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Q6ZQ88

- KDM1A_MOUSE

UniProt

Q6ZQ88 - KDM1A_MOUSE

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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

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

FADBy 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. RNA polymerase II transcription factor binding Source: BHF-UCL
  13. sequence-specific DNA binding transcription factor activity Source: MGI
  14. transcription factor binding Source: BHF-UCL
  15. 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
Complete GO annotation...

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.
REACT_256030. HDMs demethylate histones.
REACT_257106. HDACs deacetylate histones.

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
Complete GO annotation...

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

BgeeiQ6ZQ88.
CleanExiMM_AOF2.
ExpressionAtlasiQ6ZQ88. baseline and differential.
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.
InParanoidiQ6ZQ88.
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

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

PSM
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.Curated
The sequence BAC97980.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

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

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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.
InParanoidi Q6ZQ88.
KOi K11450.
OrthoDBi EOG7X9G66.
PhylomeDBi Q6ZQ88.
TreeFami TF312972.

Enzyme and pathway databases

Reactomei REACT_198649. Factors involved in megakaryocyte development and platelet production.
REACT_256030. HDMs demethylate histones.
REACT_257106. HDACs deacetylate histones.

Miscellaneous databases

ChiTaRSi Kdm1a. mouse.
NextBioi 354201.
PROi Q6ZQ88.
SOURCEi Search...

Gene expression databases

Bgeei Q6ZQ88.
CleanExi MM_AOF2.
ExpressionAtlasi Q6ZQ88. baseline and differential.
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

« Hide 'large scale' publications
  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: November 26, 2014
This is version 112 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