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P97679

- MLH1_RAT

UniProt

P97679 - MLH1_RAT

Protein

DNA mismatch repair protein Mlh1

Gene

Mlh1

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 4 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 105 (01 Oct 2014)
      Sequence version 1 (01 May 1997)
      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. mismatched DNA binding Source: InterPro
    4. single-stranded DNA binding Source: RefGenome

    GO - Biological processi

    1. ATP catabolic process Source: GOC
    2. cell cycle Source: UniProtKB-KW
    3. cellular response to organic cyclic compound Source: RGD
    4. mismatch repair Source: RefGenome
    5. response to drug Source: RGD
    6. response to hypoxia Source: RGD
    7. response to toxic substance Source: RGD
    8. somatic hypermutation of immunoglobulin genes Source: RefGenome
    9. spermatogenesis Source: RGD

    Keywords - Biological processi

    Cell cycle, DNA damage, DNA repair

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    DNA mismatch repair protein Mlh1
    Alternative name(s):
    MutL protein homolog 1
    Gene namesi
    Name:Mlh1
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494: Unplaced

    Organism-specific databases

    RGDi620937. Mlh1.

    Subcellular locationi

    Nucleus By similarity

    GO - Cellular componenti

    1. chiasma Source: RefGenome
    2. MutLalpha complex Source: RefGenome
    3. nucleus Source: RGD
    4. synaptonemal complex Source: MGI

    Keywords - Cellular componenti

    Nucleus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11RemovedBy similarity
    Chaini2 – 757756DNA mismatch repair protein Mlh1PRO_0000178002Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei2 – 21N-acetylserineBy similarity
    Modified residuei479 – 4791PhosphoserineBy similarity

    Keywords - PTMi

    Acetylation, Phosphoprotein

    Proteomic databases

    PaxDbiP97679.
    PRIDEiP97679.

    Expressioni

    Gene expression databases

    GenevestigatoriP97679.

    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

    STRINGi10116.ENSRNOP00000043097.

    Structurei

    3D structure databases

    ProteinModelPortaliP97679.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni412 – 652241Interaction with EXO1By similarityAdd
    BLAST

    Sequence similaritiesi

    Phylogenomic databases

    eggNOGiCOG0323.
    HOGENOMiHOG000176000.
    HOVERGENiHBG006374.
    InParanoidiP97679.
    KOiK08734.

    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.

    P97679-1 [UniParc]FASTAAdd to Basket

    « Hide

    MSFVAGVIRR LDETVVNRIA AGEVIQRPAN AIKEMTENCL DAKSTNIQVI    50
    VREGGLKLIQ IQDNGTGIRK EDLDIVCERF TTSKLQTFED LAMISTYGFR 100
    GEALASISHV AHVTITTKTA DGKCAYRASY SDGKLQAPPK PCAGNQGTLI 150
    TVEDLFYNII TRKKALKNPS EEYGKILEVV GRYSIHNSGI SFSVKKQGET 200
    VSDVRTLPNA TTVDNIRSIF GNAVSRELIE VGCEDKTLAF KMNGYISNAN 250
    YSVKKCIFLL FINHRLVESA ALKKAIEAVY AAYLPKNTHP FLYLILEISP 300
    QNVDVNVHPT KHEVHFLHEE SILERVQQHI ESKLLGSNSS RMYFTQTLLP 350
    GLAGPSGEAV KSTTGIASSS TSGSGDKVHA YQMVRTDSRD QKLDAFMQPV 400
    SRRLPSQPQD PVPGNRTEGS PEKAMQKDQE ISELPAPMEA AADSASLERE 450
    SVIGASEVVA PQRHPSSPGS SRKRHPEDSD VEMMENDSRK EMTAACYPRR 500
    RIINLTSVLS LQEEINDRGH ETLREMLRNH TFVGCVNPQW ALAQHQTKLY 550
    LLNTTKLSEE LFYQILIYDF ANFGVLRLPE PAPLFDFAML ALDSPESGWT 600
    EEDGPKEGLA EYIVEFLKKK AKMLADYFSV EIDEEGNLIG LPLLIDSYVP 650
    PLEGLPIFIL RLATEVNWDE EECFESLSKE CAVFYSIRKQ YILEESALSG 700
    QQSDMPGSPS KPWKWTVEHI IYKAFRSHLL PPKHFTEDGN VLQLANLPDL 750
    CKVFERC 757
    Length:757
    Mass (Da):84,540
    Last modified:May 1, 1997 - v1
    Checksum:i27E3A007D8BAB287
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U80054 mRNA. Translation: AAB38506.1.
    RefSeqiNP_112315.1. NM_031053.1.
    UniGeneiRn.20391.

    Genome annotation databases

    GeneIDi81685.
    KEGGirno:81685.
    UCSCiRGD:620937. rat.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U80054 mRNA. Translation: AAB38506.1 .
    RefSeqi NP_112315.1. NM_031053.1.
    UniGenei Rn.20391.

    3D structure databases

    ProteinModelPortali P97679.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 10116.ENSRNOP00000043097.

    Proteomic databases

    PaxDbi P97679.
    PRIDEi P97679.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 81685.
    KEGGi rno:81685.
    UCSCi RGD:620937. rat.

    Organism-specific databases

    CTDi 4292.
    RGDi 620937. Mlh1.

    Phylogenomic databases

    eggNOGi COG0323.
    HOGENOMi HOG000176000.
    HOVERGENi HBG006374.
    InParanoidi P97679.
    KOi K08734.

    Miscellaneous databases

    NextBioi 615316.
    PROi P97679.

    Gene expression databases

    Genevestigatori P97679.

    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 and sequencing of rat mismatch repair gene MLH1."
      Vani G.R., Rao M.R.S.
      Submitted (NOV-1996) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Strain: Wistar.

    Entry informationi

    Entry nameiMLH1_RAT
    AccessioniPrimary (citable) accession number: P97679
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 27, 2001
    Last sequence update: May 1, 1997
    Last modified: October 1, 2014
    This is version 105 of the entry and version 1 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. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3