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Protein

DNA mismatch repair protein Msh3

Gene

MSH3

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

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 keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi896 – 903ATPSequence analysis8

GO - Molecular functioni

GO - Biological processi

  • DNA repair Source: BHF-UCL
  • maintenance of DNA repeat elements Source: HGNC
  • mismatch repair Source: HGNC
  • negative regulation of DNA recombination Source: BHF-UCL
  • positive regulation of helicase activity Source: BHF-UCL
  • somatic recombination of immunoglobulin gene segments Source: GO_Central

Keywordsi

Molecular functionDNA-binding
Biological processDNA damage, DNA repair
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-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 Msh3
Short 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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

EuPathDBiHostDB:ENSG00000113318.9
HGNCiHGNC:7326 MSH3
MIMi600887 gene
neXtProtiNX_P20585

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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.
See also OMIM:608089
Familial 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.
See also OMIM:617100

Organism-specific databases

DisGeNETi4437
MalaCardsiMSH3
MIMi608089 phenotype
617100 phenotype
OpenTargetsiENSG00000113318
PharmGKBiPA31134

Polymorphism and mutation databases

BioMutaiMSH3
DMDMi317373576

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001151921 – 1137DNA mismatch repair protein Msh3Add BLAST1137

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei33PhosphoserineCombined sources1
Modified residuei1099PhosphothreonineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiP20585
MaxQBiP20585
PaxDbiP20585
PeptideAtlasiP20585
PRIDEiP20585
ProteomicsDBi53762

PTM databases

iPTMnetiP20585
PhosphoSitePlusiP20585

Expressioni

Gene expression databases

BgeeiENSG00000113318 Expressed in 238 organ(s), highest expression level in bronchial epithelial cell
CleanExiHS_MSH3
GenevisibleiP20585 HS

Organism-specific databases

HPAiHPA036081

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 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi110574, 41 interactors
ComplexPortaliCPX-77 DNA mismatch repair MutSbeta complex
CORUMiP20585
DIPiDIP-35127N
IntActiP20585, 16 interactors
MINTiP20585
STRINGi9606.ENSP00000265081

Structurei

Secondary structure

11137
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP20585
SMRiP20585
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni75 – 297Interaction with EXO11 PublicationAdd BLAST223

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi51 – 62Poly-AlaAdd BLAST12

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0217 Eukaryota
COG0249 LUCA
GeneTreeiENSGT00550000074949
HOGENOMiHOG000029776
HOVERGENiHBG006400
InParanoidiP20585
KOiK08736
OMAiYHLKSEF
OrthoDBiEOG091G0JQY
PhylomeDBiP20585
TreeFamiTF300525

Family and domain databases

Gene3Di3.30.420.110, 1 hit
3.40.1170.10, 1 hit
InterProiView protein in InterPro
IPR007695 DNA_mismatch_repair_MutS-lik_N
IPR017261 DNA_mismatch_repair_MutS/MSH
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
PfamiView protein in Pfam
PF01624 MutS_I, 1 hit
PF05188 MutS_II, 1 hit
PF05192 MutS_III, 1 hit
PF00488 MutS_V, 1 hit
PIRSFiPIRSF037677 DNA_mis_repair_Msh6, 1 hit
SMARTiView protein in SMART
SM00534 MUTSac, 1 hit
SM00533 MUTSd, 1 hit
SUPFAMiSSF48334 SSF48334, 1 hit
SSF52540 SSF52540, 1 hit
SSF53150 SSF53150, 2 hits
SSF55271 SSF55271, 1 hit
PROSITEiView protein in PROSITE
PS00486 DNA_MISMATCH_REPAIR_2, 1 hit

Sequencei

Sequence statusi: Complete.

P20585-1 [UniParc]FASTAAdd to basket
« Hide
        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
Length:1,137
Mass (Da):127,412
Last modified:January 11, 2011 - v4
Checksum:iFBAE6B84D3F86032
GO

Sequence cautioni

The sequence AAH11817 differs from that shown. Contaminating sequence. Potential poly-A sequence.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti61A → T in AAI30435 (PubMed:15489334).Curated1
Sequence conflicti622E → G in AAB47281 (PubMed:2722860).Curated1
Sequence conflicti622E → G in BAD27111 (Ref. 3) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02093457 – 65Missing 2 Publications9
Natural variantiVAR_02093562A → AAAA1 Publication1
Natural variantiVAR_02093679I → V6 PublicationsCorresponds to variant dbSNP:rs1650697Ensembl.1
Natural variantiVAR_016160709F → L1 PublicationCorresponds to variant dbSNP:rs1805354Ensembl.1
Natural variantiVAR_055251789Y → F. Corresponds to variant dbSNP:rs10067975Ensembl.1
Natural variantiVAR_016161949Q → R5 PublicationsCorresponds to variant dbSNP:rs184967Ensembl.1
Natural variantiVAR_0161621045A → T5 PublicationsCorresponds to variant dbSNP:rs26279Ensembl.1
Natural variantiVAR_0161631054T → 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
CCDSiCCDS34195.1
PIRiA33507
RefSeqiNP_002430.3, NM_002439.4
UniGeneiHs.280987
Hs.648635

Genome annotation databases

EnsembliENST00000265081; ENSP00000265081; ENSG00000113318
GeneIDi4437
KEGGihsa:4437
UCSCiuc003kgz.5 human

Keywords - Coding sequence diversityi

Polymorphism

Similar 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
CCDSiCCDS34195.1
PIRiA33507
RefSeqiNP_002430.3, NM_002439.4
UniGeneiHs.280987
Hs.648635

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3THWX-ray3.09B219-1134[»]
3THXX-ray2.70B219-1134[»]
3THYX-ray2.89B219-1134[»]
3THZX-ray4.30B219-1134[»]
ProteinModelPortaliP20585
SMRiP20585
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110574, 41 interactors
ComplexPortaliCPX-77 DNA mismatch repair MutSbeta complex
CORUMiP20585
DIPiDIP-35127N
IntActiP20585, 16 interactors
MINTiP20585
STRINGi9606.ENSP00000265081

PTM databases

iPTMnetiP20585
PhosphoSitePlusiP20585

Polymorphism and mutation databases

BioMutaiMSH3
DMDMi317373576

Proteomic databases

EPDiP20585
MaxQBiP20585
PaxDbiP20585
PeptideAtlasiP20585
PRIDEiP20585
ProteomicsDBi53762

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000265081; ENSP00000265081; ENSG00000113318
GeneIDi4437
KEGGihsa:4437
UCSCiuc003kgz.5 human

Organism-specific databases

CTDi4437
DisGeNETi4437
EuPathDBiHostDB:ENSG00000113318.9
GeneCardsiMSH3
H-InvDBiHIX0032037
HGNCiHGNC:7326 MSH3
HPAiHPA036081
MalaCardsiMSH3
MIMi600887 gene
608089 phenotype
617100 phenotype
neXtProtiNX_P20585
OpenTargetsiENSG00000113318
PharmGKBiPA31134
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0217 Eukaryota
COG0249 LUCA
GeneTreeiENSGT00550000074949
HOGENOMiHOG000029776
HOVERGENiHBG006400
InParanoidiP20585
KOiK08736
OMAiYHLKSEF
OrthoDBiEOG091G0JQY
PhylomeDBiP20585
TreeFamiTF300525

Enzyme and pathway databases

ReactomeiR-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

ChiTaRSiMSH3 human
GeneWikiiMSH3
GenomeRNAii4437
PROiPR:P20585
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000113318 Expressed in 238 organ(s), highest expression level in bronchial epithelial cell
CleanExiHS_MSH3
GenevisibleiP20585 HS

Family and domain databases

Gene3Di3.30.420.110, 1 hit
3.40.1170.10, 1 hit
InterProiView protein in InterPro
IPR007695 DNA_mismatch_repair_MutS-lik_N
IPR017261 DNA_mismatch_repair_MutS/MSH
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
PfamiView protein in Pfam
PF01624 MutS_I, 1 hit
PF05188 MutS_II, 1 hit
PF05192 MutS_III, 1 hit
PF00488 MutS_V, 1 hit
PIRSFiPIRSF037677 DNA_mis_repair_Msh6, 1 hit
SMARTiView protein in SMART
SM00534 MUTSac, 1 hit
SM00533 MUTSd, 1 hit
SUPFAMiSSF48334 SSF48334, 1 hit
SSF52540 SSF52540, 1 hit
SSF53150 SSF53150, 2 hits
SSF55271 SSF55271, 1 hit
PROSITEiView protein in PROSITE
PS00486 DNA_MISMATCH_REPAIR_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiMSH3_HUMAN
AccessioniPrimary (citable) accession number: P20585
Secondary accession number(s): A1L480
, A1L482, A6NMM6, Q6PJT5, Q86UQ6, Q92867
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1991
Last sequence update: January 11, 2011
Last modified: October 10, 2018
This is version 176 of the entry and version 4 of the sequence. See 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

3D-structure, Complete proteome, Reference proteome

Documents

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