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P04155 (TFF1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 152. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length84 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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 Ref.14.

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2424 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13
Chain25 – 8460Trefoil factor 1
PRO_0000023456

Regions

Domain29 – 7244P-type
Compositional bias79 – 835Glu-rich (acidic)

Amino acid modifications

Disulfide bond31 ↔ 57
Disulfide bond41 ↔ 56
Disulfide bond51 ↔ 68

Natural variations

Natural variant221T → I.
Corresponds to variant rs34795821 [ dbSNP | Ensembl ].
VAR_053563
Natural variant321T → I in a gastric carcinoma sample; somatic mutation. Ref.20
VAR_015281
Natural variant321T → K in a gastric carcinoma sample; somatic mutation. Ref.20
VAR_015282
Natural variant341A → 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 variant371E → 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 variant461V → I in a gastric adenoma sample; somatic mutation. Ref.20
VAR_015285
Natural variant551G → V in a gastric carcinoma sample; somatic mutation. Ref.20
VAR_015286

Experimental info

Mutagenesis821C → S: Abolishes inhibition of gastric cancer cell growth. Ref.21

Secondary structure

.................. 84
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P04155 [UniParc].

Last modified November 1, 1986. Version 1.
Checksum: 65198523BAD6EBC7

FASTA849,150
        10         20         30         40         50         60 
MATMENKVIC ALVLVSMLAL GTLAEAQTET CTVAPRERQN CGFPGVTPSQ CANKGCCFDD 

        70         80 
TVRGVPWCFY PNTIDVPPEE ECEF 

« Hide

References

« Hide '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. expand/collapse author list , 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, SUBCELLULAR LOCATION.
[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.

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.
CCDSCCDS13685.1.
PIRA26667.
RefSeqNP_003216.1. NM_003225.2.
UniGeneHs.162807.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1HI7NMR-A/B25-84[»]
1PS2NMR-A25-84[»]
ProteinModelPortalP04155.
SMRP04155. Positions 25-84.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112889. 16 interactions.
IntActP04155. 7 interactions.
MINTMINT-1461530.
STRING9606.ENSP00000291527.

Polymorphism databases

DMDM131127.

Proteomic databases

MaxQBP04155.
PaxDbP04155.
PeptideAtlasP04155.
PRIDEP04155.

Protocols and materials databases

DNASU7031.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000291527; ENSP00000291527; ENSG00000160182.
GeneID7031.
KEGGhsa:7031.
UCSCuc002zax.1. human.

Organism-specific databases

CTD7031.
GeneCardsGC21M043782.
HGNCHGNC:11755. TFF1.
HPACAB002170.
HPA003425.
MIM113710. gene.
neXtProtNX_P04155.
PharmGKBPA36470.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG46001.
HOGENOMHOG000121778.
HOVERGENHBG004364.
InParanoidP04155.
OMAPEEECEF.
OrthoDBEOG70W3GT.
PhylomeDBP04155.
TreeFamTF336092.

Gene expression databases

BgeeP04155.
CleanExHS_TFF1.
GenevestigatorP04155.

Family and domain databases

Gene3D4.10.110.10. 1 hit.
InterProIPR000519. P_trefoil.
IPR017994. P_trefoil_chordata.
IPR017957. P_trefoil_CS.
IPR028824. TFF1.
[Graphical view]
PANTHERPTHR13826:SF15. PTHR13826:SF15. 1 hit.
PfamPF00088. Trefoil. 1 hit.
[Graphical view]
PRINTSPR00680. PTREFOIL.
SMARTSM00018. PD. 1 hit.
[Graphical view]
SUPFAMSSF57492. SSF57492. 1 hit.
PROSITEPS00025. P_TREFOIL_1. 1 hit.
PS51448. P_TREFOIL_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSTFF1. human.
EvolutionaryTraceP04155.
GeneWikiTrefoil_factor_1.
GenomeRNAi7031.
NextBio27469.
PROP04155.
SOURCESearch...

Entry information

Entry nameTFF1_HUMAN
AccessionPrimary (citable) accession number: P04155
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1986
Last sequence update: November 1, 1986
Last modified: July 9, 2014
This is version 152 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 21

Human chromosome 21: entries, gene names and cross-references to MIM