Mlh3 mutL homolog 3 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Mlh3provided by MGI
Official Full Name: mutL homolog 3provided by MGI
Primary source: MGI:MGI:1353455
See related: Ensembl:ENSMUSG00000021245 AllianceGenome:MGI:1353455
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Summary: Enables centromeric DNA binding activity and chromatin binding activity. Acts upstream of or within meiotic nuclear division; mismatch repair; and protein localization. Located in chiasma; male germ cell nucleus; and synaptonemal complex. Part of mismatch repair complex. Is expressed in brain; early conceptus; ileum; reproductive system; and trigeminal nerve. Human ortholog(s) of this gene implicated in Lynch syndrome; colorectal cancer; endometrial cancer; and hereditary nonpolyposis colorectal cancer type 7. Orthologous to human MLH3 (mutL homolog 3). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Ubiquitous expression in bladder adult (RPKM 2.6), testis adult (RPKM 2.4) and 27 other tissues See more
Orthologs: human all
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Genomic context

Location:: 12 D1; 12 39.61 cM

Exon count:: 13

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	12	NC_000078.7 (85281240..85317421, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	12	NC_000078.6 (85234466..85270647, complement)

Chromosome 12 - NC_000078.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Human MLH1/3 variants causing aneuploidy, pregnancy loss, and premature reproductive aging.
Title: Human MLH1/3 variants causing aneuploidy, pregnancy loss, and premature reproductive aging.
A point mutation in the nuclease domain of MLH3 eliminates repeat expansions in a mouse stem cell model of the Fragile X-related disorders.
Title: A point mutation in the nuclease domain of MLH3 eliminates repeat expansions in a mouse stem cell model of the Fragile X-related disorders.
We identify, de novo, DNA sequence motifs associated with individual components that define temporally varying modes of gene expression control. Analysis of SDA components also led us to identify a rare population of macrophages within the seminiferous tubules of Mlh3(-/-) and Hormad1(-/-) mice, an area typically associated with immune privilege
Title: Unified single-cell analysis of testis gene regulation and pathology in five mouse strains.
Double mutant mice homozygous for the Mlh3DN/DN and Mus81-/- mutations show losses in chiasmata close to those observed in Mlh3-/- males, indicating that the MUS81-EME1-regulated crossover pathway can only partially account for the increased residual chiasmata in Mlh3DN/DN spermatocytes
Title: A mutation in the endonuclease domain of mouse MLH3 reveals novel roles for MutLγ during crossover formation in meiotic prophase I.
these data identify Mlh1 and Mlh3 as novel critical genetic modifiers of HTT CAG instability, point to Mlh1 genetic variation as the likely source of the instability difference in B6 and 129 strains
Title: Mismatch repair genes Mlh1 and Mlh3 modify CAG instability in Huntington's disease mice: genome-wide and candidate approaches.
MLH3-independent crossovers in mammalian meiosis,in Mus81-nullizygous mice.
Title: MUS81 generates a subset of MLH1-MLH3-independent crossovers in mammalian meiosis.
Mlh3 nullizygosity significantly increased Apc frameshift mutations and tumor multiplicity.
Title: Novel roles for MLH3 deficiency and TLE6-like amplification in DNA mismatch repair-deficient gastrointestinal tumorigenesis and progression.
These results indicate that approximately 10% of crossovers in the mouse are independent of MLH3, suggesting the existence of alternative crossover pathways in mammals.
Title: Distinct functions of MLH3 at recombination hot spots in the mouse.
Meiotic progression in female mice bearing mutations in genes of the DNA mismatch repair pathway.
Title: Comparative analysis of meiotic progression in female mice bearing mutations in genes of the DNA mismatch repair pathway.
Data show partial functional redundancy between MLH3 and PMS2 orthologues for mutation avoidance and show a role for Mlh3 in gastrointestinal and extragastrointestinal tumor suppression.
Title: Contributions by MutL homologues Mlh3 and Pms2 to DNA mismatch repair and tumor suppression in the mouse.

