TCDB is operated by the Saier Lab Bioinformatics Group

9.B.453.  The Ninjurin (NINJ) Family 

Ninjurin 1 (NINJ1) protein of humans is a 152 aas protein with a hydrophilic N-terminal half and two TMSs in the C-terminal half of the protein.  It is a homophilic transmembrane adhesion molecule involved in various processes such as inflammation, cell death, axonal growth, cell chemotaxis and angiogenesis (Kayagaki et al. 2021). It promotes cell adhesion by mediating homophilic interactions via its extracellular N-terminal adhesion motif (N-NAM) (Kim et al. 2020) and is involved in the progression of the inflammatory stress by promoting cell-to-cell interactions between immune cells and endothelial cells (Toma et al. 2020). It may mediate plasma membrane rupture (PMR) and the diffusion of inflammatory factors. PMR is a characteristic of acinar cell injury in severe acute pancreatitis (SAP). Lee et al. 2023 have shown that NINJ1 is expressed in acinar cells, and this expression is significantly upregulated in sodium-taurocholate-induced SAP. The knockout of NINJ1 delays PMR in acinar cells and alleviates SAP. Moreover, NINJ1 expression is mediated by the Ca2+ concentration in acinar cells. Ca2+ overload drives mitochondrial stress to upregulate the P53/NINJ1 pathway, inducing PMR in acinar cells, and amlodipine, a Ca2+ channel inhibitor, can reduce the occurrence of PMR by decreasing the concentration of Ca2+. These results demonstrate the mechanism by which NINJ1 induces PMR in SAP acinar cells and provide a potential new target for treatment of SAP.

References associated with 9.B.453 family:

Kayagaki, N., O.S. Kornfeld, B.L. Lee, I.B. Stowe, K. O''Rourke, Q. Li, W. Sandoval, D. Yan, J. Kang, M. Xu, J. Zhang, W.P. Lee, B.S. McKenzie, G. Ulas, J. Payandeh, M. Roose-Girma, Z. Modrusan, R. Reja, M. Sagolla, J.D. Webster, V. Cho, T.D. Andrews, L.X. Morris, L.A. Miosge, C.C. Goodnow, E.M. Bertram, and V.M. Dixit. (2021). NINJ1 mediates plasma membrane rupture during lytic cell death. Nature 591: 131-136. 33472215
Kim, S.W., H.K. Lee, S.I. Seol, D. Davaanyam, H. Lee, and J.K. Lee. (2020). Ninjurin 1 dodecamer peptide containing the N-terminal adhesion motif (N-NAM) exerts proangiogenic effects in HUVECs and in the postischemic brain. Sci Rep 10: 16656. 33028854
Lee, C., G. Xin, F. Li, C. Wan, X. Yu, L. Feng, A. Wen, Y. Cao, and W. Huang. (2023). Calcium/P53/Ninjurin 1 Signaling Mediates Plasma Membrane Rupture of Acinar Cells in Severe Acute Pancreatitis. Int J Mol Sci 24:. 37511311
Toma, L., G.M. Sanda, M. Raileanu, C.S. Stancu, L.S. Niculescu, and A.V. Sima. (2020). Ninjurin-1 upregulated by TNFα receptor 1 stimulates monocyte adhesion to human TNFα-activated endothelial cells; benefic effects of amlodipine. Life Sci 249: 117518. 32147432