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Protein

DNA mismatch repair protein Msh6

Gene

MSH6

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

Functioni

Component of the post-replicative DNA mismatch repair system (MMR). Heterodimerizes with MSH2 to form MutS alpha, which binds to DNA mismatches thereby initiating DNA repair. When bound, MutS alpha bends the DNA helix and shields approximately 20 base pairs, and recognizes single base mismatches and dinucleotide insertion-deletion loops (IDL) in the DNA. After mismatch binding, forms a ternary complex with the MutL alpha heterodimer, which is thought to be responsible for directing the downstream MMR events, including strand discrimination, excision, and resynthesis. ATP binding and hydrolysis play a pivotal role in mismatch repair functions. The ATPase activity associated with MutS alpha regulates binding similar to a molecular switch: mismatched DNA provokes ADP-->ATP exchange, resulting in a discernible conformational transition that converts MutS alpha into a sliding clamp capable of hydrolysis-independent diffusion along the DNA backbone. This transition is crucial for mismatch repair. MutS alpha may also play a role in DNA homologous recombination repair. Recruited on chromatin in G1 and early S phase via its PWWP domain that specifically binds trimethylated 'Lys-36' of histone H3 (H3K36me3): early recruitment to chromatin to be replicated allowing a quick identification of mismatch repair to initiate the DNA mismatch repair reaction.8 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi1134 – 1141ATPSequence analysis8

GO - Molecular functioni

  • ATP binding Source: GO_Central
  • chromatin binding Source: Ensembl
  • damaged DNA binding Source: GO_Central
  • DNA-dependent ATPase activity Source: GO_Central
  • enzyme binding Source: UniProtKB
  • four-way junction DNA binding Source: GO_Central
  • guanine/thymine mispair binding Source: Ensembl
  • methylated histone binding Source: UniProtKB
  • mismatched DNA binding Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionDNA-binding
Biological processDNA damage, DNA repair, Host-virus interaction
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-HSA-5358565 Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha)
R-HSA-5632928 Defective Mismatch Repair Associated With MSH2
R-HSA-5632968 Defective Mismatch Repair Associated With MSH6
SIGNORiP52701

Names & Taxonomyi

Protein namesi
Recommended name:
DNA mismatch repair protein Msh6By similarity
Short name:
hMSH61 Publication
Alternative name(s):
G/T mismatch-binding protein1 Publication
Short name:
GTBP1 Publication
Short name:
GTMBPBy similarity
MutS protein homolog 6Imported
MutS-alpha 160 kDa subunit
Short name:
p1601 Publication
Gene namesi
Name:MSH6Imported
Synonyms:GTBP
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000116062.14
HGNCiHGNC:7329 MSH6
MIMi600678 gene
neXtProtiNX_P52701

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Chromosome, Nucleus

Pathology & Biotechi

Involvement in diseasei

Hereditary non-polyposis colorectal cancer 5 (HNPCC5)9 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn 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.
See also OMIM:614350
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04394320A → V in HNPCC5, CRC and ENDMC; unknown pathological significance; normal mismatch repair activity. 2 PublicationsCorresponds to variant dbSNP:rs63750664EnsemblClinVar.1
Natural variantiVAR_06729425A → S in HNPCC5; unknown pathological significance; normal mismatch repair activity. 1 PublicationCorresponds to variant dbSNP:rs267608026EnsemblClinVar.1
Natural variantiVAR_043946128R → L in HNPCC5; unknown pathological significance; no impairment of heterodimerization with MSH2; normal mismatch repair activity. 2 PublicationsCorresponds to variant dbSNP:rs63750143EnsemblClinVar.1
Natural variantiVAR_067295326A → V in HNPCC5; unknown pathological significance; normal mismatch repair activity. 1 PublicationCorresponds to variant dbSNP:rs587779323EnsemblClinVar.1
Natural variantiVAR_012958396L → V in HNPCC5; unknown pathological significance; normal mismatch repair activity. 3 PublicationsCorresponds to variant dbSNP:rs2020908EnsemblClinVar.1
Natural variantiVAR_042275492M → V in HNPCC5; unknown pathological significance; normal mismatch repair activity. 3 PublicationsCorresponds to variant dbSNP:rs61754783EnsemblClinVar.1
Natural variantiVAR_038036503S → C in HNPCC5; unknown pathological significance; normal mismatch repair activity. 2 PublicationsCorresponds to variant dbSNP:rs63750897EnsemblClinVar.1
Natural variantiVAR_067296610K → N in HNPCC5; unknown pathological significance; normal mismatch repair activity. 1 PublicationCorresponds to variant dbSNP:rs201735525EnsemblClinVar.1
Natural variantiVAR_043953623P → L in HNPCC5; unknown pathological significance; no impairment of heterodimerization with MSH2; normal mismatch repair activity. 2 PublicationsCorresponds to variant dbSNP:rs63750462EnsemblClinVar.1
Natural variantiVAR_043956728K → T in HNPCC5; unknown pathological significance; no impairment of heterodimerization with MSH2; normal mismatch repair activity. 2 PublicationsCorresponds to variant dbSNP:rs35552856EnsemblClinVar.1
Natural variantiVAR_043958772R → W in HNPCC5. 1 PublicationCorresponds to variant dbSNP:rs63750138EnsemblClinVar.1
Natural variantiVAR_012964878V → A in HNPCC5, CRC and ENDMC; unknown pathological significance; normal mismatch repair activity. 9 PublicationsCorresponds to variant dbSNP:rs2020912EnsemblClinVar.1
Natural variantiVAR_076356881G → KS in HNPCC5; unknown pathological significance; normal mismatch repair activity. 1 Publication1
Natural variantiVAR_0672971026D → Y in HNPCC5; unknown pathological significance; normal mismatch repair activity. 1 PublicationCorresponds to variant dbSNP:rs267608054EnsemblClinVar.1
Natural variantiVAR_0672981087P → S in HNPCC5; unknown pathological significance; normal mismatch repair activity. 1 PublicationCorresponds to variant dbSNP:rs63750998EnsemblClinVar.1
Natural variantiVAR_0439691163E → V in HNPCC5. 1 PublicationCorresponds to variant dbSNP:rs63750252EnsemblClinVar.1
Natural variantiVAR_0439701193E → K in HNPCC5; decreased mismatch repair activity; displays marked impairment of heterodimerization with MSH2. 2 PublicationsCorresponds to variant dbSNP:rs63751328EnsemblClinVar.1
Natural variantiVAR_0672991225T → M in HNPCC5; unknown pathological significance; normal mismatch repair activity. 1 PublicationCorresponds to variant dbSNP:rs63750370EnsemblClinVar.1
Endometrial cancer (ENDMC)2 Publications
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:608089
Mismatch repair cancer syndrome (MMRCS)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn 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.
See also OMIM:276300
Colorectal cancer (CRC)12 Publications
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history.
See also OMIM:114500
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04394454G → A in CRC; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63751098EnsemblClinVar.1
Natural variantiVAR_04394599K → N in CRC; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63751258EnsemblClinVar.1
Natural variantiVAR_012957285S → I in CRC; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63750878EnsemblClinVar.1
Natural variantiVAR_043948340F → S in CRC, breast cancer and leukemia; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs61753793EnsemblClinVar.1
Natural variantiVAR_043951522Q → R in CRC; unknown pathological significance; normal mismatch repair activity. 2 PublicationsCorresponds to variant dbSNP:rs63751009EnsemblClinVar.1
Natural variantiVAR_043952619E → D in CRC; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63751121EnsemblClinVar.1
Natural variantiVAR_043954685G → A in CRC; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63750358EnsemblClinVar.1
Natural variantiVAR_043955725I → M in CRC; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63750304EnsemblClinVar.1
Natural variantiVAR_043957772R → Q in CRC; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63750725EnsemblClinVar.1
Natural variantiVAR_043959787A → V in CRC; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63750637EnsemblClinVar.1
Natural variantiVAR_043960800V → A in CRC; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs63750895Ensembl.1
Natural variantiVAR_012962803D → G in CRC; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63751450EnsemblClinVar.1
Natural variantiVAR_043961854K → M in CRC; unknown pathological significance. 2 PublicationsCorresponds to variant dbSNP:rs34374438EnsemblClinVar.1
Natural variantiVAR_012965976R → H in CRC; sporadic; unknown pathological significance; normal mismatch repair activity. 2 PublicationsCorresponds to variant dbSNP:rs63751113EnsemblClinVar.1
Natural variantiVAR_0439631021A → D in CRC; unknown pathological significance; normal mismatch repair activity. 2 PublicationsCorresponds to variant dbSNP:rs63750287EnsemblClinVar.1
Natural variantiVAR_0439641031D → V in CRC; unknown pathological significance; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs63750804Ensembl.1
Natural variantiVAR_0439651076R → C in CRC; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63750617EnsemblClinVar.1
Natural variantiVAR_0439671100T → M in CRC; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63750442EnsemblClinVar.1
Natural variantiVAR_0439681158C → R in CRC; unknown pathological significance; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs63750157Ensembl.1
Natural variantiVAR_0439711219T → I in CRC; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63750949EnsemblClinVar.1
Natural variantiVAR_0439721248H → D in CRC; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63750882EnsemblClinVar.1
Natural variantiVAR_0439731284T → M in CRC; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63750836EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi103Y → A: Abolishes binding to H3K36me3 and DNA mismatch repair activity. 1 Publication1
Mutagenesisi105 – 106WW → AA: Abolishes binding to H3K36me3 and DNA mismatch repair activity. 1 Publication2
Mutagenesisi1140K → R: No effect on mismatch binding, complete loss of DNA repair function when associated with MSH2 mutant R-675. 1 Publication1

