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Q6ZQ88 (KDM1A_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 105. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length853 AA.
Sequence statusComplete.
Protein existenceEvidence 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. Effector of SNAI1-mediated transcription repression of E-cadherin/CDH1, CDN7 and KRT8. Required for the maintenance of the silenced state of the SNAI1 target genes E-cadherin/CDH1 and CDN7. Ref.5 Ref.7

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. Interacts with ASXL1. Interacts with SNAI1 (via SNAG domain) By similarity. Interacts with INSM1. Ref.5 Ref.8

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.7

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 processTranscription
Transcription regulation
   Cellular componentNucleus
   DomainCoiled coil
   LigandFAD
Flavoprotein
   Molecular functionChromatin regulator
Developmental protein
Oxidoreductase
Repressor
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcell proliferation

Inferred from mutant phenotype PubMed 17392792. Source: MGI

granulocyte differentiation

Inferred from mutant phenotype Ref.5. Source: UniProtKB

histone H3-K4 demethylation

Inferred from sequence or structural similarity. Source: UniProtKB

histone H3-K9 demethylation

Inferred from sequence or structural similarity. Source: UniProtKB

in utero embryonic development

Inferred from mutant phenotype PubMed 17392792. Source: MGI

muscle cell development

Inferred from mutant phenotype PubMed 20833138. Source: BHF-UCL

negative regulation of DNA damage response, signal transduction by p53 class mediator

Inferred from electronic annotation. Source: Ensembl

negative regulation of histone H3-K4 methylation

Inferred from mutant phenotype PubMed 20123967. Source: BHF-UCL

negative regulation of histone H3-K9 methylation

Inferred from mutant phenotype PubMed 20123967. Source: BHF-UCL

negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator

Inferred from electronic annotation. Source: Ensembl

negative regulation of protein binding

Inferred from electronic annotation. Source: Ensembl

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 PubMed 19497860. Source: BHF-UCL

negative regulation of transcription, DNA-templated

Inferred from sequence or structural similarity. Source: BHF-UCL

pituitary gland development

Inferred from mutant phenotype PubMed 17392792. 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 PubMed 17392792. Source: MGI

positive regulation of megakaryocyte differentiation

Inferred from mutant phenotype Ref.5. Source: UniProtKB

positive regulation of neural precursor cell proliferation

Inferred from mutant phenotype PubMed 20123967. Source: BHF-UCL

positive regulation of sequence-specific DNA binding transcription factor activity

Inferred from electronic annotation. Source: Ensembl

positive regulation of stem cell proliferation

Inferred from mutant phenotype PubMed 20123967. Source: BHF-UCL

positive regulation of transcription from RNA polymerase II promoter

Inferred from mutant phenotype PubMed 17392792. Source: MGI

regulation of primitive erythrocyte differentiation

Inferred from mutant phenotype Ref.5. Source: UniProtKB

regulation of transcription by chromatin organization

Inferred by curator PubMed 20123967. Source: BHF-UCL

regulation of transcription from RNA polymerase II promoter

Inferred from sequence or structural similarity. Source: UniProtKB

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentnuclear chromatin

Inferred from direct assay PubMed 20833138. Source: BHF-UCL

nucleus

Inferred from sequence or structural similarity. Source: UniProtKB

transcription factor complex

Inferred from direct assay PubMed 17392792. Source: MGI

   Molecular_functionMRF binding

Inferred from physical interaction PubMed 20833138. Source: BHF-UCL

RNA polymerase II transcription factor binding

Inferred from physical interaction PubMed 20123967. 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 PubMed 17277772. Source: BHF-UCL

flavin adenine dinucleotide binding

Inferred from sequence or structural similarity. Source: UniProtKB

histone demethylase activity

Inferred from sequence or structural similarity. Source: BHF-UCL

histone demethylase activity (H3-K4 specific)

