MLH3

MutL homolog 3 (E. coli)

Identifiers

MLH3; HNPCC7; MGC138372

External IDs

OMIM: 604395 MGI: 1353455 HomoloGene: 91153 GeneCards: MLH3 Gene

Gene Ontology
Molecular function	• satellite DNA binding • protein binding • ATP binding • ATPase activity • mismatched DNA binding
Cellular component	• synaptonemal complex • nucleus • chiasma • MutLbeta complex
Biological process	• ATP catabolic process • mismatch repair • mismatch repair • reciprocal meiotic recombination • reciprocal meiotic recombination
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

n/a

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 14:
75.48 – 75.52 Mb

Chr 12:
86.58 – 86.61 Mb

PubMed search

[1]

[2]

DNA mismatch repair protein Mlh3 is a protein that in humans is encoded by the MLH3 gene.^[1]^[2]

This gene is a member of the MutL-homolog (MLH) family of DNA mismatch repair (MMR) genes. MLH genes are implicated in maintaining genomic integrity during DNA replication and after meiotic recombination. The protein encoded by this gene functions as a heterodimer with other family members. Somatic mutations in this gene frequently occur in tumors exhibiting microsatellite instability, and germline mutations have been linked to hereditary nonpolyposis colorectal cancer type 7 (HNPCC7). Several alternatively spliced transcript variants have been identified, but the full-length nature of only two transcript variants has been determined.^[2]

Interactions

MLH3 has been shown to interact with MSH4.^[3]

References

^ Lipkin SM, Wang V, Jacoby R, Banerjee-Basu S, Baxevanis AD, Lynch HT, Elliott RM, Collins FS (Feb 2000). "MLH3: a DNA mismatch repair gene associated with mammalian microsatellite instability". Nat Genet 24 (1): 27–35. doi:10.1038/71643. PMID 10615123.
^ ^a ^b "Entrez Gene: MLH3 mutL homolog 3 (E. coli)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=27030.
^ Santucci-Darmanin, Sabine; Neyton Sophie, Lespinasse Françoise, Saunières Anne, Gaudray Patrick, Paquis-Flucklinger Véronique (Jul. 2002). "The DNA mismatch-repair MLH3 protein interacts with MSH4 in meiotic cells, supporting a role for this MutL homolog in mammalian meiotic recombination". Hum. Mol. Genet. (England) 11 (15): 1697–706. doi:10.1093/hmg/11.15.1697. ISSN 0964-6906. PMID 12095912.

Sherrington R, Rogaev EI, Liang Y, et al. (1995). "Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease". Nature 375 (6534): 754–60. doi:10.1038/375754a0. PMID 7596406.
Kondo E, Horii A, Fukushige S (2001). "The interacting domains of three MutL heterodimers in man: hMLH1 interacts with 36 homologous amino acid residues within hMLH3, hPMS1 and hPMS2". Nucleic Acids Res. 29 (8): 1695–702. doi:10.1093/nar/29.8.1695. PMC 31313. PMID 11292842. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=31313.
Lipkin SM, Wang V, Stoler DL, et al. (2001). "Germline and somatic mutation analyses in the DNA mismatch repair gene MLH3: Evidence for somatic mutation in colorectal cancers". Hum. Mutat. 17 (5): 389–96. doi:10.1002/humu.1114. PMID 11317354.
Wu Y, Berends MJ, Sijmons RH, et al. (2001). "A role for MLH3 in hereditary nonpolyposis colorectal cancer". Nat. Genet. 29 (2): 137–8. doi:10.1038/ng1001-137. PMID 11586295.
Santucci-Darmanin S, Neyton S, Lespinasse F, et al. (2003). "The DNA mismatch-repair MLH3 protein interacts with MSH4 in meiotic cells, supporting a role for this MutL homolog in mammalian meiotic recombination". Hum. Mol. Genet. 11 (15): 1697–706. doi:10.1093/hmg/11.15.1697. PMID 12095912.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241.
Hienonen T, Laiho P, Salovaara R, et al. (2003). "Little evidence for involvement of MLH3 in colorectal cancer predisposition". Int. J. Cancer 106 (2): 292–6. doi:10.1002/ijc.11218. PMID 12800209.
Lenzi ML, Smith J, Snowden T, et al. (2005). "Extreme heterogeneity in the molecular events leading to the establishment of chiasmata during meiosis i in human oocytes". Am. J. Hum. Genet. 76 (1): 112–27. doi:10.1086/427268. PMC 1196414. PMID 15558497. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1196414.
Cannavo E, Marra G, Sabates-Bellver J, et al. (2006). "Expression of the MutL homologue hMLH3 in human cells and its role in DNA mismatch repair". Cancer Res. 65 (23): 10759–66. doi:10.1158/0008-5472.CAN-05-2528. PMID 16322221.
Kimura K, Wakamatsu A, Suzuki Y, et al. (2006). "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes". Genome Res. 16 (1): 55–65. doi:10.1101/gr.4039406. PMC 1356129. PMID 16344560. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1356129.
Taylor NP, Powell MA, Gibb RK, et al. (2006). "MLH3 mutation in endometrial cancer". Cancer Res. 66 (15): 7502–8. doi:10.1158/0008-5472.CAN-06-0248. PMID 16885347.
Liu HX, Li Y, Jiang XD, et al. (2007). "Mutation screening of mismatch repair gene Mlh3 in familial esophageal cancer". World J. Gastroenterol. 12 (33): 5281–6. PMID 16981255.
Korhonen MK, Raevaara TE, Lohi H, Nyström M (2007). "Conditional nuclear localization of hMLH3 suggests a minor activity in mismatch repair and supports its role as a low-risk gene in HNPCC". Oncol. Rep. 17 (2): 351–4. PMID 17203173.
Erdeniz N, Nguyen M, Deschênes SM, Liskay RM (2007). "Mutations affecting a putative MutLalpha endonuclease motif impact multiple mismatch repair functions". DNA Repair (Amst.) 6 (10): 1463–70. doi:10.1016/j.dnarep.2007.04.013. PMC 2366940. PMID 17567544. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2366940.

MLH3

Interactions

References

Further reading