Keywords - Diseasei

Disease mutation, Hereditary nonpolyposis colorectal cancer

Organism-specific databases

DisGeNETi2956
GeneReviewsiMSH6
MalaCardsiMSH6
MIMi114500 phenotype
276300 phenotype
608089 phenotype
614350 phenotype
OpenTargetsiENSG00000116062
Orphaneti252202 Constitutional mismatch repair deficiency syndrome
144 Lynch syndrome
587 Muir-Torre syndrome
PharmGKBiPA184

Polymorphism and mutation databases

BioMutaiMSH6
DMDMi68067672

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001152071 – 1360DNA mismatch repair protein Msh6Add BLAST1360

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei14PhosphoserineCombined sources1
Modified residuei41PhosphoserineCombined sources1
Modified residuei43PhosphoserineCombined sources1
Modified residuei70N6-acetyllysineCombined sources1
Modified residuei79PhosphoserineCombined sources1
Modified residuei91PhosphoserineCombined sources1
Modified residuei137PhosphoserineCombined sources1
Modified residuei200PhosphoserineCombined sources1
Modified residuei219PhosphoserineCombined sources1
Modified residuei227PhosphoserineCombined sources1
Modified residuei252PhosphoserineCombined sources1
Modified residuei254PhosphoserineCombined sources1
Modified residuei256PhosphoserineCombined sources1
Modified residuei261PhosphoserineCombined sources1
Modified residuei269PhosphothreonineCombined sources1
Modified residuei274PhosphoserineCombined sources1
Modified residuei275PhosphoserineCombined sources1
Modified residuei279PhosphoserineCombined sources1
Modified residuei280PhosphoserineCombined sources1
Modified residuei309PhosphoserineCombined sources1
Modified residuei488PhosphothreonineCombined sources1
Modified residuei504N6-acetyllysineCombined sources1
Modified residuei830PhosphoserineCombined sources1
Modified residuei935PhosphoserineCombined sources1
Modified residuei1010PhosphothreonineCombined sources1

Post-translational modificationi

The N-terminus is blocked.
Phosphorylated by PRKCZ, which may prevent MutS alpha degradation by the ubiquitin-proteasome pathway.1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP52701
MaxQBiP52701
PaxDbiP52701
PeptideAtlasiP52701
PRIDEiP52701
ProteomicsDBi56502
56503 [P52701-2]

PTM databases

CarbonylDBiP52701
iPTMnetiP52701
PhosphoSitePlusiP52701

Miscellaneous databases

PMAP-CutDBiP52701

Expressioni

Gene expression databases

BgeeiENSG00000116062 Expressed in 233 organ(s), highest expression level in female gonad
CleanExiHS_MSH6
ExpressionAtlasiP52701 baseline and differential
GenevisibleiP52701 HS

Organism-specific databases

HPAiCAB009091
CAB070870
HPA028376
HPA028446

Interactioni

Subunit structurei

Component of the DNA mismatch repair (MMR) complex composed at least of MSH2, MSH3, MSH6, PMS1 and MLH1 (PubMed:26300262). Heterodimer consisting of MSH2-MSH6 (MutS alpha) (PubMed:8942985, PubMed:7604264). Forms a ternary complex with MutL alpha (MLH1-PMS1). Interacts with MCM9 (PubMed:26300262). 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 (PubMed:10783165). This association could be a dynamic process changing throughout the cell cycle and within subnuclear domains (PubMed:10783165).4 Publications
(Microbial infection) Interacts with herpes simplex virus 1 protein UL12.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
MSH2P432467EBI-395529,EBI-355888

GO - Molecular functioni

Protein-protein interaction databases

BioGridi109211, 94 interactors
ComplexPortaliCPX-80 DNA mismatch repair MutSalpha complex
CORUMiP52701
DIPiDIP-32972N
ELMiP52701
IntActiP52701, 39 interactors
MINTiP52701
STRINGi9606.ENSP00000234420

Structurei

Secondary structure

11360
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP52701
SMRiP52701
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP52701

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini92 – 154PWWPPROSITE-ProRule annotationAdd BLAST63

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi34 – 37Poly-Ala4
Compositional biasi201 – 209Poly-Glu9
Compositional biasi1118 – 1123Poly-Glu6

Domaini

The PWWP domain specifically recognizes and binds trimethylated 'Lys-36' of histone H3 (H3K36me3).1 Publication

Sequence similaritiesi

Belongs to the DNA mismatch repair MutS family.Curated

Phylogenomic databases

eggNOGiKOG0217 Eukaryota
COG0249 LUCA
GeneTreeiENSGT00550000075024
HOGENOMiHOG000243127
HOVERGENiHBG000101
InParanoidiP52701
KOiK08737
OMAiTPMMAQY
OrthoDBiEOG091G018J
PhylomeDBiP52701
TreeFamiTF105842

Family and domain databases

Gene3Di3.30.420.110, 1 hit
3.40.1170.10, 1 hit
InterProiView protein in InterPro
IPR015536 DNA_mismatch_repair_MSH6_C
IPR007695 DNA_mismatch_repair_MutS-lik_N
IPR017261 DNA_mismatch_repair_MutS/MSH
IPR000432 DNA_mismatch_repair_MutS_C
IPR007861 DNA_mismatch_repair_MutS_clamp
IPR007696 DNA_mismatch_repair_MutS_core
IPR016151 DNA_mismatch_repair_MutS_N
IPR036187 DNA_mismatch_repair_MutS_sf
IPR007860 DNA_mmatch_repair_MutS_con_dom
IPR036678 MutS_con_dom_sf
IPR027417 P-loop_NTPase
IPR000313 PWWP_dom
PANTHERiPTHR11361:SF31 PTHR11361:SF31, 1 hit
PfamiView protein in Pfam
PF01624 MutS_I, 1 hit
PF05188 MutS_II, 1 hit
PF05192 MutS_III, 1 hit
PF05190 MutS_IV, 1 hit
PF00488 MutS_V, 1 hit
PF00855 PWWP, 1 hit
PIRSFiPIRSF037677 DNA_mis_repair_Msh6, 1 hit
SMARTiView protein in SMART
SM00534 MUTSac, 1 hit
SM00533 MUTSd, 1 hit
SM00293 PWWP, 1 hit
SUPFAMiSSF48334 SSF48334, 1 hit
SSF52540 SSF52540, 1 hit
SSF55271 SSF55271, 1 hit
PROSITEiView protein in PROSITE
PS00486 DNA_MISMATCH_REPAIR_2, 1 hit
PS50812 PWWP, 1 hit

Sequences (4+)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 4 described isoforms and 8 potential isoforms that are computationally mapped.Show allAlign All

Isoform GTBP-N (identifier: P52701-1) [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.

