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Q6ZQ88

- KDM1A_MOUSE

UniProt

Q6ZQ88 - KDM1A_MOUSE

Protein

Lysine-specific histone demethylase 1A

Gene

Kdm1a

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 110 (01 Oct 2014)
      Sequence version 2 (16 Aug 2004)
      Previous versions | rss
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    Functioni

    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.By similarity2 Publications

    Cofactori

    FAD.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei290 – 2901FADBy similarity
    Binding sitei309 – 3091FADBy similarity
    Binding sitei311 – 3111FADBy similarity
    Binding sitei317 – 3171FADBy similarity
    Binding sitei802 – 8021FADBy similarity

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi282 – 31029FADSequence AnalysisAdd
    BLAST

    GO - Molecular functioni

    1. androgen receptor binding Source: UniProtKB
    2. chromatin binding Source: UniProtKB
    3. enzyme binding Source: BHF-UCL
    4. flavin adenine dinucleotide binding Source: UniProtKB
    5. histone demethylase activity Source: BHF-UCL
    6. histone demethylase activity (H3-dimethyl-K4 specific) Source: UniProtKB
    7. histone demethylase activity (H3-K4 specific) Source: UniProtKB
    8. histone demethylase activity (H3-K9 specific) Source: UniProtKB
    9. ligand-dependent nuclear receptor transcription coactivator activity Source: UniProtKB
    10. MRF binding Source: BHF-UCL
    11. oxidoreductase activity Source: UniProtKB
    12. protein binding Source: IntAct
    13. RNA polymerase II transcription factor binding Source: BHF-UCL
    14. sequence-specific DNA binding transcription factor activity Source: MGI
    15. transcription factor binding Source: BHF-UCL
    16. transcription regulatory region DNA binding Source: BHF-UCL

    GO - Biological processi

    1. cell proliferation Source: MGI
    2. granulocyte differentiation Source: UniProtKB
    3. histone H3-K4 demethylation Source: UniProtKB
    4. histone H3-K9 demethylation Source: UniProtKB
    5. in utero embryonic development Source: MGI
    6. muscle cell development Source: BHF-UCL
    7. negative regulation of DNA damage response, signal transduction by p53 class mediator Source: Ensembl
    8. negative regulation of histone H3-K4 methylation Source: BHF-UCL
    9. negative regulation of histone H3-K9 methylation Source: BHF-UCL
    10. negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator Source: Ensembl
    11. negative regulation of protein binding Source: Ensembl
    12. negative regulation of sequence-specific DNA binding transcription factor activity Source: BHF-UCL
    13. negative regulation of transcription, DNA-templated Source: BHF-UCL
    14. negative regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
    15. pituitary gland development Source: MGI
    16. positive regulation of erythrocyte differentiation Source: UniProtKB
    17. positive regulation of hormone biosynthetic process Source: MGI
    18. positive regulation of megakaryocyte differentiation Source: UniProtKB
    19. positive regulation of neural precursor cell proliferation Source: BHF-UCL
    20. positive regulation of sequence-specific DNA binding transcription factor activity Source: Ensembl
    21. positive regulation of stem cell proliferation Source: BHF-UCL
    22. positive regulation of transcription from RNA polymerase II promoter Source: MGI
    23. regulation of primitive erythrocyte differentiation Source: UniProtKB
    24. regulation of transcription by chromatin organization Source: BHF-UCL
    25. regulation of transcription from RNA polymerase II promoter Source: UniProtKB
    26. transcription, DNA-templated Source: UniProtKB-KW

    Keywords - Molecular functioni

    Chromatin regulator, Developmental protein, Oxidoreductase, Repressor

    Keywords - Biological processi

    Transcription, Transcription regulation

    Keywords - Ligandi

    FAD, Flavoprotein

    Enzyme and pathway databases

    ReactomeiREACT_198649. Factors involved in megakaryocyte development and platelet production.

    Names & Taxonomyi

    Protein namesi
    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 namesi
    Name:Kdm1a
    Synonyms:Aof2, Kiaa0601, Lsd1
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 4

    Organism-specific databases

    MGIiMGI:1196256. Kdm1a.

