| General information about the entry |
| Entry name | MLH1_HUMAN | ||
| Primary accession number | P40692 | ||
| Secondary accession numbers | None | ||
| Entered in SWISS-PROT in | Release 31, February 1995 | ||
| Sequence was last modified in | Release 31, February 1995 | ||
| Annotations were last modified in | Release 40, October 2001 | ||
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| Protein name | DNA mismatch repair protein Mlh1 | ||
| Synonym | MutL protein homolog 1 | ||
| Gene name |
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| From |
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| Taxonomy | Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. | ||
| References |
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[1] |
SEQUENCE FROM NUCLEIC ACID. MEDLINE=94195398; PubMed=8145827; [NCBI, ExPASy, EBI, Israel, Japan] Bronner C.E., Baker S.M., Morrison P.T., Warren G., Smith L.G., Lescoe M.K., Kane M., Earibino C., Lipford J., Lindblom A., Tannergaard P., Bollag R.J., Godwin A.R., Ward D.C., Nordenskjoeld M., Fishel R., Kolodner R.D., Liskay R.M.; "Mutation in the DNA mismatch repair gene homologue hMLH1 is associated with hereditary non-polyposis colon cancer."; Nature 368:258-261(1994). |
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[2] |
SEQUENCE FROM NUCLEIC ACID. MEDLINE=95112274; PubMed=7812952; [NCBI, ExPASy, EBI, Israel, Japan] 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., Bishop D.T.; "Structure of the human MLH1 locus and analysis of a large hereditary nonpolyposis colorectal carcinoma kindred for mlh1 mutations."; Cancer Res. 55:242-248(1995). |
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[3] |
SEQUENCE FROM NUCLEIC ACID. TISSUE=Gall bladder; MEDLINE=94174309; PubMed=8128251; [NCBI, ExPASy, EBI, Israel, Japan] 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., Vogelstein B.; "Mutation of a mutL homolog in hereditary colon cancer."; Science 263:1625-1629(1994). |
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[4] |
SEQUENCE FROM NUCLEIC ACID, AND VARIANTS HNPCC L-542; P-574; V-582 AND T-618. MEDLINE=95276736; PubMed=7757073; [NCBI, ExPASy, EBI, Israel, Japan] Han H.-J., Maruyama M., Baba S., Park J.-G., Nakamura Y.; "Genomic structure of human mismatch repair gene, hMLH1, and its mutation analysis in patients with hereditary non-polyposis colorectal cancer (HNPCC)."; Hum. Mol. Genet. 4:237-242(1995). |
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[5] |
REVIEW ON VARIANTS. MEDLINE=97403931; PubMed=9259192; [NCBI, ExPASy, EBI, Israel, Japan] Papadopoulos N., Lindblom A.; "Molecular basis of HNPCC: mutations of MMR genes."; Hum. Mutat. 10:89-99(1997). |
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[6] |
VARIANT HNPCC LYS-616 DEL. MEDLINE=96152126; PubMed=8571956; [NCBI, ExPASy, EBI, Israel, Japan] 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., Fodde R.; "Majority of hMLH1 mutations responsible for hereditary nonpolyposis colorectal cancer cluster at the exonic region 15-16."; Am. J. Hum. Genet. 58:300-307(1996). |
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[7] |
VARIANTS HNPCC MET-117 AND LEU-226. MEDLINE=96163505; PubMed=8566964; [NCBI, ExPASy, EBI, Israel, Japan] Maliaka Y.K., Chudina A.P., Belev N.F., Alday P., Bochkov N.P., Buerstedde J.-M.; "CpG dinucleotides in the hMSH2 and hMLH1 genes are hotspots for HNPCC mutations."; Hum. Genet. 97:251-255(1996). |
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[8] |
