P54277 (PMS1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Probably involved in the repair of mismatches in DNA.
Subcellular location	Nucleus Potential.
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. Ref.6
Sequence similarities	Belongs to the DNA mismatch repair mutL/hexB family. Contains 1 HMG box DNA-binding domain.

Ontologies

Keywords
Biological process	DNA damage DNA repair
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Disease	Disease mutation Hereditary nonpolyposis colorectal cancer Tumor suppressor
Ligand	DNA-binding
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	mismatch repair Inferred from Biological aspect of Ancestor. Source: RefGenome reciprocal meiotic recombination Inferred from Biological aspect of Ancestor. Source: RefGenome
Cellular component	MutLalpha complex Inferred from Biological aspect of Ancestor. Source: RefGenome
Molecular function	ATP binding Inferred from electronic annotation. Source: InterPro ATPase activity Inferred from Biological aspect of Ancestor. Source: RefGenome mismatched DNA binding Inferred from Biological aspect of Ancestor. Source: RefGenome
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. Ref.2
Corresponds to variant rs5742973 [ dbSNP | Ensembl ].

VAR_019166

Natural variant

202

1

R → K. Ref.2
Corresponds to variant rs2066459 [ dbSNP | Ensembl ].

VAR_014877

Natural variant

394

1

M → T in incomplete HNPCC3. Ref.6
Corresponds to variant rs1145231 [ dbSNP | Ensembl ].

VAR_012967

Natural variant

501

1

G → R in incomplete HNPCC3. Ref.2 Ref.6
Corresponds to variant rs1145232 [ dbSNP | Ensembl ].

VAR_012968

Natural variant

632

1

N → S. Ref.2
Corresponds to variant rs2066456 [ dbSNP | Ensembl ].

VAR_014878

Natural variant

720

1

E → D. Ref.2
Corresponds to variant rs2066455 [ dbSNP | Ensembl ].

VAR_014879

Natural variant

793

1

Y → H. Ref.2
Corresponds to variant rs1145234 [ dbSNP | Ensembl ].

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 [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

	« Hide 'large scale' referencesShow 'large scale' 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 program 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]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[5]	"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.
[6]	"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

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Hereditary non-polyposis colorectal cancer db

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U13695 Genomic DNA. Translation: AAA63922.1.
AY267352 Genomic DNA. Translation: AAO89079.1.
CH471058 Genomic DNA. Translation: EAX10883.1.
CH471058 Genomic DNA. Translation: EAX10885.1.

IPI

IPI00005541.

PIR

S47597.

RefSeq

NP_000525.1. NM_000534.4.

UniGene

Hs.111749.

3D structure databases

PDBe
RCSB PDB
PDBj

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

ProteinModelPortal

P54277.

SMR

P54277. Positions 15-339, 571-649.

ModBase

Search...

Protein-protein interaction databases

IntAct

P54277. 1 interaction.

STRING

P54277.

PTM databases

PhosphoSite

P54277.

Polymorphism databases

DMDM

1709683.

Proteomic databases

PRIDE

P54277.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000441310; ENSP00000406490; ENSG00000064933.

GeneID

5378.

KEGG

hsa:5378.

UCSC

uc002urh.2. human.

Organism-specific databases

CTD

5378.

GeneCards

GC02P190648.

H-InvDB

HIX0029784.

HGNC

HGNC:9121. PMS1.

HPA

CAB010233.

MIM

600258. gene+phenotype.

neXtProt

NX_P54277.

Orphanet

144. Hereditary nonpolyposis colon cancer.

PharmGKB

PA33447.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG15452.

HOGENOM

HBG715132.

HOVERGEN

HBG031886.

InParanoid

P54277.

OMA

HKLPAEP.

OrthoDB

EOG41C6VK.

PhylomeDB

P54277.

Gene expression databases

ArrayExpress

P54277.

Bgee

P54277.

CleanEx

HS_PMS1.

Genevestigator

P54277.

GermOnline

ENSG00000064933. Homo sapiens.

Family and domain databases

InterPro

IPR003594. ATPase-like_ATP-bd.
IPR002099. DNA_mismatch_repair.
IPR013507. DNA_mismatch_repair_C.
IPR014762. DNA_mismatch_repair_CS.
IPR014763. DNA_mismatch_repair_N.
IPR000910. HMG_HMG1/HMG2.
IPR009071. HMG_superfamily.
IPR020568. Ribosomal_S5_D2-typ_fold.
IPR014721. Ribosomal_S5_D2-typ_fold_subgr.
[Graphical view]

Gene3D

G3DSA:3.30.565.10. ATP_bd_ATPase. 1 hit.
G3DSA:1.10.30.10. HMG-box. 1 hit.
G3DSA:3.30.230.10. Ribosomal_S5_D2-type_fold. 1 hit.

KO

K10864.

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]

SUPFAM

SSF55874. ATP_bd_ATPase. 1 hit.
SSF47095. HMG-box. 1 hit.
SSF54211. Ribosomal_S5_D2-typ_fold. 1 hit.

TIGRFAMs

TIGR00585. Mutl. 1 hit.

PROSITE

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

ProtoNet

Search...

Other

NextBio

20866.

SOURCE

Search...

Entry information

Entry name

PMS1_HUMAN

Accession

Primary (citable) accession number: P54277
Secondary accession number(s): D3DPI1

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	January 25, 2012
This is version 117 of the entry and version 1 of the sequence. [Complete history]

Entry status

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.