P04155 (TFF1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Trefoil factor 1

Alternative name(s):
Breast cancer estrogen-inducible protein
PNR-2
Polypeptide P1.A
Short name=hP1.A
Protein pS2

Gene names

Name:	TFF1
Synonyms:	BCEI, PS2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	84 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Stabilizer of the mucous gel overlying the gastrointestinal mucosa that provides a physical barrier against various noxious agents. May inhibit the growth of calcium oxalate crystals in urine. Ref.11
Subunit structure	Heterodimer with GKN2; disulfide linked.
Subcellular location	Secreted Ref.10.
Tissue specificity	Found in stomach, with highest levels in the upper gastric mucosal cells (at protein level). Detected in goblet cells of the small and large intestine and rectum, small submucosal glands in the esophagus, mucous acini of the sublingual gland, submucosal glands of the trachea, and epithelial cells lining the exocrine pancreatic ducts but not in the remainder of the pancreas (at protein level). Scattered expression is detected in the epithelial cells of the gallbladder and submucosal glands of the vagina, and weak expression is observed in the bronchial goblet cells of the pseudostratified epithelia in the respiratory system (at protein level). Detected in urine (at protein level). Strongly expressed in breast cancer but at low levels in normal mammary tissue. It is regulated by estrogen in MCF-7 cells. Strong expression found in normal gastric mucosa and in the regenerative tissues surrounding ulcerous lesions of gastrointestinal tract, but lower expression found in gastric cancer (at protein level). Ref.2 Ref.10 Ref.11 Ref.14 Ref.15 Ref.16 Ref.17
Sequence similarities	Contains 1 P-type (trefoil) domain.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Domain	Signal
Molecular function	Growth factor
PTM	Disulfide bond
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	carbohydrate metabolic process Traceable author statement PubMed 2303034. Source: ProtInc digestion Non-traceable author statement PubMed 9043862. Source: ProtInc maintenance of gastrointestinal epithelium Inferred from electronic annotation. Source: Compara response to estradiol stimulus Inferred from direct assay PubMed 15831516. Source: BHF-UCL response to iron ion Inferred from electronic annotation. Source: Compara response to peptide hormone stimulus Inferred from electronic annotation. Source: Compara response to stress Inferred from electronic annotation. Source: Compara
Cellular_component	extracellular space Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
BTN3A1	O00481	3	EBI-743871,EBI-2809309
BTNL8	Q6UX41	3	EBI-743871,EBI-4314379
CD300LD	Q6UXZ3	3	EBI-743871,EBI-4314468
FCRL4	Q96PJ5	3	EBI-743871,EBI-4314687
SIGLEC8	Q9NYZ4	3	EBI-743871,EBI-4314991

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 24

24

Ref.9 Ref.10 Ref.11 Ref.12 Ref.13

Chain

25 – 84

60

Trefoil factor 1

PRO_0000023456

Regions

Domain

29 – 72

44

P-type

Compositional bias

79 – 83

5

Glu-rich (acidic)

Amino acid modifications

Disulfide bond

31 ↔ 57

Disulfide bond

41 ↔ 56

Disulfide bond

51 ↔ 68

Natural variations

Natural variant

22

1

T → I.
Corresponds to variant rs34795821 [ dbSNP | Ensembl ].

VAR_053563

Natural variant

32

1

T → I in a gastric carcinoma sample; somatic mutation. Ref.20

VAR_015281

Natural variant

32

1

T → K in a gastric carcinoma sample; somatic mutation. Ref.20

VAR_015282

Natural variant

34

1

A → D in a gastric carcinoma sample; somatic mutation. Abolishes inhibition of gastric cancer cell growth. Abolishes inhibition of apoptosis in gasterointestinal epithelial cells. Increases invasive activity in epithelial cells. Ref.20 Ref.21

VAR_015283

Natural variant

37

1

E → K in a gastric carcinoma sample; somatic mutation. Abolishes inhibition of gastric cancer cell growth. Abolishes inhibition of apoptosis in gasterointestinal epithelial cells. Increases invasive activity in epithelial cells. Ref.20 Ref.21

VAR_015284

Natural variant

46

1

V → I in a gastric adenoma sample; somatic mutation. Ref.20

VAR_015285

Natural variant

55

1

G → V in a gastric carcinoma sample; somatic mutation. Ref.20

VAR_015286

Experimental info

Mutagenesis

82

1

C → S: Abolishes inhibition of gastric cancer cell growth. Ref.21

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

84

Helix Strand Turn

Details...

Beta strand

28 – 30

3

Turn

35 – 37

3

Beta strand

40 – 42

3

Helix

48 – 52

5

Turn

53 – 55

3

Beta strand

61 – 65

5

Beta strand

67 – 69

3

Beta strand

72 – 74

3

Beta strand

79 – 82

4

Sequences

	Sequence		Length	Mass (Da)
	P04155 [UniParc]. Last modified November 1, 1986. Version 1. Checksum: 65198523BAD6EBC7	FASTA	84	9,150
	10 20 30 40 50 60 MATMENKVIC ALVLVSMLAL GTLAEAQTET CTVAPRERQN CGFPGVTPSQ CANKGCCFDD 70 80 TVRGVPWCFY PNTIDVPPEE ECEF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Sequence of the pS2 mRNA induced by estrogen in the human breast cancer cell line MCF-7." Jakowlew S.B., Breathnach R., Jeltsch J.-M., Masiakowski P., Chambon P. Nucleic Acids Res. 12:2861-2878(1984) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Cloning of a gene expressed in human breast cancer and regulated by estrogen in MCF-7 cells." Prud'Homme J.-F., Fridlansky F., le Cunff M., Atger M., Mercier-Bodart C., Pichon M.-F., Milgrom E. DNA 4:11-21(1985) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY. Tissue: Mammary cancer.
[3]	"Structure of the human oestrogen-responsive gene pS2." Jeltsch J.-M., Roberts M., Schatz C., Garnier J.-M., Brown A.M.C., Chambon P. Nucleic Acids Res. 15:1401-1414(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"Expression of the pS2 gene in human gastric cancer cells derived from poorly differentiated adenocarcinoma." Takahashi H., Kida N., Fujii R., Tanaka K., Ohta M., Mori K., Hayashi K. FEBS Lett. 261:283-286(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Gastric carcinoma.
[5]	"Complete primary structure of the human estrogen-responsive gene (pS2) product." Mori K., Fujii R., Kida N., Takahashi H., Ohkubo S., Fujino M., Ohta M., Hayashi K. J. Biochem. 107:73-76(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[6]	"Refined localization of autosomal recessive nonsyndromic deafness DFNB10 locus using 34 novel microsatellite markers, genomic structure, and exclusion of six known genes in the region." Berry A., Scott H.S., Kudoh J., Talior I., Korostishevsky M., Wattenhofer M., Guipponi M., Barras C., Rossier C., Shibuya K., Wang J., Kawasaki K., Asakawa S., Minoshima S., Shimizu N., Antonarakis S.E., Bonne-Tamir B. Genomics 68:22-29(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[7]	"The DNA sequence of human chromosome 21." Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T., Park H.-S., Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y., Soeda E., Ohki M., Takagi T., Sakaki Y., Taudien S., Blechschmidt K., Polley A. , Menzel U., Delabar J., Kumpf K., Lehmann R., Patterson D., Reichwald K., Rump A., Schillhabel M., Schudy A., Zimmermann W., Rosenthal A., Kudoh J., Shibuya K., Kawasaki K., Asakawa S., Shintani A., Sasaki T., Nagamine K., Mitsuyama S., Antonarakis S.E., Minoshima S., Shimizu N., Nordsiek G., Hornischer K., Brandt P., Scharfe M., Schoen O., Desario A., Reichelt J., Kauer G., Bloecker H., Ramser J., Beck A., Klages S., Hennig S., Riesselmann L., Dagand E., Wehrmeyer S., Borzym K., Gardiner K., Nizetic D., Francis F., Lehrach H., Reinhardt R., Yaspo M.-L. Nature 405:311-319(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Colon, Kidney and Stomach.
[9]	"Primary structure of human protein pS2." Rio M.-C., Lepage P., Diemunsch P., Roitsch C., Chambon P. C. R. Acad. Sci. III, Sci. Vie 307:825-831(1988) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 25-84.
[10]	"Interaction between TFF1, a gastric tumor suppressor trefoil protein, and TFIZ1, a Brichos domain-containing protein with homology to SP-C." Westley B.R., Griffin S.M., May F.E.B. Biochemistry 44:7967-7975(2005) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 25-84, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH GKN2. Tissue: Stomach.
[11]	"Identification of human urinary trefoil factor 1 as a novel calcium oxalate crystal growth inhibitor." Chutipongtanate S., Nakagawa Y., Sritippayawan S., Pittayamateekul J., Parichatikanond P., Westley B.R., May F.E., Malasit P., Thongboonkerd V. J. Clin. Invest. 115:3613-3622(2005) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 25-63, FUNCTION, TISSUE SPECIFICITY.
[12]	"Identification of a polypeptide secreted by human breast cancer cells (MCF-7) as the human estrogen-responsive gene (pS2) product." Mori K., Fujii R., Kida N., Ohta M., Hayashi K. Biochem. Biophys. Res. Commun. 155:366-372(1988) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 25-60.
[13]	"Signal peptide prediction based on analysis of experimentally verified cleavage sites." Zhang Z., Henzel W.J. Protein Sci. 13:2819-2824(2004) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 25-39.
[14]	"Breast cancer-associated pS2 protein: synthesis and secretion by normal stomach mucosa." Rio M.C., Bellocq J.-P., Daniel J.Y., Tomasetto C., Lathe R., Chenard M.P., Batzenschlager A., Chambon P. Science 241:705-708(1988) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, SECRETION.
[15]	"Expression of trefoil factors 1 and 2 in precancerous condition and gastric cancer." Shi S.-Q., Cai J.-T., Yang J.-M. World J. Gastroenterol. 12:3119-3122(2006) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[16]	"Molecular forms of trefoil factor 1 in normal gastric mucosa and its expression in normal and abnormal gastric tissues." Ren J.L., Luo J.-Y., Lu Y.-P., Wang L., Shi H.-X. World J. Gastroenterol. 12:7361-7364(2006) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[17]	"Tissue localization of human trefoil factors 1, 2, and 3." Madsen J., Nielsen O., Tornoe I., Thim L., Holmskov U. J. Histochem. Cytochem. 55:505-513(2007) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[18]	"NMR-based structural studies of the pNR-2/pS2 single domain trefoil peptide. Similarities to porcine spasmolytic peptide and evidence for a monomeric structure." Polshakov V.I., Frenkiel T.A., Westley B.R., Chadwick M.P., May F.E.B., Carr M.D., Feeney J. Eur. J. Biochem. 233:847-855(1995) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR.
[19]	"High-resolution solution structure of human pNR-2/pS2: a single trefoil motif protein." Polshakov V.I., Williams M.A., Gargaro A.R., Frenkiel T.A., Westley B.R., Chadwick M.P., May F.E.B., Feeney J. J. Mol. Biol. 267:418-432(1997) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR.
[20]	"Somatic mutations of the trefoil factor family 1 gene in gastric cancer." Park W.-S., Oh R.-R., Park J.-Y., Lee J.-H., Shin M.-S., Kim H.-S., Lee H.-K., Kim Y.-S., Kim S.-Y., Lee S.-H., Yoo N.-J., Lee J.-Y. Gastroenterology 119:691-698(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS ILE-32; LYS-32; ASP-34; LYS-37; ILE-46 AND VAL-55.
[21]	"Trefoil factor family-1 mutations enhance gastric cancer cell invasion through distinct signaling pathways." Yio X., Diamond M., Zhang J.-Y., Weinstein H., Wang L.-H., Werther L., Itzkowitz S. Gastroenterology 130:1696-1706(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS ASP-34 AND LYS-37, MUTAGENESIS OF CYS-82.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X00474 mRNA. Translation: CAA25155.1.
M12075 mRNA. Translation: AAA52402.1.
X05030, X05321, X05322 Genomic DNA. Translation: CAA28695.1.
X52003 mRNA. Translation: CAA36254.1.
AB038162 Genomic DNA. Translation: BAB13729.1.
AP001746 Genomic DNA. Translation: BAA95532.1.
BC032811 mRNA. Translation: AAH32811.1.

