|
|
|
|
|
|
Description:
DNA mismatch repair protein Msh2 (MutS protein homolog 2).
Molecular weight: 10474
View which proteins in this organism that is involved with DNA Repair;
classified after biological processes (using data from the GOA project):
DNA repair( GO:0006281 ) mismatch repair( GO:0006298 ) postreplication repair( GO:0006301 )
Important dates:
01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
01-NOV-1995, sequence version 1.
07-MAR-2006, entry version 60.
Phylogenetic order:
Eukaryota Metazoa Chordata Craniata Vertebrata Euteleostomi Mammalia Eutheria Euarchontoglires Primates Catarrhini Hominidae Homo.
To calculate the pI (Isoelectric point - the pH where a protein has a neutral charge),
go to this page and enter the protein ID (e.g 3MG_ECOLI): http://us.expasy.org/tools/pi_tool.html
Links to references in other databases for protein MSH2_HUMAN:
| Database | Pointer | Add. info#1 | Add. info#2 |
| EMBL | U03911 | AAA18643.1 | - |
| EMBL | U04045 | AAA61870.1 | - |
| EMBL | U41221 | AAA82080.1 | ALT_SEQ |
| EMBL | U41206 | AAA82080.1 | JOINED |
| EMBL | U41207 | AAA82080.1 | JOINED |
| EMBL | U41208 | AAA82080.1 | JOINED |
| EMBL | U41210 | AAA82080.1 | JOINED |
| EMBL | U41211 | AAA82080.1 | JOINED |
| EMBL | U41212 | AAA82080.1 | JOINED |
| EMBL | U41213 | AAA82080.1 | JOINED |
| EMBL | U41214 | AAA82080.1 | JOINED |
| EMBL | U41215 | AAA82080.1 | JOINED |
| EMBL | U41216 | AAA82080.1 | JOINED |
| EMBL | U41217 | AAA82080.1 | JOINED |
| EMBL | U41218 | AAA82080.1 | JOINED |
| EMBL | U41219 | AAA82080.1 | JOINED |
| EMBL | U41220 | AAA82080.1 | JOINED |
| EMBL | L47583 | AAB59564.1 | - |
| EMBL | L47582 | AAB59565.1 | - |
| EMBL | L47581 | AAA76858.1 | - |
| EMBL | AY601851 | AAS99351.1 | - |
| EMBL | BC021566 | AAH21566.1 | - |
| EMBL | AF066081 | AAC27930.1 | ALT_FRAME |
| PIR | I64819 | I64819. | |
| HSSP | P23909 | 1NG9 | |
| Ensembl | ENSG00000095002 | Homo sapiens.1 | |
| H-InvDB | HIX0022211 | -.1 | |
| HGNC | HGNC:7325 | MSH2.1 | |
| MIM | 120435 | phenotype. | |
| MIM | 158320 | phenotype. | |
| MIM | 608089 | phenotype. | |
| MIM | 609309 | gene. | |
| GO | GO:0005634 | C:nucleus | NAS. |
| GO | GO:0003677 | F:DNA binding | IDA. |
| GO | GO:0006298 | P:mismatch repair | IDA. |
| GO | GO:0006301 | P:postreplication repair | IDA. |
| InterPro | IPR011184 | MSH2. | |
| InterPro | IPR000432 | MutS_C. | |
| InterPro | IPR007860 | MutS_II. | |
| InterPro | IPR007696 | MutS_III. | |
| InterPro | IPR007861 | MutS_IV. | |
| InterPro | IPR007695 | MutS_N. | |
| Pfam | PF01624 | MutS_I | 1. |
| Pfam | PF05188 | MutS_II | 1. |
| Pfam | PF05192 | MutS_III | 1. |
| Pfam | PF05190 | MutS_IV | 1. |
| Pfam | PF00488 | MutS_V | 1. |
| PIRSF | PIRSF005813 | MSH2 | 1. |
| ProDom | PD001263 | MutS_C | 1. |
| SMART | SM00534 | MUTSac | 1. |
| SMART | SM00533 | MUTSd | 1. |
| PROSITE | PS00486 | DNA_MISMATCH_REPAIR_2 | 1. |
Keywords:
Anti-oncogene; ATP-binding; Cell cycle; Disease mutation; DNA damage; DNA repair; DNA-binding; Hereditary nonpolyposis colorectal cancer; Nuclear protein; Nucleotide-binding; Polymorphism.
References:
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX MEDLINE=94073959; PubMed=8252616; DOI=10.1016/0092-8674(93)90546-3;
RA Fishel R., Lescoe M., Rao M., Copeland N.G., Jenkins N.A., Garber J.,
RA Kane M.F., Kolodner R.D.;
RT "The human mutator gene homolog MSH2 and its association with
RT hereditary nonpolyposis colon cancer.";
RL Cell 75:1027-1038(1993).
RN [2]
RP ERRATUM.
RX MEDLINE=94208055; PubMed=8156592;
RA Fishel R., Lescoe M., Rao M., Copeland N.G., Jenkins N.A., Garber J.,
RA Kane M.F., Kolodner R.D.;
RL Cell 77:167-167(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS HNPCC1 LEU-622 AND TYR-639.
RX MEDLINE=94084796; PubMed=8261515; DOI=10.1016/0092-8674(93)90330-S;
RA Leach F.S., Nicolaides N.C., Papadopoulos N., Liu B., Jen J.,
RA Parsons R., Peltomaeki P., Sistonen P., Aaltonen L.A.,
RA Nystroem-Lahti M., Guan X.-Y., Zhang J., Meltzer P.S., Yu J.-W.,
RA Kao F.-T., Chen D.J., Cerosaletti K.M., Fournier R.E.K., Todd S.,
RA Lewis T., Leach R.J., Naylor S.L., Weissenbach J., Mecklin J.-P.,
RA Jaervinen H., Petersen G.M., Hamilton S.R., Green J., Jass J.,
RA Watson P., Lynch H.T., Trent J.M., de la Chapelle A., Kinzler K.W.,
RA Vogelstein B.;
RT "Mutations of a mutS homolog in hereditary nonpolyposis colorectal
RT cancer.";
RL Cell 75:1215-1225(1993).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND DISEASE.
RX MEDLINE=95229152; PubMed=7713503;
RA Kolodner R.D., Hall N.R., Lipford J., Kane M.F., Rao M.R.S.,
RA Morrison P., Wirth L., Finan P.J., Burn J., Chapman P., Earabino C.,
RA Merchant E., Bishop D.T.;
RT "Structure of the human MSH2 locus and analysis of two Muir-Torre
RT kindreds for msh2 mutations.";
RL Genomics 24:516-526(1994).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT HIS-96.
RX MEDLINE=95243220; PubMed=7726159;
RA Wijnen J., Vasen H., Khan P.M., Menko F.H., van der Klift H.,
RA van Leeuwen C., van den Broek M., van Leeuwen-Cornelisse I.,
RA Nagengast F., Meijers-Heijboer A., Lindhout D., Griffioen G., Cats A.,
RA Kleibeuker J., Varesco L., Bertario L., Bisgaard M.-L., Mohr J.,
RA Fodde R.;
RT "Seven new mutations in hMSH2, an HNPCC gene, identified by denaturing
RT gradient-gel electrophoresis.";
RL Am. J. Hum. Genet. 56:1060-1066(1995).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS MET-8; CYS-43;
RP SER-127; ASP-322 AND PHE-390.
RA Livingston R.J., Rieder M.J., Chung M.-W., Ritchie T.K., Olson A.N.,
RA Nguyen C.P., Nguyen D.A., Poel C.L., Robertson P.D., Schackwitz W.S.,
RA Sherwood J.K., Sherwood A.M., Leithauser B.J., Nickerson D.A.;
RT "NIEHS-SNPs, environmental genome project, NIEHS ES15478, Department
RT of Genome Sciences, Seattle, WA (URL: http://egp.gs.washington.edu).";
RL Submitted (APR-2004) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Muscle;
RX MEDLINE=22388257; PubMed=12477932; DOI=10.1073/pnas.242603899;
RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G.,
RA Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D.,
RA Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K.,
RA Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F.,
RA Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L.,
RA Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E.,
RA Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C.,
RA Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J.,
RA Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H.,
RA Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W.,
RA Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A.,
RA Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A.,
RA Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G.,
RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C.,
RA Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M.,
RA Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E.,
RA Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.;
RT "Generation and initial analysis of more than 15,000 full-length human
RT and mouse cDNA sequences.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002).
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 375-425.
RC TISSUE=Blood;
RA Corvello C.M., Bevilacqua R.A.U., Rossi B.M., Simpson A.J.G.;
RT "A novel germline mutation at exon 7 of the hMSH2 gene (417 del G) in
RT a large HNPCC Brazilian kindred.";
RL Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP DNA-BINDING.
RX MEDLINE=95007585; PubMed=7923193;
RA Fishel R., Ewel A., Lescoe M.K.;
RT "Purified human MSH2 protein binds to DNA containing mismatched
RT nucleotides.";
RL Cancer Res. 54:5539-5542(1994).
RN [10]
RP DNA-BINDING.
