MSH2_RAT
ID MSH2_RAT Reviewed; 933 AA.
AC P54275;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=DNA mismatch repair protein Msh2;
DE AltName: Full=MutS protein homolog 2;
GN Name=Msh2;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Testis;
RX PubMed=9034308; DOI=10.1016/s0378-1119(96)00622-1;
RA Vani R.G., Rao M.R.;
RT "Cloning of the cDNA encoding rat homologue of the mismatch repair gene
RT MSH2 and its expression during spermatogenesis.";
RL Gene 185:19-26(1997).
CC -!- FUNCTION: Component of the post-replicative DNA mismatch repair system
CC (MMR). Forms two different heterodimers: MutS alpha (MSH2-MSH6
CC heterodimer) and MutS beta (MSH2-MSH3 heterodimer) which binds to DNA
CC mismatches thereby initiating DNA repair. When bound, heterodimers bend
CC the DNA helix and shields approximately 20 base pairs. MutS alpha
CC recognizes single base mismatches and dinucleotide insertion-deletion
CC loops (IDL) in the DNA. MutS beta recognizes larger insertion-deletion
CC loops up to 13 nucleotides long. After mismatch binding, MutS alpha or
CC beta forms a ternary complex with the MutL alpha heterodimer, which is
CC thought to be responsible for directing the downstream MMR events,
CC including strand discrimination, excision, and resynthesis. Recruits
CC DNA helicase MCM9 to chromatin which unwinds the mismatch containing
CC DNA strand. ATP binding and hydrolysis play a pivotal role in mismatch
CC repair functions. The ATPase activity associated with MutS alpha
CC regulates binding similar to a molecular switch: mismatched DNA
CC provokes ADP-->ATP exchange, resulting in a discernible conformational
CC transition that converts MutS alpha into a sliding clamp capable of
CC hydrolysis-independent diffusion along the DNA backbone. This
CC transition is crucial for mismatch repair. MutS alpha may also play a
CC role in DNA homologous recombination repair. In melanocytes may
CC modulate both UV-B-induced cell cycle regulation and apoptosis.
CC {ECO:0000250|UniProtKB:P43246}.
CC -!- SUBUNIT: Component of the DNA mismatch repair (MMR) complex composed at
CC least of MCM9, MCM8,MSH2, MSH3, MSH6, PMS1 and MLH1. Heterodimer
CC consisting of MSH2-MSH6 (MutS alpha) or MSH2-MSH3 (MutS beta). Both
CC heterodimers form a ternary complex with MutL alpha (MLH1-PMS1).
CC Interacts with MCM9; the interaction recruits MCM9 to chromatin.
CC Interacts with MCM8. Interacts with EXO1. Part of the BRCA1-associated
CC genome surveillance complex (BASC), which contains BRCA1, MSH2, MSH6,
CC MLH1, ATM, BLM, PMS2 and the RAD50-MRE11-NBS1 protein complex. This
CC association could be a dynamic process changing throughout the cell
CC cycle and within subnuclear domains. Interacts with ATR. Interacts with
CC SLX4/BTBD12; this interaction is direct and links MutS beta to SLX4, a
CC subunit of different structure-specific endonucleases. Interacts with
CC SMARCAD1. {ECO:0000250|UniProtKB:P43246}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P43246}.
CC Chromosome {ECO:0000250|UniProtKB:P43246}.
CC -!- SIMILARITY: Belongs to the DNA mismatch repair MutS family.
CC {ECO:0000305}.
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DR EMBL; X93591; CAA63789.1; -; mRNA.
DR PIR; JC6184; JC6184.
DR RefSeq; NP_112320.1; NM_031058.1.
DR AlphaFoldDB; P54275; -.
DR SMR; P54275; -.
DR BioGRID; 249587; 1.
DR STRING; 10116.ENSRNOP00000021538; -.
DR iPTMnet; P54275; -.
DR PhosphoSitePlus; P54275; -.
DR jPOST; P54275; -.
DR PaxDb; P54275; -.
DR PRIDE; P54275; -.
DR GeneID; 81709; -.
DR KEGG; rno:81709; -.
DR UCSC; RGD:620786; rat.
DR CTD; 4436; -.
DR RGD; 620786; Msh2.
DR eggNOG; KOG0219; Eukaryota.
DR InParanoid; P54275; -.
DR OrthoDB; 138168at2759; -.
DR PhylomeDB; P54275; -.
DR Reactome; R-RNO-5358565; Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha).
DR Reactome; R-RNO-5358606; Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta).
DR PRO; PR:P54275; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR GO; GO:0032301; C:MutSalpha complex; ISS:UniProtKB.
DR GO; GO:0032302; C:MutSbeta complex; ISO:RGD.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; ISO:RGD.
DR GO; GO:0008094; F:ATP-dependent activity, acting on DNA; ISO:RGD.
DR GO; GO:0140664; F:ATP-dependent DNA damage sensor activity; IEA:InterPro.
DR GO; GO:0019237; F:centromeric DNA binding; ISO:RGD.
DR GO; GO:0003682; F:chromatin binding; ISO:RGD.
DR GO; GO:0003684; F:damaged DNA binding; ISO:RGD.
DR GO; GO:0003677; F:DNA binding; ISS:UniProtKB.
DR GO; GO:0003690; F:double-stranded DNA binding; IBA:GO_Central.
DR GO; GO:0019899; F:enzyme binding; ISO:RGD.
DR GO; GO:0032137; F:guanine/thymine mispair binding; ISO:RGD.
DR GO; GO:0030983; F:mismatched DNA binding; ISO:RGD.
DR GO; GO:0008022; F:protein C-terminus binding; ISO:RGD.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:RGD.
DR GO; GO:0019901; F:protein kinase binding; ISO:RGD.
DR GO; GO:0030183; P:B cell differentiation; ISO:RGD.
DR GO; GO:0019724; P:B cell mediated immunity; ISO:RGD.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISO:RGD.
DR GO; GO:0008340; P:determination of adult lifespan; ISO:RGD.
DR GO; GO:0006281; P:DNA repair; ISO:RGD.
DR GO; GO:0006302; P:double-strand break repair; ISO:RGD.
DR GO; GO:0007281; P:germ cell development; ISO:RGD.
DR GO; GO:0001701; P:in utero embryonic development; ISO:RGD.
DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; ISO:RGD.
DR GO; GO:0042771; P:intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; ISO:RGD.
DR GO; GO:0045190; P:isotype switching; ISO:RGD.
DR GO; GO:0043570; P:maintenance of DNA repeat elements; ISO:RGD.
DR GO; GO:0008584; P:male gonad development; ISO:RGD.
DR GO; GO:0006298; P:mismatch repair; ISO:RGD.
DR GO; GO:0031573; P:mitotic intra-S DNA damage checkpoint signaling; ISO:RGD.
DR GO; GO:0006312; P:mitotic recombination; IBA:GO_Central.
DR GO; GO:0045910; P:negative regulation of DNA recombination; ISO:RGD.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISO:RGD.
DR GO; GO:0006119; P:oxidative phosphorylation; ISO:RGD.
DR GO; GO:0051096; P:positive regulation of helicase activity; ISO:RGD.
DR GO; GO:0048298; P:positive regulation of isotype switching to IgA isotypes; ISO:RGD.
DR GO; GO:0048304; P:positive regulation of isotype switching to IgG isotypes; ISO:RGD.
DR GO; GO:0006301; P:postreplication repair; ISS:UniProtKB.
DR GO; GO:0071168; P:protein localization to chromatin; ISO:RGD.
DR GO; GO:0051726; P:regulation of cell cycle; ISO:RGD.
DR GO; GO:0043200; P:response to amino acid; IEP:RGD.
DR GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD.
DR GO; GO:0010224; P:response to UV-B; ISO:RGD.
DR GO; GO:0010165; P:response to X-ray; ISO:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0016446; P:somatic hypermutation of immunoglobulin genes; ISO:RGD.
DR GO; GO:0016447; P:somatic recombination of immunoglobulin gene segments; ISO:RGD.
DR GO; GO:0002204; P:somatic recombination of immunoglobulin genes involved in immune response; ISO:RGD.
DR GO; GO:0007283; P:spermatogenesis; IEP:RGD.
DR Gene3D; 3.30.420.110; -; 1.
DR Gene3D; 3.40.1170.10; -; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR011184; DNA_mismatch_repair_Msh2.
DR InterPro; IPR007695; DNA_mismatch_repair_MutS-lik_N.
DR InterPro; IPR000432; DNA_mismatch_repair_MutS_C.
DR InterPro; IPR007861; DNA_mismatch_repair_MutS_clamp.
DR InterPro; IPR007696; DNA_mismatch_repair_MutS_core.
DR InterPro; IPR016151; DNA_mismatch_repair_MutS_N.
DR InterPro; IPR036187; DNA_mismatch_repair_MutS_sf.
DR InterPro; IPR007860; DNA_mmatch_repair_MutS_con_dom.
DR InterPro; IPR032642; Msh2.
DR InterPro; IPR036678; MutS_con_dom_sf.
DR InterPro; IPR045076; MutS_family.
DR InterPro; IPR027417; P-loop_NTPase.
DR PANTHER; PTHR11361; PTHR11361; 1.
DR PANTHER; PTHR11361:SF35; PTHR11361:SF35; 1.
DR Pfam; PF01624; MutS_I; 1.
DR Pfam; PF05188; MutS_II; 1.
DR Pfam; PF05192; MutS_III; 1.
DR Pfam; PF05190; MutS_IV; 1.
DR Pfam; PF00488; MutS_V; 1.
DR PIRSF; PIRSF005813; MSH2; 1.
DR SMART; SM00534; MUTSac; 1.
DR SMART; SM00533; MUTSd; 1.
DR SUPFAM; SSF48334; SSF48334; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS00486; DNA_MISMATCH_REPAIR_2; 1.
PE 2: Evidence at transcript level;
KW Acetylation; ATP-binding; Cell cycle; Chromosome; DNA damage; DNA repair;
KW DNA-binding; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P43246"
FT CHAIN 2..933
FT /note="DNA mismatch repair protein Msh2"
FT /id="PRO_0000115185"
FT REGION 601..671
FT /note="Interaction with EXO1"
FT /evidence="ECO:0000250"
FT BINDING 669..676
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:P43246"
FT MOD_RES 567
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P43247"
FT MOD_RES 921
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P43246"
SQ SEQUENCE 933 AA; 104028 MW; 768E760891EA5801 CRC64;
MAVQPKETLQ LEGAAEVGFV RFFEGMPEKP STTVGLFDRG DFYTAHGEDA LLAAREVFKT
QGVIKYMGPA GAKTLQTVVL SKMNFESFVK DLLLVRHYRV EVYKNKAGNK ASKENDWYLA
YKASPGNLSQ FEDILFGNND MATSIGIMGI KLSTVDGQRQ VGVGDVDSTQ RKLGLCEFPD
NDQFSNLEAL LIQIGPKECI LPGGETAGDM GKLRQVIQRG GILITERKRI DFSTKDIYQD
LNRLLKGRKG EQMNSAVLPE MENQVAVSSL SAVIKFLELL SDDSNFGQFE LATFDFSQYM
KLDMAAVRAL NLFQGSVEDT TGSQSLAAFL NKCKTAQGQR LVSQWIKQPL MDKNRIEERL
NLVEAFVEDS ELRRALQEDL LRRFPDLNRL AKKFQRQAAN LQDCYRLYQG VKQLPNVIQA
LEKYQGRHQA LLLAVFVTPL TDLRSDFSKF QEKIETTLDM DQVENHEFLV KPSFDPNLSE
LREVMDGLEK KMQSTLISAA RGLGLDPGKQ IKLDSSAQFG YYFRVTCKEE KVLRNNKNFS
TVDIQKNGVK FTNSELSSLN EEYTKNKGEY EEAQDAIVKE IVNISSGYVE PMQTVNDVLA
HLDAVVSFAH VSNAAPVPYV RPVILEKGKG RIIVKASRHA CVEVQHDVAF IPNDVHFEKD
KQMFHIITGP NMGGKSTYIR QTGVIVLMAQ IGCFVPCESA EVSIVDCILA RVGAGDSQLK
GVSTFMAEML ETASILRSAT KDSLIIIDEL GRGTSTYDGF GLAWAISEYI ATNIGAFCMF
ATHFHELTAL ASQIPTVNNL HVTALTTEET LTMLYQVKTG VCDQSFGIHV AELANFPRHV
IECAKQKALE LEEFQSIGTS QGHDETQPAA KRRCLEREQG EKIILEFLSK VKQVPFTDLS
EESVSVKLKQ LKAEVLAKNN SFVNEIISRV KAP