« Hide
        10         20         30         40         50
MSRQSTLYSF FPKSPALSDA NKASARASRE GGRAAAAPGA SPSPGGDAAW
60 70 80 90 100
SEAGPGPRPL ARSASPPKAK NLNGGLRRSV APAAPTSCDF SPGDLVWAKM
110 120 130 140 150
EGYPWWPCLV YNHPFDGTFI REKGKSVRVH VQFFDDSPTR GWVSKRLLKP
160 170 180 190 200
YTGSKSKEAQ KGGHFYSAKP EILRAMQRAD EALNKDKIKR LELAVCDEPS
210 220 230 240 250
EPEEEEEMEV GTTYVTDKSE EDNEIESEEE VQPKTQGSRR SSRQIKKRRV
260 270 280 290 300
ISDSESDIGG SDVEFKPDTK EEGSSDEISS GVGDSESEGL NSPVKVARKR
310 320 330 340 350
KRMVTGNGSL KRKSSRKETP SATKQATSIS SETKNTLRAF SAPQNSESQA
360 370 380 390 400
HVSGGGDDSS RPTVWYHETL EWLKEEKRRD EHRRRPDHPD FDASTLYVPE
410 420 430 440 450
DFLNSCTPGM RKWWQIKSQN FDLVICYKVG KFYELYHMDA LIGVSELGLV
460 470 480 490 500
FMKGNWAHSG FPEIAFGRYS DSLVQKGYKV ARVEQTETPE MMEARCRKMA
510 520 530 540 550
HISKYDRVVR REICRIITKG TQTYSVLEGD PSENYSKYLL SLKEKEEDSS
560 570 580 590 600
GHTRAYGVCF VDTSLGKFFI GQFSDDRHCS RFRTLVAHYP PVQVLFEKGN
610 620 630 640 650
LSKETKTILK SSLSCSLQEG LIPGSQFWDA SKTLRTLLEE EYFREKLSDG
660 670 680 690 700
IGVMLPQVLK GMTSESDSIG LTPGEKSELA LSALGGCVFY LKKCLIDQEL
710 720 730 740 750
LSMANFEEYI PLDSDTVSTT RSGAIFTKAY QRMVLDAVTL NNLEIFLNGT
760 770 780 790 800
NGSTEGTLLE RVDTCHTPFG KRLLKQWLCA PLCNHYAIND RLDAIEDLMV
810 820 830 840 850
VPDKISEVVE LLKKLPDLER LLSKIHNVGS PLKSQNHPDS RAIMYEETTY
860 870 880 890 900
SKKKIIDFLS ALEGFKVMCK IIGIMEEVAD GFKSKILKQV ISLQTKNPEG
910 920 930 940 950
RFPDLTVELN RWDTAFDHEK ARKTGLITPK AGFDSDYDQA LADIRENEQS
960 970 980 990 1000
LLEYLEKQRN RIGCRTIVYW GIGRNRYQLE IPENFTTRNL PEEYELKSTK
1010 1020 1030 1040 1050
KGCKRYWTKT IEKKLANLIN AEERRDVSLK DCMRRLFYNF DKNYKDWQSA
1060 1070 1080 1090 1100
VECIAVLDVL LCLANYSRGG DGPMCRPVIL LPEDTPPFLE LKGSRHPCIT
1110 1120 1130 1140 1150
KTFFGDDFIP NDILIGCEEE EQENGKAYCV LVTGPNMGGK STLMRQAGLL
1160 1170 1180 1190 1200
AVMAQMGCYV PAEVCRLTPI DRVFTRLGAS DRIMSGESTF FVELSETASI
1210 1220 1230 1240 1250
LMHATAHSLV LVDELGRGTA TFDGTAIANA VVKELAETIK CRTLFSTHYH
1260 1270 1280 1290 1300
SLVEDYSQNV AVRLGHMACM VENECEDPSQ ETITFLYKFI KGACPKSYGF
1310 1320 1330 1340 1350
NAARLANLPE EVIQKGHRKA REFEKMNQSL RLFREVCLAS ERSTVDAEAV
1360
HKLLTLIKEL
Length:1,360
Mass (Da):152,786
Last modified:June 21, 2005 - v2
Checksum:i4A4AA9F8ECB8FFE9
GO
Isoform GTBP-alt (identifier: P52701-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1058-1068: DVLLCLANYSR → GKTLNKLVLRL
     1069-1360: Missing.

Show »
Length:1,068
Mass (Da):120,563
Checksum:iE1E62571A314B51E
GO
Isoform 3 (identifier: P52701-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     80-209: Missing.

Note: No experimental confirmation available.
Show »
Length:1,230
Mass (Da):137,957
Checksum:iBDA2B64A2EA0D51F
GO
Isoform 4 (identifier: P52701-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-302: Missing.

Note: No experimental confirmation available.
Show »
Length:1,058
Mass (Da):119,796
Checksum:i3D50E59BEED4B837
GO

Computationally mapped potential isoform sequencesi

There are 8 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A087WYT6A0A087WYT6_HUMAN
DNA mismatch repair protein Msh6
MSH6
327Annotation score:
A0A087WWJ1A0A087WWJ1_HUMAN
DNA mismatch repair protein Msh6
MSH6
1,067Annotation score:
C9J7Y7C9J7Y7_HUMAN
DNA mismatch repair protein Msh6
MSH6
151Annotation score:
F8WAX8F8WAX8_HUMAN
DNA mismatch repair protein Msh6
MSH6
160Annotation score:
U3KQ72U3KQ72_HUMAN
DNA mismatch repair protein Msh6
MSH6
51Annotation score:
C9JH55C9JH55_HUMAN
DNA mismatch repair protein Msh6
MSH6
101Annotation score:
C9J8Y8C9J8Y8_HUMAN
DNA mismatch repair protein Msh6
MSH6
115Annotation score:
F8W7G9F8W7G9_HUMAN
DNA mismatch repair protein Msh6
MSH6
104Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti36 – 57AAPGA…AGPGP → GCPRGLSFPRRGCGLERGWA WA in BAA23674 (PubMed:9455487).CuratedAdd BLAST22
Sequence conflicti36 – 57AAPGA…AGPGP → GCPRGLSFPRRGCGLERGWA WA in BAA23675 (PubMed:9455487).CuratedAdd BLAST22
Sequence conflicti868M → V in BAG65496 (PubMed:14702039).Curated1
Sequence conflicti1358 – 1360KEL → D in AAL87401 (Ref. 4) Curated3

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03803213K → T1 PublicationCorresponds to variant dbSNP:rs41294988EnsemblClinVar.1
Natural variantiVAR_04394320A → V in HNPCC5, CRC and ENDMC; unknown pathological significance; normal mismatch repair activity. 2 PublicationsCorresponds to variant dbSNP:rs63750664EnsemblClinVar.1
Natural variantiVAR_06729425A → S in HNPCC5; unknown pathological significance; normal mismatch repair activity. 1 PublicationCorresponds to variant dbSNP:rs267608026EnsemblClinVar.1
Natural variantiVAR_03803325A → V. Corresponds to variant dbSNP:rs35462442EnsemblClinVar.1
Natural variantiVAR_00449039G → ECombined sources5 PublicationsCorresponds to variant dbSNP:rs1042821EnsemblClinVar.1
Natural variantiVAR_04394454G → A in CRC; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63751098EnsemblClinVar.1
Natural variantiVAR_03803465S → L1 PublicationCorresponds to variant dbSNP:rs41294984EnsemblClinVar.1
Natural variantiVAR_04394599K → N in CRC; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63751258EnsemblClinVar.1
Natural variantiVAR_043946128R → L in HNPCC5; unknown pathological significance; no impairment of heterodimerization with MSH2; normal mismatch repair activity. 2 PublicationsCorresponds to variant dbSNP:rs63750143EnsemblClinVar.1
Natural variantiVAR_012955144S → I in HNPCC5 and CRC; unknown pathological significance; normal mismatch repair activity. 4 PublicationsCorresponds to variant dbSNP:rs3211299EnsemblClinVar.1
Natural variantiVAR_012956220E → D1 PublicationCorresponds to variant dbSNP:rs1800938EnsemblClinVar.1
Natural variantiVAR_042274221E → D1 PublicationCorresponds to variant dbSNP:rs41557217EnsemblClinVar.1
Natural variantiVAR_012957285S → I in CRC; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63750878EnsemblClinVar.1
Natural variantiVAR_043947295K → R in multiple colorectal adenoma. Corresponds to variant dbSNP:rs267608051EnsemblClinVar.1
Natural variantiVAR_067295326A → V in HNPCC5; unknown pathological significance; normal mismatch repair activity. 1 PublicationCorresponds to variant dbSNP:rs587779323EnsemblClinVar.1
Natural variantiVAR_043948340F → S in CRC, breast cancer and leukemia; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs61753793EnsemblClinVar.1
Natural variantiVAR_012958396L → V in HNPCC5; unknown pathological significance; normal mismatch repair activity. 3 PublicationsCorresponds to variant dbSNP:rs2020908EnsemblClinVar.1
Natural variantiVAR_068710435L → P Decreased mismatch repair activity. 1 PublicationCorresponds to variant dbSNP:rs63751405EnsemblClinVar.1
Natural variantiVAR_043949449L → P in CRC and ENDMC; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63750741EnsemblClinVar.1
Natural variantiVAR_038035468R → H1 PublicationCorresponds to variant dbSNP:rs41295268EnsemblClinVar.1
Natural variantiVAR_042275492M → V in HNPCC5; unknown pathological significance; normal mismatch repair activity. 3 PublicationsCorresponds to variant dbSNP:rs61754783EnsemblClinVar.1
Natural variantiVAR_038036503S → C in HNPCC5; unknown pathological significance; normal mismatch repair activity. 2 PublicationsCorresponds to variant dbSNP:rs63750897EnsemblClinVar.1
Natural variantiVAR_043950509V → A1 PublicationCorresponds to variant dbSNP:rs63751005EnsemblClinVar.1
Natural variantiVAR_043951522Q → R in CRC; unknown pathological significance; normal mismatch repair activity. 2 PublicationsCorresponds to variant dbSNP:rs63751009EnsemblClinVar.1
Natural variantiVAR_038037538Y → S. Corresponds to variant dbSNP:rs728619Ensembl.1
Natural variantiVAR_012959566G → R in CRC and HNPCC5; decreased mismatch repair activity; loss of protein expression. 2 PublicationsCorresponds to variant dbSNP:rs63749973EnsemblClinVar.1
Natural variantiVAR_038038580S → L1 PublicationCorresponds to variant dbSNP:rs41295270EnsemblClinVar.1
Natural variantiVAR_068711585L → P Decreased mismatch repair activity. 1 PublicationCorresponds to variant dbSNP:rs587779220EnsemblClinVar.1
Natural variantiVAR_067296610K → N in HNPCC5; unknown pathological significance; normal mismatch repair activity. 1 PublicationCorresponds to variant dbSNP:rs201735525EnsemblClinVar.1
Natural variantiVAR_043952619E → D in CRC; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63751121EnsemblClinVar.1
Natural variantiVAR_029244623P → A1 PublicationCorresponds to variant dbSNP:rs3136334EnsemblClinVar.1
Natural variantiVAR_043953623P → L in HNPCC5; unknown pathological significance; no impairment of heterodimerization with MSH2; normal mismatch repair activity. 2 PublicationsCorresponds to variant dbSNP:rs63750462EnsemblClinVar.1
Natural variantiVAR_068712677S → T Normal mismatch repair activity. 1 PublicationCorresponds to variant dbSNP:rs587779224EnsemblClinVar.1
Natural variantiVAR_043954685G → A in CRC; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63750358EnsemblClinVar.1
Natural variantiVAR_012960698Q → E in HNPCC; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63750832EnsemblClinVar.1
Natural variantiVAR_043955725I → M in CRC; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63750304EnsemblClinVar.1
Natural variantiVAR_043956728K → T in HNPCC5; unknown pathological significance; no impairment of heterodimerization with MSH2; normal mismatch repair activity. 2 PublicationsCorresponds to variant dbSNP:rs35552856EnsemblClinVar.1
