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Protein

DNA mismatch repair protein Msh3

Gene

MSH3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

  • ATP binding Source: UniProtKB-KW
  • damaged DNA binding Source: GO_Central
  • enzyme binding Source: UniProtKB
  • mismatched DNA binding Source: InterPro

GO - Biological processi

  • DNA repair Source: BHF-UCL
  • maintenance of DNA repeat elements Source: HGNC
  • meiotic mismatch repair Source: GO_Central
  • mismatch repair Source: HGNC
  • negative regulation of DNA recombination Source: BHF-UCL
  • positive regulation of helicase activity Source: BHF-UCL
  • reciprocal meiotic recombination Source: GO_Central
Complete GO annotation...

Keywords - Biological processi

DNA damage, DNA repair

Keywords - Ligandi

ATP-binding, DNA-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000113318-MONOMER.
ReactomeiR-HSA-5358606. Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta).

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

HGNCiHGNC:7326. MSH3.

Subcellular locationi

GO - Cellular componenti

  • membrane Source: UniProtKB
  • MutSbeta complex Source: HGNC
  • nuclear chromosome Source: GO_Central
  • nucleoplasm Source: Reactome
Complete GO annotation...

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

Organism-specific databases

DisGeNETi4437.
MalaCardsiMSH3.
MIMi608089. 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.

PTM databases

iPTMnetiP20585.
PhosphoSitePlusiP20585.

Expressioni

Gene expression databases

BgeeiENSG00000113318.
CleanExiHS_MSH3.
GenevisibleiP20585. HS.

Organism-specific databases

HPAiHPA036080.
HPA036081.

Interactioni

Subunit structurei

Heterodimer consisting of MSH2-MSH3 (MutS beta). Forms a ternary complex with MutL alpha (MLH1-PMS1). Interacts with EXO1.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
MLH1P406923EBI-1164205,EBI-744248
MSH2P432464EBI-1164205,EBI-355888
PCNAP120045EBI-1164205,EBI-358311

GO - Molecular functioni

  • enzyme binding Source: UniProtKB

Protein-protein interaction databases

BioGridi110574. 37 interactors.
DIPiDIP-35127N.
IntActiP20585. 15 interactors.
MINTiMINT-192778.
STRINGi9606.ENSP00000265081.

Structurei

Secondary structure

11137
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi231 – 240Combined sources10
Turni241 – 245Combined sources5
Beta strandi246 – 251Combined sources6
Beta strandi253 – 259Combined sources7
Helixi260 – 270Combined sources11
Beta strandi275 – 277Combined sources3
Beta strandi280 – 286Combined sources7
Helixi287 – 289Combined sources3
Helixi290 – 300Combined sources11
Beta strandi304 – 309Combined sources6
Helixi313 – 316Combined sources4
Beta strandi328 – 334Combined sources7
Turni342 – 344Combined sources3
Beta strandi347 – 349Combined sources3
Beta strandi354 – 356Combined sources3
Beta strandi368 – 374Combined sources7
Turni382 – 384Combined sources3
Beta strandi386 – 393Combined sources8
Turni395 – 397Combined sources3
Beta strandi400 – 407Combined sources8
Helixi412 – 421Combined sources10
Beta strandi424 – 431Combined sources8
Helixi434 – 445Combined sources12
Beta strandi449 – 451Combined sources3
Beta strandi454 – 458Combined sources5
Helixi460 – 462Combined sources3
Helixi465 – 475Combined sources11
Helixi497 – 512Combined sources16
Helixi516 – 519Combined sources4
Helixi522 – 524Combined sources3
Beta strandi525 – 528Combined sources4
Turni531 – 533Combined sources3
Helixi539 – 544Combined sources6
Beta strandi547 – 549Combined sources3
Turni551 – 553Combined sources3
Helixi560 – 564Combined sources5
Helixi570 – 581Combined sources12
Helixi587 – 601Combined sources15
Helixi607 – 613Combined sources7
Turni614 – 617Combined sources4
Helixi621 – 629Combined sources9
Helixi635 – 661Combined sources27
Helixi666 – 672Combined sources7
Helixi674 – 678Combined sources5
Helixi680 – 682Combined sources3
Helixi683 – 686Combined sources4
Helixi691 – 696Combined sources6
Helixi706 – 708Combined sources3
Helixi710 – 737Combined sources28
Beta strandi745 – 747Combined sources3
Beta strandi750 – 757Combined sources8
Helixi761 – 763Combined sources3
Beta strandi769 – 773Combined sources5
Beta strandi775 – 781Combined sources7
Helixi783 – 814Combined sources32
Helixi815 – 817Combined sources3
Helixi818 – 841Combined sources24
Beta strandi843 – 845Combined sources3
Beta strandi850 – 854Combined sources5
Beta strandi856 – 862Combined sources7
Helixi865 – 870Combined sources6
Beta strandi875 – 877Combined sources3
Beta strandi880 – 884Combined sources5
Beta strandi886 – 888Combined sources3
Beta strandi891 – 896Combined sources6
Helixi900 – 917Combined sources18
Beta strandi922 – 930Combined sources9
Beta strandi933 – 938Combined sources6
Helixi952 – 965Combined sources14
Beta strandi971 – 976Combined sources6
Turni977 – 980Combined sources4
Helixi983 – 999Combined sources17
Beta strandi1004 – 1008Combined sources5
Helixi1012 – 1016Combined sources5
Helixi1017 – 1020Combined sources4
Turni1021 – 1024Combined sources4
Beta strandi1025 – 1033Combined sources9
Beta strandi1055 – 1062Combined sources8
Turni1066 – 1069Combined sources4
Helixi1070 – 1073Combined sources4
Turni1074 – 1077Combined sources4
Helixi1080 – 1111Combined sources32
Helixi1116 – 1128Combined sources13

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...

