UniProtKB - P20585 (MSH3_HUMAN)
Protein
DNA mismatch repair protein Msh3
Gene
MSH3
Organism
Homo sapiens (Human)
Status
Functioni
Component of the post-replicative DNA mismatch repair system (MMR). Heterodimerizes with MSH2 to form MutS beta which binds to DNA mismatches thereby initiating DNA repair. When bound, the MutS beta heterodimer bends the DNA helix and shields approximately 20 base pairs. MutS beta recognizes large insertion-deletion loops (IDL) up to 13 nucleotides long. After mismatch binding, forms a ternary complex with the MutL alpha heterodimer, which is thought to be responsible for directing the downstream MMR events, including strand discrimination, excision, and resynthesis.
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 896 – 903 | ATPSequence analysis | 8 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- DNA-dependent ATPase activity Source: GO_Central
- DNA insertion or deletion binding Source: GO_Central
- enzyme binding Source: UniProtKB
GO - Biological processi
- DNA repair Source: BHF-UCL
- maintenance of DNA repeat elements Source: HGNC-UCL
- meiotic mismatch repair Source: GO_Central
- mismatch repair Source: HGNC-UCL
- mitotic recombination Source: GO_Central
- negative regulation of DNA recombination Source: BHF-UCL
- positive regulation of helicase activity Source: BHF-UCL
- reciprocal meiotic recombination Source: GO_Central
- removal of nonhomologous ends Source: GO_Central
- replication fork arrest Source: GO_Central
- somatic recombination of immunoglobulin gene segments Source: GO_Central
Keywordsi
Molecular function | DNA-binding |
Biological process | DNA damage, DNA repair |
Ligand | ATP-binding, Nucleotide-binding |
Enzyme and pathway databases
PathwayCommonsi | P20585 |
Reactomei | R-HSA-5358606, Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta) R-HSA-5632927, Defective Mismatch Repair Associated With MSH3 R-HSA-5632928, Defective Mismatch Repair Associated With MSH2 |
Names & Taxonomyi
Protein namesi | Recommended name: DNA mismatch repair protein Msh3Short name: hMSH3 Alternative name(s): Divergent upstream protein Short name: DUP Mismatch repair protein 1 Short name: MRP1 |
Gene namesi | Name:MSH3 Synonyms:DUC1, DUG |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000113318.9 |
HGNCi | HGNC:7326, MSH3 |
MIMi | 600887, gene |
neXtProti | NX_P20585 |
Subcellular locationi
Nucleus
- MutSbeta complex Source: HGNC-UCL
- nucleoplasm Source: Reactome
- nucleus Source: UniProtKB
Other locations
- membrane Source: UniProtKB
- mismatch repair complex Source: GO_Central
Pathology & Biotechi
Involvement in diseasei
Endometrial cancer (ENDMC)1 Publication
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA malignancy of endometrium, the mucous lining of the uterus. Most endometrial cancers are adenocarcinomas, cancers that begin in cells that make and release mucus and other fluids.
Related information in OMIMFamilial adenomatous polyposis 4 (FAP4)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of familial adenomatous polyposis, a condition characterized by the development of multiple colorectal adenomatous polyps, benign neoplasms derived from glandular epithelium. Some affected individuals may develop colorectal carcinoma. FAP4 inheritance is autosomal recessive.
Related information in OMIMOrganism-specific databases
DisGeNETi | 4437 |
MalaCardsi | MSH3 |
MIMi | 608089, phenotype 617100, phenotype |
OpenTargetsi | ENSG00000113318 |
Orphaneti | 480536, MSH3-related attenuated familial adenomatous polyposis |
PharmGKBi | PA31134 |
Miscellaneous databases
Pharosi | P20585, Tbio |
Polymorphism and mutation databases
BioMutai | MSH3 |
DMDMi | 317373576 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000115192 | 1 – 1137 | DNA mismatch repair protein Msh3Add BLAST | 1137 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 33 | PhosphoserineCombined sources | 1 | |
Modified residuei | 1099 | PhosphothreonineCombined sources | 1 |
Keywords - PTMi
PhosphoproteinProteomic databases
EPDi | P20585 |
jPOSTi | P20585 |
MassIVEi | P20585 |
MaxQBi | P20585 |
PaxDbi | P20585 |
PeptideAtlasi | P20585 |
PRIDEi | P20585 |
ProteomicsDBi | 53762 |
PTM databases
iPTMneti | P20585 |
PhosphoSitePlusi | P20585 |
Expressioni
Gene expression databases
Bgeei | ENSG00000113318, Expressed in bronchial epithelial cell and 248 other tissues |
Genevisiblei | P20585, HS |
Organism-specific databases
HPAi | ENSG00000113318, Low tissue specificity |
Interactioni
Subunit structurei
Component of the DNA mismatch repair (MMR) complex composed at least of MSH2, MSH3, MSH6, PMS1 and MLH1 (PubMed:26300262). Heterodimer consisting of MSH2-MSH3 (MutS beta) (PubMed:8942985).
Forms a ternary complex with MutL alpha (MLH1-PMS1).
Interacts with EXO1 (PubMed:11427529).
Interacts with MCM9 (PubMed:26300262).
3 PublicationsBinary interactionsi
Hide detailsP20585
With | #Exp. | IntAct |
---|---|---|
MLH1 [P40692] | 5 | EBI-1164205,EBI-744248 |
MSH2 [P43246] | 10 | EBI-1164205,EBI-355888 |
PCNA [P12004] | 6 | EBI-1164205,EBI-358311 |
GO - Molecular functioni
- enzyme binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 110574, 54 interactors |
ComplexPortali | CPX-77, DNA mismatch repair MutSbeta complex |
CORUMi | P20585 |
DIPi | DIP-35127N |
IntActi | P20585, 22 interactors |
MINTi | P20585 |
STRINGi | 9606.ENSP00000265081 |
Miscellaneous databases
RNActi | P20585, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | P20585 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 75 – 297 | Interaction with EXO11 PublicationAdd BLAST | 223 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 51 – 62 | Poly-AlaAdd BLAST | 12 |
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG0218, Eukaryota |
GeneTreei | ENSGT00550000074949 |
HOGENOMi | CLU_002472_0_1_1 |
InParanoidi | P20585 |
OMAi | LHIAPCE |
OrthoDBi | 138168at2759 |
PhylomeDBi | P20585 |
TreeFami | TF300525 |
Family and domain databases
Gene3Di | 3.30.420.110, 1 hit 3.40.1170.10, 1 hit |
IDEALi | IID00612 |
InterProi | View protein in InterPro IPR007695, DNA_mismatch_repair_MutS-lik_N IPR000432, DNA_mismatch_repair_MutS_C IPR007696, DNA_mismatch_repair_MutS_core IPR016151, DNA_mismatch_repair_MutS_N IPR036187, DNA_mismatch_repair_MutS_sf IPR007860, DNA_mmatch_repair_MutS_con_dom IPR036678, MutS_con_dom_sf IPR027417, P-loop_NTPase |
Pfami | View protein in Pfam PF01624, MutS_I, 1 hit PF05188, MutS_II, 1 hit PF05192, MutS_III, 1 hit PF00488, MutS_V, 1 hit |
SMARTi | View protein in SMART SM00534, MUTSac, 1 hit SM00533, MUTSd, 1 hit |
SUPFAMi | SSF48334, SSF48334, 1 hit SSF52540, SSF52540, 1 hit SSF53150, SSF53150, 1 hit SSF55271, SSF55271, 1 hit |
PROSITEi | View protein in PROSITE PS00486, DNA_MISMATCH_REPAIR_2, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 4 potential isoforms that are computationally mapped.Show allAlign All
P20585-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MSRRKPASGG LAASSSAPAR QAVLSRFFQS TGSLKSTSSS TGAADQVDPG
60 70 80 90 100
AAAAAAAAAA AAPPAPPAPA FPPQLPPHIA TEIDRRKKRP LENDGPVKKK
110 120 130 140 150
VKKVQQKEGG SDLGMSGNSE PKKCLRTRNV SKSLEKLKEF CCDSALPQSR
160 170 180 190 200
VQTESLQERF AVLPKCTDFD DISLLHAKNA VSSEDSKRQI NQKDTTLFDL
210 220 230 240 250
SQFGSSNTSH ENLQKTASKS ANKRSKSIYT PLELQYIEMK QQHKDAVLCV
260 270 280 290 300
ECGYKYRFFG EDAEIAAREL NIYCHLDHNF MTASIPTHRL FVHVRRLVAK
310 320 330 340 350
GYKVGVVKQT ETAALKAIGD NRSSLFSRKL TALYTKSTLI GEDVNPLIKL
360 370 380 390 400
DDAVNVDEIM TDTSTSYLLC ISENKENVRD KKKGNIFIGI VGVQPATGEV
410 420 430 440 450
VFDSFQDSAS RSELETRMSS LQPVELLLPS ALSEQTEALI HRATSVSVQD
460 470 480 490 500
DRIRVERMDN IYFEYSHAFQ AVTEFYAKDT VDIKGSQIIS GIVNLEKPVI
510 520 530 540 550
CSLAAIIKYL KEFNLEKMLS KPENFKQLSS KMEFMTINGT TLRNLEILQN
560 570 580 590 600
QTDMKTKGSL LWVLDHTKTS FGRRKLKKWV TQPLLKLREI NARLDAVSEV
610 620 630 640 650
LHSESSVFGQ IENHLRKLPD IERGLCSIYH KKCSTQEFFL IVKTLYHLKS
660 670 680 690 700
EFQAIIPAVN SHIQSDLLRT VILEIPELLS PVEHYLKILN EQAAKVGDKT
710 720 730 740 750
ELFKDLSDFP LIKKRKDEIQ GVIDEIRMHL QEIRKILKNP SAQYVTVSGQ
760 770 780 790 800
EFMIEIKNSA VSCIPTDWVK VGSTKAVSRF HSPFIVENYR HLNQLREQLV
810 820 830 840 850
LDCSAEWLDF LEKFSEHYHS LCKAVHHLAT VDCIFSLAKV AKQGDYCRPT
860 870 880 890 900
VQEERKIVIK NGRHPVIDVL LGEQDQYVPN NTDLSEDSER VMIITGPNMG
910 920 930 940 950
GKSSYIKQVA LITIMAQIGS YVPAEEATIG IVDGIFTRMG AADNIYKGQS
960 970 980 990 1000
TFMEELTDTA EIIRKATSQS LVILDELGRG TSTHDGIAIA YATLEYFIRD
1010 1020 1030 1040 1050
VKSLTLFVTH YPPVCELEKN YSHQVGNYHM GFLVSEDESK LDPGAAEQVP
1060 1070 1080 1090 1100
DFVTFLYQIT RGIAARSYGL NVAKLADVPG EILKKAAHKS KELEGLINTK
1110 1120 1130
RKRLKYFAKL WTMHNAQDLQ KWTEEFNMEE TQTSLLH
Computationally mapped potential isoform sequencesi
There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A590UJW0 | A0A590UJW0_HUMAN | DNA mismatch repair protein Msh3 | MSH3 | 1,081 | Annotation score: | ||
A0A590UJN8 | A0A590UJN8_HUMAN | DNA mismatch repair protein Msh3 | MSH3 | 1,072 | Annotation score: | ||
A0A590UKC9 | A0A590UKC9_HUMAN | DNA mismatch repair protein Msh3 | MSH3 | 946 | Annotation score: | ||
A0A590UK39 | A0A590UK39_HUMAN | DNA mismatch repair protein Msh3 | MSH3 | 55 | Annotation score: |
Sequence cautioni
The sequence AAH11817 differs from that shown. Contaminating sequence. Potential poly-A sequence.Curated
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 61 | A → T in AAI30435 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 622 | E → G in AAB47281 (PubMed:2722860).Curated | 1 | |
Sequence conflicti | 622 | E → G in BAD27111 (Ref. 3) Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_020934 | 57 – 65 | Missing 2 Publications | 9 | |
Natural variantiVAR_020935 | 62 | A → AAAA1 Publication | 1 | |
Natural variantiVAR_020936 | 79 | I → V6 PublicationsCorresponds to variant dbSNP:rs1650697Ensembl. | 1 | |
Natural variantiVAR_016160 | 709 | F → L1 PublicationCorresponds to variant dbSNP:rs1805354EnsemblClinVar. | 1 | |
Natural variantiVAR_055251 | 789 | Y → F. Corresponds to variant dbSNP:rs10067975Ensembl. | 1 | |
Natural variantiVAR_016161 | 949 | Q → R5 PublicationsCorresponds to variant dbSNP:rs184967EnsemblClinVar. | 1 | |
Natural variantiVAR_016162 | 1045 | A → T5 PublicationsCorresponds to variant dbSNP:rs26279EnsemblClinVar. | 1 | |
Natural variantiVAR_016163 | 1054 | T → A. Corresponds to variant dbSNP:rs1805131Ensembl. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | J04810 mRNA Translation: AAB47281.1 U61981 mRNA Translation: AAB06045.1 D61419 Genomic DNA Translation: BAD27111.1 AY275681 Genomic DNA Translation: AAP13535.1 AC008434 Genomic DNA No translation available. AC010270 Genomic DNA No translation available. AC022493 Genomic DNA No translation available. BC011817 mRNA Translation: AAH11817.1 Sequence problems. BC130434 mRNA Translation: AAI30435.1 BC130436 mRNA Translation: AAI30437.1 |
CCDSi | CCDS34195.1 |
PIRi | A33507 |
RefSeqi | NP_002430.3, NM_002439.4 |
Genome annotation databases
Ensembli | ENST00000265081; ENSP00000265081; ENSG00000113318 |
GeneIDi | 4437 |
KEGGi | hsa:4437 |
UCSCi | uc003kgz.5, human |
Keywords - Coding sequence diversityi
PolymorphismSimilar proteinsi
Cross-referencesi
Web resourcesi
Atlas of Genetics and Cytogenetics in Oncology and Haematology |
NIEHS-SNPs |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | J04810 mRNA Translation: AAB47281.1 U61981 mRNA Translation: AAB06045.1 D61419 Genomic DNA Translation: BAD27111.1 AY275681 Genomic DNA Translation: AAP13535.1 AC008434 Genomic DNA No translation available. AC010270 Genomic DNA No translation available. AC022493 Genomic DNA No translation available. BC011817 mRNA Translation: AAH11817.1 Sequence problems. BC130434 mRNA Translation: AAI30435.1 BC130436 mRNA Translation: AAI30437.1 |
CCDSi | CCDS34195.1 |
PIRi | A33507 |
RefSeqi | NP_002430.3, NM_002439.4 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
3THW | X-ray | 3.09 | B | 219-1134 | [»] | |
3THX | X-ray | 2.70 | B | 219-1134 | [»] | |
3THY | X-ray | 2.89 | B | 219-1134 | [»] | |
3THZ | X-ray | 4.30 | B | 219-1134 | [»] | |
SMRi | P20585 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 110574, 54 interactors |
ComplexPortali | CPX-77, DNA mismatch repair MutSbeta complex |
CORUMi | P20585 |
DIPi | DIP-35127N |
IntActi | P20585, 22 interactors |
MINTi | P20585 |
STRINGi | 9606.ENSP00000265081 |
PTM databases
iPTMneti | P20585 |
PhosphoSitePlusi | P20585 |
Polymorphism and mutation databases
BioMutai | MSH3 |
DMDMi | 317373576 |
Proteomic databases
EPDi | P20585 |
jPOSTi | P20585 |
MassIVEi | P20585 |
MaxQBi | P20585 |
PaxDbi | P20585 |
PeptideAtlasi | P20585 |
PRIDEi | P20585 |
ProteomicsDBi | 53762 |
Protocols and materials databases
Antibodypediai | 24651, 270 antibodies |
Genome annotation databases
Ensembli | ENST00000265081; ENSP00000265081; ENSG00000113318 |
GeneIDi | 4437 |
KEGGi | hsa:4437 |
UCSCi | uc003kgz.5, human |
Organism-specific databases
CTDi | 4437 |
DisGeNETi | 4437 |
EuPathDBi | HostDB:ENSG00000113318.9 |
GeneCardsi | MSH3 |
HGNCi | HGNC:7326, MSH3 |
HPAi | ENSG00000113318, Low tissue specificity |
MalaCardsi | MSH3 |
MIMi | 600887, gene 608089, phenotype 617100, phenotype |
neXtProti | NX_P20585 |
OpenTargetsi | ENSG00000113318 |
Orphaneti | 480536, MSH3-related attenuated familial adenomatous polyposis |
PharmGKBi | PA31134 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG0218, Eukaryota |
GeneTreei | ENSGT00550000074949 |
HOGENOMi | CLU_002472_0_1_1 |
InParanoidi | P20585 |
OMAi | LHIAPCE |
OrthoDBi | 138168at2759 |
PhylomeDBi | P20585 |
TreeFami | TF300525 |
Enzyme and pathway databases
PathwayCommonsi | P20585 |
Reactomei | R-HSA-5358606, Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta) R-HSA-5632927, Defective Mismatch Repair Associated With MSH3 R-HSA-5632928, Defective Mismatch Repair Associated With MSH2 |
Miscellaneous databases
BioGRID-ORCSi | 4437, 6 hits in 849 CRISPR screens |
ChiTaRSi | MSH3, human |
GeneWikii | MSH3 |
GenomeRNAii | 4437 |
Pharosi | P20585, Tbio |
PROi | PR:P20585 |
RNActi | P20585, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000113318, Expressed in bronchial epithelial cell and 248 other tissues |
Genevisiblei | P20585, HS |
Family and domain databases
Gene3Di | 3.30.420.110, 1 hit 3.40.1170.10, 1 hit |
IDEALi | IID00612 |
InterProi | View protein in InterPro IPR007695, DNA_mismatch_repair_MutS-lik_N IPR000432, DNA_mismatch_repair_MutS_C IPR007696, DNA_mismatch_repair_MutS_core IPR016151, DNA_mismatch_repair_MutS_N IPR036187, DNA_mismatch_repair_MutS_sf IPR007860, DNA_mmatch_repair_MutS_con_dom IPR036678, MutS_con_dom_sf IPR027417, P-loop_NTPase |
Pfami | View protein in Pfam PF01624, MutS_I, 1 hit PF05188, MutS_II, 1 hit PF05192, MutS_III, 1 hit PF00488, MutS_V, 1 hit |
SMARTi | View protein in SMART SM00534, MUTSac, 1 hit SM00533, MUTSd, 1 hit |
SUPFAMi | SSF48334, SSF48334, 1 hit SSF52540, SSF52540, 1 hit SSF53150, SSF53150, 1 hit SSF55271, SSF55271, 1 hit |
PROSITEi | View protein in PROSITE PS00486, DNA_MISMATCH_REPAIR_2, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | MSH3_HUMAN | |
Accessioni | P20585Primary (citable) accession number: P20585 Secondary accession number(s): A1L480 Q92867 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | February 1, 1991 |
Last sequence update: | January 11, 2011 | |
Last modified: | December 2, 2020 | |
This is version 193 of the entry and version 4 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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
3D-structure, Reference proteomeDocuments
- Human chromosome 5
Human chromosome 5: entries, gene names and cross-references to MIM - Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations