator	P59997.
GermOnline	ENSMUSG00000054611. Mus musculus.
Family and domain databases
InterPro	IPR001810. F-box. IPR013129. TF_JmjC. IPR003347. TF_JmjC_AAH. IPR019786. Zinc_finger_PHD-type_CS. IPR002857. Znf_CXXC. IPR001965. Znf_PHD. IPR019787. Znf_PHD-finger. [Graphical view]
Pfam	PF00646. F-box. 1 hit. PF02373. JmjC. 1 hit. PF02008. zf-CXXC. 1 hit. [Graphical view]
SMART	SM00256. FBOX. 1 hit. SM00558. JmjC. 1 hit. SM00249. PHD. 1 hit. [Graphical view]
PROSITE	PS50181. FBOX. False negative. PS51184. JMJC. 1 hit. PS51058. ZF_CXXC. 1 hit. PS01359. ZF_PHD_1. 1 hit. PS50016. ZF_PHD_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	377841.
SOURCE	Search...

Entry information

Entry name

KDM2A_MOUSE

Accession

Primary (citable) accession number: P59997
Secondary accession number(s): Q3U1M5 , Q3UR56, Q3V3Q1, Q69ZT4

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 7, 2003
Last sequence update:	March 7, 2006
Last modified:	October 13, 2009
This is version 63 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)