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:
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.
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.
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:.
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.
Examples:
TC#	Name	Organismal Type	Example
9.B.453.1.1	Ninjurin 1, NINJ1, of 152 aas and 2 C-terminal TMSs with an N-terminal hydrophilic adhesin domain (see family descirption for details of its function).		NINJ1 of Homo sapiens

9.B.453.1.10	Ninjurin-2, NINJ-2-like of 171 aas and 2 C-terminal TMSs.		NINJ2 of Saccoglossus kowalevskii

9.B.453.1.2	Ninjurin 2 isoform X1 of 127 aas and 2 C-terminal TMSs.		NINJ2 of Danio rerio

9.B.453.1.3	Ninjurin-A isoform X2 of 300 aas with two C-terminal TMSs.		NINJ-A of Nymphalis io

9.B.453.1.4	Ninjurin C, isoform D of 138 aas with 2 or 3 TMSs.		NINJ-C of Drosophila melanogaster

9.B.453.1.5	Ninjurin B, NINJ-B, of 181 aas and 2 or 3 C-terminal TMSs		NINJ-B of Drosophila melanogaster

9.B.453.1.6	Uncharacterized protein of 197 aas and 3 C-terminal TMSs.		UP of Chironomus riparius

9.B.453.1.7	Ninjurin-1-like isoform X1 of 196 aas and 3 C-terminal TMSs.		NINJ1 of Paramacrobiotus metropolitanus

9.B.453.1.8	TMEM55 of 243 aas and 3 TMSs with 2 centrally located and 1 at the C-terminus.		TMEM55 of Mytilus edulis

9.B.453.1.9	Uncharacterized protein of 504 aas and 3 N-terminal TMSs, the only region that shows sequence similarity with other members of the family in TCDB.		UP of Daphnia pulicaria