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P04155

- TFF1_HUMAN

UniProt

P04155 - TFF1_HUMAN

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Protein

Trefoil factor 1

Gene

TFF1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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.1 Publication

GO - Biological processi

  1. carbohydrate metabolic process Source: ProtInc
  2. cell differentiation Source: Ensembl
  3. digestion Source: ProtInc
  4. maintenance of gastrointestinal epithelium Source: Ensembl
  5. negative regulation of cell proliferation Source: Ensembl
  6. response to estradiol Source: BHF-UCL
  7. response to iron ion Source: Ensembl
  8. response to peptide hormone Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Growth factor

Names & Taxonomyi

Protein namesi
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 namesi
Name:TFF1
Synonyms:BCEI, PS2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 21

Organism-specific databases

HGNCiHGNC:11755. TFF1.

Subcellular locationi

Secreted 2 Publications

GO - Cellular componenti

  1. extracellular space Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi82 – 821C → S: Abolishes inhibition of gastric cancer cell growth. 1 Publication

Organism-specific databases

PharmGKBiPA36470.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 24245 PublicationsAdd
BLAST
Chaini25 – 8460Trefoil factor 1PRO_0000023456Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi31 ↔ 57
Disulfide bondi41 ↔ 56
Disulfide bondi51 ↔ 68

Keywords - PTMi

Disulfide bond

Proteomic databases

MaxQBiP04155.
PaxDbiP04155.
PeptideAtlasiP04155.
PRIDEiP04155.

Expressioni

Tissue specificityi

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).7 Publications

Gene expression databases

BgeeiP04155.
CleanExiHS_TFF1.
GenevestigatoriP04155.

Organism-specific databases

HPAiCAB002170.
HPA003425.

Interactioni

Subunit structurei

Heterodimer with GKN2; disulfide linked.

Binary interactionsi

WithEntry#Exp.IntActNotes
BTN3A1O004813EBI-743871,EBI-2809309
BTNL8Q6UX413EBI-743871,EBI-4314379
CD300LDQ6UXZ33EBI-743871,EBI-4314468
FCRL4Q96PJ53EBI-743871,EBI-4314687
SIGLEC8Q9NYZ43EBI-743871,EBI-4314991

Protein-protein interaction databases

BioGridi112889. 16 interactions.
IntActiP04155. 7 interactions.
MINTiMINT-1461530.
STRINGi9606.ENSP00000291527.

Structurei

Secondary structure

1
84
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi28 – 303
Turni35 – 373
Beta strandi40 – 423
Helixi48 – 525
Turni53 – 553
Beta strandi61 – 655
Beta strandi67 – 693
Beta strandi72 – 743
Beta strandi79 – 824

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1HI7NMR-A/B25-84[»]
1PS2NMR-A25-84[»]
ProteinModelPortaliP04155.
SMRiP04155. Positions 25-84.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP04155.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini29 – 7244P-typePROSITE-ProRule annotationAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi79 – 835Glu-rich (acidic)

Sequence similaritiesi

Contains 1 P-type (trefoil) domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG46001.
GeneTreeiENSGT00390000000115.
HOGENOMiHOG000121778.
HOVERGENiHBG004364.
InParanoidiP04155.
OMAiPEEECEF.
OrthoDBiEOG70W3GT.
PhylomeDBiP04155.
TreeFamiTF336092.

Family and domain databases

Gene3Di4.10.110.10. 1 hit.
InterProiIPR000519. P_trefoil.
IPR017994. P_trefoil_chordata.
IPR017957. P_trefoil_CS.
IPR028824. TFF1.
[Graphical view]
PANTHERiPTHR13826:SF15. PTHR13826:SF15. 1 hit.
PfamiPF00088. Trefoil. 1 hit.
[Graphical view]
PRINTSiPR00680. PTREFOIL.
SMARTiSM00018. PD. 1 hit.
[Graphical view]
SUPFAMiSSF57492. SSF57492. 1 hit.
PROSITEiPS00025. P_TREFOIL_1. 1 hit.
PS51448. P_TREFOIL_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P04155-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MATMENKVIC ALVLVSMLAL GTLAEAQTET CTVAPRERQN CGFPGVTPSQ
60 70 80
CANKGCCFDD TVRGVPWCFY PNTIDVPPEE ECEF
Length:84
Mass (Da):9,150
Last modified:November 1, 1986 - v1
Checksum:i65198523BAD6EBC7
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti22 – 221T → I.
Corresponds to variant rs34795821 [ dbSNP | Ensembl ].
VAR_053563
Natural varianti32 – 321T → I in a gastric carcinoma sample; somatic mutation. 1 Publication
VAR_015281
Natural varianti32 – 321T → K in a gastric carcinoma sample; somatic mutation. 1 Publication
VAR_015282
Natural varianti34 – 341A → 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. 2 Publications
VAR_015283
Natural varianti37 – 371E → 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. 2 Publications
VAR_015284
Natural varianti46 – 461V → I in a gastric adenoma sample; somatic mutation. 1 Publication
VAR_015285
Natural varianti55 – 551G → V in a gastric carcinoma sample; somatic mutation. 1 Publication
VAR_015286

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSiCCDS13685.1.
PIRiA26667.
RefSeqiNP_003216.1. NM_003225.2.
UniGeneiHs.162807.

Genome annotation databases

EnsembliENST00000291527; ENSP00000291527; ENSG00000160182.
GeneIDi7031.
KEGGihsa:7031.
UCSCiuc002zax.1. human.

Polymorphism databases

DMDMi131127.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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 .
CCDSi CCDS13685.1.
PIRi A26667.
RefSeqi NP_003216.1. NM_003225.2.
UniGenei Hs.162807.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1HI7 NMR - A/B 25-84 [» ]
1PS2 NMR - A 25-84 [» ]
ProteinModelPortali P04155.
SMRi P04155. Positions 25-84.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 112889. 16 interactions.
IntActi P04155. 7 interactions.
MINTi MINT-1461530.
STRINGi 9606.ENSP00000291527.

Polymorphism databases

DMDMi 131127.

Proteomic databases

MaxQBi P04155.
PaxDbi P04155.
PeptideAtlasi P04155.
PRIDEi P04155.

Protocols and materials databases

DNASUi 7031.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000291527 ; ENSP00000291527 ; ENSG00000160182 .
GeneIDi 7031.
KEGGi hsa:7031.
UCSCi uc002zax.1. human.

Organism-specific databases

CTDi 7031.
GeneCardsi GC21M043782.
HGNCi HGNC:11755. TFF1.
HPAi CAB002170.
HPA003425.
MIMi 113710. gene.
neXtProti NX_P04155.
PharmGKBi PA36470.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG46001.
GeneTreei ENSGT00390000000115.
HOGENOMi HOG000121778.
HOVERGENi HBG004364.
InParanoidi P04155.
OMAi PEEECEF.
OrthoDBi EOG70W3GT.
PhylomeDBi P04155.
TreeFami TF336092.

Miscellaneous databases

ChiTaRSi TFF1. human.
EvolutionaryTracei P04155.
GeneWikii Trefoil_factor_1.
GenomeRNAii 7031.
NextBioi 27469.
PROi P04155.
SOURCEi Search...

Gene expression databases

Bgeei P04155.
CleanExi HS_TFF1.
Genevestigatori P04155.

Family and domain databases

Gene3Di 4.10.110.10. 1 hit.
InterProi IPR000519. P_trefoil.
IPR017994. P_trefoil_chordata.
IPR017957. P_trefoil_CS.
IPR028824. TFF1.
[Graphical view ]
PANTHERi PTHR13826:SF15. PTHR13826:SF15. 1 hit.
Pfami PF00088. Trefoil. 1 hit.
[Graphical view ]
PRINTSi PR00680. PTREFOIL.
SMARTi SM00018. PD. 1 hit.
[Graphical view ]
SUPFAMi SSF57492. SSF57492. 1 hit.
PROSITEi PS00025. P_TREFOIL_1. 1 hit.
PS51448. P_TREFOIL_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. 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, 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. 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.

Entry informationi

Entry nameiTFF1_HUMAN
AccessioniPrimary (citable) accession number: P04155
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1986
Last sequence update: November 1, 1986
Last modified: October 29, 2014
This is version 154 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 21
    Human chromosome 21: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3