NINJ1
The ninjurin protein is upregulated after nerve injury both in dorsal root ganglion neurons and in Schwann cells (Araki and Milbrandt, 1996 [PubMed 8780658]). It demonstrates properties of a homophilic adhesion molecule and promotes neurite outgrowth from primary cultured dorsal root ganglion neurons.
Function
Ninjurin-1
Homophilic transmembrane adhesion molecule involved in various processes such as inflammation, cell death, axonal growth, cell chemotaxis and angiogenesis (PubMed:8780658, PubMed:9261151, PubMed:33472215).
Promotes cell adhesion by mediating homophilic interactions via its extracellular N-terminal adhesion motif (N-NAM) (PubMed:33028854).
Involved in the progression of the inflammatory stress by promoting cell-to-cell interactions between immune cells and endothelial cells (PubMed:22162058, PubMed:26677008, PubMed:32147432).
Involved in leukocyte migration during inflammation by promoting transendothelial migration of macrophages via homotypic binding (By similarity).
Promotes the migration of monocytes across the brain endothelium to central nervous system inflammatory lesions (PubMed:22162058).
Acts as a regulator of Toll-like receptor 4 (TLR4) signaling triggered by lipopolysaccharide (LPS) during systemic inflammation; directly binds LPS (PubMed:26677008).
Acts as a mediator of both programmed and necrotic cell death (PubMed:33472215).
Plays a key role in the induction of plasma membrane rupture during programmed and necrotic cell death: oligomerizes in response to death stimuli to mediate plasma membrane rupture (cytolysis), leading to release intracellular molecules named damage-associated molecular patterns (DAMPs) that propagate the inflammatory response (PubMed:33472215).
Plays a role in nerve regeneration by promoting maturation of Schwann cells (PubMed:8780658, PubMed:9261151).
Acts as a regulator of angiogenesis (PubMed:33028854).
Promotes the formation of new vessels by mediating the interaction between capillary pericyte cells and endothelial cells (By similarity).
Promotes osteoclasts development by enhancing the survival of prefusion osteoclasts (By similarity).
Also involved in striated muscle growth and differentiation (By similarity).
Secreted ninjurin-1
Secreted form generated by cleavage, which has chemotactic activity (By similarity).
Acts as an anti-inflammatory mediator by promoting monocyte recruitment, thereby ameliorating atherosclerosis (PubMed:32883094).
Biological Process
AngiogenesisIEA:UniProtKB-KW
Cell adhesionManual Assertion Based On ExperimentIDA:UniProtKB
CytolysisManual Assertion Based On ExperimentIDA:UniProtKB
Heterotypic cell-cell adhesionISS:UniProtKB
Inflammatory responseIDA:UniProtKB
Leukocyte chemotaxis involved in inflammatory responseManual Assertion Based On ExperimentIDA:UniProtKB
Muscle cell differentiationISS:UniProtKB
Necrotic cell deathManual Assertion Based On ExperimentIDA:UniProtKB
Nervous system developmentManual Assertion Based On ExperimentTAS:ProtInc
Positive regulation of angiogenesisManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of inflammatory responseManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of toll-like receptor 4 signaling pathwayISS:UniProtKB
Programmed cell deathManual Assertion Based On ExperimentIDA:UniProtKB
Protein homooligomerizationManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of monocyte chemotaxisIDA:UniProtKB
Tissue regenerationIEA:InterPro
Cellular Location
Ninjurin-1
Cell membrane
Cell junction, synapse, synaptic cell membrane
Secreted ninjurin-1
Secreted
Topology
Extracellular: 1-80
Helical: 81-101
Cytoplasmic: 102-120
Helical: 121-141
Extracellular: 142-152
PTM
Ninjurin-1
Cleaved by MMP9 protease to generate the Secreted ninjurin-1 form.
Ninjurin-1
N-linked glycosylation is required for homooligomerization.