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Description:
DNA mismatch repair protein Mlh3 (MutL protein homolog 3).
Molecular weight: 1637
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:
27-APR-2001, integrated into UniProtKB/Swiss-Prot.
27-APR-2001, sequence version 2.
07-FEB-2006, entry version 43.
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 MLH3_HUMAN:
| Database | Pointer | Add. info#1 | Add. info#2 |
| EMBL | AF195657 | AAF23904.1 | - |
| EMBL | AF195658 | AAF23905.1 | - |
| EMBL | AB039667 | BAA92353.1 | - |
| EMBL | AY963685 | AAX59030.1 | - |
| EMBL | L40399 | AAC42005.1 | - |
| Ensembl | ENSG00000119684 | Homo sapiens.1 | |
| HGNC | HGNC:7128 | MLH3.1 | |
| MIM | 604395 | gene+phenotype. | |
| GO | GO:0005634 | C:nucleus | TAS. |
| GO | GO:0005515 | F:protein binding | NAS. |
| GO | GO:0003696 | F:satellite DNA binding | TAS. |
| GO | GO:0007131 | P:meiotic recombination | NAS. |
| GO | GO:0006298 | P:mismatch repair | NAS. |
| InterPro | IPR003594 | ATP_bd_ATPase. | |
| InterPro | IPR002099 | DNA_mis_repair. | |
| PANTHER | PTHR10073 | DNA_mis_repair.1 | 3. |
| Pfam | PF01119 | DNA_mis_repair | 1. |
| Pfam | PF02518 | HATPase_c | 1. |
| PROSITE | PS00058 | DNA_MISMATCH_REPAIR_1 | 1. |
Keywords:
Alternative splicing; Disease mutation; DNA damage; DNA repair; Hereditary nonpolyposis colorectal cancer; Nuclear protein; Polymorphism.
References:
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], AND ALTERNATIVE SPLICING.
RX MEDLINE=20082804; PubMed=10615123; DOI=10.1038/71643;
RA Lipkin S.M., Wang V., Jacoby R., Banerjee-Basu S., Baxevanis A.D.,
RA Lynch H.T., Elliott R.M., Collins F.S.;
RT "MLH3: a DNA mismatch repair gene associated with mammalian
RT microsatellite instability.";
RL Nat. Genet. 24:27-35(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND INTERACTIONS WITH MLH1.
RX PubMed=11292842; DOI=10.1093/nar/29.8.1695;
RA Kondo E., Horii A., Fukushige S.;
RT "The interacting domains of three MutL heterodimers in man: hMLH1
RT interacts with 36 homologous amino acid residues within hMLH3, hPMS1
RT and hPMS2.";
RL Nucleic Acids Res. 29:1695-1702(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS GLY-93; SER-120;
RP GLN-231; ILE-420; VAL-492; GLN-600; PRO-606; GLN-624; CYS-647;
RP CYS-720; ILE-723; PHE-741; HIS-797; LEU-844; GLY-845; ILE-942;
RP PRO-966; ASN-1073; GLU-1105; ASP-1163 AND ARG-1319.
RA Livingston R.J., Rieder M.J., Shaffer T., Bertucci C., Baier C.N.,
RA Rajkumar N., Willa H.T., Daniels M., Downing T.K., Stanaway I.B.,
RA Nguyen C.P., Gildersleeve H., Cassidy C.M., Johnson E.J.,
RA Swanson J.E., McFarland I., Yool B., Park C., Nickerson D.A.;
RT "NIEHS-SNPs, environmental genome project, NIEHS ES15478, Department
RT of Genome Sciences, Seattle, WA (URL: http://egp.gs.washington.edu).";
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1189-1453.
RC TISSUE=Brain;
RX MEDLINE=95319502; PubMed=7596406; DOI=10.1038/375754a0;
RA Sherrington R., Rogaev E.I., Liang Y., Rogaeva E.A., Levesque G.,
RA Ikeda M., Chi H., Lin C., Li G., Holman K., Tsuda T., Mar L.,
RA Foncin J.-F., Bruni A.C., Montesi M.P., Sorbi S., Rainero I.,
RA Pinessi L., Nee L., Chumakov I., Pollen D., Brookes A., Sanseau P.,
RA Polinsky R.J., Wasco W., da Silva H.A.R., Haines J.L.,
RA Pericak-Vance M.A., Tanzi R.E., Roses A.D., Fraser P.E., Rommens J.M.,
RA St George-Hyslop P.H.;
RT "Cloning of a gene bearing missense mutations in early-onset familial
RT Alzheimer's disease.";
RL Nature 375:754-760(1995).
RN [5]
RP VARIANTS HNPCC7 GLU-24; SER-499; GLN-624; CYS-647; GLY-817; SER-981;
RP SER-1007; THR-1394 AND LYS-1451.
RX MEDLINE=21470348; PubMed=11586295; DOI=10.1038/ng1001-137;
RA Wu Y., Berends M.J.W., Sijmons R.H., Mensink R.G.J., Verlind E.,
RA Kooi K.A., van der Sluis T., Kempinga C., van der Zee A.G.J.,
RA Hollema H., Buys C.H.C.M., Kleibeuker J.H., Hofstra R.M.W.;
RT "A role for MLH3 in hereditary nonpolyposis colorectal cancer.";
RL Nat. Genet. 29:137-138(2001).
Feature:
CHAIN 1 1453 DNA mismatch repair protein Mlh3.
/FTId=PRO_0000178003.
VARSPLIC 1215 1238 Missing (in isoform 2).
/FTId=VSP_003290.
VARIANT 24 24 Q -> E (in HNPCC7).
/FTId=VAR_012946.
VARIANT 93 93 R -> G.
/FTId=VAR_023338.
VARIANT 120 120 F -> S.
/FTId=VAR_023339.
VARIANT 231 231 K -> Q.
/FTId=VAR_023340.
VARIANT 420 420 V -> I.
/FTId=VAR_023341.
VARIANT 492 492 L -> V.
/FTId=VAR_023342.
VARIANT 494 494 H -> R.
/FTId=VAR_010790.
VARIANT 499 499 N -> S (in HNPCC7).
/FTId=VAR_012947.
VARIANT 600 600 R -> Q.
/FTId=VAR_023343.
VARIANT 606 606 T -> P.
/FTId=VAR_023344.
VARIANT 624 624 E -> Q (in HNPCC7).
/FTId=VAR_012948.
VARIANT 647 647 R -> C (in HNPCC7).
/FTId=VAR_012949.
VARIANT 720 720 Y -> C.
/FTId=VAR_023345.
VARIANT 723 723 V -> I.
/FTId=VAR_023346.
VARIANT 741 741 V -> F.
/FTId=VAR_023347.
VARIANT 797 797 R -> H.
/FTId=VAR_023348.
VARIANT 817 817 S -> G (in HNPCC7).
/FTId=VAR_012950.
VARIANT 844 844 P -> L.
/FTId=VAR_023349.
VARIANT 845 845 S -> G.
/FTId=VAR_023350.
VARIANT 942 942 T -> I.
/FTId=VAR_023351.
VARIANT 966 966 S -> P.
/FTId=VAR_023352.
VARIANT 981 981 G -> S (in HNPCC7).
/FTId=VAR_012951.
VARIANT 1007 1007 N -> S (in HNPCC7).
/FTId=VAR_012952.
VARIANT 1073 1073 D -> N.
/FTId=VAR_023353.
VARIANT 1105 1105 D -> E.
/FTId=VAR_023354.
VARIANT 1163 1163 G -> D.
/FTId=VAR_023355.
VARIANT 1319 1319 G -> R.
/FTId=VAR_023356.
VARIANT 1394 1394 A -> T (in HNPCC7).
/FTId=VAR_012953.
VARIANT 1451 1451 E -> K (in HNPCC7).
/FTId=VAR_012954.
CONFLICT 844 844 P -> L (in Ref. 1; AAF23905).
CONFLICT 1197 1203 NKFIACL -> TSLLPVW (in Ref. 4).
Comments:
-!- FUNCTION: Probably involved in the repair of mismatches in DNA.
-!- SUBUNIT: Heterodimer of MLH1 and MLH3.
