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Description:
PMS1 protein homolog 2 (DNA mismatch repair protein PMS2).
Molecular weight: 95798
View which proteins in this organism that is involved with DNA Repair;
classified after biological processes (using data from the GOA project):
DNA repair( GO:0006281 ) mismatch repair( GO:0006298 )
Important dates:
01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
01-OCT-1996, sequence version 1.
07-FEB-2006, entry version 53.
Phylogenetic order:
Eukaryota Metazoa Chordata Craniata Vertebrata Euteleostomi Mammalia Eutheria Euarchontoglires Primates Catarrhini Hominidae Homo.
To calculate the pI (Isoelectric point - the pH where a protein has a neutral charge),
go to this page and enter the protein ID (e.g 3MG_ECOLI): http://us.expasy.org/tools/pi_tool.html
Links to references in other databases for protein PMS2_HUMAN:
| Database | Pointer | Add. info#1 | Add. info#2 |
| EMBL | U13696 | AAA63923.1 | - |
| EMBL | U14658 | AAA50390.1 | - |
| PIR | S47598 | S47598. | |
| PDB | 1EA6 | X-ray | A/B=1-364. |
| PDB | 1H7S | X-ray | A/B=1-365. |
| PDB | 1H7U | X-ray | A/B=1-365. |
| SWISS-2DPAGE | P54278 | HUMAN. | |
| Ensembl | ENSG00000122512 | Homo sapiens.1 | |
| HGNC | HGNC:9122 | PMS2.1 | |
| MIM | 276300 | phenotype. | |
| MIM | 600259 | gene+phenotype. | |
| MIM | 608623 | phenotype. | |
| LinkHub | P54278 | -.1 | |
| GO | GO:0005634 | C:nucleus | TAS. |
| GO | GO:0003677 | F:DNA binding | TAS. |
| GO | GO:0006298 | P:mismatch repair | TAS. |
| InterPro | IPR003594 | ATP_bd_ATPase. | |
| InterPro | IPR002099 | DNA_mis_repair. | |
| PANTHER | PTHR10073 | DNA_mis_repair.1 | 1. |
| Pfam | PF01119 | DNA_mis_repair | 1. |
| Pfam | PF02518 | HATPase_c | 1. |
| TIGRFAMs | TIGR00585 | mutl | 1. |
| PROSITE | PS00058 | DNA_MISMATCH_REPAIR_1 | 1. |
Keywords:
3D-structure; Anti-oncogene; Cell cycle; Disease mutation; DNA damage; DNA repair; Hereditary nonpolyposis colorectal cancer; Nuclear protein; Polymorphism.
References:
RN [1]
RP NUCLEOTIDE SEQUENCE, AND VARIANT GLN-20.
RC TISSUE=Endometrial tumor;
RX MEDLINE=94352394; 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
RT cancer.";
RL Nature 371:75-80(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE, AND VARIANT SER-470.
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 [3]
RP IDENTIFICATION OF PMS2 AS MEMBER OF BASC.
RX MEDLINE=20245492; PubMed=10783165; DOI=10.1101/gad.827000;
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 [4]
RP DISEASE.
RX MEDLINE=95174843; PubMed=7661930; DOI=10.1056/NEJM199503303321302;
RA Hamilton S.R., Liu B., Parsons R.E., Papadopoulos N., Jen J.,
RA Powell S.M., Krush A.J., Berk T., Cohen Z., Tetu B., Burger P.C.,
RA Wood P.A., Taqi F., Booker S.V., Petersen G.M., Offerhaus G.J.A.,
RA Tersmette A.C., 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 [5]
RP VARIANT TURCOT SYNDROME LYS-705.
RX MEDLINE=98080146; 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 [6]
RP VARIANTS GLN-479; LYS-485; ALA-511; SER-597 AND ILE-622.
RX MEDLINE=99408236; PubMed=10480359; DOI=10.1007/s004390051067;
RA Wang Q., Lasset C., Desseigne F., Saurin J.-C., Maugard C.,
RA Navarro C., Ruano E., Descos L., Trillet-Lenoir V., Bosset J.-F.,
RA Puisieux A.;
RT "Prevalence of germline mutations of hMLH1, hMSH2, hPMS1, hPMS2, and
RT hMSH6 genes in 75 French kindreds with nonpolyposis colorectal
RT cancer.";
RL Hum. Genet. 105:79-85(1999).
