Q07654 (TFF3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Trefoil factor 3

Alternative name(s):
Intestinal trefoil factor
Short name=hITF
Polypeptide P1.B
Short name=hP1.B

Gene names

Name:	TFF3
Synonyms:	ITF, TFI

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	80 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	Involved in the maintenance and repair of the intestinal mucosa. Promotes the mobility of epithelial cells in healing processes (motogen). Ref.11
Subunit structure	Monomer. Homodimer; disulfide-linked. Ref.13
Subcellular location	Secreted › extracellular space › extracellular matrix › apical lamina Ref.8.
Tissue specificity	Expressed in goblet cells of the intestines and colon (at protein level). Expressed by goblet cells of small and large intestinal epithelia and also by the uterus. Ref.1 Ref.8
Sequence similarities	Contains 1 P-type (trefoil) domain.
Sequence caution	The sequence AAH17859.1 differs from that shown. Reason: Erroneous initiation. The sequence AAL28111.1 differs from that shown. Reason: Erroneous initiation. The sequence BAA95531.1 differs from that shown. Reason: Erroneous initiation. The sequence BAB13731.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Cellular component	Extracellular matrix Secreted
Coding sequence diversity	Alternative splicing
Domain	Signal
PTM	Disulfide bond
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	defense response Traceable author statement Ref.8. Source: ProtInc digestion Traceable author statement Ref.8PubMed 9043862. Source: ProtInc
Cellular_component	apical lamina of hyaline layer Inferred from electronic annotation. Source: UniProtKB-SubCell extracellular region Traceable author statement Ref.8. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q07654-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q07654-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MKRVLSCVPEPTVVM

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 21

21

Ref.10

Chain

22 – 80

59

Trefoil factor 3

PRO_0000023465

Regions

Domain

30 – 73

44

P-type

Amino acid modifications

Disulfide bond

32 ↔ 58

By similarity

Disulfide bond

42 ↔ 57

By similarity

Disulfide bond

52 ↔ 69

By similarity

Disulfide bond

78

Interchain

Natural variations

Alternative sequence

1

1

M → MKRVLSCVPEPTVVM in isoform 2.

VSP_045254

Experimental info

Sequence conflict

74 – 76

3

QEA → TRKT in AAA36766. Ref.8

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

80

Helix Strand Turn

Details...

