Ninj1
entrez
18081
canonical
uniprot
O70131
canonical
ensembl
ENSMUSG00000037966
resolver
ensp
ENSMUSP00000036740
resolver
ensp
ENSMUSP00000114130
resolver
enst
ENSMUST00000049022
resolver
enst
ENSMUST00000120733
resolver
genesymbol
Ninj1
resolver
uniprot
D3YW25
resolver
uniprot
Q3TXT8
resolver
uniprot_entry
D3YW25_MOUSE
resolver
uniprot_entry
NINJ1_MOUSE
resolver
uniprot_entry
Q3TXT8_MOUSE
resolver
activity_regulation
ACTIVITY REGULATION: [Ninjurin-1]: In response to death stimuli, homooligomerizes and disrupts membrane integrity by introducing the hydrophilic faces of alpha1 and alpha2 helices into the hydrophobic membrane (By similarity). Homooligomerization and ability to mediate plasma membrane rupture is inhibited by glycine; it is unclear whether glycine directly or indirectly inhibits homooligomerization (PubMed:36468682). In normal conditions, NINJ1 is autoinhibited via formation of a homodimer: in the inactive homodimer, the alpha1 and alpha2 helices (residues 44-74) form a single transmembrane region without a kink, in which hydrophilic faces of alpha1 and alpha2 helices are sequestered (PubMed:39476863). {ECO:0000250|UniProtKB:Q92982, ECO:0000269|PubMed:36468682, ECO:0000269|PubMed:39476863}.
uniprot
proteins
amino_acid_sequence
MESGTEEYELNGDLRPGSPGSPDALPPRWGLRNRPINVNHYANKKSAAESMLDIALLMANASQLKAVVEQGNDFAFFVPLVVLISISLVLQIGVGVLLIFLVKYDLNNPAKHAKLDFLNNLATGLVFIIVVVNIFITAFGVQKPVMDVAPRQ
uniprot
proteins
function
FUNCTION: [Ninjurin-1]: Effector of various programmed cell death, such as pyroptosis and necroptosis, which mediates plasma membrane rupture (cytolysis) (PubMed:19557008, PubMed:33472215, PubMed:36468682, PubMed:37196676, PubMed:37198476, PubMed:39476863). Oligomerizes in response to death stimuli and forms ring-like structures on the plasma membrane: acts by cutting and shedding membrane disks, like a cookie cutter, leading to membrane damage and loss that cannot be repaired by the cell (PubMed:33472215, PubMed:37196676, PubMed:37198476). Plasma membrane rupture leads to release intracellular molecules named damage-associated molecular patterns (DAMPs) that propagate the inflammatory response (PubMed:33472215, PubMed:37196676, PubMed:37198476). Mechanistically, mediates plasma membrane rupture by introducing hydrophilic faces of 2 alpha helices into the hydrophobic membrane (PubMed:37198476). Induces plasma membrane rupture downstream of Gasdermin (GSDMA, GSDMB, GSDMC, GSDMD, or GSDME) or MLKL during pyroptosis or necroptosis, respectively (PubMed:33472215, PubMed:37196676, PubMed:37198476). Acts as an effector of PANoptosis downstream of CASP1, CASP4, CASP8 and RIPK3 (PubMed:38409108). Also induces plasma membrane rupture in response to cell swelling caused by osmotic stress and ferroptosis downstream of lipid peroxidation (PubMed:37980412, PubMed:38396301). Acts as a regulator of Toll-like receptor 4 (TLR4) signaling triggered by lipopolysaccharide (LPS) during systemic inflammation; directly binds LPS (PubMed:25860173). Involved in leukocyte migration during inflammation by promoting transendothelial migration of macrophages via homotypic binding (PubMed:24917672). Promotes the migration of monocytes across the brain endothelium to central nervous system inflammatory lesions (By similarity). Also acts as a homophilic transmembrane adhesion molecule involved in various processes such as axonal growth, cell chemotaxis and angiogenesis (PubMed:24347169, PubMed:24917672, PubMed:31526566). Promotes cell adhesion by mediating homophilic interactions via its extracellular N-terminal adhesion motif (N-NAM) (PubMed:24917672, PubMed:30510259). Involved in the progression of the inflammatory stress by promoting cell-to-cell interactions between immune cells and endothelial cells (PubMed:24917672, PubMed:30510259). Plays a role in nerve regeneration by promoting maturation of Schwann cells (PubMed:31526566). Acts as a regulator of angiogenesis (PubMed:25766274, PubMed:30354207). Promotes the formation of new vessels by mediating the interaction between capillary pericyte cells and endothelial cells (PubMed:25766274, PubMed:30354207). Also mediates vascular functions in penile tissue as well as vascular formation (PubMed:24979788). Promotes osteoclasts development by enhancing the survival of prefusion osteoclasts (PubMed:30700695). Also involved in striated muscle growth and differentiation (PubMed:31091274). Also involved in cell senescence in a p53/TP53 manner, possibly by acting as an indirect regulator of p53/TP53 mRNA translation (PubMed:23690620, PubMed:29073078). {ECO:0000250|UniProtKB:Q92982, ECO:0000269|PubMed:19557008, ECO:0000269|PubMed:23690620, ECO:0000269|PubMed:24347169, ECO:0000269|PubMed:24917672, ECO:0000269|PubMed:24979788, ECO:0000269|PubMed:25766274, ECO:0000269|PubMed:25860173, ECO:0000269|PubMed:29073078, ECO:0000269|PubMed:30354207, ECO:0000269|PubMed:30510259, ECO:0000269|PubMed:30700695, ECO:0000269|PubMed:31091274, ECO:0000269|PubMed:31526566, ECO:0000269|PubMed:33472215, ECO:0000269|PubMed:36468682, ECO:0000269|PubMed:37196676, ECO:0000269|PubMed:37198476, ECO:0000269|PubMed:37980412, ECO:0000269|PubMed:38396301, ECO:0000269|PubMed:38409108, ECO:0000269|PubMed:39476863}.; FUNCTION: [Secreted ninjurin-1]: Secreted form generated by cleavage, which has chemotactic activity (PubMed:23142597). Acts as an anti-inflammatory mediator by promoting monocyte recruitment, thereby ameliorating atherosclerosis (PubMed:32883094). {ECO:0000269|PubMed:23142597, ECO:0000269|PubMed:32883094}.
uniprot
proteins
mass_dalton
16555
uniprot
proteins
mutagenesis
MUTAGEN 42; /note="A->W: Disrupts the face-to-face homodimer, leading to increased ability to mediate plasma membrane rupture (cytolysis)."; /evidence="ECO:0000269|PubMed:39476863"; MUTAGEN 43..46; /note="NKKS->AAAA: Abolished ability to induce plasma membrane rupture in response to death stimuli."; /evidence="ECO:0000269|PubMed:33472215"; MUTAGEN 45; /note="K->Q: Forms an inactive homodimer; strongly reduced ability to homooligomerize and mediate plasma membrane rupture (cytolysis)."; /evidence="ECO:0000269|PubMed:39476863"; MUTAGEN 45; /note="K->R: Disrupts the face-to-face homodimer, leading to increased ability to mediate plasma membrane rupture (cytolysis)."; /evidence="ECO:0000269|PubMed:39476863"; MUTAGEN 46; /note="S->A: Disrupts the face-to-face homodimer, leading to increased ability to mediate plasma membrane rupture (cytolysis)."; /evidence="ECO:0000269|PubMed:39476863"; MUTAGEN 48; /note="A->S: Disrupts the face-to-face Decreased ability to mediate plasma membrane rupture (cytolysis)."; /evidence="ECO:0000269|PubMed:39476863"; MUTAGEN 52; /note="L->N: Disrupts the face-to-face Decreased ability to mediate plasma membrane rupture (cytolysis)."; /evidence="ECO:0000269|PubMed:39476863"; MUTAGEN 59; /note="A->C: Disrupts the face-to-face Slightly decreased ability to mediate plasma membrane rupture (cytolysis)."; /evidence="ECO:0000269|PubMed:39476863"; MUTAGEN 60; /note="N->A,Q: Impaired N-glycosylation and reduced homooligomerization."; /evidence="ECO:0000269|PubMed:28067406"; MUTAGEN 119; /note="N->Q: Disrupts the face-to-face homodimer, leading to increased ability to mediate plasma membrane rupture (cytolysis)."; /evidence="ECO:0000269|PubMed:39476863
uniprot
proteins
post_translational_modification
PTM: [Ninjurin-1]: Cleaved by MMP9 protease to generate the Secreted ninjurin-1 form. {ECO:0000269|PubMed:23142597, ECO:0000269|PubMed:32883094}.; PTM: [Ninjurin-1]: N-linked glycosylation is required for homooligomerization. {ECO:0000269|PubMed:28067406}.
uniprot
proteins
protein_family
Ninjurin family
uniprot
proteins
pubmed
19557008
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
23142597
uniprot
proteins
pubmed
23690620
uniprot
proteins
pubmed
24347169
uniprot
proteins
pubmed
24917672
uniprot
proteins
pubmed
24979788
uniprot
proteins
pubmed
25766274
uniprot
proteins
pubmed
25860173
uniprot
proteins
pubmed
26677008
uniprot
proteins
pubmed
27815839
uniprot
proteins
pubmed
28067406
uniprot
proteins
pubmed
29073078
uniprot
proteins
pubmed
30354207
uniprot
proteins
pubmed
30510259
uniprot
proteins
pubmed
30700695
uniprot
proteins
pubmed
31091274
uniprot
proteins
pubmed
31526566
uniprot
proteins
pubmed
32883094
uniprot
proteins
pubmed
33472215
uniprot
proteins
pubmed
36468682
uniprot
proteins
pubmed
37196676
uniprot
proteins
pubmed
37198476
uniprot
proteins
pubmed
37980412
uniprot
proteins
pubmed
38396301
uniprot
proteins
pubmed
38409108
uniprot
proteins
pubmed
39476863
uniprot
proteins
pubmed
9465296
uniprot
proteins
sequence_length
152
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: [Ninjurin-1]: Cell membrane {ECO:0000269|PubMed:24917672, ECO:0000269|PubMed:27815839, ECO:0000269|PubMed:31091274, ECO:0000269|PubMed:33472215, ECO:0000269|PubMed:38396301}; Multi-pass membrane protein {ECO:0000255}. Synaptic cell membrane {ECO:0000269|PubMed:27815839}; Multi-pass membrane protein {ECO:0000255}.; SUBCELLULAR LOCATION: [Secreted ninjurin-1]: Secreted {ECO:0000269|PubMed:23142597, ECO:0000269|PubMed:32883094}.
uniprot
proteins
transmembrane_region
TRANSMEM 79..103; /note="Helical; Name=Helix alpha3"; /evidence="ECO:0000269|PubMed:39476863, ECO:0007744|PDB:9BIA"; TRANSMEM 114..138; /note="Helical; Name=Helix alpha4"; /evidence="ECO:0000269|PubMed:39476863, ECO:0007744|PDB:9BIA
uniprot
proteins