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Protein

DNA mismatch repair protein Msh2

Gene

Msh2

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

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).By similarity

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi669 – 676ATPSequence analysis8

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Cell cycle, DNA damage, DNA repair

Keywords - Ligandi

ATP-binding, DNA-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
DNA mismatch repair protein Msh2
Alternative name(s):
MutS protein homolog 2
Gene namesi
Name:Msh2
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi620786. Msh2.

Subcellular locationi

GO - Cellular componenti

  • MutSalpha complex Source: UniProtKB
  • MutSbeta complex Source: GO_Central
  • nuclear chromosome Source: GO_Central
  • nucleus Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00001151852 – 933DNA mismatch repair protein Msh2Add BLAST932

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineBy similarity1
Modified residuei567N6-acetyllysineBy similarity1
Modified residuei921PhosphoserineBy similarity1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

PaxDbiP54275.
PRIDEiP54275.

PTM databases

iPTMnetiP54275.
PhosphoSitePlusiP54275.

Interactioni

Subunit structurei

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).By similarity

Protein-protein interaction databases

BioGridi249587. 1 interactor.
STRINGi10116.ENSRNOP00000021538.

Structurei

3D structure databases

ProteinModelPortaliP54275.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni601 – 671Interaction with EXO1By similarityAdd BLAST71

Sequence similaritiesi

Belongs to the DNA mismatch repair MutS family.Curated

Phylogenomic databases

eggNOGiKOG0219. Eukaryota.
COG0249. LUCA.
HOGENOMiHOG000196498.
HOVERGENiHBG006399.
InParanoidiP54275.
KOiK08735.
PhylomeDBiP54275.

Family and domain databases

Gene3Di3.40.50.300. 1 hit.
InterProiIPR011184. DNA_mismatch_repair_MutS.
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.
IPR032642. Msh2.
IPR027417. P-loop_NTPase.
[Graphical view]
PANTHERiPTHR11361:SF35. PTHR11361:SF35. 1 hit.
PfamiPF01624. 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]
PIRSFiPIRSF005813. MSH2. 1 hit.
SMARTiSM00534. MUTSac. 1 hit.
SM00533. MUTSd. 1 hit.
[Graphical view]
SUPFAMiSSF48334. SSF48334. 1 hit.
SSF52540. SSF52540. 1 hit.
PROSITEiPS00486. DNA_MISMATCH_REPAIR_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P54275-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAVQPKETLQ LEGAAEVGFV RFFEGMPEKP STTVGLFDRG DFYTAHGEDA
60 70 80 90 100
LLAAREVFKT QGVIKYMGPA GAKTLQTVVL SKMNFESFVK DLLLVRHYRV
110 120 130 140 150
EVYKNKAGNK ASKENDWYLA YKASPGNLSQ FEDILFGNND MATSIGIMGI
160 170 180 190 200
KLSTVDGQRQ VGVGDVDSTQ RKLGLCEFPD NDQFSNLEAL LIQIGPKECI
210 220 230 240 250
LPGGETAGDM GKLRQVIQRG GILITERKRI DFSTKDIYQD LNRLLKGRKG
260 270 280 290 300
EQMNSAVLPE MENQVAVSSL SAVIKFLELL SDDSNFGQFE LATFDFSQYM
310 320 330 340 350
KLDMAAVRAL NLFQGSVEDT TGSQSLAAFL NKCKTAQGQR LVSQWIKQPL
360 370 380 390 400
MDKNRIEERL NLVEAFVEDS ELRRALQEDL LRRFPDLNRL AKKFQRQAAN
410 420 430 440 450
LQDCYRLYQG VKQLPNVIQA LEKYQGRHQA LLLAVFVTPL TDLRSDFSKF
460 470 480 490 500
QEKIETTLDM DQVENHEFLV KPSFDPNLSE LREVMDGLEK KMQSTLISAA
510 520 530 540 550
RGLGLDPGKQ IKLDSSAQFG YYFRVTCKEE KVLRNNKNFS TVDIQKNGVK
560 570 580 590 600
FTNSELSSLN EEYTKNKGEY EEAQDAIVKE IVNISSGYVE PMQTVNDVLA
610 620 630 640 650
HLDAVVSFAH VSNAAPVPYV RPVILEKGKG RIIVKASRHA CVEVQHDVAF
660 670 680 690 700
IPNDVHFEKD KQMFHIITGP NMGGKSTYIR QTGVIVLMAQ IGCFVPCESA
710 720 730 740 750
EVSIVDCILA RVGAGDSQLK GVSTFMAEML ETASILRSAT KDSLIIIDEL
760 770 780 790 800
GRGTSTYDGF GLAWAISEYI ATNIGAFCMF ATHFHELTAL ASQIPTVNNL
810 820 830 840 850
HVTALTTEET LTMLYQVKTG VCDQSFGIHV AELANFPRHV IECAKQKALE
860 870 880 890 900
LEEFQSIGTS QGHDETQPAA KRRCLEREQG EKIILEFLSK VKQVPFTDLS
910 920 930
EESVSVKLKQ LKAEVLAKNN SFVNEIISRV KAP
Length:933
Mass (Da):104,028
Last modified:October 1, 1996 - v1
Checksum:i768E760891EA5801
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X93591 mRNA. Translation: CAA63789.1.
PIRiJC6184.
RefSeqiNP_112320.1. NM_031058.1.
UniGeneiRn.3174.

Genome annotation databases

GeneIDi81709.
KEGGirno:81709.
UCSCiRGD:620786. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X93591 mRNA. Translation: CAA63789.1.
PIRiJC6184.
RefSeqiNP_112320.1. NM_031058.1.
UniGeneiRn.3174.

3D structure databases

ProteinModelPortaliP54275.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi249587. 1 interactor.
STRINGi10116.ENSRNOP00000021538.

PTM databases

iPTMnetiP54275.
PhosphoSitePlusiP54275.

Proteomic databases

PaxDbiP54275.
PRIDEiP54275.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi81709.
KEGGirno:81709.
UCSCiRGD:620786. rat.

Organism-specific databases

CTDi4436.
RGDi620786. Msh2.

Phylogenomic databases

eggNOGiKOG0219. Eukaryota.
COG0249. LUCA.
HOGENOMiHOG000196498.
HOVERGENiHBG006399.
InParanoidiP54275.
KOiK08735.
PhylomeDBiP54275.

Miscellaneous databases

PROiP54275.

Family and domain databases

Gene3Di3.40.50.300. 1 hit.
InterProiIPR011184. DNA_mismatch_repair_MutS.
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.
IPR032642. Msh2.
IPR027417. P-loop_NTPase.
[Graphical view]
PANTHERiPTHR11361:SF35. PTHR11361:SF35. 1 hit.
PfamiPF01624. 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]
PIRSFiPIRSF005813. MSH2. 1 hit.
SMARTiSM00534. MUTSac. 1 hit.
SM00533. MUTSd. 1 hit.
[Graphical view]
SUPFAMiSSF48334. SSF48334. 1 hit.
SSF52540. SSF52540. 1 hit.
PROSITEiPS00486. DNA_MISMATCH_REPAIR_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiMSH2_RAT
AccessioniPrimary (citable) accession number: P54275
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: November 2, 2016
This is version 110 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 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.