PMS2_HUMAN
ID PMS2_HUMAN Reviewed; 862 AA.
AC P54278; B2R610; Q52LH6; Q5FBW9; Q5FBX1; Q5FBX2; Q75MR2;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2011, sequence version 2.
DT 03-AUG-2022, entry version 219.
DE RecName: Full=Mismatch repair endonuclease PMS2 {ECO:0000305};
DE EC=3.1.-.-;
DE AltName: Full=DNA mismatch repair protein PMS2;
DE AltName: Full=PMS1 protein homolog 2;
GN Name=PMS2 {ECO:0000312|HGNC:HGNC:9122};
GN Synonyms=PMSL2 {ECO:0000312|HGNC:HGNC:9122};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS GLN-20 AND GLU-541.
RC TISSUE=Endometrial tumor;
RX PubMed=8072530; DOI=10.1038/371075a0;
RA Nicolaides N.C., Papadopoulos N., Liu B., Wei Y.-F., Carter K.C.,
RA Ruben S.M., Rosen C.A., Haseltine W.H., Fleischmann R.D., Fraser C.M.,
RA Adams M.D., Venter J.C., Dunlop M.G., Hamilton S.R., Petersen G.M.,
RA de la Chapelle A., Vogelstein B., Kinzler K.W.;
RT "Mutations of two PMS homologues in hereditary nonpolyposis colon cancer.";
RL Nature 371:75-80(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3 AND 4), AND VARIANT GLU-541.
RA Tabata Y., Sameshima E., Hayashi A., Iida K., Mitsuyama M., Kanai S.,
RA Furuya T., Saito T.;
RT "PMS2 mRNA, nirs splice variants.";
RL Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS SER-470 AND GLU-541.
RA Bronner C.E., Baker S.M., Morrison P.T., Warren G., Smith L.G.,
RA Lescoe M.K., Kane M.F., Earibino C., Lipford J., Lindblom A.,
RA Tannergaard P., Bollag R.J., Godwin A.R., Ward D.C., Nordenskjoeld M.,
RA Fishel R., Kolodner R.D., Liskay R.M.;
RL Submitted (OCT-1994) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS SER-470
RP AND GLU-541.
RC TISSUE=Amygdala;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS GLU-541
RP AND ILE-622.
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP IDENTIFICATION OF PMS2 AS MEMBER OF BASC.
RX PubMed=10783165;
RA Wang Y., Cortez D., Yazdi P., Neff N., Elledge S.J., Qin J.;
RT "BASC, a super complex of BRCA1-associated proteins involved in the
RT recognition and repair of aberrant DNA structures.";
RL Genes Dev. 14:927-939(2000).
RN [8]
RP INVOLVEMENT IN HNPCC4.
RX PubMed=15887124; DOI=10.1053/j.gastro.2005.04.008;
RA Worthley D.L., Walsh M.D., Barker M., Ruszkiewicz A., Bennett G.,
RA Phillips K., Suthers G.;
RT "Familial mutations in PMS2 can cause autosomal dominant hereditary
RT nonpolyposis colorectal cancer.";
RL Gastroenterology 128:1431-1436(2005).
RN [9]
RP FUNCTION AS AN ENDONUCLEASE.
RX PubMed=16873062; DOI=10.1016/j.cell.2006.05.039;
RA Kadyrov F.A., Dzantiev L., Constantin N., Modrich P.;
RT "Endonucleolytic function of MutLalpha in human mismatch repair.";
RL Cell 126:297-308(2006).
RN [10]
RP INVOLVEMENT IN HNPCC4.
RX PubMed=18178629; DOI=10.1136/jmg.2007.056150;
RA Clendenning M., Senter L., Hampel H., Robinson K.L., Sun S., Buchanan D.,
RA Walsh M.D., Nilbert M., Green J., Potter J., Lindblom A.,
RA de la Chapelle A.;
RT "A frame-shift mutation of PMS2 is a widespread cause of Lynch syndrome.";
RL J. Med. Genet. 45:340-345(2008).
RN [11]
RP FUNCTION.
RX PubMed=18206974; DOI=10.1016/j.molcel.2007.10.030;
RA Sacho E.J., Kadyrov F.A., Modrich P., Kunkel T.A., Erie D.A.;
RT "Direct visualization of asymmetric adenine nucleotide-induced
RT conformational changes in MutL alpha.";
RL Mol. Cell 29:112-121(2008).
RN [12]
RP REVIEW.
RX PubMed=16188885; DOI=10.1074/jbc.m509701200;
RA Constantin N., Dzantiev L., Kadyrov F.A., Modrich P.;
RT "Human mismatch repair: reconstitution of a nick-directed bidirectional
RT reaction.";
RL J. Biol. Chem. 280:39752-39761(2005).
RN [13]
RP REVIEW.
RX PubMed=16873053; DOI=10.1016/j.cell.2006.07.003;
RA Jiricny J.;
RT "MutLalpha: at the cutting edge of mismatch repair.";
RL Cell 126:239-241(2006).
RN [14]
RP REVIEW.
RX PubMed=18157157; DOI=10.1038/cr.2007.115;
RA Li G.M.;
RT "Mechanisms and functions of DNA mismatch repair.";
RL Cell Res. 18:85-98(2008).
RN [15]
RP INTERACTION WITH MTMR15.
RX PubMed=20603073; DOI=10.1016/j.molcel.2010.06.023;
RA Smogorzewska A., Desetty R., Saito T.T., Schlabach M., Lach F.P.,
RA Sowa M.E., Clark A.B., Kunkel T.A., Harper J.W., Colaiacovo M.P.,
RA Elledge S.J.;
RT "A genetic screen identifies FAN1, a Fanconi anemia-associated nuclease
RT necessary for DNA interstrand crosslink repair.";
RL Mol. Cell 39:36-47(2010).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-597, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-573, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 1-364.
RX PubMed=11574484; DOI=10.1093/emboj/20.19.5521;
RA Guarne A., Junop M.S., Yang W.;
RT "Structure and function of the N-terminal 40 kDa fragment of human PMS2: a
RT monomeric GHL ATPase.";
RL EMBO J. 20:5521-5531(2001).
RN [19]
RP INVOLVEMENT IN MMRCS4.