Submit: New GeneRIF Correction See all GeneRIFs (14)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Endonuclease-mediated (5) 1 citation
Targeted (3) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

BB126472 (e-PCR)
- UniSTS:185941

Mlh3 (e-PCR), detects polymorphism
- UniSTS:525714

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables ATP hydrolysis activity	IBA Inferred from Biological aspect of Ancestor more info
enables centromeric DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables chromatin binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
acts_upstream_of_or_within DNA damage response	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within DNA damage response	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within female meiosis I	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within male meiotic nuclear division	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in mismatch repair	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within mismatch repair	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within mismatch repair	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within protein localization	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within synaptonemal complex assembly	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in chiasma	IDA Inferred from Direct Assay more info	PubMed
located_in condensed chromosome	IDA Inferred from Direct Assay more info	PubMed
located_in condensed nuclear chromosome	IDA Inferred from Direct Assay more info	PubMed
located_in male germ cell nucleus	IDA Inferred from Direct Assay more info	PubMed
part_of mismatch repair complex	IBA Inferred from Biological aspect of Ancestor more info
part_of mismatch repair complex	IDA Inferred from Direct Assay more info	PubMed
located_in nucleoplasm	ISO Inferred from Sequence Orthology more info
located_in nucleoplasm	TAS Traceable Author Statement more info
located_in synaptonemal complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: DNA mismatch repair protein Mlh3

Names: mutL 3

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001304475.1 → NP_001291404.1 DNA mismatch repair protein Mlh3

See identical proteins and their annotated locations for NP_001291404.1

Status: VALIDATED

Description

Transcript Variant: This variant (2) differs in the 5' UTR, compared to variant 1. Both variants 1 and 2 encode the same protein.

Source sequence(s)

AK132195, BC079861, BE993968

Consensus CDS

CCDS36497.1

UniProtKB/TrEMBL

Q3V1X3, Q68FG1

Related

ENSMUSP00000129900.2, ENSMUST00000166821.8

Conserved Domains (3) summary

smart00853
Location:1153 → 1333

MutL_C; MutL C terminal dimerisation domain

cd03486
Location:206 → 349

MutL_Trans_MLH3; transducer domain, having a ribosomal S5 domain 2-like fold, found in proteins similar to yeast and human MLH3 (MutL homologue 3). MLH3 belongs to the DNA mismatch repair (MutL/MLH1/PMS2) family. This transducer domain is homologous to the second domain ...

cd16926
Location:12 → 192

HATPase_MutL-MLH-PMS-like; Histidine kinase-like ATPase domain of DNA mismatch repair proteins Escherichia coli MutL, human MutL homologs (MLH/ PMS), and related domains
NM_175337.2 → NP_780546.1 DNA mismatch repair protein Mlh3

See identical proteins and their annotated locations for NP_780546.1

Status: VALIDATED

Description

Transcript Variant: This variant (1) is the longer transcript. Both variants 1 and 2 encode the same protein.

Source sequence(s)

AK035887, BC079861, BE993968

Consensus CDS

CCDS36497.1

UniProtKB/TrEMBL

Q3V1X3, Q68FG1

Related

ENSMUSP00000019378.7, ENSMUST00000019378.8

Conserved Domains (3) summary

smart00853
Location:1153 → 1333

MutL_C; MutL C terminal dimerisation domain

cd03486
Location:206 → 349

MutL_Trans_MLH3; transducer domain, having a ribosomal S5 domain 2-like fold, found in proteins similar to yeast and human MLH3 (MutL homologue 3). MLH3 belongs to the DNA mismatch repair (MutL/MLH1/PMS2) family. This transducer domain is homologous to the second domain ...

cd16926
Location:12 → 192

HATPase_MutL-MLH-PMS-like; Histidine kinase-like ATPase domain of DNA mismatch repair proteins Escherichia coli MutL, human MutL homologs (MLH/ PMS), and related domains

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCm39 C57BL/6J

Genomic

NC_000078.7 Reference GRCm39 C57BL/6J

Range

85281240..85317421 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006515703.4 → XP_006515766.1 DNA mismatch repair protein Mlh3 isoform X1

See identical proteins and their annotated locations for XP_006515766.1

UniProtKB/TrEMBL

A0A1Y7VMP7, Q3V1X3

Related

ENSMUSP00000152840.2, ENSMUST00000220854.2

Conserved Domains (3) summary

smart00853
Location:1185 → 1365

MutL_C; MutL C terminal dimerisation domain

cd03486
Location:206 → 349

MutL_Trans_MLH3; transducer domain, having a ribosomal S5 domain 2-like fold, found in proteins similar to yeast and human MLH3 (MutL homologue 3). MLH3 belongs to the DNA mismatch repair (MutL/MLH1/PMS2) family. This transducer domain is homologous to the second domain ...

cd16926
Location:12 → 192

HATPase_MutL-MLH-PMS-like; Histidine kinase-like ATPase domain of DNA mismatch repair proteins Escherichia coli MutL, human MutL homologs (MLH/ PMS), and related domains
XM_036157329.1 → XP_036013222.1 DNA mismatch repair protein Mlh3 isoform X2

UniProtKB/TrEMBL

Q3V1X3, Q68FG1

Conserved Domains (3) summary

smart00853
Location:1153 → 1333

MutL_C; MutL C terminal dimerisation domain

cd03486
Location:206 → 349

MutL_Trans_MLH3; transducer domain, having a ribosomal S5 domain 2-like fold, found in proteins similar to yeast and human MLH3 (MutL homologue 3). MLH3 belongs to the DNA mismatch repair (MutL/MLH1/PMS2) family. This transducer domain is homologous to the second domain ...

cd16926
Location:12 → 192

HATPase_MutL-MLH-PMS-like; Histidine kinase-like ATPase domain of DNA mismatch repair proteins Escherichia coli MutL, human MutL homologs (MLH/ PMS), and related domains
XM_006515704.5 → XP_006515767.1 DNA mismatch repair protein Mlh3 isoform X1

See identical proteins and their annotated locations for XP_006515767.1

UniProtKB/TrEMBL

A0A1Y7VMP7, Q3V1X3

Conserved Domains (3) summary

smart00853
Location:1185 → 1365

MutL_C; MutL C terminal dimerisation domain

cd03486
Location:206 → 349

MutL_Trans_MLH3; transducer domain, having a ribosomal S5 domain 2-like fold, found in proteins similar to yeast and human MLH3 (MutL homologue 3). MLH3 belongs to the DNA mismatch repair (MutL/MLH1/PMS2) family. This transducer domain is homologous to the second domain ...

cd16926
Location:12 → 192

HATPase_MutL-MLH-PMS-like; Histidine kinase-like ATPase domain of DNA mismatch repair proteins Escherichia coli MutL, human MutL homologs (MLH/ PMS), and related domains
XM_006515706.5 → XP_006515769.1 DNA mismatch repair protein Mlh3 isoform X1

See identical proteins and their annotated locations for XP_006515769.1

UniProtKB/TrEMBL

A0A1Y7VMP7, Q3V1X3

Conserved Domains (3) summary

smart00853
Location:1185 → 1365

MutL_C; MutL C terminal dimerisation domain

cd03486
Location:206 → 349

MutL_Trans_MLH3; transducer domain, having a ribosomal S5 domain 2-like fold, found in proteins similar to yeast and human MLH3 (MutL homologue 3). MLH3 belongs to the DNA mismatch repair (MutL/MLH1/PMS2) family. This transducer domain is homologous to the second domain ...

cd16926
Location:12 → 192

HATPase_MutL-MLH-PMS-like; Histidine kinase-like ATPase domain of DNA mismatch repair proteins Escherichia coli MutL, human MutL homologs (MLH/ PMS), and related domains
XM_036157330.1 → XP_036013223.1 DNA mismatch repair protein Mlh3 isoform X2

UniProtKB/TrEMBL

Q3V1X3, Q68FG1

Conserved Domains (3) summary

smart00853
Location:1153 → 1333

MutL_C; MutL C terminal dimerisation domain

cd03486
Location:206 → 349

MutL_Trans_MLH3; transducer domain, having a ribosomal S5 domain 2-like fold, found in proteins similar to yeast and human MLH3 (MutL homologue 3). MLH3 belongs to the DNA mismatch repair (MutL/MLH1/PMS2) family. This transducer domain is homologous to the second domain ...

cd16926
Location:12 → 192

HATPase_MutL-MLH-PMS-like; Histidine kinase-like ATPase domain of DNA mismatch repair proteins Escherichia coli MutL, human MutL homologs (MLH/ PMS), and related domains

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_145446.1: Suppressed sequence

Description

NM_145446.1: This RefSeq was suppressed temporarily based on the calculation that the annotated protein was shorter than a protein or proteins from a putative ortholog.