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P97679 (MLH1_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 101. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
DNA mismatch repair protein Mlh1
Alternative name(s):
MutL protein homolog 1
Gene names
Name:Mlh1
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length757 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

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.

Subunit structure

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.

Subcellular location

Nucleus By similarity.

Sequence similarities

Belongs to the DNA mismatch repair MutL/HexB family.

Ontologies

Keywords
   Biological processCell cycle
DNA damage
DNA repair
   Cellular componentNucleus
   PTMAcetylation
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processATP catabolic process

Inferred from Biological aspect of Ancestor. Source: GOC

cellular response to organic cyclic compound

Inferred from expression pattern PubMed 16471326. Source: RGD

mismatch repair

Inferred from Biological aspect of Ancestor. Source: RefGenome

reciprocal meiotic recombination

Inferred from Biological aspect of Ancestor. Source: RefGenome

response to drug

Inferred from expression pattern PubMed 18253720. Source: RGD

response to hypoxia

Inferred from expression pattern PubMed 15942958. Source: RGD

response to toxic substance

Inferred from expression pattern PubMed 20127075. Source: RGD

somatic hypermutation of immunoglobulin genes

Inferred from Biological aspect of Ancestor. Source: RefGenome

spermatogenesis

Inferred from expression pattern PubMed 10644444. Source: RGD

   Cellular_componentMutLalpha complex

Inferred from Biological aspect of Ancestor. Source: RefGenome

MutLbeta complex

Inferred from Biological aspect of Ancestor. Source: RefGenome

chiasma

Inferred from Biological aspect of Ancestor. Source: RefGenome

mismatch repair complex

Inferred from Biological aspect of Ancestor. Source: RefGenome

nucleus

Inferred from direct assay PubMed 15942958. Source: RGD

synaptonemal complex

Inferred from direct assay PubMed 16968740. Source: MGI

   Molecular_functionATP binding

Inferred from electronic annotation. Source: InterPro

ATPase activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

MutSalpha complex binding

Inferred from Biological aspect of Ancestor. Source: RefGenome

mismatched DNA binding

Inferred from electronic annotation. Source: InterPro

single-stranded DNA binding

Inferred from Biological aspect of Ancestor. Source: RefGenome

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 757756DNA mismatch repair protein Mlh1
PRO_0000178002

Regions

Region412 – 652241Interaction with EXO1 By similarity

Amino acid modifications

Modified residue21N-acetylserine By similarity
Modified residue4791Phosphoserine By similarity

Sequences

Sequence LengthMass (Da)Tools
P97679 [UniParc].

Last modified May 1, 1997. Version 1.
Checksum: 27E3A007D8BAB287

FASTA75784,540
        10         20         30         40         50         60 
MSFVAGVIRR LDETVVNRIA AGEVIQRPAN AIKEMTENCL DAKSTNIQVI VREGGLKLIQ 

        70         80         90        100        110        120 
IQDNGTGIRK EDLDIVCERF TTSKLQTFED LAMISTYGFR GEALASISHV AHVTITTKTA 

       130        140        150        160        170        180 
DGKCAYRASY SDGKLQAPPK PCAGNQGTLI TVEDLFYNII TRKKALKNPS EEYGKILEVV 

       190        200        210        220        230        240 
GRYSIHNSGI SFSVKKQGET VSDVRTLPNA TTVDNIRSIF GNAVSRELIE VGCEDKTLAF 

       250        260        270        280        290        300 
KMNGYISNAN YSVKKCIFLL FINHRLVESA ALKKAIEAVY AAYLPKNTHP FLYLILEISP 

       310        320        330        340        350        360 
QNVDVNVHPT KHEVHFLHEE SILERVQQHI ESKLLGSNSS RMYFTQTLLP GLAGPSGEAV 

       370        380        390        400        410        420 
KSTTGIASSS TSGSGDKVHA YQMVRTDSRD QKLDAFMQPV SRRLPSQPQD PVPGNRTEGS 

       430        440        450        460        470        480 
PEKAMQKDQE ISELPAPMEA AADSASLERE SVIGASEVVA PQRHPSSPGS SRKRHPEDSD 

       490        500        510        520        530        540 
VEMMENDSRK EMTAACYPRR RIINLTSVLS LQEEINDRGH ETLREMLRNH TFVGCVNPQW 

       550        560        570        580        590        600 
ALAQHQTKLY LLNTTKLSEE LFYQILIYDF ANFGVLRLPE PAPLFDFAML ALDSPESGWT 

       610        620        630        640        650        660 
EEDGPKEGLA EYIVEFLKKK AKMLADYFSV EIDEEGNLIG LPLLIDSYVP PLEGLPIFIL 

       670        680        690        700        710        720 
RLATEVNWDE EECFESLSKE CAVFYSIRKQ YILEESALSG QQSDMPGSPS KPWKWTVEHI 

       730        740        750 
IYKAFRSHLL PPKHFTEDGN VLQLANLPDL CKVFERC 

« Hide

References

[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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U80054 mRNA. Translation: AAB38506.1.
RefSeqNP_112315.1. NM_031053.1.
UniGeneRn.20391.

3D structure databases

ProteinModelPortalP97679.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING10116.ENSRNOP00000043097.

Proteomic databases

PaxDbP97679.
PRIDEP97679.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID81685.
KEGGrno:81685.
UCSCRGD:620937. rat.

Organism-specific databases

CTD4292.
RGD620937. Mlh1.

Phylogenomic databases

eggNOGCOG0323.
HOGENOMHOG000176000.
HOVERGENHBG006374.
InParanoidP97679.
KOK08734.

Gene expression databases

GenevestigatorP97679.

Family and domain databases

Gene3D3.30.230.10. 1 hit.
3.30.565.10. 1 hit.
InterProIPR013507. DNA_mismatch_repair_C.
IPR014762. DNA_mismatch_repair_CS.
IPR002099. DNA_mismatch_repair_fam.
IPR011186. DNA_mismatch_repair_MLH1.
IPR003594. HATPase_ATP-bd.
IPR020568. Ribosomal_S5_D2-typ_fold.
IPR014721. Ribosomal_S5_D2-typ_fold_subgr.
[Graphical view]
PANTHERPTHR10073. PTHR10073. 1 hit.
PTHR10073:SF11. PTHR10073:SF11. 1 hit.
PfamPF01119. DNA_mis_repair. 1 hit.
[Graphical view]
SMARTSM00387. HATPase_c. 1 hit.
[Graphical view]
SUPFAMSSF54211. SSF54211. 1 hit.
SSF55874. SSF55874. 1 hit.
TIGRFAMsTIGR00585. mutl. 1 hit.
PROSITEPS00058. DNA_MISMATCH_REPAIR_1. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio615316.
PROP97679.

Entry information

Entry nameMLH1_RAT
AccessionPrimary (citable) accession number: P97679
Entry history
Integrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: May 1, 1997
Last modified: April 16, 2014
This is version 101 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families