Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

DNA mismatch repair protein Msh6

Gene

MSH6

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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: UniProtKB-KW
  • chromatin binding Source: Ensembl
  • damaged DNA binding Source: Ensembl
  • guanine/thymine mispair binding Source: Ensembl
  • methylated histone binding Source: UniProtKB
  • mismatched DNA binding Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

DNA damage, DNA repair, Host-virus interaction

Keywords - Ligandi

ATP-binding, DNA-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000116062-MONOMER.
ReactomeiR-HSA-5358565. Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha).
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

HGNCiHGNC:7329. MSH6.

Subcellular locationi

  • Nucleus 1 Publication
  • Chromosome 1 Publication

  • Note: Associates with H3K36me3 via its PWWP domain.

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Chromosome, Nucleus

Pathology & Biotechi

Involvement in diseasei

Hereditary non-polyposis colorectal cancer 5 (HNPCC5)8 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 rs63750664dbSNPEnsembl.1
Natural variantiVAR_06729425A → S in HNPCC5; unknown pathological significance; normal mismatch repair activity. 1 PublicationCorresponds to variant rs267608026dbSNPEnsembl.1
Natural variantiVAR_043946128R → L in HNPCC5; unknown pathological significance; no impairment of heterodimerization with MSH2; normal mismatch repair activity. 2 PublicationsCorresponds to variant rs63750143dbSNPEnsembl.1
Natural variantiVAR_012955144S → I in HNPCC5 and CRC; unknown pathological significance; normal mismatch repair activity. 4 PublicationsCorresponds to variant rs3211299dbSNPEnsembl.1
Natural variantiVAR_067295326A → V in HNPCC5; unknown pathological significance; normal mismatch repair activity. 1 PublicationCorresponds to variant rs587779323dbSNPEnsembl.1
Natural variantiVAR_012958396L → V in HNPCC5; unknown pathological significance; normal mismatch repair activity. 3 PublicationsCorresponds to variant rs2020908dbSNPEnsembl.1
Natural variantiVAR_042275492M → V in HNPCC5; unknown pathological significance; normal mismatch repair activity. 3 PublicationsCorresponds to variant rs61754783dbSNPEnsembl.1
Natural variantiVAR_038036503S → C in HNPCC5; unknown pathological significance; normal mismatch repair activity. 2 PublicationsCorresponds to variant rs63750897dbSNPEnsembl.1
Natural variantiVAR_012959566G → R in CRC and HNPCC5; decreased mismatch repair activity; loss of protein expression. 2 PublicationsCorresponds to variant rs63749973dbSNPEnsembl.1
Natural variantiVAR_067296610K → N in HNPCC5; unknown pathological significance; normal mismatch repair activity. 1 PublicationCorresponds to variant rs201735525dbSNPEnsembl.1
Natural variantiVAR_043953623P → L in HNPCC5; unknown pathological significance; no impairment of heterodimerization with MSH2; normal mismatch repair activity. 2 PublicationsCorresponds to variant rs63750462dbSNPEnsembl.1
Natural variantiVAR_043956728K → T in HNPCC5; unknown pathological significance; no impairment of heterodimerization with MSH2; normal mismatch repair activity. 2 PublicationsCorresponds to variant rs35552856dbSNPEnsembl.1
Natural variantiVAR_043958772R → W in HNPCC5. 1 PublicationCorresponds to variant rs63750138dbSNPEnsembl.1
Natural variantiVAR_012963850Y → C in HNPCC5 and CRC; unknown pathological significance; normal mismatch repair activity. 3 PublicationsCorresponds to variant rs63750389dbSNPEnsembl.1
Natural variantiVAR_012964878V → A in HNPCC5, CRC and ENDMC; unknown pathological significance; normal mismatch repair activity. 9 PublicationsCorresponds to variant rs2020912dbSNPEnsembl.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 rs267608054dbSNPEnsembl.1
