PMS2

Protein identityUniProt · HPA

UniProt accession

P54278

Gene

PMS2

Ensembl

ENSG00000122512

Chromosome

7

Canonical length

862 aa

Protein class

Cancer-related genes, Disease related genes, Human disease related genes, Predicted intracellular proteins

Subcellular location

Nucleoplasm,Cytosol

OverviewNCBI Gene

The protein encoded by this gene is a key component of the mismatch repair system that functions to correct DNA mismatches and small insertions and deletions that can occur during DNA replication and homologous recombination. This protein forms heterodimers with the gene product of the mutL homolog 1 (MLH1) gene to form the MutL-alpha heterodimer. The MutL-alpha heterodimer possesses an endonucleolytic activity that is activated following recognition of mismatches and insertion/deletion loops by the MutS-alpha and MutS-beta heterodimers, and is necessary for removal of the mismatched DNA. There is a DQHA(X)2E(X)4E motif found at the C-terminus of the protein encoded by this gene that forms part of the active site of the nuclease. Mutations in this gene have been associated with hereditary nonpolyposis colorectal cancer (HNPCC; also known as Lynch syndrome) and Turcot syndrome. [provided by RefSeq, Apr 2016]

Canonical amino-acid sequenceUniProt

862 residues, UniProt reviewed canonical sequence.

>P54278|PMS2
     1  MERAESSSTE PAKAIKPIDR KSVHQICSGQ VVLSLSTAVK ELVENSLDAG ATNIDLKLKD
    61  YGVDLIEVSD NGCGVEEENF EGLTLKHHTS KIQEFADLTQ VETFGFRGEA LSSLCALSDV
   121  TISTCHASAK VGTRLMFDHN GKIIQKTPYP RPRGTTVSVQ QLFSTLPVRH KEFQRNIKKE
   181  YAKMVQVLHA YCIISAGIRV SCTNQLGQGK RQPVVCTGGS PSIKENIGSV FGQKQLQSLI
   241  PFVQLPPSDS VCEEYGLSCS DALHNLFYIS GFISQCTHGV GRSSTDRQFF FINRRPCDPA
   301  KVCRLVNEVY HMYNRHQYPF VVLNISVDSE CVDINVTPDK RQILLQEEKL LLAVLKTSLI
   361  GMFDSDVNKL NVSQQPLLDV EGNLIKMHAA DLEKPMVEKQ DQSPSLRTGE EKKDVSISRL
   421  REAFSLRHTT ENKPHSPKTP EPRRSPLGQK RGMLSSSTSG AISDKGVLRP QKEAVSSSHG
   481  PSDPTDRAEV EKDSGHGSTS VDSEGFSIPD TGSHCSSEYA ASSPGDRGSQ EHVDSQEKAP
   541  KTDDSFSDVD CHSNQEDTGC KFRVLPQPTN LATPNTKRFK KEEILSSSDI CQKLVNTQDM
   601  SASQVDVAVK INKKVVPLDF SMSSLAKRIK QLHHEAQQSE GEQNYRKFRA KICPGENQAA
   661  EDELRKEISK TMFAEMEIIG QFNLGFIITK LNEDIFIVDQ HATDEKYNFE MLQQHTVLQG
   721  QRLIAPQTLN LTAVNEAVLI ENLEIFRKNG FDFVIDENAP VTERAKLISL PTSKNWTFGP
   781  QDVDELIFML SDSPGVMCRP SRVKQMFASR ACRKSVMIGT ALNTSEMKKL ITHMGEMDHP
   841  WNCPHGRPTM RHIANLGVIS QN

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PMS2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.41

Highest tissue expression

12 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about PMS2.

Disease | AllUniProt

Conditions PMS2 is implicated in, by any mechanism.

• Lynch syndrome 4 (LYNCH4) MIM:614337
• Mismatch repair cancer syndrome 4 (MMRCS4) MIM:619101

Disease | GeneticClinVar

996 pathogenic / likely-pathogenic of 6,005 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Hereditary cancer-predisposing syndrome
• Lynch syndrome 4
• Hereditary nonpolyposis colorectal neoplasms
• Lynch syndrome
• Hereditary nonpolyposis colon cancer

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.27

gnomAD pLI

0

gnomAD missense Z

-0.56

DepMap mean gene effect

0.07

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 12% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• mismatch repair
• positive regulation of isotype switching to IgA isotypes
• positive regulation of isotype switching to IgG isotypes
• response to xenobiotic stimulus
• somatic hypermutation of immunoglobulin genes
• somatic recombination of immunoglobulin gene segments

Molecular functions

• ATP binding
• ATP hydrolysis activity
• ATP-dependent DNA damage sensor activity
• DNA binding
• endonuclease activity
• single base insertion or deletion binding

Cellular components

• cytosol
• MutLalpha complex
• nucleoplasm
• nucleus

Protein domainsUniProt · Pfam · InterPro

• DNA mismatch repair protein MutL/Mlh/PMS
• DNA mismatch repair protein, S5 domain 2-like
• Small ribosomal subunit protein uS5 domain 2-type fold, subgroup
• DNA mismatch repair, conserved site
• MutL, C-terminal, dimerisation
• Ribosomal protein uS5 domain 2-type superfamily
• Histidine kinase/HSP90-like ATPase superfamily
• MutL, C-terminal domain superfamily
• DNA mismatch repair protein MutL/Mlh/Pms-like
• MutL, C-terminal domain, dimerisation subdomain
• MutL, C-terminal domain, regulatory subdomain
• DNA mismatch repair protein, C-terminal domain
• MutL C terminal dimerisation domain
• Histidine kinase-, DNA gyrase B-, and HSP90-like ATPase

KeywordsUniProt

• ATP-binding
• DNA damage
• DNA repair
• DNA-binding
• Endonuclease
• Hereditary nonpolyposis colorectal cancer
• Hydrolase
• Nuclease
• Nucleotide-binding
• Nucleus
• Phosphoprotein
• Tumor suppressor

InteractionsUniProt · HPA

Protein binding partners of PMS2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• FAN1
• MLH1