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 PubMed 17392792. Source: MGI

transcription factor binding

Inferred from physical interaction PubMed 20833138. Source: BHF-UCL

transcription regulatory region DNA binding

Inferred from direct assay PubMed 19497860. Source: BHF-UCL

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Rnf2Q9CQJ43EBI-1216284,EBI-927321

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 853853Lysine-specific histone demethylase 1A
PRO_0000099882

Regions

Domain175 – 274100SWIRM
Nucleotide binding282 – 31029FAD Potential
Region301 – 853553Demethylase activity By similarity
Coiled coil111 – 15242 Potential
Coiled coil429 – 51587 Potential
Compositional bias7 – 5650Ala-rich
Compositional bias153 – 1575Poly-Pro

Sites

Binding site2901FAD By similarity
Binding site3091FAD By similarity
Binding site3111FAD By similarity
Binding site3171FAD By similarity
Binding site8021FAD By similarity

Amino acid modifications

Modified residue1051Phosphothreonine By similarity
Modified residue1271Phosphoserine By similarity
Modified residue1321Phosphoserine By similarity
Modified residue1381Phosphoserine By similarity
Modified residue1671Phosphoserine Ref.6
Modified residue8501Phosphoserine By similarity

Experimental info

Sequence conflict2261P → S in AAH59885. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Q6ZQ88 [UniParc].

Last modified August 16, 2004. Version 2.
Checksum: 43CD401FA0452B2F

FASTA85392,851
        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 

« Hide

References

« Hide '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] [Europe PMC] [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. expand/collapse author list , 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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6J.
[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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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 phagosomal proteome in interferon-gamma-activated macrophages."
Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P.
Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-167, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[7]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION, DEVELOPMENTAL STAGE.
[8]"Insm1 controls development of pituitary endocrine cells and requires a SNAG domain for function and for recruitment of histone-modifying factors."
Welcker J.E., Hernandez-Miranda L.R., Paul F.E., Jia S., Ivanov A., Selbach M., Birchmeier C.
Development 140:4947-4958(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH INSM1.
+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.
RefSeqNP_598633.2. NM_133872.2.
UniGeneMm.28540.

3D structure databases

ProteinModelPortalQ6ZQ88.
SMRQ6ZQ88. Positions 172-837.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid221360. 13 interactions.
DIPDIP-38599N.
IntActQ6ZQ88. 7 interactions.
MINTMINT-4100561.

PTM databases

PhosphoSiteQ6ZQ88.

Proteomic databases

PaxDbQ6ZQ88.
PRIDEQ6ZQ88.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000116273; ENSMUSP00000111977; ENSMUSG00000036940.
GeneID99982.
KEGGmmu:99982.
UCSCuc008vig.2. mouse.

Organism-specific databases

CTD23028.
MGIMGI:1196256. Kdm1a.
RougeSearch...

Phylogenomic databases

eggNOGCOG1231.
GeneTreeENSGT00530000062888.
HOGENOMHOG000246945.
KOK11450.
OrthoDBEOG7X9G66.
PhylomeDBQ6ZQ88.
TreeFamTF312972.

Gene expression databases

ArrayExpressQ6ZQ88.
BgeeQ6ZQ88.
CleanExMM_AOF2.
GenevestigatorQ6ZQ88.

Family and domain databases

Gene3D1.10.10.10. 1 hit.
InterProIPR002937. Amino_oxidase.
IPR017366. Hist_Lys-spec_deMease.
IPR009057. Homeodomain-like.
IPR007526. SWIRM.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamPF01593. Amino_oxidase. 1 hit.
PF04433. SWIRM. 1 hit.
[Graphical view]
PIRSFPIRSF038051. Histone_Lys-demethylase. 1 hit.
SUPFAMSSF46689. SSF46689. 1 hit.
PROSITEPS50934. SWIRM. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSKDM1A. mouse.
NextBio354201.
PROQ6ZQ88.
SOURCESearch...

Entry information

Entry nameKDM1A_MOUSE
AccessionPrimary (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: April 16, 2014
This is version 105 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot