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P40692

- MLH1_HUMAN

UniProt

P40692 - MLH1_HUMAN

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Protein

DNA mismatch repair protein Mlh1

Gene

MLH1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

Heterodimerizes with PMS2 to form MutL alpha, a component of the post-replicative DNA mismatch repair system (MMR). 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. MutL 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. Heterodimerizes with MLH3 to form MutL gamma which plays a role in meiosis.2 Publications

GO - Molecular functioni

  1. ATPase activity Source: RefGenome
  2. ATP binding Source: InterPro
  3. guanine/thymine mispair binding Source: Ensembl

GO - Biological processi

  1. ATP catabolic process Source: GOC
  2. double-strand break repair via nonhomologous end joining Source: Ensembl
  3. intrinsic apoptotic signaling pathway in response to DNA damage Source: Ensembl
  4. isotype switching Source: Ensembl
  5. male meiosis chromosome segregation Source: Ensembl
  6. meiotic metaphase I plate congression Source: Ensembl
  7. mismatch repair Source: MGI
  8. negative regulation of mitotic recombination Source: Ensembl
  9. nuclear-transcribed mRNA poly(A) tail shortening Source: Ensembl
  10. oogenesis Source: Ensembl
  11. resolution of meiotic recombination intermediates Source: Ensembl
  12. somatic hypermutation of immunoglobulin genes Source: RefGenome
  13. spermatogenesis Source: Ensembl
  14. spindle midzone assembly involved in meiosis Source: Ensembl
  15. synapsis Source: Ensembl
Complete GO annotation...

Keywords - Biological processi

Cell cycle, DNA damage, DNA repair

Enzyme and pathway databases

ReactomeiREACT_27271. Meiotic recombination.

Names & Taxonomyi

Protein namesi
Recommended name:
DNA mismatch repair protein Mlh1
Alternative name(s):
MutL protein homolog 1
Gene namesi
Name:MLH1
Synonyms:COCA2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 3

Organism-specific databases

HGNCiHGNC:7127. MLH1.

Subcellular locationi

Nucleus 2 Publications

GO - Cellular componenti

  1. chiasma Source: RefGenome
  2. male germ cell nucleus Source: Ensembl
  3. membrane Source: UniProtKB
  4. MutLalpha complex Source: RefGenome
  5. nucleus Source: HGNC
  6. synaptonemal complex Source: RefGenome
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

