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Q9JK91 (MLH1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified May 29, 2013. Version 100. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | 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
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
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length760 AA.
Sequence statusComplete.
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
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processdouble-strand break repair via nonhomologous end joining

Inferred from mutant phenotype PubMed 15084308. Source: MGI

intrinsic apoptotic signaling pathway in response to DNA damage

Inferred from mutant phenotype PubMed 14562041. Source: MGI

isotype switching

Inferred from mutant phenotype PubMed 12743174. Source: MGI

male meiosis chromosome segregation

Inferred from mutant phenotype PubMed 8796278. Source: MGI

meiotic metaphase I plate congression

Inferred from mutant phenotype PubMed 10385520. Source: MGI

mismatch repair

Inferred from direct assay PubMed 10747038. Source: MGI

negative regulation of mitotic recombination

Inferred from mutant phenotype PubMed 15480418. Source: MGI

nuclear-transcribed mRNA poly(A) tail shortening

Inferred from mutant phenotype PubMed 11337385. Source: MGI

oogenesis

Inferred from mutant phenotype Ref.3. Source: MGI

resolution of meiotic recombination intermediates

Inferred from mutant phenotype PubMed 10385520PubMed 12217320. Source: MGI

somatic hypermutation of immunoglobulin genes

Inferred from mutant phenotype PubMed 10092760PubMed 10429667. Source: MGI

spermatogenesis

Inferred from mutant phenotype PubMed 12217320Ref.3. Source: MGI

spindle midzone assembly involved in meiosis

Inferred from mutant phenotype PubMed 10385520. Source: MGI

synapsis

Inferred from mutant phenotype Ref.3. Source: MGI

   Cellular_componentMutLalpha complex

Inferred from direct assay PubMed 16713580. Source: MGI

MutLbeta complex

Inferred from Biological aspect of Ancestor. Source: RefGenome

chiasma

Inferred from direct assay PubMed 17291760PubMed 17696610PubMed 21743440. Source: MGI

male germ cell nucleus

Inferred from direct assay PubMed 17696610. Source: MGI

nucleoplasm

Traceable author statement. Source: Reactome

synaptonemal complex

Inferred from direct assay PubMed 15467367PubMed 16260499. 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

guanine/thymine mispair binding

Inferred from genetic interaction PubMed 16713580. Source: MGI

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

Chain1 – 760760DNA mismatch repair protein Mlh1
PRO_0000178001

Regions

Region412 – 654243Interaction with EXO1 By similarity

Amino acid modifications

Modified residue4811Phosphoserine By similarity

Experimental info

Sequence conflict3901E → D in AAF64514. Ref.1
Sequence conflict4041G → V in AAF64514. Ref.1
Sequence conflict5281M → I in AAF64514. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Q9JK91 [UniParc].

Last modified July 27, 2011. Version 2.
Checksum: B789D812F497FDF7

FASTA76084,670
        10         20         30         40         50         60 
MAFVAGVIRR LDETVVNRIA AGEVIQRPAN AIKEMIENCL DAKSTNIQVV VKEGGLKLIQ 

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

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

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

       250        260        270        280        290        300 
KMNGYISNAN YSVKKCIFLL FINHRLVESA ALRKAIETVY AAYLPKNTHP FLYLSLEISP 

       310        320        330        340        350        360 
QNVDVNVHPT KHEVHFLHEE SILQRVQQHI ESKLLGSNSS RMYFTQTLLP GLAGPSGEAA 

       370        380        390        400        410        420 
RPTTGVASSS TSGSGDKVYA YQMVRTDSRE QKLDAFLQPV SSLGPSQPQD PAPVRGARTE 

       430        440        450        460        470        480 
GSPERATRED EEMLALPAPA EAAAESENLE RESLMETSDA AQKAAPTSSP GSSRKRHRED 

       490        500        510        520        530        540 
SDVEMVENAS GKEMTAACYP RRRIINLTSV LSLQEEISER CHETLREMLR NHSFVGCVNP 

