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Protein

DNA mismatch repair protein Mlh3

Gene

MLH3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Probably involved in the repair of mismatches in DNA.

GO - Molecular functioni

GO - Biological processi

  • female meiosis I Source: Ensembl
  • male meiosis Source: Ensembl
  • mismatch repair Source: UniProtKB
  • protein localization Source: Ensembl
  • reciprocal meiotic recombination Source: UniProtKB
  • synaptonemal complex assembly Source: Ensembl
Complete GO annotation...

Keywords - Biological processi

DNA damage, DNA repair

Enzyme and pathway databases

BioCyciZFISH:ENSG00000119684-MONOMER.
ReactomeiR-HSA-912446. Meiotic recombination.

Names & Taxonomyi

Protein namesi
Recommended name:
DNA mismatch repair protein Mlh3
Alternative name(s):
MutL protein homolog 3
Gene namesi
Name:MLH3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 14

Organism-specific databases

HGNCiHGNC:7128. MLH3.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

Hereditary non-polyposis colorectal cancer 7 (HNPCC7)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal dominant disease associated with marked increase in cancer susceptibility. It is characterized by a familial predisposition to early-onset colorectal carcinoma (CRC) and extra-colonic tumors of the gastrointestinal, urological and female reproductive tracts. HNPCC is reported to be the most common form of inherited colorectal cancer in the Western world. Clinically, HNPCC is often divided into two subgroups. Type I is characterized by hereditary predisposition to colorectal cancer, a young age of onset, and carcinoma observed in the proximal colon. Type II is characterized by increased risk for cancers in certain tissues such as the uterus, ovary, breast, stomach, small intestine, skin, and larynx in addition to the colon. Diagnosis of classical HNPCC is based on the Amsterdam criteria: 3 or more relatives affected by colorectal cancer, one a first degree relative of the other two; 2 or more generation affected; 1 or more colorectal cancers presenting before 50 years of age; exclusion of hereditary polyposis syndromes. The term 'suspected HNPCC' or 'incomplete HNPCC' can be used to describe families who do not or only partially fulfill the Amsterdam criteria, but in whom a genetic basis for colon cancer is strongly suspected.
See also OMIM:614385
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01294624Q → E in HNPCC7. 1 PublicationCorresponds to variant rs28937870dbSNPEnsembl.1
Natural variantiVAR_012947499N → S in HNPCC7. 1 PublicationCorresponds to variant rs28937871dbSNPEnsembl.1
Natural variantiVAR_012948624E → Q in HNPCC7. 2 PublicationsCorresponds to variant rs28756986dbSNPEnsembl.1
Natural variantiVAR_012949647R → C in HNPCC7. 2 PublicationsCorresponds to variant rs28756987dbSNPEnsembl.1
Natural variantiVAR_012950817S → G in HNPCC7. 1 PublicationCorresponds to variant rs143278116dbSNPEnsembl.1
Natural variantiVAR_012951981G → S in HNPCC7. 1 PublicationCorresponds to variant rs377337763dbSNPEnsembl.1
Natural variantiVAR_0129521007N → S in HNPCC7. 1 PublicationCorresponds to variant rs776639203dbSNPEnsembl.1
Natural variantiVAR_0129531394A → T in HNPCC7. 1 PublicationCorresponds to variant rs138006166dbSNPEnsembl.1
Natural variantiVAR_0129541451E → K in HNPCC7. 1 PublicationCorresponds to variant rs28939071dbSNPEnsembl.1
Colorectal cancer (CRC)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history.
See also OMIM:114500

Keywords - Diseasei

Disease mutation, Hereditary nonpolyposis colorectal cancer

Organism-specific databases

DisGeNETi27030.
MalaCardsiMLH3.
MIMi114500. phenotype.
614385. phenotype.
OpenTargetsiENSG00000119684.
Orphaneti144. Hereditary nonpolyposis colon cancer.
PharmGKBiPA30845.

Polymorphism and mutation databases

BioMutaiMLH3.
DMDMi317373417.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001780031 – 1453DNA mismatch repair protein Mlh3Add BLAST1453

Proteomic databases

PaxDbiQ9UHC1.
PeptideAtlasiQ9UHC1.
PRIDEiQ9UHC1.

PTM databases

iPTMnetiQ9UHC1.
PhosphoSitePlusiQ9UHC1.

Expressioni

Tissue specificityi

Ubiquitous.

Gene expression databases

BgeeiENSG00000119684.
CleanExiHS_MLH3.
ExpressionAtlasiQ9UHC1. baseline and differential.
GenevisibleiQ9UHC1. HS.

Organism-specific databases

HPAiHPA060570.

Interactioni

Subunit structurei

Heterodimer of MLH1 and MLH3. Interacts with MTMR15/FAN1.2 Publications

Protein-protein interaction databases

BioGridi117961. 7 interactors.
IntActiQ9UHC1. 41 interactors.
STRINGi9606.ENSP00000348020.

Structurei

3D structure databases

ProteinModelPortaliQ9UHC1.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG1977. Eukaryota.
COG0323. LUCA.
GeneTreeiENSGT00800000124176.
HOGENOMiHOG000140944.
HOVERGENiHBG006375.
InParanoidiQ9UHC1.
KOiK08739.
OMAiCEYDVCM.
OrthoDBiEOG091G08LH.
PhylomeDBiQ9UHC1.
TreeFamiTF329597.

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.
IPR003594. HATPase_C.
IPR028830. Mlh3.
IPR014790. MutL_C.
IPR020568. Ribosomal_S5_D2-typ_fold.
IPR014721. Ribosomal_S5_D2-typ_fold_subgr.
[Graphical view]
PANTHERiPTHR10073:SF7. PTHR10073:SF7. 3 hits.
PfamiPF01119. DNA_mis_repair. 1 hit.
PF08676. MutL_C. 1 hit.
[Graphical view]
SMARTiSM01340. DNA_mis_repair. 1 hit.
SM00853. MutL_C. 1 hit.
[Graphical view]
SUPFAMiSSF54211. SSF54211. 1 hit.
SSF55874. SSF55874. 1 hit.
PROSITEiPS00058. DNA_MISMATCH_REPAIR_1. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9UHC1-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MIKCLSVEVQ AKLRSGLAIS SLGQCVEELA LNSIDAEAKC VAVRVNMETF
60 70 80 90 100
QVQVIDNGFG MGSDDVEKVG NRYFTSKCHS VQDLENPRFY GFRGEALANI
110 120 130 140 150
ADMASAVEIS SKKNRTMKTF VKLFQSGKAL KACEADVTRA SAGTTVTVYN
160 170 180 190 200
LFYQLPVRRK CMDPRLEFEK VRQRIEALSL MHPSISFSLR NDVSGSMVLQ
210 220 230 240 250
LPKTKDVCSR FCQIYGLGKS QKLREISFKY KEFELSGYIS SEAHYNKNMQ
260 270 280 290 300
FLFVNKRLVL RTKLHKLIDF LLRKESIICK PKNGPTSRQM NSSLRHRSTP
310 320 330 340 350
ELYGIYVINV QCQFCEYDVC MEPAKTLIEF QNWDTLLFCI QEGVKMFLKQ
360 370 380 390 400
EKLFVELSGE DIKEFSEDNG FSLFDATLQK RVTSDERSNF QEACNNILDS
410 420 430 440 450
YEMFNLQSKA VKRKTTAENV NTQSSRDSEA TRKNTNDAFL YIYESGGPGH
460 470 480 490 500
SKMTEPSLQN KDSSCSESKM LEQETIVASE AGENEKHKKS FLEHSSLENP
510 520 530 540 550
CGTSLEMFLS PFQTPCHFEE SGQDLEIWKE STTVNGMAAN ILKNNRIQNQ
560 570 580 590 600
PKRFKDATEV GCQPLPFATT LWGVHSAQTE KEKKKESSNC GRRNVFSYGR
610 620 630 640 650
VKLCSTGFIT HVVQNEKTKS TETEHSFKNY VRPGPTRAQE TFGNRTRHSV
660 670 680 690 700
ETPDIKDLAS TLSKESGQLP NKKNCRTNIS YGLENEPTAT YTMFSAFQEG
710 720 730 740 750
SKKSQTDCIL SDTSPSFPWY RHVSNDSRKT DKLIGFSKPI VRKKLSLSSQ
760 770 780 790 800
LGSLEKFKRQ YGKVENPLDT EVEESNGVTT NLSLQVEPDI LLKDKNRLEN
810 820 830 840 850
SDVCKITTME HSDSDSSCQP ASHILNSEKF PFSKDEDCLE QQMPSLRESP
860 870 880 890 900
MTLKELSLFN RKPLDLEKSS ESLASKLSRL KGSERETQTM GMMSRFNELP
910 920 930 940 950
NSDSSRKDSK LCSVLTQDFC MLFNNKHEKT ENGVIPTSDS ATQDNSFNKN
960 970 980 990 1000
SKTHSNSNTT ENCVISETPL VLPYNNSKVT GKDSDVLIRA SEQQIGSLDS
1010 1020 1030 1040 1050
PSGMLMNPVE DATGDQNGIC FQSEESKARA CSETEESNTC CSDWQRHFDV
1060 1070 1080 1090 1100
ALGRMVYVNK MTGLSTFIAP TEDIQAACTK DLTTVAVDVV LENGSQYRCQ
1110 1120 1130 1140 1150
PFRSDLVLPF LPRARAERTV MRQDNRDTVD DTVSSESLQS LFSEWDNPVF
1160 1170 1180 1190 1200
ARYPEVAVDV SSGQAESLAV KIHNILYPYR FTKGMIHSMQ VLQQVDNKFI
1210 1220 1230 1240 1250
ACLMSTKTEE NGEAGGNLLV LVDQHAAHER IRLEQLIIDS YEKQQAQGSG
1260 1270 1280 1290 1300
RKKLLSSTLI PPLEITVTEE QRRLLWCYHK NLEDLGLEFV FPDTSDSLVL
1310 1320 1330 1340 1350
VGKVPLCFVE REANELRRGR STVTKSIVEE FIREQLELLQ TTGGIQGTLP
1360 1370 1380 1390 1400
LTVQKVLASQ ACHGAIKFND GLSLQESCRL IEALSSCQLP FQCAHGRPSM
1410 1420 1430 1440 1450
LPLADIDHLE QEKQIKPNLT KLRKMAQAWR LFGKAECDTR QSLQQSMPPC

EPP
Length:1,453
Mass (Da):163,711
Last modified:January 11, 2011 - v3
Checksum:i3D063427457DB033
GO
Isoform 2 (identifier: Q9UHC1-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1215-1238: Missing.

Show »
Length:1,429
Mass (Da):161,021
Checksum:iD65538977F9D7AA4
GO

Sequence cautioni

The sequence AAC42005 differs from that shown. Contaminating sequence. Sequence of unknown origin in the N-terminal part.Curated
The sequence AAC42005 differs from that shown. Reason: Frameshift at several positions.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01294624Q → E in HNPCC7. 1 PublicationCorresponds to variant rs28937870dbSNPEnsembl.1
Natural variantiVAR_02333893R → G.1 PublicationCorresponds to variant rs28756978dbSNPEnsembl.1
Natural variantiVAR_023339120F → S.1 PublicationCorresponds to variant rs28756979dbSNPEnsembl.1
Natural variantiVAR_023340231K → Q.1 PublicationCorresponds to variant rs28756981dbSNPEnsembl.1
Natural variantiVAR_023341420V → I.1 PublicationCorresponds to variant rs28756982dbSNPEnsembl.1
Natural variantiVAR_023342492L → V.1 PublicationCorresponds to variant rs28756983dbSNPEnsembl.1
Natural variantiVAR_010790494H → R.Corresponds to variant rs760778201dbSNPEnsembl.1
Natural variantiVAR_012947499N → S in HNPCC7. 1 PublicationCorresponds to variant rs28937871dbSNPEnsembl.1
Natural variantiVAR_023343600R → Q.1 PublicationCorresponds to variant rs28756984dbSNPEnsembl.1
Natural variantiVAR_023344606T → P.1 PublicationCorresponds to variant rs28756985dbSNPEnsembl.1
Natural variantiVAR_012948624E → Q in HNPCC7. 2 PublicationsCorresponds to variant rs28756986dbSNPEnsembl.1
Natural variantiVAR_012949647R → C in HNPCC7. 2 PublicationsCorresponds to variant rs28756987dbSNPEnsembl.1
Natural variantiVAR_023345720Y → C.1 PublicationCorresponds to variant rs28756988dbSNPEnsembl.1
Natural variantiVAR_023346723V → I.1 PublicationCorresponds to variant rs28756989dbSNPEnsembl.1
Natural variantiVAR_023347741V → F.1 PublicationCorresponds to variant rs28756990dbSNPEnsembl.1
Natural variantiVAR_023348797R → H.1 PublicationCorresponds to variant rs28756991dbSNPEnsembl.1
Natural variantiVAR_012950817S → G in HNPCC7. 1 PublicationCorresponds to variant rs143278116dbSNPEnsembl.1
Natural variantiVAR_036781826N → D.3 PublicationsCorresponds to variant rs175081dbSNPEnsembl.1
Natural variantiVAR_023349844P → L.2 PublicationsCorresponds to variant rs175080dbSNPEnsembl.1
Natural variantiVAR_023350845S → G.1 PublicationCorresponds to variant rs28756992dbSNPEnsembl.1
Natural variantiVAR_023351942T → I.1 PublicationCorresponds to variant rs17102999dbSNPEnsembl.1
Natural variantiVAR_023352966S → P.1 PublicationCorresponds to variant rs17782839dbSNPEnsembl.1
Natural variantiVAR_012951981G → S in HNPCC7. 1 PublicationCorresponds to variant rs377337763dbSNPEnsembl.1
Natural variantiVAR_0129521007N → S in HNPCC7. 1 PublicationCorresponds to variant rs776639203dbSNPEnsembl.1
Natural variantiVAR_0233531073D → N.1 PublicationCorresponds to variant rs28756993dbSNPEnsembl.1
Natural variantiVAR_0233541105D → E.1 PublicationCorresponds to variant rs28757008dbSNPEnsembl.1
Natural variantiVAR_0233551163G → D.1 PublicationCorresponds to variant rs28757011dbSNPEnsembl.1
Natural variantiVAR_0233561319G → R.1 Publication1
Natural variantiVAR_0129531394A → T in HNPCC7. 1 PublicationCorresponds to variant rs138006166dbSNPEnsembl.1
Natural variantiVAR_0129541451E → K in HNPCC7. 1 PublicationCorresponds to variant rs28939071dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0032901215 – 1238Missing in isoform 2. CuratedAdd BLAST24

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF195657 mRNA. Translation: AAF23904.1.
AF195658 Genomic DNA. Translation: AAF23905.1.
AB039667 mRNA. Translation: BAA92353.1.
AY963685 Genomic DNA. Translation: AAX59030.1.
AL049780 Genomic DNA. No translation available.
L40399 mRNA. Translation: AAC42005.1. Sequence problems.
CCDSiCCDS32123.1. [Q9UHC1-1]
CCDS9837.1. [Q9UHC1-2]
RefSeqiNP_001035197.1. NM_001040108.1. [Q9UHC1-1]
XP_006720179.1. XM_006720116.3. [Q9UHC1-1]
XP_016876708.1. XM_017021219.1. [Q9UHC1-2]
UniGeneiHs.436650.