Hereditary non-polyposis colorectal cancer 2 (HNPCC2) [MIM:609310]: An autosomal dominant disease associated with marked increase in cancer susceptibility. It is characterized by a familial predisposition to early-onset colorectal carcinoma (CRC) and extra-colonic tumors 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. Clinically, HNPCC is often divided into two subgroups. Type I is characterized by hereditary predisposition to colorectal cancer, a young age of onset, and carcinoma observed in the proximal colon. Type II is characterized by 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.55 Publications
Note: The disease is caused by mutations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti18 – 181R → C in HNPCC2. 1 Publication
VAR_022663
Natural varianti19 – 191I → F in HNPCC2; unknown pathological significance. 1 Publication
VAR_043383
Natural varianti21 – 211A → V in HNPCC2. 1 Publication
VAR_043384
Natural varianti25 – 251I → F in HNPCC2. 1 Publication
VAR_043385
Natural varianti28 – 281P → L in HNPCC2. 5 Publications
VAR_004433
Natural varianti29 – 291A → S in HNPCC2; unknown pathological significance; has no effect on ex vivo splicing assay. 2 Publications
VAR_043386
Natural varianti35 – 351M → K in HNPCC2; unknown pathological significance. 1 Publication
VAR_043387
Natural varianti35 – 351M → R in HNPCC2.
VAR_004434
Natural varianti38 – 381N → H in HNPCC2. 1 Publication
VAR_043389
Natural varianti41 – 411D → G in HNPCC2. 1 Publication
VAR_043390
Natural varianti41 – 411D → H Associated with HNPCC2; has no effect on ex vivo splicing assay. 1 Publication
VAR_054522
Natural varianti44 – 441S → F in HNPCC2; the equivalent substitution in yeast causes loss of function in a mismatch repair assay; has no effect on ex vivo splicing assay. 1 Publication
VAR_004436
Natural varianti45 – 473TSI → CF in HNPCC2.
VAR_043391
Natural varianti62 – 621Q → K in HNPCC2; reduced repair efficiency in a yeast mismatch repair assay. 1 Publication
VAR_004437
Natural varianti63 – 631D → E in HNPCC2. 1 Publication
VAR_043392
Natural varianti64 – 641N → S in HNPCC2. 1 Publication
VAR_004438
Natural varianti67 – 671G → R in HNPCC2; the equivalent substitution in yeast causes loss of function in a mismatch repair assay; has no effect on ex vivo splicing assay. 8 Publications
VAR_004439
Natural varianti67 – 671G → W in HNPCC2. 2 Publications
VAR_012903
Natural varianti68 – 681I → N in HNPCC2; the equivalent substitution in yeast causes loss of function in a mismatch repair assay. 1 Publication
VAR_004440
Natural varianti69 – 691R → K in HNPCC2; reduced repair efficiency in a mismatch repair assay. 1 Publication
VAR_004441
Natural varianti71 – 711Missing in HNPCC2. 1 Publication
VAR_043393
Natural varianti77 – 771C → R in HNPCC2 and CRC; sporadic; normal interaction with PMS2; loss of function in a mismatch repair assay. 3 Publications
VAR_004442
Natural varianti80 – 801F → V in HNPCC2. 2 Publications
VAR_012905
Natural varianti84 – 841K → E in HNPCC2. 2 Publications
VAR_012906
Natural varianti98 – 981G → S Associated with HNPCC2; has no effect on ex vivo splicing assay. 1 Publication
VAR_054523
Natural varianti101 – 1011G → D in HNPCC2; has no effect on ex vivo splicing assay. 2 Publications
VAR_022664
Natural varianti101 – 1011G → S Associated with HNPCC2; has no effect on ex vivo splicing assay. 1 Publication
VAR_054524
Natural varianti102 – 1021E → K in HNPCC2; unknown pathological significance. 1 Publication
VAR_043394
Natural varianti107 – 1071I → R in HNPCC2; normal interaction with PMS2; loss of function in a mismatch repair assay. 1 Publication
VAR_004444
Natural varianti111 – 1111A → V in HNPCC2; unknown pathological significance. 2 Publications
VAR_012907
Natural varianti116 – 1161T → K Associated with HNPCC2; has no effect on ex vivo splicing assay. 1 Publication
VAR_054525