IPI

IPI00022283.

PIR

A26667.

RefSeq

NP_003216.1. NM_003225.2.

UniGene

Hs.162807.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1HI7	NMR	-	A/B	25-84	[»]
1PS2	NMR	-	A	25-84	[»]

ProteinModelPortal

P04155.

ModBase

Search...

Protein-protein interaction databases

IntAct

P04155. 7 interactions.

MINT

MINT-1461530.

STRING

9606.ENSP00000291527.

Polymorphism databases

DMDM

131127.

Proteomic databases

PaxDb

P04155.

PeptideAtlas

P04155.

PRIDE

P04155.

Protocols and materials databases

DNASU

7031.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000291527; ENSP00000291527; ENSG00000160182.

GeneID

7031.

KEGG

hsa:7031.

UCSC

uc002zax.1. human.

Organism-specific databases

CTD

7031.

GeneCards

GC21M043782.

HGNC

HGNC:11755. TFF1.

HPA

CAB002170.
HPA003425.

MIM

113710. gene.

neXtProt

NX_P04155.

PharmGKB

PA36470.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG46001.

HOGENOM

HOG000121778.

HOVERGEN

HBG004364.

InParanoid

P04155.

OMA

PEEECEF.

OrthoDB

EOG4907BN.

PhylomeDB

P04155.

Enzyme and pathway databases

Pathway_Interaction_DB

hnf3apathway. FOXA1 transcription factor network.

Gene expression databases

Bgee

P04155.

CleanEx

HS_TFF1.

Genevestigator

P04155.

GermOnline

ENSG00000160182. Homo sapiens.

Family and domain databases

Gene3D

4.10.110.10. 1 hit.

InterPro

IPR000519. P_trefoil.
IPR017994. P_trefoil_chordata.
IPR017957. P_trefoil_CS.
[Graphical view]

Pfam

PF00088. Trefoil. 1 hit.
[Graphical view]

PRINTS

PR00680. PTREFOIL.

SMART

SM00018. PD. 1 hit.
[Graphical view]

SUPFAM

SSF57492. P_trefoil. 1 hit.

PROSITE

PS00025. P_TREFOIL_1. 1 hit.
PS51448. P_TREFOIL_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

TFF1. human.

EvolutionaryTrace

P04155.

GenomeRNAi

7031.

NextBio

27469.

SOURCE

Search...

Entry information

Entry name

TFF1_HUMAN

Accession

Primary (citable) accession number: P04155

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1986
Last sequence update:	November 1, 1986
Last modified:	May 29, 2013
This is version 141 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.