RX PubMed=7661930; DOI=10.1056/nejm199503303321302;
RA Hamilton S.R., Liu B., Parsons R.E., Papadopoulos N., Jen J., Powell S.M.,
RA Krush A.J., Berk T., Cohen Z., Tetu B., Burger P.C., Wood P.A., Taqi F.,
RA Booker S.V., Petersen G.M., Offerhaus G.J.A., Tersmette A.C.,
RA Giardiello F.M., Vogelstein B., Kinzler K.W.;
RT "The molecular basis of Turcot's syndrome.";
RL N. Engl. J. Med. 332:839-847(1995).
RN [20]
RP VARIANT MMRCS4 LYS-705.
RX PubMed=9419979; DOI=10.1038/sj.onc.1201668;
RA Miyaki M., Nishio J., Konishi M., Kikuchi-Yanoshita R., Tanaka K.,
RA Muraoka M., Nagato M., Chong J.-M., Koike M., Terada T., Kawahara Y.,
RA Fukutome A., Tomiyama J., Chuganji Y., Momoi M., Utsunomiya J.;
RT "Drastic genetic instability of tumors and normal tissues in Turcot
RT syndrome.";
RL Oncogene 15:2877-2881(1997).
RN [21]
RP VARIANTS HNPCC4 GLN-479 AND ILE-622, AND VARIANTS LYS-485; ALA-511 AND
RP SER-597.
RX PubMed=10480359; DOI=10.1007/s004399900064;
RA Wang Q., Lasset C., Desseigne F., Saurin J.-C., Maugard C., Navarro C.,
RA Ruano E., Descos L., Trillet-Lenoir V., Bosset J.-F., Puisieux A.;
RT "Prevalence of germline mutations of hMLH1, hMSH2, hPMS1, hPMS2, and hMSH6
RT genes in 75 French kindreds with nonpolyposis colorectal cancer.";
RL Hum. Genet. 105:79-85(1999).
RN [22]
RP CHARACTERIZATION OF VARIANT HNPCC4 ILE-622, AND CHARACTERIZATION OF VARIANT
RP SER-597.
RX PubMed=11793469; DOI=10.1002/humu.10040;
RA Yuan Z.Q., Gottlieb B., Beitel L.K., Wong N., Gordon P.H., Wang Q.,
RA Puisieux A., Foulkes W.D., Trifiro M.;
RT "Polymorphisms and HNPCC: PMS2-MLH1 protein interactions diminished by
RT single nucleotide polymorphisms.";
RL Hum. Mutat. 19:108-113(2002).
RN [23]
RP INVOLVEMENT IN MMRCS4.
RX PubMed=15077197; DOI=10.1086/420796;
RA De Vos M., Hayward B.E., Picton S., Sheridan E., Bonthron D.T.;
RT "Novel PMS2 pseudogenes can conceal recessive mutations causing a
RT distinctive childhood cancer syndrome.";
RL Am. J. Hum. Genet. 74:954-964(2004).
RN [24]
RP VARIANTS HNPCC4 ILE-585 AND ILE-622, AND VARIANTS VAL-18; GLN-20; SER-470;
RP LYS-485; GLU-541; SER-597 AND ALA-857.
RX PubMed=16472587; DOI=10.1053/j.gastro.2005.10.052;
RA Hendriks Y.M., Jagmohan-Changur S., van der Klift H.M., Morreau H.,
RA van Puijenbroek M., Tops C., van Os T., Wagner A., Ausems M.G., Gomez E.,
RA Breuning M.H., Broecker-Vriends A.H., Vasen H.F., Wijnen J.T.;
RT "Heterozygous mutations in PMS2 cause hereditary nonpolyposis colorectal
RT carcinoma (Lynch syndrome).";
RL Gastroenterology 130:312-322(2006).
RN [25]
RP VARIANTS HNPCC4 THR-182 AND ARG-797, AND VARIANTS VAL-18 AND LEU-563.
RX PubMed=16619239; DOI=10.1002/humu.20318;
RA Clendenning M., Hampel H., LaJeunesse J., Lindblom A., Lockman J.,
RA Nilbert M., Senter L., Sotamaa K., de la Chapelle A.;
RT "Long-range PCR facilitates the identification of PMS2-specific
RT mutations.";
RL Hum. Mutat. 27:490-495(2006).
RN [26]
RP VARIANT MMRCS4 ILE-46.
RX PubMed=17557300; DOI=10.1002/humu.20569;
RA Auclair J., Leroux D., Desseigne F., Lasset C., Saurin J.C., Joly M.O.,
RA Pinson S., Xu X.L., Montmain G., Ruano E., Navarro C., Puisieux A.,
RA Wang Q.;
RT "Novel biallelic mutations in MSH6 and PMS2 genes: gene conversion as a
RT likely cause of PMS2 gene inactivation.";
RL Hum. Mutat. 28:1084-1090(2007).
RN [27]
RP VARIANTS HNPCC4 ASN-46; ILE-46; PRO-205; ILE-622; ALA-663; LYS-705; ASP-750
RP AND TYR-843, AND VARIANT LEU-563.
RX PubMed=18602922; DOI=10.1053/j.gastro.2008.04.026;
RA Senter L., Clendenning M., Sotamaa K., Hampel H., Green J., Potter J.D.,
RA Lindblom A., Lagerstedt K., Thibodeau S.N., Lindor N.M., Young J.,
RA Winship I., Dowty J.G., White D.M., Hopper J.L., Baglietto L.,
RA Jenkins M.A., de la Chapelle A.;
RT "The clinical phenotype of Lynch syndrome due to germ-line PMS2
RT mutations.";
RL Gastroenterology 135:419-428(2008).
RN [28]
RP VARIANT HNPCC4 GLU-207.
RX PubMed=19479271; DOI=10.1007/s00384-009-0731-1;
RA Montazer Haghighi M., Radpour R., Aghajani K., Zali N., Molaei M.,
RA Zali M.R.;
RT "Four novel germline mutations in the MLH1 and PMS2 mismatch repair genes
RT in patients with hereditary nonpolyposis colorectal cancer.";
RL Int. J. Colorectal Dis. 24:885-893(2009).
RN [29]
RP VARIANTS THR-423; MET-511 AND PRO-511.
RX PubMed=20186689; DOI=10.1002/humu.21223;
RA Ganster C., Wernstedt A., Kehrer-Sawatzki H., Messiaen L., Schmidt K.,
RA Rahner N., Heinimann K., Fonatsch C., Zschocke J., Wimmer K.;
RT "Functional PMS2 hybrid alleles containing a pseudogene-specific missense
RT variant trace back to a single ancient intrachromosomal recombination
RT event.";
RL Hum. Mutat. 31:552-560(2010).