Natural variantiVAR_0672981087P → S in HNPCC5; unknown pathological significance; normal mismatch repair activity. 1 PublicationCorresponds to variant rs63750998dbSNPEnsembl.1
Natural variantiVAR_0129661087P → T in CRC and HNPCC5; unknown pathological significance. 2 PublicationsCorresponds to variant rs63750998dbSNPEnsembl.1
Natural variantiVAR_0439661095R → H in CRC and HNPCC5; unknown pathological significance; normal mismatch repair activity. 3 PublicationsCorresponds to variant rs63750253dbSNPEnsembl.1
Natural variantiVAR_0439691163E → V in HNPCC5. 1 PublicationCorresponds to variant rs63750252dbSNPEnsembl.1
Natural variantiVAR_0439701193E → K in HNPCC5; decreased mismatch repair activity; displays marked impairment of heterodimerization with MSH2. 2 PublicationsCorresponds to variant rs63751328dbSNPEnsembl.1
Natural variantiVAR_0672991225T → M in HNPCC5; unknown pathological significance; normal mismatch repair activity. 1 PublicationCorresponds to variant rs63750370dbSNPEnsembl.1
Natural variantiVAR_0439741354L → Q in CRC and HNPCC5; unknown pathological significance; normal mismatch repair activity. 3 PublicationsCorresponds to variant rs267608140dbSNPEnsembl.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
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 rs63750664dbSNPEnsembl.1
Natural variantiVAR_043949449L → P in CRC and ENDMC; unknown pathological significance. 1 PublicationCorresponds to variant rs63750741dbSNPEnsembl.1
Natural variantiVAR_012964878V → A in HNPCC5, CRC and ENDMC; unknown pathological significance; normal mismatch repair activity. 9 PublicationsCorresponds to variant rs2020912dbSNPEnsembl.1
Natural variantiVAR_043962901R → H in CRC and ENDMC; unknown pathological significance. 1 PublicationCorresponds to variant rs63749889dbSNPEnsembl.1
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)11 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_04394320A → V in HNPCC5, CRC and ENDMC; unknown pathological significance; normal mismatch repair activity. 2 PublicationsCorresponds to variant rs63750664dbSNPEnsembl.1
Natural variantiVAR_04394454G → A in CRC; unknown pathological significance. 1 PublicationCorresponds to variant rs63751098dbSNPEnsembl.1
Natural variantiVAR_04394599K → N in CRC; unknown pathological significance. 1 PublicationCorresponds to variant rs63751258dbSNPEnsembl.1
Natural variantiVAR_012955144S → I in HNPCC5 and CRC; unknown pathological significance; normal mismatch repair activity. 4 PublicationsCorresponds to variant rs3211299dbSNPEnsembl.1
Natural variantiVAR_012957285S → I in CRC; unknown pathological significance. 1 PublicationCorresponds to variant rs63750878dbSNPEnsembl.1
Natural variantiVAR_043948340F → S in CRC, breast cancer and leukemia; unknown pathological significance. 1 PublicationCorresponds to variant rs61753793dbSNPEnsembl.1
Natural variantiVAR_043949449L → P in CRC and ENDMC; unknown pathological significance. 1 PublicationCorresponds to variant rs63750741dbSNPEnsembl.1
Natural variantiVAR_043951522Q → R in CRC; unknown pathological significance; normal mismatch repair activity. 2 PublicationsCorresponds to variant rs63751009dbSNPEnsembl.1
Natural variantiVAR_012959566G → R in CRC and HNPCC5; decreased mismatch repair activity; loss of protein expression. 2 PublicationsCorresponds to variant rs63749973dbSNPEnsembl.1
Natural variantiVAR_043952619E → D in CRC; unknown pathological significance. 1 PublicationCorresponds to variant rs63751121dbSNPEnsembl.1
Natural variantiVAR_043954685G → A in CRC; unknown pathological significance. 1 PublicationCorresponds to variant rs63750358dbSNPEnsembl.1
