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Q9JK91

- MLH1_MOUSE

UniProt

Q9JK91 - MLH1_MOUSE

Protein

DNA mismatch repair protein Mlh1

Gene

Mlh1

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 114 (01 Oct 2014)
      Sequence version 2 (27 Jul 2011)
      Previous versions | rss
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    Functioni

    Heterodimerizes with Pms2 to form MutL alpha, a component of the post-replicative DNA mismatch repair system (MMR). DNA repair is initiated by MutS alpha (Msh2-Msh6) or MutS beta (Msh2-Msh6) binding to a dsDNA mismatch, then MutL alpha is recruited to the heteroduplex. Assembly of the MutL-MutS-heteroduplex ternary complex in presence of RFC and PCNA is sufficient to activate endonuclease activity of Pms2. It introduces single-strand breaks near the mismatch and thus generates new entry points for the exonuclease EXO1 to degrade the strand containing the mismatch. DNA methylation would prevent cleavage and therefore assure that only the newly mutated DNA strand is going to be corrected. MutL alpha (Mlh1-Pms2) interacts physically with the clamp loader subunits of DNA polymerase III, suggesting that it may play a role to recruit the DNA polymerase III to the site of the MMR. Also implicated in DNA damage signaling, a process which induces cell cycle arrest and can lead to apoptosis in case of major DNA damages. Heterodimerizes with Mlh3 to form MutL gamma which plays a role in meiosis By similarity.By similarity

    GO - Molecular functioni

    1. ATPase activity Source: RefGenome
    2. ATP binding Source: InterPro
    3. guanine/thymine mispair binding Source: MGI
    4. single-stranded DNA binding Source: RefGenome
    5. structure-specific DNA binding Source: MGI

    GO - Biological processi

    1. ATP catabolic process Source: GOC
    2. cellular response to DNA damage stimulus Source: MGI
    3. DNA repair Source: MGI
    4. double-strand break repair via nonhomologous end joining Source: MGI
    5. intrinsic apoptotic signaling pathway in response to DNA damage Source: MGI
    6. isotype switching Source: MGI
    7. male meiosis Source: MGI
    8. male meiosis chromosome segregation Source: MGI
    9. meiotic chromosome segregation Source: MGI
    10. meiotic metaphase I plate congression Source: MGI
    11. meiotic nuclear division Source: MGI
    12. mismatch repair Source: MGI
    13. negative regulation of mitotic recombination Source: MGI
    14. nuclear-transcribed mRNA poly(A) tail shortening Source: MGI
    15. oogenesis Source: MGI
    16. reciprocal meiotic recombination Source: MGI
    17. resolution of meiotic recombination intermediates Source: MGI
    18. somatic hypermutation of immunoglobulin genes Source: MGI
    19. somatic recombination of immunoglobulin gene segments Source: MGI
    20. somatic recombination of immunoglobulin genes involved in immune response Source: MGI
    21. spermatogenesis Source: MGI
    22. spindle midzone assembly involved in meiosis Source: MGI
    23. synapsis Source: MGI

    Keywords - Biological processi

    Cell cycle, DNA damage, DNA repair

    Enzyme and pathway databases

    ReactomeiREACT_198629. Meiotic recombination.
    REACT_27235. Meiotic Recombination.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    DNA mismatch repair protein Mlh1
    Alternative name(s):
    MutL protein homolog 1
    Gene namesi
    Name:Mlh1
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 9

    Organism-specific databases

    MGIiMGI:101938. Mlh1.

    Subcellular locationi

    Nucleus By similarity

    GO - Cellular componenti

    1. chiasma Source: MGI
    2. chromosome Source: MGI
    3. condensed chromosome Source: MGI
    4. condensed nuclear chromosome Source: MGI
    5. male germ cell nucleus Source: MGI
    6. MutLalpha complex Source: MGI
    7. nucleoplasm Source: Reactome
    8. synaptonemal complex Source: MGI

    Keywords - Cellular componenti

    Nucleus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11RemovedBy similarity
    Chaini2 – 760759DNA mismatch repair protein Mlh1PRO_0000178001Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei481 – 4811PhosphoserineBy similarity

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiQ9JK91.
    PaxDbiQ9JK91.
    PRIDEiQ9JK91.

    PTM databases

    PhosphoSiteiQ9JK91.

    Expressioni

    Gene expression databases

    ArrayExpressiQ9JK91.
    BgeeiQ9JK91.
    CleanExiMM_MLH1.
    GenevestigatoriQ9JK91.

