CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-000925
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
268LINFGIYKRIKPLPTubiquitination[1]
276RIKPLPTKKTGKVIIubiquitination[1]
277IKPLPTKKTGKVIIIubiquitination[1]
280LPTKKTGKVIIIGSGubiquitination[1]
322GRVATFRKGNYVADLubiquitination[1]
355QVNMELAKIKQKCPLubiquitination[1, 2]
359ELAKIKQKCPLYEANubiquitination[1, 3]
372ANGQAVPKEKDEMVEubiquitination[1]
374GQAVPKEKDEMVEQEubiquitination[1]
424QLQEKHVKDEQIEHWubiquitination[1, 2]
432DEQIEHWKKIVKTQEubiquitination[1]
433EQIEHWKKIVKTQEEubiquitination[1]
436EHWKKIVKTQEELKEubiquitination[1]
442VKTQEELKELLNKMVubiquitination[1, 2]
447ELKELLNKMVNLKEKubiquitination[1, 4]
452LNKMVNLKEKIKELHubiquitination[1]
454KMVNLKEKIKELHQQubiquitination[1]
456VNLKEKIKELHQQYKubiquitination[1, 2]
469YKEASEVKPPRDITAubiquitination[1]
481ITAEFLVKSKHRDLTubiquitination[1, 2]
492RDLTALCKEYDELAEubiquitination[1]
503ELAETQGKLEEKLQEubiquitination[1, 2]
507TQGKLEEKLQELEANubiquitination[1]
585LAEGLDIKLNTAVRQubiquitination[1, 5]
617TSQTFIYKCDAVLCTubiquitination[1]
631TLPLGVLKQQPPAVQubiquitination[1]
647VPPLPEWKTSAVQRMubiquitination[1, 2, 5]
661MGFGNLNKVVLCFDRubiquitination[1]
732GRCLAILKGIFGSSAubiquitination[1]
744SSAVPQPKETVVSRWubiquitination[1, 2]
Reference
 [1] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [2] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [3] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [4] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [5] Ubiquitin ligase substrate identification through quantitative proteomics at both the protein and peptide levels.
 Lee KA, Hammerle LP, Andrews PS, Stokes MP, Mustelin T, Silva JC, Black RA, Doedens JR.
 J Biol Chem. 2011 Dec 2;286(48):41530-8. [PMID: 21987572] 
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 PSGVEGAAFQ 180
SRLPHDRMTS QEAACFPDII SGPQQTQKVF LFIRNRTLQL WLDNPKIQLT FEATLQQLEA 240
PYNSDTVLVH RVHSYLERHG LINFGIYKRI KPLPTKKTGK VIIIGSGVSG LAAARQLQSF 300
GMDVTLLEAR DRVGGRVATF RKGNYVADLG AMVVTGLGGN PMAVVSKQVN MELAKIKQKC 360
PLYEANGQAV PKEKDEMVEQ EFNRLLEATS YLSHQLDFNV LNNKPVSLGQ ALEVVIQLQE 420
KHVKDEQIEH WKKIVKTQEE LKELLNKMVN LKEKIKELHQ QYKEASEVKP PRDITAEFLV 480
KSKHRDLTAL CKEYDELAET QGKLEEKLQE LEANPPSDVY LSSRDRQILD WHFANLEFAN 540
ATPLSTLSLK HWDQDDDFEF TGSHLTVRNG YSCVPVALAE GLDIKLNTAV RQVRYTASGC 600
EVIAVNTRST SQTFIYKCDA VLCTLPLGVL KQQPPAVQFV PPLPEWKTSA VQRMGFGNLN 660
KVVLCFDRVF WDPSVNLFGH VGSTTASRGE LFLFWNLYKA PILLALVAGE AAGIMENISD 720
DVIVGRCLAI LKGIFGSSAV PQPKETVVSR WRADPWARGS YSYVAAGSSG NDYDLMAQPI 780
TPGPSIPGAP QPIPRLFFAG EHTIRNYPAT VHGALLSGLR EAGRIADQFL GAMYTLPRQA 840
TPGVPAQQSP SM 852 
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