Granzyme B inhibitor. (updated: Sept. 12, 2018)
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
No sequence conservation computed yet.
Total structural coverage: 100%
No model available.
(right-click above to access to more options from the contextual menu)
The reference OMIM entry for this protein is 601799
Protease inhibitor 9, ovalbumin type; pi9
Cytoplasmic antiproteinase 3; cap3
Serpinb9
DESCRIPTION
PI9 belongs to the large superfamily of serine proteinase inhibitors (serpins), which bind to and inactivate serine proteinases. These interactions are involved in many cellular processes, including coagulation, fibrinolysis, complement fixation, matrix remodeling, and apoptosis (Sprecher et al., 1995).
CLONING
Sprecher et al. (1995) isolated PI8 (
601697) and PI9 cDNAs from a human placenta cDNA library. PI9 encodes a 374-amino acid polypeptide that shares more than 60% identity with PI6 (
173321). Northern blot analysis detected 2 PI9 transcripts of 3.4 and 4.4 kb that were most abundant in lung and placenta. In searching for serpins related to PI6, Sun et al. (1996) isolated and cloned PI9 from human bone marrow mRNA using a PCR cloning strategy. They confirmed that the sequence of PI9 is closely related to PI6 and the viral serpin CrmA. Sun et al. (1996) observed that PI9 was expressed in immune tissue, including lymphocytes, natural killer cell leukemia cell lines, and peripheral blood mononuclear cells. Fractionation experiments showed that PI9 is localized to the cytosol, in a separate subcellular compartment from granzyme B (
123910), with which it forms a complex. By immunohistochemical and Western blot analyses, Bladergroen et al. (2001) demonstrated cytoplasmic expression of the 42-kD PI9 protein in dendritic cell populations, but not macrophage populations, of lymphoid organs. B- and T-cell populations were variably positive in different lymphoid organs, and only endothelial cells expressed PI9 in nonlymphoid organs. Notably, PI9 expression was high in immunologically privileged sites, such as eye lens, testis, ovary, and placenta. Bladergroen et al. (2001) concluded that PI9 expression patterns are distinct from those of other OVA serpins, such as PI6 and PAI2 (
173390). They proposed that PI9 expression may be important for resistance to granzyme B-induced apoptosis, preserving vessel integrity, and maintaining immune privilege.
GENE FUNCTION
Sun et al. (1996) showed that PI9 forms an SDS-resistant complex with granzyme B, suggesting that these 2 proteins may form a physiologically significant serpin-serine proteinase interaction. PI9 was identified as an endogenous inhibitor of caspase-1 (
147678). Krieg et al. (2001) reported that PI9 mRNA and protein are rapidly and directly induced by estrogen in human liver cells. Using transient transfections to assay PI9 promoter truncations and mutations, they showed that this strong estrogen induction is mediated by a unique downstream estrogen responsive unit (ERU) approximately 200 nucleotides downstream of the transcription start site. They also demonstrated estrogen-dependent binding of ER to the cellular PI9 promoter. The ERU consists of an imperfect estrogen response element (ERE) palindrome immediately adjacent to a direct repeat containing two consensus ERE half-sites separated by 13 nucleotides (DR13). In transient transfections, all 4 of the ERE half-sites in the imperfect ERE and in the DR13 were important for estrogen inducibility. They concluded that a direct repeat can function with an imperfect ERE palindrome to confer estrogen inducibility on a native gene, which extends the repertoire of DNA sequences able to function as EREs. Barrie et al. (2004) noted that virally infected hepatocytes resist cytotoxic T-lymphocyte (CTL) or natural killer (NK) killing by perforin (PRF1;
170280)- and granzyme-dependent cytotoxic effector pat ...
More on the omim web site
Subscribe to this protein entry history
June 30, 2020: Protein entry updated
Automatic update: OMIM entry 601799 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).