UniProtKB - P54278 (PMS2_HUMAN)
Mismatch repair endonuclease PMS2
PMS2
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 PublicationsGO - Molecular functioni
- ATP binding Source: InterPro
- ATP hydrolysis activity Source: GO_Central
- DNA binding Source: HGNC-UCL
- endonuclease activity Source: Reactome
- single base insertion or deletion binding Source: HGNC-UCL
GO - Biological processi
- mismatch repair Source: UniProtKB
- response to xenobiotic stimulus Source: Ensembl
- somatic hypermutation of immunoglobulin genes Source: GO_Central
Keywordsi
Molecular function | Endonuclease, Hydrolase, Nuclease |
Biological process | DNA damage, DNA repair |
Enzyme and pathway databases
PathwayCommonsi | P54278 |
Reactomei | R-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 |
SignaLinki | P54278 |
SIGNORi | P54278 |
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 | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:9122, PMS2 |
MIMi | 600259, gene |
neXtProti | NX_P54278 |
VEuPathDBi | HostDB:ENSG00000122512 |
Subcellular locationi
Nucleus
- Nucleus 1 Publication
Cytosol
- cytosol Source: HPA
Nucleus
- MutLalpha complex Source: GO_Central
- nucleoplasm Source: HPA
- nucleus Source: UniProtKB
Plasma Membrane
- plasma membrane Source: HPA
Other locations
- cytoplasmic ribonucleoprotein granule Source: HPA
- mismatch repair complex Source: GO_Central
Keywords - Cellular componenti
NucleusPathology & Biotechi
Involvement in diseasei
Hereditary non-polyposis colorectal cancer 4 (HNPCC4)10 Publications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_066838 | 46 | S → I in MMRCS4 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_078518 | 46 | S → N in HNPCC4; strongly decreased DNA mismatch repair activity. 2 PublicationsCorresponds to variant dbSNP:rs121434629EnsemblClinVar. | 1 | |
Natural variantiVAR_078523 | 182 | A → T in HNPCC4; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs587779341EnsemblClinVar. | 1 | |
Natural variantiVAR_078524 | 205 | Q → P in MMRCS4 and HNPCC4; unknown pathological significance; normal DNA mismatch repair activity. 3 PublicationsCorresponds to variant dbSNP:rs587779342EnsemblClinVar. | 1 | |
Natural variantiVAR_078525 | 207 | G → E in HNPCC4; unknown pathological significance; normal DNA mismatch repair activity. 2 PublicationsCorresponds to variant dbSNP:rs374704824EnsemblClinVar. | 1 | |
Natural variantiVAR_078526 | 263 | L → V in MMRCS4 and HNPCC4; unknown pathological significance; normal DNA mismatch repair activity. 2 PublicationsCorresponds to variant dbSNP:rs587779345EnsemblClinVar. | 1 | |
Natural variantiVAR_012969 | 479 | H → Q in MMRCS4 and HNPCC4; unknown pathological significance; normal DNA mismatch repair activity. 3 PublicationsCorresponds to variant dbSNP:rs63750685EnsemblClinVar. | 1 | |
Natural variantiVAR_078533 | 585 | L → I in MMRCS4 and HNPCC4; unknown pathological significance; normal DNA mismatch repair activity. 3 PublicationsCorresponds to variant dbSNP:rs63750947EnsemblClinVar. | 1 | |
Natural variantiVAR_012973 | 622 | M → 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_078534 | 663 | E → A in HNPCC4; unknown pathological significance; normal DNA mismatch repair activity. 2 PublicationsCorresponds to variant dbSNP:rs587779332Ensembl. | 1 | |
Natural variantiVAR_012974 | 705 | E → K in MMRCS4 and HNPCC4; decreases DNA mismatch repair activity. 3 PublicationsCorresponds to variant dbSNP:rs267608161EnsemblClinVar. | 1 | |
Natural variantiVAR_078535 | 750 | G → D in HNPCC4; unknown pathological significance; decreased DNA mismatch repair activity. 2 PublicationsCorresponds to variant dbSNP:rs587779337EnsemblClinVar. | 1 | |