       550        560        570        580        590        600 
QWALAQHQTK LYLLNTTKLS EELFYQILIY DFANFGVLRL SEPAPLFDLA MLALDSPESG 

       610        620        630        640        650        660 
WTEDDGPKEG LAEYIVEFLK KKAEMLADYF SVEIDEEGNL IGLPLLIDSY VPPLEGLPIF 

       670        680        690        700        710        720 
ILRLATEVNW DEEKECFESL SKECAMFYSI RKQYILEEST LSGQQSDMPG STSKPWKWTV 

       730        740        750        760 
EHIIYKAFRS HLLPPKHFTE DGNVLQLANL PDLYKVFERC

« Hide

References

« Hide 'large scale' references
[1]"Cloning of the cDNA of the MutL homolog, MLH1 from mouse testis."
Kumaran M., Rao M.R.S.
Submitted (MAR-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Testis.
[2]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6J.
Tissue: Heart.
[3]"Meiotic pachytene arrest in MLH1-deficient mice."
Edelmann W., Cohen P.E., Kane M., Lau K., Morrow B., Bennett S., Umar A., Kunkel T., Cattoretti G., Chaganti R., Pollard J.W., Kolodner R.D., Kucherlapati R.
Cell 85:1125-1134(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-151.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ		AF250844 mRNA. Translation: AAF64514.1.
AK168849 mRNA. Translation: BAE40671.1.
U60872 expand/collapse EMBL AC list , U59881, U59882, U59883, U59884 Genomic DNA. Translation: AAC52672.1.
IPIIPI00122425.
RefSeqNP_081086.2. NM_026810.2.
UniGeneMm.486383.

3D structure databases

ProteinModelPortalQ9JK91.
SMRQ9JK91. Positions 3-335, 492-755.
ModBaseSearch...

Protein-protein interaction databases

STRING10090.ENSMUSP00000035079.

PTM databases

PhosphoSiteQ9JK91.

Proteomic databases

PaxDbQ9JK91.
PRIDEQ9JK91.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000035079; ENSMUSP00000035079; ENSMUSG00000032498.
GeneID17350.
KEGGmmu:17350.
UCSCuc009rvp.2. mouse.

Organism-specific databases

CTD4292.
MGIMGI:101938. Mlh1.

Phylogenomic databases

eggNOGCOG0323.
GeneTreeENSGT00550000074923.
HOGENOMHOG000176000.
HOVERGENHBG006374.
InParanoidQ3TG77.
KOK08734.
OMASIQVVVK.
OrthoDBEOG43N7C7.

Enzyme and pathway databases

ReactomeREACT_120463. Meiosis.
REACT_27235. Meiotic Recombination (mouse).

Gene expression databases

ArrayExpressQ9JK91.
BgeeQ9JK91.
CleanExMM_MLH1.
GenevestigatorQ9JK91.
GermOnlineENSMUSG00000032498. Mus musculus.

Family and domain databases

Gene3D3.30.230.10. 1 hit.
3.30.565.10. 1 hit.
InterProIPR002099. DNA_mismatch_repair.
IPR013507. DNA_mismatch_repair_C.
IPR014762. DNA_mismatch_repair_CS.
IPR011186. DNA_mismatch_repair_MLH1.
IPR014763. DNA_mismatch_repair_N.
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]
SUPFAMSSF55874. ATP_bd_ATPase. 1 hit.
SSF54211. Ribosomal_S5_D2-typ_fold. 1 hit.
TIGRFAMsTIGR00585. mutl. 1 hit.
PROSITEPS00058. DNA_MISMATCH_REPAIR_1. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSMlh1. mouse.
NextBio291948.
SOURCESearch...

Entry information

Entry nameMLH1_MOUSE
AccessionPrimary (citable) accession number: Q9JK91
Secondary accession number(s): Q3TG77, Q62454
Entry history
Integrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: July 27, 2011
Last modified: May 29, 2013
This is version 100 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents