Q6ZQ88 (KDM1A_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Lysine-specific histone demethylase 1A
EC=1.-.-.-

Alternative name(s):
BRAF35-HDAC complex protein BHC110
Flavin-containing amine oxidase domain-containing protein 2

Gene names

Name:	Kdm1a
Synonyms:	Aof2, Kiaa0601, Lsd1

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 › Mus

Protein attributes

Sequence length	853 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Histone demethylase that demethylates both 'Lys-4' (H3K4me) and 'Lys-9' (H3K9me) of histone H3, thereby acting as a coactivator or a corepressor, depending on the context. Acts by oxidizing the substrate by FAD to generate the corresponding imine that is subsequently hydrolyzed. Acts as a corepressor by mediating demethylation of H3K4me, a specific tag for epigenetic transcriptional activation. Demethylates both mono- (H3K4me1) and di-methylated (H3K4me2) H3K4me. May play a role in the repression of neuronal genes. Alone, it is unable to demethylate H3K4me on nucleosomes and requires the presence of RCOR1/CoREST to achieve such activity. Also acts as a coactivator of androgen receptor (ANDR)-dependent transcription, by being recruited to ANDR target genes and mediating demethylation of H3K9me, a specific tag for epigenetic transcriptional repression. The presence of PRKCB in ANDR-containing complexes, which mediates phosphorylation of 'Thr-6' of histone H3 (H3T6ph), a specific tag that prevents demethylation H3K4me, prevents H3K4me demethylase activity of KDM1A. Demethylates di-methylated 'Lys-370' of p53/TP53 which prevents interaction of p53/TP53 with TP53BP1 and represses p53/TP53-mediated transcriptional activation By similarity. Demethylates and stabilizes the DNA methylase DNMT1. Required for gastrulation during embryogenesis. Component of a RCOR/GFI/KDM1A/HDAC complex that suppresses, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development. Ref.5 Ref.6
Cofactor	FAD By similarity.
Subunit structure	Component of a BHC histone deacetylase complex that contains HDAC1, HDAC2, HMG20B, KDM1A, RCOR1 and PHF21A. The BHC complex may also contain ZMYM2, ZNF217, ZMYM3, GSE1 and GTF2I. In the complex, RCOR1 strongly enhances the demethylase activity and protects it from the proteasome while PHF21A inhibits the demethylase activity. Interacts with the androgen receptor (AR) By similarity. Component of a RCOR/GFI/KDM1A/HDAC complex. Interacts directly with GFI1 and GFI1B. Ref.5
Subcellular location	Nucleus By similarity.
Tissue specificity	Ubiquitously expressed. Ref.4
Developmental stage	Zygotic expression first appears at the morula stage. In blastocysts, expressed in the inner cell mass and trophectodermal cells. In postimplantation embryos, expression becomes ubiquitous. Ref.6
Domain	The SWIRM domain may act as an anchor site for a histone tail By similarity.
Sequence similarities	Belongs to the flavin monoamine oxidase family. Contains 1 SWIRM domain.
Sequence caution	The sequence AAH59885.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence BAC97980.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Domain	Coiled coil
Ligand	FAD
Molecular function	Chromatin regulator Developmental protein Oxidoreductase Repressor
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Uncategorized	regulation of transcription from RNA polymerase II promoter by nuclear hormone receptor Inferred from sequence or structural similarity. Source: UniProtKB
Biological process	cell proliferation Inferred from mutant phenotype. Source: MGI granulocyte differentiation Inferred from mutant phenotype Ref.5. Source: UniProtKB in utero embryonic development Inferred from mutant phenotype. Source: MGI muscle cell development Inferred from mutant phenotype. Source: BHF-UCL negative regulation of sequence-specific DNA binding transcription factor activity Inferred from sequence or structural similarity. Source: BHF-UCL negative regulation of transcription from RNA polymerase II promoter Inferred from direct assay. Source: BHF-UCL pituitary gland development Inferred from mutant phenotype. Source: MGI positive regulation of erythrocyte differentiation Inferred from mutant phenotype Ref.5. Source: UniProtKB positive regulation of hormone biosynthetic process Inferred from mutant phenotype. Source: MGI positive regulation of megakaryocyte differentiation Inferred from mutant phenotype Ref.5. Source: UniProtKB positive regulation of transcription from RNA polymerase II promoter Inferred from mutant phenotype. Source: MGI regulation of primitive erythrocyte differentiation Inferred from mutant phenotype Ref.5. Source: UniProtKB transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	nuclear chromatin Inferred from direct assay. Source: BHF-UCL transcription factor complex Inferred from direct assay. Source: MGI
Molecular function	MyoD binding Inferred from physical interaction. Source: BHF-UCL androgen receptor binding Inferred from sequence or structural similarity. Source: UniProtKB chromatin binding Inferred from sequence or structural similarity. Source: UniProtKB enzyme binding Inferred from physical interaction. Source: BHF-UCL flavin adenine dinucleotide binding Inferred from sequence or structural similarity. Source: UniProtKB histone demethylase activity (H3-K9 specific) Inferred from sequence or structural similarity. Source: UniProtKB histone demethylase activity (H3-dimethyl-K4 specific) Inferred from sequence or structural similarity. Source: UniProtKB ligand-dependent nuclear receptor transcription coactivator activity Inferred from sequence or structural similarity. Source: UniProtKB oxidoreductase activity Inferred from sequence or structural similarity. Source: UniProtKB sequence-specific DNA binding transcription factor activity Inferred from direct assay. Source: MGI transcription regulatory region DNA binding Inferred from direct assay. Source: BHF-UCL
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Rnf2	Q9CQJ4	3	EBI-1216284,EBI-927321

