| |
LOCUS MLH1_HUMAN 756 aa linear PRI 15-JUN-2002
DEFINITION DNA mismatch repair protein Mlh1 (MutL protein homolog 1).
ACCESSION P40692
VERSION P40692 GI:730028
DBSOURCE swissprot: locus MLH1_HUMAN, accession P40692;
class: standard.
created: Feb 1, 1995.
sequence updated: Feb 1, 1995.
annotation updated: Jun 15, 2002.
xrefs: gi: 463988, gi: 463989, gi: 1079785, gi: 1079787, gi:
1079767, gi: 1079768, gi: 1079769, gi: 1079770, gi: 1079771, gi:
1079772, gi: 1079773, gi: 1079774, gi: 1079775, gi: 1079776, gi:
1079777, gi: 1079778, gi: 1079779, gi: 1079780, gi: 1079781, gi:
1079782, gi: 1079783, gi: 1079784, gi: 466461, gi: 466462, gi:
604367, gi: 604369, gi: 604349, gi: 604350, gi: 604351, gi: 604352,
gi: 604353, gi: 604354, gi: 604355, gi: 604356, gi: 604357, gi:
604358, gi: 604359, gi: 604361, gi: 604362, gi: 604363, gi: 604364,
gi: 604365, gi: 604366, gi: 631299
xrefs (non-sequence databases): HSSPP23367, MIM120436, MIM158320,
MIM276300, InterProIPR003594, InterProIPR002099, PfamPF01119,
PfamPF02518, PROSITEPS00058
KEYWORDS DNA repair; Nuclear protein; Disease mutation; Anti-oncogene;
Polymorphism; Hereditary nonpolyposis colorectal cancer.
SOURCE Homo sapiens
ORGANISM Homo sapiens
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo.
REFERENCE 1 (residues 1 to 756)
AUTHORS Bronner,C.E., Baker,S.M., Morrison,P.T., Warren,G., Smith,L.G.,
Lescoe,M.K., Kane,M.F., Earibino,C., Lipford,J., Lindblom,A.,
Tannergaard,P., Bollag,R.J., Godwin,A.R., Ward,D.C.,
Nordenskjoeld,M., Fishel,R., Kolodner,R.D. and Liskay,R.M.
TITLE Mutation in the DNA mismatch repair gene homologue hMLH1 is
associated with hereditary non-polyposis colon cancer
JOURNAL Nature 368 (6468), 258-261 (1994)
MEDLINE 94195398
PUBMED 8145827
REMARK SEQUENCE FROM N.A.
REFERENCE 2 (residues 1 to 756)
AUTHORS Kolodner,R.D., Hall,N.R., Lipford,J.R., Kane,M.F., Morrison,P.,
Finan,P.J., Burn,J., Chapman,P., Earabino,C., Merchant,E. and
Bishop,D.T.
TITLE Structure of the human MLH1 locus and analysis of a large
hereditary nonpolyposis colorectal carcinoma kindred for mlh1
mutations
JOURNAL Cancer Res. 55 (2), 242-248 (1995)
MEDLINE 95112274
PUBMED 7812952
REMARK SEQUENCE FROM N.A.
REFERENCE 3 (residues 1 to 756)
AUTHORS Papadopoulos,N., Nicolaides,N.C., Wei,Y.-F., Ruben,S.M.,
Carter,K.C., Rosen,C.A., Haseltine,W.A., Fleischmann,R.D.,
Fraser,C.M., Adams,M.D., Venter,J.C., Hamilton,S.R., Petersen,G.M.,
Watson,P., Lynch,H.T., Peltomaeki,P., Mecklin,J.-P., de la
Chapelle,A., Kinzler,K.W. and Vogelstein,B.
TITLE Mutation of a mutL homolog in hereditary colon cancer
JOURNAL Science 263 (5153), 1625-1629 (1994)
MEDLINE 94174309
PUBMED 8128251
REMARK SEQUENCE FROM N.A.
TISSUE=Gall bladder
REFERENCE 4 (residues 1 to 756)
AUTHORS Han,H.J., Maruyama,M., Baba,S., Park,J.G. and Nakamura,Y.
TITLE Genomic structure of human mismatch repair gene, hMLH1, and its
mutation analysis in patients with hereditary non-polyposis
colorectal cancer (HNPCC)
JOURNAL Hum. Mol. Genet. 4 (2), 237-242 (1995)
MEDLINE 95276736
PUBMED 7757073
REMARK SEQUENCE FROM N.A., AND VARIANTS HNPCC L-542; P-574; V-582 AND
T-618.
REFERENCE 5 (residues 1 to 756)
AUTHORS Wang,Y., Cortez,D., Yazdi,P., Neff,N., Elledge,S.J. and Qin,J.
TITLE BASC, a super complex of BRCA1-associated proteins involved in the
recognition and repair of aberrant DNA structures
JOURNAL Genes Dev. 14 (8), 927-939 (2000)
MEDLINE 20245492
PUBMED 10783165
REMARK IDENTIFICATION OF MLH1 AS MEMBER OF BASC.
REFERENCE 6 (residues 1 to 756)
AUTHORS Bapat,B., Xia,L., Madlensky,L., Mitri,A., Tonin,P., Narod,S.A. and
Gallinger,S.
TITLE The genetic basis of Muir-Torre syndrome includes the hMLH1 locus
JOURNAL Am. J. Hum. Genet. 59 (3), 736-739 (1996)
MEDLINE 96354569
PUBMED 8751876
REMARK DISEASE.
REFERENCE 7 (residues 1 to 756)
AUTHORS Papadopoulos,N. and Lindblom,A.
TITLE Molecular basis of HNPCC: mutations of MMR genes
JOURNAL Hum. Mutat. 10 (2), 89-99 (1997)
MEDLINE 97403931
PUBMED 9259192
REMARK REVIEW ON VARIANTS.
REFERENCE 8 (residues 1 to 756)
AUTHORS Hamilton,S.R., Liu,B., Parsons,R.E., Papadopoulos,N., Jen,J.,
Powell,S.M., Krush,A.J., Berk,T., Cohen,Z., Tetu,B., Burger,P.C.,
Wood,P.A., Taqi,F., Booker,S.V., Petersen,G.M., Offerhaus,G.J.A.,
Tersmette,A.C., Giardiello,F.M., Vogelstein,B. and Kinzler,K.W.
TITLE The molecular basis of Turcot's syndrome
JOURNAL N. Engl. J. Med. 332 (13), 839-847 (1995)
MEDLINE 95174843
PUBMED 7661930
REMARK VARIANT TURCOT SYNDROME LYS-616 DEL.
REFERENCE 9 (residues 1 to 756)
AUTHORS Wijnen,J., Khan,P.M., Vasen,H., Menko,F., van der Klift,H., van den
Broek,M., van Leeuwen-Cornelisse,I., Nagengast,F.,
Meijers-Heijboer,E.J., Lindhout,D., Griffioen,G., Cats,A.,
Kleibeuker,J., Varesco,L., Bertario,L., Bisgaard,M.-L., Mohr,J.,
Kolodner,R.D. and Fodde,R.
TITLE Majority of hMLH1 mutations responsible for hereditary nonpolyposis
colorectal cancer cluster at the exonic region 15-16
JOURNAL Am. J. Hum. Genet. 58 (2), 300-307 (1996)
MEDLINE 96152126
PUBMED 8571956
REMARK VARIANT HNPCC LYS-616 DEL.
REFERENCE 10 (residues 1 to 756)
AUTHORS Maliaka,Y.K., Chudina,A.P., Belev,N.F., Alday,P., Bochkov,N.P. and
Buerstedde,J.M.
TITLE CpG dinucleotides in the hMSH2 and hMLH1 genes are hotspots for
HNPCC mutations
JOURNAL Hum. Genet. 97 (2), 251-255 (1996)
MEDLINE 96163505
PUBMED 8566964
REMARK VARIANTS HNPCC MET-117 AND LEU-226.
REFERENCE 11 (residues 1 to 756)
AUTHORS Moslein,G., Tester,D.J., Lindor,N.M., Honchel,R., Cunningham,J.M.,
French,A.J., Halling,K.C., Schwab,M., Goretzki,P. and
Thibodeau,S.N.
TITLE Microsatellite instability and mutation analysis of hMSH2 and hMLH1
in patients with sporadic, familial and hereditary colorectal
cancer
JOURNAL Hum. Mol. Genet. 5 (9), 1245-1252 (1996)
MEDLINE 97026284
PUBMED 8872463
REMARK VARIANTS HNPCC LYS-616 DEL AND THR-618, AND VARIANT CRC THR-492.
REFERENCE 12 (residues 1 to 756)
AUTHORS Han,H.-J., Yuan,Y., Ku,J.-L., Oh,J.-H., Won,Y.-J., Kang,K.J.,
Kim,K.Y., Kim,S., Kim,C.Y., Kim,J.-P., Oh,N.-G., Lee,K.H.,
Choe,K.J., Nakamura,Y. and Park,J.-G.
TITLE Germline mutations of hMLH1 and hMSH2 genes in Korean hereditary
nonpolyposis colorectal cancer
JOURNAL J. Natl. Cancer Inst. 88 (18), 1317-1319 (1996)
MEDLINE 96390800
PUBMED 8797773
REMARK VARIANTS HNPCC CYS-217; LEU-542; PRO-549 AND PRO-574.
REFERENCE 13 (residues 1 to 756)
AUTHORS Kobayashi,K., Matsushima,M., Koi,S., Saito,H., Sagae,S., Kudo,R.
and Nakamura,Y.
TITLE Mutational analysis of mismatch repair genes, hMLH1 and hMSH2, in
sporadic endometrial carcinomas with microsatellite instability
JOURNAL Jpn. J. Cancer Res. 87 (2), 141-145 (1996)
MEDLINE 96183273
PUBMED 8609062
REMARK VARIANT CANCER LEU-ASN-HIS-37 INS, AND VARIANT ASP-384.
REFERENCE 14 (residues 1 to 756)
AUTHORS Wijnen,J., Khan,P.M., Vasen,H., van der Klift,H., Mulder,A., van
Leeuwen-Cornelisse,I., Bakker,B., Losekoot,M., Moller,P. and
Fodde,R.
TITLE Hereditary nonpolyposis colorectal cancer families not complying
with the Amsterdam criteria show extremely low frequency of
mismatch-repair-gene mutations
JOURNAL Am. J. Hum. Genet. 61 (2), 329-335 (1997)
MEDLINE 97456423
PUBMED 9311737
REMARK VARIANTS HNPCC LYS-62; SER-64; ALA-618; PRO-659 AND LYS-616 DEL.
REFERENCE 15 (residues 1 to 756)
AUTHORS Viel,A., Genuardi,M., Capozzi,E., Leonardi,F., Bellacosa,A.,
Paravatou-Petsotas,M., Pomponi,M.G., Fornasarig,M., Percesepe,A.,
Roncucci,L., Tamassia,M.G., Benatti,P., Ponz de Leon,M.,
Valenti,A., Covino,M., Anti,M., Foletto,M., Boiocchi,M. and Neri,G.
TITLE Characterization of MSH2 and MLH1 mutations in Italian families
with hereditary nonpolyposis colorectal cancer
JOURNAL Genes Chromosomes Cancer 18 (1), 8-18 (1997)
MEDLINE 97147120
PUBMED 8993976
REMARK VARIANT HNPCC LYS-616 DEL, AND VARIANT HIS-265.
REFERENCE 16 (residues 1 to 756)
AUTHORS Wu,Y., Nystrom-Lahti,M., Osinga,J., Looman,M.W., Peltomaki,P.,
Aaltonen,L.A., de la Chapelle,A., Hofstra,R.M. and Buys,C.H.
TITLE MSH2 and MLH1 mutations in sporadic replication error-positive
colorectal carcinoma as assessed by two-dimensional DNA
electrophoresis
JOURNAL Genes Chromosomes Cancer 18 (4), 269-278 (1997)
MEDLINE 97242567
PUBMED 9087566
REMARK VARIANTS CRC GLU-54; VAL-244 AND GLN-325, AND VARIANTS VAL-219 AND
ASN-406.
REFERENCE 17 (residues 1 to 756)
AUTHORS Pensotti,V., Radice,P., Presciuttini,S., Calistri,D., Gazzoli,I.,
Grimalt Perez,A.P., Mondini,P., Buonsanti,G., Sala,P., Rossetti,C.,
Ranzani,G.N., Bertario,L. and Pierotti,M.A.
TITLE Mean age of tumor onset in hereditary nonpolyposis colorectal
cancer (HNPCC) families correlates with the presence of mutations
in DNA mismatch repair genes
JOURNAL Genes Chromosomes Cancer 19 (3), 135-142 (1997)
MEDLINE 97362529
PUBMED 9218993
REMARK VARIANTS HNPCC PRO-128 AND ASP-244, AND VARIANT VAL-219.
REFERENCE 18 (residues 1 to 756)
AUTHORS Sasaki,S., Tokino,T., Miyatsu,T., Muto,T. and Nakamura,Y.
TITLE Mutational analysis of the hMLH1 gene using an automated
two-dimensional DNA typing system
JOURNAL Hum. Mutat. 9 (2), 164-171 (1997)
MEDLINE 97220595
PUBMED 9067757
REMARK VARIANT HNPCC ARG-67, AND VARIANT VAL-219.
REFERENCE 19 (residues 1 to 756)
AUTHORS Beck,N.E., Tomlinson,I.P., Homfray,T., Frayling,I., Hodgson,S.V.,
Harocopos,C. and Bodmer,W.F.
TITLE Use of SSCP analysis to identify germline mutations in HNPCC
families fulfilling the Amsterdam criteria
JOURNAL Hum. Genet. 99 (2), 219-224 (1997)
MEDLINE 97201114
PUBMED 9048925
REMARK VARIANT HNPCC 626-SER-THR-627.
REFERENCE 20 (residues 1 to 756)
AUTHORS Wang,Y., Friedl,W., Lamberti,C., Ruelfs,C., Kruse,R. and
Propping,P.
TITLE Hereditary nonpolyposis colorectal cancer: causative role of a
germline missense mutation in the hMLH1 gene confirmed by the
independent occurrence of the same somatic mutation in tumour
tissue
JOURNAL Hum. Genet. 100 (3-4), 362-364 (1997)
MEDLINE 97418119
PUBMED 9272156
REMARK VARIANT HNPCC PRO-329.
REFERENCE 21 (residues 1 to 756)
AUTHORS Wehner,M., Buschhausen,L., Lamberti,C., Kruse,R., Caspari,R.,
Propping,P. and Friedl,W.
TITLE Hereditary nonpolyposis colorectal cancer (HNPCC): eight novel
germline mutations in hMSH2 or hMLH1 genes
JOURNAL Hum. Mutat. 10 (3), 241-244 (1997)
MEDLINE 97442278
PUBMED 9298827
REMARK VARIANT HNPCC LEU-28.
REFERENCE 22 (residues 1 to 756)
AUTHORS Wang,Q., Desseigne,F., Lasset,C., Saurin,J.-C., Navarro,C.,
Yagci,T., Keser,I., Bagci,H., Luleci,G., Gelen,T.,
Chayvialle,J.-A., Puisieux,A. and Ozturk,M.
TITLE Germline hMSH2 and hMLH1 gene mutations in incomplete HNPCC
families
JOURNAL Int. J. Cancer 73 (6), 831-836 (1997)
MEDLINE 98060582
PUBMED 9399661
REMARK VARIANTS HNPCC GLY-182; THR-295 AND THR-551.
REFERENCE 23 (residues 1 to 756)
AUTHORS Tomlinson,I.P., Beck,N.E., Homfray,T., Harocopos,C.J. and
Bodmer,W.F.
TITLE Germline HNPCC gene variants have little influence on the risk for
sporadic colorectal cancer
JOURNAL J. Med. Genet. 34 (1), 39-42 (1997)
MEDLINE 97184879
PUBMED 9032648
REMARK VARIANT CRC TYR-77, AND VARIANT VAL-219.
REFERENCE 24 (residues 1 to 756)
AUTHORS Hackman,P., Tannergard,P., Osei-Mensa,S., Chen,J., Kane,M.F.,
Kolodner,R., Lambert,B., Hellgren,D. and Lindblom,A.
TITLE A human compound heterozygote for two MLH1 missense mutations
JOURNAL Nat. Genet. 17 (2), 135-136 (1997)
MEDLINE 97467715
PUBMED 9326924
REMARK VARIANTS HNPCC PHE-44 AND THR-441.
REFERENCE 25 (residues 1 to 756)
AUTHORS Farrington,S.M., Lin-Goerke,J., Ling,J., Wang,Y., Burczak,J.D.,
Robbins,D.J. and Dunlop,M.G.
TITLE Systematic analysis of hMSH2 and hMLH1 in young colon cancer
patients and controls
JOURNAL Am. J. Hum. Genet. 63 (3), 749-759 (1998)
MEDLINE 98386069
PUBMED 9718327
REMARK VARIANTS HNPCC, AND VARIANTS.
REFERENCE 26 (residues 1 to 756)
AUTHORS Liu,T., Wahlberg,S., Rubio,C., Holmberg,E., Gronberg,H. and
Lindblom,A.
TITLE DGGE screening of mutations in mismatch repair genes (hMSH2 and
hMLH1) in 34 Swedish families with colorectal cancer
JOURNAL Clin. Genet. 53 (2), 131-135 (1998)
MEDLINE 98272630
PUBMED 9611074
REMARK VARIANT CRC GLY-268.
REFERENCE 27 (residues 1 to 756)
AUTHORS Yuan,Y., Han,H.J., Zheng,S. and Park,J.G.
TITLE Germline mutations of hMLH1 and hMSH2 genes in patients with
suspected hereditary nonpolyposis colorectal cancer and sporadic
early-onset colorectal cancer
JOURNAL Dis Colon Rectum 41 (4), 434-440 (1998)
MEDLINE 98218529
PUBMED 9559627
REMARK VARIANT HNPCC CYS-217.
REFERENCE 28 (residues 1 to 756)
AUTHORS Klaus,K., Herfarth,F., Ogunbiyi,O.A., Moley,J.F., Kodner,I.J.,
Wells,S.A. Jr. and Goodfellow,P.J.
TITLE Four new mutations in the DNA mismatch repair gene MLH1 in
colorectal cancers with microsatellite instability. Mutations in
brief no. 157. Online
JOURNAL Hum. Mutat. 12 (1), 73 (1998)
MEDLINE 20089933
PUBMED 10627141
REMARK VARIANT HNPCC LYS-69.
REFERENCE 29 (residues 1 to 756)
AUTHORS Panariello,L., Scarano,M.I., de Rosa,M., Capasso,L., Renda,A.,
Riegler,G., Rossi,G.B., Salvatore,F. and Izzo,P.
TITLE hMLH1 mutations in hereditary nonpolyposis colorectal cancer
kindreds. Mutations in brief no. 182. Online
JOURNAL Hum. Mutat. 12 (3), 216-217 (1998)
MEDLINE 20123068
PUBMED 10660333
REMARK VARIANTS HNPCC ARG-77 AND PRO-193.
REFERENCE 30 (residues 1 to 756)
AUTHORS Quaresima,B., Grandinetti,C., Baudi,F., Tassone,P., Barbieri,V.,
Conforti,S., Avvedimento,E.V., Costanzo,F. and Venuta,S.
TITLE Hereditary nonpolyposis coloretal cancer: identification of novel
germline mutations in two kindreds not fulfulling the Amsterdam
criteria. Mutations in brief no. 203. Online
JOURNAL Hum. Mutat. 12 (6), 433 (1998)
MEDLINE 20133866
PUBMED 10671064
REMARK VARIANT HNPCC GLY-93.
REFERENCE 31 (residues 1 to 756)
AUTHORS Hutter,P., Couturier,A., Membrez,V., Joris,F., Sappino,A.P. and
Chappuis,P.O.
TITLE Excess of hMLH1 germline mutations in Swiss families with
hereditary non-polyposis colorectal cancer
JOURNAL Int. J. Cancer 78 (6), 680-684 (1998)
MEDLINE 99049505
PUBMED 9833759
REMARK VARIANTS HNPCC ARG-67; ILE-262 DEL; THR-551; PHE-565 AND MET-716,
AND VARIANT VAL-219.
REFERENCE 32 (residues 1 to 756)
AUTHORS Lamberti,C., Kruse,R., Ruelfs,C., Caspari,R., Wang,Y., Jungck,M.,
Mathiak,M., Malayeri,H.R.H., Friedl,W., Sauerbruch,T. and
Propping,P.
TITLE Microsatellite instability, a useful diagnostic tool to select
patients at high risk for hereditary non-polyposis colorectal
cancer: a study in different groups of patients with colorectal
cancer
JOURNAL Gut 44, 839-843 (1999)
REMARK VARIANTS HNPCC LEU-28; GLU-84 AND PRO-329.
REFERENCE 33 (residues 1 to 756)
AUTHORS Wang,Q., Lasset,C., Desseigne,F., Saurin,J.-C., Maugard,C.,
Navarro,C., Ruano,E., Descos,L., Trillet-Lenoir,V., Bosset,J.-F.
and Puisieux,A.
TITLE Prevalence of germline mutations of hMLH1, hMSH2, hPMS1, hPMS2, and
hMSH6 genes in 75 French kindreds with nonpolyposis colorectal
cancer
JOURNAL Hum. Genet. 105 (1-2), 79-85 (1999)
MEDLINE 99408236
PUBMED 10480359
REMARK VARIANTS HNPCC TRP-67; MET-117; GLY-182; LYS-616 DEL AND TRP-755.
REFERENCE 34 (residues 1 to 756)
AUTHORS Liu,T., Tannergard,P., Hackman,P., Rubio,C., Kressner,U.,
Lindmark,G., Hellgren,D., Lambert,B. and Lindblom,A.
TITLE Missense mutations in hMLH1 associated with colorectal cancer
JOURNAL Hum. Genet. 105 (5), 437-441 (1999)
MEDLINE 20065868
PUBMED 10598809
REMARK VARIANT CRC GLY-578; AND VARIANT HNPCC ALA-618.
REFERENCE 35 (residues 1 to 756)
AUTHORS Nomura,S., Sugano,K., Kashiwabara,H., Taniguchi,T., Fukayama,N.,
Fujita,S., Akasu,T., Moriya,Y., Ohhigashi,S., Kakizoe,T. and
Sekiya,T.
TITLE Enhanced detection of deleterious and other germline mutations of
hMSH2 and hMLH1 in Japanese hereditary nonpolyposis colorectal
cancer kindreds
JOURNAL Biochem. Biophys. Res. Commun. 271 (1), 120-129 (2000)
MEDLINE 20241830
PUBMED 10777691
REMARK VARIANTS HNPCC VAL-111 AND PRO-588, AND VARIANTS VAL-219 AND
ASP-384.
REFERENCE 36 (residues 1 to 756)
AUTHORS Fidalgo,P., Almeida,M.R., West,S., Gaspar,C., Maia,L., Wijnen,J.,
Albuquerque,C., Curtis,A., Cravo,M., Fodde,R., Leitao,C.N. and
Burn,J.
TITLE Detection of mutations in mismatch repair genes in Portuguese
families with hereditary non-polyposis colorectal cancer (HNPCC) by
a multi-method approach
JOURNAL Eur. J. Hum. Genet. 8 (1), 49-53 (2000)
MEDLINE 20178226
PUBMED 10713887
REMARK VARIANTS HNPCC MET-213; HIS-607; ALA-618 AND LEU-659.
REFERENCE 37 (residues 1 to 756)
AUTHORS Stone,J.G., Coleman,G., Gusterson,B., Marossy,A., Lakhani,S.R.,
Ward,A., Nash,A., McKinna,A., A'Hern,R., Stratton,M.R. and
Houlston,R.S.
TITLE Contribution of germline MLH1 and MSH2 mutations to lobular
carcinoma in situ of the breast
JOURNAL Cancer Lett. 167 (2), 171-174 (2001)
MEDLINE 21261646
PUBMED 11369138
REMARK VARIANT LCIS HIS-607.
REFERENCE 38 (residues 1 to 756)
AUTHORS Mueller-Koch,Y., Kopp,R., Lohse,P., Baretton,G., Stoetzer,A.,
Aust,D., Daum,J., Kerker,B., Gross,M., Dietmeier,W. and
Holinski-Feder,E.
TITLE Sixteen rare sequence variants of the hMLH1 and hMSH2 genes found
in a cohort of 254 suspected HNPCC (hereditary non-polyposis
colorectal cancer) patients: mutations or polymorphisms?
JOURNAL Eur. J. Med. Res. 6 (11), 473-482 (2001)
MEDLINE 21583375
PUBMED 11726306
REMARK VARIANTS HNPCC V-80; P-329; R-603; A-618; L-648; L-662; R-689 AND
M-716.
REFERENCE 39 (residues 1 to 756)
AUTHORS Ellison,A.R., Lofing,J. and Bitter,G.A.
TITLE Functional analysis of human MLH1 and MSH2 missense variants and
hybrid human-yeast MLH1 proteins in Saccharomyces cerevisiae
JOURNAL Hum. Mol. Genet. 10 (18), 1889-1900 (2001)
MEDLINE 21439334
PUBMED 11555625
REMARK CHARACTERIZATION OF VARIANTS.
REFERENCE 40 (residues 1 to 756)
AUTHORS Jakubowska,A., Gorski,B., Kurzawski,G., Debniak,T., Hadaczek,P.,
Cybulski,C., Kladny,J., Oszurek,O., Scott,R.J. and Lubinski,J.
TITLE Optimization of experimental conditions for RNA-based sequencing of
MLH1 and MSH2 genes
JOURNAL Hum. Mutat. 17 (1), 52-60 (2001)
MEDLINE 20579875
PUBMED 11139242
REMARK VARIANT HNPCC ARG-751.
REFERENCE 41 (residues 1 to 756)
AUTHORS Godino,J., de La Hoya,M., Diaz-Rubio,E., Benito,M. and Caldes,T.
TITLE Eight novel germline MLH1 and MSH2 mutations in hereditary
non-polyposis colorectal cancer families from Spain
JOURNAL Hum. Mutat. 18 (6), 549 (2001)
MEDLINE 21614892
PUBMED 11748856
REMARK VARIANTS HNPCC HIS-622 AND TRP-687.
REFERENCE 42 (residues 1 to 756)
AUTHORS Jager,A.C., Rasmussen,M., Bisgaard,H.C., Singh,K.K., Nielsen,F.C.
and Rasmussen,L.J.
TITLE HNPCC mutations in the human DNA mismatch repair gene hMLH1
influence assembly of hMutLalpha and hMLH1-hEXO1 complexes
JOURNAL Oncogene 20 (27), 3590-3595 (2001)
MEDLINE 21322829
PUBMED 11429708
REMARK CHARACTERIZATION OF VARIANT MET-117.
REFERENCE 43 (residues 1 to 756)
AUTHORS Trojan,J., Zeuzem,S., Randolph,A., Hemmerle,C., Brieger,A.,
Raedle,J., Plotz,G., Jiricny,J. and Marra,G.
TITLE Functional analysis of hMLH1 variants and HNPCC-related mutations
using a human expression system
JOURNAL Gastroenterology 122 (1), 211-219 (2002)
MEDLINE 21640300
PUBMED 11781295
REMARK CHARACTERIZATION OF VARIANTS M-117; G-185; C-217; VAL-219; D-244;
C-265; H-265 AND A-326.
REFERENCE 44 (residues 1 to 756)
AUTHORS Nystroem-Lahti,M., Perrera,C., Raeschle,M., Panyushkina-Seiler,E.,
Marra,G., Curci,A., Quaresima,B., Costanzo,F., D'Urso,M., Venuta,S.
and Jiricny,J.
