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Protein

DNA mismatch repair protein Mlh1

Gene

Mlh1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at transcript leveli

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: GO_Central
  2. ATP binding Source: InterPro
  3. mismatched DNA binding Source: InterPro
  4. single-stranded DNA binding Source: GO_Central

GO - Biological processi

  1. cell cycle Source: UniProtKB-KW
  2. cellular response to organic cyclic compound Source: RGD
  3. mismatch repair Source: GO_Central
  4. response to drug Source: RGD
  5. response to hypoxia Source: RGD
  6. response to toxic substance Source: RGD
  7. somatic hypermutation of immunoglobulin genes Source: GO_Central
  8. spermatogenesis Source: RGD
Complete GO annotation...

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 Componenti: Unplaced

Organism-specific databases

RGDi620937. Mlh1.

Subcellular locationi

Nucleus By similarity

GO - Cellular componenti

  1. chiasma Source: GO_Central
  2. MutLalpha complex Source: GO_Central
  3. nucleus Source: RGD
  4. synaptonemal complex Source: MGI
Complete GO annotation...

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_C.
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

        10         20         30         40         50
MSFVAGVIRR LDETVVNRIA AGEVIQRPAN AIKEMTENCL DAKSTNIQVI
60 70 80 90 100
VREGGLKLIQ IQDNGTGIRK EDLDIVCERF TTSKLQTFED LAMISTYGFR
110 120 130 140 150
GEALASISHV AHVTITTKTA DGKCAYRASY SDGKLQAPPK PCAGNQGTLI
160 170 180 190 200
TVEDLFYNII TRKKALKNPS EEYGKILEVV GRYSIHNSGI SFSVKKQGET
210 220 230 240 250
VSDVRTLPNA TTVDNIRSIF GNAVSRELIE VGCEDKTLAF KMNGYISNAN
260 270 280 290 300
YSVKKCIFLL FINHRLVESA ALKKAIEAVY AAYLPKNTHP FLYLILEISP
310 320 330 340 350
QNVDVNVHPT KHEVHFLHEE SILERVQQHI ESKLLGSNSS RMYFTQTLLP
360 370 380 390 400
GLAGPSGEAV KSTTGIASSS TSGSGDKVHA YQMVRTDSRD QKLDAFMQPV
410 420 430 440 450
SRRLPSQPQD PVPGNRTEGS PEKAMQKDQE ISELPAPMEA AADSASLERE
460 470 480 490 500
SVIGASEVVA PQRHPSSPGS SRKRHPEDSD VEMMENDSRK EMTAACYPRR
510 520 530 540 550
RIINLTSVLS LQEEINDRGH ETLREMLRNH TFVGCVNPQW ALAQHQTKLY
560 570 580 590 600
LLNTTKLSEE LFYQILIYDF ANFGVLRLPE PAPLFDFAML ALDSPESGWT
610 620 630 640 650
EEDGPKEGLA EYIVEFLKKK AKMLADYFSV EIDEEGNLIG LPLLIDSYVP
660 670 680 690 700
PLEGLPIFIL RLATEVNWDE EECFESLSKE CAVFYSIRKQ YILEESALSG
710 720 730 740 750
QQSDMPGSPS KPWKWTVEHI IYKAFRSHLL PPKHFTEDGN VLQLANLPDL

CKVFERC
Length:757
Mass (Da):84,540
Last modified:May 1, 1997 - v1
Checksum:i27E3A007D8BAB287
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
Links Updated
U80054 mRNA. Translation: AAB38506.1.
RefSeqiNP_112315.1. NM_031053.1.
UniGeneiRn.20391.

3D structure databases

ProteinModelPortaliP97679.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000043097.

Proteomic databases

PaxDbiP97679.
PRIDEiP97679.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi4292.
RGDi620937. Mlh1.

Phylogenomic databases

eggNOGiCOG0323.
HOGENOMiHOG000176000.
HOVERGENiHBG006374.
InParanoidiP97679.
KOiK08734.

Miscellaneous databases

NextBioi615316.
PROiP97679.

Gene expression databases

GenevestigatoriP97679.

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_C.
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]
ProtoNetiSearch...

Publicationsi

  1. "Cloning and sequencing of rat mismatch repair gene MLH1."
    Vani G.R., Rao M.R.S.
    Submitted (OCT-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: March 4, 2015
This is version 109 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.