Reviewed, UniProtKB/Swiss-Prot P54277 (PMS1_HUMAN)

Names and origin

Protein names

Recommended name:
    PMS1 protein homolog 1
Alternative name(s):
    DNA mismatch repair protein PMS1

Gene names

Name:	PMS1
Synonyms:	PMSL1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	932 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Probably involved in the repair of mismatches in DNA.
Subcellular location	NucleusPotential.
Involvement in disease	Defects in PMS1 are the cause of hereditary non-polyposis colorectal cancer type 3 (HNPCC3) [MIM:600258]. Mutations in more than one gene locus can be involved alone or in combination in the production of the HNPCC phenotype (also called Lynch syndrome). Most families with clinically recognized HNPCC have mutations in either MLH1 or MSH2 genes. HNPCC is an autosomal, dominantly inherited disease associated with marked increase in cancer susceptibility. It is characterized by a familial predisposition to early onset colorectal carcinoma (CRC) and extra-colonic cancers 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, and accounts for 15% of all colon cancers. Cancers in HNPCC originate within benign neoplastic polyps termed adenomas. Clinically, HNPCC is often divided into two subgroups. Type I: hereditary predisposition to colorectal cancer, a young age of onset, and carcinoma observed in the proximal colon. Type II: patients have an 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.
Sequence similarities	Belongs to the DNA mismatch repair mutL/hexB family. Contains 1 HMG box DNA-binding domain.

Ontologies

Keywords
Biological process	Cell cycle DNA damage DNA repair
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Disease	Disease mutation Hereditary nonpolyposis colorectal cancer
Molecular function	Anti-oncogene
Technical term	3D-structure
Gene Ontology (GO)
Biological process	mismatch repair Ref.1 Traceable author statement. Source: ProtInc negative regulation of cell cycle Inferred from electronic annotation. Source: UniProtKB-KW regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: InterPro
Cellular component	nucleus Ref.1 Traceable author statement. Source: ProtInc
Molecular function	ATP binding Inferred from electronic annotation. Source: InterPro mismatched DNA binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 932

932

PMS1 protein homolog 1

PRO_0000178004

Regions

DNA binding

571 – 639

69

HMG box

Natural variations

Natural variant

27

1

E → Q: dbSNP rs5742973.

VAR_019166

Natural variant

202

1

R → K: dbSNP rs2066459.

VAR_014877

Natural variant

394

1

M → T in incomplete HNPCC3. dbSNP rs1145231.

VAR_012967

Natural variant

501

1

G → R in incomplete HNPCC3. dbSNP rs1145232.

VAR_012968

Natural variant

632

1

N → S: dbSNP rs2066456.

VAR_014878

Natural variant

720

1

E → D: dbSNP rs2066455.

VAR_014879

Natural variant

793

1

Y → H: dbSNP rs1145234.

VAR_014880

Secondary structure

1

.

.

.

.

.

.

.

.

.

932

Helix Strand Turn

Details...

Helix

577 – 592

16

Helix

598 – 610

13

Helix

614 – 625

12

Turn

626 – 628

3

Helix

629 – 638

10

Sequences

	Sequence		Length	Mass (Da)
	P54277-1 [UniParc]. Last modified October 1, 1996. Version 1. Checksum: EC4F402937B616DF	FASTA	932	105,830
	10 20 30 40 50 60 MKQLPAATVR LLSSSQIITS VVSVVKELIE NSLDAGATSV DVKLENYGFD KIEVRDNGEG 70 80 90 100 110 120 IKAVDAPVMA MKYYTSKINS HEDLENLTTY GFRGEALGSI CCIAEVLITT RTAADNFSTQ 130 140 150 160 170 180 YVLDGSGHIL SQKPSHLGQG TTVTALRLFK NLPVRKQFYS TAKKCKDEIK KIQDLLMSFG 190 200 210 220 230 240 ILKPDLRIVF VHNKAVIWQK SRVSDHKMAL MSVLGTAVMN NMESFQYHSE ESQIYLSGFL 250 260 270 280 290 300 PKCDADHSFT SLSTPERSFI FINSRPVHQK DILKLIRHHY NLKCLKESTR LYPVFFLKID 310 320 330 340 350 360 VPTADVDVNL TPDKSQVLLQ NKESVLIALE NLMTTCYGPL PSTNSYENNK TDVSAADIVL 370 380 390 400 410 420 SKTAETDVLF NKVESSGKNY SNVDTSVIPF QNDMHNDESG KNTDDCLNHQ ISIGDFGYGH 430 440 450 460 470 480 CSSEISNIDK NTKNAFQDIS MSNVSWENSQ TEYSKTCFIS SVKHTQSENG NKDHIDESGE 490 500 510 520 530 540 NEEEAGLENS SEISADEWSR GNILKNSVGE NIEPVKILVP EKSLPCKVSN NNYPIPEQMN 550 560 570 580 590 600 LNEDSCNKKS NVIDNKSGKV TAYDLLSNRV IKKPMSASAL FVQDHRPQFL IENPKTSLED 610 620 630 640 650 660 ATLQIEELWK TLSEEEKLKY EEKATKDLER YNSQMKRAIE QESQMSLKDG RKKIKPTSAW 670 680 690 700 710 720 NLAQKHKLKT SLSNQPKLDE LLQSQIEKRR SQNIKMVQIP FSMKNLKINF KKQNKVDLEE 730 740 750 760 770 780 KDEPCLIHNL RFPDAWLMTS KTEVMLLNPY RVEEALLFKR LLENHKLPAE PLEKPIMLTE 790 800 810 820 830 840 SLFNGSHYLD VLYKMTADDQ RYSGSTYLSD PRLTANGFKI KLIPGVSITE NYLEIEGMAN 850 860 870 880 890 900 CLPFYGVADL KEILNAILNR NAKEVYECRP RKVISYLEGE AVRLSRQLPM YLSKEDIQDI 910 920 930 IYRMKHQFGN EIKECVHGRP FFHHLTYLPE TT

