WERAM Information

Tag Content
WERAM ID WERAM-Hos-0001
Ensembl Protein ID ENSP00000349049.3
Uniprot Accession O60341; KDM1A_HUMAN; A8MWP9; Q5TH94; Q5TH95; Q86VT7; Q8IXK4; Q8NDP6; Q8TAZ3; Q96AW4
Genbank Protein ID NP_001009999.1; NP_055828.2
Protein Name Lysine-specific histone demethylase 1A
Genbank Nucleotide ID NM_001009999.2; NM_015013.3
Gene Name KDM1A;LSD1
Ensembl Information
Ensembl Gene ID Ensembl Transcript ID Ensembl Protein ID
ENSG00000004487.15 ENST00000356634.7 ENSP00000349049.3
Details
Type Family Domain Substrates AA References (PMIDs)
HDM LSD1_KDM1 Demethylaseactivity H3K4me1/2; H3K9 K 16983801; 20889125; 20951770; 17291768; 20889120; 26872725
Status Reviewed
Classification
Type Family E-value Score Start End
HDM LSD1_KDM1 6.10e-211 704.5 224 852
Organism Homo sapiens
NCBI Taxa ID 9606
Functional Description
(View)		 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.
Domain Profile
  HDM LSD1_KDM1
           LSD1.txt 163 laesenkleeklqllvaelksfvylssrdkkiLsws.lavael.envyPlstldl 215
                        + + + ++e +lq l+a  +s+  l  r + +L+ + l +  + + + Pl t ++
  ENSP00000349049.3 224 NPKIQLTFEATLQQLEAPYNSDTVLVHRVHSYLERHgLINFGIyKRIKPLPTKKT 278
                        5667889999***************999999999874444433467777766655 PP
           LSD1.txt   1 lppkvvilEAkeRvGGri..yskavpvsdleasevsslasnsnavssksvnlelkkvkdkstldsdpLyelssqqlslekvemveref.... 86 
                        ++++v++lEA++RvGGr+  ++k+++v+dl+a++v++l++n++av+sk+vn+el+k+k+k+     pLye+++q++++ek+emve+ef    
  ENSP00000349049.3 300 FGMDVTLLEARDRVGGRVatFRKGNYVADLGAMVVTGLGGNPMAVVSKQVNMELAKIKQKC-----PLYEANGQAVPKEKDEMVEQEFnrll 386
                        79***********************************************************.....************************** PP
           LSD1.txt  87 .....vlheldtkvld............vvevqklfvlfeklleyvkvvkskeelkelinkeeslkikileqiqly...........isiEa 150
                             ++h+ld++vl+            v+++q+++v++e++++++k+vk++eelkel+nk+++lk+ki+e++q+y           i++E+
  ENSP00000349049.3 387 eatsyLSHQLDFNVLNnkpvslgqalevVIQLQEKHVKDEQIEHWKKIVKTQEELKELLNKMVNLKEKIKELHQQYkeasevkpprdITAEF 478
                        ******************************************************************************************** PP
           LSD1.txt 151 lpkslkkdLsel......laesenkleeklqllvaelksfvylssrdkkiLswslavaelenvyPlstldl.......dlellgekvavrrG 229
                        l+ks+++dL++l      lae+++kleeklq+l+a+++s+vylssrd++iL+w++a++e++n++Plstl+l       d+e++g++++vr+G
  ENSP00000349049.3 479 LVKSKHRDLTALckeydeLAETQGKLEEKLQELEANPPSDVYLSSRDRQILDWHFANLEFANATPLSTLSLkhwdqddDFEFTGSHLTVRNG 570
                        ******************************************************************************************** PP
           LSD1.txt 230 lsdlpvaLastPspLdiklekavrkvkleddkvelsavness......ykvDkvvialpldklksq..lieFePpLpefktkaikridFknl 313
                        +s++pvaLa   ++Ldikl++avr+v+++++++e++avn++s      yk+D+v+++lpl++lk+q  +++F+PpLpe+kt+a++r++F+nl
  ENSP00000349049.3 571 YSCVPVALA---EGLDIKLNTAVRQVRYTASGCEVIAVNTRStsqtfiYKCDAVLCTLPLGVLKQQppAVQFVPPLPEWKTSAVQRMGFGNL 659
                        *********...******************************************************************************** PP
