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Q96EQ9

- PRDM9_MOUSE

UniProt

Q96EQ9 - PRDM9_MOUSE

Protein

Histone-lysine N-methyltransferase PRDM9

Gene

Prdm9

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 107 (01 Oct 2014)
      Sequence version 2 (10 Feb 2009)
      Previous versions | rss
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    Functioni

    Histone methyltransferase that specifically trimethylates 'Lys-4' of histone H3 during meiotic prophase and is essential for proper meiotic progression. Does not have the ability to mono- and dimethylate 'Lys-4' of histone H3. H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation. Plays a central role in the transcriptional activation of genes during early meiotic prophase.1 Publication

    Catalytic activityi

    S-adenosyl-L-methionine + L-lysine-[histone] = S-adenosyl-L-homocysteine + N(6)-methyl-L-lysine-[histone].1 Publication

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri388 – 41124C2H2-type 1PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri513 – 53119C2H2-type 2; degeneratePROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri537 – 55923C2H2-type 3PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri565 – 58723C2H2-type 4PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri593 – 61523C2H2-type 5PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri621 – 64323C2H2-type 6PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri649 – 67123C2H2-type 7PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri677 – 69923C2H2-type 8PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri705 – 72723C2H2-type 9PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri733 – 75523C2H2-type 10PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri761 – 78323C2H2-type 11PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri789 – 81123C2H2-type 12PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri817 – 83923C2H2-type 13PROSITE-ProRule annotationAdd
    BLAST

    GO - Molecular functioni

    1. histone methyltransferase activity (H3-K4 specific) Source: MGI
    2. metal ion binding Source: UniProtKB-KW
    3. recombination hotspot binding Source: MGI
    4. sequence-specific DNA binding Source: MGI

    GO - Biological processi

    1. histone H3-K4 methylation Source: GOC
    2. histone lysine methylation Source: MGI
    3. histone methylation Source: MGI
    4. meiotic nuclear division Source: UniProtKB-KW
    5. positive regulation of meiosis I Source: MGI
    6. positive regulation of reciprocal meiotic recombination Source: MGI
    7. positive regulation of transcription from RNA polymerase II promoter Source: MGI
    8. spermatogenesis Source: MGI
    9. transcription, DNA-templated Source: UniProtKB-KW

    Keywords - Molecular functioni

    Activator, Chromatin regulator, Methyltransferase, Transferase

    Keywords - Biological processi

    Meiosis, Transcription, Transcription regulation

    Keywords - Ligandi

    Metal-binding, S-adenosyl-L-methionine, Zinc

    Enzyme and pathway databases

    ReactomeiREACT_198629. Meiotic recombination.
    REACT_209769. Meiotic recombination.
    REACT_27235. Meiotic Recombination.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Histone-lysine N-methyltransferase PRDM9 (EC:2.1.1.43)
    Alternative name(s):
    Hybrid sterility protein 1
    Meiosis-induced factor containing a PR/SET domain and zinc-finger motif
    PR domain zinc finger protein 9
    PR domain-containing protein 9
    Gene namesi
    Name:Prdm9
    Synonyms:Hst1, Meisetz
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 17

    Organism-specific databases

    MGIiMGI:2384854. Prdm9.

    Subcellular locationi

    Nucleus Curated. Chromosome Curated

    GO - Cellular componenti

    1. chromosome Source: UniProtKB-SubCell
    2. nucleoplasm Source: Reactome

    Keywords - Cellular componenti

    Chromosome, Nucleus

    Pathology & Biotechi

    Disruption phenotypei

    Sterility in both sexes due to severe impairment of the double-stranded break repair pathway, deficient pairing of homologous chromosomes and impaired sex body formation. In testis, H3 'Lys-4' trimethylation is attenuated and meiotic gene transcription is altered.1 Publication

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi276 – 2761Y → F: Abolishes enzyme methyltransferase. 1 Publication
    Mutagenesisi278 – 2781G → A: Abolishes enzyme methyltransferase. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 843843Histone-lysine N-methyltransferase PRDM9PRO_0000363960Add
    BLAST

    Proteomic databases

    PRIDEiQ96EQ9.

    PTM databases

    PhosphoSiteiQ96EQ9.

