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Protein

Lysine-specific histone demethylase 1B

Gene

Kdm1b

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Histone demethylase that demethylates 'Lys-4' of histone H3, a specific tag for epigenetic transcriptional activation, thereby acting as a corepressor. Required for de novo DNA methylation of a subset of imprinted genes during oogenesis. Acts by oxidizing the substrate by FAD to generate the corresponding imine that is subsequently hydrolyzed. Demethylates both mono- and di-methylated 'Lys-4' of histone H3. Has no effect on tri-methylated 'Lys-4', mono-, di- or tri-methylated 'Lys-9', mono-, di- or tri-methylated 'Lys-27', mono-, di- or tri-methylated 'Lys-36' of histone H3, or on mono-, di- or tri-methylated 'Lys-20' of histone H4.2 Publications

Miscellaneous

Acetylation of 'Lys-9' decreases the binding of the substrate, while hyperacetylation of 'Lys-9', 'Lys-14' and 'Lys-18', phosphorylation of 'Thr3' or 'Ser-10', and methylation of 'Arg-2' or 'Arg-8' abolishes its binding. Methylation of 'Lys-9' and 'Arg-17' are the only two epigenetic modifications that have no significant effect on catalysis.

Cofactori

Protein has several cofactor binding sites:
  • FAD1 Publication
  • Zn2+By similarityNote: Binds 3 Zn2+ ions per subunit.By similarity

Enzyme regulationi

Inhibited by tranylcypromine, but not by pargyline, deprenyl or rasagiline (PubMed:19407342). Histone H3K4me1 and H3K4me2 demethylase activity is enhanced by GLYR1 (By similarity).By similarity1 Publication

Kineticsi

  1. KM=9.2 µM for mono-methylated 'Lys-4' histone H3 N-terminal peptide1 Publication
  2. KM=11.3 µM for di-methylated 'Lys-4' histone H3 N-terminal peptide1 Publication
  3. KM=9.0 µM for mono-methylated 'Lys-4', mono-methylated 'Lys-9' histone H3 N-terminal peptide1 Publication
  4. KM=6.6 µM for di-methylated 'Lys-4', di-methylated 'Lys-9' histone H3 N-terminal peptide1 Publication
  5. KM=70.5 µM for mono-methylated 'Lys-4', acetylated 'Lys-9' histone H3 N-terminal peptide1 Publication
  6. KM=8.1 µM for mono-methylated 'Lys-4', mono-methylated 'Arg-17' histone H3 N-terminal peptide1 Publication

    pH dependencei

    Optimum pH is 8.5.1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Metal bindingi53Zinc 1By similarity1
    Metal bindingi58Zinc 1By similarity1
    Metal bindingi65Zinc 2By similarity1
    Metal bindingi73Zinc 2By similarity1
    Metal bindingi84Zinc 1; via pros nitrogenBy similarity1
    Metal bindingi90Zinc 1; via tele nitrogenBy similarity1
    Metal bindingi92Zinc 2By similarity1
    Metal bindingi95Zinc 2By similarity1
    Metal bindingi142Zinc 3By similarity1
    Metal bindingi147Zinc 3By similarity1
    Metal bindingi169Zinc 3By similarity1
    Metal bindingi185Zinc 3By similarity1
    Binding sitei604FAD; via amide nitrogen and carbonyl oxygenBy similarity1
    Binding sitei799FAD; via amide nitrogenBy similarity1

    Regions

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Zinc fingeri133 – 193CW-typePROSITE-ProRule annotationAdd BLAST61
    Nucleotide bindingi389 – 445FADSequence analysisBy similarityAdd BLAST57
    Nucleotide bindingi807 – 809FADBy similarity3

    GO - Molecular functioni

    • DNA binding Source: InterPro
    • FAD binding Source: UniProtKB
    • flavin adenine dinucleotide binding Source: UniProtKB
    • histone binding Source: Ensembl
    • histone demethylase activity (H3-dimethyl-K4 specific) Source: UniProtKB
    • histone demethylase activity (H3-monomethyl-K4 specific) Source: UniProtKB
    • zinc ion binding Source: UniProtKB

    GO - Biological processi

    • DNA methylation involved in gamete generation Source: MGI
    • histone H3-K4 demethylation Source: UniProtKB
    • multicellular organism development Source: UniProtKB-KW
    • regulation of DNA methylation Source: UniProtKB
    • regulation of gene expression by genetic imprinting Source: UniProtKB
    • regulation of transcription, DNA-templated Source: UniProtKB-KW
    • transcription, DNA-templated Source: UniProtKB-KW

    Keywordsi

    Molecular functionChromatin regulator, Developmental protein, Oxidoreductase, Repressor
    Biological processTranscription, Transcription regulation
    LigandFAD, Flavoprotein, Metal-binding, Zinc

    Enzyme and pathway databases

    ReactomeiR-MMU-3214842. HDMs demethylate histones.
    R-MMU-5689603. UCH proteinases.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Lysine-specific histone demethylase 1B (EC:1.-.-.-)
    Alternative name(s):
    Flavin-containing amine oxidase domain-containing protein 1
    Lysine-specific histone demethylase 2
    Gene namesi
    Name:Kdm1b
    Synonyms:Aof1, Lsd2
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
    Proteomesi
    • UP000000589 Componenti: Chromosome 13

    Organism-specific databases

    MGIiMGI:2145261. Kdm1b.

