ID   MLH1_DICDI              Reviewed;         884 AA.
AC   Q54KD8;
DT   29-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT   24-MAY-2005, sequence version 1.
DT   03-AUG-2022, entry version 119.
DE   RecName: Full=DNA mismatch repair protein Mlh1;
DE   AltName: Full=MutL protein homolog 1;
GN   Name=mlh1; ORFNames=DDB_G0287393;
OS   Dictyostelium discoideum (Slime mold).
OC   Eukaryota; Amoebozoa; Evosea; Eumycetozoa; Dictyostelia; Dictyosteliales;
OC   Dictyosteliaceae; Dictyostelium.
OX   NCBI_TaxID=44689;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=AX4;
RX   PubMed=15875012; DOI=10.1038/nature03481;
RA   Eichinger L., Pachebat J.A., Gloeckner G., Rajandream M.A., Sucgang R.,
RA   Berriman M., Song J., Olsen R., Szafranski K., Xu Q., Tunggal B.,
RA   Kummerfeld S., Madera M., Konfortov B.A., Rivero F., Bankier A.T.,
RA   Lehmann R., Hamlin N., Davies R., Gaudet P., Fey P., Pilcher K., Chen G.,
RA   Saunders D., Sodergren E.J., Davis P., Kerhornou A., Nie X., Hall N.,
RA   Anjard C., Hemphill L., Bason N., Farbrother P., Desany B., Just E.,
RA   Morio T., Rost R., Churcher C.M., Cooper J., Haydock S., van Driessche N.,
RA   Cronin A., Goodhead I., Muzny D.M., Mourier T., Pain A., Lu M., Harper D.,
RA   Lindsay R., Hauser H., James K.D., Quiles M., Madan Babu M., Saito T.,
RA   Buchrieser C., Wardroper A., Felder M., Thangavelu M., Johnson D.,
RA   Knights A., Loulseged H., Mungall K.L., Oliver K., Price C., Quail M.A.,
RA   Urushihara H., Hernandez J., Rabbinowitsch E., Steffen D., Sanders M.,
RA   Ma J., Kohara Y., Sharp S., Simmonds M.N., Spiegler S., Tivey A.,
RA   Sugano S., White B., Walker D., Woodward J.R., Winckler T., Tanaka Y.,
RA   Shaulsky G., Schleicher M., Weinstock G.M., Rosenthal A., Cox E.C.,
RA   Chisholm R.L., Gibbs R.A., Loomis W.F., Platzer M., Kay R.R.,
RA   Williams J.G., Dear P.H., Noegel A.A., Barrell B.G., Kuspa A.;
RT   "The genome of the social amoeba Dictyostelium discoideum.";
RL   Nature 435:43-57(2005).
CC   -!- FUNCTION: Heterodimerizes with pms1 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 pms1.
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 (By similarity). {ECO:0000250}.
CC   -!- SUBUNIT: Heterodimer of mlh1 and pms1 (MutL alpha), and mlh1 and mlh3
CC       (MutL gamma). Forms a ternary complex with MutS alpha (msh2-msh6) or
CC       MutS beta (msh2-msh3). Interacts with exo1 (By similarity).
CC       {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the DNA mismatch repair MutL/HexB family.
CC       {ECO:0000305}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; AAFI02000100; EAL63764.1; -; Genomic_DNA.
DR   RefSeq; XP_637285.1; XM_632193.1.
DR   AlphaFoldDB; Q54KD8; -.
DR   SMR; Q54KD8; -.
DR   STRING; 44689.DDB0232418; -.
DR   PaxDb; Q54KD8; -.
DR   EnsemblProtists; EAL63764; EAL63764; DDB_G0287393.
DR   GeneID; 8626116; -.
DR   KEGG; ddi:DDB_G0287393; -.
DR   dictyBase; DDB_G0287393; mlh1.
DR   eggNOG; KOG1979; Eukaryota.
DR   HOGENOM; CLU_004131_2_0_1; -.
DR   InParanoid; Q54KD8; -.
DR   OMA; ANYHVKK; -.
DR   PhylomeDB; Q54KD8; -.
DR   Reactome; R-DDI-5358565; Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha).
DR   PRO; PR:Q54KD8; -.
DR   Proteomes; UP000002195; Chromosome 5.
DR   GO; GO:0032300; C:mismatch repair complex; IBA:GO_Central.
DR   GO; GO:0032389; C:MutLalpha complex; IBA:GO_Central.
DR   GO; GO:0005524; F:ATP binding; ISS:dictyBase.
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:0003677; F:DNA binding; ISS:dictyBase.
DR   GO; GO:0030983; F:mismatched DNA binding; IEA:InterPro.
DR   GO; GO:0032407; F:MutSalpha complex binding; ISS:dictyBase.
DR   GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR   GO; GO:0006298; P:mismatch repair; IBA:GO_Central.
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   3: Inferred from homology;
KW   Cell cycle; DNA damage; DNA repair; Nucleus; Reference proteome.
FT   CHAIN           1..884
FT                   /note="DNA mismatch repair protein Mlh1"
FT                   /id="PRO_0000331655"
FT   REGION          1..21
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          297..318
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          442..522
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          544..605
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        442..475
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        476..490
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        491..514
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        544..599
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ   SEQUENCE   884 AA;  98753 MW;  B934EB45D9855718 CRC64;
     MDFLKSLPPL QTTDSNSTTA AVNTTTTTAT NTATTTATNT ATTTTTTTTT NLNNLINESK
     KKIHRLTQEV VNKISAGEVI QRPSNALKEL LENCLDAKST TITVTVKDGG MKFLQIQDNG
     SGIRLEDMGI VCERFTTSKL TKFEDLRSIQ SFGFRGEALS SISHVSHLKI LTKTADSPCA
     YRACYLNGKL TPPSPNEQSS DPKPCAGVNG TQITVEDLFF NTPSRKNVLK NTVDEHSRIV
     LLMKKYAINN PTVSFILKKQ GDPTPEVHTS GGQNSLEKDV IGSLYGTDLS KELKIITIDP
     NNPNPNNDDD DNISGSQIKN SNLNRLDFTM KGFFSSTNYN SKKINFILFI NGRLVDSKNL
     KTGLEQVYSK YLPKGTHPFM FIRLLVPPKN IDVNIHPTKS EVKILHEEQI IEFIQQKVDQ
     ELSISSNSKT FSTQILLPGF DQDNVSSSQK KQKNSQSSST QTKSTNNNNN PTSRKEPIEY
     AKDKIRSDSK SQTLDAFLNP MDYNNNNDSS IDDNDGSGIG RYDDVDGSAG AAGAGGKFND
     NLIFNDNSEN EAPRDIDNPL SSVTPIKSKE QRQQQSTTTT TTTTTTTATT KSNSPASKND
     IKKLQEHTFI TPRKTRKYKQ VELTSIKTLI SEFQSNVHDG LKEFFNDCVF VGCLDHSYAL
     VQFGKKLYLI NLENITKELF YQLSLLRFSD FDSIKFSQSL SIYSLLLVSL DSPLSGWMES
     DGPKDKIADY LTKLLISKKE LLNEYFSIEI NEDGELVGIP QVLDHYVPCT DNLPIFLLKL
     ATEVEWEFEK ECFAGIVKEI SSFFKIEPSF LKLRDTQVNN QQQTNSTTTT NNINFIKKDG
     KEWIIQHLIF PAFRKLSPPK KFANDGSVIQ ITTLDNLYKV FERC