    Subcellular locationi

    Nucleus By similarity

    GO - Cellular componenti

    1. nuclear chromatin Source: BHF-UCL
    2. nucleus Source: UniProtKB
    3. transcription factor complex Source: MGI

    Keywords - Cellular componenti

    Nucleus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 853853Lysine-specific histone demethylase 1APRO_0000099882Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei105 – 1051PhosphothreonineBy similarity
    Modified residuei127 – 1271PhosphoserineBy similarity
    Modified residuei132 – 1321PhosphoserineBy similarity
    Modified residuei138 – 1381PhosphoserineBy similarity
    Modified residuei167 – 1671Phosphoserine1 Publication
    Modified residuei850 – 8501PhosphoserineBy similarity

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiQ6ZQ88.
    PaxDbiQ6ZQ88.
    PRIDEiQ6ZQ88.

    PTM databases

    PhosphoSiteiQ6ZQ88.

    Expressioni

    Tissue specificityi

    Ubiquitously expressed.1 Publication

    Developmental stagei

    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.1 Publication

    Gene expression databases

    ArrayExpressiQ6ZQ88.
    BgeeiQ6ZQ88.
    CleanExiMM_AOF2.
    GenevestigatoriQ6ZQ88.

    Interactioni

    Subunit structurei

    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.By similarity2 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    Rnf2Q9CQJ43EBI-1216284,EBI-927321

    Protein-protein interaction databases

    BioGridi221360. 14 interactions.
    DIPiDIP-38599N.
    IntActiQ6ZQ88. 7 interactions.
    MINTiMINT-4100561.

    Structurei

    3D structure databases

    ProteinModelPortaliQ6ZQ88.
    SMRiQ6ZQ88. Positions 172-837.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini175 – 274100SWIRMPROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni301 – 853553Demethylase activityBy similarityAdd
    BLAST

    Coiled coil

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Coiled coili111 – 15242Sequence AnalysisAdd
    BLAST
    Coiled coili429 – 51587Sequence AnalysisAdd
    BLAST

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi7 – 5650Ala-richAdd
    BLAST
    Compositional biasi153 – 1575Poly-Pro

    Domaini

    The SWIRM domain may act as an anchor site for a histone tail.By similarity

    Sequence similaritiesi

    Belongs to the flavin monoamine oxidase family.Curated
    Contains 1 SWIRM domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Coiled coil

    Phylogenomic databases

    eggNOGiCOG1231.
    GeneTreeiENSGT00530000062888.
    HOGENOMiHOG000246945.
    KOiK11450.
    OrthoDBiEOG7X9G66.
    PhylomeDBiQ6ZQ88.
    TreeFamiTF312972.

    Family and domain databases

    Gene3Di1.10.10.10. 1 hit.
    InterProiIPR002937. Amino_oxidase.
    IPR017366. Hist_Lys-spec_deMease.
    IPR009057. Homeodomain-like.
    IPR007526. SWIRM.
    IPR011991. WHTH_DNA-bd_dom.
    [Graphical view]
    PfamiPF01593. Amino_oxidase. 1 hit.
    PF04433. SWIRM. 1 hit.
    [Graphical view]
    PIRSFiPIRSF038051. Histone_Lys-demethylase. 1 hit.
    SUPFAMiSSF46689. SSF46689. 1 hit.
    PROSITEiPS50934. SWIRM. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q6ZQ88-1 [UniParc]FASTAAdd to Basket