-!- SUBCELLULAR LOCATION: Nucleus (Potential).
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=2;
Name=1;
IsoId=Q9UHC1-1; Sequence=Displayed;
Name=2;
IsoId=Q9UHC1-2; Sequence=VSP_003290;
-!- TISSUE SPECIFICITY: Ubiquitous.
-!- DISEASE: Defects in MLH3 are the cause of hereditary non-polyposis
colorectal cancer type 7 (HNPCC7) [MIM:604395]. 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.
-!- SIMILARITY: Belongs to the DNA mismatch repair mutL/hexB family.
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Sequence length: 1453
MIKCLSVEVQ AKLRSGLAIS SLGQCVEELA LNSIDAEAKC VAVRVNMETF QVQVIDNGFG
MGSDDVEKVG NRYFTSKCHS VQDLENPRFY GFRGEALANI ADMASAVEIS SKKNRTMKTF
VKLFQSGKAL KACEADVTRA SAGTTVTVYN LFYQLPVRRK CMDPRLEFEK VRQRIEALSL
MHPSISFSLR NDVSGSMVLQ LPKTKDVCSR FCQIYGLGKS QKLREISFKY KEFELSGYIS
SEAHYNKNMQ FLFVNKRLVL RTKLHKLIDF LLRKESIICK PKNGPTSRQM NSSLRHRSTP
ELYGIYVINV QCQFCEYDVC MEPAKTLIEF QNWDTLLFCI QEGVKMFLKQ EKLFVELSGE
DIKEFSEDNG FSLFDATLQK RVTSDERSNF QEACNNILDS YEMFNLQSKA VKRKTTAENV
NTQSSRDSEA TRKNTNDAFL YIYESGGPGH SKMTEPSLQN KDSSCSESKM LEQETIVASE
AGENEKHKKS FLEHSSLENP CGTSLEMFLS PFQTPCHFEE SGQDLEIWKE STTVNGMAAN
ILKNNRIQNQ PKRFKDATEV GCQPLPFATT LWGVHSAQTE KEKKKESSNC GRRNVFSYGR
VKLCSTGFIT HVVQNEKTKS TETEHSFKNY VRPGPTRAQE TFGNRTRHSV ETPDIKDLAS
TLSKESGQLP NKKNCRTNIS YGLENEPTAT YTMFSAFQEG SKKSQTDCIL SDTSPSFPWY
RHVSNDSRKT DKLIGFSKPI VRKKLSLSSQ LGSLEKFKRQ YGKVENPLDT EVEESNGVTT
NLSLQVEPDI LLKDKNRLEN SDVCKITTME HSDSDSSCQP ASHILDSEKF PFSKDEDCLE
QQMPSLRESP MTLKELSLFN RKPLDLEKSS ESLASKLSRL KGSERETQTM GMMSRFNELP
NSDSSRKDSK LCSVLTQDFC MLFNNKHEKT ENGVIPTSDS ATQDNSFNKN SKTHSNSNTT
ENCVISETPL VLPYNNSKVT GKDSDVLIRA SEQQIGSLDS PSGMLMNPVE DATGDQNGIC
FQSEESKARA CSETEESNTC CSDWQRHFDV ALGRMVYVNK MTGLSTFIAP TEDIQAACTK
DLTTVAVDVV LENGSQYRCQ PFRSDLVLPF LPRARAERTV MRQDNRDTVD DTVSSESLQS
LFSEWDNPVF ARYPEVAVDV SSGQAESLAV KIHNILYPYR FTKGMIHSMQ VLQQVDNKFI
ACLMSTKTEE NGEAGGNLLV LVDQHAAHER IRLEQLIIDS YEKQQAQGSG RKKLLSSTLI
PPLEITVTEE QRRLLWCYHK NLEDLGLEFV FPDTSDSLVL VGKVPLCFVE REANELRRGR
STVTKSIVEE FIREQLELLQ TTGGIQGTLP LTVQKVLASQ ACHGAIKFND GLSLQESCRL
IEALSSCQLP FQCAHGRPSM LPLADIDHLE QEKQIKPNLT KLRKMAQAWR LFGKAECDTR
QSLQQSMPPC EPP