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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

Cofactori

FAD1 Publication

Enzyme regulationi

Inhibited by tranylcypromine, but not by pargyline, deprenyl or rasagiline.1 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

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri133 – 19361CW-typePROSITE-ProRule annotationAdd
    BLAST
    Nucleotide bindingi389 – 44557FADSequence analysisAdd
    BLAST

    GO - Molecular functioni

    • DNA binding Source: InterPro
    • flavin adenine dinucleotide binding Source: UniProtKB
    • 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
    Complete GO annotation...

    Keywords - Molecular functioni

    Chromatin regulator, Developmental protein, Oxidoreductase, Repressor

    Keywords - Biological processi

    Transcription, Transcription regulation

    Keywords - Ligandi

    FAD, Flavoprotein, Metal-binding, Zinc

    Enzyme and pathway databases

    ReactomeiR-MMU-3214842. HDMs demethylate histones.

    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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    Proteomesi
    • UP000000589 Componenti: Chromosome 13

    Organism-specific databases

    MGIiMGI:2145261. Kdm1b.

    Subcellular locationi

    GO - Cellular componenti

    • nucleus Source: UniProtKB
    Complete GO annotation...

    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)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi667 – 6671K → A: Loss of activity. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 826826Lysine-specific histone demethylase 1BPRO_0000247337Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei17 – 171PhosphoserineCombined sources
    Modified residuei26 – 261PhosphoserineBy similarity
    Modified residuei253 – 2531PhosphoserineCombined sources

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    EPDiQ8CIG3.
    MaxQBiQ8CIG3.
    PaxDbiQ8CIG3.
    PeptideAtlasiQ8CIG3.
    PRIDEiQ8CIG3.

    PTM databases

    iPTMnetiQ8CIG3.
    PhosphoSiteiQ8CIG3.

    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

    Does not form a complex with RCOR1/CoREST.

    Protein-protein interaction databases

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

    Structurei

    3D structure databases

    ProteinModelPortaliQ8CIG3.
    SMRiQ8CIG3. Positions 49-826.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini281 – 37999SWIRMPROSITE-ProRule annotationAdd
    BLAST

    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 CW-type zinc finger.PROSITE-ProRule annotation
    Contains 1 SWIRM domain.PROSITE-ProRule annotation

    Zinc finger

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri133 – 19361CW-typePROSITE-ProRule annotationAdd
    BLAST

    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.
    3.40.50.720. 1 hit.
    InterProiIPR002937. Amino_oxidase.
    IPR023753. FAD/NAD-binding_dom.
    IPR009057. Homeodomain-like.
    IPR016040. NAD(P)-bd_dom.
    IPR007526. SWIRM.
    IPR011991. WHTH_DNA-bd_dom.
    IPR011124. Znf_CW.
    [Graphical view]
    PfamiPF01593. Amino_oxidase. 1 hit.
    PF04433. SWIRM. 1 hit.
    PF07496. zf-CW. 1 hit.
    [Graphical view]
    SUPFAMiSSF46689. SSF46689. 1 hit.
    SSF51905. SSF51905. 2 hits.
    PROSITEiPS50934. SWIRM. 1 hit.
    PS51050. ZF_CW. 1 hit.
    [Graphical view]

    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)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 621621Missing in isoform 3. 1 PublicationVSP_019968Add
    BLAST
    Alternative sequencei459 – 558100Missing in isoform 2. 1 PublicationVSP_019969Add
    BLAST

    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

    Cross-referencesi

    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.

    3D structure databases

    ProteinModelPortaliQ8CIG3.
    SMRiQ8CIG3. Positions 49-826.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

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

    PTM databases

    iPTMnetiQ8CIG3.
    PhosphoSiteiQ8CIG3.

    Proteomic databases

    EPDiQ8CIG3.
    MaxQBiQ8CIG3.
    PaxDbiQ8CIG3.
    PeptideAtlasiQ8CIG3.
    PRIDEiQ8CIG3.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    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]

    Organism-specific databases

    CTDi221656.
    MGIiMGI:2145261. Kdm1b.

    Phylogenomic databases

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

    Enzyme and pathway databases

    ReactomeiR-MMU-3214842. HDMs demethylate histones.

    Miscellaneous databases

    ChiTaRSiKdm1b. mouse.
    PROiQ8CIG3.
    SOURCEiSearch...

    Gene expression databases

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

    Family and domain databases

    Gene3Di1.10.10.10. 1 hit.
    3.40.50.720. 1 hit.
    InterProiIPR002937. Amino_oxidase.
    IPR023753. FAD/NAD-binding_dom.
    IPR009057. Homeodomain-like.
    IPR016040. NAD(P)-bd_dom.
    IPR007526. SWIRM.
    IPR011991. WHTH_DNA-bd_dom.
    IPR011124. Znf_CW.
    [Graphical view]
    PfamiPF01593. Amino_oxidase. 1 hit.
    PF04433. SWIRM. 1 hit.
    PF07496. zf-CW. 1 hit.
    [Graphical view]
    SUPFAMiSSF46689. SSF46689. 1 hit.
    SSF51905. SSF51905. 2 hits.
    PROSITEiPS50934. SWIRM. 1 hit.
    PS51050. ZF_CW. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Entry informationi

    Entry nameiKDM1B_MOUSE
    AccessioniPrimary (citable) accession number: Q8CIG3
    Secondary accession number(s): Q8C5C4, Q8CEC1
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 25, 2006
    Last sequence update: March 1, 2003
    Last modified: September 7, 2016
    This is version 108 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    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.

    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

    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.