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P20585 (MSH3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 132. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:MSH3
Synonyms:DUC1, DUG
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1137 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Subunit structure

Heterodimer consisting of MSH2-MSH3 (MutS beta). Forms a ternary complex with MutL alpha (MLH1-PMS1). Interacts with EXO1. Ref.2 Ref.7

Involvement in disease

Endometrial cancer (ENDMC) [MIM:608089]: A 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.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry.

Sequence similarities

Belongs to the DNA mismatch repair MutS family. MSH3 subfamily.

Sequence caution

The sequence AAH11817.1 differs from that shown. Reason: Contaminating sequence. Potential poly-A sequence.

Ontologies

Keywords
   Biological processDNA damage
DNA repair
   Coding sequence diversityPolymorphism
   LigandATP-binding
DNA-binding
Nucleotide-binding
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processATP catabolic process

Inferred from Biological aspect of Ancestor. Source: GOC

DNA repair

Inferred from direct assay Ref.2. Source: BHF-UCL

maintenance of DNA repeat elements

Inferred from mutant phenotype PubMed 16388310. Source: HGNC

meiotic mismatch repair

Inferred from Biological aspect of Ancestor. Source: RefGenome

mismatch repair

Inferred from mutant phenotype PubMed 8782829. Source: HGNC

negative regulation of DNA recombination

Inferred from direct assay PubMed 17715146. Source: BHF-UCL

positive regulation of helicase activity

Inferred from direct assay PubMed 17715146. Source: BHF-UCL

reciprocal meiotic recombination

Inferred from Biological aspect of Ancestor. Source: RefGenome

somatic recombination of immunoglobulin gene segments

Inferred from Biological aspect of Ancestor. Source: RefGenome

   Cellular_componentMutSbeta complex

Inferred from direct assay Ref.2. Source: HGNC

nuclear chromosome

Inferred from Biological aspect of Ancestor. Source: RefGenome

nucleus

Inferred from direct assay. Source: HPA

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

DNA-dependent ATPase activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

Y-form DNA binding

Inferred from Biological aspect of Ancestor. Source: RefGenome

centromeric DNA binding

Inferred from electronic annotation. Source: Ensembl

damaged DNA binding

Inferred from electronic annotation. Source: Ensembl

double-strand/single-strand DNA junction binding

Inferred from Biological aspect of Ancestor. Source: RefGenome

enzyme binding

Inferred from physical interaction Ref.7. Source: UniProtKB

loop DNA binding

Inferred from Biological aspect of Ancestor. Source: RefGenome

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

MSH2P432464EBI-1164205,EBI-355888

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 11371137DNA mismatch repair protein Msh3
PRO_0000115192

Regions

Nucleotide binding896 – 9038ATP Potential
Region75 – 297223Interaction with EXO1
Compositional bias51 – 6212Poly-Ala

Amino acid modifications

Modified residue10991Phosphothreonine Ref.8 Ref.10

Natural variations

Natural variant57 – 659Missing.
VAR_020934
Natural variant621A → AAAA. Ref.11
VAR_020935
Natural variant791I → V. Ref.1 Ref.2 Ref.3 Ref.4 Ref.6 Ref.12
Corresponds to variant rs1650697 [ dbSNP | Ensembl ].
VAR_020936
Natural variant7091F → L. Ref.4
Corresponds to variant rs1805354 [ dbSNP | Ensembl ].
VAR_016160
Natural variant7891Y → F.
Corresponds to variant rs10067975 [ dbSNP | Ensembl ].
VAR_055251
Natural variant9491Q → R. Ref.1 Ref.2 Ref.3 Ref.4 Ref.6
Corresponds to variant rs184967 [ dbSNP | Ensembl ].
VAR_016161
Natural variant10451A → T. Ref.1 Ref.3 Ref.4 Ref.6 Ref.12
Corresponds to variant rs26279 [ dbSNP | Ensembl ].
VAR_016162
Natural variant10541T → A.
Corresponds to variant rs1805131 [ dbSNP | Ensembl ].
VAR_016163

Experimental info

Sequence conflict6221E → G in AAB47281. Ref.1
Sequence conflict6221E → G in BAD27111. Ref.3

Secondary structure

....................................................................................................................................................... 1137
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P20585 [UniParc].

Last modified January 11, 2011. Version 4.
Checksum: FBAE6B84D3F86032

FASTA1,137127,412
        10         20         30         40         50         60 
MSRRKPASGG LAASSSAPAR QAVLSRFFQS TGSLKSTSSS TGAADQVDPG AAAAAAAAAA 

        70         80         90        100        110        120 
AAPPAPPAPA FPPQLPPHIA TEIDRRKKRP LENDGPVKKK VKKVQQKEGG SDLGMSGNSE 

       130        140        150        160        170        180 
PKKCLRTRNV SKSLEKLKEF CCDSALPQSR VQTESLQERF AVLPKCTDFD DISLLHAKNA 

       190        200        210        220        230        240 
VSSEDSKRQI NQKDTTLFDL SQFGSSNTSH ENLQKTASKS ANKRSKSIYT PLELQYIEMK 

       250        260        270        280        290        300 
QQHKDAVLCV ECGYKYRFFG EDAEIAAREL NIYCHLDHNF MTASIPTHRL FVHVRRLVAK 

       310        320        330        340        350        360 
GYKVGVVKQT ETAALKAIGD NRSSLFSRKL TALYTKSTLI GEDVNPLIKL DDAVNVDEIM 

       370        380        390        400        410        420 
TDTSTSYLLC ISENKENVRD KKKGNIFIGI VGVQPATGEV VFDSFQDSAS RSELETRMSS 

       430        440        450        460        470        480 
LQPVELLLPS ALSEQTEALI HRATSVSVQD DRIRVERMDN IYFEYSHAFQ AVTEFYAKDT 

       490        500        510        520        530        540 
VDIKGSQIIS GIVNLEKPVI CSLAAIIKYL KEFNLEKMLS KPENFKQLSS KMEFMTINGT 

       550        560        570        580        590        600 
TLRNLEILQN QTDMKTKGSL LWVLDHTKTS FGRRKLKKWV TQPLLKLREI NARLDAVSEV 

       610        620        630        640        650        660 
LHSESSVFGQ IENHLRKLPD IERGLCSIYH KKCSTQEFFL IVKTLYHLKS EFQAIIPAVN 

       670        680        690        700        710        720 
SHIQSDLLRT VILEIPELLS PVEHYLKILN EQAAKVGDKT ELFKDLSDFP LIKKRKDEIQ 

       730        740        750        760        770        780 
GVIDEIRMHL QEIRKILKNP SAQYVTVSGQ EFMIEIKNSA VSCIPTDWVK VGSTKAVSRF 

       790        800        810        820        830        840 
HSPFIVENYR HLNQLREQLV LDCSAEWLDF LEKFSEHYHS LCKAVHHLAT VDCIFSLAKV 

       850        860        870        880        890        900 
AKQGDYCRPT VQEERKIVIK NGRHPVIDVL LGEQDQYVPN NTDLSEDSER VMIITGPNMG 

       910        920        930        940        950        960 
GKSSYIKQVA LITIMAQIGS YVPAEEATIG IVDGIFTRMG AADNIYKGQS TFMEELTDTA 

       970        980        990       1000       1010       1020 
EIIRKATSQS LVILDELGRG TSTHDGIAIA YATLEYFIRD VKSLTLFVTH YPPVCELEKN 

      1030       1040       1050       1060       1070       1080 
YSHQVGNYHM GFLVSEDESK LDPGAAEQVP DFVTFLYQIT RGIAARSYGL NVAKLADVPG 

