MSH2_BOVIN
ID MSH2_BOVIN Reviewed; 934 AA.
AC Q3MHE4;
DT 24-JAN-2006, integrated into UniProtKB/Swiss-Prot.
DT 25-OCT-2005, sequence version 1.
DT 03-AUG-2022, entry version 105.
DE RecName: Full=DNA mismatch repair protein Msh2;
DE AltName: Full=MutS protein homolog 2;
GN Name=MSH2;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Ascending colon;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
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 MSH2, MSH3, MSH6, PMS1 and MLH1. Heterodimer consisting of
CC MSH2-MSH6 (MutS alpha) or MSH2-MSH3 (MutS beta). Both heterodimers form
CC a ternary complex with MutL alpha (MLH1-PMS1). Interacts with MCM9; the
CC interaction recruits MCM9 to chromatin. Interacts with MCM8. Interacts
CC with EXO1. Part of the BRCA1-associated genome surveillance complex
CC (BASC), which contains BRCA1, MSH2, MSH6, MLH1, ATM, BLM, PMS2 and the
CC RAD50-MRE11-NBS1 protein complex. This association could be a dynamic
CC process changing throughout the cell cycle and within subnuclear
CC domains. Interacts with ATR. Interacts with SLX4/BTBD12; this
CC interaction is direct and links MutS beta to SLX4, a subunit of
CC different structure-specific endonucleases. Interacts with SMARCAD1.
CC {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; BC105268; AAI05269.1; -; mRNA.
DR RefSeq; NP_001029756.1; NM_001034584.1.
DR AlphaFoldDB; Q3MHE4; -.
DR SMR; Q3MHE4; -.
DR STRING; 9913.ENSBTAP00000003556; -.
DR PaxDb; Q3MHE4; -.
DR PRIDE; Q3MHE4; -.
DR Ensembl; ENSBTAT00000003556; ENSBTAP00000003556; ENSBTAG00000002742.
DR GeneID; 533115; -.
DR KEGG; bta:533115; -.
DR CTD; 4436; -.
DR VEuPathDB; HostDB:ENSBTAG00000002742; -.
DR VGNC; VGNC:31693; MSH2.
DR eggNOG; KOG0219; Eukaryota.
DR GeneTree; ENSGT00550000074867; -.
DR HOGENOM; CLU_002472_10_0_1; -.
DR InParanoid; Q3MHE4; -.
DR OMA; LFRIYQV; -.
DR OrthoDB; 138168at2759; -.
DR TreeFam; TF351780; -.
DR Reactome; R-BTA-5358565; Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha).
DR Reactome; R-BTA-5358606; Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta).
DR Proteomes; UP000009136; Chromosome 11.
DR Bgee; ENSBTAG00000002742; Expressed in caput epididymis and 107 other tissues.
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; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0043531; F:ADP binding; IEA:Ensembl.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:Ensembl.
DR GO; GO:0140664; F:ATP-dependent DNA damage sensor activity; IEA:InterPro.
DR GO; GO:0019237; F:centromeric DNA binding; IEA:Ensembl.
DR GO; GO:0003682; F:chromatin binding; IEA:Ensembl.
DR GO; GO:0032181; F:dinucleotide repeat insertion binding; IEA:Ensembl.
DR GO; GO:0003690; F:double-stranded DNA binding; IBA:GO_Central.
DR GO; GO:0000400; F:four-way junction DNA binding; IEA:Ensembl.
DR GO; GO:0032137; F:guanine/thymine mispair binding; IEA:Ensembl.
DR GO; GO:0000287; F:magnesium ion binding; IEA:Ensembl.
DR GO; GO:0030983; F:mismatched DNA binding; IBA:GO_Central.
DR GO; GO:0032405; F:MutLalpha complex binding; IEA:Ensembl.
DR GO; GO:0032357; F:oxidized purine DNA binding; IEA:Ensembl.
DR GO; GO:0008022; F:protein C-terminus binding; IEA:Ensembl.
DR GO; GO:0042803; F:protein homodimerization activity; IEA:Ensembl.
DR GO; GO:0019901; F:protein kinase binding; IEA:Ensembl.
DR GO; GO:0032142; F:single guanine insertion binding; IEA:Ensembl.
DR GO; GO:0032143; F:single thymine insertion binding; IEA:Ensembl.
DR GO; GO:0003697; F:single-stranded DNA binding; IEA:Ensembl.
DR GO; GO:0030183; P:B cell differentiation; IEA:Ensembl.
DR GO; GO:0008340; P:determination of adult lifespan; IEA:Ensembl.
DR GO; GO:0006302; P:double-strand break repair; IEA:Ensembl.
DR GO; GO:0007281; P:germ cell development; IEA:Ensembl.
DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl.
DR GO; GO:0042771; P:intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; IEA:Ensembl.
DR GO; GO:0045190; P:isotype switching; IEA:Ensembl.
DR GO; GO:0043570; P:maintenance of DNA repeat elements; IEA:Ensembl.
DR GO; GO:0008584; P:male gonad development; IEA:Ensembl.
DR GO; GO:0006298; P:mismatch repair; IBA:GO_Central.
DR GO; GO:0031573; P:mitotic intra-S DNA damage checkpoint signaling; IEA:Ensembl.
DR GO; GO:0006312; P:mitotic recombination; IBA:GO_Central.
DR GO; GO:0045910; P:negative regulation of DNA recombination; IEA:Ensembl.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IEA:Ensembl.
DR GO; GO:0006119; P:oxidative phosphorylation; IEA:Ensembl.
DR GO; GO:0051096; P:positive regulation of helicase activity; IEA:Ensembl.
DR GO; GO:0048298; P:positive regulation of isotype switching to IgA isotypes; IEA:Ensembl.
DR GO; GO:0048304; P:positive regulation of isotype switching to IgG isotypes; IEA:Ensembl.
DR GO; GO:0006301; P:postreplication repair; IEA:Ensembl.
DR GO; GO:0071168; P:protein localization to chromatin; IEA:Ensembl.
DR GO; GO:0010224; P:response to UV-B; IEA:Ensembl.
DR GO; GO:0010165; P:response to X-ray; IEA:Ensembl.
DR GO; GO:0016446; P:somatic hypermutation of immunoglobulin genes; IEA:Ensembl.
DR GO; GO:0002204; P:somatic recombination of immunoglobulin genes involved in immune response; IBA:GO_Central.
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..934
FT /note="DNA mismatch repair protein Msh2"
FT /id="PRO_0000115181"
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 555
FT /note="N6-acetyllysine"
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 934 AA; 104922 MW; B10C540F741C8832 CRC64;
MAVQPKDTLQ LDSAAEVGFV RFFQGMPEKP TTTVRLFDRG DFYTAHREDA LLAAREVFKT
QGVVKYMGPA GAKTLESVVL SKMNFESFVK DLLLVRQYRV EVYKNRAGNK ASKENDWYLA
FKASPGNLSQ FEDILFGNND MSASIGVVGV KMSTVDGQRQ VGVGYVDSTQ RKLGLCEFPD
NDQFSNLEAL LIQIGPKECV MPGGETAGDM GKLRQVIQRG GILITERKRA DFSTKDIYQD
LNRLLKGKKG EQVNSAVLPE MENQVAVSSL SAVIKFLELL SDDSNFGQFE LTTFDFSQYM
KLDIAAVRAL NLFQGSVEDT SGSQSLAALL NKCKTPQGQR LVNQWIKQPL MDKNRIEERL
NLVEAFVEDA ELRQNLQEDL LRRFPDLNRL AKKFQRQAAN LQDCYRLYQG INQLPNVIQA
LEKYEGKHQA LFLAVFVTPL IDLRSDFSKF QEMIETTLDM DQVENHEFLV KPSFDPNLSE
LREIMDDLEK KMQSTLVSAA RDLGLDPGKQ IKLDSSTQFG YYFRVTCKEE KVLRNNKNFS
TVDIQKNGVK FTNSKLTSLN EEYTKNKTEY EEAQNAIVKE IVNISSGYVE PMQTLNDVLA
QLDAVVSFAH VSDAAPVPYV RPVILEKGRG RITLKASRHA CVEVQDEVAF IPNDVHFEKD
KQMFHIITGP NMGGKSTYIR QTGVVVLMAQ IGCFVPCEWA EVSIVDCILA RVGAGDSQLK
GVSTFMAEML ETASILRSAT KDSLIIIDEL GRGTSTYDGF GLAWAISEYI ATKIGAFCMF
ATHFHELTAL ANQIPTVNNL HVTALTTEET LTMLYQVKKG VCDQSFGIHV AELANFPRHV
IECAKQKALE LEEFQNIGKP QECDEMEPAA KRCYLEREQG EKIIQEFLSK VKQVPFTEMS
EESITRKLKQ LKAEVIAKNN SFVNEIISRI KVTA