           LSD1.txt 314 kKviLifkaaFWepnislFGsvpkstarelifdevlrfwnllkePiLlalvkveaidimenisddviqglvsailkvikgkseaadpletvv 405
                        +Kv+L+f+++FW+p+++lFG+v+++ta++   +e+++fwnl+k+PiLlalv++ea++imenisddvi+g+++ailk+i+g+s++++p+etvv
  ENSP00000349049.3 660 NKVVLCFDRVFWDPSVNLFGHVGSTTASR---GELFLFWNLYKAPILLALVAGEAAGIMENISDDVIVGRCLAILKGIFGSSAVPQPKETVV 748
                        *****************************...************************************************************ PP
           LSD1.txt 406 snWeadslt 414
                        s+W+ad ++
  ENSP00000349049.3 749 SRWRADPWA 757
                        *****8654 PP
           LSD1.txt 537 lLvaellgpsPepPskPsanPyLlyqktqwhvckaladedkrrltGdstaratknevrakLgktlReldslgkqplvdeiaarReayagkla 628
                         L+a++++p+P++P++P+++P+L++                   +G++t+r+++++v+++L+++lRe++++++q+l+++++++R+a++g++a
  ENSP00000349049.3 774 DLMAQPITPGPSIPGAPQPIPRLFF-------------------AGEHTIRNYPATVHGALLSGLREAGRIADQFLGAMYTLPRQATPGVPA 846
                        59***********************...................************************************************ PP
           LSD1.txt 629 eyqrsi 634
                        ++++s+
  ENSP00000349049.3 847 QQSPSM 852
                        ***997 PP
Protein Sequence
(Fasta)		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
Nucleotide Sequence
(Fasta)		GGCGCGGCGG GAGCGCGCTT GGCGCGTGCG TACGCGACGG CGGTTGGCGG CGCGCGGGCA 60
GCGTGAAGCG AGGCGAGGCA AGGCTTTTCG GACCCACGGA GCGACAGAGC GAGCGGCCCC 120
TACGGCCGTC GGCGGCCCGG CGGCCCGAGA TGTTATCTGG GAAGAAGGCG GCAGCCGCGG 180
CGGCGGCGGC TGCAGCGGCA GCAACCGGGA CGGAGGCTGG CCCTGGGACA GCAGGCGGCT 240
CCGAGAACGG GTCTGAGGTG GCCGCGCAGC CCGCGGGCCT GTCGGGCCCA GCCGAGGTCG 300
GGCCGGGGGC GGTGGGGGAG CGCACACCCC GCAAGAAAGA GCCTCCGCGG GCCTCGCCCC 360
CCGGGGGCCT GGCGGAACCG CCGGGGTCCG CAGGGCCTCA GGCCGGCCCT ACTGTCGTGC 420
CTGGGTCTGC GACCCCCATG GAAACTGGAA TAGCAGAGAC TCCGGAGGGG CGTCGGACCA 480
GCCGGCGCAA GCGGGCGAAG GTAGAGTACA GAGAGATGGA TGAAAGCTTG GCCAACCTCT 540
CAGAAGATGA GTATTATTCA GAAGAAGAGA GAAATGCCAA AGCAGAGAAG GAAAAGAAGC 600
TTCCCCCACC ACCCCCTCAA GCCCCACCTG AGGAAGAAAA TGAAAGTGAG CCTGAAGAAC 660
CATCGGGTGT GGAGGGCGCA GCTTTCCAGA GCCGACTTCC TCATGACCGG ATGACTTCTC 720
AAGAAGCAGC CTGTTTTCCA GATATTATCA GTGGACCACA ACAGACCCAG AAGGTTTTTC 780
TTTTCATTAG AAACCGCACA CTGCAGTTGT GGTTGGATAA TCCAAAGATT CAGCTGACAT 840
TTGAGGCTAC TCTCCAACAA TTAGAAGCAC CTTATAACAG TGATACTGTG CTTGTCCACC 900
GAGTTCACAG TTATTTAGAG CGTCATGGTC TTATCAACTT CGGCATCTAT AAGAGGATAA 960
AACCCCTACC AACTAAAAAG ACAGGAAAGG TAATTATTAT AGGCTCTGGG GTCTCAGGCT 1020
TGGCAGCAGC TCGACAGTTA CAAAGTTTTG GAATGGATGT CACACTTTTG GAAGCCAGGG 1080
ATCGTGTGGG TGGACGAGTT GCCACATTTC GCAAAGGAAA CTATGTAGCT GATCTTGGAG 1140
CCATGGTGGT AACAGGTCTT GGAGGGAATC CTATGGCTGT GGTCAGCAAA CAAGTAAATA 1200
TGGAACTGGC CAAGATCAAG CAAAAATGCC CACTTTATGA AGCCAACGGA CAAGCTGTTC 1260
CTAAAGAGAA AGATGAAATG GTAGAGCAAG AGTTTAACCG GTTGCTAGAA GCTACATCTT 1320
ACCTTAGTCA TCAACTAGAC TTCAATGTCC TCAATAATAA GCCTGTGTCC CTTGGCCAGG 1380
CATTGGAAGT TGTCATTCAG TTACAAGAGA AGCATGTCAA AGATGAGCAG ATTGAACATT 1440
GGAAGAAGAT AGTGAAAACT CAGGAAGAAT TGAAAGAACT TCTTAATAAG ATGGTAAATT 1500
TGAAAGAGAA AATTAAAGAA CTCCATCAGC AATACAAAGA AGCATCTGAA GTAAAGCCAC 1560