VARIANT CANCER LEU-ASN-HIS-37 INS, AND VARIANT ASP-384. MEDLINE=96183273; PubMed=8609062; [NCBI, ExPASy, EBI, Israel, Japan] Kobayashi K., Matsushima M., Koi S., Saito H., Sagae S., Kudo R., Nakamura Y.; "Mutational analysis of mismatch repair genes, hMLH1 and hMSH2, in sporadic endometrial carcinomas with microsatellite instability."; Jpn. J. Cancer Res. 87:141-145(1996). |
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[9] |
VARIANTS HNPCC LYS-62; SER-64; ALA-618; PRO-659 AND LYS-616 DEL. MEDLINE=97456423; PubMed=9311737; [NCBI, ExPASy, EBI, Israel, Japan] Wijnen J., Khan P.M., Vasen H., van der Klift H., Mulder A., van Leeuwen-Cornelisse I., Bakker B., Losekoot M., Moeller P., Fodde R.; "Hereditary nonpolyposis colorectal cancer families not complying with the Amsterdam criteria show extremely low frequency of mismatch-repair-gene mutations."; Am. J. Hum. Genet. 61:329-335(1997). |
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[10] |
VARIANT HNPCC ARG-67, AND VARIANT VAL-219. MEDLINE=97220595; PubMed=9067757; [NCBI, ExPASy, EBI, Israel, Japan] Sasaki S., Tokino T., Miyatsu T., Muto T., Nakamura Y.; "Mutational analysis of the hMLH1 gene using an automated two-dimensional DNA typing system."; Hum. Mutat. 9:164-171(1997). |
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[11] |
VARIANT HNPCC 626-SER-THR-627. MEDLINE=97201114; PubMed=9048925; [NCBI, ExPASy, EBI, Israel, Japan] Beck N.E., Tomlinson I.P.M., Homfray T., Frayling I., Hodgson S.V., Harocopos C., Bodmer W.F.; "Use of SSCP analysis to identify germline mutations in HNPCC families fulfilling the Amsterdam criteria."; Hum. Genet. 99:219-224(1997). |
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[12] |
VARIANT HNPCC LEU-28. MEDLINE=97442278; PubMed=9298827; [NCBI, ExPASy, EBI, Israel, Japan] Wehner M., Buschhausen L., Lamberti C., Kruse R., Caspari R., Propping P., Friedl W.; "Hereditary nonpolyposis colorectal cancer (HNPCC): eight novel germline mutations in hMSH2 or hMLH1 genes."; Hum. Mutat. 10:241-244(1997). |
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[13] |
VARIANTS HNPCC, AND VARIANTS. MEDLINE=98386069; PubMed=9718327; [NCBI, ExPASy, EBI, Israel, Japan] Farrington S.M., Lin-Goerke J., Ling J., Wang Y., Burczak J.D., Robbins D.J., Dunlop M.G.; "Systematic analysis of hMSH2 and hMLH1 in young colon cancer patients and controls."; Am. J. Hum. Genet. 63:749-759(1998). |
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[14] |
VARIANT HNPCC LYS-69. Herfarth K.K.-F., Ogunbiyi O.A., Moley J.F., Kodner I.J., Wells S.A. Jr., Goodfellow P.J.; "Four new mutations in the DNA mismatch repair gene MLH1 in colorectal cancers with microsatellite instability."; Hum. Mutat. 12:73-73(1998). |
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[15] |
VARIANTS HNPCC ARG-77 AND PRO-193. Panariello L., Scarano M.I., de Rosa M., Capasso L., Renda A., Riegler G., Rossi G.B., Salvatore F., Izzo P.; "hMLH1 mutations in hereditary nonpolyposis colorectal cancer kindreds."; Hum. Mutat. 12:216-217(1998). |
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[16] |
VARIANT HNPCC GLY-93. Quaresima B., Grandinetti C., Baudi F., Tassone P., Barbieri V., Conforti S., Avvedimento E.V., Costanzo F., Venuta S.; "Hereditary nonpolyposis colorectal cancer: identification of novel germline mutations in two kindreds not fulfilling the Amsterdam criteria."; Hum. Mutat. 12:433-433(1998). |
| Comments |
- FUNCTION: PROBABLY INVOLVED IN THE REPAIR OF MISMATCHES IN DNA.
- SUBUNIT: HETERODIMER OF MLH1 AND PMS2 OR MLH1 AND MLH3.