    Subcellular locationi

    GO - Cellular componenti

    • nucleosome Source: Ensembl
    • nucleus Source: UniProtKB

    Keywords - Cellular componenti

    Nucleus

    Pathology & Biotechi

    Disruption phenotypei

    No effect on mouse development and oogenesis, but embryos derived from oocytes from Kdm1b-deficient females die before mid-gestation.1 Publication

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi667K → A: Loss of activity. 1 Publication1

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00002473371 – 826Lysine-specific histone demethylase 1BAdd BLAST826

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei17PhosphoserineCombined sources1
    Modified residuei26PhosphoserineBy similarity1
    Modified residuei253PhosphoserineCombined sources1

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    EPDiQ8CIG3.
    PaxDbiQ8CIG3.
    PeptideAtlasiQ8CIG3.
    PRIDEiQ8CIG3.

    PTM databases

    iPTMnetiQ8CIG3.
    PhosphoSitePlusiQ8CIG3.

    Expressioni

    Tissue specificityi

    Expressed in growing oocytes and in intestinal gland.1 Publication

    Gene expression databases

    BgeeiENSMUSG00000038080.
    CleanExiMM_AOF1.
    ExpressionAtlasiQ8CIG3. baseline and differential.
    GenevisibleiQ8CIG3. MM.

    Interactioni

    Subunit structurei

    Interacts with its cofactor GLYR1 at nucleosomes; this interaction stimulates H3K4me1 and H3K4me2 demethylation (By similarity). Does not form a complex with RCOR1/CoREST.By similarity

    GO - Molecular functioni

    Protein-protein interaction databases

    BioGridi230002. 1 interactor.
    DIPiDIP-59111N.
    STRINGi10090.ENSMUSP00000038373.

    Structurei

    3D structure databases

    ProteinModelPortaliQ8CIG3.
    SMRiQ8CIG3.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Domaini281 – 379SWIRMPROSITE-ProRule annotationAdd BLAST99

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni279 – 298GLYR1-bindingBy similarityAdd BLAST20
    Regioni444 – 473Histone H3-bindingBy similarityAdd BLAST30
    Regioni493 – 504Histone H3-bindingBy similarityAdd BLAST12
    Regioni544 – 578Histone H3-bindingBy similarityAdd BLAST35
    Regioni570 – 572GLYR1-bindingBy similarity3
    Regioni802 – 818GLYR1-bindingBy similarityAdd BLAST17

    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

    Zinc finger

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Zinc fingeri133 – 193CW-typePROSITE-ProRule annotationAdd BLAST61

    Keywords - Domaini

    Zinc-finger

    Phylogenomic databases

    eggNOGiKOG0029. Eukaryota.
    ENOG410XSNC. LUCA.
    GeneTreeiENSGT00530000062888.
    HOGENOMiHOG000230870.
    InParanoidiQ8CIG3.
    KOiK19413.
    OMAiPFYQPNE.
    OrthoDBiEOG091G04NO.
    PhylomeDBiQ8CIG3.
    TreeFamiTF352593.

    Family and domain databases

    Gene3Di1.10.10.10. 1 hit.
    3.50.50.60. 1 hit.
    InterProiView protein in InterPro
    IPR002937. Amino_oxidase.
    IPR023753. FAD/NAD-binding_dom.
    IPR009057. Homeobox-like.
    IPR007526. SWIRM.
    IPR011991. WHTH_DNA-bd_dom.
    IPR011124. Znf_CW.
    PfamiView protein in Pfam
    PF01593. Amino_oxidase. 1 hit.
    PF04433. SWIRM. 1 hit.
    PF07496. zf-CW. 1 hit.
    SUPFAMiSSF46689. SSF46689. 1 hit.
    SSF51905. SSF51905. 2 hits.
    PROSITEiView protein in PROSITE
    PS50934. SWIRM. 1 hit.
    PS51050. ZF_CW. 1 hit.

    Sequences (3)i

    Sequence statusi: Complete.

    This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform 1 (identifier: Q8CIG3-1) [UniParc]FASTAAdd to basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

            10         20         30         40         50
    MAASRGRSKK RSNLELSPDN LPLRSSGRQA KKKAVEIPDE DEDGSSEKKY
    60 70 80 90 100
    RKCEKAGCTA AYPVCFASAS ERCAKNGYTS RWYHLSCGEH FCNECFDHYY
    110 120 130 140 150
    RSHKDGYDKY SAWKRVWTSN GKTEPSPKAF MADQQLPYWV QCTKPECGKW
    160 170 180 190 200
    RQLTKEIQLT PHMARTYRCG MKPNTITKPD TPDHCSFPED LRVLEVSNHW
    210 220 230 240 250
    WYPMLIQPPL LKDSVAAPLL SAYYPDCVGM SPSCTSTHRA TVTAATTTTG
    260 270 280 290 300
    SASPGEMEPS KAAPSSLVLG MNRYFQPFYQ PNECGKALCV RPDVMELDEL
    310 320 330 340 350
    YEFPEYSRDP TMYLALRNLI LALWYTNCKE ALTPQKCIPH IIVRGLVRIR
    360 370 380 390 400
    CVQEVERILY FMTRKGLINT GVLTVAAGQH LLPKHYHNKS VLVVGAGPAG
    410 420 430 440 450
    LAAARQLHNF GMKVTVLEAK DRIGGRVWDD KSFKGVVVGR GPQIVNGCIN
    460 470 480 490 500
    NPVALMCEQL GISMRKLGER CDLIQEGGRI TDPTVDKRMD FHFNALLDVV
    510 520 530 540 550
    SEWRKDKTLL QDVPLGEKIE EIYRAFVKES GIQFSELEGQ VLQFHLSNLE
    560 570 580 590 600
    YACGSSLHQV SARSWDHNEF FAQFAGDHTL LTPGYSTIIE KLAEGLDIRL
    610 620 630 640 650
    KSPVQSIDYT GDEVQVTTTD GMGHSAQKVL VTVPLAILQR GAIQFNPPLS
    660 670 680 690 700
    EKKMKAINSL GAGIIEKIAL QFPYRFWDSK VQGADFFGHV PPSASQRGLF
    710 720 730 740 750
    AVFYDMDSQQ SVLMSVITGE AVASLRTMDD KQVLQQCMGI LRELFKEQEI
    760 770 780 790 800
    PEPTKYFVTR WSTEPWIQMA YSFVKTFGSG EAYDIIAEEI QGTVFFAGEA
    810 820
    TNRHFPQTVT GAYLSGVREA SKIAAF
    Length:826
    Mass (Da):92,633
    Last modified:March 1, 2003 - v1
    Checksum:i02FD6FE991B1C030
    GO
    Isoform 2 (identifier: Q8CIG3-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         459-558: Missing.

    Note: No experimental confirmation available.
    Show »
    Length:726
    Mass (Da):81,183
    Checksum:iA1DDEA3678E43BE8
    GO
    Isoform 3 (identifier: Q8CIG3-3) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-621: Missing.

    Note: No experimental confirmation available.
    Show »
    Length:205
    Mass (Da):22,813
    Checksum:i1277A6D29E57E50C
    GO

    Sequence cautioni

    The sequence BAC26005 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
    The sequence BAC37460 differs from that shown. Reason: Frameshift at position 825.Curated

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_0199681 – 621Missing in isoform 3. 1 PublicationAdd BLAST621
    Alternative sequenceiVSP_019969459 – 558Missing in isoform 2. 1 PublicationAdd BLAST100

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AK028553 mRNA. Translation: BAC26005.1. Different initiation.
    AK078920 mRNA. Translation: BAC37460.1. Frameshift.
    BC023917 mRNA. Translation: AAH23917.1.
    CCDSiCCDS26489.1. [Q8CIG3-1]
    RefSeqiNP_758466.1. NM_172262.3. [Q8CIG3-1]
    UniGeneiMm.31259.

    Genome annotation databases

    EnsembliENSMUST00000037025; ENSMUSP00000038373; ENSMUSG00000038080. [Q8CIG3-1]
    GeneIDi218214.
    KEGGimmu:218214.
    UCSCiuc007qht.3. mouse. [Q8CIG3-1]
    uc007qhu.3. mouse. [Q8CIG3-2]
    uc011yyy.2. mouse. [Q8CIG3-3]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.

    Entry informationi

    Entry nameiKDM1B_MOUSE
    AccessioniPrimary (citable) accession number: Q8CIG3
    Secondary accession number(s): Q8C5C4, Q8CEC1
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 25, 2006
    Last sequence update: March 1, 2003
    Last modified: May 10, 2017
    This is version 115 of the entry and version 1 of the sequence. See 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