Human Gene PMS2 (ENST00000265849.12) from GENCODE V44
Description: Homo sapiens PMS1 homolog 2, mismatch repair system component (PMS2), transcript variant 1, mRNA. (from RefSeq NM_000535) RefSeq Summary (NM_000535): The protein encoded by this gene is a key component of the mismatch repair system that functions to correct DNA mismatches and small insertions and deletions that can occur during DNA replication and homologous recombination. This protein forms heterodimers with the gene product of the mutL homolog 1 (MLH1) gene to form the MutL-alpha heterodimer. The MutL-alpha heterodimer possesses an endonucleolytic activity that is activated following recognition of mismatches and insertion/deletion loops by the MutS-alpha and MutS-beta heterodimers, and is necessary for removal of the mismatched DNA. There is a DQHA(X)2E(X)4E motif found at the C-terminus of the protein encoded by this gene that forms part of the active site of the nuclease. Mutations in this gene have been associated with hereditary nonpolyposis colorectal cancer (HNPCC; also known as Lynch syndrome) and Turcot syndrome. [provided by RefSeq, Apr 2016]. Gencode Transcript: ENST00000265849.12 Gencode Gene: ENSG00000122512.17 Transcript (Including UTRs) Position: hg38 chr7:5,970,925-6,009,049 Size: 38,125 Total Exon Count: 15 Strand: - Coding Region Position: hg38 chr7:5,973,399-6,009,019 Size: 35,621 Coding Exon Count: 15
ID:PMS2_HUMAN DESCRIPTION: RecName: Full=Mismatch repair endonuclease PMS2; EC=3.1.-.-; AltName: Full=DNA mismatch repair protein PMS2; AltName: Full=PMS1 protein homolog 2; 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. Interacts with MTMR15/FAN1. INTERACTION: P40692:MLH1; NbExp=3; 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:614337]. 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, and accounts for 15% of all colon cancers. 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 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; URL="http://www.nfdht.nl/"; WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/PMS2";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P54278
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0006281 DNA repair GO:0006298 mismatch repair GO:0006974 cellular response to DNA damage stimulus GO:0016446 somatic hypermutation of immunoglobulin genes GO:0042493 response to drug GO:0090305 nucleic acid phosphodiester bond hydrolysis
BX537558 - Homo sapiens mRNA; cDNA DKFZp686J1569 (from clone DKFZp686J1569). AK125607 - Homo sapiens cDNA FLJ43619 fis, clone SPLEN2021560. JD208414 - Sequence 189438 from Patent EP1572962. JD468026 - Sequence 449050 from Patent EP1572962. JD437225 - Sequence 418249 from Patent EP1572962. JD484738 - Sequence 465762 from Patent EP1572962. DQ575836 - Homo sapiens piRNA piR-43948, complete sequence. JD120172 - Sequence 101196 from Patent EP1572962. JD066687 - Sequence 47711 from Patent EP1572962. JD176486 - Sequence 157510 from Patent EP1572962. JD138442 - Sequence 119466 from Patent EP1572962. JD306454 - Sequence 287478 from Patent EP1572962. JD169824 - Sequence 150848 from Patent EP1572962. JD529512 - Sequence 510536 from Patent EP1572962. JD395360 - Sequence 376384 from Patent EP1572962. JD125537 - Sequence 106561 from Patent EP1572962. JD529359 - Sequence 510383 from Patent EP1572962. JD430283 - Sequence 411307 from Patent EP1572962. JD092528 - Sequence 73552 from Patent EP1572962. JD306268 - Sequence 287292 from Patent EP1572962. JD420909 - Sequence 401933 from Patent EP1572962. JD370232 - Sequence 351256 from Patent EP1572962. JD148381 - Sequence 129405 from Patent EP1572962. JD463898 - Sequence 444922 from Patent EP1572962. JD478646 - Sequence 459670 from Patent EP1572962. JD543364 - Sequence 524388 from Patent EP1572962. JD425612 - Sequence 406636 from Patent EP1572962. JD304354 - Sequence 285378 from Patent