RX PubMed=8769132; DOI=10.1006/bbrc.1996.1168;
RA Whitehouse A., Taylor G.R., Deeble J., Phillips S.E., Meredith D.M.,
RA Markham A.F.;
RT "A carboxy terminal domain of the hMSH-2 gene product is sufficient
RT for binding specific mismatched oligonucleotides.";
RL Biochem. Biophys. Res. Commun. 225:289-295(1996).
RN [11]
RP INTERACTION WITH EXO1.
RX MEDLINE=99002645; PubMed=9788596;
RA Schmutte C., Marinescu R.C., Sadoff M.M., Guerrette S., Overhauser J.,
RA Fishel R.;
RT "Human exonuclease I interacts with the mismatch repair protein
RT hMSH2.";
RL Cancer Res. 58:4537-4542(1998).
RN [12]
RP IDENTIFICATION OF MSH2 AS MEMBER OF BASC.
RX MEDLINE=20245492; PubMed=10783165; DOI=10.1101/gad.827000;
RA Wang Y., Cortez D., Yazdi P., Neff N., Elledge S.J., Qin J.;
RT "BASC, a super complex of BRCA1-associated proteins involved in the
RT recognition and repair of aberrant DNA structures.";
RL Genes Dev. 14:927-939(2000).
RN [13]
RP INTERACTION WITH EXO1, AND TISSUE SPECIFICITY.
RX MEDLINE=20316168; PubMed=10856833; DOI=10.1016/S0921-8777(00)00012-4;
RA Rasmussen L.J., Rasmussen M., Lee B.-I., Rasmussen A.K.,
RA Wilson D.M. III, Nielsen F.C., Bisgaard H.C.;
RT "Identification of factors interacting with hMSH2 in the fetal liver
RT utilizing the yeast two-hybrid system. In vivo interaction through the
RT C-terminal domains of hEXO1 and hMSH2 and comparative expression
RT analysis.";
RL Mutat. Res. 460:41-52(2000).
RN [14]
RP INTERACTION WITH EXO1.
RX PubMed=11427529; DOI=10.1074/jbc.M102670200;
RA Schmutte C., Sadoff M.M., Shim K.-S., Acharya S., Fishel R.;
RT "The interaction of DNA mismatch repair proteins with human
RT exonuclease I.";
RL J. Biol. Chem. 276:33011-33018(2001).
RN [15]
RP INTERACTION WITH EXO1.
RX PubMed=11429708; DOI=10.1038/sj/onc/1204467;
RA Jaeger A.C., Rasmussen M., Bisgaard H.C., Singh K.K., Nielsen F.C.,
RA Rasmussen L.J.;
RT "HNPCC mutations in the human DNA mismatch repair gene hMLH1 influence
RT assembly of hMutLalpha and hMLH1-hEXO1 complexes.";
RL Oncogene 20:3590-3595(2001).
RN [16]
RP INTERACTION WITH EXO1.
RA Sun X., Zheng L., Shen B.;
RT "Functional alterations of human exonuclease 1 mutants identified in
RT atypical hereditary nonpolyposis colorectal cancer syndrome.";
RL Cancer Res. 62:6026-6030(2002).
RN [17]
RP INTERACTION WITH ATR, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=14657349; DOI=10.1073/pnas.2536810100;
RA Wang Y., Qin J.;
RT "MSH2 and ATR form a signaling module and regulate two branches of the
RT damage response to DNA methylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:15387-15392(2003).
RN [18]
RP INTERACTION WITH EXO1.
RX PubMed=14676842; DOI=10.1038/sj.onc.1207265;
RA Nielsen F.C., Jaeger A.C., Luetzen A., Bundgaard J.R., Rasmussen L.J.;
RT "Characterization of human exonuclease 1 in complex with mismatch
RT repair proteins, subcellular localization and association with PCNA.";
RL Oncogene 23:1457-1468(2004).
RN [19]
RP REVIEW.
RX MEDLINE=94310688; PubMed=8036718; DOI=10.1016/0168-9525(94)90093-0;
RA Jiricny J.;
RT "Colon cancer and DNA repair: have mismatches met their match?";
RL Trends Genet. 10:164-168(1994).
RN [20]
RP REVIEW ON VARIANTS.
RX MEDLINE=97403931; PubMed=9259192;
RX DOI=10.1002/(SICI)1098-1004(1997)10:2<89::AID-HUMU1>3.3.CO;2-K;
RA Papadopoulos N., Lindblom A.;
RT "Molecular basis of HNPCC: mutations of MMR genes.";
RL Hum. Mutat. 10:89-99(1997).
RN [21]
RP VARIANT HNPCC1 ASN-596 DEL.
RX MEDLINE=95179130; PubMed=7874129;
RA Mary J.-L., Bishop T., Kolodner R.D., Lipford J.R., Kane M.F.,
RA Weber W., Torhorst J., Mueller H., Spycher M., Scott R.J.;
RT "Mutational analysis of the hMSH2 gene reveals a three base pair
RT deletion in a family predisposed to colorectal cancer development.";
RL Hum. Mol. Genet. 3:2067-2069(1994).
RN [22]
RP VARIANTS PHE-390 AND LYS-419.
RX MEDLINE=96305098; PubMed=8690195;
RA Konishi M., Kikuchi-Yanoshita R., Tanaka K., Muraoka M., Onda A.,
RA Okumura Y., Kishi N., Iwama T., Mori T., Koike M., Ushio K., Chiba M.,
RA Nomizu S., Konishi F., Utsunomiya J., Miyaki M.;
RT "Molecular nature of colon tumors in hereditary nonpolyposis colon
RT cancer, familial polyposis, and sporadic colon cancer.";
RL Gastroenterology 111:307-317(1996).
RN [23]
RP VARIANT ASP-322.
RX MEDLINE=96163505; PubMed=8566964;
RA Maliaka Y.K., Chudina A.P., Belev N.F., Alday P., Bochkov N.P.,
RA Buerstedde J.-M.;
RT "CpG dinucleotides in the hMSH2 and hMLH1 genes are hotspots for HNPCC
RT mutations.";
RL Hum. Genet. 97:251-255(1996).
RN [24]
RP VARIANT HNPCC1 ASN-596 DEL, AND VARIANT HIS-167.
RX MEDLINE=97026284; PubMed=8872463; DOI=10.1093/hmg/5.9.1245;
RA Moslein G., Tester D.J., Lindor N.M., Honchel R., Cunningham J.M.,
RA French A.J., Halling K.C., Schwab M., Goretzki P., Thibodeau S.N.;
RT "Microsatellite instability and mutation analysis of hMSH2 and hMLH1
RT in patients with sporadic, familial and hereditary colorectal
RT cancer.";
RL Hum. Mol. Genet. 5:1245-1252(1996).
RN [25]
RP VARIANT CRC TYR-506.
RX MEDLINE=96390800; PubMed=8797773;
RA Han H.-J., Yuan Y., Ku J.-L., Oh J.-H., Won Y.-J., Kang K.J.,
RA Kim K.Y., Kim S., Kim C.Y., Kim J.-P., Oh N.-G., Lee K.H., Choe K.J.,
RA Nakamura Y., Park J.-G.;
RT "Germline mutations of hMLH1 and hMSH2 genes in Korean hereditary
RT nonpolyposis colorectal cancer.";
RL J. Natl. Cancer Inst. 88:1317-1319(1996).
RN [26]
RP VARIANT HNPCC1 GLN-46.
RX MEDLINE=96293410; PubMed=8700523;
RA Bubb V.J., Curtis L.J., Cunningham C., Dunlop M.G., Carothers A.D.,
RA Morris R.G., White S., Bird C.C., Wyllie A.H.;
RT "Microsatellite instability and the role of hMSH2 in sporadic
RT colorectalcancer.";
RL Oncogene 12:2641-2649(1996).
RN [27]
RP VARIANTS HNPCC1 THR-305; ASN-596 DEL AND THR-834.
RX MEDLINE=97456423; PubMed=9311737;
RA Wijnen J., Khan P.M., Vasen H., van der Klift H., Mulder A.,
RA van Leeuwen-Cornelisse I., Bakker B., Losekoot M., Moeller P.,
RA Fodde R.;
RT "Hereditary nonpolyposis colorectal cancer families not complying with
RT the Amsterdam criteria show extremely low frequency of mismatch-
RT repair-gene mutations.";
RL Am. J. Hum. Genet. 61:329-335(1997).
RN [28]
RP VARIANT HNPCC1 CYS-323.
RX MEDLINE=97382414; PubMed=9240418; DOI=10.1006/bbrc.1997.6942;
RA Akiyama Y., Tsubouchi N., Yuasa Y.;
RT "Frequent somatic mutations of hMSH3 with reference to microsatellite
RT instability in hereditary nonpolyposis colorectal cancers.";
RL Biochem. Biophys. Res. Commun. 236:248-252(1997).
RN [29]
RP VARIANT SER-596.
RX MEDLINE=97147120; PubMed=8993976;
RX DOI=10.1002/(SICI)1098-2264(199701)18:1<8::AID-GCC2>3.0.CO;2-7;
RA Viel A., Genuardi M., Capozzi E., Leonardi F., Bellacosa A.,
RA Paravatou-Petsotas M., Pomponi M.G., Fornasarig M., Percesepe A.,
RA Roncucci L., Tamassia M.G., Benatti P., Ponz de Leon M., Valenti A.,
RA Covino M., Anti M., Foletto M., Boiocchi M., Neri G.;
RT "Characterization of MSH2 and MLH1 mutations in Italian families with
RT hereditary nonpolyposis colorectal cancer.";
RL Genes Chromosomes Cancer 18:8-18(1997).
RN [30]
RP VARIANT ASP-322.
RX MEDLINE=97242567; PubMed=9087566;
RX DOI=10.1002/(SICI)1098-2264(199704)18:4<269::AID-GCC4>3.3.CO;2-9;
RA Wu Y., Nystroem-Lahti M., Osinga J., Looman M.W.G., Peltomaeki P.,
RA Aaltonen L.A., de la Chapelle A., Hofstra R.M.W., Buys C.H.C.M.;
RT "MSH2 and MLH1 mutations in sporadic replication error-positive
RT colorectal carcinoma as assessed by two-dimensional DNA
RT electrophoresis.";
RL Genes Chromosomes Cancer 18:269-278(1997).
RN [31]
RP VARIANT HNPCC1 VAL-562.
RX MEDLINE=97201114; PubMed=9048925; DOI=10.1007/s004390050343;
RA Beck N.E., Tomlinson I.P.M., Homfray T., Frayling I., Hodgson S.V.,
RA Harocopos C.J., Bodmer W.F.;
RT "Use of SSCP analysis to identify germline mutations in HNPCC families
RT fulfilling the Amsterdam criteria.";
RL Hum. Genet. 99:219-224(1997).
RN [32]
RP VARIANT HNPCC1 PHE-697, AND VARIANT ASP-322.
RX MEDLINE=97442278; PubMed=9298827;
RX DOI=10.1002/(SICI)1098-1004(1997)10:3<241::AID-HUMU12>3.3.CO;2-3;
RA Wehner M., Buschhausen L., Lamberti C., Kruse R., Caspari R.,
RA Propping P., Friedl W.;
RT "Hereditary nonpolyposis colorectal cancer (HNPCC): eight novel
RT germline mutations in hMSH2 or hMLH1 genes.";
RL Hum. Mutat. 10:241-244(1997).
RN [33]
RP VARIANT HNPCC1 265-VAL--GLN-314 DEL, AND VARIANTS GLY-641 AND VAL-770.
RX MEDLINE=98386069; PubMed=9718327;
RA Farrington S.M., Lin-Goerke J., Ling J., Wang Y., Burczak J.D.,
RA Robbins D.J., Dunlop M.G.;
RT "Systematic analysis of hMSH2 and hMLH1 in young colon cancer patients
RT and controls.";
RL Am. J. Hum. Genet. 63:749-759(1998).
RN [34]
RP VARIANT GLIOMA ARG-199.
RX MEDLINE=98449379; PubMed=9777949;
RA Leung S.Y., Chan T.L., Chung L.P., Chan A.S.Y., Fan Y.W., Hung K.N.,
RA Kwong W.K., Ho J.W.C., Yuen S.T.;
RT "Microsatellite instability and mutation of DNA mismatch repair genes
RT in gliomas.";
RL Am. J. Pathol. 153:1181-1188(1998).
RN [35]
RP VARIANT CRC TYR-506, AND VARIANT HNPCC1 ILE-688.
RX MEDLINE=98218529; PubMed=9559627;
RA Yuan Y., Han H.-J., Zheng S., Park J.-G.;
RT "Germline mutations of hMLH1 and hMSH2 genes in patients with
RT suspected hereditary nonpolyposis colorectal cancer and sporadic
RT early-onset colorectal cancer.";
RL Dis. Colon Rectum 41:434-440(1998).
RN [36]
RP VARIANT ASP-322.
RX MEDLINE=99147408; PubMed=10023327; DOI=10.1016/S0959-8049(98)00217-2;
RA Liu T., Stathopoulos P., Lindblom P., Rubio C., Wasteson Arver B.,
RA Iselius L., Holmberg E., Groenberg H., Lindblom A.;
RT "MSH2 codon 322 Gly to Asp seems not to confer an increased risk for
RT colorectal cancer susceptibility.";
RL Eur. J. Cancer 34:1981-1981(1998).
RN [37]
RP VARIANT PHE-390.
RX MEDLINE=98284542; PubMed=9621522; DOI=10.1007/s100380050057;
RA Okamura S., Koyama K., Miyoshi Y., Monden M., Takami M.;
RT "Novel germline mutations of hMSH2 in a patient with hereditary
RT nonpolyposis colorectal cancer 'HNPCC' and in a patient with six
RT primary cancers.";
RL J. Hum. Genet. 43:143-145(1998).
RN [38]
RP CHARACTERIZATION OF VARIANTS ASP-322; PHE-390; LYS-419; TYR-506;
RP PRO-524; LEU-622 AND PHE-697.
RX MEDLINE=99400995; PubMed=10469597; DOI=10.1016/S0960-9822(99)80396-0;
RA Drotschmann K., Clark A.B., Kunkel T.A.;
RT "Mutator phenotypes of common polymorphisms and missense mutations in
RT MSH2.";
RL Curr. Biol. 9:907-910(1999).
RN [39]
RP VARIANT HNPCC1 PRO-636.
RX MEDLINE=99456130; PubMed=10528862;
RA Yuan Z.Q., Wong N., Foulkes W.D., Alpert L., Manganaro F.,
RA Andreutti-Zaugg C., Iggo R., Anthony K., Hsieh E., Redston M.,
RA Pinsky L., Trifiro M., Gordon P.H., Lasko D.;
RT "A missense mutation in both hMSH2 and APC in an Ashkenazi Jewish
RT HNPCC kindred: implications for clinical screening.";
RL J. Med. Genet. 36:792-793(1999).
RN [40]
RP VARIANTS HNPCC1 ILE-688 AND GLU-845, AND VARIANT MET-8.
RX MEDLINE=20241830; PubMed=10777691; DOI=10.1006/bbrc.2000.2547;
RA Nomura S., Sugano K., Kashiwabara H., Taniguchi T., Fukayama N.,
RA Fujita S., Akasu T., Moriya Y., Ohhigashi S., Kakizoe T., Sekiya T.;
RT "Enhanced detection of deleterious and other germline mutations of
RT hMSH2 and hMLH1 in Japanese hereditary nonpolyposis colorectal cancer
RT kindreds.";
RL Biochem. Biophys. Res. Commun. 271:120-129(2000).
RN [41]
RP VARIANT ASP-322.
RX MEDLINE=20178226; PubMed=10713887; DOI=10.1038/sj.ejhg.5200393;
RA Fidalgo P., Almeida M.R., West S., Gaspar C., Maia L., Wijnen J.,
RA Albuquerque C., Curtis A., Cravo M., Fodde R., Leitao C.N., Burn J.;
RT "Detection of mutations in mismatch repair genes in Portuguese
RT families with hereditary non-polyposis colorectal cancer (HNPCC) by a
RT multi-method approach.";
RL Eur. J. Hum. Genet. 8:49-53(2000).
RN [42]
RP VARIANTS HNPCC1 ARG-692 AND ARG-697.
RX MEDLINE=20081064; PubMed=10612836;
RX DOI=10.1002/(SICI)1098-1004(200001)15:1<116::AID-HUMU24>3.0.CO;2-Q;
RA Isidro G., Veiga I., Matos P., Almeida S., Bizarro S., Marshall B.,
RA Baptista M., Leite J., Regateiro F., Soares J., Castedo S.,
RA Boavida M.G.;
RT "Four novel MSH2 / MLH1 gene mutations in Portuguese HNPCC families.";
RL Hum. Mutat. 15:116-116(2000).
RN [43]
RP VARIANTS HNPCC1 ASP-161; VAL-216 AND ARG-554.
RX MEDLINE=21583375; PubMed=11726306;
RA Mueller-Koch Y., Kopp R., Lohse P., Baretton G., Stoetzer A., Aust D.,
RA Daum J., Kerker B., Gross M., Dietmeier W., Holinski-Feder E.;
RT "Sixteen rare sequence variants of the hMLH1 and hMSH2 genes found in
RT a cohort of 254 suspected HNPCC (hereditary non-polyposis colorectal
RT cancer) patients: mutations or polymorphisms?";
RL Eur. J. Med. Res. 6:473-482(2001).
RN [44]
RP CHARACTERIZATION OF VARIANTS ASP-322; LEU-622 AND TYR-639.
RX MEDLINE=21439334; PubMed=11555625; DOI=10.1093/hmg/10.18.1889;
RA Ellison A.R., Lofing J., Bitter G.A.;
RT "Functional analysis of human MLH1 and MSH2 missense variants and
RT hybrid human-yeast MLH1 proteins in Saccharomyces cerevisiae.";
RL Hum. Mol. Genet. 10:1889-1900(2001).
RN [45]
RP INVOLVEMENT IN MULTIPLE CAFE-AU-LAIT SPOTS WITH LEUKEMIA.
RA Whiteside D., McLeod R., Graham G., Steckley J.L., Booth K.,
RA Somerville M.J., Andrew S.E.;
RT "A homozygous germ-line mutation in the human MSH2 gene predisposes to
RT hematological malignancy and multiple cafe-au-lait spots.";
RL Cancer Res. 62:359-362(2002).