    Expressioni

    Tissue specificityi

    Specifically expressed in germ cells entering meiotic prophase in female fetal gonads and in postnatal testis.1 Publication

    Developmental stagei

    Specifically expressed during meiotic prophase. Transiently increases in female gonads from E13.5 to E16.5, the time during which meiosis proceeds from pre-meiotic replication to pachytene stages. Its expression is barely detectable in fetal male gonads. In adults, it is expressed in testis, but not in any other tissue tested. Abundance increases from 10 d post partum (dpp) to 18 dpp, during which time the first wave of spermatogenesis proceeds synchronously from pre-leptotene to pachytene stages.1 Publication

    Gene expression databases

    ArrayExpressiQ96EQ9.
    BgeeiQ96EQ9.
    GenevestigatoriQ96EQ9.

    Interactioni

    Protein-protein interaction databases

    STRINGi10090.ENSMUSP00000040727.

    Structurei

    Secondary structure

    1
    843
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi203 – 2053
    Turni206 – 2094
    Beta strandi210 – 2145
    Turni217 – 2193
    Helixi237 – 2404
    Beta strandi246 – 2505
    Beta strandi258 – 2625
    Beta strandi278 – 2814
    Helixi286 – 2883
    Beta strandi289 – 2968
    Beta strandi298 – 3003
    Beta strandi302 – 3065
    Turni310 – 3123
    Helixi315 – 3184
    Turni325 – 3273
    Beta strandi330 – 3356
    Beta strandi338 – 3458
    Helixi359 – 3646

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    4C1QX-ray2.30A/B198-368[»]
    ProteinModelPortaliQ96EQ9.
    SMRiQ96EQ9. Positions 195-411, 489-843.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini23 – 8664KRAB-relatedPROSITE-ProRule annotationAdd
    BLAST
    Domaini244 – 358115SETPROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Belongs to the class V-like SAM-binding methyltransferase superfamily.PROSITE-ProRule annotation
    Contains 13 C2H2-type zinc fingers.PROSITE-ProRule annotation
    Contains 1 KRAB-related domain.PROSITE-ProRule annotation
    Contains 1 SET domain.PROSITE-ProRule annotation

    Zinc finger

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri388 – 41124C2H2-type 1PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri513 – 53119C2H2-type 2; degeneratePROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri537 – 55923C2H2-type 3PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri565 – 58723C2H2-type 4PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri593 – 61523C2H2-type 5PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri621 – 64323C2H2-type 6PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri649 – 67123C2H2-type 7PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri677 – 69923C2H2-type 8PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri705 – 72723C2H2-type 9PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri733 – 75523C2H2-type 10PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri761 – 78323C2H2-type 11PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri789 – 81123C2H2-type 12PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri817 – 83923C2H2-type 13PROSITE-ProRule annotationAdd
    BLAST

    Keywords - Domaini

    Repeat, Zinc-finger

    Phylogenomic databases

    eggNOGiNOG241438.
    GeneTreeiENSGT00530000063157.
    HOGENOMiHOG000234617.
    HOVERGENiHBG108291.
    PhylomeDBiQ96EQ9.

    Family and domain databases

    Gene3Di3.30.160.60. 12 hits.
    InterProiIPR001909. Krueppel-associated_box.
    IPR003655. Krueppel-associated_box-rel.
    IPR001214. SET_dom.
    IPR019041. SSXRD_motif.
    IPR007087. Znf_C2H2.
    IPR015880. Znf_C2H2-like.
    IPR013087. Znf_C2H2/integrase_DNA-bd.
    [Graphical view]
    PfamiPF01352. KRAB. 1 hit.
    PF09514. SSXRD. 1 hit.
    [Graphical view]
    SMARTiSM00349. KRAB. 1 hit.
    SM00317. SET. 1 hit.
    SM00355. ZnF_C2H2. 13 hits.
    [Graphical view]
    SUPFAMiSSF109640. SSF109640. 1 hit.
    PROSITEiPS50806. KRAB_RELATED. 1 hit.
    PS50280. SET. 1 hit.
    PS00028. ZINC_FINGER_C2H2_1. 12 hits.
    PS50157. ZINC_FINGER_C2H2_2. 12 hits.
    [Graphical view]

    Sequences (4)i

    Sequence statusi: Complete.

    This entry describes 4 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q96EQ9-1) [UniParc]FASTAAdd to Basket

    Also known as: Meisetz

    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

    MNTNKLEENS PEEDTGKFEW KPKVKDEFKD ISIYFSKEEW AEMGEWEKIR    50
    YRNVKRNYKM LISIGLRAPR PAFMCYQRQA MKPQINDSED SDEEWTPKQQ 100
    VSPPWVPFRV KHSKQQKESS RMPFSGESNV KEGSGIENLL NTSGSEHVQK 150
    PVSSLEEGNT SGQHSGKKLK LRKKNVEVKM YRLRERKGLA YEEVSEPQDD 200
    DYLYCEKCQN FFIDSCPNHG PPLFVKDSMV DRGHPNHSVL SLPPGLRISP 250
    SGIPEAGLGV WNEASDLPVG LHFGPYEGQI TEDEEAANSG YSWLITKGRN 300
    CYEYVDGQDE SQANWMRYVN CARDDEEQNL VAFQYHRKIF YRTCRVIRPG 350
    CELLVWYGDE YGQELGIKWG SKMKKGFTAG RELRTEIHPC LLCSLAFSSQ 400
    KFLTQHMEWN HRTEIFPGTS ARINPKPGDP CSDQLQEQHV DSQNKNDKAS 450
    NEVKRKSKPR QRISTTFPST LKEQMRSEES KRTVEELRTG QTTNTEDTVK 500
    SFIASEISSI ERQCGQYFSD KSNVNEHQKT HTGEKPYVCR ECGRGFTQNS 550
    HLIQHQRTHT GEKPYVCREC GRGFTQKSDL IKHQRTHTGE KPYVCRECGR 600
    GFTQKSDLIK HQRTHTGEKP YVCRECGRGF TQKSVLIKHQ RTHTGEKPYV 650
    CRECGRGFTQ KSVLIKHQRT HTGEKPYVCR ECGRGFTAKS VLIQHQRTHT 700
    GEKPYVCREC GRGFTAKSNL IQHQRTHTGE KPYVCRECGR GFTAKSVLIQ 750
    HQRTHTGEKP YVCRECGRGF TAKSVLIQHQ RTHTGEKPYV CRECGRGFTQ 800
    KSNLIKHQRT HTGEKPYVCR ECGWGFTQKS DLIQHQRTHT REK 843
    Length:843
    Mass (Da):97,365
    Last modified:February 10, 2009 - v2
    Checksum:i323DD4F00447D598
    GO
    Isoform 2 (identifier: Q96EQ9-2) [UniParc]FASTAAdd to Basket

    Also known as: Meisetz-S1

    The sequence of this isoform differs from the canonical sequence as follows:
         382-404: ELRTEIHPCLLCSLAFSSQKFLT → GGHYYDSLKKKEKREFSLRIFIF
         405-843: Missing.

    Show »
    Length:404
    Mass (Da):46,856
    Checksum:iE8D64C40EFB5EC84
    GO
    Isoform 3 (identifier: Q96EQ9-3) [UniParc]FASTAAdd to Basket

    Also known as: Meisetz-S2

    The sequence of this isoform differs from the canonical sequence as follows:
         382-418: ELRTEIHPCLLCSLAFSSQKFLTQHMEWNHRTEIFPG → DLFIIICKYTVAVFRHTRRGSQILLRMVVSHHVVAGI
         419-843: Missing.

    Show »
    Length:418
    Mass (Da):48,244
    Checksum:i0EBDF88F535CEE94
    GO
    Isoform 4 (identifier: Q96EQ9-4) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-121: Missing.
         382-404: ELRTEIHPCLLCSLAFSSQKFLT → GGHYYDSLKKKEKREFSLRIFIF
         405-843: Missing.

    Show »
    Length:283
    Mass (Da):32,241
    Checksum:iF4FE5CE36B04C03E
    GO

    Sequence cautioni

    The sequence AAH49903.1 differs from that shown. Reason: Erroneous initiation.

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 121121Missing in isoform 4. 1 PublicationVSP_036374Add
    BLAST
    Alternative sequencei382 – 41837ELRTE…EIFPG → DLFIIICKYTVAVFRHTRRG SQILLRMVVSHHVVAGI in isoform 3. CuratedVSP_036375Add
    BLAST
    Alternative sequencei382 – 40423ELRTE…QKFLT → GGHYYDSLKKKEKREFSLRI FIF in isoform 2 and isoform 4. 1 PublicationVSP_036376Add
    BLAST
    Alternative sequencei405 – 843439Missing in isoform 2 and isoform 4. 1 PublicationVSP_036377Add
    BLAST
    Alternative sequencei419 – 843425Missing in isoform 3. CuratedVSP_036378Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AY294423 Genomic DNA. Translation: AAQ01511.1.
    AC154378 Genomic DNA. No translation available.
    CT033750 Genomic DNA. Translation: CAX15894.1.
    BC012016 mRNA. Translation: AAH12016.1.
    BC049903 mRNA. Translation: AAH49903.1. Different initiation.
    UniGeneiMm.215162.

