NINJ1
entrez
4814
canonical
uniprot
Q92982
canonical
ensembl
ENSG00000131669
resolver
ensp
ENSP00000364595
resolver
ensp
ENSP00000548702
resolver
ensp
ENSP00000548703
resolver
ensp
ENSP00000616756
resolver
enst
ENST00000375446
resolver
enst
ENST00000878643
resolver
enst
ENST00000878644
resolver
enst
ENST00000946697
resolver
genesymbol
NINJ1
resolver
hgnc
HGNC:7824
resolver
uniprot
Q6GU89
resolver
uniprot
Q8WUV5
resolver
uniprot
Q9BT07
resolver
uniprot_entry
NINJ1_HUMAN
resolver
uniprot_sec
Q6GU89
resolver
uniprot_sec
Q8WUV5
resolver
uniprot_sec
Q9BT07
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 (PubMed:37198476). 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 (By similarity). {ECO:0000250|UniProtKB:O70131, ECO:0000269|PubMed:36468682, ECO:0000269|PubMed:37198476}.
uniprot
proteins
amino_acid_sequence
MDSGTEEYELNGGLPPGTPGSPDASPARWGWRHGPINVNHYASKKSAAESMLDIALLMANASQLKAVVEQGPSFAFYVPLVVLISISLVLQIGVGVLLIFLVKYDLNNPAKHAKLDFLNNLATGLVFIIVVVNIFITAFGVQKPLMDMAPQQ
uniprot
proteins
function
FUNCTION: [Ninjurin-1]: Effector of various programmed cell death, such as pyroptosis and necroptosis, which mediates plasma membrane rupture (cytolysis) (PubMed:33472215, PubMed:36468682, PubMed:37196676, PubMed:37198476, PubMed:38614101, PubMed:39667936). 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:38614101). Plasma membrane rupture leads to release intracellular molecules named damage-associated molecular patterns (DAMPs) that propagate the inflammatory response (PubMed:33472215, PubMed:36468682, PubMed:37196676, PubMed:37198476). Mechanistically, mediates plasma membrane rupture by introducing hydrophilic faces of 2 alpha helices into the hydrophobic membrane (PubMed:37198476, PubMed:38614101). Induces plasma membrane rupture downstream of Gasdermin (GSDMA, GSDMB, GSDMC, GSDMD, or GSDME) or MLKL during pyroptosis or necroptosis, respectively (PubMed:33472215, PubMed:36468682, PubMed:37196676, PubMed:37198476). Acts as an effector of PANoptosis downstream of CASP1, CASP4, CASP8 and RIPK3 (By similarity). Also induces plasma membrane rupture in response to cell swelling caused by osmotic stress and ferroptosis downstream of lipid peroxidation (By similarity). Acts as a regulator of Toll-like receptor 4 (TLR4) signaling triggered by lipopolysaccharide (LPS) during systemic inflammation; directly binds LPS (PubMed:26677008). 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). Also acts as a homophilic transmembrane adhesion molecule involved in various processes such as axonal growth, cell chemotaxis and angiogenesis (PubMed:33028854, PubMed:8780658, PubMed:9261151). Promotes cell adhesion by mediating homophilic interactions via its extracellular N-terminal adhesion motif (N-NAM) (PubMed:33028854, PubMed:8780658, PubMed:9261151). 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). 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). {ECO:0000250|UniProtKB:O70131, ECO:0000269|PubMed:22162058, ECO:0000269|PubMed:26677008, ECO:0000269|PubMed:32147432, ECO:0000269|PubMed:33028854, ECO:0000269|PubMed:33472215, ECO:0000269|PubMed:36468682, ECO:0000269|PubMed:37196676, ECO:0000269|PubMed:37198476, ECO:0000269|PubMed:38614101, ECO:0000269|PubMed:39667936, ECO:0000269|PubMed:8780658, ECO:0000269|PubMed:9261151}.; FUNCTION: [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). {ECO:0000250|UniProtKB:O70131, ECO:0000269|PubMed:32883094}.
uniprot
proteins
mass_dalton
16345
uniprot
proteins
mutagenesis
MUTAGEN 44..45; /note="KK->QQ: Strongly reduced ability to mediate plasma membrane rupture."; /evidence="ECO:0000269|PubMed:38614101"; MUTAGEN 45; /note="K->Q: Strongly reduced ability to homooligomerize and mediate plasma membrane rupture (cytolysis)."; /evidence="ECO:0000269|PubMed:37198476"; MUTAGEN 47; /note="A->L: Does not affect ability to homooligomerize in vitro. Slightly reduced ability to mediate plasma membrane rupture."; /evidence="ECO:0000269|PubMed:37198476, ECO:0000269|PubMed:38614101"; MUTAGEN 49; /note="E->K: Strongly reduced ability to mediate plasma membrane rupture."; /evidence="ECO:0000269|PubMed:38614101"; MUTAGEN 53; /note="D->A: Strongly reduced ability to homooligomerize and mediate plasma membrane rupture (cytolysis)."; /evidence="ECO:0000269|PubMed:37198476"; MUTAGEN 76..82; /note="FYVPLVV->YYTTLVT: In mutant M4(exo); decreased ability to mediate plasma membrane rupture."; /evidence="ECO:0000269|PubMed:39667936"; MUTAGEN 82; /note="V->F: Does not affect ability to homooligomerize, but shows slightly reduced ability to mediate plasma membrane rupture (cytolysis)."; /evidence="ECO:0000269|PubMed:37198476, ECO:0000269|PubMed:38614101"; MUTAGEN 82; /note="V->W: Does not affect ability to homooligomerize and mediate plasma membrane rupture (cytolysis)."; /evidence="ECO:0000269|PubMed:37198476"; MUTAGEN 84; /note="I->F: Strongly reduced ability to homooligomerize and mediate plasma membrane rupture (cytolysis)."; /evidence="ECO:0000269|PubMed:37198476"; MUTAGEN 86; /note="I->F: Reduced ability to mediate plasma membrane rupture."; /evidence="ECO:0000269|PubMed:38614101"; MUTAGEN 90; /note="L->W: Strongly reduced ability to mediate plasma membrane rupture."; /evidence="ECO:0000269|PubMed:38614101"; MUTAGEN 91; /note="Q->A: Strongly reduced ability to homooligomerize and mediate plasma membrane rupture (cytolysis)."; /evidence="ECO:0000269|PubMed:37198476"; MUTAGEN 93; /note="G->L: Reduced ability to mediate plasma membrane rupture."; /evidence="ECO:0000269|PubMed:38614101"; MUTAGEN 93; /note="G->V: In mutant M5(cyto); decreased ability to mediate plasma membrane rupture; when associated with V-100, Q-117, A-121 and I-124."; /evidence="ECO:0000269|PubMed:39667936"; MUTAGEN 95; /note="G->L: Strongly reduced ability to homooligomerize and mediate plasma membrane rupture (cytolysis)."; /evidence="ECO:0000269|PubMed:37198476, ECO:0000269|PubMed:38614101"; MUTAGEN 100; /note="F->V: In mutant M5(cyto); decreased ability to mediate plasma membrane rupture; when associated with V-93, Q-117, A-121 and I-124."; /evidence="ECO:0000269|PubMed:39667936"; MUTAGEN 103; /note="K->E: Strongly reduced ability to mediate plasma membrane rupture."; /evidence="ECO:0000269|PubMed:38614101"; MUTAGEN 111; /note="K->E: Strongly reduced ability to mediate plasma membrane rupture."; /evidence="ECO:0000269|PubMed:38614101"; MUTAGEN 114; /note="K->E: Slightly reduced ability to mediate plasma membrane rupture."; /evidence="ECO:0000269|PubMed:38614101"; MUTAGEN 117; /note="F->Q: Decreased ability to mediate plasma membrane rupture. In mutant M5(cyto); decreased ability to mediate plasma membrane rupture; when associated with V-93, V-100, A-121 and I-124."; /evidence="ECO:0000269|PubMed:39667936"; MUTAGEN 121; /note="L->A: In mutant M5(cyto); decreased