Natural variantiVAR_078536 | 797 | M → R in HNPCC4; unknown pathological significance; normal DNA mismatch repair activity. 2 PublicationsCorresponds to variant dbSNP:rs267608152Ensembl. | 1 | |
Natural variantiVAR_078538 | 843 | C → Y in HNPCC4; decreased DNA mismatch repair activity. 2 PublicationsCorresponds to variant dbSNP:rs267608174Ensembl. | 1 |
Mismatch repair cancer syndrome 4 (MMRCS4)5 Publications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_066838 | 46 | S → I in MMRCS4 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_078520 | 66 | I → T in MMRCS4; unknown pathological significance; normal DNA mismatch repair activity. 1 PublicationCorresponds to variant dbSNP:rs769554577EnsemblClinVar. | 1 | |
Natural variantiVAR_078521 | 107 | R → W in MMRCS4; decreased DNA mismatch repair activity. 1 PublicationCorresponds to variant dbSNP:rs188006077EnsemblClinVar. | 1 | |
Natural variantiVAR_078522 | 115 | C → G in MMRCS4; decreased DNA mismatch repair activity. 1 Publication | 1 | |
Natural variantiVAR_078524 | 205 | Q → P in MMRCS4 and HNPCC4; unknown pathological significance; normal DNA mismatch repair activity. 3 PublicationsCorresponds to variant dbSNP:rs587779342EnsemblClinVar. | 1 | |
Natural variantiVAR_078526 | 263 | L → V in MMRCS4 and HNPCC4; unknown pathological significance; normal DNA mismatch repair activity. 2 PublicationsCorresponds to variant dbSNP:rs587779345EnsemblClinVar. | 1 | |
Natural variantiVAR_078527 | 307 | N → K in MMRCS4; unknown pathological significance; decreased DNA mismatch repair activity. 1 PublicationCorresponds to variant dbSNP:rs587779346EnsemblClinVar. | 1 | |
Natural variantiVAR_078528 | 437 | P → S in MMRCS4; unknown pathological significance; normal DNA mismatch repair activity. 1 PublicationCorresponds to variant dbSNP:rs200726484EnsemblClinVar. | 1 | |
Natural variantiVAR_012969 | 479 | H → Q in MMRCS4 and HNPCC4; unknown pathological significance; normal DNA mismatch repair activity. 3 PublicationsCorresponds to variant dbSNP:rs63750685EnsemblClinVar. | 1 | |
Natural variantiVAR_078529 | 488 | A → V in MMRCS4; unknown pathological significance; normal DNA mismatch repair activity. 1 PublicationCorresponds to variant dbSNP:rs587779328EnsemblClinVar. | 1 | |
Natural variantiVAR_078530 | 504 | E → Q in MMRCS4; unknown pathological significance; normal DNA mismatch repair activity. 1 PublicationCorresponds to variant dbSNP:rs368516768EnsemblClinVar. | 1 | |
Natural variantiVAR_078533 | 585 | L → I in MMRCS4 and HNPCC4; unknown pathological significance; normal DNA mismatch repair activity. 3 PublicationsCorresponds to variant dbSNP:rs63750947EnsemblClinVar. | 1 | |
Natural variantiVAR_012974 | 705 | E → K in MMRCS4 and HNPCC4; decreases DNA mismatch repair activity. 3 PublicationsCorresponds to variant dbSNP:rs267608161EnsemblClinVar. | 1 | |
Natural variantiVAR_078537 | 815 | S → L in MMRCS4; decreased DNA mismatch repair activity. 1 PublicationCorresponds to variant dbSNP:rs587779338EnsemblClinVar. | 1 |
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 41 | E → A: Decreased DNA mismatch repair activity. 1 Publication | 1 | |
Mutagenesisi | 70 | D → N: No effect on protein abundance, no effect on subcellular localization and loss of DNA mismatch repair activity. 1 Publication | 1 | |
Mutagenesisi | 519 | Y → C: No effect on DNA mismatch repair activity. 1 Publication | 1 |
Keywords - Diseasei
Disease variant, Hereditary nonpolyposis colorectal cancer, Tumor suppressorOrganism-specific databases
DisGeNETi | 5395 |
GeneReviewsi | PMS2 |
MalaCardsi | PMS2 |
MIMi | 614337, phenotype 619101, phenotype |
OpenTargetsi | ENSG00000122512 |
Orphaneti | 252202, Constitutional mismatch repair deficiency syndrome 144, Lynch syndrome |
PharmGKBi | PA33448 |