Natural varianti117 – 1171T → M in HNPCC2; fails to interact with PMS2 and EXO1; loss of function in a mismatch repair assay; has no effect on ex vivo splicing assay. 7 Publications
VAR_004445
Natural varianti117 – 1171T → R in HNPCC2; equivalent substitution in yeast causes loss of function in mismatch repair assay. 1 Publication
VAR_004446
Natural varianti126 – 1261Y → N Associated with HNPCC2; has no effect on ex vivo splicing assay. 1 Publication
Corresponds to variant rs200076893 [ dbSNP | Ensembl ].
VAR_054526
Natural varianti128 – 1281A → P in HNPCC2. 1 Publication
VAR_012908
Natural varianti155 – 1551L → R in HNPCC2. 1 Publication
VAR_043397
Natural varianti182 – 1821R → G in HNPCC2; incomplete. 2 Publications
VAR_012909
Natural varianti182 – 1821R → K in HNPCC2. 1 Publication
VAR_022666
Natural varianti185 – 1851V → G in HNPCC2; defective in a mismatch repair assay; has no effect on ex vivo splicing assay. 1 Publication
VAR_004447
Natural varianti185 – 1851V → L in HNPCC2; unknown pathological significance. 1 Publication
VAR_043398
Natural varianti193 – 1931S → P in HNPCC2. 1 Publication
VAR_004448
Natural varianti213 – 2131V → M Associated with HNPCC2; has no effect on ex vivo splicing assay. 5 Publications
Corresponds to variant rs2308317 [ dbSNP | Ensembl ].
VAR_012910
Natural varianti215 – 2151N → S Associated with HNPCC2; has no effect on ex vivo splicing assay. 1 Publication
VAR_054527
Natural varianti216 – 2161I → S Associated with HNPCC2; has no effect on ex vivo splicing assay. 1 Publication
VAR_054528
Natural varianti217 – 2171R → C in HNPCC2; unknown pathological significance; proficient in a mismatch repair assay. 3 Publications
Corresponds to variant rs4986984 [ dbSNP | Ensembl ].
VAR_004449
Natural varianti226 – 29570Missing in HNPCC2.
VAR_004452Add
BLAST
Natural varianti226 – 2261R → L in HNPCC2. 1 Publication
VAR_004451
Natural varianti234 – 2341E → G in HNPCC2; unknown pathological significance. 1 Publication
VAR_043399
Natural varianti244 – 2441G → D in HNPCC2; defective in a mismatch repair assay. 2 Publications
VAR_012911
Natural varianti247 – 2471S → P in HNPCC2. 2 Publications
VAR_043400
Natural varianti260 – 2601L → F Associated with HNPCC2; has no effect on ex vivo splicing assay. 1 Publication
VAR_054529
Natural varianti262 – 2621Missing in HNPCC2. 1 Publication
VAR_012913
Natural varianti264 – 2641H → Y in HNPCC2. 1 Publication
VAR_043402
Natural varianti265 – 2651R → C Associated with HNPCC2; results in partial exon 10 skipping on ex vivo splicing assay. 1 Publication
VAR_054530
Natural varianti265 – 2651R → H Rare polymorphism; associated with HNPCC2; slightly lower mismatch repair efficiency; results in partial exon 10 skipping on ex vivo splicing assay. 3 Publications
VAR_012914
Natural varianti282 – 2821A → G in HNPCC2. 1 Publication
VAR_043403
Natural varianti292 – 2921L → P in HNPCC2; unknown pathological significance. 2 Publications
VAR_043404
Natural varianti295 – 2951S → T in HNPCC2. 1 Publication
VAR_012916
Natural varianti304 – 3041D → V in HNPCC2. 1 Publication
VAR_043405
Natural varianti320 – 3201E → D Associated with HNPCC2; has no effect on ex vivo splicing assay. 1 Publication
VAR_054531
Natural varianti321 – 3211S → I in HNPCC2; unknown pathological significance. 1 Publication
VAR_043406
Natural varianti326 – 3261V → A in HNPCC2; proficient in a mismatch repair assay. 2 Publications
Corresponds to variant rs63751049 [ dbSNP | Ensembl ].
VAR_004453
Natural varianti329 – 3291H → P in HNPCC2. 4 Publications
VAR_012918
Natural varianti330 – 3301Missing in HNPCC2; results in weak exon 11 skipping on ex vivo splicing assay. 2 Publications
VAR_043408
Natural varianti338 – 3381N → S in HNPCC2. 1 Publication
VAR_043409
Natural varianti379 – 3791Y → C in HNPCC2. 1 Publication
VAR_022667
Natural varianti385 – 3851R → C in HNPCC2; unknown pathological significance. 1 Publication
VAR_043410
Natural varianti385 – 3851R → P in HNPCC2; unknown pathological significance. 1 Publication
VAR_043411
