MSH2_CHLAE
ID MSH2_CHLAE Reviewed; 933 AA.
AC Q5XXB5;
DT 24-JAN-2006, integrated into UniProtKB/Swiss-Prot.
DT 23-NOV-2004, sequence version 1.
DT 03-AUG-2022, entry version 69.
DE RecName: Full=DNA mismatch repair protein Msh2;
DE AltName: Full=MutS protein homolog 2;
GN Name=MSH2;
OS Chlorocebus aethiops (Green monkey) (Cercopithecus aethiops).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Chlorocebus.
OX NCBI_TaxID=9534;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Jacobs A.T., Marnett L.J.;
RL Submitted (AUG-2004) 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; AY728093; AAU85549.1; -; mRNA.
DR AlphaFoldDB; Q5XXB5; -.
DR SMR; Q5XXB5; -.
DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR GO; GO:0032301; C:MutSalpha complex; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0140664; F:ATP-dependent DNA damage sensor activity; IEA:InterPro.
DR GO; GO:0030983; F:mismatched DNA binding; IEA:InterPro.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0006298; P:mismatch repair; IEA:InterPro.
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; Isopeptide bond; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Ubl conjugation.
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_0000115182"
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 920
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P43246"
FT CROSSLNK 430
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P43246"
SQ SEQUENCE 933 AA; 104752 MW; BCC5B2C448B764FF CRC64;
MAVQPKETLQ LESAAEVGFV RFFQSMPEKP TTTVRLFDRG DFYTAHGEDA LLAAREVFKT
QGVIKYMGPA GAKNLQSVVL SKMNFESFVK DLLLVRQYRV EVYKNRAGNK ASKENDWYLA
YKASPGNLSQ FEDILFGNND MSASIGVVGV KMSTVDGQRQ VGVGYVDSTQ RKLGLCEFPD
NDQFSNLEAL LIQIGPKECV LPGGETAGDM GKLRQIIQRG GILITERKKA DFSTKDIYQD
LNRLLKGKKG EQMNSAVLPE MENQVAVSSL SAVIKFLELL SDDSNFGQFE LTTFDFSQYM
KLDIAAVRAL NLFQGSVEDT TGSQSLAALL NKCKTPQGQR LVNQWIKQPL MDKNRIEERL
NLVEAFVEDA ELRQTLQEDL LRRFPDLNRL AKKFQRQAAN LQDCYRLYQG INQLPNVIQA
LEKHEGKHQK LLLAVFVTPL TDLRSDFSKF QEMIETTLDM DQVENHEFLV KPSFDPNLSE
LREIMNDLEK KMQSTLISAA RDLGLDPGKQ IKLDSSTQFG YYFRVTCKEE KVLRNNKNFS
TVDIQKNGVK FTNSKLTSLN EEYTKNKTEY EEAQDAIVKE IVNISSGYVE PMQTLNDVLA
QLDAVVSFAH VSNGAPVPYV RPAILEKGQG RIILKASRHA CVEVQDEITF IPNDIYFEKD
KQMFHIITGP NMGGKSTYIR QTGVIVLMAQ IGCFVPCESA EVSIVDCILA RVGAGDSQLK
GVSTFMAEML ETASILRSAT KDSLIIIDEL GRGTSTYDGF GLAWAISEYI ATKIGAFCMF
ATHFHELTAL ANQIPTVNNL HVTALTTEET LTMLYQVKKG VCDQSFGIHV AELANFPKHV
IECAKQKALE LEEFQYIGES QGYDMEPAAK KCYLEREQGE KIIQEFLSKV KQMPFTEMSE
ENITIKLKQL KAEVIAKNNS FVNEIISRIK VTT