RN [46]
RP VARIANTS HNPCC1 GLY-163 AND GLY-660.
RX PubMed=14635101; DOI=10.1002/humu.10291;
RA Taylor C.F., Charlton R.S., Burn J., Sheridan E., Taylor G.R.;
RT "Genomic deletions in MSH2 or MLH1 are a frequent cause of hereditary
RT non-polyposis colorectal cancer: identification of novel and recurrent
RT deletions by MLPA.";
RL Hum. Mutat. 22:428-433(2003).
Feature:
CHAIN 1 934 DNA mismatch repair protein Msh2.
/FTId=PRO_0000115183.
NP_BIND 669 676 ATP (Potential).
REGION 601 671 Interaction with EXO1.
VARIANT 8 8 T -> M (in dbSNP:17217716).
/FTId=VAR_013171.
VARIANT 43 43 Y -> C.
/FTId=VAR_019233.
VARIANT 46 46 H -> Q (in HNPCC1).
/FTId=VAR_004470.
VARIANT 96 96 R -> H.
/FTId=VAR_004471.
VARIANT 127 127 N -> S (in dbSNP:17217772).
/FTId=VAR_019234.
VARIANT 139 139 N -> S (in HNPCC1).
/FTId=VAR_004472.
VARIANT 145 145 I -> M.
/FTId=VAR_004473.
VARIANT 161 161 V -> D (in HNPCC1; could be a
polymorphism).
/FTId=VAR_012936.
VARIANT 163 163 V -> G (in HNPCC1).
/FTId=VAR_022670.
VARIANT 167 167 D -> H.
/FTId=VAR_004474.
VARIANT 199 199 C -> R (in glioma).
/FTId=VAR_012937.
VARIANT 216 216 I -> V (in HNPCC1; could be a
polymorphism).
/FTId=VAR_012938.
VARIANT 265 314 Missing (in HNPCC1).
/FTId=VAR_004475.
VARIANT 305 305 A -> T (in HNPCC1).
/FTId=VAR_004476.
VARIANT 322 322 G -> D (common polymorphism; may be
associated with increased colorectal
cancer susceptibility; the equivalent
substitution in yeast reduces the
mismatch repair efficiency in vitro;
dbSNP:4987188).
/FTId=VAR_004477.
VARIANT 323 323 S -> C (in HNPCC1).
/FTId=VAR_012939.
VARIANT 390 390 L -> F (may be associated with HNPCC1;
the equivalent substitution in yeast
partially affects mismatch repair in
vitro).
/FTId=VAR_004478.
VARIANT 419 419 Q -> K (the equivalent substitution in
yeast partially affects mismatch repair
in vitro).
/FTId=VAR_012940.
VARIANT 506 506 D -> Y (in CRC; sporadic; early onset;
the equivalent substitution in yeast
partially affects mismatch repair in
vitro).
/FTId=VAR_012941.
VARIANT 524 524 R -> P (in HNPCC1; defective in mismatch
repair activity).
/FTId=VAR_004479.
VARIANT 554 554 S -> R (in HNPCC1; could be a
polymorphism).
/FTId=VAR_012942.
VARIANT 562 562 E -> V (in HNPCC1).
/FTId=VAR_004480.
VARIANT 596 596 N -> S.
/FTId=VAR_012943.
VARIANT 596 596 Missing (in HNPCC1).
/FTId=VAR_004481.
VARIANT 622 622 P -> L (in HNPCC1; the equivalent
substituion in yeast causes loss of
function in a mismatch repair assay).
/FTId=VAR_004482.
VARIANT 636 636 A -> P (in HNPCC1; partial functional
loss).
/FTId=VAR_012944.
VARIANT 639 639 H -> Y (in HNPCC1; the equivalent
substitution in yeast does not affect
mismatch repair efficiency in vitro).
/FTId=VAR_004483.
VARIANT 641 641 C -> G.
/FTId=VAR_004484.
VARIANT 660 660 D -> G (in HNPCC1).
/FTId=VAR_022671.
VARIANT 674 674 G -> S (in HNPCC1; somatic mutation).
/FTId=VAR_004485.
VARIANT 688 688 M -> I (in HNPCC1).
/FTId=VAR_012945.
VARIANT 692 692 G -> R (in HNPCC1).
/FTId=VAR_009250.
VARIANT 697 697 C -> F (in HNPCC1; the equivalent
substitution in yeast causes loss of
function in a mismatch repair assay).
/FTId=VAR_004486.
VARIANT 697 697 C -> R (in HNPCC1).
/FTId=VAR_009251.
VARIANT 770 770 I -> V.
/FTId=VAR_004487.
VARIANT 834 834 A -> T (in HNPCC1).