Natural variantiVAR_043957772R → Q in CRC; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63750725EnsemblClinVar.1
Natural variantiVAR_043958772R → W in HNPCC5. 1 PublicationCorresponds to variant dbSNP:rs63750138EnsemblClinVar.1
Natural variantiVAR_043959787A → V in CRC; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63750637EnsemblClinVar.1
Natural variantiVAR_043960800V → A in CRC; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs63750895Ensembl.1
Natural variantiVAR_012961800V → L1 PublicationCorresponds to variant dbSNP:rs61748083EnsemblClinVar.1
Natural variantiVAR_012962803D → G in CRC; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63751450EnsemblClinVar.1
Natural variantiVAR_012963850Y → C in HNPCC5 and CRC; unknown pathological significance; normal mismatch repair activity. 3 PublicationsCorresponds to variant dbSNP:rs63750389EnsemblClinVar.1
Natural variantiVAR_043961854K → M in CRC; unknown pathological significance. 2 PublicationsCorresponds to variant dbSNP:rs34374438EnsemblClinVar.1
Natural variantiVAR_012964878V → A in HNPCC5, CRC and ENDMC; unknown pathological significance; normal mismatch repair activity. 9 PublicationsCorresponds to variant dbSNP:rs2020912EnsemblClinVar.1
Natural variantiVAR_076356881G → KS in HNPCC5; unknown pathological significance; normal mismatch repair activity. 1 Publication1
Natural variantiVAR_014902886I → V1 PublicationCorresponds to variant dbSNP:rs2020914EnsemblClinVar.1
Natural variantiVAR_043962901R → H in CRC and ENDMC; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63749889EnsemblClinVar.1
Natural variantiVAR_012965976R → H in CRC; sporadic; unknown pathological significance; normal mismatch repair activity. 2 PublicationsCorresponds to variant dbSNP:rs63751113EnsemblClinVar.1
Natural variantiVAR_0439631021A → D in CRC; unknown pathological significance; normal mismatch repair activity. 2 PublicationsCorresponds to variant dbSNP:rs63750287EnsemblClinVar.1
Natural variantiVAR_0672971026D → Y in HNPCC5; unknown pathological significance; normal mismatch repair activity. 1 PublicationCorresponds to variant dbSNP:rs267608054EnsemblClinVar.1
Natural variantiVAR_0439641031D → V in CRC; unknown pathological significance; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs63750804Ensembl.1
Natural variantiVAR_0439651076R → C in CRC; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63750617EnsemblClinVar.1
Natural variantiVAR_0763571087P → R1 PublicationCorresponds to variant dbSNP:rs63750753EnsemblClinVar.1
Natural variantiVAR_0672981087P → S in HNPCC5; unknown pathological significance; normal mismatch repair activity. 1 PublicationCorresponds to variant dbSNP:rs63750998EnsemblClinVar.1
Natural variantiVAR_0129661087P → T in CRC and HNPCC5; unknown pathological significance. 2 PublicationsCorresponds to variant dbSNP:rs63750998EnsemblClinVar.1
Natural variantiVAR_0439661095R → H in CRC and HNPCC5; unknown pathological significance; normal mismatch repair activity. 3 PublicationsCorresponds to variant dbSNP:rs63750253EnsemblClinVar.1
Natural variantiVAR_0439671100T → M in CRC; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63750442EnsemblClinVar.1
Natural variantiVAR_0439681158C → R in CRC; unknown pathological significance; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs63750157Ensembl.1
Natural variantiVAR_0439691163E → V in HNPCC5. 1 PublicationCorresponds to variant dbSNP:rs63750252EnsemblClinVar.1
Natural variantiVAR_0439701193E → K in HNPCC5; decreased mismatch repair activity; displays marked impairment of heterodimerization with MSH2. 2 PublicationsCorresponds to variant dbSNP:rs63751328EnsemblClinVar.1
Natural variantiVAR_0044911213D → V1 Publication1
Natural variantiVAR_0439711219T → I in CRC; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63750949EnsemblClinVar.1
Natural variantiVAR_0672991225T → M in HNPCC5; unknown pathological significance; normal mismatch repair activity. 1 PublicationCorresponds to variant dbSNP:rs63750370EnsemblClinVar.1
Natural variantiVAR_0380391232V → L1 PublicationCorresponds to variant dbSNP:rs41295276EnsemblClinVar.1
Natural variantiVAR_0380401234E → Q. Corresponds to variant dbSNP:rs35717727Ensembl.1
Natural variantiVAR_0439721248H → D in CRC; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63750882EnsemblClinVar.1
Natural variantiVAR_0044921260V → I1 PublicationCorresponds to variant dbSNP:rs63750673Ensembl.1
Natural variantiVAR_0439731284T → M in CRC; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63750836EnsemblClinVar.1
Natural variantiVAR_0380411321R → G1 PublicationCorresponds to variant dbSNP:rs41295278EnsemblClinVar.1
Natural variantiVAR_0439741354L → Q in CRC and HNPCC5; unknown pathological significance; normal mismatch repair activity. 3 PublicationsCorresponds to variant dbSNP:rs267608140EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0550201 – 302Missing in isoform 4. 1 PublicationAdd BLAST302
Alternative sequenceiVSP_05441980 – 209Missing in isoform 3. 1 PublicationAdd BLAST130
Alternative sequenceiVSP_0032911058 – 1068DVLLCLANYSR → GKTLNKLVLRL in isoform GTBP-alt. CuratedAdd BLAST11
Alternative sequenceiVSP_0032921069 – 1360Missing in isoform GTBP-alt. CuratedAdd BLAST292

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U73737
, U73732, U73733, U73734, U73736 Genomic DNA Translation: AAB47425.1
D89645 Genomic DNA Translation: BAA23674.1
D89646 mRNA Translation: BAA23675.1
AK293921 mRNA Translation: BAG57302.1
AK304735 mRNA Translation: BAG65496.1
AY082894 Genomic DNA Translation: AAL87401.1
AC006509 Genomic DNA No translation available.
BC004246 mRNA Translation: AAH04246.1
U54777 mRNA Translation: AAB39212.2
U28946 mRNA Translation: AAC50461.1
CCDSiCCDS1836.1 [P52701-1]
CCDS62906.1 [P52701-3]
CCDS62907.1 [P52701-4]
PIRiJC5839
RefSeqiNP_000170.1, NM_000179.2 [P52701-1]
NP_001268421.1, NM_001281492.1 [P52701-3]
NP_001268422.1, NM_001281493.1 [P52701-4]
NP_001268423.1, NM_001281494.1 [P52701-4]
UniGeneiHs.445052

Genome annotation databases

EnsembliENST00000234420; ENSP00000234420; ENSG00000116062 [P52701-1]
ENST00000538136; ENSP00000438580; ENSG00000116062 [P52701-4]
ENST00000540021; ENSP00000446475; ENSG00000116062 [P52701-3]
ENST00000614496; ENSP00000477844; ENSG00000116062 [P52701-4]
GeneIDi2956
KEGGihsa:2956
UCSCiuc002rwd.5 human [P52701-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi