CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-000926
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Lysine-specific histone demethylase 1A 
Protein Synonyms/Alias
 BRAF35-HDAC complex protein BHC110; Flavin-containing amine oxidase domain-containing protein 2 
Gene Name
 KDM1A 
Gene Synonyms/Alias
 AOF2; KDM1; KIAA0601; LSD1 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
288LINFGIYKRIKPLPTubiquitination[1]
448QLQEKHVKDEQIEHWubiquitination[1]
471ELKELLNKMVNLKEKubiquitination[2]
671VPPLPEWKTSAVQRMubiquitination[1, 3]
768SSAVPQPKETVVSRWubiquitination[3]
Reference
 [1] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [2] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [3] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724] 
Functional Description
 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. 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. 
Sequence Annotation
 DOMAIN 174 273 SWIRM.
 NP_BIND 281 309 FAD (Potential).
 NP_BIND 332 333 FAD.
 NP_BIND 810 811 FAD.
 REGION 300 852 Demethylase activity.
 BINDING 289 289 FAD.
 BINDING 308 308 FAD.
 BINDING 310 310 FAD.
 BINDING 316 316 FAD.
 BINDING 801 801 FAD.
 MOD_RES 104 104 Phosphothreonine.
 MOD_RES 126 126 Phosphoserine.
 MOD_RES 131 131 Phosphoserine.
 MOD_RES 137 137 Phosphoserine.
 MOD_RES 166 166 Phosphoserine.
 MOD_RES 849 849 Phosphoserine.  
Keyword
 3D-structure; Alternative splicing; Chromatin regulator; Coiled coil; Complete proteome; Developmental protein; Direct protein sequencing; FAD; Nucleus; Oxidoreductase; Phosphoprotein; Reference proteome; Repressor; Transcription; Transcription regulation. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 852 AA 
Protein Sequence
MLSGKKAAAA AAAAAAAATG TEAGPGTAGG SENGSEVAAQ PAGLSGPAEV GPGAVGERTP 60
RKKEPPRASP PGGLAEPPGS AGPQAGPTVV PGSATPMETG IAETPEGRRT SRRKRAKVEY 120
REMDESLANL SEDEYYSEEE RNAKAEKEKK LPPPPPQAPP EEENESEPEE PSGQAGGLQD 180
DSSGGYGDGQ ASGVEGAAFQ SRLPHDRMTS QEAACFPDII SGPQQTQKVF LFIRNRTLQL 240
WLDNPKIQLT FEATLQQLEA PYNSDTVLVH RVHSYLERHG LINFGIYKRI KPLPTKKTGK 300
VIIIGSGVSG LAAARQLQSF GMDVTLLEAR DRVGGRVATF RKGNYVADLG AMVVTGLGGN 360
PMAVVSKQVN MELAKIKQKC PLYEANGQAD TVKVPKEKDE MVEQEFNRLL EATSYLSHQL 420
DFNVLNNKPV SLGQALEVVI QLQEKHVKDE QIEHWKKIVK TQEELKELLN KMVNLKEKIK 480
ELHQQYKEAS EVKPPRDITA EFLVKSKHRD LTALCKEYDE LAETQGKLEE KLQELEANPP 540
SDVYLSSRDR QILDWHFANL EFANATPLST LSLKHWDQDD DFEFTGSHLT VRNGYSCVPV 600
ALAEGLDIKL NTAVRQVRYT ASGCEVIAVN TRSTSQTFIY KCDAVLCTLP LGVLKQQPPA 660
VQFVPPLPEW KTSAVQRMGF GNLNKVVLCF DRVFWDPSVN LFGHVGSTTA SRGELFLFWN 720
LYKAPILLAL VAGEAAGIME NISDDVIVGR CLAILKGIFG SSAVPQPKET VVSRWRADPW 780
ARGSYSYVAA GSSGNDYDLM AQPITPGPSI PGAPQPIPRL FFAGEHTIRN YPATVHGALL 840
SGLREAGRIA DQFLGAMYTL PRQATPGVPA QQSPSM 876 
Gene Ontology
 GO:0000790; C:nuclear chromatin; IDA:BHF-UCL.
 GO:0005667; C:transcription factor complex; ISS:UniProtKB.
 GO:0050681; F:androgen receptor binding; IDA:UniProtKB.
 GO:0003682; F:chromatin binding; IDA:UniProtKB.
 GO:0050660; F:flavin adenine dinucleotide binding; IDA:UniProtKB.
 GO:0034648; F:histone demethylase activity (H3-dimethyl-K4 specific); IDA:UniProtKB.
 GO:0032454; F:histone demethylase activity (H3-K9 specific); IDA:UniProtKB.
 GO:0030374; F:ligand-dependent nuclear receptor transcription coactivator activity; IMP:UniProtKB.
 GO:0043426; F:MRF binding; IDA:BHF-UCL.
 GO:0016491; F:oxidoreductase activity; IDA:UniProtKB.
 GO:0003700; F:sequence-specific DNA binding transcription factor activity; IEA:Compara.
 GO:0044212; F:transcription regulatory region DNA binding; ISS:BHF-UCL.
 GO:0007596; P:blood coagulation; TAS:Reactome.
 GO:0008283; P:cell proliferation; IEA:Compara.
 GO:0030851; P:granulocyte differentiation; IEA:Compara.
 GO:0001701; P:in utero embryonic development; IEA:Compara.
 GO:0055001; P:muscle cell development; ISS:BHF-UCL.
 GO:0043066; P:negative regulation of apoptotic process; IMP:BHF-UCL.
 GO:0043392; P:negative regulation of DNA binding; IC:BHF-UCL.
 GO:0043518; P:negative regulation of DNA damage response, signal transduction by p53 class mediator; IMP:BHF-UCL.
 GO:0051572; P:negative regulation of histone H3-K4 methylation; IEA:Compara.
 GO:0051573; P:negative regulation of histone H3-K9 methylation; IEA:Compara.
 GO:0032091; P:negative regulation of protein binding; IMP:BHF-UCL.
 GO:0043433; P:negative regulation of sequence-specific DNA binding transcription factor activity; IDA:BHF-UCL.
 GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IMP:BHF-UCL.
 GO:0021983; P:pituitary gland development; IEA:Compara.
 GO:0045648; P:positive regulation of erythrocyte differentiation; IEA:Compara.
 GO:0046886; P:positive regulation of hormone biosynthetic process; IEA:Compara.
 GO:0045654; P:positive regulation of megakaryocyte differentiation; IEA:Compara.
 GO:2000179; P:positive regulation of neural precursor cell proliferation; IEA:Compara.
 GO:0051091; P:positive regulation of sequence-specific DNA binding transcription factor activity; IDA:BHF-UCL.
 GO:2000648; P:positive regulation of stem cell proliferation; IEA:Compara.
 GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:BHF-UCL.
 GO:0010725; P:regulation of primitive erythrocyte differentiation; IEA:Compara.
 GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW. 
Interpro
 IPR002937; Amino_oxidase.
 IPR017366; Hist_Lys-spec_deMease.
 IPR009057; Homeodomain-like.
 IPR007526; SWIRM.
 IPR011991; WHTH_DNA-bd_dom. 
Pfam
 PF01593; Amino_oxidase
 PF04433; SWIRM 
SMART
  
PROSITE
 PS50934; SWIRM 
PRINTS