CCAGAGATAT TACTGCCGAG TTCTTAGTGA AAAGCAAACA CAGGGATCTG ACCGCCCTAT 1620
GCAAGGAATA TGATGAATTA GCTGAAACAC AAGGAAAGCT AGAAGAAAAA CTTCAGGAGT 1680
TGGAAGCGAA TCCCCCAAGT GATGTATATC TCTCATCAAG AGACAGACAA ATACTTGATT 1740
GGCATTTTGC AAATCTTGAA TTTGCTAATG CCACACCTCT CTCAACTCTC TCCCTTAAGC 1800
ACTGGGATCA GGATGATGAC TTTGAGTTCA CTGGCAGCCA CCTGACAGTA AGGAATGGCT 1860
ACTCGTGTGT GCCTGTGGCT TTAGCAGAAG GCCTAGACAT TAAACTGAAT ACAGCAGTGC 1920
GACAGGTTCG CTACACGGCT TCAGGATGTG AAGTGATAGC TGTGAATACC CGCTCCACGA 1980
GTCAAACCTT TATTTATAAA TGCGACGCAG TTCTCTGTAC CCTTCCCCTG GGTGTGCTGA 2040
AGCAGCAGCC ACCAGCCGTT CAGTTTGTGC CACCTCTCCC TGAGTGGAAA ACATCTGCAG 2100
TCCAAAGGAT GGGATTTGGC AACCTTAACA AGGTGGTGTT GTGTTTTGAT CGGGTGTTCT 2160
GGGATCCAAG TGTCAATTTG TTCGGGCATG TTGGCAGTAC GACTGCCAGC AGGGGTGAGC 2220
TCTTCCTCTT CTGGAACCTC TATAAAGCTC CAATACTGTT GGCACTAGTG GCAGGAGAAG 2280
CTGCTGGTAT CATGGAAAAC ATAAGTGACG ATGTGATTGT TGGCCGATGC CTGGCCATTC 2340
TCAAAGGGAT TTTTGGTAGC AGTGCAGTAC CTCAGCCCAA AGAAACTGTG GTGTCTCGTT 2400
GGCGTGCTGA TCCCTGGGCT CGGGGCTCTT ATTCCTATGT TGCTGCAGGA TCATCTGGAA 2460
ATGACTATGA TTTAATGGCT CAGCCAATCA CTCCTGGCCC CTCGATTCCA GGTGCCCCAC 2520
AGCCGATTCC ACGACTCTTC TTTGCGGGAG AACATACGAT CCGTAACTAC CCAGCCACAG 2580
TGCATGGTGC TCTGCTGAGT GGGCTGCGAG AAGCGGGAAG AATTGCAGAC CAGTTTTTGG 2640
GGGCCATGTA TACGCTGCCT CGCCAGGCCA CACCAGGTGT TCCTGCACAG CAGTCCCCAA 2700
GCATGTGAGA CAGATGCATT CTAAGGGAAG AGGCCCATGT GCCTGTTTCT GCCATGTAAG 2760
GAAGGCTCTT CTAGCAATAC TAGATCCCAC TGAGAAAATC CACCCTGGCA TCTGGGCTCC 2820
TGATCAGCTG ATGGAGCTCC TGATTTGACA AAGGAGCTTG CCTCCTTTGA ATGACCTAGA 2880
GCACAGGGAG GAACTTGTCC ATTAGTTTGG AATTGTGTTC TTCGTAAAGA CTGAGGCAAG 2940
CAAGTGCTGT GAAATAACAT CATCTTAGTC CCTTGGTGTG TGGGGTTTTT GTTTTTTTTT 3000
TATATTTTGA GAATAAAACT TCATATAAAA TTG 3034
Sequence Source Ensembl
Keyword

KW-0002--3D-structure
KW-0025--Alternative splicing
KW-0156--Chromatin regulator
KW-0175--Coiled coil
KW-0181--Complete proteome
KW-0217--Developmental protein
KW-0903--Direct protein sequencing
KW-0274--FAD
KW-0285--Flavoprotein
KW-0539--Nucleus
KW-0560--Oxidoreductase
KW-0597--Phosphoprotein
KW-1185--Reference proteome
KW-0678--Repressor
KW-0804--Transcription
KW-0805--Transcription regulation
--
Interpro

IPR002937--Amino_oxidase
IPR023753--FAD/NAD-binding_dom
IPR017366--Hist_Lys-spec_deMease
IPR009057--Homeodomain-like
IPR007526--SWIRM
IPR011991--WHTH_DNA-bd_dom
PROSITE

PS50934--SWIRM
Pfam

PF01593--Amino_oxidase
PF04433--SWIRM
Gene Ontology

GO:1990391--C:DNA repair complex
GO:0000790--C:nuclear chromatin
GO:0000784--C:nuclear chromosome, telomeric region
GO:0005654--C:nucleoplasm
GO:0005634--C:nucleus
GO:0043234--C:protein complex
GO:0005667--C:transcription factor complex
GO:0050681--F:androgen receptor binding
GO:0003682--F:chromatin binding
GO:0032451--F:demethylase activity
GO:0019899--F:enzyme binding
GO:0050660--F:flavin adenine dinucleotide binding
GO:0004407--F:histone deacetylase activity
GO:0032452--F:histone demethylase activity
GO:0034648--F:histone demethylase activity (H3-dimethyl-K4 specific)
GO:0032453--F:histone demethylase activity (H3-K4 specific)
GO:0032454--F:histone demethylase activity (H3-K9 specific)
GO:0030374--F:ligand-dependent nuclear receptor transcription coactivator activity