Natural varianti441 – 4411A → T in HNPCC2. 2 Publications
VAR_012920
Natural varianti474 – 4741R → Q in HNPCC2; unknown pathological significance. 2 Publications
VAR_043414
Natural varianti474 – 4741R → W Associated with HNPCC2; has no effect on ex vivo splicing assay. 1 Publication
VAR_054532
Natural varianti485 – 4851D → E in HNPCC2. 1 Publication
VAR_043415
Natural varianti485 – 4851D → H in HNPCC2; unknown pathological significance. 1 Publication
VAR_043416
Natural varianti492 – 4921A → T in HNPCC2 and CRC; sporadic. 1 Publication
VAR_004455
Natural varianti506 – 5061V → A in HNPCC2.
VAR_004456
Natural varianti539 – 5391A → D Associated with HNPCC2; has no effect on ex vivo splicing assay. 1 Publication
VAR_054533
Natural varianti542 – 5421Q → L in HNPCC2; type II; equivalent substitution in yeast causes loss of function in a mismatch repair assay. 3 Publications
VAR_004457
Natural varianti542 – 5421Q → P in HNPCC2. 1 Publication
VAR_043417
Natural varianti549 – 5491L → P in HNPCC2; has no effect on ex vivo splicing assay. 3 Publications
VAR_012921
Natural varianti550 – 5501L → P in HNPCC2. 1 Publication
VAR_043418
Natural varianti551 – 5511N → T in HNPCC2; has no effect on ex vivo splicing assay. 3 Publications
VAR_012922
Natural varianti559 – 5591L → R in HNPCC2. 1 Publication
VAR_022668
Natural varianti565 – 5651I → F in HNPCC2. 1 Publication
VAR_012923
Natural varianti574 – 5741L → P in HNPCC2; type I; abrogates interaction with EXO1. 3 Publications
VAR_004458
Natural varianti578 – 5781E → G in HNPCC2 and CRC. 1 Publication
VAR_004459
Natural varianti582 – 5821L → V in HNPCC2; type II. 1 Publication
Corresponds to variant rs63751713 [ dbSNP | Ensembl ].
VAR_004460
Natural varianti585 – 5851L → R Associated with HNPCC2; has no effect on ex vivo splicing assay. 1 Publication
VAR_054534
Natural varianti586 – 5861A → P in HNPCC2. 1 Publication
VAR_015689
Natural varianti588 – 5881L → P in HNPCC2. 1 Publication
VAR_012924
Natural varianti589 – 5891A → D in HNPCC2. 1 Publication
VAR_043419
Natural varianti596 – 5961Missing in HNPCC2.
VAR_043420
Natural varianti603 – 6031P → R in HNPCC2; unknown pathological significance; has no effect on ex vivo splicing assay. 3 Publications
Corresponds to variant rs35831931 [ dbSNP | Ensembl ].
VAR_012925
Natural varianti607 – 6071L → H in LCIS and HNPCC2; unknown pathological significance; has no effect on ex vivo splicing assay; could determine an increased risk of colon cancer. 5 Publications
Corresponds to variant rs41295284 [ dbSNP | Ensembl ].
VAR_012926
Natural varianti612 – 6121Missing in HNPCC2. 1 Publication
VAR_043422
Natural varianti616 – 6161Missing in HNPCC2 and MMRCS; abrogates interaction with EXO1; has no effect on ex vivo splicing assay. 9 Publications
VAR_004461
Natural varianti618 – 6181K → T in HNPCC2; type II. 5 Publications
VAR_004463
Natural varianti618 – 6181Missing in HNPCC2. 1 Publication
VAR_043423
Natural varianti619 – 6191A → P Associated with HNPCC2; has no effect on ex vivo splicing assay. 1 Publication
VAR_054535
Natural varianti622 – 6221L → H in HNPCC2. 1 Publication
VAR_012927
Natural varianti623 – 6231A → P in HNPCC2; unknown pathological significance. 1 Publication
VAR_043425
Natural varianti626 – 6272FS → ST in HNPCC2.
VAR_004464
Natural varianti631 – 6311D → A in HNPCC2; unknown pathological significance. 1 Publication
VAR_043426
Natural varianti636 – 6361L → P in HNPCC2. 1 Publication
VAR_043428
Natural varianti640 – 6401P → L Associated with HNPCC2; has no effect on ex vivo splicing assay. 1 Publication
VAR_054536
Natural varianti640 – 6401P → S in HNPCC2; has no effect on ex vivo splicing assay. 2 Publications
VAR_043429
Natural varianti646 – 6461Y → C in HNPCC2; unknown pathological significance. 2 Publications
Corresponds to variant rs35045067 [ dbSNP | Ensembl ].
VAR_043430
Natural varianti648 – 6481P → L in HNPCC2. 2 Publications
VAR_012928
