P20585 (MSH3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	MSH3
Synonyms:	DUC1, DUG

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1137 AA.
Sequence status	Complete.
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
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 process	DNA damage DNA repair
Coding sequence diversity	Polymorphism
Ligand	ATP-binding DNA-binding Nucleotide-binding
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	maintenance of DNA repeat elements Inferred from mutant phenotype PubMed 16388310. Source: HGNC meiotic mismatch repair Inferred from Biological aspect of Ancestor. Source: RefGenome 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_component	MutSbeta complex Inferred from direct assay Ref.2. Source: HGNC nuclear chromosome Inferred from Biological aspect of Ancestor. Source: RefGenome
Molecular_function	ATP 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: Compara damaged DNA binding Inferred from electronic annotation. Source: Compara double-strand/single-strand DNA junction binding Inferred from Biological aspect of Ancestor. Source: RefGenome loop DNA binding Inferred from Biological aspect of Ancestor. Source: RefGenome
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
MSH2	P43246	4	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

1099

1

Phosphothreonine Ref.8 Ref.10

Natural variations

Natural variant

57 – 65

9

Missing.

VAR_020934

Natural variant

62

1

A → AAAA. Ref.11

VAR_020935

Natural variant

79

1

I → V. Ref.1 Ref.2 Ref.3 Ref.4 Ref.6 Ref.12
Corresponds to variant rs1650697 [ dbSNP | Ensembl ].

VAR_020936

Natural variant

709

1

F → L. Ref.4
Corresponds to variant rs1805354 [ dbSNP | Ensembl ].

VAR_016160

Natural variant

789

1

Y → F.
Corresponds to variant rs10067975 [ dbSNP | Ensembl ].

VAR_055251

Natural variant

949

1

Q → R. Ref.1 Ref.2 Ref.3 Ref.4 Ref.6
Corresponds to variant rs184967 [ dbSNP | Ensembl ].

VAR_016161

Natural variant

1045

1

A → T. Ref.1 Ref.3 Ref.4 Ref.6 Ref.12
Corresponds to variant rs26279 [ dbSNP | Ensembl ].

VAR_016162

Natural variant

1054

1

T → A.
Corresponds to variant rs1805131 [ dbSNP | Ensembl ].

VAR_016163

Experimental info

Sequence conflict

622

1

E → G in AAB47281. Ref.1

Sequence conflict

622

1

E → G in BAD27111. Ref.3

Secondary structure

1

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1137

Helix Strand Turn

Details...

Helix

231 – 240

10

Turn

241 – 245

5

Beta strand

246 – 251

6

Beta strand

253 – 259

7

Helix

260 – 270

11

Beta strand

275 – 277

3

Beta strand

280 – 286

7

Helix

287 – 289

3

Helix

290 – 300

11

Beta strand

304 – 309

6

Helix

313 – 316

4

Beta strand

328 – 334

7

Turn

342 – 344

3

Beta strand

347 – 349

3

Beta strand

354 – 356

3

Beta strand

368 – 374

7

Turn

382 – 384

3

Beta strand

386 – 393

8

Turn

395 – 397

3

Beta strand

400 – 407

8

Helix

412 – 421

10

Beta strand

424 – 431

8

Helix

434 – 445

12

Beta strand

449 – 451

3

Beta strand

454 – 458

5

Helix

460 – 462

3

Helix

465 – 475

11

Helix

497 – 512

16

Helix

516 – 519

4

Helix

522 – 524

3

Beta strand

525 – 528

4

Turn

531 – 533

3

Helix

539 – 544

6

Beta strand

547 – 549

3

Turn

551 – 553

3

Helix

560 – 564

5

Helix

570 – 581

12

Helix

587 – 601

15

Helix

607 – 613

7

Turn

614 – 617

4

Helix

621 – 629

9

Helix

635 – 661

27

Helix

666 – 672

7

Helix

674 – 678

5

Helix

680 – 682

3

Helix

683 – 686

4

Helix

691 – 696

6

Helix

706 – 708

3

Helix

710 – 737

28

Beta strand

745 – 747

3

Beta strand

750 – 757

8

Helix

761 – 763

3

Beta strand

769 – 773

5

Beta strand

775 – 781

7

Helix

783 – 814

32

Helix

815 – 817

3

Helix

818 – 841

24

Beta strand

843 – 845

3

Beta strand

850 – 854

5

Beta strand

856 – 862

7

Helix

865 – 870

6

Beta strand

875 – 877

3

Beta strand

880 – 884

5

Beta strand

886 – 888

3

Beta strand

891 – 896

6

Helix

900 – 917

18

Beta strand

922 – 930

9

Beta strand

933 – 938

6

Helix

952 – 965

14

Beta strand

971 – 976

6

Turn

977 – 980

4

Helix

983 – 999

17

Beta strand

1004 – 1008

5

Helix

1012 – 1016

5

Helix

1017 – 1020

4

Turn

1021 – 1024

4

Beta strand

1025 – 1033

9

Beta strand

1055 – 1062

8

Turn

1066 – 1069

4

Helix

1070 – 1073

4

Turn

1074 – 1077

4

Helix

1080 – 1111

32

Helix

1116 – 1128

13

Sequences

	Sequence		Length	Mass (Da)
	P20585 [UniParc]. Last modified January 11, 2011. Version 4. Checksum: FBAE6B84D3F86032	FASTA	1,137	127,412
	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

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] [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. , 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, MASS SPECTROMETRY. 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, 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] [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.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

NIEHS-SNPs

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.

IPI

IPI00329605.

PIR

A33507.

RefSeq

NP_002430.3. NM_002439.4.

UniGene

Hs.280987.
Hs.648635.

3D structure databases

PDBe
RCSB PDB
PDBj

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	[»]

ProteinModelPortal

P20585.

SMR

P20585. Positions 225-1123.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-35127N.

IntAct

P20585. 4 interactions.

MINT

MINT-192778.

STRING

9606.ENSP00000265081.

PTM databases

PhosphoSite

P20585.

Polymorphism databases

DMDM

229462953.

Proteomic databases

PaxDb

P20585.

PRIDE

P20585.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000265081; ENSP00000265081; ENSG00000113318.

GeneID

4437.

KEGG

hsa:4437.

UCSC

uc003kgz.3. human.

Organism-specific databases

CTD

4437.

GeneCards

GC05P079986.

H-InvDB

HIX0032037.

HGNC

HGNC:7326. MSH3.

HPA

HPA036080.
HPA036081.

MIM

600887. gene.
608089. phenotype.

neXtProt

NX_P20585.

PharmGKB

PA31134.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0249.

HOGENOM

HOG000029776.

HOVERGEN

HBG006400.

InParanoid

P20585.

KO

K08736.

OMA

HYFELTV.

OrthoDB

EOG434W57.

Gene expression databases

ArrayExpress

P20585.

Bgee

P20585.

CleanEx

HS_MSH3.

Genevestigator

P20585.

GermOnline

ENSG00000113318. Homo sapiens.

Family and domain databases

Gene3D

3.30.420.110. 1 hit.
3.40.1170.10. 1 hit.

InterPro

IPR007695. 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]

Pfam

PF01624. 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]

SMART

SM00534. MUTSac. 1 hit.
SM00533. MUTSd. 1 hit.
[Graphical view]

SUPFAM

SSF53150. DNA_mismatch_repair_MutS_connt. 1 hit.
SSF55271. DNA_mismatch_repair_MutS_N. 1 hit.
SSF48334. DNA_repair_MutS_domIII. 1 hit.
SSF52540. SSF52540. 1 hit.

PROSITE

PS00486. DNA_MISMATCH_REPAIR_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

GenomeRNAi

4437.

NextBio

17293.

SOURCE

Search...

Entry information

Entry name

MSH3_HUMAN

Accession

Primary (citable) accession number: P20585
Secondary accession number(s): A1L482 , A6NMM6, Q6PJT5, Q86UQ6, Q92867

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1991
Last sequence update:	January 11, 2011
Last modified:	May 29, 2013
This is version 124 of the entry and version 4 of the sequence. [Complete history]

Entry status

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.