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Q9JK91

- MLH1_MOUSE

UniProt

Q9JK91 - MLH1_MOUSE

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Protein

DNA mismatch repair protein Mlh1

Gene
Mlh1
Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 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.

GO - Molecular functioni

  1. ATPase activity Source: RefGenome
  2. ATP binding Source: InterPro
  3. guanine/thymine mispair binding Source: MGI
  4. single-stranded DNA binding Source: RefGenome
  5. structure-specific DNA binding Source: MGI

GO - Biological processi

  1. ATP catabolic process Source: GOC
  2. cellular response to DNA damage stimulus Source: MGI
  3. DNA repair Source: MGI
  4. double-strand break repair via nonhomologous end joining Source: MGI
  5. intrinsic apoptotic signaling pathway in response to DNA damage Source: MGI
  6. isotype switching Source: MGI
  7. male meiosis Source: MGI
  8. male meiosis chromosome segregation Source: MGI
  9. meiotic chromosome segregation Source: MGI
  10. meiotic metaphase I plate congression Source: MGI
  11. meiotic nuclear division Source: MGI
  12. mismatch repair Source: MGI
  13. negative regulation of mitotic recombination Source: MGI
  14. nuclear-transcribed mRNA poly(A) tail shortening Source: MGI
  15. oogenesis Source: MGI
  16. reciprocal meiotic recombination Source: MGI
  17. resolution of meiotic recombination intermediates Source: MGI
  18. somatic hypermutation of immunoglobulin genes Source: MGI
  19. somatic recombination of immunoglobulin gene segments Source: MGI
  20. somatic recombination of immunoglobulin genes involved in immune response Source: MGI
  21. spermatogenesis Source: MGI
  22. spindle midzone assembly involved in meiosis Source: MGI
  23. synapsis Source: MGI
Complete GO annotation...

Keywords - Biological processi

Cell cycle, DNA damage, DNA repair

Enzyme and pathway databases

ReactomeiREACT_198629. Meiotic recombination.
REACT_27235. Meiotic Recombination.

Names & Taxonomyi

Protein namesi
Recommended name:
DNA mismatch repair protein Mlh1
Alternative name(s):
MutL protein homolog 1
Gene namesi
Name:Mlh1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 9

Organism-specific databases

MGIiMGI:101938. Mlh1.

Subcellular locationi

Nucleus By similarity

GO - Cellular componenti

  1. chiasma Source: MGI
  2. chromosome Source: MGI
  3. condensed chromosome Source: MGI
  4. condensed nuclear chromosome Source: MGI
  5. male germ cell nucleus Source: MGI
  6. MutLalpha complex Source: MGI
  7. nucleoplasm Source: Reactome
  8. synaptonemal complex Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11Removed By similarity
Chaini2 – 760759DNA mismatch repair protein Mlh1PRO_0000178001Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei481 – 4811Phosphoserine By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ9JK91.
PaxDbiQ9JK91.
PRIDEiQ9JK91.

PTM databases

PhosphoSiteiQ9JK91.

Expressioni

Gene expression databases

ArrayExpressiQ9JK91.
BgeeiQ9JK91.
CleanExiMM_MLH1.
GenevestigatoriQ9JK91.

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.

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000035079.

Structurei

3D structure databases

ProteinModelPortaliQ9JK91.
SMRiQ9JK91. Positions 3-335, 492-755.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni412 – 654243Interaction with EXO1 By similarityAdd
BLAST

Sequence similaritiesi

Phylogenomic databases

eggNOGiCOG0323.
GeneTreeiENSGT00550000074923.
HOGENOMiHOG000176000.
HOVERGENiHBG006374.
InParanoidiQ3TG77.
KOiK08734.
OMAiINHRCVE.
OrthoDBiEOG7MSMNH.
TreeFamiTF300493.

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_ATP-bd.
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.

Q9JK91-1 [UniParc]FASTAAdd to Basket

« Hide

MAFVAGVIRR LDETVVNRIA AGEVIQRPAN AIKEMIENCL DAKSTNIQVV    50
VKEGGLKLIQ IQDNGTGIRK EDLDIVCERF TTSKLQTFED LASISTYGFR 100
GEALASISHV AHVTITTKTA DGKCAYRASY SDGKLQAPPK PCAGNQGTLI 150
TVEDLFYNII TRRKALKNPS EEYGKILEVV GRYSIHNSGI SFSVKKQGET 200
VSDVRTLPNA TTVDNIRSIF GNAVSRELIE VGCEDKTLAF KMNGYISNAN 250
YSVKKCIFLL FINHRLVESA ALRKAIETVY AAYLPKNTHP FLYLSLEISP 300
QNVDVNVHPT KHEVHFLHEE SILQRVQQHI ESKLLGSNSS RMYFTQTLLP 350
GLAGPSGEAA RPTTGVASSS TSGSGDKVYA YQMVRTDSRE QKLDAFLQPV 400
SSLGPSQPQD PAPVRGARTE GSPERATRED EEMLALPAPA EAAAESENLE 450
RESLMETSDA AQKAAPTSSP GSSRKRHRED SDVEMVENAS GKEMTAACYP 500
RRRIINLTSV LSLQEEISER CHETLREMLR NHSFVGCVNP QWALAQHQTK 550
LYLLNTTKLS EELFYQILIY DFANFGVLRL SEPAPLFDLA MLALDSPESG 600
WTEDDGPKEG LAEYIVEFLK KKAEMLADYF SVEIDEEGNL IGLPLLIDSY 650
VPPLEGLPIF ILRLATEVNW DEEKECFESL SKECAMFYSI RKQYILEEST 700
LSGQQSDMPG STSKPWKWTV EHIIYKAFRS HLLPPKHFTE DGNVLQLANL 750
PDLYKVFERC 760
Length:760
Mass (Da):84,670
Last modified:July 27, 2011 - v2
Checksum:iB789D812F497FDF7
GO