/FTId=VAR_004488.
VARIANT 845 845 K -> E (in HNPCC1).
/FTId=VAR_013172.
VARIANT 905 905 T -> R (in HNPCC1).
/FTId=VAR_004489.
Comments:
-!- FUNCTION: Involved in postreplication mismatch repair. Binds
specifically to DNA containing mismatched nucleotides thereby
marking the region to be excised.
-!- SUBUNIT: Heterodimer of MSH2 and MSH6 (GTBP). 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.
-!- SUBCELLULAR LOCATION: Nucleus (Potential).
-!- TISSUE SPECIFICITY: Ubiquitously expressed.
-!- DISEASE: Defects in MSH2 are the cause of hereditary non-polyposis
colorectal cancer type 1 (HNPCC1) [MIM:120435]. Mutations in more
than one gene locus can be involved alone or in combination in the
production of the HNPCC phenotype (also called Lynch syndrome).
Most families with clinically recognized HNPCC have mutations in
either MLH1 or MSH2 genes. HNPCC is an autosomal, dominantly
inherited disease associated with marked increase in cancer
susceptibility. It is characterized by a familial predisposition
to early onset colorectal carcinoma (CRC) and extra-colonic
cancers of the gastrointestinal, urological and female
reproductive tracts. HNPCC is reported to be the most common form
of inherited colorectal cancer in the Western world. Cancers in
HNPCC originate within benign neoplastic polyps termed adenomas.
Clinically, HNPCC is often divided into two subgroups. Type I:
hereditary predisposition to colorectal cancer, a young age of
onset, and carcinoma observed in the proximal colon. Type II:
patients have an increased risk for cancers in certain tissues
such as the uterus, ovary, breast, stomach, small intestine, skin,
and larynx in addition to the colon. Diagnosis of classical HNPCC
is based on the Amsterdam criteria: 3 or more relatives affected
by colorectal cancer, one a first degree relative of the other
two; 2 or more generation affected; 1 or more colorectal cancers
presenting before 50 years of age; exclusion of hereditary
polyposis syndromes. The term "suspected HNPCC" or "incomplete
HNPCC" can be used to describe families who do not or only
partially fulfill the Amsterdam criteria, but in whom a genetic
basis for colon cancer is strongly suspected. MSH2 mutations may
predispose to hematological malignancies and multiple cafe-au-lait
spots.
-!- DISEASE: Defects in MSH2 are a cause of Muir-Torre syndrome (MTS)
[MIM:158320]. MTS is a rare autosomal dominant disorder
characterized by sebaceous neoplasms and visceral malignancy.
-!- DISEASE: Defects in MSH2 are a cause of susceptibility to
endometrial cancer [MIM:608089].
-!- SIMILARITY: Belongs to the DNA mismatch repair mutS family.
-!- CAUTION: Ref.8 sequence differs from that shown due to a
frameshift in position 417. The frameshift is caused by a single
nucleotide deletion which is found in a HNPCC kindred.
-!- DATABASE: NAME=Hereditary non-polyposis colorectal cancer db;
WWW="http://www.nfdht.nl/".
-----------------------------------------------------------------------
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
Distributed under the Creative Commons Attribution-NoDerivs License
-----------------------------------------------------------------------
Sequence length: 934
MAVQPKETLQ LESAAEVGFV RFFQGMPEKP TTTVRLFDRG DFYTAHGEDA LLAAREVFKT
QGVIKYMGPA GAKNLQSVVL SKMNFESFVK DLLLVRQYRV EVYKNRAGNK ASKENDWYLA
YKASPGNLSQ FEDILFGNND MSASIGVVGV KMSAVDGQRQ VGVGYVDSIQ 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 IKLDSSAQFG YYFRVTCKEE KVLRNNKNFS
TVDIQKNGVK FTNSKLTSLN EEYTKNKTEY EEAQDAIVKE IVNISSGYVE PMQTLNDVLA
QLDAVVSFAH VSNGAPVPYV RPAILEKGQG RIILKASRHA CVEVQDEIAF IPNDVYFEKD
KQMFHIITGP NMGGKSTYIR QTGVIVLMAQ IGCFVPCESA EVSIVDCILA RVGAGDSQLK
GVSTFMAEML ETASILRSAT KDSLIIIDEL GRGTSTYDGF GLAWAISEYI ATKIGAFCMF
ATHFHELTAL ANQIPTVNNL HVTALTTEET LTMLYQVKKG VCDQSFGIHV AELANFPKHV
IECAKQKALE LEEFQYIGES QGYDIMEPAA KKCYLEREQG EKIIQEFLSK VKQMPFTEMS
EENITIKLKQ LKAEVIAKNN SFVNEIISRI KVTT