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UniProtKB - P54278 (PMS2_HUMAN)

Protein

Mismatch repair endonuclease PMS2

Gene

PMS2

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 MLH1 to form MutL alpha. DNA repair is initiated by MutS alpha (MSH2-MSH6) or MutS beta (MSH2-MSH3) 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.3 Publications

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionEndonuclease, Hydrolase, Nuclease
Biological processDNA damage, DNA repair

Enzyme and pathway databases

ReactomeiR-HSA-5358565 Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha)
R-HSA-5358606 Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta)
R-HSA-5545483 Defective Mismatch Repair Associated With MLH1
R-HSA-5632987 Defective Mismatch Repair Associated With PMS2
R-HSA-6796648 TP53 Regulates Transcription of DNA Repair Genes
SIGNORiP54278

Names & Taxonomyi

Protein namesi
Recommended name:
Mismatch repair endonuclease PMS2Curated (EC:3.1.-.-)
Alternative name(s):
DNA mismatch repair protein PMS2
PMS1 protein homolog 2
Gene namesi
Name:PMS2Imported
Synonyms:PMSL2Imported
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

EuPathDBiHostDB:ENSG00000122512.14
HGNCiHGNC:9122 PMS2
MIMi600259 gene
neXtProtiNX_P54278

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

Nucleus

Pathology & Biotechi

Involvement in diseasei

Hereditary non-polyposis colorectal cancer 4 (HNPCC4)10 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:614337
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07851846S → N in HNPCC4; strongly decreased DNA mismatch repair activity. 2 PublicationsCorresponds to variant dbSNP:rs121434629EnsemblClinVar.1
Natural variantiVAR_078523182A → T in HNPCC4; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs587779341EnsemblClinVar.1
Natural variantiVAR_078525207G → E in HNPCC4; unknown pathological significance; normal DNA mismatch repair activity. 2 PublicationsCorresponds to variant dbSNP:rs374704824EnsemblClinVar.1
Natural variantiVAR_012973622M → I in HNPCC4; unknown pathological significance; significantly reduced interaction with MLH1; normal DNA mismatch repair activity. 6 PublicationsCorresponds to variant dbSNP:rs1805324EnsemblClinVar.1
Natural variantiVAR_078534663E → A in HNPCC4; unknown pathological significance; normal DNA mismatch repair activity. 2 PublicationsCorresponds to variant dbSNP:rs587779332EnsemblClinVar.1
Natural variantiVAR_078535750G → D in HNPCC4; unknown pathological significance; decreased DNA mismatch repair activity. 2 PublicationsCorresponds to variant dbSNP:rs587779337EnsemblClinVar.1
Natural variantiVAR_078536797M → R in HNPCC4; unknown pathological significance; normal DNA mismatch repair activity. 2 PublicationsCorresponds to variant dbSNP:rs267608152EnsemblClinVar.1
Natural variantiVAR_078538843C → Y in HNPCC4; decreased DNA mismatch repair activity. 2 PublicationsCorresponds to variant dbSNP:rs267608174EnsemblClinVar.1
Mismatch repair cancer syndrome (MMRCS)5 Publications
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
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07852066I → T in MMRCS; unknown pathological significance; normal DNA mismatch repair activity. 1 PublicationCorresponds to variant dbSNP:rs769554577EnsemblClinVar.1
Natural variantiVAR_078521107R → W in MMRCS; decreased DNA mismatch repair activity. 1 PublicationCorresponds to variant dbSNP:rs188006077EnsemblClinVar.1
Natural variantiVAR_078522115C → G in MMRCS; decreased DNA mismatch repair activity. 1 Publication1
Natural variantiVAR_078527307N → K in MMRCS; unknown pathological significance; decreased DNA mismatch repair activity. 1 PublicationCorresponds to variant dbSNP:rs587779346EnsemblClinVar.1
Natural variantiVAR_078528437P → S in MMRCS; unknown pathological significance; normal DNA mismatch repair activity. 1 PublicationCorresponds to variant dbSNP:rs200726484EnsemblClinVar.1
Natural variantiVAR_078529488A → V in MMRCS; unknown pathological significance; normal DNA mismatch repair activity. 1 PublicationCorresponds to variant dbSNP:rs587779328EnsemblClinVar.1
Natural variantiVAR_078530504E → Q in MMRCS; unknown pathological significance; normal DNA mismatch repair activity. 1 PublicationCorresponds to variant dbSNP:rs368516768EnsemblClinVar.1
Natural variantiVAR_078537815S → L in MMRCS; decreased DNA mismatch repair activity. 1 PublicationCorresponds to variant dbSNP:rs587779338EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi41E → A: Decreased DNA mismatch repair activity. 1 Publication1
Mutagenesisi70D → N: No effect on protein abundance, no effect on subcellular localization and loss of DNA mismatch repair activity. 1 Publication1
Mutagenesisi519Y → C: No effect on DNA mismatch repair activity. 1 Publication1

Keywords - Diseasei

Disease mutation, Hereditary nonpolyposis colorectal cancer, Tumor suppressor

Organism-specific databases

DisGeNETi107984056
5395
GeneReviewsiPMS2
MalaCardsiPMS2
MIMi276300 phenotype
614337 phenotype
OpenTargetsiENSG00000122512
Orphaneti252202 Constitutional mismatch repair deficiency syndrome
144 Hereditary nonpolyposis colon cancer
99817 Non-polyposis Turcot syndrome
PharmGKBiPA33448

Chemistry databases

DrugBankiDB02930 Phosphothiophosphoric Acid-Adenylate Ester

Polymorphism and mutation databases

BioMutaiPMS2
DMDMi317373266

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001780051 – 862Mismatch repair endonuclease PMS2Add BLAST862

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei573PhosphothreonineCombined sources1
Modified residuei597PhosphothreonineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiP54278
MaxQBiP54278
PaxDbiP54278
PeptideAtlasiP54278
PRIDEiP54278
ProteomicsDBi56669
56670 [P54278-2]
56671 [P54278-3]
56672 [P54278-4]

2D gel databases

SWISS-2DPAGEiP54278

PTM databases

iPTMnetiP54278
PhosphoSitePlusiP54278

Expressioni

Gene expression databases

BgeeiENSG00000122512 Expressed in 93 organ(s), highest expression level in kidney
CleanExiHS_PMS2
ExpressionAtlasiP54278 baseline and differential
GenevisibleiP54278 HS

Organism-specific databases

HPAiCAB010235
HPA044400
HPA066490
HPA070310

Interactioni

Subunit structurei

Heterodimer of PMS2 and MLH1 (MutL alpha). 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 MTMR15/FAN1.1 Publication

Binary interactionsi

Protein-protein interaction databases

BioGridi111404, 55 interactors
CORUMiP54278
DIPiDIP-46295N
IntActiP54278, 26 interactors
MINTiP54278
STRINGi9606.ENSP00000265849

Structurei

Secondary structure

1862
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP54278
SMRiP54278
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP54278

Family & Domainsi

Sequence similaritiesi

Belongs to the DNA mismatch repair MutL/HexB family.Curated

Phylogenomic databases

eggNOGiKOG1978 Eukaryota
COG0323 LUCA
GeneTreeiENSGT00530000063289
HOGENOMiHOG000165474
HOVERGENiHBG008219
InParanoidiP54278
KOiK10858
OMAiFFFINQR
OrthoDBiEOG091G07MF
PhylomeDBiP54278
TreeFamiTF300711