GO:0043426--F:MRF binding
GO:0016491--F:oxidoreductase activity
GO:0002039--F:p53 binding
GO:0042162--F:telomeric DNA binding
GO:0061752--F:telomeric repeat-containing RNA binding
GO:0003700--F:transcription factor activity, sequence-specific DNA binding
GO:0008134--F:transcription factor binding
GO:0044212--F:transcription regulatory region DNA binding
GO:0007596--P:blood coagulation
GO:0008283--P:cell proliferation
GO:0071480--P:cellular response to gamma radiation
GO:0034644--P:cellular response to UV
GO:0030851--P:granulocyte differentiation
GO:0016575--P:histone deacetylation
GO:0034720--P:histone H3-K4 demethylation
GO:0033169--P:histone H3-K9 demethylation
GO:0001701--P:in utero embryonic development
GO:0055001--P:muscle cell development
GO:0043392--P:negative regulation of DNA binding
GO:0043518--P:negative regulation of DNA damage response, signal transduction by p53 class mediator
GO:0051572--P:negative regulation of histone H3-K4 methylation
GO:0051573--P:negative regulation of histone H3-K9 methylation
GO:1902166--P:negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
GO:0032091--P:negative regulation of protein binding
GO:0043433--P:negative regulation of sequence-specific DNA binding transcription factor activity
GO:0000122--P:negative regulation of transcription from RNA polymerase II promoter
GO:0045892--P:negative regulation of transcription, DNA-templated
GO:0021983--P:pituitary gland development
GO:0045648--P:positive regulation of erythrocyte differentiation
GO:0033184--P:positive regulation of histone ubiquitination
GO:0046886--P:positive regulation of hormone biosynthetic process
GO:0045654--P:positive regulation of megakaryocyte differentiation
GO:2000179--P:positive regulation of neural precursor cell proliferation
GO:0051091--P:positive regulation of sequence-specific DNA binding transcription factor activity
GO:2000648--P:positive regulation of stem cell proliferation
GO:0045944--P:positive regulation of transcription from RNA polymerase II promoter
GO:0006482--P:protein demethylation
GO:1903827--P:regulation of cellular protein localization
GO:0010569--P:regulation of double-strand break repair via homologous recombination
GO:0010725--P:regulation of primitive erythrocyte differentiation
GO:0006357--P:regulation of transcription from RNA polymerase II promoter
GO:0006351--P:transcription, DNA-templated
Orthology
WERAM ID Ensembl Protein ID Species Identity E-value Score
WERAM-Mam-0080 ENSMMUP00000012794.2 Macaca mulatta 100 0.0 1500
WERAM-Caj-0060 ENSCJAP00000010405.2 Callithrix jacchus 99 0.0 1496
WERAM-Caf-0144 ENSCAFP00000040032.1 Canis familiaris 100 0.0 1492
WERAM-Mum-0144 ENSMUSP00000111977.2 Mus musculus 99 0.0 1480
WERAM-Orc-0010 ENSOCUP00000001013.2 Oryctolagus cuniculus 96 0.0 1399
WERAM-Aim-0167 ENSAMEP00000015737.1 Ailuropoda melanoleuca 95 0.0 1389
WERAM-Fec-0137 ENSFCAP00000012799.3 Felis catus 100 0.0 1320
WERAM-Ova-0079 ENSOARP00000008285.1 Ovis aries 100 0.0 1319
WERAM-Eqc-0161 ENSECAP00000017401.1 Equus caballus 100 0.0 1319
WERAM-Myl-0119 ENSMLUP00000009662.2 Myotis lucifugus 100 0.0 1317
WERAM-Scp-0022 SPBC146.09c.1:pep Schizosaccharomyces pombe 26 2e-16 85.9
Created Date 25-Jun-2016