Alternative titles; symbols
HGNC Approved Gene Symbol: WFIKKN1
Cytogenetic location: 16p13.3 Genomic coordinates (GRCh38) : 16:630,985-634,117 (from NCBI)
By searching genomic databases for sequences containing an NTR metalloprotease inhibitor domain, followed by PCR of a lung cDNA library, Trexler et al. (2001) cloned WFIKKN. The deduced 548-amino acid protein contains an N-terminal secretory signal sequence, followed by a WAP 4-disulfide core domain, a cysteine-rich follistatin (136470) module of the Kazal type, an immunoglobulin (Ig) domain, 2 tandem Kunitz-type protease inhibitor modules, and an NTR domain near the C terminus. RT-PCR detected high expression of WFIKKN in pancreas, kidney, liver, placenta, and lung, and weak expression in brain, heart, and skeletal muscle. Trexler et al. (2001) also identified WFIKKN EST clones from cervical tumor and squamous cell lung carcinoma.
By Northern blot analysis of 16 adult mouse tissues, Lee and Lee (2013) detected Gasp2 expression in testis only. Gasp2 was expressed in several sites in embryonic mouse at 9.5 days postcoitum, including retina, otocyst, and neural tube.
Nagy et al. (2003) expressed the second Kunitz-type protease inhibitor domain of WFIKKN in E. coli and assayed its inhibitory specificity. They found that the recombinant protein inhibited trypsin (276000), but it had no inhibitory activity toward elastase (130120), chymotrypsin (see 118890), or several other proteases with trypsin-like specificity.
Lee and Lee (2013) found that mouse Gasp1 and Gasp2 blocked myostatin (601788) and GDF11 (603936) reporter gene activity following expression in CHO cells. They did not block activities of other TGF-beta family ligands. A C-terminal dimer of human GDF11 bound readily to a soluble form of its receptor ACVR2B (602730) in vitro, and binding was blocked in a dose-dependent manner by Gasp1 and Gasp2.
Trexler et al. (2001) determined that the WFIKKN1 gene contains 2 exons.
By genomic sequence analysis, Trexler et al. (2001) mapped the WFIKKN1 gene to chromosome 16p13.3.
Lee and Lee (2013) found that Gasp1 -/- and Gasp2 -/- mice were viable and fertile; however, many Gasp2 -/- mice showed posteriorly directed homeotic transformation throughout the axial skeleton. Skeletons of Gasp1/Gdf11 double-knockout mice were indistinguishable from skeletons of Gdf11 single-knockout mice, consistent with overactivity of Gdf11 in Gasp2 -/- mice. Gasp1 -/- and Gasp2 -/- mice also showed a small but significant decrease in muscle mass, predominantly in male mutants, with a shift in gastrocnemius fiber type from fast glycolytic type IIb fibers to fast oxidative type IIa fibers, suggesting that Gasp1 and Gasp2 inhibit myostatin. Gasp1 -/-, Gasp2 -/-, and double-knockout mice showed delayed muscle regeneration and blunted genetic response following cardiotoxin-induced injury.
Lee, Y.-S., Lee, S.-J. Regulation of GDF-11 and myostatin activity by GASP-1 and GASP-2. Proc. Nat. Acad. Sci. 110: E3713-E3722, 2013. Note: Electronic Article. [PubMed: 24019467] [Full Text: https://doi.org/10.1073/pnas.1309907110]
Nagy, A., Trexler, M., Patthy, L. Expression, purification and characterization of the second Kunitz-type protease inhibitor domain of the human WFIKKN protein. Europ. J. Biochem. 270: 2101-2107, 2003. [PubMed: 12709070] [Full Text: https://doi.org/10.1046/j.1432-1033.2003.03593.x]
Trexler, M., Banyai, L., Patthy, L. A human protein containing multiple types of protease-inhibitory modules. Proc. Nat. Acad. Sci. 98: 3705-3709, 2001. [PubMed: 11274388] [Full Text: https://doi.org/10.1073/pnas.061028398]