ability to mediate plasma membrane rupture; when associated with V-93, V-100, Q-117 and I-124."; /evidence="ECO:0000269|PubMed:39667936"; MUTAGEN 121; /note="L->F: Does not affect ability to homooligomerize and mediate plasma membrane rupture (cytolysis)."; /evidence="ECO:0000269|PubMed:37198476"; MUTAGEN 121; /note="L->W: Does not affect ability to homooligomerize, but shows reduced ability to mediate plasma membrane rupture (cytolysis)."; /evidence="ECO:0000269|PubMed:37198476, ECO:0000269|PubMed:38614101"; MUTAGEN 123; /note="T->L: Strongly reduced ability to homooligomerize and mediate plasma membrane rupture (cytolysis)."; /evidence="ECO:0000269|PubMed:37198476"; MUTAGEN 124; /note="G->I: In mutant M5(cyto); decreased ability to mediate plasma membrane rupture; when associated with V-93, V-100, Q-117 and A-121."; /evidence="ECO:0000269|PubMed:39667936"; MUTAGEN 124; /note="G->L: Reduced ability to mediate plasma membrane rupture."; /evidence="ECO:0000269|PubMed:38614101"; MUTAGEN 125; /note="L->W: Strongly reduced ability to mediate plasma membrane rupture."; /evidence="ECO:0000269|PubMed:38614101"; MUTAGEN 128; /note="I->F: Slightly reduced ability to mediate plasma membrane rupture."; /evidence="ECO:0000269|PubMed:38614101"; MUTAGEN 134; /note="I->F: Strongly reduced ability to homooligomerize and mediate plasma membrane rupture (cytolysis)."; /evidence="ECO:0000269|PubMed:37198476"; MUTAGEN 138; /note="A->L: Strongly reduced ability to homooligomerize and mediate plasma membrane rupture (cytolysis)."; /evidence="ECO:0000269|PubMed:37198476
uniprot
proteins
post_translational_modification
PTM: [Ninjurin-1]: Cleaved by MMP9 protease to generate the Secreted ninjurin-1 form. {ECO:0000305|PubMed:32883094}.; PTM: [Ninjurin-1]: N-linked glycosylation is required for homooligomerization. {ECO:0000250|UniProtKB:O70131}.
uniprot
proteins
protein_family
Ninjurin family
uniprot
proteins
pubmed
15164053
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
22162058
uniprot
proteins
pubmed
22814378
uniprot
proteins
pubmed
26677008
uniprot
proteins
pubmed
32147432
uniprot
proteins
pubmed
32883094
uniprot
proteins
pubmed
33028854
uniprot
proteins
pubmed
33472215
uniprot
proteins
pubmed
36468682
uniprot
proteins
pubmed
37196676
uniprot
proteins
pubmed
37198476
uniprot
proteins
pubmed
38396301
uniprot
proteins
pubmed
38614101
uniprot
proteins
pubmed
39667936
uniprot
proteins
pubmed
8780658
uniprot
proteins
pubmed
9261151
uniprot
proteins
pubmed
9465296
uniprot
proteins
sequence_length
152
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: [Ninjurin-1]: Cell membrane {ECO:0000269|PubMed:37198476, ECO:0000269|PubMed:38396301, ECO:0000269|PubMed:39667936}; Multi-pass membrane protein {ECO:0000269|PubMed:37198476, ECO:0000269|PubMed:39667936}. Synaptic cell membrane {ECO:0000250|UniProtKB:O70131}; Multi-pass membrane protein {ECO:0000255}.; SUBCELLULAR LOCATION: [Secreted ninjurin-1]: Secreted {ECO:0000305|PubMed:32883094}.
uniprot
proteins
transmembrane_region
TRANSMEM 79..103; /note="Helical; Name=Helix alpha3"; /evidence="ECO:0000269|PubMed:37198476, ECO:0000269|PubMed:39667936, ECO:0007744|PDB:8CQR, ECO:0007744|PDB:8SZA"; TRANSMEM 114..138; /note="Helical; Name=Helix alpha4"; /evidence="ECO:0000269|PubMed:37198476, ECO:0000269|PubMed:39667936, ECO:0007744|PDB:8CQR, ECO:0007744|PDB:8SZA
uniprot
proteins