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti390 – 3901E → D in AAF64514. 1 Publication
Sequence conflicti404 – 4041G → V in AAF64514. 1 Publication
Sequence conflicti528 – 5281M → I in AAF64514. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AF250844 mRNA. Translation: AAF64514.1.
AK168849 mRNA. Translation: BAE40671.1.
U60872
, U59881, U59882, U59883, U59884 Genomic DNA. Translation: AAC52672.1.
CCDSiCCDS40784.1.
RefSeqiNP_081086.2. NM_026810.2.
UniGeneiMm.486383.

Genome annotation databases

EnsembliENSMUST00000035079; ENSMUSP00000035079; ENSMUSG00000032498.
GeneIDi17350.
KEGGimmu:17350.
UCSCiuc009rvp.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AF250844 mRNA. Translation: AAF64514.1 .
AK168849 mRNA. Translation: BAE40671.1 .
U60872
, U59881 , U59882 , U59883 , U59884 Genomic DNA. Translation: AAC52672.1 .
CCDSi CCDS40784.1.
RefSeqi NP_081086.2. NM_026810.2.
UniGenei Mm.486383.

3D structure databases

ProteinModelPortali Q9JK91.
SMRi Q9JK91. Positions 3-335, 492-755.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

STRINGi 10090.ENSMUSP00000035079.

PTM databases

PhosphoSitei Q9JK91.

Proteomic databases

MaxQBi Q9JK91.
PaxDbi Q9JK91.
PRIDEi Q9JK91.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000035079 ; ENSMUSP00000035079 ; ENSMUSG00000032498 .
GeneIDi 17350.
KEGGi mmu:17350.
UCSCi uc009rvp.2. mouse.

Organism-specific databases

CTDi 4292.
MGIi MGI:101938. Mlh1.

Phylogenomic databases

eggNOGi COG0323.
GeneTreei ENSGT00550000074923.
HOGENOMi HOG000176000.
HOVERGENi HBG006374.
InParanoidi Q3TG77.
KOi K08734.
OMAi INHRCVE.
OrthoDBi EOG7MSMNH.
TreeFami TF300493.

Enzyme and pathway databases

Reactomei REACT_198629. Meiotic recombination.
REACT_27235. Meiotic Recombination.

Miscellaneous databases

ChiTaRSi Mlh1. mouse.
NextBioi 291948.
PROi Q9JK91.
SOURCEi Search...

Gene expression databases

ArrayExpressi Q9JK91.
Bgeei Q9JK91.
CleanExi MM_MLH1.
Genevestigatori Q9JK91.

Family and domain databases

Gene3Di 3.30.230.10. 1 hit.
3.30.565.10. 1 hit.
InterProi IPR013507. DNA_mismatch_repair_C.
IPR014762. DNA_mismatch_repair_CS.
IPR002099. DNA_mismatch_repair_fam.
IPR011186. DNA_mismatch_repair_MLH1/HexB.
IPR003594. HATPase_ATP-bd.
IPR020568. Ribosomal_S5_D2-typ_fold.
IPR014721. Ribosomal_S5_D2-typ_fold_subgr.
[Graphical view ]
PANTHERi PTHR10073:SF12. PTHR10073:SF12. 1 hit.
Pfami PF01119. DNA_mis_repair. 1 hit.
[Graphical view ]
SMARTi SM00387. HATPase_c. 1 hit.
[Graphical view ]
SUPFAMi SSF54211. SSF54211. 1 hit.
SSF55874. SSF55874. 1 hit.
TIGRFAMsi TIGR00585. mutl. 1 hit.
PROSITEi PS00058. DNA_MISMATCH_REPAIR_1. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-151.

Entry informationi

Entry nameiMLH1_MOUSE
AccessioniPrimary (citable) accession number: Q9JK91
Secondary accession number(s): Q3TG77, Q62454
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: July 27, 2011
Last modified: September 3, 2014
This is version 113 of the entry and version 2 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. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi