| |
LOCUS MLH1 2484 bp mRNA linear PRI 05-NOV-2002
DEFINITION Homo sapiens mutL homolog 1, colon cancer, nonpolyposis type 2 (E.
coli) (MLH1), mRNA.
ACCESSION NM_000249
VERSION NM_000249.1 GI:4557756
KEYWORDS .
SOURCE Homo sapiens (human)
ORGANISM Homo sapiens
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo.
REFERENCE 1 (bases 1 to 2484)
AUTHORS Lindblom,A., Tannergard,P., Werelius,B. and Nordenskjold,M.
TITLE Genetic mapping of a second locus predisposing to hereditary
non-polyposis colon cancer
JOURNAL Nat. Genet. 5 (3), 279-282 (1993)
MEDLINE 94100984
PUBMED 7903889
REFERENCE 2 (bases 1 to 2484)
AUTHORS Bronner,C.E., Baker,S.M., Morrison,P.T., Warren,G., Smith,L.G.,
Lescoe,M.K., Kane,M., Earabino,C., Lipford,J., Lindblom,A. et al.
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
REFERENCE 3 (bases 1 to 2484)
AUTHORS Papadopoulos N, Nicolaides NC, Wei YF, Ruben SM, Carter KC, Rosen
CA, Haseltine WA, Fleischmann RD, Fraser CM, Adams MD et al.
TITLE Mutation of a mutL homolog in hereditary colon cancer
JOURNAL Science 263 (5153), 1625-1629 (1994)
MEDLINE 94174309
PUBMED 8128251
REFERENCE 4 (bases 1 to 2484)
AUTHORS Kolodner RD, Hall NR, Lipford J, Kane MF, Morrison PT, Finan PJ,
Burn J, Chapman P, Earabino C, Merchant E et al.
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
REFERENCE 5 (bases 1 to 2484)
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
REFERENCE 6 (bases 1 to 2484)
AUTHORS Charbonnier,F., Martin,C., Scotte,M., Sibert,L., Moreau,V. and
Frebourg,T.
TITLE Alternative splicing of MLH1 messenger RNA in human normal cells
JOURNAL Cancer Res. 55 (9), 1839-1841 (1995)
MEDLINE 95246019
PUBMED 7728749
REFERENCE 7 (bases 1 to 2484)
AUTHORS Kolodner,R.D.
TITLE Mismatch repair: mechanisms and relationship to cancer
susceptibility
JOURNAL Trends Biochem. Sci. 20 (10), 397-401 (1995)
MEDLINE 96072350
PUBMED 8533151
REFERENCE 8 (bases 1 to 2484)
AUTHORS Peltomaki,P. and de la Chapelle,A.
TITLE Mutations predisposing to hereditary nonpolyposis colorectal cancer
JOURNAL Adv. Cancer Res. 71, 93-119 (1997)
MEDLINE 97266060
PUBMED 9111864
REFERENCE 9 (bases 1 to 2484)
AUTHORS Ban,C. and Yang,W.
TITLE Crystal structure and ATPase activity of MutL: implications for DNA
repair and mutagenesis
JOURNAL Cell 95 (4), 541-552 (1998)
MEDLINE 99043508
PUBMED 9827806
REFERENCE 10 (bases 1 to 2484)
AUTHORS Chadwick,R.B., Pyatt,R.E., Niemann,T.H., Richards,S.K.,
Johnson,C.K., Stevens,M.W., Meek,J.E., Hampel,H., Prior,T.W. and de
la Chapelle,A.
TITLE Hereditary and somatic DNA mismatch repair gene mutations in
sporadic endometrial carcinoma
JOURNAL J. Med. Genet. 38 (7), 461-466 (2001)
MEDLINE 21367231
PUBMED 11474654
REFERENCE 11 (bases 1 to 2484)
AUTHORS Cunningham,J.M., Kim,C.Y., Christensen,E.R., Tester,D.J., Parc,Y.,
Burgart,L.J., Halling,K.C., McDonnell,S.K., Schaid,D.J., Walsh
Vockley,C., Kubly,V., Nelson,H., Michels,V.V. and Thibodeau,S.N.
TITLE The frequency of hereditary defective mismatch repair in a
prospective series of unselected colorectal carcinomas
JOURNAL Am. J. Hum. Genet. 69 (4), 780-790 (2001)
MEDLINE 21426337
PUBMED 11524701
REFERENCE 12 (bases 1 to 2484)
AUTHORS Pedrazzi,G., Perrera,C., Blaser,H., Kuster,P., Marra,G.,
Davies,S.L., Ryu,G.H., Freire,R., Hickson,I.D., Jiricny,J. and
Stagljar,I.
