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PMS2 |
Protein FULL name:
mismatch repair endonuclease PMS2 isoform a [Homo sapiens]
PMS2 (Homo sapiens) is product of expression of PMS2 gene.
Human diseases related to this protein:
- LYNCH SYNDROME I (#120435 )
- MISMATCH REPAIR CANCER SYNDROME (#276300 )
- COLORECTAL CANCER (#114500 )
- COLORECTAL CANCER, HEREDITARY NONPOLYPOSIS, TYPE 4 (+600259)
PMS2 is involved in:
MMR in Homo sapiens
Keywords:
FUNCTION: Component of the post-replicative DNA mismatch repair system (MMR). Heterodimerizes with MLH1 to form MutL alpha. DNA repair is initiated by MutS alpha (MSH2-MSH6) or MutS beta (MSH2- MSH6) binding to a dsDNA mismatch, then MutL alpha is recruited to the heteroduplex. Assembly of the MutL-MutS-heteroduplex ternary complex in presence of RFC and PCNA is sufficient to activate endonuclease activity of PMS2. It introduces single-strand breaks near the mismatch and thus generates new entry points for the exonuclease EXO1 to degrade the strand containing the mismatch. DNA methylation would prevent cleavage and therefore assure that only the newly mutated DNA strand is going to be corrected. MulL alpha (MLH1-PMS2) interacts physically with the clamp loader subunits of DNA polymerase III, suggesting that it may play a role to recruit the DNA polymerase III to the site of the MMR. Also implicated in DNA damage signaling, a process which induces cell cycle arrest and can lead to apoptosis in case of major DNA damages.
SUBUNIT: Heterodimer of PMS2 and MLH1 (MutL alpha). Forms a ternary complex with MutS alpha (MSH2-MSH6) or MutS beta (MSH2- MSH3). 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.
INTERACTION: P40692:MLH1; NbExp=1; IntAct=EBI-1162561, EBI-744248;
SUBCELLULAR LOCATION: Nucleus.
DISEASE: Defects in PMS2 are the cause of hereditary non-polyposis colorectal cancer type 4 (HNPCC4) [MIM:600259]. Mutations in more than one gene locus can be involved alone or in combination in the production of the HNPphenotype (also called Lynch syndrome). Most families with clinically recognized HNPhave mutations in either MLH1 or MSH2 genes. HNPis 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. HNPis reported to be the most common form of inherited colorectal cancer in the Western world, and accounts for 15% of all colon cancers. Cancers in HNPoriginate within benign neoplastic polyps termed adenomas. Clinically, HNPis 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 HNPis 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 PMS2 are a cause of mismatch repair cancer syndrome (MMRCS) [MIM:276300]; also known as Turcot syndrome or brain tumor-polyposis syndrome 1 (BTPS1). MMRCS is 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.
SIMILARITY: Belongs to the DNA mismatch repair mutL/hexB family.
WEB RESOURCE: Name=Hereditary non-polyposis colorectal cancer db; [LINK]
WEB RESOURCE: Name=GeneReviews; [LINK]
This protein can be a part of a given complexes:
| NCBI GenPept GI number(s): |
4505913 |
| Species: | Homo sapiens |
Links to other databases:
| Database | ID | Link |
| Uniprot | P54278 |
P54278 |
| PFAM: | - |
P54278 (Link - using uniprot id) |
| InterPro: | - |
P54278 (Link - using uniprot id) |
| CATH: | None | |
| SCOP: | None | |
| PDB: | - | - |
Protein sequence:
|
MERAESSSTEPAKAIKPIDRKSVHQICSGQVVLSLSTAVKELVENSLDAG ATNIDLKLKDYGVDLIEVSDNGCGVEEENFEGLTLKHHTSKIQEFADLTQ VETFGFRGEALSSLCALSDVTISTCHASAKVGTRLMFDHNGKIIQKTPYP RPRGTTVSVQQLFSTLPVRHKEFQRNIKKEYAKMVQVLHAYCIISAGIRV SCTNQLGQGKRQPVVCTGGSPSIKENIGSVFGQKQLQSLIPFVQLPPSDS VCEEYGLSCSDALHNLFYISGFISQCTHGVGRSSTDRQFFFINRRPCDPA KVCRLVNEVYHMYNRHQYPFVVLNISVDSECVDINVTPDKRQILLQEEKL LLAVLKTSLIGMFDSDVNKLNVSQQPLLDVEGNLIKMHAADLEKPMVEKQ DQSPSLRTGEEKKDVSISRLREAFSLRHTTENKPHSPKTPEPRRSPLGQK RGMLSSSTSGAISDKGVLRPQKEAVSSSHGPSDPTDRAEVEKDSGHGSTS VDSEGFSIPDTGSHCSSEYAASSPGDRGSQEHVDSQEKAPETDDSFSDVD CHSNQEDTGCKFRVLPQPTNLATPNTKRFKKEEILSSSDICQKLVNTQDM SASQVDVAVKINKKVVPLDFSMSSLAKRIKQLHHEAQQSEGEQNYRKFRA KICPGENQAAEDELRKEISKTMFAEMEIIGQFNLGFIITKLNEDIFIVDQ HATDEKYNFEMLQQHTVLQGQRLIAPQTLNLTAVNEAVLIENLEIFRKNG FDFVIDENAPVTERAKLISLPTSKNWTFGPQDVDELIFMLSDSPGVMCRP SRVKQMFASRACRKSVMIGTALNTSEMKKLITHMGEMDHPWNCPHGRPTM RHIANLGVISQN |
PMS2 (Homo sapiens) belongs to following protein families:
References:
| Title | Authors | Journal |
| Endonucleolytic function of MutLalpha in human mismatch repair. | Kadyrov FA, Dzantiev L, Constantin N, Modrich P |
|
| Mutations of two PMS homologues in hereditary nonpolyposis colon cancer. | Nicolaides NC, Papadopoulos N, Liu B, Wei YF, Carter KC, Ruben SM, Rosen CA, Haseltine WA, Fleischmann RD, Fraser CM, et al. | Nature Sept. 1, 1994 |
| The molecular basis of Turcot's syndrome. | Hamilton SR, Liu B, Parsons RE, Papadopoulos N, Jen J, Powell SM, Krush AJ, Berk T, Cohen Z, Tetu B, et al. | N Engl J Med March 1, 1995 |
| Drastic genetic instability of tumors and normal tissues in Turcot syndrome. | Miyaki M, Nishio J, Konishi M, Kikuchi-Yanoshita R, Tanaka K, Muraoka M, Nagato M, Chong JM, Koike M, Terada T, Kawahara Y, Fukutome A, Tomiyama J, Chuganji Y, Momoi M, Utsunomiya J | Oncogene Dec. 4, 1997 |
| Prevalence of germline mutations of hMLH1, hMSH2, hPMS1, hPMS2, and hMSH6 genes in 75 French kindreds with nonpolyposis colorectal cancer. | Wang Q, Lasset C, Desseigne F, Saurin JC, Maugard C, Navarro C, Ruano E, Descos L, Trillet-Lenoir V, Bosset JF, Puisieux A | Hum Genet Jan. 1, 1999 |
| BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures. | Wang Y, Cortez D, Yazdi P, Neff N, Elledge SJ, Qin J | Genes Dev April 15, 2000 |
| Structure and function of the N-terminal 40 kDa fragment of human PMS2: a monomeric GHL ATPase. | Guarne A, Junop MS, Yang W | EMBO J Oct. 1, 2001 |
| Polymorphisms and HNPCC: PMS2-MLH1 protein interactions diminished by single nucleotide polymorphisms. | Yuan ZQ, Gottlieb B, Beitel LK, Wong N, Gordon PH, Wang Q, Puisieux A, Foulkes WD, Trifiro M | Hum Mutat Jan. 1, 2002 |
| The DNA sequence of human chromosome 7. | Hillier LW, Fulton RS, Fulton LA, Graves TA, Pepin KH, Wagner-McPherson C, Layman D, Maas J, Jaeger S, Walker R, Wylie K, Sekhon M, Becker MC, O'Laughlin MD, Schaller ME, Fewell GA, Delehaunty KD, Miner TL, Nash WE, Cordes M, Du H, Sun H, Edwards J, Bradshaw-Cordum H, Ali J, Andrews S, Isak A, Vanbrunt A, Nguyen C, Du F, Lamar B, Courtney L, Kalicki J, Ozersky P, Bielicki L, Scott K, Holmes A, Harkins R, Harris A, Strong CM, Hou S, Tomlinson C, Dauphin-Kohlberg S, Kozlowicz-Reilly A, Leonard S, Rohlfing T, Rock SM, Tin-Wollam AM, Abbott A, Minx P, Maupin R, Strowmatt C, Latreille P, Miller N, Johnson D, Murray J, Woessner JP, Wendl MC, Yang SP, Schultz BR, Wallis JW, Spieth J, Bieri TA, Nelson JO, Berkowicz N, Wohldmann PE, Cook LL, Hickenbotham MT, Eldred J, Williams D, Bedell JA, Mardis ER, Clifton SW, Chissoe SL, Marra MA, Raymond C, Haugen E, Gillett W, Zhou Y, James R, Phelps K, Iadanoto S, Bubb K, Simms E, Levy R, Clendenning J, Kaul R, Kent WJ, Furey TS, Baertsch RA, Brent MR, Keibler E, Flicek P, Bork P, Suyama M, Bailey JA, Portnoy ME, Torrents D, Chinwalla AT, Gish WR, Eddy SR, McPherson JD, Olson MV, Eichler EE, Green ED, Waterston RH, Wilson RK | Nature July 10, 2003 |
| Complete sequencing and characterization of 21,243 full-length human cDNAs. | Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S | Nat Genet Feb. 1, 2004 |
| Novel PMS2 pseudogenes can conceal recessive mutations causing a distinctive childhood cancer syndrome. | De Vos M, Hayward BE, Picton S, Sheridan E, Bonthron DT | Am J Hum Genet May 1, 2004 |
| The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). | Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J | Genome Res Oct. 1, 2004 |
| Human mismatch repair: reconstitution of a nick-directed bidirectional reaction. | Constantin N, Dzantiev L, Kadyrov FA, Modrich P | J Biol Chem Dec. 2, 2005 |
| MutLalpha: at the cutting edge of mismatch repair. | Jiricny J | Cell July 28, 2006 |
| A probability-based approach for high-throughput protein phosphorylation analysis and site localization. | Beausoleil SA, Villen J, Gerber SA, Rush J, Gygi SP | Nat Biotechnol Oct. 1, 2006 |
| Mechanisms and functions of DNA mismatch repair | Guo-Min Li | Cell Res. Jan. 18, 2008 |
| Direct visualization of asymmetric adenine-nucleotide-induced conformational changes in MutL alpha. | Sacho EJ, Kadyrov FA, Modrich P, Kunkel TA, Erie DA | Mol Cell Feb. 18, 2008 |
Last modification of this entry: Oct. 14, 2010.
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