      1090       1100       1110       1120       1130 
EILKKAAHKS KELEGLINTK RKRLKYFAKL WTMHNAQDLQ KWTEEFNMEE TQTSLLH 

« Hide

References

« Hide 'large scale' references
[1]"Isolation and characterization of cDNA clones derived from the divergently transcribed gene in the region upstream from the human dihydrofolate reductase gene."
Fujii H., Shimada T.
J. Biol. Chem. 264:10057-10064(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS VAL-79; ARG-949 AND THR-1045.
[2]"hMSH2 forms specific mispair-binding complexes with hMSH3 and hMSH6."
Acharya S., Wilson T., Gradia S., Kane M.F., Guerrette S., Marsischky G.T., Kolodner R.D., Fishel R.
Proc. Natl. Acad. Sci. U.S.A. 93:13629-13634(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH MSH2, VARIANTS 57-ALA--ALA-65 DEL; VAL-79 AND ARG-949.
[3]Shimada T., Ikejima M., Watanabe A., Orimo H.
Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS VAL-79; ARG-949 AND THR-1045.
[4]NIEHS SNPs program
Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ALA-ALA-ALA-62 INS; VAL-79; LEU-709; ARG-949 AND THR-1045.
[5]"The DNA sequence and comparative analysis of human chromosome 5."
Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S. expand/collapse author list , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.
Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS 57-ALA--ALA-65 DEL; VAL-79; ARG-949 AND THR-1045.
Tissue: Muscle.
[7]"The interaction of DNA mismatch repair proteins with human exonuclease I."
Schmutte C., Sadoff M.M., Shim K.-S., Acharya S., Fishel R.
J. Biol. Chem. 276:33011-33018(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH EXO1.
[8]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-1099, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[9]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-1099, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]"Nine-bp repeat polymorphism in exon 1 of the hMSH3 gene."
Nakajima E., Orimo H., Ikejima M., Shimada T.
Jpn. J. Hum. Genet. 40:343-345(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ALA-ALA-ALA-62 INS.
[12]"Association between single nucleotide polymorphisms in the hMSH3 gene and sporadic colon cancer with microsatellite instability."
Orimo H., Nakajima E., Yamamoto M., Ikejima M., Emi M., Shimada T.
J. Hum. Genet. 45:228-230(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS VAL-79 AND THR-1045.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
BC130436 mRNA. Translation: AAI30437.1.
PIRA33507.
RefSeqNP_002430.3. NM_002439.4.
UniGeneHs.280987.
Hs.648635.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3THWX-ray3.09B219-1134[»]
3THXX-ray2.70B219-1134[»]
3THYX-ray2.89B219-1134[»]
3THZX-ray4.30B219-1134[»]
ProteinModelPortalP20585.
SMRP20585. Positions 225-1123.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110574. 22 interactions.
DIPDIP-35127N.
IntActP20585. 5 interactions.
MINTMINT-192778.
STRING9606.ENSP00000265081.

PTM databases

PhosphoSiteP20585.

Polymorphism databases

DMDM317373576.

Proteomic databases

PaxDbP20585.
PRIDEP20585.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000265081; ENSP00000265081; ENSG00000113318.
GeneID4437.
KEGGhsa:4437.
UCSCuc003kgz.4. human.

Organism-specific databases

CTD4437.
GeneCardsGC05P079986.
H-InvDBHIX0032037.
HGNCHGNC:7326. MSH3.
HPAHPA036080.
HPA036081.
MIM600887. gene.
608089. phenotype.
neXtProtNX_P20585.
PharmGKBPA31134.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0249.
HOGENOMHOG000029776.
HOVERGENHBG006400.
InParanoidP20585.
KOK08736.
OMAELSIVCI.
OrthoDBEOG7X6KZF.
PhylomeDBP20585.
TreeFamTF300525.

Gene expression databases

BgeeP20585.
CleanExHS_MSH3.
GenevestigatorP20585.

Family and domain databases

Gene3D3.30.420.110. 1 hit.
3.40.1170.10. 1 hit.
3.40.50.300. 1 hit.
InterProIPR007695. DNA_mismatch_repair_MutS-lik_N.
IPR000432. DNA_mismatch_repair_MutS_C.
IPR007861. DNA_mismatch_repair_MutS_clamp.
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]
PfamPF01624. MutS_I. 1 hit.
PF05188. MutS_II. 1 hit.
PF05192. MutS_III. 1 hit.
PF05190. MutS_IV. 1 hit.
PF00488. MutS_V. 1 hit.
[Graphical view]
SMARTSM00534. MUTSac. 1 hit.
SM00533. MUTSd. 1 hit.
[Graphical view]
SUPFAMSSF48334. SSF48334. 1 hit.
SSF52540. SSF52540. 1 hit.
SSF53150. SSF53150. 2 hits.
SSF55271. SSF55271. 1 hit.
PROSITEPS00486. DNA_MISMATCH_REPAIR_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiMSH3.
GenomeRNAi4437.
NextBio17293.
PROP20585.
SOURCESearch...

Entry information

Entry nameMSH3_HUMAN
AccessionPrimary (citable) accession number: P20585
Secondary accession number(s): A1L482 expand/collapse secondary AC list , A6NMM6, Q6PJT5, Q86UQ6, Q92867
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1991
Last sequence update: January 11, 2011
Last modified: April 16, 2014
This is version 132 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM