Reviewed, UniProtKB/Swiss-Prot P20585 (MSH3_HUMAN)

Names and origin

Protein names

Recommended name:
    DNA mismatch repair protein Msh3
Alternative name(s):
    Divergent upstream protein
      Short name=DUP
    Mismatch repair protein 1
      Short name=MRP1

Gene names

Name:	MSH3
Synonyms:	DUC1, DUG

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1137 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence 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
Post-translational modification	Phosphorylated upon DNA damage, probably by ATM or ATR. Ref.8 Ref.9
Involvement in disease	Defects in MSH3 are a cause of susceptibility to endometrial cancer [MIM:608089].
Sequence similarities	Belongs to the DNA mismatch repair mutS family. MSH3 subfamily.
Sequence caution	The sequence AAH11817.1 differs from that shown. Reason: Miscellaneous discrepancy. Contaminating sequence. Potential poly-A sequence.

Ontologies

Keywords
Biological process	DNA damage DNA repair
Coding sequence diversity	Polymorphism
Ligand	ATP-binding DNA-binding Nucleotide-binding
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	maintenance of DNA repeat elements Inferred from mutant phenotype. Source: HGNC mismatch repair Inferred from mutant phenotype. Source: HGNC negative regulation of DNA recombination Inferred from direct assay. Source: UniProtKB positive regulation of helicase activity Inferred from direct assay. Source: UniProtKB
Cellular component	MutSbeta complex Ref.2 Inferred from direct assay. Source: HGNC
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW mismatched DNA binding Ref.2 Inferred from electronic annotation. Source: InterPro protein binding Ref.2 Ref.7 Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
MSH2	P43246	1	EBI-1164205,EBI-355888

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1137	1137	DNA mismatch repair protein Msh3		PRO_0000115192
Regions
	Nucleotide binding	896 – 903	8	ATP Potential
	Region	75 – 297	223	Interaction with EXO1
	Compositional bias	51 – 62	12	Poly-Ala
Amino acid modifications
	Modified residue	201	1	Phosphoserine Ref.9
	Modified residue	1068	1	Phosphotyrosine Ref.8
Natural variations
	Natural variant	57 – 65	9	Missing Ref.6		VAR_020934
	Natural variant	62	1	A → AAAA		VAR_020935
	Natural variant	79	1	I → V: dbSNP rs1650697.		VAR_020936
	Natural variant	709	1	F → L: dbSNP rs1805354. Ref.4		VAR_016160
	Natural variant	789	1	Y → F: dbSNP rs10067975.		VAR_055251
	Natural variant	949	1	R → Q: dbSNP rs184967. Ref.4		VAR_016161
	Natural variant	1045	1	A → T: dbSNP rs26279.		VAR_016162
	Natural variant	1054	1	T → A: dbSNP rs1805131.		VAR_016163
Experimental info
	Sequence conflict	622	1	E → G Ref.1
	Sequence conflict	622	1	E → G Ref.3

Sequences

	Sequence		Length	Mass (Da)
	P20585-1 [UniParc]. Last modified May 5, 2009. Version 3. Checksum: 55B3BB86022B61E0	FASTA	1,137	127,440
	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 AADNIYKGRS 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

References

	« Hide 'large scale' referencesShow '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: 2722860] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS VAL-79 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: 8942985] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH MSH2, VARIANTS 57-ALA--ALA-65 DEL AND VAL-79.
[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 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; GLN-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. , 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: 15372022] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT GLN-949.
[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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-852, VARIANTS 57-ALA--ALA-65 DEL AND VAL-79. 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: 11427529] [Abstract] Cited for: INTERACTION WITH EXO1.
[8]	"Tyrosine phosphorylated Par3 regulates epithelial tight junction assembly promoted by EGFR signaling." Wang Y., Du D., Fang L., Yang G., Zhang C., Zeng R., Ullrich A., Lottspeich F., Chen Z. EMBO J. 25:5058-5070(2006) [PubMed: 17053785] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-1068, MASS SPECTROMETRY.
[9]	"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed: 17525332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-201, MASS SPECTROMETRY.
[10]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[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: 8851770] [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: 10944853] [Abstract] Cited for: VARIANTS VAL-79 AND THR-1045.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

NIEHS-SNPs

Cross-references

Sequence databases
EMBLGenBankDDBJ	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.
IPI	IPI00329605.
PIR	A33507.
RefSeq	NP_002430.2.
UniGene	Hs.280987 Hs.648635
3D structure databases
HSSP	HSSP built from PDB template 1NG9 based on UniProtKB P23909.
ModBase	Search...
Protein-protein interaction databases
IntAct	P20585. 2 interactions.
PTM databases
PhosphoSite	P20585.
Genome annotation databases
Ensembl	ENSG00000113318. Homo sapiens. [Contig view]
GeneID	4437.
KEGG	hsa:4437.
Organism-specific databases
GeneCards	GC05P079986.
H-InvDB	HIX0032037.
HGNC	HGNC:7326. MSH3.
MIM	600887. gene. 608089. phenotype.
PharmGKB	PA31134.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	P20585.
Gene expression databases
ArrayExpress	P20585.
Bgee	P20585.
CleanEx	HS_MSH3.
GermOnline	ENSG00000113318. Homo sapiens.
Family and domain databases
InterPro	IPR007695. DNA_mismatch_repair_MutS-lik_N. IPR000432. DNA_mismatch_repair_MutS_C. IPR007860. DNA_mismatch_repair_MutS_connt. IPR007696. DNA_mismatch_repair_MutS_core. IPR016151. DNA_mismatch_repair_MutS_N. [Graphical view]
Gene3D	G3DSA:3.40.1170.10. DNA_mismatch_repair_MutS_N. 1 hit.
PANTHER	PTHR11361. MutS_C. 1 hit.
Pfam	PF01624. MutS_I. 1 hit. PF05188. MutS_II. 1 hit. PF05192. MutS_III. 1 hit. PF00488. MutS_V. 1 hit. [Graphical view]
ProDom	PD001263. MutS_C. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00534. MUTSac. 1 hit. SM00533. MUTSd. 1 hit. [Graphical view]
PROSITE	PS00486. DNA_MISMATCH_REPAIR_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	17293.
SOURCE	Search...

Entry information

Entry name

MSH3_HUMAN

Accession

Primary (citable) accession number: P20585
Secondary accession number(s): A6NMM6 , Q6PJT5, Q86UQ6, Q92867

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1991
Last sequence update:	May 5, 2009
Last modified:	June 16, 2009
This is version 83 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)