Natural varianti648 – 6481P → S in HNPCC2; protein unstable but still functional in mismatch repair. 3 Publications
VAR_022669
Natural varianti654 – 6541P → L in HNPCC2. 1 Publication
VAR_043431
Natural varianti655 – 6551I → V Found in an endometrial cancer sample; also associated with HNPCC2; has no effect on ex vivo splicing assay. 2 Publications
Corresponds to variant rs55907433 [ dbSNP | Ensembl ].
VAR_043432
Natural varianti656 – 6561F → S Associated with HNPCC2; has no effect on ex vivo splicing assay. 1 Publication
VAR_054537
Natural varianti657 – 6571Missing in HNPCC2; unknown pathological significance. 1 Publication
VAR_043433
Natural varianti659 – 6591R → L in HNPCC2. 1 Publication
VAR_012929
Natural varianti659 – 6591R → P in HNPCC2; interacts only very weakly with PMS2; equivalent substitution in yeast causes almost complete loss of function in a mismatch repair assay; abrogates interaction with EXO1. 2 Publications
VAR_004465
Natural varianti662 – 6621T → P in HNPCC2; unknown pathological significance. 2 Publications
VAR_012930
Natural varianti666 – 6661W → R Associated with HNPCC2; has no effect on ex vivo splicing assay. 1 Publication
VAR_054538
Natural varianti681 – 6811A → T in HNPCC2; unknown pathological significance; equivalent substitution in yeast does not affect mismatch repair; abrogates interaction with EXO1. 5 Publications
VAR_004466
Natural varianti687 – 6871R → W in HNPCC2; unknown pathological significance. 3 Publications
VAR_012931
Natural varianti718 – 7181H → Y in HNPCC2; unknown pathological significance. 3 Publications
Corresponds to variant rs2020873 [ dbSNP | Ensembl ].
VAR_004467
Natural varianti719 – 7191I → INVFHI in HNPCC2.
VAR_043435
Natural varianti724 – 7241L → M in HNPCC2. 1 Publication
VAR_043436
Natural varianti751 – 7511K → R in HNPCC2; unknown pathological significance. 3 Publications
VAR_012934
Mismatch repair cancer syndrome (MMRCS) [MIM:276300]: An autosomal recessive, rare, childhood cancer predisposition syndrome encompassing a broad tumor spectrum. This includes hematological malignancies, central nervous system tumors, Lynch syndrome-associated malignancies such as colorectal tumors as well as multiple intestinal polyps, embryonic tumors and rhabdomyosarcoma. Multiple cafe-au-lait macules, a feature reminiscent of neurofibromatosis type 1, are often found as first manifestation of the underlying cancer. Areas of skin hypopigmentation have also been reported in MMRCS patients.2 Publications
Note: The disease is caused by mutations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti35 – 351M → N in MMRCS; requires 2 nucleotide substitutions. 2 Publications
VAR_043388
Natural varianti616 – 6161Missing in HNPCC2 and MMRCS; abrogates interaction with EXO1; has no effect on ex vivo splicing assay. 9 Publications
VAR_004461
Muir-Torre syndrome (MRTES) [MIM:158320]: Rare autosomal dominant disorder characterized by sebaceous neoplasms and visceral malignancy.1 Publication
Note: The disease is caused by mutations affecting the gene represented in this entry.
Defects in MLH1 may contribute to lobular carcinoma in situ (LCIS), a non-invasive neoplastic disease of the breast.
Endometrial cancer (ENDMC) [MIM:608089]: A malignancy of endometrium, the mucous lining of the uterus. Most endometrial cancers are adenocarcinomas, cancers that begin in cells that make and release mucus and other fluids.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry.
Some epigenetic changes can be transmitted unchanged through the germline (termed 'epigenetic inheritance'). Evidence that this mechanism occurs in humans is provided by the identification of individuals in whom 1 allele of the MLH1 gene is epigenetically silenced throughout the soma (implying a germline event). These individuals are affected by HNPCC but does not have identifiable mutations in MLH1, even though it is silenced, which demonstrates that an epimutation can phenocopy a genetic disease.