Miscellaneous databases
Pharosi | P54278, Tbio |
Chemistry databases
DrugBanki | DB02930, Adenosine 5'-[gamma-thio]triphosphate |
Genetic variation databases
BioMutai | PMS2 |
DMDMi | 317373266 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000178005 | 1 – 862 | Mismatch repair endonuclease PMS2Add BLAST | 862 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 573 | PhosphothreonineCombined sources | 1 | |
Modified residuei | 597 | PhosphothreonineCombined sources | 1 |
Keywords - PTMi
PhosphoproteinProteomic databases
EPDi | P54278 |
jPOSTi | P54278 |
MassIVEi | P54278 |
MaxQBi | P54278 |
PaxDbi | P54278 |
PeptideAtlasi | P54278 |
PRIDEi | P54278 |
ProteomicsDBi | 56669 [P54278-1] 56670 [P54278-2] 56671 [P54278-3] 56672 [P54278-4] |
2D gel databases
SWISS-2DPAGEi | P54278 |
PTM databases
GlyGeni | P54278, 1 site, 1 O-linked glycan (1 site) |
iPTMneti | P54278 |
PhosphoSitePlusi | P54278 |
Expressioni
Gene expression databases
Bgeei | ENSG00000122512, Expressed in kidney and 120 other tissues |
ExpressionAtlasi | P54278, baseline and differential |
Genevisiblei | P54278, HS |
Organism-specific databases
HPAi | ENSG00000122512, Low tissue specificity |
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 PublicationBinary interactionsi
P54278
With | #Exp. | IntAct |
---|---|---|
MLH1 [P40692] | 21 | EBI-1162561,EBI-744248 |
Isoform 1 [P54278-1]
With | #Exp. | IntAct |
---|---|---|
TP73 [O15350] | 3 | EBI-15726984,EBI-389606 |
Isoform 2 [P54278-2]
With | #Exp. | IntAct |
---|---|---|
MEOX2 [Q6FHY5] | 3 | EBI-12176841,EBI-16439278 |
Protein-protein interaction databases
BioGRIDi | 111404, 71 interactors |
CORUMi | P54278 |
DIPi | DIP-46295N |
IntActi | P54278, 30 interactors |
MINTi | P54278 |
STRINGi | 9606.ENSP00000265849 |
Miscellaneous databases
RNActi | P54278, protein |
Structurei
Secondary structure
3D structure databases
SMRi | P54278 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P54278 |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 391 – 552 | DisorderedSequence analysisAdd BLAST | 162 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 391 – 440 | Basic and acidic residuesSequence analysisAdd BLAST | 50 | |
Compositional biasi | 450 – 464 | Polar residuesSequence analysisAdd BLAST | 15 | |
Compositional biasi | 484 – 498 | Basic and acidic residuesSequence analysisAdd BLAST | 15 | |
Compositional biasi | 499 – 524 | Polar residuesSequence analysisAdd BLAST | 26 | |
Compositional biasi | 530 – 552 | Basic and acidic residuesSequence analysisAdd BLAST | 23 |
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG1978, Eukaryota |
GeneTreei | ENSGT00940000155381 |
HOGENOMi | CLU_004131_0_2_1 |
InParanoidi | P54278 |
OMAi | HIPRPSK |
OrthoDBi | 735423at2759 |
PhylomeDBi | P54278 |
TreeFami | TF300711 |
Family and domain databases
Gene3Di | 3.30.1370.100, 1 hit 3.30.1540.20, 1 hit 3.30.230.10, 1 hit 3.30.565.10, 1 hit |
InterProi | View protein in InterPro IPR014762, DNA_mismatch_repair_CS IPR002099, DNA_mismatch_repair_N IPR013507, DNA_mismatch_S5_2-like IPR036890, HATPase_C_sf IPR038973, MutL/Mlh/Pms IPR014790, MutL_C IPR042120, MutL_C_dimsub IPR042121, MutL_C_regsub IPR037198, MutL_C_sf IPR020568, Ribosomal_S5_D2-typ_fold IPR014721, Ribosomal_S5_D2-typ_fold_subgr |
PANTHERi | PTHR10073, PTHR10073, 1 hit |
Pfami | View protein in Pfam PF01119, DNA_mis_repair, 1 hit PF08676, MutL_C, 1 hit |
SMARTi | View protein in SMART SM01340, DNA_mis_repair, 1 hit SM00853, MutL_C, 1 hit |
SUPFAMi | SSF118116, SSF118116, 1 hit SSF54211, SSF54211, 1 hit SSF55874, SSF55874, 1 hit |
TIGRFAMsi | TIGR00585, mutl, 1 hit |
PROSITEi | View protein in PROSITE PS00058, DNA_MISMATCH_REPAIR_1, 1 hit |
s (4+)i Sequence
Sequence statusi: Complete.
This entry describes 4 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 4 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketC9J167 | C9J167_HUMAN | Mismatch repair endonuclease PMS2 | PMS2 | 756 | Annotation score: | ||
A0A2R8Y6S3 | A0A2R8Y6S3_HUMAN | Mismatch repair endonuclease PMS2 | PMS2 | 727 | Annotation score: |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_078517 | 18 | I → V Normal DNA mismatch repair activity. 4 PublicationsCorresponds to variant dbSNP:rs63750123EnsemblClinVar. | 1 | |
Natural variantiVAR_004469 | 20 | R → Q No effect on protein abundance; no effect on subcellular localization; normal DNA mismatch repair activity. 4 PublicationsCorresponds to variant dbSNP:rs10254120EnsemblClinVar. | 1 | |
Natural variantiVAR_079817 | 36 | S → R No effect on protein levels. 1 PublicationCorresponds to variant dbSNP:rs587781918EnsemblClinVar. | 1 | |
Natural variantiVAR_066838 | 46 | S → I in MMRCS4 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_078518 | 46 | S → N in HNPCC4; strongly decreased DNA mismatch repair activity. 2 PublicationsCorresponds to variant dbSNP:rs121434629EnsemblClinVar. | 1 | |
Natural variantiVAR_078519 | 60 | D → E Normal DNA mismatch repair activity. 2 PublicationsCorresponds to variant dbSNP:rs200313585EnsemblClinVar. | 1 | |
Natural variantiVAR_078520 | 66 | I → T in MMRCS4; unknown pathological significance; normal DNA mismatch repair activity. 1 PublicationCorresponds to variant dbSNP:rs769554577EnsemblClinVar. | 1 | |
Natural variantiVAR_078521 | 107 | R → W in MMRCS4; decreased DNA mismatch repair activity. 1 PublicationCorresponds to variant dbSNP:rs188006077EnsemblClinVar. | 1 | |
Natural variantiVAR_078522 | 115 | C → G in MMRCS4; decreased DNA mismatch repair activity. 1 Publication | 1 | |
Natural variantiVAR_078523 | 182 | A → T in HNPCC4; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs587779341EnsemblClinVar. | 1 | |
Natural variantiVAR_078524 | 205 | Q → P in MMRCS4 and HNPCC4; unknown pathological significance; normal DNA mismatch repair activity. 3 PublicationsCorresponds to variant dbSNP:rs587779342EnsemblClinVar. | 1 | |
Natural variantiVAR_078525 | 207 | G → E in HNPCC4; unknown pathological significance; normal DNA mismatch repair activity. 2 PublicationsCorresponds to variant dbSNP:rs374704824EnsemblClinVar. | 1 | |
Natural variantiVAR_078526 | 263 | L → V in MMRCS4 and HNPCC4; unknown pathological significance; normal DNA mismatch repair activity. 2 PublicationsCorresponds to variant dbSNP:rs587779345EnsemblClinVar. | 1 | |
Natural variantiVAR_016133 | 277 | T → K. Corresponds to variant dbSNP:rs1805322EnsemblClinVar. | 1 | |
Natural variantiVAR_078527 | 307 | N → K in MMRCS4; unknown pathological significance; decreased DNA mismatch repair activity. 1 PublicationCorresponds to variant dbSNP:rs587779346EnsemblClinVar. | 1 | |
Natural variantiVAR_079012 | 423 | A → T Normal DNA mismatch repair activity. 2 PublicationsCorresponds to variant dbSNP:rs587778619EnsemblClinVar. | 1 | |
Natural variantiVAR_078528 | 437 | P → S in MMRCS4; unknown pathological significance; normal DNA mismatch repair activity. 1 PublicationCorresponds to variant dbSNP:rs200726484EnsemblClinVar. | 1 | |
Natural variantiVAR_016134 | 470 | P → S No effect on protein abundance; no effect on subcellular localization; normal DNA mismatch repair activity. 5 PublicationsCorresponds to variant dbSNP:rs1805321EnsemblClinVar. | 1 | |
Natural variantiVAR_079818 | 475 | V → E No effect on protein levels. 1 PublicationCorresponds to variant dbSNP:rs587781827EnsemblClinVar. | 1 | |
Natural variantiVAR_012969 | 479 | H → Q in MMRCS4 and HNPCC4; unknown pathological significance; normal DNA mismatch repair activity. 3 PublicationsCorresponds to variant dbSNP:rs63750685EnsemblClinVar. | 1 | |
Natural variantiVAR_012970 | 485 | T → K Normal DNA mismatch repair activity. 3 PublicationsCorresponds to variant dbSNP:rs1805323EnsemblClinVar. | 1 | |
Natural variantiVAR_078529 | 488 | A → V in MMRCS4; unknown pathological significance; normal DNA mismatch repair activity. 1 PublicationCorresponds to variant dbSNP:rs587779328EnsemblClinVar. | 1 | |
Natural variantiVAR_078530 | 504 | E → Q in MMRCS4; unknown pathological significance; normal DNA mismatch repair activity. 1 PublicationCorresponds to variant dbSNP:rs368516768EnsemblClinVar. | 1 | |
Natural variantiVAR_012971 | 511 | T → A Normal DNA mismatch repair activity. 2 PublicationsCorresponds to variant dbSNP:rs2228007EnsemblClinVar. | 1 | |
Natural variantiVAR_079013 | 511 | T → M Normal DNA mismatch repair activity. 2 PublicationsCorresponds to variant dbSNP:rs74902811EnsemblClinVar. | 1 | |
Natural variantiVAR_079014 | 511 | T → P1 PublicationCorresponds to variant dbSNP:rs2228007EnsemblClinVar. | 1 | |
Natural variantiVAR_024541 | 541 | K → E Normal DNA mismatch repair activity. 7 PublicationsCorresponds to variant dbSNP:rs2228006EnsemblClinVar. | 1 | |
Natural variantiVAR_078531 | 563 | R → L Normal DNA mismatch repair activity. 4 PublicationsCorresponds to variant dbSNP:rs63750668EnsemblClinVar. | 1 | |
Natural variantiVAR_078532 | 571 | L → I Normal DNA mismatch repair activity. 2 PublicationsCorresponds to variant dbSNP:rs63750055EnsemblClinVar. | 1 | |
Natural variantiVAR_078533 | 585 | L → I in MMRCS4 and HNPCC4; unknown pathological significance; normal DNA mismatch repair activity. 3 PublicationsCorresponds to variant dbSNP:rs63750947EnsemblClinVar. | 1 | |
Natural variantiVAR_012972 | 597 | T → S Normal DNA mismatch repair activity; significantly reduced interaction with MLH1. 5 PublicationsCorresponds to variant dbSNP:rs1805318EnsemblClinVar. | 1 | |
Natural variantiVAR_012973 | 622 | M → 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_078534 | 663 | E → A in HNPCC4; unknown pathological significance; normal DNA mismatch repair activity. 2 PublicationsCorresponds to variant dbSNP:rs587779332Ensembl. | 1 | |
Natural variantiVAR_079819 | 699 | D → H No effect on protein levels. 1 PublicationCorresponds to variant dbSNP:rs587781317EnsemblClinVar. | 1 | |
Natural variantiVAR_012974 | 705 | E → K in MMRCS4 and HNPCC4; decreases DNA mismatch repair activity. 3 PublicationsCorresponds to variant dbSNP:rs267608161EnsemblClinVar. | 1 | |
Natural variantiVAR_078535 | 750 | G → D in HNPCC4; unknown pathological significance; decreased DNA mismatch repair activity. 2 PublicationsCorresponds to variant dbSNP:rs587779337EnsemblClinVar. | 1 | |
Natural variantiVAR_016135 | 775 | N → S Normal DNA mismatch repair activity. 2 PublicationsCorresponds to variant dbSNP:rs17420802EnsemblClinVar. | 1 | |
