HGNC Approved Gene Symbol: ITIH5
Cytogenetic location: 10p14 Genomic coordinates (GRCh38): 10:7,559,270-7,666,966 (from NCBI)
The inter-alpha-trypsin inhibitors (ITI) are a family of structurally related plasma serine protease inhibitors involved in extracellular matrix stabilization and in prevention of tumor metastasis. The ITI family contains multiple proteins made up of a light chain (see 176870) and a variable number of heavy chains (Salier et al., 1987; Himmelfarb et al., 2004).
Using an EST-based bioinformatics approach, Himmelfarb et al. (2004) identified a novel gene, ITIH5, that is differentially expressed in human breast tumor tissue. They cloned the complete cDNA sequence from mammary gland tissue. ITIH5 encodes a deduced 942-amino acid protein that contains 2 conserved ITIH domains: a vault inter-alpha-trypsin (VIT) domain and a von Willebrand type A (VWA) domain. ITIH5 also contains a putative 18-amino acid signal peptide and a conserved cleavage site in the C-terminal segment, containing a multicopper oxidase domain, which is cleaved during chain assembly. Northern blot analysis detected expression of a 3.6-kb ITIH5 transcript at highest levels in placenta, at less abundant levels in mammary gland and ovary, and at barely detectable levels in all other tissues tested. Real-time PCR confirmed the predominant expression of ITIH5 in placenta.
By dot-blot hybridization and real-time PCR, Himmelfarb et al. (2004) found that the expression of ITIH5 was significantly downregulated in breast tumor as compared to normal breast samples. ITIH5 expression was undetected by real-time PCR in all breast carcinoma and epithelial cell lines examined. In situ hybridization revealed expression of ITIH5 mRNA in the epithelial cells of normal mammary gland. Expression was detectable in lobules and ducts but not in the stromal cells. ITIH5 mRNA was not detectable or only very weakly expressed in invasive ductal carcinoma. Himmelfarb et al. (2004) suggested that ITIH5 may play a role in breast tumorigenesis.
Himmelfarb et al. (2004) determined that the ITIH5 gene contains 14 exons and spans 82.7 kb.
By sequence analysis, Himmelfarb et al. (2004) mapped the ITIH5 gene to chromosome 10p15, separated from the ITIH2 gene (146640) by 36.4 kb.
Himmelfarb, M., Klopocki, E., Grube, S., Staub, E., Klaman, I., Hinzmann, B., Kristiansen, G., Rosenthal, A., Durst, M., Dahl, E. ITIH5, a novel member of the inter-alpha-trypsin inhibitor heavy chain family is downregulated in breast cancer. Cancer Lett. 204: 69-77, 2004. [PubMed: 14744536] [Full Text: https://doi.org/10.1016/j.canlet.2003.09.011]
Salier, J. P., Diarra-Mehrpour, M., Sesboue, R., Bourguignon, J., Benarous, R., Ohkubo, I., Kurachi, S., Kurachi, K., Martin, J. P. Isolation and characterization of cDNAs encoding the heavy chain of human inter-alpha-trypsin inhibitor (IATI): unambiguous evidence for multipolypeptide chain structure of IATI. Proc. Nat. Acad. Sci. 84: 8272-8276, 1987. [PubMed: 2446322] [Full Text: https://doi.org/10.1073/pnas.84.23.8272]