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 853	853	Lysine-specific histone demethylase 1A		PRO_0000099882
Regions
	Domain	175 – 274	100	SWIRM
	Nucleotide binding	282 – 310	29	FAD Potential
	Region	301 – 853	553	Demethylase activity By similarity
	Coiled coil	111 – 152	42	Potential
	Coiled coil	429 – 515	87	Potential
	Compositional bias	7 – 56	50	Ala-rich
	Compositional bias	153 – 157	5	Poly-Pro
Sites
	Binding site	290	1	FAD By similarity
	Binding site	309	1	FAD By similarity
	Binding site	311	1	FAD By similarity
	Binding site	317	1	FAD By similarity
	Binding site	802	1	FAD By similarity
Amino acid modifications
	Modified residue	81	1	Phosphoserine By similarity
	Modified residue	105	1	Phosphothreonine By similarity
	Modified residue	127	1	Phosphoserine By similarity
	Modified residue	132	1	Phosphoserine By similarity
	Modified residue	138	1	Phosphoserine By similarity
	Modified residue	167	1	Phosphoserine By similarity
	Modified residue	850	1	Phosphoserine By similarity
Experimental info
	Sequence conflict	226	1	P → S in AAH59885. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Q6ZQ88 [UniParc]. Last modified August 16, 2004. Version 2. Checksum: 43CD401FA0452B2F	FASTA	853	92,851
	10 20 30 40 50 60 MLSGKKAAAA AAAAAAAAAA GTEAGSGAAG GAENGSEVAA PPAGLTGPTD MATGAAGERT 70 80 90 100 110 120 PRKKEPPRAS PPGGLAEPPG SAGPQAGPTA GPGSATPMET GIAETPEGRR TSRRKRAKVE 130 140 150 160 170 180 YREMDESLAN LSEDEYYSEE ERNAKAEKEK KLPPPPPQAP PEEENESEPE EPSGVEGAAF 190 200 210 220 230 240 QSRLPHDRMT SQEAACFPDI ISGPQQTQKV FLFIRNRTLQ LWLDNPKIQL TFEATLQQLE 250 260 270 280 290 300 APYNSDTVLV HRVHSYLERH GLINFGIYKR IKPLPIKKTG KVIIIGSGVS GLAAARQLQS 310 320 330 340 350 360 FGMDVTLLEA RDRVGGRVAT FRKGNYVADL GAMVVTGLGG NPMAVVSKQV NMELAKIKQK 370 380 390 400 410 420 CPLYEANGQA VPKEKDEMVE QEFNRLLEAT SYLSHQLDFN VLNNKPVSLG QALEVVIQLQ 430 440 450 460 470 480 EKHVKDEQIE HWKKIVKTQE ELKELLNKMV NLKEKIKELH QQYKEASEVK PPRDITAEFL 490 500 510 520 530 540 VKSKHRDLTA LCKEYDELAE TQGKLEEKLQ ELEANPPSDV YLSSRDRQIL DWHFANLEFA 550 560 570 580 590 600 NATPLSTLSL KHWDQDDDFE FTGSHLTVRN GYSCVPVALA EGLDIKLNTA VRQVRYTASG 610 620 630 640 650 660 CEVIAVNTRS TSQTFIYKCD AVLCTLPLGV LKQQPPAVQF VPPLPEWKTS AVQRMGFGNL 670 680 690 700 710 720 NKVVLCFDRV FWDPSVNLFG HVGSTTASRG ELFLFWNLYK APILLALVAG EAAGIMENIS 730 740 750 760 770 780 DDVIVGRCLA ILKGIFGSSA VPQPKETVVS RWRADPWARG SYSYVAAGSS GNDYDLMAQP 790 800 810 820 830 840 ITPGPSIPGA PQPIPRLFFA GEHTIRNYPA TVHGALLSGL REAGRIADQF LGAMYTLPRQ 850 ATPGVPAQQS PSM