Keywords - Diseasei

Disease mutation, Hereditary nonpolyposis colorectal cancer, Tumor suppressor

Organism-specific databases

MIMi158320. phenotype.
276300. phenotype.
608089. phenotype.
609310. phenotype.
Orphaneti252202. Constitutional mismatch repair deficiency syndrome.
144. Hereditary nonpolyposis colon cancer.
587. Muir-Torre syndrome.
99817. Non-polyposis Turcot syndrome.
PharmGKBiPA240.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11Removed1 Publication
Chaini2 – 756755DNA mismatch repair protein Mlh1PRO_0000178000Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylserine1 Publication
Modified residuei477 – 4771Phosphoserine3 Publications

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiP40692.
PaxDbiP40692.
PRIDEiP40692.

PTM databases

PhosphoSiteiP40692.

Miscellaneous databases

PMAP-CutDBP40692.

Expressioni

Tissue specificityi

Colon, lymphocytes, breast, lung, spleen, testis, prostate, thyroid, gall bladder and heart.

Gene expression databases

BgeeiP40692.
CleanExiHS_MLH1.
ExpressionAtlasiP40692. baseline and differential.
GenevestigatoriP40692.

Organism-specific databases

HPAiCAB013294.
HPA052707.

Interactioni

Subunit structurei

Heterodimer of MLH1 and PMS2 (MutL alpha), MLH1 and PMS1 (MutL beta) or MLH1 and MLH3 (MutL gamma). 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 MBD4. Interacts with EXO1 and MTMR15/FAN1.6 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ACTG1P632617EBI-744248,EBI-351292
ANXA2P073557EBI-744248,EBI-352622
BRIP1Q9BX6311EBI-744248,EBI-3509650
CTSBP078587EBI-744248,EBI-715062
DESP176617EBI-744248,EBI-1055572
FSCN1Q166587EBI-744248,EBI-351076
NT5C3BQ969T73EBI-744248,EBI-2932564
PMS2P542784EBI-744248,EBI-1162561
SPTAN1Q138137EBI-744248,EBI-351450
TMSB4XP6232816EBI-744248,EBI-712598
ZC3H11AO751523EBI-744248,EBI-748480

Protein-protein interaction databases

BioGridi110438. 117 interactions.
DIPiDIP-27601N.
IntActiP40692. 97 interactions.
MINTiMINT-257265.
STRINGi9606.ENSP00000231790.

Structurei

Secondary structure

1
756
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi13 – 2513
Helixi28 – 4114
Beta strandi45 – 528
Turni53 – 564
Beta strandi57 – 637
Helixi70 – 723
Turni73 – 775
Helixi103 – 1097
Beta strandi110 – 1189
Beta strandi122 – 13110
Beta strandi134 – 1374
Beta strandi140 – 1423
Beta strandi146 – 1549
Turni155 – 1584
Helixi160 – 1656
Helixi169 – 18618
Turni187 – 1893
Beta strandi190 – 1967
Beta strandi203 – 2053
Helixi212 – 2209
Helixi222 – 2254
Beta strandi228 – 2358
Turni236 – 2394
Beta strandi240 – 2478
Beta strandi253 – 2553
Beta strandi257 – 2626
Helixi270 – 28112
Beta strandi291 – 2988
Helixi322 – 33514
Helixi504 – 51613
Helixi519 – 5268
Beta strandi529 – 54315
Beta strandi546 – 5516
Helixi552 – 56615
Beta strandi572 – 58110
Helixi582 – 5909
Helixi593 – 5953
Helixi604 – 62623
Beta strandi634 – 6418
Helixi650 – 6523
Helixi653 – 66210
Helixi669 – 68416
Helixi688 – 6903
Helixi712 – 7187
Helixi720 – 7245
Helixi732 – 7354
Beta strandi737 – 7459

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3NA3X-ray2.50A1-347[»]
3RBNX-ray2.16A/B486-751[»]
4P7AX-ray2.30A1-347[»]
ProteinModelPortaliP40692.
SMRiP40692. Positions 3-336, 487-751.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP40692.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni410 – 650241Interaction with EXO1Add
BLAST

Sequence similaritiesi

Phylogenomic databases

eggNOGiCOG0323.
GeneTreeiENSGT00550000074923.
HOGENOMiHOG000176000.
HOVERGENiHBG006374.
InParanoidiP40692.
KOiK08734.
OMAiINHRCVE.
OrthoDBiEOG7MSMNH.
PhylomeDBiP40692.
TreeFamiTF300493.

Family and domain databases

Gene3Di3.30.230.10. 1 hit.
3.30.565.10. 1 hit.
InterProiIPR013507. DNA_mismatch_repair_C.
IPR014762. DNA_mismatch_repair_CS.
IPR002099. DNA_mismatch_repair_fam.
IPR011186. DNA_mismatch_repair_MLH1/HexB.
IPR003594. HATPase_C.
IPR020568. Ribosomal_S5_D2-typ_fold.
IPR014721. Ribosomal_S5_D2-typ_fold_subgr.
[Graphical view]
PANTHERiPTHR10073:SF12. PTHR10073:SF12. 1 hit.
PfamiPF01119. DNA_mis_repair. 1 hit.
[Graphical view]
SMARTiSM00387. HATPase_c. 1 hit.
[Graphical view]
SUPFAMiSSF54211. SSF54211. 1 hit.
SSF55874. SSF55874. 1 hit.
TIGRFAMsiTIGR00585. mutl. 1 hit.
PROSITEiPS00058. DNA_MISMATCH_REPAIR_1. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: P40692-1) [UniParc]FASTAAdd to Basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