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.
OMAiSGGYLLC.
OrthoDBiEOG091G0JQY.
PhylomeDBiP20585.
TreeFamiTF300525.

Family and domain databases

Gene3Di3.30.420.110. 1 hit.
3.40.1170.10. 1 hit.
3.40.50.300. 1 hit.
InterProiIPR007695. DNA_mismatch_repair_MutS-lik_N.
IPR000432. DNA_mismatch_repair_MutS_C.
IPR007696. DNA_mismatch_repair_MutS_core.
IPR016151. DNA_mismatch_repair_MutS_N.
IPR007860. DNA_mmatch_repair_MutS_con_dom.
IPR027417. P-loop_NTPase.
[Graphical view]
PfamiPF01624. MutS_I. 1 hit.
PF05188. MutS_II. 1 hit.
PF05192. MutS_III. 1 hit.
PF00488. MutS_V. 1 hit.
[Graphical view]
SMARTiSM00534. MUTSac. 1 hit.
SM00533. MUTSd. 1 hit.
[Graphical view]
SUPFAMiSSF48334. SSF48334. 1 hit.
SSF52540. SSF52540. 1 hit.
SSF53150. SSF53150. 2 hits.
SSF55271. SSF55271. 1 hit.
PROSITEiPS00486. DNA_MISMATCH_REPAIR_2. 1 hit.
[Graphical view]

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 → AAAA.1 Publication1
Natural variantiVAR_02093679I → V.6 PublicationsCorresponds to variant rs1650697dbSNPEnsembl.1
Natural variantiVAR_016160709F → L.1 PublicationCorresponds to variant rs1805354dbSNPEnsembl.1
Natural variantiVAR_055251789Y → F.Corresponds to variant rs10067975dbSNPEnsembl.1
Natural variantiVAR_016161949Q → R.5 PublicationsCorresponds to variant rs184967dbSNPEnsembl.1
Natural variantiVAR_0161621045A → T.5 PublicationsCorresponds to variant rs26279dbSNPEnsembl.1
Natural variantiVAR_0161631054T → A.Corresponds to variant rs1805131dbSNPEnsembl.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

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. 37 interactors.
DIPiDIP-35127N.
IntActiP20585. 15 interactors.
MINTiMINT-192778.
STRINGi9606.ENSP00000265081.

PTM databases

iPTMnetiP20585.
PhosphoSitePlusiP20585.

Polymorphism and mutation databases

BioMutaiMSH3.
DMDMi317373576.

Proteomic databases

EPDiP20585.
MaxQBiP20585.
PaxDbiP20585.
PeptideAtlasiP20585.
PRIDEiP20585.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi4437.
DisGeNETi4437.
GeneCardsiMSH3.
H-InvDBHIX0032037.
HGNCiHGNC:7326. MSH3.
HPAiHPA036080.
HPA036081.
MalaCardsiMSH3.
MIMi600887. gene.
608089. phenotype.
neXtProtiNX_P20585.
OpenTargetsiENSG00000113318.
PharmGKBiPA31134.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciZFISH:ENSG00000113318-MONOMER.
ReactomeiR-HSA-5358606. Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta).

Miscellaneous databases

ChiTaRSiMSH3. human.
GeneWikiiMSH3.
GenomeRNAii4437.
PROiP20585.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000113318.
CleanExiHS_MSH3.
GenevisibleiP20585. HS.

Family and domain databases

Gene3Di3.30.420.110. 1 hit.
3.40.1170.10. 1 hit.
3.40.50.300. 1 hit.
InterProiIPR007695. DNA_mismatch_repair_MutS-lik_N.
IPR000432. DNA_mismatch_repair_MutS_C.
IPR007696. DNA_mismatch_repair_MutS_core.
IPR016151. DNA_mismatch_repair_MutS_N.
IPR007860. DNA_mmatch_repair_MutS_con_dom.
IPR027417. P-loop_NTPase.
[Graphical view]
PfamiPF01624. MutS_I. 1 hit.
PF05188. MutS_II. 1 hit.
PF05192. MutS_III. 1 hit.
PF00488. MutS_V. 1 hit.
[Graphical view]
SMARTiSM00534. MUTSac. 1 hit.
SM00533. MUTSd. 1 hit.
[Graphical view]
SUPFAMiSSF48334. SSF48334. 1 hit.
SSF52540. SSF52540. 1 hit.
SSF53150. SSF53150. 2 hits.
SSF55271. SSF55271. 1 hit.
PROSITEiPS00486. DNA_MISMATCH_REPAIR_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiMSH3_HUMAN
AccessioniPrimary (citable) accession number: P20585
Secondary accession number(s): A1L480
, A1L482, A6NMM6, Q6PJT5, Q86UQ6, Q92867
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1991
Last sequence update: January 11, 2011
Last modified: November 30, 2016
This is version 160 of the entry and version 4 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 5
    Human chromosome 5: 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. 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.