    Interactioni

    Subunit structurei

    Heterodimer of Mlh1 and Pms2 (MutL alpha), Mlh1 and Pms1 (MutL beta) or Mlh1 and Mlh3 (MutL gamma). Forms a ternary complex with MutS alpha (Msh2-Msh6) or MutS beta (Msh2-Msh3). Part of the BRCA1-associated genome surveillance complex (BASC), which contains BRCA1, Msh2, Msh6, Mlh1, Atm, Blm, Pms2 and the RAD50-MRE11-NBS1 protein complex. This association could be a dynamic process changing throughout the cell cycle and within subnuclear domains. Interacts with MBD4. Interacts with EXO1 and MTMR15/FAN1 By similarity.By similarity

    Protein-protein interaction databases

    STRINGi10090.ENSMUSP00000035079.

    Structurei

    3D structure databases

    ProteinModelPortaliQ9JK91.
    SMRiQ9JK91. Positions 3-335, 492-755.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni412 – 654243Interaction with EXO1By similarityAdd
    BLAST

    Sequence similaritiesi

    Phylogenomic databases

    eggNOGiCOG0323.
    GeneTreeiENSGT00550000074923.
    HOGENOMiHOG000176000.
    HOVERGENiHBG006374.
    InParanoidiQ3TG77.
    KOiK08734.
    OMAiINHRCVE.
    OrthoDBiEOG7MSMNH.
    TreeFamiTF300493.

    Family and domain databases

    Gene3Di3.30.230.10. 1 hit.
    3.30.565.10. 1 hit.
    InterProiIPR013507. DNA_mismatch_repair_C.
    IPR014762. DNA_mismatch_repair_CS.
    IPR002099. DNA_mismatch_repair_fam.
    IPR011186. DNA_mismatch_repair_MLH1/HexB.
    IPR003594. HATPase_ATP-bd.
    IPR020568. Ribosomal_S5_D2-typ_fold.
    IPR014721. Ribosomal_S5_D2-typ_fold_subgr.
    [Graphical view]
    PANTHERiPTHR10073:SF12. PTHR10073:SF12. 1 hit.
    PfamiPF01119. DNA_mis_repair. 1 hit.
    [Graphical view]
    SMARTiSM00387. HATPase_c. 1 hit.
    [Graphical view]
    SUPFAMiSSF54211. SSF54211. 1 hit.
    SSF55874. SSF55874. 1 hit.
    TIGRFAMsiTIGR00585. mutl. 1 hit.
    PROSITEiPS00058. DNA_MISMATCH_REPAIR_1. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    Q9JK91-1 [UniParc]FASTAAdd to Basket

    « Hide

    MAFVAGVIRR LDETVVNRIA AGEVIQRPAN AIKEMIENCL DAKSTNIQVV    50
    VKEGGLKLIQ IQDNGTGIRK EDLDIVCERF TTSKLQTFED LASISTYGFR 100
    GEALASISHV AHVTITTKTA DGKCAYRASY SDGKLQAPPK PCAGNQGTLI 150
    TVEDLFYNII TRRKALKNPS EEYGKILEVV GRYSIHNSGI SFSVKKQGET 200
    VSDVRTLPNA TTVDNIRSIF GNAVSRELIE VGCEDKTLAF KMNGYISNAN 250
    YSVKKCIFLL FINHRLVESA ALRKAIETVY AAYLPKNTHP FLYLSLEISP 300
    QNVDVNVHPT KHEVHFLHEE SILQRVQQHI ESKLLGSNSS RMYFTQTLLP 350
    GLAGPSGEAA RPTTGVASSS TSGSGDKVYA YQMVRTDSRE QKLDAFLQPV 400
    SSLGPSQPQD PAPVRGARTE GSPERATRED EEMLALPAPA EAAAESENLE 450
    RESLMETSDA AQKAAPTSSP GSSRKRHRED SDVEMVENAS GKEMTAACYP 500
    RRRIINLTSV LSLQEEISER CHETLREMLR NHSFVGCVNP QWALAQHQTK 550
    LYLLNTTKLS EELFYQILIY DFANFGVLRL SEPAPLFDLA MLALDSPESG 600
    WTEDDGPKEG LAEYIVEFLK KKAEMLADYF SVEIDEEGNL IGLPLLIDSY 650
    VPPLEGLPIF ILRLATEVNW DEEKECFESL SKECAMFYSI RKQYILEEST 700
    LSGQQSDMPG STSKPWKWTV EHIIYKAFRS HLLPPKHFTE DGNVLQLANL 750
    PDLYKVFERC 760
    Length:760
    Mass (Da):84,670
    Last modified:July 27, 2011 - v2
    Checksum:iB789D812F497FDF7
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti390 – 3901E → D in AAF64514. 1 PublicationCurated
    Sequence conflicti404 – 4041G → V in AAF64514. 1 PublicationCurated
    Sequence conflicti528 – 5281M → I in AAF64514. 1 PublicationCurated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF250844 mRNA. Translation: AAF64514.1.
    AK168849 mRNA. Translation: BAE40671.1.
    U60872
    , U59881, U59882, U59883, U59884 Genomic DNA. Translation: AAC52672.1.
    CCDSiCCDS40784.1.
    RefSeqiNP_081086.2. NM_026810.2.
    UniGeneiMm.486383.

    Genome annotation databases

    EnsembliENSMUST00000035079; ENSMUSP00000035079; ENSMUSG00000032498.
    GeneIDi17350.
    KEGGimmu:17350.
    UCSCiuc009rvp.2. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF250844 mRNA. Translation: AAF64514.1 .
    AK168849 mRNA. Translation: BAE40671.1 .
    U60872
    , U59881 , U59882 , U59883 , U59884 Genomic DNA. Translation: AAC52672.1 .
    CCDSi CCDS40784.1.
    RefSeqi NP_081086.2. NM_026810.2.
    UniGenei Mm.486383.

    3D structure databases

    ProteinModelPortali Q9JK91.
    SMRi Q9JK91. Positions 3-335, 492-755.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 10090.ENSMUSP00000035079.

    PTM databases

    PhosphoSitei Q9JK91.

    Proteomic databases

    MaxQBi Q9JK91.
    PaxDbi Q9JK91.
    PRIDEi Q9JK91.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000035079 ; ENSMUSP00000035079 ; ENSMUSG00000032498 .
    GeneIDi 17350.
    KEGGi mmu:17350.
    UCSCi uc009rvp.2. mouse.

    Organism-specific databases

    CTDi 4292.
    MGIi MGI:101938. Mlh1.

    Phylogenomic databases

    eggNOGi COG0323.
    GeneTreei ENSGT00550000074923.
    HOGENOMi HOG000176000.
    HOVERGENi HBG006374.
    InParanoidi Q3TG77.
    KOi K08734.
    OMAi INHRCVE.
    OrthoDBi EOG7MSMNH.
    TreeFami TF300493.

    Enzyme and pathway databases

    Reactomei REACT_198629. Meiotic recombination.
    REACT_27235. Meiotic Recombination.

    Miscellaneous databases

    ChiTaRSi Mlh1. mouse.
    NextBioi 291948.
    PROi Q9JK91.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q9JK91.
    Bgeei Q9JK91.
    CleanExi MM_MLH1.
    Genevestigatori Q9JK91.

    Family and domain databases

    Gene3Di 3.30.230.10. 1 hit.
    3.30.565.10. 1 hit.
    InterProi IPR013507. DNA_mismatch_repair_C.
    IPR014762. DNA_mismatch_repair_CS.
    IPR002099. DNA_mismatch_repair_fam.
    IPR011186. DNA_mismatch_repair_MLH1/HexB.
    IPR003594. HATPase_ATP-bd.
    IPR020568. Ribosomal_S5_D2-typ_fold.
    IPR014721. Ribosomal_S5_D2-typ_fold_subgr.
    [Graphical view ]
    PANTHERi PTHR10073:SF12. PTHR10073:SF12. 1 hit.
    Pfami PF01119. DNA_mis_repair. 1 hit.
    [Graphical view ]
    SMARTi SM00387. HATPase_c. 1 hit.
    [Graphical view ]
    SUPFAMi SSF54211. SSF54211. 1 hit.
    SSF55874. SSF55874. 1 hit.
    TIGRFAMsi TIGR00585. mutl. 1 hit.
    PROSITEi PS00058. DNA_MISMATCH_REPAIR_1. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Cloning of the cDNA of the MutL homolog, MLH1 from mouse testis."
      Kumaran M., Rao M.R.S.
      Submitted (MAR-2000) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Testis.
    2. "The transcriptional landscape of the mammalian genome."
      Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
      , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
      Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Strain: C57BL/6J.
      Tissue: Heart.
    3. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-151.

    Entry informationi

    Entry nameiMLH1_MOUSE
    AccessioniPrimary (citable) accession number: Q9JK91
    Secondary accession number(s): Q3TG77, Q62454
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 27, 2001
    Last sequence update: July 27, 2011
    Last modified: October 1, 2014
    This is version 114 of the entry and version 2 of the sequence. [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

    External Data

    Dasty 3