TITLE Functional analysis of MLH1 mutations linked to hereditary
nonpolyposis colon cancer
JOURNAL Genes Chromosomes Cancer 33 (2), 160-167 (2002)
MEDLINE 21652714
PUBMED 11793442
REMARK CHARACTERIZATION OF VARIANTS ARG-77; GLY-93; ARG-107 AND PRO-659.
REFERENCE 45 (residues 1 to 756)
AUTHORS Krueger,S., Plaschke,J., Pistorius,S., Jeske,B., Haas,S.,
Kraemer,H., Hinterseher,I., Bier,A., Kreuz,F.R., Theissig,F.,
Saeger,H.D. and Schackert,H.K.
TITLE Seven novel MLH1 and MSH2 germline mutations in hereditary
nonpolyposis colorectal cancer
JOURNAL Hum. Mutat. 19, 82-82 (2002)
REMARK VARIANT HNPCC PRO-662, AND VARIANT VAL-219.
COMMENT -------------------------------------------------------------------
This SWISS-PROT entry is copyright. It is produced through a
collaboration between the Swiss Institute of Bioinformatics and
the EMBL outstation - the European Bioinformatics Institute.
The original entry is available from http://www.expasy.ch/sprot
and http://www.ebi.ac.uk/sprot
------------------------------------------------------------------.
[FUNCTION] Involved in the repair of mismatches in DNA.
[SUBUNIT] HETERODIMER OF MLH1 AND PMS2 OR MLH1 AND MLH3. 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.
[SUBCELLULAR LOCATION] Nuclear.
[TISSUE SPECIFICITY] COLON, LYMPHOCYTES, BREAST, LUNG, SPLEEN,
TESTIS, PROSTATE, THYROID, GALL BLADDER AND HEART.
[DISEASE] DEFECTS IN MLH1 ARE A CAUSE OF HEREDITARY NON-POLYPOSIS
COLORECTAL CANCER (HNPCC) (LYNCH SYNDROME). 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.
[DISEASE] Defects in MLH1 are a cause of Turcot syndrome, an
autosomal dominant disorder characterized by malignant tumors of
the brain associated with multiple colorectal adenomas. Skin
features include sebaceous cysts, hyperpigmented and cafe au lait
spots.
[DISEASE] Defects in MLH1 are a cause of Muir-Torre syndrome (MTS),
a rare autosomal dominant disorder characterized by sebaceous
neoplasms and visceral malignancy.
[DISEASE] Defects in MLH1 may contribute to lobular carcinoma in
situ (LCIS), a non-invasive neoplastic disease of the breast.
[SIMILARITY] BELONGS TO THE DNA MISMATCH REPAIR MUTL/HEXB FAMILY.
[DATABASE] NAME=Hereditary non-polyposis colorectal cancer db;
WWW='http://www.nfdht.nl/'.
FEATURES Location/Qualifiers
source 1..756
/organism="Homo sapiens"
/db_xref="taxon:9606"
gene 1..756
/gene="MLH1"
/note="synonym: COCA2"
Protein 1..756
/gene="MLH1"
/product="DNA mismatch repair protein Mlh1"
Region 28
/gene="MLH1"
/region_name="Variant"
/note="P -> L (IN HNPCC). /FTId=VAR_004433."
Region 35
/gene="MLH1"
/region_name="Variant"
/note="M -> R (IN HNPCC). /FTId=VAR_004434."
Region 37
/gene="MLH1"
/region_name="Variant"
/note="E -> ELNH (IN ENDOMETRIAL CANCER; SOMATIC).
/FTId=VAR_004435."
Region 44
/gene="MLH1"
/region_name="Variant"
/note="S -> F (IN HNPCC; THE EQUIVALENT SUBSTITUTION IN
YEAST CAUSES LOSS OF FUNCTION IN A MISMATCH REPAIR ASSAY).
/FTId=VAR_004436."
Region 54
/gene="MLH1"
/region_name="Variant"
/note="G -> E (IN SPORADIC CRC; SOMATIC MUTATION).
/FTId=VAR_012902."
Region 62
/gene="MLH1"
/region_name="Variant"
/note="Q -> K (IN HNPCC; REDUCED REPAIR EFFICIENCY IN A
YEAST MISMATCH REPAIR ASSAY). /FTId=VAR_004437."
Region 64
/gene="MLH1"
/region_name="Variant"
/note="N -> S (IN HNPCC). /FTId=VAR_004438."
Region 67
/gene="MLH1"
/region_name="Variant"
/note="G -> R (IN HNPCC; THE EQUIVALENT SUBSTITUTION IN
YEAST CAUSES LOSS OF FUNCTION IN A MISMATCH REPAIR ASSAY).
/FTId=VAR_004439."
Region 67
/gene="MLH1"
/region_name="Variant"
/note="G -> W (IN HNPCC). /FTId=VAR_012903."
Region 68
/gene="MLH1"
/region_name="Variant"
/note="I -> N (IN HNPCC; THE EQUIVALENT SUBSTITUTION IN
YEAST CAUSES LOSS OF FUNCTION IN A MISMATCH REPAIR ASSAY).
/FTId=VAR_004440."
Region 69
/gene="MLH1"
/region_name="Variant"
/note="R -> K (IN HNPCC; REDUCED REPAIR EFFICIENCY IN A
MISMATCH REPAIR ASSAY). /FTId=VAR_004441."
Region 77
/gene="MLH1"
/region_name="Variant"
/note="C -> R (IN HNPCC AND SPORADIC CRC; NORMAL
INTERACTION WITH PMS2; LOSS OF FUNCTION IN A MISMATCH
REPAIR ASSAY). /FTId=VAR_004442."
Region 77
/gene="MLH1"
/region_name="Variant"
/note="C -> Y (IN SPORADIC CRC; EARLY ONSET).
/FTId=VAR_012904."