Natural variantiVAR_079820 | 792 | D → N No effect on protein levels. 1 PublicationCorresponds to variant dbSNP:rs587781265EnsemblClinVar. | 1 | |
Natural variantiVAR_078536 | 797 | M → R in HNPCC4; unknown pathological significance; normal DNA mismatch repair activity. 2 PublicationsCorresponds to variant dbSNP:rs267608152Ensembl. | 1 | |
Natural variantiVAR_078537 | 815 | S → L in MMRCS4; decreased DNA mismatch repair activity. 1 PublicationCorresponds to variant dbSNP:rs587779338EnsemblClinVar. | 1 | |
Natural variantiVAR_078538 | 843 | C → Y in HNPCC4; decreased DNA mismatch repair activity. 2 PublicationsCorresponds to variant dbSNP:rs267608174Ensembl. | 1 | |
Natural variantiVAR_079821 | 853 | I → M No effect on protein levels. 1 PublicationCorresponds to variant dbSNP:rs371673459EnsemblClinVar. | 1 | |
Natural variantiVAR_078539 | 857 | G → A Normal DNA mismatch repair activity. 2 PublicationsCorresponds to variant dbSNP:rs1802683EnsemblClinVar. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_029384 | 180 – 183 | EYAK → QASV in isoform 4. 1 Publication | 4 | |
Alternative sequenceiVSP_029385 | 184 – 862 | Missing in isoform 4. 1 PublicationAdd BLAST | 679 | |
Alternative sequenceiVSP_029386 | 269 – 669 | Missing in isoform 2. 1 PublicationAdd BLAST | 401 | |
Alternative sequenceiVSP_029387 | 560 – 572 | CKFRV…PTNLA → LKTGPSDPRTSMN in isoform 3. 1 PublicationAdd BLAST | 13 | |
Alternative sequenceiVSP_029388 | 573 – 862 | Missing in isoform 3. 1 PublicationAdd BLAST | 290 |
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 |
CCDSi | CCDS5343.1 [P54278-1] |
PIRi | S47598 |
RefSeqi | NP_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 |
Genome annotation databases
Ensembli | ENST00000265849; ENSP00000265849; ENSG00000122512 ENST00000382321; ENSP00000371758; ENSG00000122512 [P54278-2] ENST00000643595; ENSP00000494497; ENSG00000122512 [P54278-4] |
GeneIDi | 5395 |
KEGGi | hsa:5395 |
MANE-Selecti | ENST00000265849.12; ENSP00000265849.7; NM_000535.7; NP_000526.2 |
UCSCi | uc003spl.4, human [P54278-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar 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 |
CCDSi | CCDS5343.1 [P54278-1] |
PIRi | S47598 |
RefSeqi | NP_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 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1EA6 | X-ray | 2.70 | A/B | 1-364 | [»] | |
1H7S | X-ray | 1.95 | A/B | 1-365 | [»] | |
1H7U | X-ray | 2.70 | A/B | 1-365 | [»] | |
5U5R | X-ray | 2.10 | B | 573-583 | [»] | |
6MFQ | X-ray | 2.60 | A/B | 1-365 | [»] | |
SMRi | P54278 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 111404, 71 interactors |
CORUMi | P54278 |
DIPi | DIP-46295N |
IntActi | P54278, 30 interactors |
MINTi | P54278 |
STRINGi | 9606.ENSP00000265849 |
Chemistry databases
DrugBanki | DB02930, Adenosine 5'-[gamma-thio]triphosphate |
PTM databases
GlyGeni | P54278, 1 site, 1 O-linked glycan (1 site) |
iPTMneti | P54278 |
PhosphoSitePlusi | P54278 |
Genetic variation databases
BioMutai | PMS2 |
DMDMi | 317373266 |
2D gel databases
SWISS-2DPAGEi | P54278 |
Proteomic databases
EPDi | P54278 |
jPOSTi | P54278 |
MassIVEi | P54278 |
MaxQBi | P54278 |
PaxDbi | P54278 |
PeptideAtlasi | P54278 |
PRIDEi | P54278 |
ProteomicsDBi | 56669 [P54278-1] 56670 [P54278-2] 56671 [P54278-3] 56672 [P54278-4] |
Protocols and materials databases
Antibodypediai | 4134, 541 antibodies from 42 providers |
DNASUi | 5395 |
Genome annotation databases
Ensembli | ENST00000265849; ENSP00000265849; ENSG00000122512 ENST00000382321; ENSP00000371758; ENSG00000122512 [P54278-2] ENST00000643595; ENSP00000494497; ENSG00000122512 [P54278-4] |
GeneIDi | 5395 |
KEGGi | hsa:5395 |
MANE-Selecti | ENST00000265849.12; ENSP00000265849.7; NM_000535.7; NP_000526.2 |
UCSCi | uc003spl.4, human [P54278-1] |
Organism-specific databases
CTDi | 5395 |
DisGeNETi | 5395 |
GeneCardsi | PMS2 |
GeneReviewsi | PMS2 |
HGNCi | HGNC:9122, PMS2 |
HPAi | ENSG00000122512, Low tissue specificity |
MalaCardsi | PMS2 |
MIMi | 600259, gene 614337, phenotype 619101, phenotype |
neXtProti | NX_P54278 |
OpenTargetsi | ENSG00000122512 |
Orphaneti | 252202, Constitutional mismatch repair deficiency syndrome 144, Lynch syndrome |
PharmGKBi | PA33448 |
VEuPathDBi | HostDB:ENSG00000122512 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG1978, Eukaryota |
GeneTreei | ENSGT00940000155381 |
HOGENOMi | CLU_004131_0_2_1 |
InParanoidi | P54278 |
OMAi | HIPRPSK |
OrthoDBi | 735423at2759 |
PhylomeDBi | P54278 |
TreeFami | TF300711 |
Enzyme and pathway databases
PathwayCommonsi | P54278 |
Reactomei | R-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 |
SignaLinki | P54278 |
SIGNORi | P54278 |
Miscellaneous databases
BioGRID-ORCSi | 5395, 10 hits in 1038 CRISPR screens |
ChiTaRSi | PMS2, human |
EvolutionaryTracei | P54278 |
GeneWikii | PMS2 |
Pharosi | P54278, Tbio |
PROi | PR:P54278 |
RNActi | P54278, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000122512, Expressed in kidney and 120 other tissues |
ExpressionAtlasi | P54278, baseline and differential |
Genevisiblei | P54278, HS |
Family and domain databases
Gene3Di | 3.30.1370.100, 1 hit 3.30.1540.20, 1 hit 3.30.230.10, 1 hit 3.30.565.10, 1 hit |
InterProi | View protein in InterPro IPR014762, DNA_mismatch_repair_CS IPR002099, DNA_mismatch_repair_N IPR013507, DNA_mismatch_S5_2-like IPR036890, HATPase_C_sf IPR038973, MutL/Mlh/Pms IPR014790, MutL_C IPR042120, MutL_C_dimsub IPR042121, MutL_C_regsub IPR037198, MutL_C_sf IPR020568, Ribosomal_S5_D2-typ_fold IPR014721, Ribosomal_S5_D2-typ_fold_subgr |
PANTHERi | PTHR10073, PTHR10073, 1 hit |
Pfami | View protein in Pfam PF01119, DNA_mis_repair, 1 hit PF08676, MutL_C, 1 hit |
SMARTi | View protein in SMART SM01340, DNA_mis_repair, 1 hit SM00853, MutL_C, 1 hit |
SUPFAMi | SSF118116, SSF118116, 1 hit SSF54211, SSF54211, 1 hit SSF55874, SSF55874, 1 hit |
TIGRFAMsi | TIGR00585, mutl, 1 hit |
PROSITEi | View protein in PROSITE PS00058, DNA_MISMATCH_REPAIR_1, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | PMS2_HUMAN | |
Accessioni | P54278Primary (citable) accession number: P54278 Secondary accession number(s): B2R610 Q75MR2 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | October 1, 1996 |
Last sequence update: | January 11, 2011 | |
Last modified: | February 23, 2022 | |
This is version 217 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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, Reference proteomeDocuments
- Human chromosome 7
Human chromosome 7: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families