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Prediction of the coding sequences of mouse homologues of KIAA gene: III. 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., Nagase T., Ohara O., Koga H. DNA Res. 10:167-180(2003) [PubMed: 14621295] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[2]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed: 19468303] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6.
[3]	"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]. Strain: C57BL/6. Tissue: Brain and Mammary gland.
[4]	"LSD1 demethylates repressive histone marks to promote androgen-receptor-dependent transcription." Metzger E., Wissmann M., Yin N., Mueller J.M., Schneider R., Peters A.H.F.M., Guenther T., Buettner R., Schuele R. Nature 437:436-439(2005) [PubMed: 16079795] [Abstract] Cited for: TISSUE SPECIFICITY.
[5]	"Epigenetic regulation of hematopoietic differentiation by Gfi-1 and Gfi-1b is mediated by the cofactors CoREST and LSD1." Saleque S., Kim J., Rooke H.M., Orkin S.H. Mol. Cell 27:562-572(2007) [PubMed: 17707228] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY AS A COMPONENT OF A GFI-RCOR-KDM1A-HDAC COMPLEX, INTERACTION WITH GFI1 AND GFI1B, FUNCTION.
[6]	"The lysine demethylase LSD1 (KDM1) is required for maintenance of global DNA methylation." Wang J., Hevi S., Kurash J.K., Lei H., Gay F., Bajko J., Su H., Sun W., Chang H., Xu G., Gaudet F., Li E., Chen T. Nat. Genet. 41:125-129(2009) [PubMed: 19098913] [Abstract] Cited for: FUNCTION, DEVELOPMENTAL STAGE.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AK129170 mRNA. Translation: BAC97980.1. Different initiation. AL671173 Genomic DNA. Translation: CAM46211.1. BC019417 mRNA. Translation: AAH19417.1. BC059885 mRNA. Translation: AAH59885.1. Different initiation.
IPI	IPI00453837.
RefSeq	NP_598633.2. NM_133872.2.
UniGene	Mm.28540.
3D structure databases
ProteinModelPortal	Q6ZQ88.
SMR	Q6ZQ88. Positions 172-837.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-38599N.
IntAct	Q6ZQ88. 4 interactions.
STRING	Q6ZQ88.
PTM databases
PhosphoSite	Q6ZQ88.
Proteomic databases
PRIDE	Q6ZQ88.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000116273; ENSMUSP00000111977; ENSMUSG00000036940.
GeneID	99982.
KEGG	mmu:99982.
UCSC	uc008vig.2. mouse.
Organism-specific databases
CTD	23028.
MGI	MGI:1196256. Kdm1a.
Rouge	Search...
Phylogenomic databases
GeneTree	ENSGT00530000062888.
OrthoDB	EOG4R7V9M.
PhylomeDB	Q6ZQ88.
Gene expression databases
ArrayExpress	Q6ZQ88.
Bgee	Q6ZQ88.
CleanEx	MM_AOF2.
Genevestigator	Q6ZQ88.
GermOnline	ENSMUSG00000036940. Mus musculus.
Family and domain databases
InterPro	IPR002937. Amino_oxidase. IPR017366. Hist_Lys-spec_deMease. IPR009057. Homeodomain-like. IPR007526. SWIRM. IPR011991. WHTH_trsnscrt_rep_DNA-bd. [Graphical view]
Gene3D	G3DSA:1.10.10.10. Wing_hlx_DNA_bd. 1 hit.
KO	K11450.
Pfam	PF01593. Amino_oxidase. 1 hit. PF04433. SWIRM. 1 hit. [Graphical view]
PIRSF	PIRSF038051. Histone_Lys-demethylase. 1 hit.
SUPFAM	SSF46689. Homeodomain_like. 1 hit.
PROSITE	PS50934. SWIRM. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	354201.
SOURCE	Search...

Entry information

Entry name

KDM1A_MOUSE

Accession

Primary (citable) accession number: Q6ZQ88
Secondary accession number(s): A3KG94, Q6PB53, Q8VEA1

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 16, 2004
Last sequence update:	August 16, 2004
Last modified:	December 14, 2011
This is version 86 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program