Region 80
/gene="MLH1"
/region_name="Variant"
/note="F -> V (IN SUSPECTED HNPCC). /FTId=VAR_012905."
Region 84
/gene="MLH1"
/region_name="Variant"
/note="K -> E (IN SUSPECTED HNPCC). /FTId=VAR_012906."
Region 93
/gene="MLH1"
/region_name="Variant"
/note="S -> G (IN HNPCC; COULD BE A POLYMORPHISM; NORMAL
INTERACTION WITH PMS2; NO FUNCTIONAL ALTERATION DETECTED
BY AN IN VITRO MISMATCH REPAIR ASSAY). /FTId=VAR_004443."
Region 107
/gene="MLH1"
/region_name="Variant"
/note="I -> R (IN HNPCC; NORMAL INTERACTION WITH PMS2;
LOSS OF FUNCTION IN A MISMATCH REPAIR ASSAY).
/FTId=VAR_004444."
Region 111
/gene="MLH1"
/region_name="Variant"
/note="A -> V (IN HNPCC). /FTId=VAR_012907."
Region 117
/gene="MLH1"
/region_name="Variant"
/note="T -> M (IN HNPCC; FAILS TO INTERACT WITH PMS2 AND
EXO1; LOSS OF FUNCTION IN A MISMATCH REPAIR ASSAY).
/FTId=VAR_004445."
Region 117
/gene="MLH1"
/region_name="Variant"
/note="T -> R (IN HNPCC; EQUIVALENT SUBSTITUTION IN YEAST
CAUSES LOSS OF FUNCTION IN MISMATCH REPAIR ASSAY).
/FTId=VAR_004446."
Region 128
/gene="MLH1"
/region_name="Variant"
/note="A -> P (IN HNPCC). /FTId=VAR_012908."
Region 182
/gene="MLH1"
/region_name="Variant"
/note="R -> G (IN HNPCC; INCOMPLETE). /FTId=VAR_012909."
Region 185
/gene="MLH1"
/region_name="Variant"
/note="V -> G (IN HNPCC; DEFECTIVE IN A MISMATCH REPAIR
ASSAY). /FTId=VAR_004447."
Region 193
/gene="MLH1"
/region_name="Variant"
/note="S -> P (IN HNPCC). /FTId=VAR_004448."
Region 213
/gene="MLH1"
/region_name="Variant"
/note="V -> M (IN HNPCC). /FTId=VAR_012910."
Region 217
/gene="MLH1"
/region_name="Variant"
/note="R -> C (IN HNPCC; PROFICIENT IN A MISMATCH REPAIR
ASSAY). /FTId=VAR_004449."
Region 219
/gene="MLH1"
/region_name="Variant"
/note="I -> V (IN 37% OF ALLELES). /FTId=VAR_004450."
Region 226..295
/gene="MLH1"
/region_name="Variant"
/note="MISSING (IN HNPCC). /FTId=VAR_004452."
Region 226
/gene="MLH1"
/region_name="Variant"
/note="R -> L (IN HNPCC). /FTId=VAR_004451."
Region 244
/gene="MLH1"
/region_name="Variant"
/note="G -> D (IN HNPCC; DEFECTIVE IN A MISMATCH REPAIR
ASSAY). /FTId=VAR_012911."
Region 244
/gene="MLH1"
/region_name="Variant"
/note="G -> V (IN SPORADIC CRC; SOMATIC MUTATION; COULD BE
A POLYMORPHISM). /FTId=VAR_012912."
Region 262
/gene="MLH1"
/region_name="Variant"
/note="MISSING (IN HNPCC). /FTId=VAR_012913."
Region 265
/gene="MLH1"
/region_name="Variant"
/note="R -> H (RARE POLYMORPHISM; SLIGHTLY LOWER MISMATCH
REPAIR EFFICIENCY). /FTId=VAR_012914."
Region 268
/gene="MLH1"
/region_name="Variant"
/note="E -> G (IN CRC). /FTId=VAR_012915."
Region 295
/gene="MLH1"
/region_name="Variant"
/note="S -> T (IN HNPCC). /FTId=VAR_012916."
Region 325
/gene="MLH1"
/region_name="Variant"
/note="R -> Q (IN SPORADIC CRC; SOMATIC MUTATION; COULD BE
A POLYMORPHISM). /FTId=VAR_012917."
Region 326
/gene="MLH1"
/region_name="Variant"
/note="V -> A (IN HNPCC; PROFICIENT IN A MISMATCH REPAIR
ASSAY). /FTId=VAR_004453."
Region 329
/gene="MLH1"
/region_name="Variant"
/note="H -> P (IN HNPCC). /FTId=VAR_012918."
Region 384
/gene="MLH1"
/region_name="Variant"
/note="V -> D. /FTId=VAR_004454."
Region 406
/gene="MLH1"
/region_name="Variant"
/note="S -> N. /FTId=VAR_012919."
Region 441
/gene="MLH1"
/region_name="Variant"
/note="A -> T (IN HNPCC). /FTId=VAR_012920."
Region 492
/gene="MLH1"
/region_name="Variant"
/note="A -> T (IN HNPCC AND SPORADIC CRC).
/FTId=VAR_004455."
Region 506
/gene="MLH1"
/region_name="Variant"
/note="V -> A (IN HNPCC). /FTId=VAR_004456."
Region 542
/gene="MLH1"
/region_name="Variant"
/note="Q -> L (IN HNPCC; TYPE II; EQUIVALENT SUBSTITUTION
IN YEAST CAUSES LOSS OF FUNCTION IN A MISMATCH REPAIR
ASSAY). /FTId=VAR_004457."
Region 549
/gene="MLH1"
/region_name="Variant"
/note="L -> P (IN HNPCC). /FTId=VAR_012921."
