Q8IVG9
uniprot
Q8IVG9
canonical
amino_acid_sequence
MAPRGFSCLLLLTSEIDLPVKRRA
uniprot
proteins
function
FUNCTION: Plays a role as a neuroprotective factor (PubMed:11371646, PubMed:11717357, PubMed:12154011, PubMed:12787071, PubMed:12860203, PubMed:19386761). Protects against neuronal cell death induced by multiple different familial Alzheimer disease genes and amyloid-beta proteins in Alzheimer disease (PubMed:11371646, PubMed:11717357, PubMed:12154011, PubMed:12787071, PubMed:12860203, PubMed:19386761). Mediates its neuroprotective effect by binding to the humanin receptor complex; binding of MT-RNR2 activates the intracellular JAK-STAT3 signaling pathways (PubMed:16005025, PubMed:19386761, PubMed:27384491). Also acts as a ligand for G protein-coupled receptors FPR2/FPRL1 and FPR3/FPRL2 (PubMed:15465011). Inhibits amyloid-beta protein 40 fibril formation (PubMed:27349871). Also inhibits amyloid-beta protein 42 fibril formation (PubMed:28282805). Suppresses apoptosis by binding to BAX and preventing the translocation of BAX from the cytosol to mitochondria (PubMed:12732850, PubMed:26990160). Also suppresses apoptosis by binding to BID and inhibiting the interaction of BID with BAX and BAK which prevents oligomerization of BAX and BAK and suppresses release of apoptogenic proteins from mitochondria (PubMed:15661737). Forms fibers with BAX and also with BID, inducing BAX and BID conformational changes and sequestering them into the fibers which prevents their activation (PubMed:31690630, PubMed:33106313). Can also suppress apoptosis by interacting with BIM isoform BimEL, inhibiting BimEL-induced activation of BAX, blocking oligomerization of BAX and BAK, and preventing release of apoptogenic proteins from mitochondria (PubMed:15661735). Plays a role in up-regulation of anti-apoptotic protein BIRC6/APOLLON, leading to inhibition of neuronal cell death (PubMed:25138702). Binds to IGFBP3 and specifically blocks IGFBP3-induced cell death (PubMed:14561895, PubMed:26216267). Competes with importin KPNB1 for binding to IGFBP3 which is likely to block IGFBP3 nuclear import (PubMed:26216267). Induces chemotaxis of mononuclear phagocytes via FPR2/FPRL1 (PubMed:15153530). Reduces aggregation and fibrillary formation by suppressing the effect of APP on mononuclear phagocytes and acts by competitively inhibiting the access of FPR2 to APP (PubMed:15153530). Protects retinal pigment epithelium (RPE) cells against oxidative stress-induced and endoplasmic reticulum (ER) stress-induced apoptosis (PubMed:26990160, PubMed:27783653). Promotes mitochondrial biogenesis in RPE cells following oxidative stress and promotes STAT3 phosphorylation which leads to inhibition of CASP3 release (PubMed:26990160). Also reduces CASP4 levels in RPE cells, suppresses ER stress-induced mitochondrial superoxide production and plays a role in up-regulation of mitochondrial glutathione (PubMed:27783653). Reduces testicular hormone deprivation-induced apoptosis of germ cells at the nonandrogen-sensitive stages of the seminiferous epithelium cycle (PubMed:19952275). Protects endothelial cells against free fatty acid-induced inflammation by suppressing oxidative stress, reducing expression of TXNIP and inhibiting activation of the NLRP3 inflammasome which inhibits expression of pro-inflammatory cytokines IL1B and IL18 (PubMed:32923762). Protects against high glucose-induced endothelial cell dysfunction by mediating activation of ERK5 which leads to increased expression of transcription factor KLF2 and prevents monocyte adhesion to endothelial cells (PubMed:30029058). Inhibits the inflammatory response in astrocytes (PubMed:23277413). Increases the expression of PPARGC1A/PGC1A in pancreatic beta cells which promotes mitochondrial biogenesis (PubMed:29432738). Increases insulin sensitivity (PubMed:19623253). {ECO:0000269|PubMed:11371646, ECO:0000269|PubMed:11717357, ECO:0000269|PubMed:12154011, ECO:0000269|PubMed:12732850, ECO:0000269|PubMed:12787071, ECO:0000269|PubMed:12860203, ECO:0000269|PubMed:14561895, ECO:0000269|PubMed:15153530, ECO:0000269|PubMed:15465011, ECO:0000269|PubMed:15661735, ECO:0000269|PubMed:15661737, ECO:0000269|PubMed:16005025, ECO:0000269|PubMed:19386761, ECO:0000269|PubMed:19623253, ECO:0000269|PubMed:19952275, ECO:0000269|PubMed:23277413, ECO:0000269|PubMed:25138702, ECO:0000269|PubMed:26216267, ECO:0000269|PubMed:26990160, ECO:0000269|PubMed:27349871, ECO:0000269|PubMed:27384491, ECO:0000269|PubMed:27783653, ECO:0000269|PubMed:28282805, ECO:0000269|PubMed:29432738, ECO:0000269|PubMed:30029058, ECO:0000269|PubMed:31690630, ECO:0000269|PubMed:32923762, ECO:0000269|PubMed:33106313}.