Natural variantiVAR_043955725I → M in CRC; unknown pathological significance. 1 PublicationCorresponds to variant rs63750304dbSNPEnsembl.1
Natural variantiVAR_043957772R → Q in CRC; unknown pathological significance. 1 PublicationCorresponds to variant rs63750725dbSNPEnsembl.1
Natural variantiVAR_043959787A → V in CRC; unknown pathological significance. 1 PublicationCorresponds to variant rs63750637dbSNPEnsembl.1
Natural variantiVAR_043960800V → A in CRC; somatic mutation. 1 PublicationCorresponds to variant rs63750895dbSNPEnsembl.1
Natural variantiVAR_012962803D → G in CRC; unknown pathological significance. 1 PublicationCorresponds to variant rs63751450dbSNPEnsembl.1
Natural variantiVAR_012963850Y → C in HNPCC5 and CRC; unknown pathological significance; normal mismatch repair activity. 3 PublicationsCorresponds to variant rs63750389dbSNPEnsembl.1
Natural variantiVAR_043961854K → M in CRC; unknown pathological significance. 2 PublicationsCorresponds to variant rs34374438dbSNPEnsembl.1
Natural variantiVAR_012964878V → A in HNPCC5, CRC and ENDMC; unknown pathological significance; normal mismatch repair activity. 9 PublicationsCorresponds to variant rs2020912dbSNPEnsembl.1
Natural variantiVAR_043962901R → H in CRC and ENDMC; unknown pathological significance. 1 PublicationCorresponds to variant rs63749889dbSNPEnsembl.1
Natural variantiVAR_012965976R → H in CRC; sporadic; unknown pathological significance; normal mismatch repair activity. 2 PublicationsCorresponds to variant rs63751113dbSNPEnsembl.1
Natural variantiVAR_0439631021A → D in CRC; unknown pathological significance; normal mismatch repair activity. 2 PublicationsCorresponds to variant rs63750287dbSNPEnsembl.1
Natural variantiVAR_0439641031D → V in CRC; unknown pathological significance; somatic mutation. 1 PublicationCorresponds to variant rs63750804dbSNPEnsembl.1
Natural variantiVAR_0439651076R → C in CRC; unknown pathological significance. 1 PublicationCorresponds to variant rs63750617dbSNPEnsembl.1
Natural variantiVAR_0129661087P → T in CRC and HNPCC5; unknown pathological significance. 2 PublicationsCorresponds to variant rs63750998dbSNPEnsembl.1
Natural variantiVAR_0439661095R → H in CRC and HNPCC5; unknown pathological significance; normal mismatch repair activity. 3 PublicationsCorresponds to variant rs63750253dbSNPEnsembl.1
Natural variantiVAR_0439671100T → M in CRC; unknown pathological significance. 1 PublicationCorresponds to variant rs63750442dbSNPEnsembl.1
Natural variantiVAR_0439681158C → R in CRC; unknown pathological significance; somatic mutation. 1 PublicationCorresponds to variant rs63750157dbSNPEnsembl.1
Natural variantiVAR_0439711219T → I in CRC; unknown pathological significance. 1 PublicationCorresponds to variant rs63750949dbSNPEnsembl.1
Natural variantiVAR_0439721248H → D in CRC; unknown pathological significance. 1 PublicationCorresponds to variant rs63750882dbSNPEnsembl.1
Natural variantiVAR_0439731284T → M in CRC; unknown pathological significance. 1 PublicationCorresponds to variant rs63750836dbSNPEnsembl.1
Natural variantiVAR_0439741354L → Q in CRC and HNPCC5; unknown pathological significance; normal mismatch repair activity. 3 PublicationsCorresponds to variant rs267608140dbSNPEnsembl.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.
MalaCardsiMSH6.
MIMi114500. phenotype.
276300. phenotype.
608089. phenotype.
614350. phenotype.
OpenTargetsiENSG00000116062.
Orphaneti252202. Constitutional mismatch repair deficiency syndrome.
144. Hereditary nonpolyposis colon cancer.
587. Muir-Torre syndrome.
99817. Non-polyposis Turcot 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.

PTM databases

iPTMnetiP52701.
PhosphoSitePlusiP52701.

Miscellaneous databases

PMAP-CutDBP52701.

Expressioni

Gene expression databases

BgeeiENSG00000116062.
CleanExiHS_MSH6.
ExpressionAtlasiP52701. baseline and differential.
GenevisibleiP52701. HS.

Organism-specific databases

HPAiCAB009091.
HPA028376.
HPA028446.

Interactioni

Subunit structurei

Heterodimer consisting of MSH2-MSH6 (MutS alpha). Forms a ternary complex with MutL alpha (MLH1-PMS1). Interacts with EXO1. 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 ATR. Interacts with herpes simplex virus 1 protein UL12 (PubMed:21957315).1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
MSH2P432466EBI-395529,EBI-355888

GO - Molecular functioni

  • methylated histone binding Source: UniProtKB

Protein-protein interaction databases

BioGridi109211. 80 interactors.
DIPiDIP-32972N.
IntActiP52701. 36 interactors.
MINTiMINT-131993.
STRINGi9606.ENSP00000234420.

Structurei

Secondary structure

11360
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi74 – 79Combined sources6
Beta strandi94 – 98Combined sources5
Beta strandi106 – 109Combined sources4
Beta strandi120 – 125Combined sources6
Beta strandi127 – 133Combined sources7
Beta strandi135 – 137Combined sources3
Beta strandi139 – 143Combined sources5
Helixi145 – 147Combined sources3
Beta strandi148 – 151Combined sources4
Turni157 – 159Combined sources3
Helixi170 – 183Combined sources14
Helixi187 – 191Combined sources5
Turni192 – 195Combined sources4
Beta strandi197 – 199Combined sources3
Helixi366 – 369Combined sources4
Helixi371 – 373Combined sources3
Turni375 – 377Combined sources3
Helixi400 – 403Combined sources4
Helixi408 – 419Combined sources12
Beta strandi423 – 429Combined sources7
Beta strandi432 – 436Combined sources5
Helixi437 – 447Combined sources11
Beta strandi453 – 456Combined sources4
Beta strandi458 – 462Combined sources5
Helixi463 – 465Combined sources3
Helixi466 – 475Combined sources10
Beta strandi480 – 485Combined sources6
Helixi489 – 497Combined sources9
Helixi505 – 507Combined sources3
Beta strandi511 – 517Combined sources7
Helixi519 – 521Combined sources3
Beta strandi526 – 528Combined sources3
Beta strandi538 – 546Combined sources9
Beta strandi554 – 561Combined sources8
Turni563 – 565Combined sources3
Beta strandi568 – 575Combined sources8
Helixi580 – 588Combined sources9
Beta strandi591 – 597Combined sources7
Turni598 – 600Combined sources3
Helixi603 – 609Combined sources7
Turni610 – 615Combined sources6
Beta strandi616 – 621Combined sources6
Turni624 – 626Combined sources3
Helixi630 – 639Combined sources10
Turni640 – 643Combined sources4
Beta strandi644 – 647Combined sources4
Helixi657 – 661Combined sources5
Beta strandi667 – 669Combined sources3
Beta strandi671 – 673Combined sources3
Helixi675 – 677Combined sources3
Helixi678 – 693Combined sources16
Helixi697 – 701Combined sources5
Beta strandi706 – 708Combined sources3
Helixi712 – 715Combined sources4
Helixi737 – 742Combined sources6
Beta strandi746 – 748Combined sources3
Beta strandi750 – 753Combined sources4
Helixi758 – 762Combined sources5
Helixi768 – 779Combined sources12
Helixi785 – 799Combined sources15
Helixi802 – 812Combined sources11
Helixi818 – 829Combined sources12
Helixi831 – 836Combined sources6
Helixi838 – 841Combined sources4
Helixi847 – 879Combined sources33
Helixi885 – 890Combined sources6
Turni894 – 896Combined sources3
Beta strandi897 – 900Combined sources4
Helixi906 – 913Combined sources8
Helixi918 – 923Combined sources6
Helixi936 – 955Combined sources20
Helixi959 – 961Combined sources3
Beta strandi968 – 970Combined sources3
Helixi973 – 975Combined sources3
Beta strandi978 – 981Combined sources4
Turni983 – 986Combined sources4
Beta strandi995 – 999Combined sources5
Beta strandi1002 – 1005Combined sources4
Turni1008 – 1010Combined sources3
Helixi1011 – 1041Combined sources31
Helixi1044 – 1066Combined sources23
Beta strandi1070 – 1072Combined sources3
Turni1082 – 1084Combined sources3
Beta strandi1089 – 1094Combined sources6
Beta strandi1111 – 1116Combined sources6
Beta strandi1120 – 1122Combined sources3
Beta strandi1129 – 1133Combined sources5
Beta strandi1136 – 1138Combined sources3
Helixi1140 – 1154Combined sources15
Turni1155 – 1157Combined sources3
Beta strandi1160 – 1167Combined sources8
Beta strandi1171 – 1176Combined sources6
Helixi1189 – 1203Combined sources15
Beta strandi1209 – 1213Combined sources5
Turni1215 – 1218Combined sources4
Helixi1221 – 1237Combined sources17
Beta strandi1242 – 1246Combined sources5
Helixi1250 – 1255Combined sources6
Turni1256 – 1258Combined sources3
Beta strandi1260 – 1269Combined sources10
Beta strandi1285 – 1292Combined sources8
Helixi1298 – 1305Combined sources8
Helixi1310 – 1322Combined sources13
Turni1323 – 1326Combined sources4
Turni1330 – 1332Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2GFUNMR-A68-201[»]
2O8BX-ray2.75B341-1360[»]
2O8CX-ray3.37B341-1360[»]
2O8DX-ray3.00B341-1360[»]
2O8EX-ray3.30B341-1360[»]
2O8FX-ray3.25B341-1360[»]
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
Contains 1 PWWP domain.PROSITE-ProRule annotation

Phylogenomic databases

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

Family and domain databases

Gene3Di3.40.1170.10. 1 hit.
3.40.50.300. 1 hit.
InterProiIPR007695. DNA_mismatch_repair_MutS-lik_N.
IPR000432. DNA_mismatch_repair_MutS_C.
IPR007861. DNA_mismatch_repair_MutS_clamp.
IPR007696. DNA_mismatch_repair_MutS_core.
IPR016151. DNA_mismatch_repair_MutS_N.
IPR007860. DNA_mmatch_repair_MutS_con_dom.
IPR027417. P-loop_NTPase.
IPR000313. PWWP_dom.
[Graphical view]
PfamiPF01624. 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.
[Graphical view]
SMARTiSM00534. MUTSac. 1 hit.
SM00533. MUTSd. 1 hit.
SM00293. PWWP. 1 hit.
[Graphical view]
SUPFAMiSSF48334. SSF48334. 1 hit.
SSF52540. SSF52540. 1 hit.
SSF55271. SSF55271. 1 hit.
PROSITEiPS00486. DNA_MISMATCH_REPAIR_2. 1 hit.
PS50812. PWWP. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

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

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

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 → T.1 PublicationCorresponds to variant rs41294988dbSNPEnsembl.1
Natural variantiVAR_04394320A → V in HNPCC5, CRC and ENDMC; unknown pathological significance; normal mismatch repair activity. 2 PublicationsCorresponds to variant rs63750664dbSNPEnsembl.1
Natural variantiVAR_06729425A → S in HNPCC5; unknown pathological significance; normal mismatch repair activity. 1 PublicationCorresponds to variant rs267608026dbSNPEnsembl.1
Natural variantiVAR_03803325A → V.Corresponds to variant rs35462442dbSNPEnsembl.1
Natural variantiVAR_00449039G → E.Combined sources5 PublicationsCorresponds to variant rs1042821dbSNPEnsembl.1
Natural variantiVAR_04394454G → A in CRC; unknown pathological significance. 1 PublicationCorresponds to variant rs63751098dbSNPEnsembl.1
Natural variantiVAR_03803465S → L.1 PublicationCorresponds to variant rs41294984dbSNPEnsembl.1
Natural variantiVAR_04394599K → N in CRC; unknown pathological significance. 1 PublicationCorresponds to variant rs63751258dbSNPEnsembl.1
Natural variantiVAR_043946128R → L in HNPCC5; unknown pathological significance; no impairment of heterodimerization with MSH2; normal mismatch repair activity. 2 PublicationsCorresponds to variant rs63750143dbSNPEnsembl.1
Natural variantiVAR_012955144S → I in HNPCC5 and CRC; unknown pathological significance; normal mismatch repair activity. 4 PublicationsCorresponds to variant rs3211299dbSNPEnsembl.1
Natural variantiVAR_012956220E → D.1 PublicationCorresponds to variant rs1800938dbSNPEnsembl.1
Natural variantiVAR_042274221E → D.1 PublicationCorresponds to variant rs41557217dbSNPEnsembl.1
Natural variantiVAR_012957285S → I in CRC; unknown pathological significance. 1 PublicationCorresponds to variant rs63750878dbSNPEnsembl.1
Natural variantiVAR_043947295K → R in multiple colorectal adenoma. Corresponds to variant rs267608051dbSNPEnsembl.1
Natural variantiVAR_067295326A → V in HNPCC5; unknown pathological significance; normal mismatch repair activity. 1 PublicationCorresponds to variant rs587779323dbSNPEnsembl.1
Natural variantiVAR_043948340F → S in CRC, breast cancer and leukemia; unknown pathological significance. 1 PublicationCorresponds to variant rs61753793dbSNPEnsembl.1
Natural variantiVAR_012958396L → V in HNPCC5; unknown pathological significance; normal mismatch repair activity. 3 PublicationsCorresponds to variant rs2020908dbSNPEnsembl.1
Natural variantiVAR_068710435L → P Decreased mismatch repair activity. 1 PublicationCorresponds to variant rs63751405dbSNPEnsembl.1
Natural variantiVAR_043949449L → P in CRC and ENDMC; unknown pathological significance. 1 PublicationCorresponds to variant rs63750741dbSNPEnsembl.1
Natural variantiVAR_038035468R → H.1 PublicationCorresponds to variant rs41295268dbSNPEnsembl.1
Natural variantiVAR_042275492M → V in HNPCC5; unknown pathological significance; normal mismatch repair activity. 3 PublicationsCorresponds to variant rs61754783dbSNPEnsembl.1
Natural variantiVAR_038036503S → C in HNPCC5; unknown pathological significance; normal mismatch repair activity. 2 PublicationsCorresponds to variant rs63750897dbSNPEnsembl.1
Natural variantiVAR_043950509V → A.1 PublicationCorresponds to variant rs63751005dbSNPEnsembl.1
Natural variantiVAR_043951522Q → R in CRC; unknown pathological significance; normal mismatch repair activity. 2 PublicationsCorresponds to variant rs63751009dbSNPEnsembl.1
Natural variantiVAR_038037538Y → S.Corresponds to variant rs728619dbSNPEnsembl.1
Natural variantiVAR_012959566G → R in CRC and HNPCC5; decreased mismatch repair activity; loss of protein expression. 2 PublicationsCorresponds to variant rs63749973dbSNPEnsembl.1
Natural variantiVAR_038038580S → L.1 PublicationCorresponds to variant rs41295270dbSNPEnsembl.1
Natural variantiVAR_068711585L → P Decreased mismatch repair activity. 1 PublicationCorresponds to variant rs587779220dbSNPEnsembl.1
Natural variantiVAR_067296610K → N in HNPCC5; unknown pathological significance; normal mismatch repair activity. 1 PublicationCorresponds to variant rs201735525dbSNPEnsembl.1
Natural variantiVAR_043952619E → D in CRC; unknown pathological significance. 1 PublicationCorresponds to variant rs63751121dbSNPEnsembl.1
Natural variantiVAR_029244623P → A.1 PublicationCorresponds to variant rs3136334dbSNPEnsembl.1
Natural variantiVAR_043953623P → L in HNPCC5; unknown pathological significance; no impairment of heterodimerization with MSH2; normal mismatch repair activity. 2 PublicationsCorresponds to variant rs63750462dbSNPEnsembl.1
Natural variantiVAR_068712677S → T Normal mismatch repair activity. 1 PublicationCorresponds to variant rs587779224dbSNPEnsembl.1
Natural variantiVAR_043954685G → A in CRC; unknown pathological significance. 1 PublicationCorresponds to variant rs63750358dbSNPEnsembl.1
Natural variantiVAR_012960698Q → E in HNPCC; unknown pathological significance. 1 PublicationCorresponds to variant rs63750832dbSNPEnsembl.1
Natural variantiVAR_043955725I → M in CRC; unknown pathological significance. 1 PublicationCorresponds to variant rs63750304dbSNPEnsembl.1
Natural variantiVAR_043956728K → T in HNPCC5; unknown pathological significance; no impairment of heterodimerization with MSH2; normal mismatch repair activity. 2 PublicationsCorresponds to variant rs35552856dbSNPEnsembl.1
Natural variantiVAR_043957772R → Q in CRC; unknown pathological significance. 1 PublicationCorresponds to variant rs63750725dbSNPEnsembl.1
Natural variantiVAR_043958772R → W in HNPCC5. 1 PublicationCorresponds to variant rs63750138dbSNPEnsembl.1
Natural variantiVAR_043959787A → V in CRC; unknown pathological significance. 1 PublicationCorresponds to variant rs63750637dbSNPEnsembl.1
Natural variantiVAR_043960800V → A in CRC; somatic mutation. 1 PublicationCorresponds to variant rs63750895dbSNPEnsembl.1
Natural variantiVAR_012961800V → L.1 PublicationCorresponds to variant rs61748083dbSNPEnsembl.1
Natural variantiVAR_012962803D → G in CRC; unknown pathological significance. 1 Publication