Genome annotation databases

EnsembliENST00000355774; ENSP00000348020; ENSG00000119684. [Q9UHC1-1]
ENST00000380968; ENSP00000370355; ENSG00000119684. [Q9UHC1-2]
ENST00000556740; ENSP00000452316; ENSG00000119684. [Q9UHC1-1]
GeneIDi27030.
KEGGihsa:27030.
UCSCiuc001xrd.1. human. [Q9UHC1-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF195657 mRNA. Translation: AAF23904.1.
AF195658 Genomic DNA. Translation: AAF23905.1.
AB039667 mRNA. Translation: BAA92353.1.
AY963685 Genomic DNA. Translation: AAX59030.1.
AL049780 Genomic DNA. No translation available.
L40399 mRNA. Translation: AAC42005.1. Sequence problems.
CCDSiCCDS32123.1. [Q9UHC1-1]
CCDS9837.1. [Q9UHC1-2]
RefSeqiNP_001035197.1. NM_001040108.1. [Q9UHC1-1]
XP_006720179.1. XM_006720116.3. [Q9UHC1-1]
XP_016876708.1. XM_017021219.1. [Q9UHC1-2]
UniGeneiHs.436650.

3D structure databases

ProteinModelPortaliQ9UHC1.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi117961. 7 interactors.
IntActiQ9UHC1. 41 interactors.
STRINGi9606.ENSP00000348020.

PTM databases

iPTMnetiQ9UHC1.
PhosphoSitePlusiQ9UHC1.

Polymorphism and mutation databases

BioMutaiMLH3.
DMDMi317373417.

Proteomic databases

PaxDbiQ9UHC1.
PeptideAtlasiQ9UHC1.
PRIDEiQ9UHC1.

Protocols and materials databases

DNASUi27030.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000355774; ENSP00000348020; ENSG00000119684. [Q9UHC1-1]
ENST00000380968; ENSP00000370355; ENSG00000119684. [Q9UHC1-2]
ENST00000556740; ENSP00000452316; ENSG00000119684. [Q9UHC1-1]
GeneIDi27030.
KEGGihsa:27030.
UCSCiuc001xrd.1. human. [Q9UHC1-1]

Organism-specific databases

CTDi27030.
DisGeNETi27030.
GeneCardsiMLH3.
GeneReviewsiMLH3.
HGNCiHGNC:7128. MLH3.
HPAiHPA060570.
MalaCardsiMLH3.
MIMi114500. phenotype.
604395. gene.
614385. phenotype.
neXtProtiNX_Q9UHC1.
OpenTargetsiENSG00000119684.
Orphaneti144. Hereditary nonpolyposis colon cancer.
PharmGKBiPA30845.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1977. Eukaryota.
COG0323. LUCA.
GeneTreeiENSGT00800000124176.
HOGENOMiHOG000140944.
HOVERGENiHBG006375.
InParanoidiQ9UHC1.
KOiK08739.
OMAiCEYDVCM.
OrthoDBiEOG091G08LH.
PhylomeDBiQ9UHC1.
TreeFamiTF329597.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000119684-MONOMER.
ReactomeiR-HSA-912446. Meiotic recombination.

Miscellaneous databases

ChiTaRSiMLH3. human.
GeneWikiiMLH3.
GenomeRNAii27030.
PROiQ9UHC1.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000119684.
CleanExiHS_MLH3.
ExpressionAtlasiQ9UHC1. baseline and differential.
GenevisibleiQ9UHC1. HS.

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.
IPR003594. HATPase_C.
IPR028830. Mlh3.
IPR014790. MutL_C.
IPR020568. Ribosomal_S5_D2-typ_fold.
IPR014721. Ribosomal_S5_D2-typ_fold_subgr.
[Graphical view]
PANTHERiPTHR10073:SF7. PTHR10073:SF7. 3 hits.
PfamiPF01119. DNA_mis_repair. 1 hit.
PF08676. MutL_C. 1 hit.
[Graphical view]
SMARTiSM01340. DNA_mis_repair. 1 hit.
SM00853. MutL_C. 1 hit.
[Graphical view]
SUPFAMiSSF54211. SSF54211. 1 hit.
SSF55874. SSF55874. 1 hit.
PROSITEiPS00058. DNA_MISMATCH_REPAIR_1. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiMLH3_HUMAN
AccessioniPrimary (citable) accession number: Q9UHC1
Secondary accession number(s): P49751
, Q56DK9, Q9P292, Q9UHC0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: January 11, 2011
Last modified: November 2, 2016
This is version 152 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 14
    Human chromosome 14: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.