TITLE Direct association of Bloom's syndrome gene product with the human
mismatch repair protein MLH1
JOURNAL Nucleic Acids Res. 29 (21), 4378-4386 (2001)
MEDLINE 21550136
PUBMED 11691925
COMMENT REVIEWED REFSEQ: This record has been curated by NCBI staff. The
reference sequence was derived from U07343.1.
Summary: MLH1 was identified as a locus frequently mutated in
hereditary nonpolyposis colon cancer (HNPCC). When cloned, it was
discovered to be a human homolog of the E. coli mismatch repair
gene mutS, consistent with the characteristic alterations in
microsatellite sequences (RER+ phenotype) found in HNPCC.
FEATURES Location/Qualifiers
source 1..2484
/organism="Homo sapiens"
/db_xref="taxon:9606"
/chromosome="3"
/map="3p21.3"
gene 1..2484
/gene="MLH1"
/note="synonyms: FCC2, COCA2, HNPCC, hMLH1, HNPCC2"
/db_xref="LocusID:4292"
/db_xref="MIM:120436"
CDS 22..2292
/gene="MLH1"
/note="mutL (E. coli) homolog 1; mutL (E. coli) homolog 1
(colon cancer, nonpolyposis type 2)"
/codon_start=1
/product="mutL homolog 1"
/protein_id="NP_000240.1"
/db_xref="GI:4557757"
/db_xref="LocusID:4292"
/db_xref="MIM:120436"
/translation="MSFVAGVIRRLDETVVNRIAAGEVIQRPANAIKEMIENCLDAKS
TSIQVIVKEGGLKLIQIQDNGTGIRKEDLDIVCERFTTSKLQSFEDLASISTYGFRGE
ALASISHVAHVTITTKTADGKCAYRASYSDGKLKAPPKPCAGNQGTQITVEDLFYNIA
TRRKALKNPSEEYGKILEVVGRYSVHNAGISFSVKKQGETVADVRTLPNASTVDNIRS
IFGNAVSRELIEIGCEDKTLAFKMNGYISNANYSVKKCIFLLFINHRLVESTSLRKAI
ETVYAAYLPKNTHPFLYLSLEISPQNVDVNVHPTKHEVHFLHEESILERVQQHIESKL
LGSNSSRMYFTQTLLPGLAGPSGEMVKSTTSLTSSSTSGSSDKVYAHQMVRTDSREQK
LDAFLQPLSKPLSSQPQAIVTEDKTDISSGRARQQDEEMLELPAPAEVAAKNQSLEGD
TTKGTSEMSEKRGPTSSNPRKRHREDSDVEMVEDDSRKEMTAACTPRRRIINLTSVLS
LQEEINEQGHEVLREMLHNHSFVGCVNPQWALAQHQTKLYLLNTTKLSEELFYQILIY
DFANFGVLRLSEPAPLFDLAMLALDSPESGWTEEDGPKEGLAEYIVEFLKKKAEMLAD
YFSLEIDEEGNLIGLPLLIDNYVPPLEGLPIFILRLATEVNWDEEKECFESLSKECAM
FYSIRKQYISEESTLSGQQSEVPGSIPNSWKWTVEHIVYKALRSHILPPKHFTEDGNI
LQLANLPDLYKVFERC"
misc_feature 112..393
/gene="MLH1"
/note="HATPase_c; Region: Histidine kinase-, DNA gyrase
B-, and HSP90-like ATPase. This family represents the
structurally related ATPase domains of histidine kinase,
DNA gyrase B and HSP90"
/db_xref="CDD:pfam02518"
misc_feature 112..282
/gene="MLH1"
/note="HATPase_c; Region: Histidine kinase-like ATPases"
/db_xref="CDD:smart00387"
misc_feature 682..1023
/gene="MLH1"
/note="DNA_mis_repair; Region: DNA mismatch repair
protein, C-terminal domain. This family represents the
C-terminal domain of the mutL/hexB/PMS1 family. This
domain has a ribosomal S5 domain 2-like fold"
/db_xref="CDD:pfam01119"
variation 658
/gene="MLH1"
/allele="A"
/allele="G"
/db_xref="dbSNP:2308317"
variation 676
/gene="MLH1"
/allele="A"
/allele="G"
/db_xref="dbSNP:2229023"
variation 1980
/gene="MLH1"
/allele="G"
/allele="T"
/db_xref="dbSNP:1800146"
variation 2173
/gene="MLH1"
/allele="C"
/allele="T"
/db_xref="dbSNP:2020873"
variation 2393
/gene="MLH1"
/allele="G"
/allele="T"
/db_xref="dbSNP:1803985"
BASE COUNT 720 a 535 c 594 g 635 t
ORIGIN
1 cttggctctt ctggcgccaa aatgtcgttc gtggcagggg ttattcggcg gctggacgag
61 acagtggtga accgcatcgc ggcgggggaa gttatccagc ggccagctaa tgctatcaaa
121 gagatgattg agaactgttt agatgcaaaa tccacaagta ttcaagtgat tgttaaagag
181 ggaggcctga agttgattca gatccaagac aatggcaccg ggatcaggaa agaagatctg
241 gatattgtat gtgaaaggtt cactactagt aaactgcagt cctttgagga tttagccagt
301 atttctacct atggctttcg aggtgaggct ttggccagca taagccatgt ggctcatgtt
361 actattacaa cgaaaacagc tgatggaaag tgtgcataca gagcaagtta ctcagatgga
421 aaactgaaag cccctcctaa accatgtgct ggcaatcaag ggacccagat cacggtggag
481 gacctttttt acaacatagc cacgaggaga aaagctttaa aaaatccaag tgaagaatat
541 gggaaaattt tggaagttgt tggcaggtat tcagtacaca atgcaggcat tagtttctca
601 gttaaaaaac aaggagagac agtagctgat gttaggacac tacccaatgc ctcaaccgtg
661 gacaatattc gctccatctt tggaaatgct gttagtcgag aactgataga aattggatgt
721 gaggataaaa ccctagcctt caaaatgaat ggttacatat ccaatgcaaa ctactcagtg
781 aagaagtgca tcttcttact cttcatcaac catcgtctgg tagaatcaac ttccttgaga
841 aaagccatag aaacagtgta tgcagcctat ttgcccaaaa acacacaccc attcctgtac
901 ctcagtttag aaatcagtcc ccagaatgtg gatgttaatg tgcaccccac aaagcatgaa
961 gttcacttcc tgcacgagga gagcatcctg gagcgggtgc agcagcacat cgagagcaag
1021 ctcctgggct ccaattcctc caggatgtac ttcacccaga ctttgctacc aggacttgct
1081 ggcccctctg gggagatggt taaatccaca acaagtctga cctcgtcttc tacttctgga
1141 agtagtgata aggtctatgc ccaccagatg gttcgtacag attcccggga acagaagctt
1201 gatgcatttc tgcagcctct gagcaaaccc ctgtccagtc agccccaggc cattgtcaca
1261 gaggataaga cagatatttc tagtggcagg gctaggcagc aagatgagga gatgcttgaa
1321 ctcccagccc ctgctgaagt ggctgccaaa aatcagagct tggaggggga tacaacaaag
1381 gggacttcag aaatgtcaga gaagagagga cctacttcca gcaaccccag aaagagacat
1441 cgggaagatt ctgatgtgga aatggtggaa gatgattccc gaaaggaaat gactgcagct
1501 tgtacccccc ggagaaggat cattaacctc actagtgttt tgagtctcca ggaagaaatt
1561 aatgagcagg gacatgaggt tctccgggag atgttgcata accactcctt cgtgggctgt
1621 gtgaatcctc agtgggcctt ggcacagcat caaaccaagt tataccttct caacaccacc
1681 aagcttagtg aagaactgtt ctaccagata ctcatttatg attttgccaa ttttggtgtt
1741 ctcaggttat cggagccagc accgctcttt gaccttgcca tgcttgcctt agatagtcca
1801 gagagtggct ggacagagga agatggtccc aaagaaggac ttgctgaata cattgttgag
1861 tttctgaaga agaaggctga gatgcttgca gactatttct ctttggaaat tgatgaggaa
1921 gggaacctga ttggattacc ccttctgatt gacaactatg tgcccccttt ggagggactg
1981 cctatcttca ttcttcgact agccactgag gtgaattggg acgaagaaaa ggaatgtttt
2041 gaaagcctca gtaaagaatg cgctatgttc tattccatcc ggaagcagta catatctgag
2101 gagtcgaccc tctcaggcca gcagagtgaa gtgcctggct ccattccaaa ctcctggaag
2161 tggactgtgg aacacattgt ctataaagcc ttgcgctcac acattctgcc tcctaaacat
2221 ttcacagaag atggaaatat cctgcagctt gctaacctgc ctgatctata caaagtcttt
2281 gagaggtgtt aaatatggtt atttatgcac tgtgggatgt gttcttcttt ctctgtattc
2341 cgatacaaag tgttgtatca aagtgtgata tacaaagtgt accaacataa gtgttggtag
2401 cacttaagac ttatacttgc cttctgatag tattccttta tacacagtgg attgattata
2461 aataaataga tgtgtcttaa cata
//
|
|