Family and domain databases

CDDicd00075 HATPase_c, 1 hit
Gene3Di3.30.230.10, 1 hit
3.30.565.10, 1 hit
InterProiView protein in InterPro
IPR014762 DNA_mismatch_repair_CS
IPR002099 DNA_mismatch_repair_N
IPR013507 DNA_mismatch_S5_2-like
IPR003594 HATPase_C
IPR036890 HATPase_C_sf
IPR038973 MutL/Mlh/Pms
IPR014790 MutL_C
IPR037198 MutL_C_sf
IPR020568 Ribosomal_S5_D2-typ_fold
IPR014721 Ribosomal_S5_D2-typ_fold_subgr
PANTHERiPTHR10073 PTHR10073, 1 hit
PfamiView protein in Pfam
PF01119 DNA_mis_repair, 1 hit
PF08676 MutL_C, 1 hit
SMARTiView protein in SMART
SM01340 DNA_mis_repair, 1 hit
SM00853 MutL_C, 1 hit
SUPFAMiSSF118116 SSF118116, 1 hit
SSF54211 SSF54211, 1 hit
SSF55874 SSF55874, 1 hit
TIGRFAMsiTIGR00585 mutl, 1 hit
PROSITEiView protein in PROSITE
PS00058 DNA_MISMATCH_REPAIR_1, 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 2 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: P54278-1) [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
MERAESSSTE PAKAIKPIDR KSVHQICSGQ VVLSLSTAVK ELVENSLDAG 
        60         70         80         90        100
ATNIDLKLKD YGVDLIEVSD NGCGVEEENF EGLTLKHHTS KIQEFADLTQ 
       110        120        130        140        150
VETFGFRGEA LSSLCALSDV TISTCHASAK VGTRLMFDHN GKIIQKTPYP 
       160        170        180        190        200
RPRGTTVSVQ QLFSTLPVRH KEFQRNIKKE YAKMVQVLHA YCIISAGIRV 
       210        220        230        240        250
SCTNQLGQGK RQPVVCTGGS PSIKENIGSV FGQKQLQSLI PFVQLPPSDS 
       260        270        280        290        300
VCEEYGLSCS DALHNLFYIS GFISQCTHGV GRSSTDRQFF FINRRPCDPA 
       310        320        330        340        350
KVCRLVNEVY HMYNRHQYPF VVLNISVDSE CVDINVTPDK RQILLQEEKL 
       360        370        380        390        400
LLAVLKTSLI GMFDSDVNKL NVSQQPLLDV EGNLIKMHAA DLEKPMVEKQ 
       410        420        430        440        450
DQSPSLRTGE EKKDVSISRL REAFSLRHTT ENKPHSPKTP EPRRSPLGQK 
       460        470        480        490        500
RGMLSSSTSG AISDKGVLRP QKEAVSSSHG PSDPTDRAEV EKDSGHGSTS 
       510        520        530        540        550
VDSEGFSIPD TGSHCSSEYA ASSPGDRGSQ EHVDSQEKAP KTDDSFSDVD 
       560        570        580        590        600
CHSNQEDTGC KFRVLPQPTN LATPNTKRFK KEEILSSSDI CQKLVNTQDM 
       610        620        630        640        650
SASQVDVAVK INKKVVPLDF SMSSLAKRIK QLHHEAQQSE GEQNYRKFRA 
       660        670        680        690        700
KICPGENQAA EDELRKEISK TMFAEMEIIG QFNLGFIITK LNEDIFIVDQ 
       710        720        730        740        750
HATDEKYNFE MLQQHTVLQG QRLIAPQTLN LTAVNEAVLI ENLEIFRKNG 
       760        770        780        790        800
FDFVIDENAP VTERAKLISL PTSKNWTFGP QDVDELIFML SDSPGVMCRP 
       810        820        830        840        850
SRVKQMFASR ACRKSVMIGT ALNTSEMKKL ITHMGEMDHP WNCPHGRPTM 
       860 
RHIANLGVIS QN
Length:862
Mass (Da):95,797
Last modified:January 11, 2011 - v2
Checksum:iB1B9547280ECAF9A
GO
Isoform 2 (identifier: P54278-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     269-669: Missing.

Note: No experimental confirmation available.
Show »
Length:461
Mass (Da):51,251
Checksum:i26A7DCBA84C6FEA5
GO
Isoform 3 (identifier: P54278-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     560-572: CKFRVLPQPTNLA → LKTGPSDPRTSMN
     573-862: Missing.

Note: No experimental confirmation available.
Show »
Length:572
Mass (Da):62,751
Checksum:i508F176091F469A4
GO
Isoform 4 (identifier: P54278-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     180-183: EYAK → QASV
     184-862: Missing.

Note: No experimental confirmation available.
Show »
Length:183
Mass (Da):20,073
Checksum:iECC6B3983021FF07
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
C9J167C9J167_HUMAN
Mismatch repair endonuclease PMS2
PMS2
756Annotation score:
A0A2R8Y6S3A0A2R8Y6S3_HUMAN
Mismatch repair endonuclease PMS2
PMS2
727Annotation score:

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07851718I → V Polymorphism; normal DNA mismatch repair activity. 4 PublicationsCorresponds to variant dbSNP:rs63750123EnsemblClinVar.1
Natural variantiVAR_00446920R → Q Polymorphism; no effect on protein abundance; no effect on subcellular localization; normal DNA mismatch repair activity. 4 PublicationsCorresponds to variant dbSNP:rs10254120EnsemblClinVar.1
Natural variantiVAR_07981736S → R Polymorphism; no effect on protein levels. 1 PublicationCorresponds to variant dbSNP:rs587781918EnsemblClinVar.1
Natural variantiVAR_06683846S → I in MMRCS and HNPCC4; strongly decreased DNA mismatch repair activity; no effect on protein abundance; no effect on subcellular localization. 5 PublicationsCorresponds to variant dbSNP:rs121434629EnsemblClinVar.1
Natural variantiVAR_07851846S → N in HNPCC4; strongly decreased DNA mismatch repair activity. 2 PublicationsCorresponds to variant dbSNP:rs121434629EnsemblClinVar.1
Natural variantiVAR_07851960D → E Polymorphism; normal DNA mismatch repair activity. 2 PublicationsCorresponds to variant dbSNP:rs200313585EnsemblClinVar.1
Natural variantiVAR_07852066I → T in MMRCS; unknown pathological significance; normal DNA mismatch repair activity. 1 PublicationCorresponds to variant dbSNP:rs769554577EnsemblClinVar.1
Natural variantiVAR_078521107R → W in MMRCS; decreased DNA mismatch repair activity. 1 PublicationCorresponds to variant dbSNP:rs188006077EnsemblClinVar.1
Natural variantiVAR_078522115C → G in MMRCS; decreased DNA mismatch repair activity. 1 Publication1
Natural variantiVAR_078523182A → T in HNPCC4; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs587779341EnsemblClinVar.1
Natural variantiVAR_078524205Q → P in MMRCS and HNPCC4; unknown pathological significance; normal DNA mismatch repair activity. 3 PublicationsCorresponds to variant dbSNP:rs587779342EnsemblClinVar.1
Natural variantiVAR_078525207G → E in HNPCC4; unknown pathological significance; normal DNA mismatch repair activity. 2 PublicationsCorresponds to variant dbSNP:rs374704824EnsemblClinVar.1
Natural variantiVAR_078526263L → V in MMRCS and HNPCC4; unknown pathological significance; normal DNA mismatch repair activity. 2 PublicationsCorresponds to variant dbSNP:rs587779345EnsemblClinVar.1
Natural variantiVAR_016133277T → K. Corresponds to variant dbSNP:rs1805322EnsemblClinVar.1
Natural variantiVAR_078527307N → K in MMRCS; unknown pathological significance; decreased DNA mismatch repair activity. 1 PublicationCorresponds to variant dbSNP:rs587779346EnsemblClinVar.1
Natural variantiVAR_079012423A → T Polymorphism; normal DNA mismatch repair activity. 2 PublicationsCorresponds to variant dbSNP:rs587778619EnsemblClinVar.1
Natural variantiVAR_078528437P → S in MMRCS; unknown pathological significance; normal DNA mismatch repair activity. 1 PublicationCorresponds to variant dbSNP:rs200726484EnsemblClinVar.1
Natural variantiVAR_016134470P → S Polymorphism; no effect on protein abundance; no effect on subcellular localization; normal DNA mismatch repair activity. 5 PublicationsCorresponds to variant dbSNP:rs1805321EnsemblClinVar.1
Natural variantiVAR_079818475V → E Polymorphism; no effect on protein levels. 1 PublicationCorresponds to variant dbSNP:rs587781827EnsemblClinVar.1
Natural variantiVAR_012969479H → Q in MMRCS and HNPCC4; unknown pathological significance; normal DNA mismatch repair activity. 3 PublicationsCorresponds to variant dbSNP:rs63750685EnsemblClinVar.1
Natural variantiVAR_012970485T → K Polymorphism; normal DNA mismatch repair activity. 3 PublicationsCorresponds to variant dbSNP:rs1805323EnsemblClinVar.1
Natural variantiVAR_078529488A → V in MMRCS; unknown pathological significance; normal DNA mismatch repair activity. 1 PublicationCorresponds to variant dbSNP:rs587779328EnsemblClinVar.1
Natural variantiVAR_078530504E → Q in MMRCS; unknown pathological significance; normal DNA mismatch repair activity. 1 PublicationCorresponds to variant dbSNP:rs368516768EnsemblClinVar.1
Natural variantiVAR_012971511T → A Polymorphism; normal DNA mismatch repair activity. 2 PublicationsCorresponds to variant dbSNP:rs2228007EnsemblClinVar.1
Natural variantiVAR_079013511T → M Polymorphism; normal DNA mismatch repair activity. 2 PublicationsCorresponds to variant dbSNP:rs74902811EnsemblClinVar.1
Natural variantiVAR_079014511T → P1 PublicationCorresponds to variant dbSNP:rs2228007EnsemblClinVar.1
Natural variantiVAR_024541541K → E Polymorphism; normal DNA mismatch repair activity. 7 PublicationsCorresponds to variant dbSNP:rs2228006EnsemblClinVar.1
Natural variantiVAR_078531563R → L Polymorphism; normal DNA mismatch repair activity. 4 PublicationsCorresponds to variant dbSNP:rs63750668EnsemblClinVar.1
Natural variantiVAR_078532571L → I Polymorphism; normal DNA mismatch repair activity. 2 PublicationsCorresponds to variant dbSNP:rs63750055EnsemblClinVar.1
Natural variantiVAR_078533585L → I in MMRCS and HNPCC4; unknown pathological significance; normal DNA mismatch repair activity. 3 PublicationsCorresponds to variant dbSNP:rs63750947EnsemblClinVar.1
Natural variantiVAR_012972597T → S Polymorphism; normal DNA mismatch repair activity; significantly reduced interaction with MLH1. 5 PublicationsCorresponds to variant dbSNP:rs1805318EnsemblClinVar.1
Natural variantiVAR_012973622M → I in HNPCC4; unknown pathological significance; significantly reduced interaction with MLH1; normal DNA mismatch repair activity. 6 PublicationsCorresponds to variant dbSNP:rs1805324EnsemblClinVar.1
Natural variantiVAR_078534663E → A in HNPCC4; unknown pathological significance; normal DNA mismatch repair activity. 2 PublicationsCorresponds to variant dbSNP:rs587779332EnsemblClinVar.1
Natural variantiVAR_079819699D → H Polymorphism; no effect on protein levels. 1 PublicationCorresponds to variant dbSNP:rs587781317EnsemblClinVar.1
Natural variantiVAR_012974705E → K in MMRCS and HNPCC4; decreases DNA mismatch repair activity. 3 PublicationsCorresponds to variant dbSNP:rs267608161EnsemblClinVar.1
Natural variantiVAR_078535750G → D in HNPCC4; unknown pathological significance; decreased DNA mismatch repair activity. 2 PublicationsCorresponds to variant dbSNP:rs587779337EnsemblClinVar.1
Natural variantiVAR_016135775N → S Polymorphism; normal DNA mismatch repair activity. 2 PublicationsCorresponds to variant dbSNP:rs17420802EnsemblClinVar.1
Natural variantiVAR_079820792D → N Polymorphism; no effect on protein levels. 1 PublicationCorresponds to variant dbSNP:rs587781265EnsemblClinVar.1
Natural variantiVAR_078536797M → R in HNPCC4; unknown pathological significance; normal DNA mismatch repair activity. 2 PublicationsCorresponds to variant dbSNP:rs267608152EnsemblClinVar.1
Natural variantiVAR_078537815S → L in MMRCS; decreased DNA mismatch repair activity. 1 PublicationCorresponds to variant dbSNP:rs587779338EnsemblClinVar.1
Natural variantiVAR_078538843C → Y in HNPCC4; decreased DNA mismatch repair activity. 2 PublicationsCorresponds to variant dbSNP:rs267608174EnsemblClinVar.1
Natural variantiVAR_079821853I → M Polymorphism; no effect on protein levels. 1 PublicationCorresponds to variant dbSNP:rs371673459EnsemblClinVar.1
Natural variantiVAR_078539857G → A Polymorphism; normal DNA mismatch repair activity. 2 PublicationsCorresponds to variant dbSNP:rs1802683EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_029384180 – 183EYAK → QASV in isoform 4. 1 Publication4
Alternative sequenceiVSP_029385184 – 862Missing in isoform 4. 1 PublicationAdd BLAST679
Alternative sequenceiVSP_029386269 – 669Missing in isoform 2. 1 PublicationAdd BLAST401
Alternative sequenceiVSP_029387560 – 572CKFRV…PTNLA → LKTGPSDPRTSMN in isoform 3. 1 PublicationAdd BLAST13
Alternative sequenceiVSP_029388573 – 862Missing in isoform 3. 1 PublicationAdd BLAST290

