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Protein

DNA mismatch repair protein Msh2

Gene

Msh2

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -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

Keywordsi

Molecular functionDNA-binding
Biological processCell cycle, DNA damage, DNA repair
LigandATP-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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi620786 Msh2

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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
SMRiP54275
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

Gene3Di3.30.420.110, 1 hit
3.40.1170.10, 1 hit
InterProiView protein in 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
IPR016151 DNA_mismatch_repair_MutS_N
IPR036187 DNA_mismatch_repair_MutS_sf
IPR007860 DNA_mmatch_repair_MutS_con_dom
IPR032642 Msh2
IPR036678 MutS_con_dom_sf
IPR027417 P-loop_NTPase
PANTHERiPTHR11361:SF35 PTHR11361:SF35, 1 hit
PfamiView protein in 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
PIRSFiPIRSF005813 MSH2, 1 hit
SMARTiView protein in SMART
SM00534 MUTSac, 1 hit
SM00533 MUTSd, 1 hit
SUPFAMiSSF48334 SSF48334, 1 hit
SSF52540 SSF52540, 1 hit
PROSITEiView protein in PROSITE
PS00486 DNA_MISMATCH_REPAIR_2, 1 hit

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

Similar proteinsi

Entry informationi

Entry nameiMSH2_RAT
AccessioniPrimary (citable) accession number: P54275
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: May 23, 2018
This is version 118 of the entry and version 1 of the sequence. See 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

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