    « Hide

    MLSGKKAAAA AAAAAAAAAA GTEAGSGAAG GAENGSEVAA PPAGLTGPTD    50
    MATGAAGERT PRKKEPPRAS PPGGLAEPPG SAGPQAGPTA GPGSATPMET 100
    GIAETPEGRR TSRRKRAKVE YREMDESLAN LSEDEYYSEE ERNAKAEKEK 150
    KLPPPPPQAP PEEENESEPE EPSGVEGAAF QSRLPHDRMT SQEAACFPDI 200
    ISGPQQTQKV FLFIRNRTLQ LWLDNPKIQL TFEATLQQLE APYNSDTVLV 250
    HRVHSYLERH GLINFGIYKR IKPLPIKKTG KVIIIGSGVS GLAAARQLQS 300
    FGMDVTLLEA RDRVGGRVAT FRKGNYVADL GAMVVTGLGG NPMAVVSKQV 350
    NMELAKIKQK CPLYEANGQA VPKEKDEMVE QEFNRLLEAT SYLSHQLDFN 400
    VLNNKPVSLG QALEVVIQLQ EKHVKDEQIE HWKKIVKTQE ELKELLNKMV 450
    NLKEKIKELH QQYKEASEVK PPRDITAEFL VKSKHRDLTA LCKEYDELAE 500
    TQGKLEEKLQ ELEANPPSDV YLSSRDRQIL DWHFANLEFA NATPLSTLSL 550
    KHWDQDDDFE FTGSHLTVRN GYSCVPVALA EGLDIKLNTA VRQVRYTASG 600
    CEVIAVNTRS TSQTFIYKCD AVLCTLPLGV LKQQPPAVQF VPPLPEWKTS 650
    AVQRMGFGNL NKVVLCFDRV FWDPSVNLFG HVGSTTASRG ELFLFWNLYK 700
    APILLALVAG EAAGIMENIS DDVIVGRCLA ILKGIFGSSA VPQPKETVVS 750
    RWRADPWARG SYSYVAAGSS GNDYDLMAQP ITPGPSIPGA PQPIPRLFFA 800
    GEHTIRNYPA TVHGALLSGL REAGRIADQF LGAMYTLPRQ ATPGVPAQQS 850
    PSM 853
    Length:853
    Mass (Da):92,851
    Last modified:August 16, 2004 - v2
    Checksum:i43CD401FA0452B2F
    GO

    Sequence cautioni

    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.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti226 – 2261P → S in AAH59885. (PubMed:15489334)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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.
    CCDSiCCDS51331.1.
    RefSeqiNP_598633.2. NM_133872.2.
    UniGeneiMm.28540.

    Genome annotation databases

    EnsembliENSMUST00000116273; ENSMUSP00000111977; ENSMUSG00000036940.
    GeneIDi99982.
    KEGGimmu:99982.
    UCSCiuc008vig.2. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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.
    CCDSi CCDS51331.1.
    RefSeqi NP_598633.2. NM_133872.2.
    UniGenei Mm.28540.

    3D structure databases

    ProteinModelPortali Q6ZQ88.
    SMRi Q6ZQ88. Positions 172-837.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 221360. 14 interactions.
    DIPi DIP-38599N.
    IntActi Q6ZQ88. 7 interactions.
    MINTi MINT-4100561.

    PTM databases

    PhosphoSitei Q6ZQ88.

    Proteomic databases

    MaxQBi Q6ZQ88.
    PaxDbi Q6ZQ88.
    PRIDEi Q6ZQ88.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000116273 ; ENSMUSP00000111977 ; ENSMUSG00000036940 .
    GeneIDi 99982.
    KEGGi mmu:99982.
    UCSCi uc008vig.2. mouse.

    Organism-specific databases

    CTDi 23028.
    MGIi MGI:1196256. Kdm1a.
    Rougei Search...

    Phylogenomic databases

    eggNOGi COG1231.
    GeneTreei ENSGT00530000062888.
    HOGENOMi HOG000246945.
    KOi K11450.
    OrthoDBi EOG7X9G66.
    PhylomeDBi Q6ZQ88.
    TreeFami TF312972.

    Enzyme and pathway databases

    Reactomei REACT_198649. Factors involved in megakaryocyte development and platelet production.

    Miscellaneous databases

    ChiTaRSi KDM1A. mouse.
    NextBioi 354201.
    PROi Q6ZQ88.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q6ZQ88.
    Bgeei Q6ZQ88.
    CleanExi MM_AOF2.
    Genevestigatori Q6ZQ88.

    Family and domain databases

    Gene3Di 1.10.10.10. 1 hit.
    InterProi IPR002937. Amino_oxidase.
    IPR017366. Hist_Lys-spec_deMease.
    IPR009057. Homeodomain-like.
    IPR007526. SWIRM.
    IPR011991. WHTH_DNA-bd_dom.
    [Graphical view ]
    Pfami PF01593. Amino_oxidase. 1 hit.
    PF04433. SWIRM. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF038051. Histone_Lys-demethylase. 1 hit.
    SUPFAMi SSF46689. SSF46689. 1 hit.
    PROSITEi PS50934. SWIRM. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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. 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.

    Entry informationi

    Entry nameiKDM1A_MOUSE
    AccessioniPrimary (citable) accession number: Q6ZQ88
    Secondary accession number(s): A3KG94, Q6PB53, Q8VEA1
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 16, 2004
    Last sequence update: August 16, 2004
    Last modified: October 1, 2014
    This is version 110 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

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3