P43247 (MSH2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
DNA mismatch repair protein Msh2

Alternative name(s):
MutS protein homolog 2

Gene names

Name:

Msh2

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	935 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	Component of the post-replicative DNA mismatch repair system (MMR). Forms two different heterodimers: MutS alpha (MSH2-MSH6 heterodimer) and MutS beta (MSH2-MSH3 heterodimer) which binds to DNA mismatches thereby initiating DNA repair. When bound, heterodimers bend the DNA helix and shields approximately 20 base pairs. MutS alpha recognizes single base mismatches and dinucleotide insertion-deletion loops (IDL) in the DNA. MutS beta recognizes larger insertion-deletion loops up to 13 nucleotides long. After mismatch binding, MutS alpha or beta 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. ATP binding and hydrolysis play a pivotal role in mismatch repair functions. The ATPase activity associated with MutS alpha regulates binding similar to a molecular switch: mismatched DNA provokes ADP-->ATP exchange, resulting in a discernible conformational transition that converts MutS alpha into a sliding clamp capable of hydrolysis-independent diffusion along the DNA backbone. This transition is crucial for mismatch repair. MutS alpha may also play a role in DNA homologous recombination repair. In melanocytes may modulate both UV-B-induced cell cycle regulation and apoptosis By similarity.
Subunit structure	Heterodimer consisting of MSH2-MSH6 (MutS alpha) or MSH2-MSH3 (MutS beta). Both heterodimer form a ternary complex with MutL alpha (MLH1-PMS1). Interacts with EXO1. Part of the BRCA1-associated genome surveillance complex (BASC), which contains BRCA1, MSH2, MSH6, MLH1, ATM, BLM, PMS2 and the RAD50-MRE11-NBS1 protein complex. This association could be a dynamic process changing throughout the cell cycle and within subnuclear domains. Interacts with ATR. Interacts with SLX4/BTBD12; this interaction is direct and links MutS beta to SLX4, a subunit of different structure-specific endonucleases By similarity. Interacts with SMARCAD1 By similarity.
Subcellular location	Nucleus Probable.
Sequence similarities	Belongs to the DNA mismatch repair MutS family.

Ontologies

Keywords
Biological process	Cell cycle DNA damage DNA repair
Cellular component	Nucleus
Ligand	ATP-binding DNA-binding Nucleotide-binding
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	B cell differentiation Inferred from mutant phenotype PubMed 9697843. Source: MGI cell cycle arrest Inferred from mutant phenotype PubMed 12687013. Source: MGI determination of adult lifespan Inferred from mutant phenotype PubMed 10545954. Source: MGI double-strand break repair Inferred from mutant phenotype PubMed 17912366. Source: MGI germ cell development Inferred from mutant phenotype PubMed 17912366. Source: MGI in utero embryonic development Inferred from genetic interaction PubMed 9288110. Source: MGI intra-S DNA damage checkpoint Inferred from genetic interaction PubMed 15533840. Source: MGI intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator Inferred from Biological aspect of Ancestor. Source: RefGenome isotype switching Inferred from mutant phenotype PubMed 10430621PubMed 12743174. Source: MGI maintenance of DNA repeat elements Inferred from Biological aspect of Ancestor. Source: RefGenome male gonad development Inferred from mutant phenotype PubMed 17912366. Source: MGI meiotic gene conversion Inferred from Biological aspect of Ancestor. Source: RefGenome meiotic mismatch repair Inferred from Biological aspect of Ancestor. Source: RefGenome negative regulation of neuron apoptotic process Inferred from mutant phenotype PubMed 16805809. Source: MGI negative regulation of reciprocal meiotic recombination Inferred from Biological aspect of Ancestor. Source: RefGenome oxidative phosphorylation Inferred from mutant phenotype PubMed 16805809. Source: MGI positive regulation of helicase activity Inferred from electronic annotation. Source: Compara postreplication repair Inferred from sequence or structural similarity. Source: UniProtKB response to UV-B Inferred from mutant phenotype PubMed 15166087. Source: MGI response to X-ray Inferred from mutant phenotype PubMed 12687013. Source: MGI somatic hypermutation of immunoglobulin genes Inferred from mutant phenotype PubMed 14568978PubMed 9607916PubMed 9697842PubMed 9697843. Source: MGI
Cellular_component	MutSalpha complex Inferred from direct assay PubMed 16713580. Source: MGI MutSbeta complex Inferred from Biological aspect of Ancestor. Source: RefGenome nuclear chromosome Inferred from Biological aspect of Ancestor. Source: RefGenome
Molecular_function	ADP binding Inferred from electronic annotation. Source: Compara 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 direct assay PubMed 16260499. Source: MGI damaged DNA binding Inferred from mutant phenotype PubMed 10545954PubMed 7628020. Source: MGI dinucleotide repeat insertion binding Inferred from electronic annotation. Source: Compara double-strand/single-strand DNA junction binding Inferred from Biological aspect of Ancestor. Source: RefGenome four-way junction DNA binding Inferred from Biological aspect of Ancestor. Source: RefGenome guanine/thymine mispair binding Inferred from sequence orthology PubMed 16713580. Source: MGI loop DNA binding Inferred from Biological aspect of Ancestor. Source: RefGenome magnesium ion binding Inferred from electronic annotation. Source: Compara oxidized purine DNA binding Inferred from electronic annotation. Source: Compara single base insertion or deletion binding Inferred from Biological aspect of Ancestor. Source: RefGenome single guanine insertion binding Inferred from electronic annotation. Source: Compara single thymine insertion binding Inferred from electronic annotation. Source: Compara single-stranded DNA binding Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 935	935	DNA mismatch repair protein Msh2		PRO_0000115184
Regions
	Nucleotide binding	669 – 676	8	ATP Potential
	Region	601 – 671	71	Interaction with EXO1 By similarity
Experimental info
	Sequence conflict	733	1	A → S in AAA75027. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P43247 [UniParc]. Last modified November 1, 1995. Version 1. Checksum: 2111E9D5E3A8548A	FASTA	935	104,151
	10 20 30 40 50 60 MAVQPKETLQ LEGAAEAGFV RFFEGMPEKP STTVRLFDRG DFYTAHGEDA LLAAREVFKT 70 80 90 100 110 120 QGVIKYMGPA GSKTLQSVVL SKMNFESFVK DLLLVRQYRV EVYKNKAGNK ASKENEWYLA 130 140 150 160 170 180 FKASPGNLSQ FEDILFGNND MSASVGVMGI KMAVVDGQRH VGVGYVDSTQ RKLGLCEFPE 190 200 210 220 230 240 NDQFSNLEAL LIQIGPKECV LPGGETTGDM GKLRQVIQRG GILITERKRA DFSTKDIYQD 250 260 270 280 290 300 LNRLLKGKKG EQINSAALPE MENQVAVSSL SAVIKFLELL SDDSNFGQFE LATFDFSQYM 310 320 330 340 350 360 KLDMAAVRAL NLFQGSVEDT TGSQSLAALL NKCKTAQGQR LVNQWIKQPL MDRNRIEERL 370 380 390 400 410 420 NLVEAFVEDS ELRQSLQEDL LRRFPDLNRL AKKFQRQAAN LQDCYRLYQG INQLPSVIQA 430 440 450 460 470 480 LEKYEGRHQA LLLAVFVTPL IDLRSDFSKF QEMIETTLDM DQVENHEFLV KPSFDPNLSE 490 500 510 520 530 540 LREVMDGLEK KMQSTLINAA RGLGLDPGKQ IKLDSSAQFG YYFRVTCKEE KVLRNNKNFS 550 560 570 580 590 600 TVDIQKNGVK FTNSELSSLN EEYTKNKGEY EEAQDAIVKE IVNISSGYVE PMQTLNDVLA 610 620 630 640 650 660 HLDAIVSFAH VSNAAPVPYV RPVILEKGKG RIILKASRHA CVEVQDEVAF IPNDVHFEKD 670 680 690 700 710 720 KQMFHIITGP NMGGKSTYIR QTGVIVLMAQ IGCFVPCESA EVSIVDCILA RVGAGDSQLK 730 740 750 760 770 780 GVSTFMAEML ETASILRSAT KDSLIIIDEL GRGTSTYDGF GLAWAISDYI ATKIGAFCMF 790 800 810 820 830 840 ATHFHELTAL ANQIPTVNNL HVTALTTEET LTMLYQVKKG VCDQSFGIHV AELANFPRHV 850 860 870 880 890 900 IACAKQKALE LEEFQNIGTS LGCDEAEPAA KRRCLEREQG EKIILEFLSK VKQVPFTAMS 910 920 930 EESISAKLKQ LKAEVVAKNN SFVNEIISRI KAPAP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and expression of the Xenopus and mouse Msh2 DNA mismatch repair genes." Varlet I., Pallard C., Radman M., Moreau J., de Wind N. Nucleic Acids Res. 22:5723-5728(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: BALB/c.
[2]	"Mouse MutS homolog 2 (mMSH2) c-DNA sequence from -56." Lipford J.R., Kane M.F., Kolodner R.D. Submitted (APR-1995) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"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]. Strain: FVB/N. Tissue: Mammary gland.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X81143 mRNA. Translation: CAA57049.1. U21011 mRNA. Translation: AAA75027.1. BC047117 mRNA. Translation: AAH47117.1.
IPI	IPI00118158.
PIR	S53608.
RefSeq	NP_032654.1. NM_008628.2.
UniGene	Mm.4619.
3D structure databases
ProteinModelPortal	P43247.
SMR	P43247. Positions 1-930.
ModBase	Search...
Protein-protein interaction databases
IntAct	P43247. 1 interaction.
STRING	10090.ENSMUSP00000024967.
PTM databases
PhosphoSite	P43247.
Proteomic databases
PaxDb	P43247.
PRIDE	P43247.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000024967; ENSMUSP00000024967; ENSMUSG00000024151.
GeneID	17685.
KEGG	mmu:17685.
Organism-specific databases
CTD	4436.
MGI	MGI:101816. Msh2.
Phylogenomic databases
eggNOG	COG0249.
HOGENOM	HOG000196498.
HOVERGEN	HBG006399.
InParanoid	P43247.
KO	K08735.
OMA	WAISEHI.
OrthoDB	EOG4D26P5.
Gene expression databases
ArrayExpress	P43247.
Bgee	P43247.
CleanEx	MM_MSH2.
Genevestigator	P43247.
GermOnline	ENSMUSG00000024151. Mus musculus.
Family and domain databases
Gene3D	3.30.420.110. 1 hit.
InterPro	IPR011184. DNA_mismatch_repair_MSH2. 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. IPR007860. DNA_mmatch_repair_MutS_con_dom. [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]
PIRSF	PIRSF005813. MSH2. 1 hit.
SMART	SM00534. MUTSac. 1 hit. SM00533. MUTSd. 1 hit. [Graphical view]
SUPFAM	SSF48334. DNA_repair_MutS_domIII. 1 hit.
PROSITE	PS00486. DNA_MISMATCH_REPAIR_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	292252.
SOURCE	Search...

Entry information

Entry name

MSH2_MOUSE

Accession

Primary (citable) accession number: P43247

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	November 1, 1995
Last modified:	April 3, 2013
This is version 106 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program