Region 551
/gene="MLH1"
/region_name="Variant"
/note="N -> T (IN HNPCC). /FTId=VAR_012922."
Region 565
/gene="MLH1"
/region_name="Variant"
/note="I -> F (IN HNPCC). /FTId=VAR_012923."
Region 574
/gene="MLH1"
/region_name="Variant"
/note="L -> P (IN HNPCC; TYPE I). /FTId=VAR_004458."
Region 578
/gene="MLH1"
/region_name="Variant"
/note="E -> G (IN HNPCC AND CRC). /FTId=VAR_004459."
Region 582
/gene="MLH1"
/region_name="Variant"
/note="L -> V (IN HNPCC; TYPE II). /FTId=VAR_004460."
Region 588
/gene="MLH1"
/region_name="Variant"
/note="L -> P (IN HNPCC). /FTId=VAR_012924."
Region 603
/gene="MLH1"
/region_name="Variant"
/note="P -> R (IN SUSPECTED HNPCC; COULD BE A
POLYMORPHISM). /FTId=VAR_012925."
Region 607
/gene="MLH1"
/region_name="Variant"
/note="L -> H (IN LCIS AND HNPCC). /FTId=VAR_012926."
Region 616
/gene="MLH1"
/region_name="Variant"
/note="MISSING (IN HNPCC AND TURCOT SYNDROME).
/FTId=VAR_004461."
Region 618
/gene="MLH1"
/region_name="Variant"
/note="K -> A (IN HNPCC; REQUIRES 2 NUCLEOTIDE
SUBSTITUTIONS). /FTId=VAR_004462."
Region 618
/gene="MLH1"
/region_name="Variant"
/note="K -> T (IN HNPCC; TYPE II). /FTId=VAR_004463."
Region 622
/gene="MLH1"
/region_name="Variant"
/note="L -> H (IN HNPCC). /FTId=VAR_012927."
Region 626..627
/gene="MLH1"
/region_name="Variant"
/note="FS -> ST (IN HNPCC). /FTId=VAR_004464."
Region 648
/gene="MLH1"
/region_name="Variant"
/note="P -> L (IN SUSPECTED HNPCC). /FTId=VAR_012928."
Region 659
/gene="MLH1"
/region_name="Variant"
/note="R -> L (IN HNPCC). /FTId=VAR_012929."
Region 659
/gene="MLH1"
/region_name="Variant"
/note="R -> P (IN HNPCC; INTERACTS ONLY VERY WEAKLY WITH
PMS2; EQUIVALENT SUBSTITUTION IN YEAST CAUSES ALMOST
COMPLETE LOSS OF FUNCTION IN A MISMATCH REPAIR ASSAY).
/FTId=VAR_004465."
Region 662
/gene="MLH1"
/region_name="Variant"
/note="T -> P (IN HNPCC; COULD BE A RARE POLYMORPHISM).
/FTId=VAR_012930."
Region 681
/gene="MLH1"
/region_name="Variant"
/note="A -> T (IN HNPCC; EQUIVALENT SUBSTITUTION IN YEAST
DOES NOT AFFECT MISMATCH REPAIR). /FTId=VAR_004466."
Region 687
/gene="MLH1"
/region_name="Variant"
/note="R -> W (IN HNPCC). /FTId=VAR_012931."
Region 689
/gene="MLH1"
/region_name="Variant"
/note="Q -> R (IN SUSPECTED HNPCC; COULD BE A
POLYMORPHISM). /FTId=VAR_012932."
Region 708..711
/gene="MLH1"
/region_name="Conflict"
/note="MISSING (IN REF. 4)."
Region 716
/gene="MLH1"
/region_name="Variant"
/note="V -> M (IN HNPCC; COULD BE A POLYMORPHISM).
/FTId=VAR_012933."
Region 718
/gene="MLH1"
/region_name="Variant"
/note="H -> Y. /FTId=VAR_004467."
Region 729
/gene="MLH1"
/region_name="Variant"
/note="L -> V. /FTId=VAR_004468."
Region 751
/gene="MLH1"
/region_name="Variant"
/note="K -> R (IN HNPCC). /FTId=VAR_012934."
Region 755
/gene="MLH1"
/region_name="Variant"
/note="R -> W (IN HNPCC; INCOMPLETE). /FTId=VAR_012935."
ORIGIN
1 msfvagvirr ldetvvnria ageviqrpan aikemiencl dakstsiqvi vkegglkliq
61 iqdngtgirk edldivcerf ttsklqsfed lasistygfr gealasishv ahvtittkta
121 dgkcayrasy sdgklkappk pcagnqgtqi tvedlfynia trrkalknps eeygkilevv
181 grysvhnagi sfsvkkqget vadvrtlpna stvdnirsif gnavsrelie igcedktlaf
241 kmngyisnan ysvkkcifll finhrlvest slrkaietvy aaylpknthp flylsleisp
301 qnvdvnvhpt khevhflhee silervqqhi eskllgsnss rmyftqtllp glagpsgemv
361 ksttsltsss tsgssdkvya hqmvrtdsre qkldaflqpl skplssqpqa ivtedktdis
421 sgrarqqdee mlelpapaev aaknqslegd ttkgtsemse krgptssnpr krhredsdve
481 mveddsrkem taactprrri inltsvlslq eeineqghev lremlhnhsf vgcvnpqwal
541 aqhqtklyll nttklseelf yqiliydfan fgvlrlsepa plfdlamlal dspesgwtee
601 dgpkeglaey iveflkkkae mladyfslei deegnliglp llidnyvppl eglpifilrl
661 atevnwdeek ecfeslskec amfysirkqy iseestlsgq qsevpgsipn swkwtvehiv
721 ykalrshilp pkhftedgni lqlanlpdly kvferc
//
|
|