References

[1]	"Mutations of two PMS homologues in hereditary nonpolyposis colon cancer." Nicolaides N.C., Papadopoulos N., Liu B., Wei Y.-F., Carter K.C., Ruben S.M., Rosen C.A., Haseltine W.H., Fleischmann R.D., Fraser C.M., Adams M.D., Venter J.C., Dunlop M.G., Hamilton S.R., Petersen G.M., de la Chapelle A., Vogelstein B., Kinzler K.W. Nature 371:75-80(1994) [PubMed: 8072530] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Gall bladder.
[2]	"NIEHS-SNPs, environmental genome project, NIEHS ES15478, Department of Genome Sciences, Seattle, WA (URL: http://egp.gs.washington.edu)." Rieder M.J., Livingston R.J., Daniels M.R., Chung M.-W., Miyamoto K.E., Nguyen C.P., Nguyen D.A., Poel C.L., Robertson P.D., Schackwitz W.S., Sherwood J.K., Witrak L.A., Nickerson D.A. Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS GLN-27; LYS-202; ARG-501; SER-632; ASP-720 AND HIS-793.
[3]	"Solution structure of the HMG domain of human DNA mismatch repair protein." RIKEN structural genomics initiative (RSGI) Submitted (NOV-2005) to the PDB data bank Cited for: STRUCTURE BY NMR OF 571-649.
[4]	"Prevalence of germline mutations of hMLH1, hMSH2, hPMS1, hPMS2, and hMSH6 genes in 75 French kindreds with nonpolyposis colorectal cancer." Wang Q., Lasset C., Desseigne F., Saurin J.-C., Maugard C., Navarro C., Ruano E., Descos L., Trillet-Lenoir V., Bosset J.-F., Puisieux A. Hum. Genet. 105:79-85(1999) [PubMed: 10480359] [Abstract] Cited for: VARIANTS HNPCC3 THR-394 AND ARG-501.
+	Additional computationally mapped references.

Web resources

Hereditary non-polyposis colorectal cancer db

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBLGenBankDDBJ

U13695 Genomic DNA. Translation: AAA63922.1.
AY267352 Genomic DNA. Translation: AAO89079.1.

PIR

S47597.

RefSeq

NP_000525.1.

UniGene

Hs.111749

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2CS1	NMR	-	A	571-649	[»]

ModBase

Search...

PTM databases

PhosphoSite

P54277.

Polymorphism databases

NIEHS-SNPs

Search...

Genome annotation databases

Ensembl

ENSG00000064933. Homo sapiens. [Contig view]

GeneID

5378.

KEGG

hsa:5378.

Organism-specific databases

HGNC

HGNC:9121. PMS1.

HPA

CAB010233.

MIM

600258. gene+phenotype.

Orphanet

144. Colon cancer, familial nonpolyposis.

PharmGKB

PA33447.

GenAtlas

Search...

GeneCards

Search...

Phylogenomic databases

HOGENOM

P54277.

HOVERGEN

P54277.

Gene expression databases

ArrayExpress

P54277.

CleanEx

HS_PMS1.

GermOnline

ENSG00000064933. Homo sapiens.

Family and domain databases

InterPro

IPR003594. ATP_bd_ATPase.
IPR002099. DNA_mismatch_repair.
IPR013507. DNA_mismatch_repair_C.
IPR014762. DNA_mismatch_repair_CS.
IPR014763. DNA_mismatch_repair_N.
IPR000910. HMG_1/2_box.
[Graphical view]

Gene3D

G3DSA:3.30.565.10. ATP_bd_ATPase. 1 hit.
G3DSA:1.10.30.10. HMG-box. 1 hit.

PANTHER

PTHR10073. DNA_mis_repair. 1 hit.

Pfam

PF01119. DNA_mis_repair. 1 hit.
PF02518. HATPase_c. 1 hit.
PF00505. HMG_box. 1 hit.
[Graphical view]

SMART

SM00387. HATPase_c. 1 hit.
SM00398. HMG. 1 hit.
[Graphical view]

TIGRFAMs

TIGR00585. mutl. 1 hit.

PROSITE

PS00058. DNA_MISMATCH_REPAIR_1. 1 hit.
PS50118. HMG_BOX_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

20866.

SOURCE

Search...

Entry information

Entry name

PMS1_HUMAN

Accession

Primary (citable) accession number: P54277

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	November 25, 2008
This is version 83 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)