Alternative titles; symbols
HGNC Approved Gene Symbol: TFF2
Cytogenetic location: 21q22.3 Genomic coordinates (GRCh38): 21:42,346,357-42,350,994 (from NCBI)
Spasmolytic protein, initially identified as a contaminant in commercial insulin stocks prepared from porcine pancreatic extracts, is an inhibitor of spasmolytic activity and gastric acid secretion in the pig. Its human homolog exhibits homology to the pS2 protein (TFF1; 113710), an estrogen-dependent breast cancer marker and a member of the trefoil protein family. Trefoil proteins are small secretory proteins characterized by a 40-amino acid trefoil motif that contains 3 conserved disulfide bonds. The 3 intrachain disulfide bonds form the trefoil motif (TFF domain). They serve to maintain or repair the epithelial mucosa, and promote cell migration. They are predominantly found in gastrointestinal tissues, and are upregulated around areas of epithelial damage and in meta- and neoplasia. See also TFF3 (600633).
Tomasetto et al. (1990) cloned a pig SP cDNA using an oligonucleotide probe based on the protein sequence. The porcine gene was used to clone human and mouse SP cDNAs from stomach cDNA libraries. The human SP cDNA encodes a predicted 129-amino acid protein. Northern blot analysis showed that human SP is expressed exclusively in normal stomach epithelium; unlike pS2, it is not expressed in breast carcinoma.
Hanby et al. (1993) found that SP mRNA colocalizes with pS2 peptide and mRNA in the gastric foveolar and surface epithelium throughout the stomach. They stated that the distribution of SP and pS2 suggests involvement in repair-enhancing mechanisms.
Itoh et al. (1996) examined the expression of rat SP, rat pS2, and rat intestinal trefoil factor (Itf, or Tff3) during the course of acetic acid-induced colitis. They detected pS2 mRNA during the acute phase of colitis but not during recovery or in normal controls. Itf was downregulated during the acute phase of colitis and then upregulated during recovery. SP mRNA was not detected throughout the course of the induced colitis.
Seib et al. (1997) found that the SP gene consists of 4 exons spanning 5.1 kb, with exons 2 and 3 encoding 1 trefoil domain each.
By in situ hybridization, Tomasetto et al. (1992) assigned the SML1 gene to 21q22.3. Using pulsed field gel electrophoresis, they found SML1 to be within 230 kb of the BCEI (TFF1) gene. Theisinger et al. (1992) mapped the SML1 gene to chromosome 21 by Southern blot analysis of genomic DNAs from a panel of human-rodent somatic cell hybrids carrying different complements of human chromosomes.
Seib et al. (1997) found that the SML1 gene (SP) is clustered with the TFF1 and TFF3 genes within a 55-kb region, suggesting that these genes have evolved from a common ancestor gene via duplication.
May and Westley (1997) determined that the physical distance between the TFF1 and TFF2 genes is only 12.5 kb. The TFF1 and TFF2 genes have similar patterns of expression, suggesting that they may share common regulatory elements.
The TFF1, TFF2, and TFF3 genes are clustered in 21q22.3. TFF2 is the only gene encoding 2 TFF-domains on separate exons. Between these 2 exons, in intron 2, Kayademir et al. (1998) identified a novel 25-bp sequence that is tandemly repeated approximately 48 times, and is unique in the human genome. A diallelic polymorphism with a second allele comprising approximately 53 repeat units was present in some individuals. Kayademir et al. (1998) cloned both alleles on BAC recombinants. In 78 Caucasians, they found allele frequencies of 0.85 and 0.15, respectively, representing a frequency of heterozygosity of 26%. Ape and monkey species exhibited homologous repeats of shorter total array length, whereas none is found in other mammals.
Hanby, A. M., Poulsom, R., Singh, S., Elia, G., Jeffery, R. E., Wright, N. A. Spasmolytic polypeptide is a major antral peptide: distribution of the trefoil peptides human spasmolytic polypeptide and pS2 in the stomach. Gastroenterology 105: 1110-1116, 1993. [PubMed: 8405856] [Full Text: https://doi.org/10.1016/0016-5085(93)90956-d]
Itoh, H., Tomita, M., Uchino, H., Kobayashi, T., Kataoka, H., Sekiya, R., Nawa, Y. cDNA cloning of rat pS2 peptide and expression of trefoil peptides in acetic acid-induced colitis. Biochem. J. 318: 939-944, 1996. [PubMed: 8836141] [Full Text: https://doi.org/10.1042/bj3180939]
Kayademir, T., dos Santos Silva, E., Pusch, C., Beck, S., Machado, J.-C., Gott, P. A novel 25 bp tandem repeat within the human trefoil peptide gene TFF2 in 21q22.3: polymorphism and mammalian evolution. Europ. J. Hum. Genet. 6: 121-128, 1998. [PubMed: 9781055] [Full Text: https://doi.org/10.1038/sj.ejhg.5200166]
May, F. E. B., Westley, B. R. Close physical linkage of the genes encoding the pNR-2/pS2 protein and human spasmolytic protein (hSP). Hum. Genet. 99: 303-307, 1997. [PubMed: 9050913] [Full Text: https://doi.org/10.1007/s004390050362]
Seib, T., Blin, N., Hilgert, K., Seifert, M., Theisinger, B., Engel, M., Dooley, S., Zang, K.-D., Welter, C. The three human trefoil genes TFF1, TFF2, and TFF3 are located within a region of 55 kb on chromosome 21q22.3. Genomics 40: 200-202, 1997. [PubMed: 9070946] [Full Text: https://doi.org/10.1006/geno.1996.4511]
Theisinger, B., Welter, C., Grzeschik, K.-H., Blin, N. Assignment of the gene for human spasmolytic protein (hSP/SML1) to chromosome 21. Hum. Genet. 89: 681-682, 1992. [PubMed: 1511987] [Full Text: https://doi.org/10.1007/BF00221962]
Tomasetto, C., Rio, M.-C., Gautier, C., Wolf, C., Hareuveni, M., Chambon, P., Lathe, R. hSP, the domain-duplicated homolog of pS2 protein, is co-expressed with pS2 in stomach but not in breast carcinoma. EMBO J. 9: 407-414, 1990. [PubMed: 2303034] [Full Text: https://doi.org/10.1002/j.1460-2075.1990.tb08125.x]
Tomasetto, C., Rockel, N., Mattei, M. G., Fujita, R., Rio, M. C. The gene encoding the human spasmolytic protein (SML1/hSP) is in 21q22.3, physically linked to the homologous breast cancer marker gene BCEI/pS2. Genomics 13: 1328-1330, 1992. [PubMed: 1505966] [Full Text: https://doi.org/10.1016/0888-7543(92)90059-2]