    Genome annotation databases

    EnsembliENSMUST00000147532; ENSMUSP00000118454; ENSMUSG00000051977. [Q96EQ9-4]
    UCSCiuc008aos.1. mouse. [Q96EQ9-4]
    uc029tan.1. mouse. [Q96EQ9-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AY294423 Genomic DNA. Translation: AAQ01511.1 .
    AC154378 Genomic DNA. No translation available.
    CT033750 Genomic DNA. Translation: CAX15894.1 .
    BC012016 mRNA. Translation: AAH12016.1 .
    BC049903 mRNA. Translation: AAH49903.1 . Different initiation.
    UniGenei Mm.215162.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    4C1Q X-ray 2.30 A/B 198-368 [» ]
    ProteinModelPortali Q96EQ9.
    SMRi Q96EQ9. Positions 195-411, 489-843.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 10090.ENSMUSP00000040727.

    PTM databases

    PhosphoSitei Q96EQ9.

    Proteomic databases

    PRIDEi Q96EQ9.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000147532 ; ENSMUSP00000118454 ; ENSMUSG00000051977 . [Q96EQ9-4 ]
    UCSCi uc008aos.1. mouse. [Q96EQ9-4 ]
    uc029tan.1. mouse. [Q96EQ9-1 ]

    Organism-specific databases

    MGIi MGI:2384854. Prdm9.

    Phylogenomic databases

    eggNOGi NOG241438.
    GeneTreei ENSGT00530000063157.
    HOGENOMi HOG000234617.
    HOVERGENi HBG108291.
    PhylomeDBi Q96EQ9.

    Enzyme and pathway databases

    Reactomei REACT_198629. Meiotic recombination.
    REACT_209769. Meiotic recombination.
    REACT_27235. Meiotic Recombination.

    Miscellaneous databases

    NextBioi 13887360.
    PROi Q96EQ9.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q96EQ9.
    Bgeei Q96EQ9.
    Genevestigatori Q96EQ9.

    Family and domain databases

    Gene3Di 3.30.160.60. 12 hits.
    InterProi IPR001909. Krueppel-associated_box.
    IPR003655. Krueppel-associated_box-rel.
    IPR001214. SET_dom.
    IPR019041. SSXRD_motif.
    IPR007087. Znf_C2H2.
    IPR015880. Znf_C2H2-like.
    IPR013087. Znf_C2H2/integrase_DNA-bd.
    [Graphical view ]
    Pfami PF01352. KRAB. 1 hit.
    PF09514. SSXRD. 1 hit.
    [Graphical view ]
    SMARTi SM00349. KRAB. 1 hit.
    SM00317. SET. 1 hit.
    SM00355. ZnF_C2H2. 13 hits.
    [Graphical view ]
    SUPFAMi SSF109640. SSF109640. 1 hit.
    PROSITEi PS50806. KRAB_RELATED. 1 hit.
    PS50280. SET. 1 hit.
    PS00028. ZINC_FINGER_C2H2_1. 12 hits.
    PS50157. ZINC_FINGER_C2H2_2. 12 hits.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Genomic sequence analysis in the mouse T-complex region."
      Brathwaite M., Waeltz P., Nagaraja R.
      Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: C57BL/6J.
    2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: C57BL/6J.
    3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
      Tissue: Eye.
    4. "A histone H3 methyltransferase controls epigenetic events required for meiotic prophase."
      Hayashi K., Yoshida K., Matsui Y.
      Nature 438:374-378(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, CATALYTIC ACTIVITY, ALTERNATIVE SPLICING (ISOFORMS 1; 2 AND 3), TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE, MUTAGENESIS OF TYR-276 AND GLY-278.
    5. "A mouse speciation gene encodes a meiotic histone H3 methyltransferase."
      Mihola O., Trachtulec Z., Vlcek C., Schimenti J.C., Forejt J.
      Science 323:373-375(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION AS A SPECIATION GENE.

    Entry informationi

    Entry nameiPRDM9_MOUSE
    AccessioniPrimary (citable) accession number: Q96EQ9
    Secondary accession number(s): B8JJZ8, Q0D2N4
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 10, 2009
    Last sequence update: February 10, 2009
    Last modified: October 1, 2014
    This is version 107 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Miscellaneous

    Represents a speciation gene in mus genus. Prdm9 is one of several genes responsible for hybrid sterility between M.musculus and house mouse. Hybrid sterility is defined as a situation where parental forms, each fertile inter se, produce infertile offspring. Intersubspecific hybrids of house mouse display spermatogenic failures that are due to variations in the Prdm9 gene.

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3