RN [30]
RP CHARACTERIZATION OF VARIANTS VAL-18; GLN-20; ALA-41; GLU-60; THR-423;
RP LYS-485; ALA-511; MET-511; GLU-541; LEU-563; ILE-571; SER-597 AND ALA-857,
RP CHARACTERIZATION OF VARIANTS HNPCC4 ASN-46; ILE-46; PRO-205; GLU-207;
RP VAL-263; GLN-479; ILE-622; ALA-663; LYS-705; ASP-750; ARG-797 AND TYR-843,
RP AND MUTAGENESIS OF GLU-41 AND TYR-519.
RX PubMed=24027009; DOI=10.1002/humu.22426;
RA Drost M., Koppejan H., de Wind N.;
RT "Inactivation of DNA mismatch repair by variants of uncertain significance
RT in the PMS2 gene.";
RL Hum. Mutat. 34:1477-1480(2013).
RN [31]
RP VARIANT HNPCC4 ILE-46, VARIANTS GLN-20; SER-470; SER-597 AND SER-775,
RP CHARACTERIZATION OF VARIANT HNPCC4 ILE-46, CHARACTERIZATION OF VARIANTS
RP GLN-20 AND SER-470, MUTAGENESIS OF ASP-70, FUNCTION, AND SUBCELLULAR
RP LOCATION.
RX PubMed=23709753; DOI=10.1136/jmedgenet-2012-101511;
RA Borras E., Pineda M., Cadinanos J., Del Valle J., Brieger A.,
RA Hinrichsen I., Cabanillas R., Navarro M., Brunet J., Sanjuan X.,
RA Musulen E., van der Klift H., Lazaro C., Plotz G., Blanco I., Capella G.;
RT "Refining the role of PMS2 in Lynch syndrome: germline mutational analysis
RT improved by comprehensive assessment of variants.";
RL J. Med. Genet. 50:552-563(2013).
RN [32]
RP VARIANTS MMRCS4 ILE-46; THR-66; TRP-107; GLY-115; PRO-205; VAL-263;
RP LYS-307; SER-437; GLN-479; VAL-488; GLN-504; ILE-585 AND LEU-815,
RP CHARACTERIZATION OF VARIANTS MMRCS4 ILE-46; THR-66; TRP-107; GLY-115;
RP LYS-307; SER-437; VAL-488; GLN-504 AND LEU-815, VARIANTS VAL-18; GLU-60;
RP SER-470; LEU-563; ILE-571 AND SER-775, AND CHARACTERIZATION OF VARIANTS
RP SER-470 AND SER-775.
RX PubMed=27435373; DOI=10.1002/humu.23052;
RA van der Klift H.M., Mensenkamp A.R., Drost M., Bik E.C., Vos Y.J.,
RA Gille H.J., Redeker B.E., Tiersma Y., Zonneveld J.B., Garcia E.G.,
RA Letteboer T.G., Olderode-Berends M.J., van Hest L.P., van Os T.A.,
RA Verhoef S., Wagner A., van Asperen C.J., Ten Broeke S.W., Hes F.J.,
RA de Wind N., Nielsen M., Devilee P., Ligtenberg M.J., Wijnen J.T.,
RA Tops C.M.;
RT "Comprehensive mutation analysis of PMS2 in a large cohort of probands
RT suspected of lynch syndrome or constitutional mismatch repair deficiency
RT syndrome.";
RL Hum. Mutat. 37:1162-1179(2016).
RN [33]
RP VARIANTS ARG-36; GLU-475; HIS-699; ASN-792 AND MET-853, AND
RP CHARACTERIZATION OF VARIANTS ARG-36; GLU-475; HIS-699; ASN-792 AND MET-853.
RX PubMed=28494185; DOI=10.1080/15384047.2017.1326439;
RA Arora S., Huwe P.J., Sikder R., Shah M., Browne A.J., Lesh R., Nicolas E.,
RA Deshpande S., Hall M.J., Dunbrack R.L. Jr., Golemis E.A.;
RT "Functional analysis of rare variants in mismatch repair proteins augments
RT results from computation-based predictive methods.";
RL Cancer Biol. Ther. 18:519-533(2017).
CC -!- FUNCTION: Component of the post-replicative DNA mismatch repair system
CC (MMR). Heterodimerizes with MLH1 to form MutL alpha. DNA repair is
CC initiated by MutS alpha (MSH2-MSH6) or MutS beta (MSH2-MSH3) binding to
CC a dsDNA mismatch, then MutL alpha is recruited to the heteroduplex.
CC Assembly of the MutL-MutS-heteroduplex ternary complex in presence of
CC RFC and PCNA is sufficient to activate endonuclease activity of PMS2.
CC It introduces single-strand breaks near the mismatch and thus generates
CC new entry points for the exonuclease EXO1 to degrade the strand
CC containing the mismatch. DNA methylation would prevent cleavage and
CC therefore assure that only the newly mutated DNA strand is going to be
CC corrected. MutL alpha (MLH1-PMS2) interacts physically with the clamp
CC loader subunits of DNA polymerase III, suggesting that it may play a
CC role to recruit the DNA polymerase III to the site of the MMR. Also
CC implicated in DNA damage signaling, a process which induces cell cycle
CC arrest and can lead to apoptosis in case of major DNA damages.
CC {ECO:0000269|PubMed:16873062, ECO:0000269|PubMed:18206974,
CC ECO:0000269|PubMed:23709753}.
CC -!- SUBUNIT: Heterodimer of PMS2 and MLH1 (MutL alpha). Forms a ternary
CC complex with MutS alpha (MSH2-MSH6) or MutS beta (MSH2-MSH3). Part of
CC the BRCA1-associated genome surveillance complex (BASC), which contains
CC BRCA1, MSH2, MSH6, MLH1, ATM, BLM, PMS2 and the RAD50-MRE11-NBS1
CC protein complex. This association could be a dynamic process changing
CC throughout the cell cycle and within subnuclear domains. Interacts with
CC MTMR15/FAN1. {ECO:0000269|PubMed:20603073}.
CC -!- INTERACTION:
CC P54278; P40692: MLH1; NbExp=21; IntAct=EBI-1162561, EBI-744248;
CC P54278-1; O15350: TP73; NbExp=3; IntAct=EBI-15726984, EBI-389606;
CC P54278-2; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-12176841, EBI-16439278;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:23709753}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=P54278-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P54278-2; Sequence=VSP_029386;
CC Name=3;
CC IsoId=P54278-3; Sequence=VSP_029387, VSP_029388;
CC Name=4;
CC IsoId=P54278-4; Sequence=VSP_029384, VSP_029385;
CC -!- DISEASE: Hereditary non-polyposis colorectal cancer 4 (HNPCC4)
CC [MIM:614337]: An autosomal dominant disease associated with marked
CC increase in cancer susceptibility. It is characterized by a familial
CC predisposition to early-onset colorectal carcinoma (CRC) and extra-
CC colonic tumors of the gastrointestinal, urological and female
CC reproductive tracts. HNPCC is reported to be the most common form of
CC inherited colorectal cancer in the Western world. Clinically, HNPCC is
CC often divided into two subgroups. Type I is characterized by hereditary
CC predisposition to colorectal cancer, a young age of onset, and
CC carcinoma observed in the proximal colon. Type II is characterized by
CC increased risk for cancers in certain tissues such as the uterus,
CC ovary, breast, stomach, small intestine, skin, and larynx in addition
CC to the colon. Diagnosis of classical HNPCC is based on the Amsterdam
CC criteria: 3 or more relatives affected by colorectal cancer, one a
CC first degree relative of the other two; 2 or more generation affected;
CC 1 or more colorectal cancers presenting before 50 years of age;
CC exclusion of hereditary polyposis syndromes. The term 'suspected HNPCC'
CC or 'incomplete HNPCC' can be used to describe families who do not or
CC only partially fulfill the Amsterdam criteria, but in whom a genetic
CC basis for colon cancer is strongly suspected.
CC {ECO:0000269|PubMed:10480359, ECO:0000269|PubMed:11793469,
CC ECO:0000269|PubMed:15887124, ECO:0000269|PubMed:16472587,
CC ECO:0000269|PubMed:16619239, ECO:0000269|PubMed:18178629,
CC ECO:0000269|PubMed:18602922, ECO:0000269|PubMed:19479271,
CC ECO:0000269|PubMed:23709753, ECO:0000269|PubMed:24027009}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Mismatch repair cancer syndrome 4 (MMRCS4) [MIM:619101]: An
CC autosomal recessive form of mismatch repair cancer syndrome, a
CC childhood cancer predisposition syndrome encompassing a broad tumor
CC spectrum. This includes hematological malignancies, central nervous
CC system tumors, Lynch syndrome-associated malignancies such as
CC colorectal tumors as well as multiple intestinal polyps, embryonic
CC tumors and rhabdomyosarcoma. Multiple cafe-au-lait macules, a feature
CC reminiscent of neurofibromatosis type 1, are often found as first
CC manifestation of the underlying cancer. {ECO:0000269|PubMed:15077197,
CC ECO:0000269|PubMed:17557300, ECO:0000269|PubMed:27435373,
CC ECO:0000269|PubMed:7661930, ECO:0000269|PubMed:9419979}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the DNA mismatch repair MutL/HexB family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Hereditary non-polyposis colorectal cancer db;
CC URL="http://www.nfdht.nl/";
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; U13696; AAA63923.1; -; Genomic_DNA.
DR EMBL; AB103082; BAD89425.1; -; mRNA.
DR EMBL; AB103083; BAD89426.1; -; mRNA.
DR EMBL; AB103085; BAD89428.1; -; mRNA.
DR EMBL; U14658; AAA50390.1; -; mRNA.
DR EMBL; AK312390; BAG35307.1; -; mRNA.
DR EMBL; AC005995; AAS00390.1; -; Genomic_DNA.
DR EMBL; BC093921; AAH93921.1; -; mRNA.
DR CCDS; CCDS5343.1; -. [P54278-1]
DR PIR; S47598; S47598.
DR RefSeq; NP_000526.2; NM_000535.6. [P54278-1]
DR RefSeq; NP_001308932.1; NM_001322003.1.
DR RefSeq; NP_001308933.1; NM_001322004.1.
DR RefSeq; NP_001308934.1; NM_001322005.1.
DR RefSeq; NP_001308935.1; NM_001322006.1.
DR RefSeq; NP_001308936.1; NM_001322007.1.
DR RefSeq; NP_001308937.1; NM_001322008.1.
DR RefSeq; NP_001308938.1; NM_001322009.1.
DR RefSeq; NP_001308939.1; NM_001322010.1.
DR RefSeq; NP_001308940.1; NM_001322011.1.
DR RefSeq; NP_001308941.1; NM_001322012.1.
DR RefSeq; NP_001308942.1; NM_001322013.1.
DR RefSeq; NP_001308943.1; NM_001322014.1.
DR RefSeq; NP_001308944.1; NM_001322015.1.
DR RefSeq; XP_016885888.1; XM_017030399.1.
DR PDB; 1EA6; X-ray; 2.70 A; A/B=1-364.
DR PDB; 1H7S; X-ray; 1.95 A; A/B=1-365.
DR PDB; 1H7U; X-ray; 2.70 A; A/B=1-365.
DR PDB; 5U5R; X-ray; 2.10 A; B=573-583.
DR PDB; 6MFQ; X-ray; 2.60 A; A/B=1-365.
DR PDB; 7RCB; X-ray; 2.00 A; A/B=1-365.
DR PDB; 7RCI; X-ray; 2.12 A; A/B=1-365.
DR PDB; 7RCK; X-ray; 2.04 A; A/B=1-365.
DR PDBsum; 1EA6; -.
DR PDBsum; 1H7S; -.
DR PDBsum; 1H7U; -.
DR PDBsum; 5U5R; -.
DR PDBsum; 6MFQ; -.
DR PDBsum; 7RCB; -.
DR PDBsum; 7RCI; -.
DR PDBsum; 7RCK; -.
DR AlphaFoldDB; P54278; -.
DR SMR; P54278; -.
DR BioGRID; 111404; 71.
DR CORUM; P54278; -.
DR DIP; DIP-46295N; -.
DR IntAct; P54278; 30.
DR MINT; P54278; -.
DR STRING; 9606.ENSP00000265849; -.
DR DrugBank; DB02930; Adenosine 5'-[gamma-thio]triphosphate.
DR GlyGen; P54278; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P54278; -.
DR PhosphoSitePlus; P54278; -.
DR BioMuta; PMS2; -.
DR DMDM; 317373266; -.
DR SWISS-2DPAGE; P54278; -.
DR EPD; P54278; -.
DR jPOST; P54278; -.
DR MassIVE; P54278; -.
DR MaxQB; P54278; -.
DR PaxDb; P54278; -.
DR PeptideAtlas; P54278; -.
DR PRIDE; P54278; -.
DR ProteomicsDB; 56669; -. [P54278-1]
DR ProteomicsDB; 56670; -. [P54278-2]
DR ProteomicsDB; 56671; -. [P54278-3]
DR ProteomicsDB; 56672; -. [P54278-4]
DR Antibodypedia; 4134; 558 antibodies from 43 providers.
DR CPTC; P54278; 1 antibody.
DR DNASU; 5395; -.
DR Ensembl; ENST00000265849.12; ENSP00000265849.7; ENSG00000122512.16. [P54278-1]
DR Ensembl; ENST00000382321.5; ENSP00000371758.4; ENSG00000122512.16. [P54278-2]
DR Ensembl; ENST00000643595.1; ENSP00000494497.1; ENSG00000122512.16. [P54278-4]
DR GeneID; 5395; -.
DR KEGG; hsa:5395; -.
DR MANE-Select; ENST00000265849.12; ENSP00000265849.7; NM_000535.7; NP_000526.2.
DR UCSC; uc003spl.4; human. [P54278-1]
DR CTD; 5395; -.
DR DisGeNET; 5395; -.
DR GeneCards; PMS2; -.
DR GeneReviews; PMS2; -.
DR HGNC; HGNC:9122; PMS2.
DR HPA; ENSG00000122512; Low tissue specificity.
DR MalaCards; PMS2; -.
DR MIM; 600259; gene.
DR MIM; 614337; phenotype.
DR MIM; 619101; phenotype.
DR neXtProt; NX_P54278; -.
DR OpenTargets; ENSG00000122512; -.
DR Orphanet; 252202; Constitutional mismatch repair deficiency syndrome.
DR Orphanet; 144; Lynch syndrome.
DR PharmGKB; PA33448; -.
DR VEuPathDB; HostDB:ENSG00000122512; -.
DR eggNOG; KOG1978; Eukaryota.
DR GeneTree; ENSGT00940000155381; -.
DR HOGENOM; CLU_004131_0_2_1; -.
DR InParanoid; P54278; -.
DR OMA; HIPRPSK; -.
DR OrthoDB; 735423at2759; -.
DR PhylomeDB; P54278; -.
DR TreeFam; TF300711; -.
DR PathwayCommons; P54278; -.
DR Reactome; R-HSA-5358565; Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha).
DR Reactome; R-HSA-5358606; Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta).
DR Reactome; R-HSA-5545483; Defective Mismatch Repair Associated With MLH1.
DR Reactome; R-HSA-5632987; Defective Mismatch Repair Associated With PMS2.
DR Reactome; R-HSA-6796648; TP53 Regulates Transcription of DNA Repair Genes.
DR SignaLink; P54278; -.
DR SIGNOR; P54278; -.
DR BioGRID-ORCS; 5395; 15 hits in 1063 CRISPR screens.
DR ChiTaRS; PMS2; human.
DR EvolutionaryTrace; P54278; -.
DR GeneWiki; PMS2; -.
DR Pharos; P54278; Tbio.
DR PRO; PR:P54278; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; P54278; protein.
DR Bgee; ENSG00000122512; Expressed in thymus and 108 other tissues.
DR ExpressionAtlas; P54278; baseline and differential.
DR Genevisible; P54278; HS.
DR GO; GO:0036464; C:cytoplasmic ribonucleoprotein granule; IDA:HPA.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0032300; C:mismatch repair complex; IBA:GO_Central.
DR GO; GO:0032389; C:MutLalpha complex; IBA:GO_Central.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0005524; F:ATP binding; IEA:InterPro.
DR GO; GO:0016887; F:ATP hydrolysis activity; IBA:GO_Central.
DR GO; GO:0140664; F:ATP-dependent DNA damage sensor activity; IEA:InterPro.
DR GO; GO:0003677; F:DNA binding; IDA:HGNC-UCL.
DR GO; GO:0004519; F:endonuclease activity; TAS:Reactome.
DR GO; GO:0032138; F:single base insertion or deletion binding; IDA:HGNC-UCL.
DR GO; GO:0006298; P:mismatch repair; IDA:UniProtKB.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0016446; P:somatic hypermutation of immunoglobulin genes; IBA:GO_Central.
DR Gene3D; 3.30.1370.100; -; 1.
DR Gene3D; 3.30.1540.20; -; 1.
DR Gene3D; 3.30.230.10; -; 1.
DR Gene3D; 3.30.565.10; -; 1.
DR InterPro; IPR014762; DNA_mismatch_repair_CS.
DR InterPro; IPR002099; DNA_mismatch_repair_N.
DR InterPro; IPR013507; DNA_mismatch_S5_2-like.
DR InterPro; IPR036890; HATPase_C_sf.
DR InterPro; IPR038973; MutL/Mlh/Pms.
DR InterPro; IPR014790; MutL_C.
DR InterPro; IPR042120; MutL_C_dimsub.
DR InterPro; IPR042121; MutL_C_regsub.
DR InterPro; IPR037198; MutL_C_sf.
DR InterPro; IPR020568; Ribosomal_S5_D2-typ_fold.
DR InterPro; IPR014721; Ribosomal_S5_D2-typ_fold_subgr.
DR PANTHER; PTHR10073; PTHR10073; 1.
DR Pfam; PF01119; DNA_mis_repair; 1.
DR Pfam; PF08676; MutL_C; 1.
DR SMART; SM01340; DNA_mis_repair; 1.
DR SMART; SM00853; MutL_C; 1.
DR SUPFAM; SSF118116; SSF118116; 1.
DR SUPFAM; SSF54211; SSF54211; 1.
DR SUPFAM; SSF55874; SSF55874; 1.
DR TIGRFAMs; TIGR00585; mutl; 1.
DR PROSITE; PS00058; DNA_MISMATCH_REPAIR_1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Disease variant; DNA damage;
KW DNA repair; Endonuclease; Hereditary nonpolyposis colorectal cancer;
KW Hydrolase; Nuclease; Nucleus; Phosphoprotein; Reference proteome;
KW Tumor suppressor.