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U13696 Genomic DNA Translation: AAA63923.1
AB103082 mRNA Translation: BAD89425.1
AB103083 mRNA Translation: BAD89426.1
AB103085 mRNA Translation: BAD89428.1
U14658 mRNA Translation: AAA50390.1
AK312390 mRNA Translation: BAG35307.1
AC005995 Genomic DNA Translation: AAS00390.1
BC093921 mRNA Translation: AAH93921.1
CCDSiCCDS5343.1 [P54278-1]
PIRiS47598
RefSeqiNP_000526.2, NM_000535.6 [P54278-1]
NP_001308932.1, NM_001322003.1
NP_001308933.1, NM_001322004.1
NP_001308934.1, NM_001322005.1
NP_001308935.1, NM_001322006.1
NP_001308936.1, NM_001322007.1
NP_001308937.1, NM_001322008.1
NP_001308938.1, NM_001322009.1
NP_001308939.1, NM_001322010.1
NP_001308940.1, NM_001322011.1
NP_001308941.1, NM_001322012.1
NP_001308942.1, NM_001322013.1
NP_001308943.1, NM_001322014.1
NP_001308944.1, NM_001322015.1
XP_016885888.1, XM_017030399.1
UniGeneiHs.632637
Hs.715590

Genome annotation databases

EnsembliENST00000265849; ENSP00000265849; ENSG00000122512 [P54278-1]
ENST00000382321; ENSP00000371758; ENSG00000122512 [P54278-2]
ENST00000643595; ENSP00000494497; ENSG00000122512 [P54278-4]
GeneIDi5395
KEGGihsa:5395
UCSCiuc003spl.4 human [P54278-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

Hereditary non-polyposis colorectal cancer db

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U13696 Genomic DNA Translation: AAA63923.1
AB103082 mRNA Translation: BAD89425.1
AB103083 mRNA Translation: BAD89426.1
AB103085 mRNA Translation: BAD89428.1
U14658 mRNA Translation: AAA50390.1
AK312390 mRNA Translation: BAG35307.1
AC005995 Genomic DNA Translation: AAS00390.1
BC093921 mRNA Translation: AAH93921.1
CCDSiCCDS5343.1 [P54278-1]
PIRiS47598
RefSeqiNP_000526.2, NM_000535.6 [P54278-1]
NP_001308932.1, NM_001322003.1
NP_001308933.1, NM_001322004.1
NP_001308934.1, NM_001322005.1
NP_001308935.1, NM_001322006.1
NP_001308936.1, NM_001322007.1
NP_001308937.1, NM_001322008.1
NP_001308938.1, NM_001322009.1
NP_001308939.1, NM_001322010.1
NP_001308940.1, NM_001322011.1
NP_001308941.1, NM_001322012.1
NP_001308942.1, NM_001322013.1
NP_001308943.1, NM_001322014.1
NP_001308944.1, NM_001322015.1
XP_016885888.1, XM_017030399.1
UniGeneiHs.632637
Hs.715590

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1EA6X-ray2.70A/B1-364[»]
1H7SX-ray1.95A/B1-365[»]
1H7UX-ray2.70A/B1-365[»]
5U5RX-ray2.10B573-583[»]
ProteinModelPortaliP54278
SMRiP54278
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111404, 55 interactors
CORUMiP54278
DIPiDIP-46295N
IntActiP54278, 26 interactors
MINTiP54278
STRINGi9606.ENSP00000265849

Chemistry databases

DrugBankiDB02930 Phosphothiophosphoric Acid-Adenylate Ester

PTM databases

iPTMnetiP54278
PhosphoSitePlusiP54278

Polymorphism and mutation databases

BioMutaiPMS2
DMDMi317373266

2D gel databases

SWISS-2DPAGEiP54278

Proteomic databases

EPDiP54278
MaxQBiP54278
PaxDbiP54278
PeptideAtlasiP54278
PRIDEiP54278
ProteomicsDBi56669
56670 [P54278-2]
56671 [P54278-3]
56672 [P54278-4]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000265849; ENSP00000265849; ENSG00000122512 [P54278-1]
ENST00000382321; ENSP00000371758; ENSG00000122512 [P54278-2]
ENST00000643595; ENSP00000494497; ENSG00000122512 [P54278-4]
GeneIDi5395
KEGGihsa:5395
UCSCiuc003spl.4 human [P54278-1]

Organism-specific databases

CTDi5395
DisGeNETi107984056
5395
EuPathDBiHostDB:ENSG00000122512.14
GeneCardsiPMS2
GeneReviewsiPMS2
HGNCiHGNC:9122 PMS2
HPAiCAB010235
HPA044400
HPA066490
HPA070310
MalaCardsiPMS2
MIMi276300 phenotype
600259 gene
614337 phenotype
neXtProtiNX_P54278
OpenTargetsiENSG00000122512
Orphaneti252202 Constitutional mismatch repair deficiency syndrome
144 Hereditary nonpolyposis colon cancer
99817 Non-polyposis Turcot syndrome
PharmGKBiPA33448
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1978 Eukaryota
COG0323 LUCA
GeneTreeiENSGT00530000063289
HOGENOMiHOG000165474
HOVERGENiHBG008219
InParanoidiP54278
KOiK10858
OMAiFFFINQR
OrthoDBiEOG091G07MF
PhylomeDBiP54278
TreeFamiTF300711

Enzyme and pathway databases

ReactomeiR-HSA-5358565 Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha)
R-HSA-5358606 Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta)
R-HSA-5545483 Defective Mismatch Repair Associated With MLH1
R-HSA-5632987 Defective Mismatch Repair Associated With PMS2
R-HSA-6796648 TP53 Regulates Transcription of DNA Repair Genes
SIGNORiP54278

Miscellaneous databases

ChiTaRSiPMS2 human
EvolutionaryTraceiP54278
GeneWikiiPMS2
GenomeRNAii5395
PROiPR:P54278
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000122512 Expressed in 93 organ(s), highest expression level in kidney
CleanExiHS_PMS2
ExpressionAtlasiP54278 baseline and differential
GenevisibleiP54278 HS

Family and domain databases

CDDicd00075 HATPase_c, 1 hit
Gene3Di3.30.230.10, 1 hit
3.30.565.10, 1 hit
InterProiView protein in InterPro
IPR014762 DNA_mismatch_repair_CS
IPR002099 DNA_mismatch_repair_N
IPR013507 DNA_mismatch_S5_2-like
IPR003594 HATPase_C
IPR036890 HATPase_C_sf
IPR038973 MutL/Mlh/Pms
IPR014790 MutL_C
IPR037198 MutL_C_sf
IPR020568 Ribosomal_S5_D2-typ_fold
IPR014721 Ribosomal_S5_D2-typ_fold_subgr
PANTHERiPTHR10073 PTHR10073, 1 hit
PfamiView protein in Pfam
PF01119 DNA_mis_repair, 1 hit
PF08676 MutL_C, 1 hit
SMARTiView protein in SMART
SM01340 DNA_mis_repair, 1 hit
SM00853 MutL_C, 1 hit
SUPFAMiSSF118116 SSF118116, 1 hit
SSF54211 SSF54211, 1 hit
SSF55874 SSF55874, 1 hit
TIGRFAMsiTIGR00585 mutl, 1 hit
PROSITEiView protein in PROSITE
PS00058 DNA_MISMATCH_REPAIR_1, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiPMS2_HUMAN
AccessioniPrimary (citable) accession number: P54278
Secondary accession number(s): B2R610
, Q52LH6, Q5FBW9, Q5FBX1, Q5FBX2, Q75MR2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: January 11, 2011
Last modified: October 10, 2018
This is version 196 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. SIMILARITY comments
    Index of protein domains and families
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  6. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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