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Overview

Uniprot IDP43246
Protein NameDNA mismatch repair protein Msh2
Gene NameMSH2
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
110 YKNRAGNKASKENDW
172 YVDSIQRKLGLCEFP
537 EKVLRNNKNFSTVDI
546 FSTVDIQKNGVKFTN

Function

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. Recruits DNA helicase MCM9 to chromatin which unwinds the mismatch containing DNA strand (PubMed:26300262). 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

Protein Sequence

10 MAVQPKETLQ 20 LESAAEVGFV 30 RFFQGMPEKP 40 TTTVRLFDRG 50 DFYTAHGEDA 60 LLAAREVFKT 70 QGVIKYMGPA 80 GAKNLQSVVL 90 SKMNFESFVK 100 DLLLVRQYRV 110 EVYKNRAGNK 120 ASKENDWYLA 130 YKASPGNLSQ 140 FEDILFGNND 150 MSASIGVVGV 160 KMSAVDGQRQ 170 VGVGYVDSIQ 180 RKLGLCEFPD 190 NDQFSNLEAL 200 LIQIGPKECV 210 LPGGETAGDM 220 GKLRQIIQRG 230 GILITERKKA 240 DFSTKDIYQD 250 LNRLLKGKKG 260 EQMNSAVLPE 270 MENQVAVSSL 280 SAVIKFLELL 290 SDDSNFGQFE 300 LTTFDFSQYM 310 KLDIAAVRAL 320 NLFQGSVEDT 330 TGSQSLAALL 340 NKCKTPQGQR 350 LVNQWIKQPL 360 MDKNRIEERL 370 NLVEAFVEDA 380 ELRQTLQEDL 390 LRRFPDLNRL 400 AKKFQRQAAN 410 LQDCYRLYQG 420 INQLPNVIQA 430 LEKHEGKHQK 440 LLLAVFVTPL 450 TDLRSDFSKF 460 QEMIETTLDM 470 DQVENHEFLV 480 KPSFDPNLSE 490 LREIMNDLEK 500 KMQSTLISAA 510 RDLGLDPGKQ 520 IKLDSSAQFG 530 YYFRVTCKEE 540 KVLRNNKNFS 550 TVDIQKNGVK 560 FTNSKLTSLN 570 EEYTKNKTEY 580 EEAQDAIVKE 590 IVNISSGYVE 600 PMQTLNDVLA 610 QLDAVVSFAH 620 VSNGAPVPYV 630 RPAILEKGQG 640 RIILKASRHA 650 CVEVQDEIAF 660 IPNDVYFEKD 670 KQMFHIITGP 680 NMGGKSTYIR 690 QTGVIVLMAQ 700 IGCFVPCESA 710 EVSIVDCILA 720 RVGAGDSQLK 730 GVSTFMAEML 740 ETASILRSAT 750 KDSLIIIDEL 760 GRGTSTYDGF 770 GLAWAISEYI 780 ATKIGAFCMF 790 ATHFHELTAL 800 ANQIPTVNNL 810 HVTALTTEET 820 LTMLYQVKKG 830 VCDQSFGIHV 840 AELANFPKHV 850 IECAKQKALE 860 LEEFQYIGES 870 QGYDIMEPAA 880 KKCYLEREQG 890 EKIIQEFLSK 900 VKQMPFTEMS 910 EENITIKLKQ 920 LKAEVIAKNN 930 SFVNEIISRI KVTT

Gene Ontology

Classification GO ID Description
Cellular Component GO:0000781 chromosome, telomeric region
Cellular Component GO:0016020 membrane
Cellular Component GO:0032301 MutSalpha complex
Cellular Component GO:0032302 MutSbeta complex
Cellular Component GO:0005654 nucleoplasm
Cellular Component GO:0005634 nucleus
Molecular Function GO:0005524 ATP binding
Molecular Function GO:0016887 ATP hydrolysis activity
Molecular Function GO:0008094 ATP-dependent activity, acting on DNA
Molecular Function GO:0140664 ATP-dependent DNA damage sensor activity
Molecular Function GO:0019237 centromeric DNA binding
Molecular Function GO:0003682 chromatin binding
Molecular Function GO:0003684 damaged DNA binding
Molecular Function GO:0003677 DNA binding
Molecular Function GO:0008047 enzyme activator activity
Molecular Function GO:0032137 guanine/thymine mispair binding
Molecular Function GO:0042803 protein homodimerization activity
Biological Process GO:0030183 B cell differentiation
Biological Process GO:0019724 B cell mediated immunity
Biological Process GO:0006301 DNA damage tolerance
Biological Process GO:0006281 DNA repair
Biological Process GO:0045190 isotype switching
Biological Process GO:0043570 maintenance of DNA repeat elements
Biological Process GO:0008584 male gonad development
Biological Process GO:0006298 mismatch repair
Biological Process GO:0006312 mitotic recombination
Biological Process GO:0045910 negative regulation of DNA recombination
Biological Process GO:0043524 negative regulation of neuron apoptotic process
Biological Process GO:0048298 positive regulation of isotype switching to IgA isotypes
Biological Process GO:0048304 positive regulation of isotype switching to IgG isotypes
Biological Process GO:0010224 response to UV-B
Biological Process GO:0010165 response to X-ray
Biological Process GO:0016447 somatic recombination of immunoglobulin gene segments
Biological Process GO:0002204 somatic recombination of immunoglobulin genes involved in immune response

Reference

[1] Yang D, Yin J, Shan L, Yi X, Zhang W et al.. Identification of lysine-lactylated substrates in gastric cancer cells.. iScience 25(7):104630. 2022 Jul 15. PMID: 35800753.

[2] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.

[3] He C, Zhang J, Bai X, Lu C, Zhang K. Lysine lactylation-based insight to understanding the characterization of cervical cancer.. Biochim Biophys Acta Mol Basis Dis 1870(7):167356. 2024 Oct. PMID: 39025375.

[4] Guo X, Ren X, Yan C, Huang H. Quantitative Proteomics Reveals the Role of Lysine Lactylation in Lenalidomide-Resistance in Multiple Myeloma Cells.. ACS Chem Biol 20(7):1728-1738. 2025 Jul 18. PMID: 40590393.

[5] He J, Lai T, Zhou Z, Yang H, Lei Z et al.. Multiomics profiling reveals the involvement of protein lactylation in nonhomologous end joining pathway conferring radioresistance in lung adenocarcinoma cell.. Sci Rep 15(1):24651. 2025 Jul 9. PMID: 40634431.

[6] Wu Q, Li Z, Gong T, Zheng X, Zhou X et al.. Porphyromonas gingivalis infection induces lysine lactylation reprogramming in human umbilical vein endothelial cells.. Front Cell Infect Microbiol 16:1706727. 2026. PMID: 41696360.