Q9Y4C1 (KDM3A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	KDM3A
Synonyms:	JHDM2A, JMJD1, JMJD1A, KIAA0742, TSGA

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1321 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. Involved in spermatogenesis by regulating expression of target genes such as PRM1 and TMP1 which are required for packaging and condensation of sperm chromatin. Involved in obesity resistance through regulation of metabolic genes such as PPARA and UCP1. Ref.5
Cofactor	Binds 1 Fe2+ ion per subunit. Ref.5
Subcellular location	Cytoplasm By similarity. Nucleus By similarity. Note: Nuclear in round spermatids. When spermatids start to elongate, localizes to the cytoplasm where it forms distinct foci which disappear in mature spermatozoa By similarity.
Domain	The JmjC domain and the C6-type zinc-finger are required for the demethylation activity. Ref.5 Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs are known to mediate the association with nuclear receptors By similarity. Ref.5
Sequence similarities	Belongs to the JHDM2 histone demethylase family. Contains 1 JmjC domain.
Sequence caution	The sequence BAA34462.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Biological process	Differentiation Spermatogenesis Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
Domain	Zinc-finger
Ligand	Iron Metal-binding Zinc
Molecular function	Activator Chromatin regulator Dioxygenase Oxidoreductase
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	androgen receptor signaling pathway Inferred from direct assay Ref.5. Source: UniProtKB cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW formaldehyde biosynthetic process Inferred from direct assay Ref.5. Source: UniProtKB histone H3-K9 demethylation Inferred from direct assay Ref.5. Source: UniProtKB hormone-mediated signaling pathway Inferred from direct assay Ref.5. Source: UniProtKB positive regulation of transcription, DNA-dependent Inferred from mutant phenotype Ref.5. Source: UniProtKB spermatogenesis Inferred from electronic annotation. Source: UniProtKB-KW transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from direct assay Ref.5. Source: UniProtKB
Molecular function	androgen receptor binding Inferred from direct assay Ref.5. Source: UniProtKB iron ion binding Inferred from mutant phenotype Ref.5. Source: UniProtKB oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1321	1321	Lysine-specific demethylase 3A		PRO_0000084285
Regions
	Domain	1058 – 1281	224	JmjC
	Zinc finger	662 – 687	26	C6-type Potential
	Motif	885 – 889	5	LXXLL motif
Sites
	Metal binding	1120	1	Iron; catalytic Probable
	Metal binding	1122	1	Iron; catalytic By similarity
	Metal binding	1249	1	Iron; catalytic By similarity
Amino acid modifications
	Modified residue	445	1	Phosphoserine Ref.6
	Modified residue	895	1	N6-acetyllysine Ref.7
Natural variations
	Natural variant	187	1	D → H in a breast cancer sample; somatic mutation. Ref.8		VAR_035940
	Natural variant	194	1	E → K. Corresponds to variant rs13424350 [ dbSNP | Ensembl ].		VAR_030623
	Natural variant	212	1	I → V. Ref.1 Ref.2 Ref.4 Corresponds to variant rs2030259 [ dbSNP | Ensembl ].		VAR_026220
	Natural variant	447	1	S → P. Ref.2 Corresponds to variant rs34605051 [ dbSNP | Ensembl ].		VAR_055977
	Natural variant	710	1	V → E. Corresponds to variant rs11677451 [ dbSNP | Ensembl ].		VAR_030624
Experimental info
	Mutagenesis	1120	1	H → Y: Abolishes histone demethylase activity. Ref.5
	Sequence conflict	24	1	D → G in CAH18459. Ref.2
	Sequence conflict	24	1	D → G in CAH18373. Ref.2
	Sequence conflict	51	1	V → A in CAE45820. Ref.2
	Sequence conflict	500	1	S → G in CAH18373. Ref.2
	Sequence conflict	698	1	G → GG in CAH18459. Ref.2
	Sequence conflict	729	1	K → KG in CAH18459. Ref.2
	Sequence conflict	767	1	K → R in CAH18459. Ref.2
	Sequence conflict	773	1	T → TQT in CAH18459. Ref.2
	Sequence conflict	980	1	G → R in CAE45820. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q9Y4C1 [UniParc]. Last modified October 5, 2010. Version 4. Checksum: 9689B3279F450C8A	FASTA	1,321	147,341
	10 20 30 40 50 60 MVLTLGESWP VLVGRRFLSL SAADGSDGSH DSWDVERVAE WPWLSGTIRA VSHTDVTKKD 70 80 90 100 110 120 LKVCVEFDGE SWRKRRWIEV YSLLRRAFLV EHNLVLAERK SPEISERIVQ WPAITYKPLL 130 140 150 160 170 180 DKAGLGSITS VRFLGDQQRV FLSKDLLKPI QDVNSLRLSL TDNQIVSKEF QALIVKHLDE 190 200 210 220 230 240 SHLLKGDKNL VGSEVKIYSL DPSTQWFSAT VINGNPASKT LQVNCEEIPA LKIVDPSLIH 250 260 270 280 290 300 VEVVHDNLVT CGNSARIGAV KRKSSENNGT LVSKQAKSCS EASPSMCPVQ SVPTTVFKEI 310 320 330 340 350 360 LLGCTAATPP SKDPRQQSTP QAANSPPNLG AKIPQGCHKQ SLPEEISSCL NTKSEALRTK 370 380 390 400 410 420 PDVCKAGLLS KSSQIGTGDL KILTEPKGSC TQPKTNTDQE NRLESVPQAL TGLPKECLPT 430 440 450 460 470 480 KASSKAELEI ANPPELQKHL EHAPSPSDVS NAPEVKAGVN SDSPNNCSGK KVEPSALACR 490 500 510 520 530 540 SQNLKESSVK VDNESCCSRS NNKIQNAPSR KSVLTDPAKL KKLQQSGEAF VQDDSCVNIV 550 560 570 580 590 600 AQLPKCRECR LDSLRKDKEQ QKDSPVFCRF FHFRRLQFNK HGVLRVEGFL TPNKYDNEAI 610 620 630 640 650 660 GLWLPLTKNV VGIDLDTAKY ILANIGDHFC QMVISEKEAM STIEPHRQVA WKRAVKGVRE 670 680 690 700 710 720 MCDVCDTTIF NLHWVCPRCG FGVCVDCYRM KRKNCQQGAA YKTFSWLKCV KSQIHEPENL 730 740 750 760 770 780 MPTQIIPGKA LYDVGDIVHS VRAKWGIKAN CPCSNRQFKL FSKPASKEDL KQTSLAGEKP 790 800 810 820 830 840 TLGAVLQQNP SVLEPAAVGG EAASKPAGSM KPACPASTSP LNWLADLTSG NVNKENKEKQ 850 860 870 880 890 900 PTMPILKNEI KCLPPLPPLS KSSTVLHTFN STILTPVSNN NSGFLRNLLN SSTGKTENGL 910 920 930 940 950 960 KNTPKILDDI FASLVQNKTT SDLSKRPQGL TIKPSILGFD TPHYWLCDNR LLCLQDPNNK 970 980 990 1000 1010 1020 SNWNVFRECW KQGQPVMVSG VHHKLNSELW KPESFRKEFG EQEVDLVNCR TNEIITGATV 1030 1040 1050 1060 1070 1080 GDFWDGFEDV PNRLKNEKEP MVLKLKDWPP GEDFRDMMPS RFDDLMANIP LPEYTRRDGK 1090 1100 1110 1120 1130 1140 LNLASRLPNY FVRPDLGPKM YNAYGLITPE DRKYGTTNLH LDVSDAANVM VYVGIPKGQC 1150 1160 1170 1180 1190 1200 EQEEEVLKTI QDGDSDELTI KRFIEGKEKP GALWHIYAAK DTEKIREFLK KVSEEQGQEN 1210 1220 1230 1240 1250 1260 PADHDPIHDQ SWYLDRSLRK RLHQEYGVQG WAIVQFLGDV VFIPAGAPHQ VHNLYSCIKV 1270 1280 1290 1300 1310 1320 AEDFVSPEHV KHCFWLTQEF RYLSQTHTNH EDKLQVKNVI YHAVKDAVAM LKASESSFGK P

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Prediction of the coding sequences of unidentified human genes. XI. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro." Nagase T., Ishikawa K., Suyama M., Kikuno R., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 5:277-286(1998) [PubMed: 9872452] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT VAL-212. Tissue: Brain.
[2]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed: 17974005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS VAL-212 AND PRO-447. Tissue: Fetal kidney, Salivary gland and Testis.
[3]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed: 15815621] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT VAL-212.
[5]	"JHDM2A, a JmjC-containing H3K9 demethylase, facilitates transcription activation by androgen receptor." Yamane K., Toumazou C., Tsukada Y.I., Erdjument-Bromage H., Tempst P., Wong J., Zhang Y. Cell 125:483-495(2006) [PubMed: 16603237] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, CATALYTIC ACTIVITY, COFACTOR, DOMAIN, MUTAGENESIS OF HIS-1120.
[6]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-445, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[7]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-895, MASS SPECTROMETRY.
[8]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed: 16959974] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] HIS-187.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB018285 mRNA. Translation: BAA34462.2. Different initiation. AL832150 Transcribed RNA. Translation: CAH18459.3. BX640698 mRNA. Translation: CAE45820.1. CR749581 mRNA. Translation: CAH18373.1. AC068288 Genomic DNA. Translation: AAY24210.1. CH471053 Genomic DNA. Translation: EAW99453.1. CH471053 Genomic DNA. Translation: EAW99456.1.
IPI	IPI00479545.
RefSeq	NP_001140160.1. NM_001146688.1. NP_060903.2. NM_018433.5.
UniGene	Hs.557425.
3D structure databases
ProteinModelPortal	Q9Y4C1.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9Y4C1. 2 interactions.
STRING	Q9Y4C1.
PTM databases
PhosphoSite	Q9Y4C1.
Polymorphism databases
DMDM	308153659.
Proteomic databases
PRIDE	Q9Y4C1.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000312912; ENSP00000323659; ENSG00000115548. ENST00000409064; ENSP00000386516; ENSG00000115548. ENST00000409556; ENSP00000386660; ENSG00000115548.
GeneID	55818.
KEGG	hsa:55818.
UCSC	uc002sri.2. human.
Organism-specific databases
CTD	55818.
GeneCards	GC02P086667.
H-InvDB	HIX0002238.
HGNC	HGNC:20815. KDM3A.
MIM	611512. gene.
neXtProt	NX_Q9Y4C1.
PharmGKB	PA134942779. PA164721293.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG05405.
GeneTree	ENSGT00530000063039.
HOGENOM	HBG444153.
InParanoid	Q9Y4C1.
OMA	GESWPVL.
OrthoDB	EOG4FFD0Z.
PhylomeDB	Q9Y4C1.
Enzyme and pathway databases
Pathway_Interaction_DB	ar_pathway. Coregulation of Androgen receptor activity.
Gene expression databases
ArrayExpress	Q9Y4C1.
Bgee	Q9Y4C1.
CleanEx	HS_JMJD1A.
Genevestigator	Q9Y4C1.
GermOnline	ENSG00000115548. Homo sapiens.
Family and domain databases
InterPro	IPR013129. TF_JmjC. IPR003347. TF_JmjC_AAH. [Graphical view]
KO	K15601.
Pfam	PF02373. JmjC. 1 hit. [Graphical view]
SMART	SM00558. JmjC. 1 hit. [Graphical view]
PROSITE	PS51184. JMJC. 1 hit. [Graphical view]
ProtoNet	Search...
Other
SOURCE	Search...

Entry information

Entry name

KDM3A_HUMAN

Accession

Primary (citable) accession number: Q9Y4C1
Secondary accession number(s): D6W5M3 , Q53S72, Q68D47, Q68UT9, Q6N050, Q8IY08

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 22, 2005
Last sequence update:	October 5, 2010
Last modified:	January 25, 2012
This is version 87 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.