Helix

30 – 32

3

Beta strand

36 – 39

4

Turn

49 – 54

6

Beta strand

55 – 58

4

Beta strand

68 – 70

3

Helix

74 – 76

3

Turn

77 – 79

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 1, 1994. Version 1. Checksum: 8E117A58C0342013	FASTA	80	8,641
	10 20 30 40 50 60 MAARALCMLG LVLALLSSSS AEEYVGLSAN QCAVPAKDRV DCGYPHVTPK ECNNRGCCFD 70 80 SRIPGVPWCF KPLQEAECTF
	Isoform 2 [UniParc]. Checksum: 02276443AEE4CEA5	FASTA	94	10,181
	10 20 30 40 50 60 MKRVLSCVPE PTVVMAARAL CMLGLVLALL SSSSAEEYVG LSANQCAVPA KDRVDCGYPH 70 80 90 VTPKECNNRG CCFDSRIPGV PWCFKPLQEA ECTF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"hP1.B, a human P-domain peptide homologous with rat intestinal trefoil factor, is expressed also in the ulcer-associated cell lineage and the uterus." Hauser F., Poulsom R., Chinery R., Rogers L.A., Hanby A.M., Wright N.A., Hoffmann W. Proc. Natl. Acad. Sci. U.S.A. 90:6961-6965(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY. Tissue: Small intestine.
[2]	"The three human trefoil genes TFF1, TFF2, and TFF3 are located within a region of 55 kb on chromosome 21q22.3." Seib T., Blin N., Hilgert K., Seifert M., Theisinger B., Engel M., Dooley S., Zang K.D., Welter C. Genomics 40:200-202(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"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].
[4]	"Transcriptome analysis of human gastric cancer." Oh J.H., Yang J.O., Hahn Y., Kim M.R., Byun S.S., Jeon Y.J., Kim J.M., Song K.S., Noh S.M., Kim S., Yoo H.S., Kim Y.S., Kim N.S. Mamm. Genome 16:942-954(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[5]	"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].
[6]	"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] (ISOFORM 1). Tissue: Lung.
[7]	"mRNA 5' region sequence incompleteness: a potential source of systematic errors in translation initiation codon assignment in human mRNAs." Casadei R., Strippoli P., D'Addabbo P., Canaider S., Lenzi L., Vitale L., Giannone S., Frabetti F., Facchin F., Carinci P., Zannotti M. Gene 321:185-193(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-51 (ISOFORM 1). Tissue: Heart.
[8]	"Identification of human intestinal trefoil factor. Goblet cell-specific expression of a peptide targeted for apical secretion." Podolsky D.K., Lynch-Devaney K., Stow J.L., Oates P., Murgue B., Debeaumont M., Sands B.E., Mahida Y.R. J. Biol. Chem. 268:6694-6702(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 8-80 (ISOFORM 1), SUBCELLULAR LOCATION, TISSUE SPECIFICITY. Tissue: Colon.
[9]	Erratum Podolsky D.K., Lynch-Devaney K., Stow J.L., Oates P., Murgue B., De-Beaumont M., Sands B.E., Mahida Y.R. J. Biol. Chem. 268:12230-12230(1993)
[10]	"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 22-36.
[11]	"Trefoil factor family-peptides promote migration of human bronchial epithelial cells: synergistic effect with epidermal growth factor." Oertel M., Graness A., Thim L., Buhling F., Kalbacher H., Hoffmann W. Am. J. Respir. Cell Mol. Biol. 25:418-424(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[12]	"Incorporation of mannose and glucose into prenylphosphate sugars in isolated human platelet membranes." De Luca S. Biochim. Biophys. Acta 498:341-348(1977) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 22-80.
[13]	"Solution structure of the disulfide-linked dimer of human intestinal trefoil factor (TFF3): the intermolecular orientation and interactions are markedly different from those of other dimeric trefoil proteins." Muskett F.W., May F.E., Westley B.R., Feeney J. Biochemistry 42:15139-15147(2003) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 22-80, SUBUNIT.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

L15203 mRNA. Translation: AAA59981.1.
U25657, U25654, U25656 Genomic DNA. Translation: AAA83628.1.
AB038162 Genomic DNA. Translation: BAB13731.1. Different initiation.
BM743413 mRNA. No translation available.
AP001746 Genomic DNA. Translation: BAA95531.1. Different initiation.
BC017859 mRNA. Translation: AAH17859.1. Different initiation.
AF432265 mRNA. Translation: AAL28111.1. Different initiation.
L08044 mRNA. Translation: AAA36766.1.

IPI

IPI00018909.

PIR

A48284.

RefSeq

NP_003217.3. NM_003226.3.

UniGene

Hs.82961.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1E9T	NMR	-	A	22-80	[»]
1PE3	NMR	-	1/2	22-80	[»]

ProteinModelPortal

Q07654.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000291525.

Polymorphism databases

DMDM

585328.

Proteomic databases

PaxDb

Q07654.

PRIDE

Q07654.

Protocols and materials databases

DNASU

7033.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000518498; ENSP00000430690; ENSG00000160180.

GeneID

7033.

KEGG

hsa:7033.

Organism-specific databases

CTD

7033.

GeneCards

GC21M043726.

H-InvDB

HIX0016137.

HGNC

HGNC:11757. TFF3.

HPA

CAB020681.

MIM

600633. gene.

neXtProt

NX_Q07654.

PharmGKB

PA36472.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG79314.

HOGENOM

HOG000121778.

HOVERGEN

HBG004364.

OrthoDB

EOG4907BN.

Enzyme and pathway databases

Pathway_Interaction_DB

hif1_tfpathway. HIF-1-alpha transcription factor network.
il4_2pathway. IL4-mediated signaling events.

Gene expression databases

ArrayExpress

Q07654.

Bgee

Q07654.

CleanEx

HS_TFF3.

Genevestigator

Q07654.

GermOnline

ENSG00000160180. 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

EvolutionaryTrace

Q07654.

GenomeRNAi

7033.

NextBio

27477.

SOURCE

Search...

Entry information

Entry name

TFF3_HUMAN

Accession

Primary (citable) accession number: Q07654
Secondary accession number(s): E9PBB5, Q96NX0, Q9UDA5

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1994
Last sequence update:	October 1, 1994
Last modified:	May 1, 2013
This is version 122 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.