RN [7]
RP CHARACTERIZATION OF VARIANTS SER-597 AND ILE-622.
RX MEDLINE=21652732; 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 [8]
RP INVOLVEMENT IN SUPRATENTORIAL PRIMITIVE NEUROECTODERMAL TUMORS WITH
RP CAFE-AU-LAIT SPOTS.
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).
Feature:
CHAIN 1 862 PMS1 protein homolog 2.
/FTId=PRO_0000178005.
VARIANT 20 20 R -> Q (in dbSNP:10254120).
/FTId=VAR_004469.
VARIANT 277 277 T -> K (in dbSNP:1805322).
/FTId=VAR_016133.
VARIANT 470 470 P -> S (in dbSNP:1805321).
/FTId=VAR_016134.
VARIANT 479 479 H -> Q.
/FTId=VAR_012969.
VARIANT 485 485 T -> K (in dbSNP:1805323).
/FTId=VAR_012970.
VARIANT 511 511 T -> A (in dbSNP:2228007).
/FTId=VAR_012971.
VARIANT 541 541 E -> K (in dbSNP:2228006).
/FTId=VAR_024541.
VARIANT 597 597 T -> S (may be associated with increased
susceptibility to colorectal cancer;
significantly reduced interaction with
MLH1; dbSNP:1805318).
/FTId=VAR_012972.
VARIANT 622 622 M -> I (may be associated with increased
susceptibility to colorectal cancer;
significantly reduced interaction with
MLH1; dbSNP:1805324).
/FTId=VAR_012973.
VARIANT 705 705 E -> K (in Turcot syndrome; could be a
rare polymorphism).
/FTId=VAR_012974.
VARIANT 775 775 N -> S (in dbSNP:1059060).
/FTId=VAR_016135.
STRAND 30 32
HELIX 35 48
TURN 49 50
STRAND 52 59
HELIX 60 62
TURN 63 63
STRAND 64 70
STRAND 72 72
HELIX 77 79
STRAND 80 80
HELIX 81 84
TURN 98 99
STRAND 101 109
HELIX 110 117
STRAND 118 125
TURN 127 128
STRAND 130 131
STRAND 133 137
TURN 139 140
STRAND 141 141
STRAND 143 148
STRAND 153 161
TURN 162 165
STRAND 166 166
HELIX 167 175
TURN 176 176
HELIX 177 194
TURN 196 197
STRAND 199 205
TURN 207 208
STRAND 209 209
STRAND 211 216
STRAND 221 222
HELIX 223 231
HELIX 233 237
TURN 238 238
STRAND 239 241
HELIX 249 255
TURN 256 256
TURN 259 263
STRAND 264 264
STRAND 268 274
STRAND 277 277
TURN 278 280
STRAND 281 285
TURN 286 287
STRAND 288 292
TURN 293 294
STRAND 295 297
HELIX 300 311
TURN 312 313
TURN 315 316
STRAND 318 318
STRAND 321 326
HELIX 329 331
STRAND 332 334
STRAND 343 345
TURN 346 347
HELIX 348 363
Comments:
-!- FUNCTION: Involved in the repair of mismatches in DNA.
-!- SUBUNIT: Heterodimer of PMS2 and MLH1. 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.
-!- 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 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 Turcot syndrome
[MIM:276300]. Turcot syndrome 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.
-!- DISEASE: Defects in PMS2 are a cause of supratentorial primitive
neuroectodermal tumors with cafe-au-lait spots (SNTCL)
[MIM:608623]. Supratentorial primitive neuroectodermal tumor
(SPNET) is a rare and aggressive embryonal tumor, most likely
derived from primitive neuroepithelial cells. SPNET has a poor
prognosis, with median survival of less than 2 years.
-!- SIMILARITY: Belongs to the DNA mismatch repair mutL/hexB family.
-!- DATABASE: NAME=Hereditary non-polyposis colorectal cancer db;
WWW="http://www.nfdht.nl/".
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Sequence length: 862
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
ETDDSFSDVD 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