FT CHAIN 1..862
FT /note="Mismatch repair endonuclease PMS2"
FT /id="PRO_0000178005"
FT REGION 391..552
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 391..440
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 450..464
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 484..498
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 499..524
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 530..552
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 573
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 597
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT VAR_SEQ 180..183
FT /note="EYAK -> QASV (in isoform 4)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_029384"
FT VAR_SEQ 184..862
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_029385"
FT VAR_SEQ 269..669
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_029386"
FT VAR_SEQ 560..572
FT /note="CKFRVLPQPTNLA -> LKTGPSDPRTSMN (in isoform 3)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_029387"
FT VAR_SEQ 573..862
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_029388"
FT VARIANT 18
FT /note="I -> V (normal DNA mismatch repair activity;
FT dbSNP:rs63750123)"
FT /evidence="ECO:0000269|PubMed:16472587,
FT ECO:0000269|PubMed:16619239, ECO:0000269|PubMed:24027009,
FT ECO:0000269|PubMed:27435373"
FT /id="VAR_078517"
FT VARIANT 20
FT /note="R -> Q (no effect on protein abundance; no effect on
FT subcellular localization; normal DNA mismatch repair
FT activity; dbSNP:rs10254120)"
FT /evidence="ECO:0000269|PubMed:16472587,
FT ECO:0000269|PubMed:23709753, ECO:0000269|PubMed:24027009,
FT ECO:0000269|PubMed:8072530"
FT /id="VAR_004469"
FT VARIANT 36
FT /note="S -> R (no effect on protein levels;
FT dbSNP:rs587781918)"
FT /evidence="ECO:0000269|PubMed:28494185"
FT /id="VAR_079817"
FT VARIANT 46
FT /note="S -> I (in MMRCS4 and HNPCC4; strongly decreased DNA
FT mismatch repair activity; no effect on protein abundance;
FT no effect on subcellular localization; dbSNP:rs121434629)"
FT /evidence="ECO:0000269|PubMed:17557300,
FT ECO:0000269|PubMed:18602922, ECO:0000269|PubMed:23709753,
FT ECO:0000269|PubMed:24027009, ECO:0000269|PubMed:27435373"
FT /id="VAR_066838"
FT VARIANT 46
FT /note="S -> N (in HNPCC4; strongly decreased DNA mismatch
FT repair activity; dbSNP:rs121434629)"
FT /evidence="ECO:0000269|PubMed:18602922,
FT ECO:0000269|PubMed:24027009"
FT /id="VAR_078518"
FT VARIANT 60
FT /note="D -> E (normal DNA mismatch repair activity;
FT dbSNP:rs200313585)"
FT /evidence="ECO:0000269|PubMed:24027009,
FT ECO:0000269|PubMed:27435373"
FT /id="VAR_078519"
FT VARIANT 66
FT /note="I -> T (in MMRCS4; unknown pathological
FT significance; normal DNA mismatch repair activity;
FT dbSNP:rs769554577)"
FT /evidence="ECO:0000269|PubMed:27435373"
FT /id="VAR_078520"
FT VARIANT 107
FT /note="R -> W (in MMRCS4; decreased DNA mismatch repair
FT activity; dbSNP:rs188006077)"
FT /evidence="ECO:0000269|PubMed:27435373"
FT /id="VAR_078521"
FT VARIANT 115
FT /note="C -> G (in MMRCS4; decreased DNA mismatch repair
FT activity)"
FT /evidence="ECO:0000269|PubMed:27435373"
FT /id="VAR_078522"
FT VARIANT 182
FT /note="A -> T (in HNPCC4; unknown pathological
FT significance; dbSNP:rs587779341)"
FT /evidence="ECO:0000269|PubMed:16619239"
FT /id="VAR_078523"
FT VARIANT 205
FT /note="Q -> P (in MMRCS4 and HNPCC4; unknown pathological
FT significance; normal DNA mismatch repair activity;
FT dbSNP:rs587779342)"
FT /evidence="ECO:0000269|PubMed:18602922,
FT ECO:0000269|PubMed:24027009, ECO:0000269|PubMed:27435373"
FT /id="VAR_078524"
FT VARIANT 207
FT /note="G -> E (in HNPCC4; unknown pathological
FT significance; normal DNA mismatch repair activity;
FT dbSNP:rs374704824)"
FT /evidence="ECO:0000269|PubMed:19479271,
FT ECO:0000269|PubMed:24027009"
FT /id="VAR_078525"
FT VARIANT 263
FT /note="L -> V (in MMRCS4 and HNPCC4; unknown pathological
FT significance; normal DNA mismatch repair activity;
FT dbSNP:rs587779345)"
FT /evidence="ECO:0000269|PubMed:24027009,
FT ECO:0000269|PubMed:27435373"
FT /id="VAR_078526"
FT VARIANT 277
FT /note="T -> K (in dbSNP:rs1805322)"
FT /id="VAR_016133"
FT VARIANT 307
FT /note="N -> K (in MMRCS4; unknown pathological
FT significance; decreased DNA mismatch repair activity;
FT dbSNP:rs587779346)"
FT /evidence="ECO:0000269|PubMed:27435373"
FT /id="VAR_078527"
FT VARIANT 423
FT /note="A -> T (normal DNA mismatch repair activity;
FT dbSNP:rs587778619)"
FT /evidence="ECO:0000269|PubMed:20186689,
FT ECO:0000269|PubMed:24027009"
FT /id="VAR_079012"
FT VARIANT 437
FT /note="P -> S (in MMRCS4; unknown pathological
FT significance; normal DNA mismatch repair activity;
FT dbSNP:rs200726484)"
FT /evidence="ECO:0000269|PubMed:27435373"
FT /id="VAR_078528"
FT VARIANT 470
FT /note="P -> S (no effect on protein abundance; no effect on
FT subcellular localization; normal DNA mismatch repair
FT activity; dbSNP:rs1805321)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:16472587, ECO:0000269|PubMed:23709753,
FT ECO:0000269|PubMed:27435373, ECO:0000269|Ref.3"
FT /id="VAR_016134"
FT VARIANT 475
FT /note="V -> E (no effect on protein levels;
FT dbSNP:rs587781827)"
FT /evidence="ECO:0000269|PubMed:28494185"
FT /id="VAR_079818"
FT VARIANT 479
FT /note="H -> Q (in MMRCS4 and HNPCC4; unknown pathological
FT significance; normal DNA mismatch repair activity;
FT dbSNP:rs63750685)"
FT /evidence="ECO:0000269|PubMed:10480359,
FT ECO:0000269|PubMed:24027009, ECO:0000269|PubMed:27435373"
FT /id="VAR_012969"
FT VARIANT 485
FT /note="T -> K (normal DNA mismatch repair activity;
FT dbSNP:rs1805323)"
FT /evidence="ECO:0000269|PubMed:10480359,
FT ECO:0000269|PubMed:16472587, ECO:0000269|PubMed:24027009"
FT /id="VAR_012970"
FT VARIANT 488
FT /note="A -> V (in MMRCS4; unknown pathological
FT significance; normal DNA mismatch repair activity;
FT dbSNP:rs587779328)"
FT /evidence="ECO:0000269|PubMed:27435373"
FT /id="VAR_078529"
FT VARIANT 504
FT /note="E -> Q (in MMRCS4; unknown pathological
FT significance; normal DNA mismatch repair activity;
FT dbSNP:rs368516768)"
FT /evidence="ECO:0000269|PubMed:27435373"
FT /id="VAR_078530"
FT VARIANT 511
FT /note="T -> A (normal DNA mismatch repair activity;
FT dbSNP:rs2228007)"
FT /evidence="ECO:0000269|PubMed:10480359,
FT ECO:0000269|PubMed:24027009"
FT /id="VAR_012971"
FT VARIANT 511
FT /note="T -> M (normal DNA mismatch repair activity;
FT dbSNP:rs74902811)"
FT /evidence="ECO:0000269|PubMed:20186689,
FT ECO:0000269|PubMed:24027009"
FT /id="VAR_079013"
FT VARIANT 511
FT /note="T -> P (in dbSNP:rs2228007)"
FT /evidence="ECO:0000269|PubMed:20186689"
FT /id="VAR_079014"
FT VARIANT 541
FT /note="K -> E (normal DNA mismatch repair activity;
FT dbSNP:rs2228006)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:16472587,
FT ECO:0000269|PubMed:24027009, ECO:0000269|PubMed:8072530,
FT ECO:0000269|Ref.2, ECO:0000269|Ref.3"
FT /id="VAR_024541"
FT VARIANT 563
FT /note="R -> L (normal DNA mismatch repair activity;
FT dbSNP:rs63750668)"
FT /evidence="ECO:0000269|PubMed:16619239,
FT ECO:0000269|PubMed:18602922, ECO:0000269|PubMed:24027009,
FT ECO:0000269|PubMed:27435373"
FT /id="VAR_078531"
FT VARIANT 571
FT /note="L -> I (normal DNA mismatch repair activity;
FT dbSNP:rs63750055)"
FT /evidence="ECO:0000269|PubMed:24027009,
FT ECO:0000269|PubMed:27435373"
FT /id="VAR_078532"
FT VARIANT 585
FT /note="L -> I (in MMRCS4 and HNPCC4; unknown pathological
FT significance; normal DNA mismatch repair activity;
FT dbSNP:rs63750947)"
FT /evidence="ECO:0000269|PubMed:16472587,
FT ECO:0000269|PubMed:24027009, ECO:0000269|PubMed:27435373"
FT /id="VAR_078533"
FT VARIANT 597
FT /note="T -> S (normal DNA mismatch repair activity;
FT significantly reduced interaction with MLH1;
FT dbSNP:rs1805318)"
FT /evidence="ECO:0000269|PubMed:10480359,
FT ECO:0000269|PubMed:11793469, ECO:0000269|PubMed:16472587,
FT ECO:0000269|PubMed:23709753, ECO:0000269|PubMed:24027009"
FT /id="VAR_012972"
FT VARIANT 622
FT /note="M -> I (in HNPCC4; unknown pathological
FT significance; significantly reduced interaction with MLH1;
FT normal DNA mismatch repair activity; dbSNP:rs1805324)"
FT /evidence="ECO:0000269|PubMed:10480359,
FT ECO:0000269|PubMed:11793469, ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:16472587, ECO:0000269|PubMed:18602922,
FT ECO:0000269|PubMed:24027009"
FT /id="VAR_012973"
FT VARIANT 663
FT /note="E -> A (in HNPCC4; unknown pathological
FT significance; normal DNA mismatch repair activity;
FT dbSNP:rs587779332)"
FT /evidence="ECO:0000269|PubMed:18602922,
FT ECO:0000269|PubMed:24027009"
FT /id="VAR_078534"
FT VARIANT 699
FT /note="D -> H (no effect on protein levels;
FT dbSNP:rs587781317)"
FT /evidence="ECO:0000269|PubMed:28494185"
FT /id="VAR_079819"
FT VARIANT 705
FT /note="E -> K (in MMRCS4 and HNPCC4; decreases DNA mismatch
FT repair activity; dbSNP:rs267608161)"
FT /evidence="ECO:0000269|PubMed:18602922,
FT ECO:0000269|PubMed:24027009, ECO:0000269|PubMed:9419979"
FT /id="VAR_012974"
FT VARIANT 750
FT /note="G -> D (in HNPCC4; unknown pathological
FT significance; decreased DNA mismatch repair activity;
FT dbSNP:rs587779337)"
FT /evidence="ECO:0000269|PubMed:18602922,
FT ECO:0000269|PubMed:24027009"
FT /id="VAR_078535"
FT VARIANT 775
FT /note="N -> S (normal DNA mismatch repair activity;
FT dbSNP:rs17420802)"
FT /evidence="ECO:0000269|PubMed:23709753,
FT ECO:0000269|PubMed:27435373"
FT /id="VAR_016135"
FT VARIANT 792
FT /note="D -> N (no effect on protein levels;
FT dbSNP:rs587781265)"
FT /evidence="ECO:0000269|PubMed:28494185"
FT /id="VAR_079820"
FT VARIANT 797
FT /note="M -> R (in HNPCC4; unknown pathological
FT significance; normal DNA mismatch repair activity;
FT dbSNP:rs267608152)"
FT /evidence="ECO:0000269|PubMed:16619239,
FT ECO:0000269|PubMed:24027009"
FT /id="VAR_078536"
FT VARIANT 815
FT /note="S -> L (in MMRCS4; decreased DNA mismatch repair
FT activity; dbSNP:rs587779338)"
FT /evidence="ECO:0000269|PubMed:27435373"
FT /id="VAR_078537"
FT VARIANT 843
FT /note="C -> Y (in HNPCC4; decreased DNA mismatch repair
FT activity; dbSNP:rs267608174)"
FT /evidence="ECO:0000269|PubMed:18602922,
FT ECO:0000269|PubMed:24027009"
FT /id="VAR_078538"
FT VARIANT 853
FT /note="I -> M (no effect on protein levels;
FT dbSNP:rs371673459)"
FT /evidence="ECO:0000269|PubMed:28494185"
FT /id="VAR_079821"
FT VARIANT 857
FT /note="G -> A (normal DNA mismatch repair activity;
FT dbSNP:rs1802683)"
FT /evidence="ECO:0000269|PubMed:16472587,
FT ECO:0000269|PubMed:24027009"
FT /id="VAR_078539"
FT MUTAGEN 41
FT /note="E->A: Decreased DNA mismatch repair activity."
FT /evidence="ECO:0000269|PubMed:24027009"
FT MUTAGEN 70
FT /note="D->N: No effect on protein abundance, no effect on
FT subcellular localization and loss of DNA mismatch repair
FT activity."
FT /evidence="ECO:0000269|PubMed:23709753"
FT MUTAGEN 519
FT /note="Y->C: No effect on DNA mismatch repair activity."
FT /evidence="ECO:0000269|PubMed:24027009"
FT STRAND 30..32
FT /evidence="ECO:0007829|PDB:1H7S"
FT HELIX 35..48
FT /evidence="ECO:0007829|PDB:1H7S"
FT STRAND 52..59
FT /evidence="ECO:0007829|PDB:1H7S"
FT HELIX 60..62
FT /evidence="ECO:0007829|PDB:1H7S"
FT STRAND 64..70
FT /evidence="ECO:0007829|PDB:1H7S"
FT HELIX 77..79
FT /evidence="ECO:0007829|PDB:1H7S"
FT HELIX 81..84
FT /evidence="ECO:0007829|PDB:1H7S"
FT STRAND 101..109
FT /evidence="ECO:0007829|PDB:1H7S"
FT HELIX 110..117
FT /evidence="ECO:0007829|PDB:1H7S"
FT STRAND 118..125
FT /evidence="ECO:0007829|PDB:1H7S"
FT STRAND 133..137
FT /evidence="ECO:0007829|PDB:1H7S"
FT STRAND 143..148
FT /evidence="ECO:0007829|PDB:1H7S"
FT STRAND 153..161
FT /evidence="ECO:0007829|PDB:1H7S"
FT TURN 162..165
FT /evidence="ECO:0007829|PDB:1H7S"
FT HELIX 167..175
FT /evidence="ECO:0007829|PDB:1H7S"
FT HELIX 177..194
FT /evidence="ECO:0007829|PDB:1H7S"
FT STRAND 199..205
FT /evidence="ECO:0007829|PDB:1H7S"
FT STRAND 211..216
FT /evidence="ECO:0007829|PDB:1H7S"
FT HELIX 223..231
FT /evidence="ECO:0007829|PDB:1H7S"
FT HELIX 233..237
FT /evidence="ECO:0007829|PDB:1H7S"
FT STRAND 239..241
FT /evidence="ECO:0007829|PDB:1H7S"
FT HELIX 249..255
FT /evidence="ECO:0007829|PDB:1H7S"
FT TURN 259..263
FT /evidence="ECO:0007829|PDB:1H7S"
FT STRAND 268..274
FT /evidence="ECO:0007829|PDB:1H7S"
FT TURN 278..280
FT /evidence="ECO:0007829|PDB:1H7S"
FT STRAND 281..285
FT /evidence="ECO:0007829|PDB:1H7S"
FT STRAND 288..292
FT /evidence="ECO:0007829|PDB:1H7S"
FT STRAND 295..297
FT /evidence="ECO:0007829|PDB:1H7S"
FT HELIX 300..311
FT /evidence="ECO:0007829|PDB:1H7S"
FT STRAND 321..326
FT /evidence="ECO:0007829|PDB:1H7S"
FT HELIX 329..331
FT /evidence="ECO:0007829|PDB:1H7S"
FT STRAND 332..334
FT /evidence="ECO:0007829|PDB:1H7S"
FT STRAND 343..345
FT /evidence="ECO:0007829|PDB:1H7S"
FT HELIX 348..363
FT /evidence="ECO:0007829|PDB:1H7S"
SQ SEQUENCE 862 AA; 95797 MW; B1B9547280ECAF9A CRC64;
MERAESSSTE PAKAIKPIDR KSVHQICSGQ VVLSLSTAVK ELVENSLDAG ATNIDLKLKD
YGVDLIEVSD NGCGVEEENF EGLTLKHHTS KIQEFADLTQ VETFGFRGEA LSSLCALSDV
TISTCHASAK VGTRLMFDHN GKIIQKTPYP RPRGTTVSVQ QLFSTLPVRH KEFQRNIKKE
YAKMVQVLHA YCIISAGIRV SCTNQLGQGK RQPVVCTGGS PSIKENIGSV FGQKQLQSLI
PFVQLPPSDS VCEEYGLSCS DALHNLFYIS GFISQCTHGV GRSSTDRQFF FINRRPCDPA
KVCRLVNEVY HMYNRHQYPF VVLNISVDSE CVDINVTPDK RQILLQEEKL LLAVLKTSLI
GMFDSDVNKL NVSQQPLLDV EGNLIKMHAA DLEKPMVEKQ DQSPSLRTGE EKKDVSISRL
REAFSLRHTT ENKPHSPKTP EPRRSPLGQK RGMLSSSTSG AISDKGVLRP QKEAVSSSHG
PSDPTDRAEV EKDSGHGSTS VDSEGFSIPD TGSHCSSEYA ASSPGDRGSQ EHVDSQEKAP
KTDDSFSDVD CHSNQEDTGC KFRVLPQPTN LATPNTKRFK KEEILSSSDI CQKLVNTQDM
SASQVDVAVK INKKVVPLDF SMSSLAKRIK QLHHEAQQSE GEQNYRKFRA KICPGENQAA
EDELRKEISK TMFAEMEIIG QFNLGFIITK LNEDIFIVDQ HATDEKYNFE MLQQHTVLQG
QRLIAPQTLN LTAVNEAVLI ENLEIFRKNG FDFVIDENAP VTERAKLISL PTSKNWTFGP
QDVDELIFML SDSPGVMCRP SRVKQMFASR ACRKSVMIGT ALNTSEMKKL ITHMGEMDHP
WNCPHGRPTM RHIANLGVIS QN