EP1572962. AK294661 - Homo sapiens cDNA FLJ60089 complete cds, highly similar to PMS1 protein homolog 2. BC031832 - Homo sapiens PMS2 postmeiotic segregation increased 2 (S. cerevisiae), mRNA (cDNA clone IMAGE:4419131). U14658 - Human DNA mismatch repair gene homologue (hPMS2) mRNA, complete cds. JD369754 - Sequence 350778 from Patent EP1572962. BC093921 - Homo sapiens PMS2 postmeiotic segregation increased 2 (S. cerevisiae), mRNA (cDNA clone MGC:120956 IMAGE:7939766), complete cds. BC143397 - Homo sapiens cDNA clone IMAGE:9051904, with apparent retained intron. JD289879 - Sequence 270903 from Patent EP1572962. JD298266 - Sequence 279290 from Patent EP1572962. JD493116 - Sequence 474140 from Patent EP1572962. AB103086 - Homo sapiens PMS2 mRNA for postmeiotic segregation increased 2 nirs variant 5, complete cds. AB103083 - Homo sapiens PMS2 mRNA for postmeiotic segregation increased 2 nirs variant 2, complete cds. AK312390 - Homo sapiens cDNA, FLJ92721, highly similar to Homo sapiens PMS2 postmeiotic segregation increased 2 (S.cerevisiae) (PMS2), mRNA. JD376437 - Sequence 357461 from Patent EP1572962. KJ905672 - Synthetic construct Homo sapiens clone ccsbBroadEn_15328 PMS2CL gene, encodes complete protein. KJ905275 - Synthetic construct Homo sapiens clone ccsbBroadEn_14772 PMS2 gene, encodes complete protein. AB587472 - Synthetic construct DNA, clone: pF1KB8500, Homo sapiens PMS2 gene for PMS2 postmeiotic segregation increased 2, without stop codon, in Flexi system. JD485344 - Sequence 466368 from Patent EP1572962. JD378403 - Sequence 359427 from Patent EP1572962. JD435623 - Sequence 416647 from Patent EP1572962. JD522655 - Sequence 503679 from Patent EP1572962. AB103082 - Homo sapiens PMS2 mRNA for postmeiotic segregation increased 2 nirs variant 1, complete cds. JD484416 - Sequence 465440 from Patent EP1572962. AB103087 - Homo sapiens PMS2 mRNA for postmeiotic segregation increased 2 nirs variant 6, complete cds. JD208069 - Sequence 189093 from Patent EP1572962. JD214335 - Sequence 195359 from Patent EP1572962. BC008400 - Homo sapiens PMS2 postmeiotic segregation increased 2 (S. cerevisiae), mRNA (cDNA clone IMAGE:4273792). AB103085 - Homo sapiens PMS2 mRNA for postmeiotic segregation increased 2 nirs variant 4, complete cds. AB103084 - Homo sapiens PMS2 mRNA for postmeiotic segregation increased 2 nirs variant 3, complete cds. JD538559 - Sequence 519583 from Patent EP1572962. JD316586 - Sequence 297610 from Patent EP1572962.
Biochemical and Signaling Pathways
KEGG - Kyoto Encyclopedia of Genes and Genomes hsa03430 - Mismatch repair
Reactome (by CSHL, EBI, and GO)
Protein P54278 (Reactome details) participates in the following event(s):
R-HSA-5444523 Formation of MSH1:PMS2 Complex R-HSA-5358510 MSH2:MSH6 recruits MLH1:PMS2 to mismatch and interacts with PCNA R-HSA-5358519 MSH2:MSH3 recruits MLH1:PMS2 to mismatch and interacts with PCNA R-HSA-5358518 MLH1:PMS2 makes single strand incision near 1-2 base mismatch R-HSA-5358545 EXO1 interacts with MSH2:MSH3 (MutSbeta) and MLH1:PMS2 (MutLalpha) R-HSA-5358512 MLH1:PMS2 makes single strand incision near insertion/deletion loop of 2 bases or more R-HSA-5358597 EXO1 interacts with MSH2:MSH6 (MutSalpha) and MLH1:PMS2 (MutLalpha) R-HSA-5358565 Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha) R-HSA-5545483 Defective Mismatch Repair Associated With MLH1 R-HSA-6796648 TP53 Regulates Transcription of DNA Repair Genes R-HSA-5358606 Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta) R-HSA-5358508 Mismatch Repair R-HSA-5423599 Diseases of Mismatch Repair (MMR) R-HSA-3700989 Transcriptional Regulation by TP53 R-HSA-5632987 Defective Mismatch Repair Associated With PMS2 R-HSA-73894 DNA Repair R-HSA-1643685 Disease R-HSA-212436 Generic Transcription Pathway R-HSA-73857 RNA Polymerase II Transcription R-HSA-74160 Gene expression (Transcription)
US Server
