MLH1_RAT
ID MLH1_RAT Reviewed; 757 AA.
AC P97679;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 03-AUG-2022, entry version 139.
DE RecName: Full=DNA mismatch repair protein Mlh1;
DE AltName: Full=MutL protein homolog 1;
GN Name=Mlh1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Wistar;
RA Vani G.R., Rao M.R.S.;
RT "Cloning and sequencing of rat mismatch repair gene MLH1.";
RL Submitted (NOV-1996) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Heterodimerizes with Pms2 to form MutL alpha, a component of
CC the post-replicative DNA mismatch repair system (MMR). DNA repair is
CC initiated by MutS alpha (Msh2-Msh6) or MutS beta (MSH2-MSH3) binding to
CC a dsDNA mismatch, then MutL alpha is recruited to the heteroduplex.
CC Assembly of the MutL-MutS-heteroduplex ternary complex in presence of
CC RFC and PCNA is sufficient to activate endonuclease activity of Pms2.
CC It introduces single-strand breaks near the mismatch and thus generates
CC new entry points for the exonuclease EXO1 to degrade the strand
CC containing the mismatch. DNA methylation would prevent cleavage and
CC therefore assure that only the newly mutated DNA strand is going to be
CC corrected. MutL alpha (Mlh1-Pms2) interacts physically with the clamp
CC loader subunits of DNA polymerase III, suggesting that it may play a
CC role to recruit the DNA polymerase III to the site of the MMR. Also
CC implicated in DNA damage signaling, a process which induces cell cycle
CC arrest and can lead to apoptosis in case of major DNA damages.
CC Heterodimerizes with Mlh3 to form MutL gamma which plays a role in
CC meiosis (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Component of the DNA mismatch repair (MMR) complex composed at
CC least of MSH2, MSH3, MSH6, PMS1 and MLH1. Heterodimer of MLH1 and PMS2
CC (MutL alpha), MLH1 and PMS1 (MutL beta) or MLH1 and MLH3 (MutL gamma).
CC Forms a ternary complex with MutS alpha (MSH2-MSH6) or MutS beta (MSH2-
CC MSH3). Part of the BRCA1-associated genome surveillance complex (BASC),
CC which contains BRCA1, MSH2, MSH6, MLH1, ATM, BLM, PMS2 and the RAD50-
CC MRE11-NBS1 protein complex. This association could be a dynamic process
CC changing throughout the cell cycle and within subnuclear domains.
CC Interacts with MCM9; the interaction recruits MLH1 to chromatin.
CC Interacts MCM8. Interacts with PMS2. Interacts with MBD4. Interacts
CC with EXO1. Interacts with MTMR15/FAN1. {ECO:0000250|UniProtKB:P40692}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P40692}.
CC Chromosome {ECO:0000250|UniProtKB:P40692}. Note=Recruited to chromatin
CC in a MCM9-dependent manner. {ECO:0000250|UniProtKB:P40692}.
CC -!- SIMILARITY: Belongs to the DNA mismatch repair MutL/HexB family.
CC {ECO:0000305}.
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DR EMBL; U80054; AAB38506.1; -; mRNA.
DR RefSeq; NP_112315.1; NM_031053.1.
DR AlphaFoldDB; P97679; -.
DR SMR; P97679; -.
DR STRING; 10116.ENSRNOP00000061834; -.
DR PhosphoSitePlus; P97679; -.
DR PaxDb; P97679; -.
DR PRIDE; P97679; -.
DR GeneID; 81685; -.
DR KEGG; rno:81685; -.
DR UCSC; RGD:620937; rat.
DR CTD; 4292; -.
DR RGD; 620937; Mlh1.
DR eggNOG; KOG1979; Eukaryota.
DR InParanoid; P97679; -.
DR OrthoDB; 735423at2759; -.
DR Reactome; R-RNO-5358565; Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha).
DR PRO; PR:P97679; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005712; C:chiasma; ISO:RGD.
DR GO; GO:0005694; C:chromosome; ISO:RGD.
DR GO; GO:0000793; C:condensed chromosome; ISO:RGD.
DR GO; GO:0000794; C:condensed nuclear chromosome; ISO:RGD.
DR GO; GO:0005715; C:late recombination nodule; ISO:RGD.
DR GO; GO:0001673; C:male germ cell nucleus; ISO:RGD.
DR GO; GO:0032300; C:mismatch repair complex; IBA:GO_Central.
DR GO; GO:0032389; C:MutLalpha complex; ISO:RGD.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0000795; C:synaptonemal complex; IDA:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IBA:GO_Central.
DR GO; GO:0140664; F:ATP-dependent DNA damage sensor activity; IEA:InterPro.
DR GO; GO:0003682; F:chromatin binding; ISO:RGD.
DR GO; GO:0019899; F:enzyme binding; ISO:RGD.
DR GO; GO:0032137; F:guanine/thymine mispair binding; ISO:RGD.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISO:RGD.
DR GO; GO:0071407; P:cellular response to organic cyclic compound; IEP:RGD.
DR GO; GO:0006281; P:DNA repair; ISO:RGD.
DR GO; GO:0006303; P:double-strand break repair via nonhomologous end joining; ISO:RGD.
DR GO; GO:0016321; P:female meiosis chromosome segregation; ISO:RGD.
DR GO; GO:0007129; P:homologous chromosome pairing at meiosis; ISO:RGD.
DR GO; GO:0045143; P:homologous chromosome segregation; ISO:RGD.
DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; ISO:RGD.
DR GO; GO:0045190; P:isotype switching; ISO:RGD.
DR GO; GO:0007060; P:male meiosis chromosome segregation; ISO:RGD.
DR GO; GO:0007140; P:male meiotic nuclear division; ISO:RGD.
DR GO; GO:0051321; P:meiotic cell cycle; ISO:RGD.
DR GO; GO:0045132; P:meiotic chromosome segregation; ISO:RGD.
DR GO; GO:0043060; P:meiotic metaphase I plate congression; ISO:RGD.
DR GO; GO:0051257; P:meiotic spindle midzone assembly; ISO:RGD.
DR GO; GO:0045141; P:meiotic telomere clustering; ISO:RGD.
DR GO; GO:0006298; P:mismatch repair; ISO:RGD.
DR GO; GO:0045950; P:negative regulation of mitotic recombination; ISO:RGD.
DR GO; GO:0000289; P:nuclear-transcribed mRNA poly(A) tail shortening; ISO:RGD.
DR GO; GO:0048477; P:oogenesis; ISO:RGD.
DR GO; GO:0048298; P:positive regulation of isotype switching to IgA isotypes; ISO:RGD.
DR GO; GO:0048304; P:positive regulation of isotype switching to IgG isotypes; ISO:RGD.
DR GO; GO:0007131; P:reciprocal meiotic recombination; ISO:RGD.
DR GO; GO:0000712; P:resolution of meiotic recombination intermediates; ISO:RGD.
DR GO; GO:0009617; P:response to bacterium; ISO:RGD.
DR GO; GO:0001666; P:response to hypoxia; IEP:RGD.
DR GO; GO:0009636; P:response to toxic substance; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0016446; P:somatic hypermutation of immunoglobulin genes; ISO:RGD.
DR GO; GO:0016447; P:somatic recombination of immunoglobulin gene segments; ISO:RGD.
DR GO; GO:0002204; P:somatic recombination of immunoglobulin genes involved in immune response; ISO:RGD.
DR GO; GO:0007283; P:spermatogenesis; IEP:RGD.
DR Gene3D; 3.30.230.10; -; 1.
DR Gene3D; 3.30.565.10; -; 1.
DR InterPro; IPR014762; DNA_mismatch_repair_CS.
DR InterPro; IPR002099; DNA_mismatch_repair_N.
DR InterPro; IPR013507; DNA_mismatch_S5_2-like.
DR InterPro; IPR036890; HATPase_C_sf.
DR InterPro; IPR032189; Mlh1_C.
DR InterPro; IPR038973; MutL/Mlh/Pms.
DR InterPro; IPR020568; Ribosomal_S5_D2-typ_fold.
DR InterPro; IPR014721; Ribosomal_S5_D2-typ_fold_subgr.
DR PANTHER; PTHR10073; PTHR10073; 1.
DR Pfam; PF01119; DNA_mis_repair; 1.
DR Pfam; PF16413; Mlh1_C; 1.
DR SMART; SM01340; DNA_mis_repair; 1.
DR SUPFAM; SSF54211; SSF54211; 1.
DR SUPFAM; SSF55874; SSF55874; 1.
DR TIGRFAMs; TIGR00585; mutl; 1.
DR PROSITE; PS00058; DNA_MISMATCH_REPAIR_1; 1.
PE 2: Evidence at transcript level;
KW Acetylation; ATP-binding; Cell cycle; Chromosome; DNA damage; DNA repair;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P40692"
FT CHAIN 2..757
FT /note="DNA mismatch repair protein Mlh1"
FT /id="PRO_0000178002"
FT REGION 355..378
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 400..434
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 412..652
FT /note="Interaction with EXO1"
FT /evidence="ECO:0000250|UniProtKB:P40692"
FT REGION 456..487
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 361..377
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 470..487
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 38
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P40692"
FT BINDING 63
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P40692"
FT BINDING 82..84
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P40692"
FT BINDING 100..104
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P40692"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000250|UniProtKB:P40692"
FT MOD_RES 479
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P40692"
SQ SEQUENCE 757 AA; 84540 MW; 27E3A007D8BAB287 CRC64;
MSFVAGVIRR LDETVVNRIA AGEVIQRPAN AIKEMTENCL DAKSTNIQVI VREGGLKLIQ
IQDNGTGIRK EDLDIVCERF TTSKLQTFED LAMISTYGFR GEALASISHV AHVTITTKTA
DGKCAYRASY SDGKLQAPPK PCAGNQGTLI TVEDLFYNII TRKKALKNPS EEYGKILEVV
GRYSIHNSGI SFSVKKQGET VSDVRTLPNA TTVDNIRSIF GNAVSRELIE VGCEDKTLAF
KMNGYISNAN YSVKKCIFLL FINHRLVESA ALKKAIEAVY AAYLPKNTHP FLYLILEISP
QNVDVNVHPT KHEVHFLHEE SILERVQQHI ESKLLGSNSS RMYFTQTLLP GLAGPSGEAV
KSTTGIASSS TSGSGDKVHA YQMVRTDSRD QKLDAFMQPV SRRLPSQPQD PVPGNRTEGS
PEKAMQKDQE ISELPAPMEA AADSASLERE SVIGASEVVA PQRHPSSPGS SRKRHPEDSD
VEMMENDSRK EMTAACYPRR RIINLTSVLS LQEEINDRGH ETLREMLRNH TFVGCVNPQW
ALAQHQTKLY LLNTTKLSEE LFYQILIYDF ANFGVLRLPE PAPLFDFAML ALDSPESGWT
EEDGPKEGLA EYIVEFLKKK AKMLADYFSV EIDEEGNLIG LPLLIDSYVP PLEGLPIFIL
RLATEVNWDE EECFESLSKE CAVFYSIRKQ YILEESALSG QQSDMPGSPS KPWKWTVEHI
IYKAFRSHLL PPKHFTEDGN VLQLANLPDL CKVFERC