- TISSUE SPECIFICITY: COLON, LYMPHOCYTES, BREAST, LUNG, SPLEEN, TESTIS, PROSTATE, THYROID, GALL BLADDER AND HEART.
- DISEASE: ASSOCIATED WITH FAMILIAL HEREDITARY NONPOLYPOSIS COLON CANCER (HNPCC) (LYNCH SYNDROME). HNPCC IS ONE OF THE MOST COMMON GENETIC DISEASES IN THE WESTERN WORLD, AND ACCOUNTS FOR 15% OF ALL COLON CANCERS. IT 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.
- SIMILARITY: BELONGS TO THE DNA MISMATCH REPAIR MUTL/HEXB FAMILY.
| Copyright |
| Cross-references |
| EMBL |
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| PIR | S43085; S43085. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HSSP | P23367; 1BKN. [HSSP ENTRY / PDB] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| MIM | 120436 [NCBI / EBI]. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| GeneCards | MLH1. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| GeneLynx | MLH1. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| InterPro | IPR002099; DNA_mis_repair. IPR003594; HATPase_c. Graphical view of domain structure. |
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| Pfam | PF01119; DNA_mis_repair; 1. PF02518; HATPase_c; 1. |
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| PROSITE | PS00058; DNA_MISMATCH_REPAIR_1; 1. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| ProDom | [Domain structure / List of seq. sharing at least 1 domain]. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BLOCKS | P40692. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DOMO | P40692. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| ProtoMap | P40692. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| PRESAGE | P40692. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DIP | P40692. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ensembl | P40692. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| SWISS-2DPAGE | GET REGION ON 2D PAGE. |
| Keywords |
| DNA repair; Disease mutation; Anti-oncogene; Polymorphism. |
| Features |
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| Sequence information |
| Length: 756 AA | Molecular weight: 84600 Da | CRC64: C9231FC406C2CA20 [This is a checksum on the sequence] |
10 20 30 40 50 60
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MSFVAGVIRR LDETVVNRIA AGEVIQRPAN AIKEMIENCL DAKSTSIQVI VKEGGLKLIQ
70 80 90 100 110 120
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IQDNGTGIRK EDLDIVCERF TTSKLQSFED LASISTYGFR GEALASISHV AHVTITTKTA
130 140 150 160 170 180
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DGKCAYRASY SDGKLKAPPK PCAGNQGTQI TVEDLFYNIA TRRKALKNPS EEYGKILEVV
190 200 210 220 230 240
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GRYSVHNAGI SFSVKKQGET VADVRTLPNA STVDNIRSIF GNAVSRELIE IGCEDKTLAF
250 260 270 280 290 300
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KMNGYISNAN YSVKKCIFLL FINHRLVEST SLRKAIETVY AAYLPKNTHP FLYLSLEISP
310 320 330 340 350 360
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QNVDVNVHPT KHEVHFLHEE SILERVQQHI ESKLLGSNSS RMYFTQTLLP GLAGPSGEMV
370 380 390 400 410 420
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KSTTSLTSSS TSGSSDKVYA HQMVRTDSRE QKLDAFLQPL SKPLSSQPQA IVTEDKTDIS
430 440 450 460 470 480
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SGRARQQDEE MLELPAPAEV AAKNQSLEGD TTKGTSEMSE KRGPTSSNPR KRHREDSDVE
490 500 510 520 530 540
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MVEDDSRKEM TAACTPRRRI INLTSVLSLQ EEINEQGHEV LREMLHNHSF VGCVNPQWAL
550 560 570 580 590 600
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AQHQTKLYLL NTTKLSEELF YQILIYDFAN FGVLRLSEPA PLFDLAMLAL DSPESGWTEE
610 620 630 640 650 660
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DGPKEGLAEY IVEFLKKKAE MLADYFSLEI DEEGNLIGLP LLIDNYVPPL EGLPIFILRL
670 680 690 700 710 720
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ATEVNWDEEK ECFESLSKEC AMFYSIRKQY ISEESTLSGQ QSEVPGSIPN SWKWTVEHIV
730 740 750
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YKALRSHILP PKHFTEDGNI LQLANLPDLY KVFERC
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P40692 in FASTA format |