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        10         20         30         40         50
MSFVAGVIRR LDETVVNRIA AGEVIQRPAN AIKEMIENCL DAKSTSIQVI
60 70 80 90 100
VKEGGLKLIQ IQDNGTGIRK EDLDIVCERF TTSKLQSFED LASISTYGFR
110 120 130 140 150
GEALASISHV AHVTITTKTA DGKCAYRASY SDGKLKAPPK PCAGNQGTQI
160 170 180 190 200
TVEDLFYNIA TRRKALKNPS EEYGKILEVV GRYSVHNAGI SFSVKKQGET
210 220 230 240 250
VADVRTLPNA STVDNIRSIF GNAVSRELIE IGCEDKTLAF KMNGYISNAN
260 270 280 290 300
YSVKKCIFLL FINHRLVEST SLRKAIETVY AAYLPKNTHP FLYLSLEISP
310 320 330 340 350
QNVDVNVHPT KHEVHFLHEE SILERVQQHI ESKLLGSNSS RMYFTQTLLP
360 370 380 390 400
GLAGPSGEMV KSTTSLTSSS TSGSSDKVYA HQMVRTDSRE QKLDAFLQPL
410 420 430 440 450
SKPLSSQPQA IVTEDKTDIS SGRARQQDEE MLELPAPAEV AAKNQSLEGD
460 470 480 490 500
TTKGTSEMSE KRGPTSSNPR KRHREDSDVE MVEDDSRKEM TAACTPRRRI
510 520 530 540 550
INLTSVLSLQ EEINEQGHEV LREMLHNHSF VGCVNPQWAL AQHQTKLYLL
560 570 580 590 600
NTTKLSEELF YQILIYDFAN FGVLRLSEPA PLFDLAMLAL DSPESGWTEE
610 620 630 640 650
DGPKEGLAEY IVEFLKKKAE MLADYFSLEI DEEGNLIGLP LLIDNYVPPL
660 670 680 690 700
EGLPIFILRL ATEVNWDEEK ECFESLSKEC AMFYSIRKQY ISEESTLSGQ
710 720 730 740 750
QSEVPGSIPN SWKWTVEHIV YKALRSHILP PKHFTEDGNI LQLANLPDLY

KVFERC
Length:756
Mass (Da):84,601
Last modified:February 1, 1995 - v1
Checksum:iC9231FC406C2CA20
GO
Isoform 2 (identifier: P40692-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-241: Missing.

Show »
Length:515
Mass (Da):58,375
Checksum:iDCD9320AB8E5ADF5
GO
Isoform 3 (identifier: P40692-3) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-101: MSFVAGVIRR...ASISTYGFRG → MAF

Note: No experimental confirmation available.

Show »
Length:658
Mass (Da):73,837
Checksum:iC7ED5BB8A39DA389
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti352 – 3521L → H in BAG60773. (PubMed:14702039)Curated
Sequence conflicti708 – 7114Missing in AAA85687. (PubMed:7757073)Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti18 – 181R → C in HNPCC2. 1 Publication
VAR_022663
Natural varianti19 – 191I → F in HNPCC2; unknown pathological significance. 1 Publication
VAR_043383
Natural varianti21 – 211A → V in HNPCC2. 1 Publication
VAR_043384
Natural varianti22 – 221G → A.1 Publication
Corresponds to variant rs41295280 [ dbSNP | Ensembl ].
VAR_038023
Natural varianti25 – 251I → F in HNPCC2. 1 Publication
VAR_043385
Natural varianti28 – 281P → L in HNPCC2. 5 Publications
VAR_004433
Natural varianti29 – 291A → S in HNPCC2; unknown pathological significance; has no effect on ex vivo splicing assay. 2 Publications
VAR_043386
Natural varianti32 – 321I → V.1 Publication
Corresponds to variant rs2020872 [ dbSNP | Ensembl ].
VAR_014876
Natural varianti35 – 351M → K in HNPCC2; unknown pathological significance. 1 Publication
VAR_043387
Natural varianti35 – 351M → N in MMRCS; requires 2 nucleotide substitutions. 2 Publications
VAR_043388
Natural varianti35 – 351M → R in HNPCC2.
VAR_004434
Natural varianti37 – 371E → ELNH Found in an endometrial cancer sample; somatic mutation.
VAR_004435
Natural varianti38 – 381N → H in HNPCC2. 1 Publication
VAR_043389
Natural varianti41 – 411D → G in HNPCC2. 1 Publication
VAR_043390
Natural varianti41 – 411D → H Associated with HNPCC2; has no effect on ex vivo splicing assay. 1 Publication
VAR_054522
Natural varianti44 – 441S → F in HNPCC2; the equivalent substitution in yeast causes loss of function in a mismatch repair assay; has no effect on ex vivo splicing assay. 1 Publication