uniprot
proteins
mass_dalton
2687
uniprot
proteins
mutagenesis
MUTAGEN 1..6; /note="Missing: No effect on binding to BAX."; /evidence="ECO:0000269|PubMed:12732850"; MUTAGEN 1..3; /note="Missing: Abolishes neuroprotective activity."; /evidence="ECO:0000269|PubMed:11717357"; MUTAGEN 1..2; /note="Missing: No effect on neuroprotective activity."; /evidence="ECO:0000269|PubMed:11717357"; MUTAGEN 3; /note="P->A: Abolishes neuroprotective activity."; /evidence="ECO:0000269|PubMed:11717357, ECO:0000269|PubMed:12860203"; MUTAGEN 4..6; /note="RGF->AGA: Potentiates neuroprotective activity."; /evidence="ECO:0000269|PubMed:11717357"; MUTAGEN 6; /note="F->A: Abolishes binding to IGFBP3 and increases insulin sensitivity."; /evidence="ECO:0000269|PubMed:14561895, ECO:0000269|PubMed:19623253"; MUTAGEN 7; /note="S->A: Abolishes neuroprotective activity and dimerization. No effect on insulin sensitivity."; /evidence="ECO:0000269|PubMed:12787071, ECO:0000269|PubMed:12860203, ECO:0000269|PubMed:19623253"; MUTAGEN 8; /note="C->A: Abolishes neuroprotective activity. Formation of short irregularly shaped fibers with BAX with fibers showing non-uniform diameters. Formation of thin irregularly kinked fibers with BID."; /evidence="ECO:0000269|PubMed:11717357, ECO:0000269|PubMed:12732850, ECO:0000269|PubMed:12860203, ECO:0000269|PubMed:31690630, ECO:0000269|PubMed:33106313"; MUTAGEN 8; /note="C->D,E,F,G,I,L,M,N,Q,S,T,V,W,Y: Abolishes neuroprotective activity."; /evidence="ECO:0000269|PubMed:11717357, ECO:0000269|PubMed:12732850"; MUTAGEN 8; /note="C->H: Significantly reduces neuroprotective activity."; /evidence="ECO:0000269|PubMed:11717357, ECO:0000269|PubMed:12732850"; MUTAGEN 8; /note="C->K,R: No effect on neuroprotective activity."; /evidence="ECO:0000269|PubMed:11717357, ECO:0000269|PubMed:12732850"; MUTAGEN 8; /note="C->P: Abolishes neuroprotective activity and interaction with BAX and BID. Abolishes BID-induced caspase activation and mitochondrial release of SMAC. Greatly reduced interaction with BIM. Abolishes BIM-induced caspase activation and apoptosis."; /evidence="ECO:0000269|PubMed:11717357, ECO:0000269|PubMed:12732850, ECO:0000269|PubMed:15661735, ECO:0000269|PubMed:15661737"; MUTAGEN 9; /note="L->A: Abolishes neuroprotective activity and dimerization."; /evidence="ECO:0000269|PubMed:11717357, ECO:0000269|PubMed:12732850, ECO:0000269|PubMed:12860203"; MUTAGEN 9; /note="L->R: Abolishes binding to BAX. Abolishes secretion."; /evidence="ECO:0000269|PubMed:11371646, ECO:0000269|PubMed:11717357, ECO:0000269|PubMed:12732850, ECO:0000269|PubMed:12860203"; MUTAGEN 10; /note="L->D: Abolishes secretion."; /evidence="ECO:0000269|PubMed:12860203"; MUTAGEN 10; /note="L->R: Abolishes secretion."; /evidence="ECO:0000269|PubMed:12860203"; MUTAGEN 11; /note="L->R: Abolishes secretion."; /evidence="ECO:0000269|PubMed:12860203"; MUTAGEN 12; /note="L->A: Abolishes neuroprotective activity."; /evidence="ECO:0000269|PubMed:11717357, ECO:0000269|PubMed:12860203"; MUTAGEN 13; /note="T->A: Abolishes neuroprotective activity."; /evidence="ECO:0000269|PubMed:11717357, ECO:0000269|PubMed:12860203"; MUTAGEN 14; /note="S->A,R,W,E,P: Abolishes neuroprotective activity."; /evidence="ECO:0000269|PubMed:11717357, ECO:0000269|PubMed:12787071, ECO:0000269|PubMed:12860203"; MUTAGEN 14; /note="S->G: Potentiates neuroprotective activity. Increased inhibition of amyloid-beta protein 40 fibril formation. Reduced levels of amyloid-beta 42 protein. Affects fiber formation with BAX with fewer fibers running in parallel. Affects fiber formation with BID with formation of shorter fibers. No effect on binding to BID or on BID-induced caspase activation and mitochondrial release of SMAC. Does not affect interaction with FPR2 or FPR3."; /evidence="ECO:0000269|PubMed:11717357, ECO:0000269|PubMed:15465011, ECO:0000269|PubMed:15661737, ECO:0000269|PubMed:27349871, ECO:0000269|PubMed:28282805, ECO:0000269|PubMed:31690630, ECO:0000269|PubMed:33106313"; MUTAGEN 19..24; /note="Missing: Abolishes neuroprotective activity."; /evidence="ECO:0000269|PubMed:11717357"; MUTAGEN 19; /note="P->A: Abolishes neuroprotective activity."; /evidence="ECO:0000269|PubMed:11717357, ECO:0000269|PubMed:12860203"; MUTAGEN 19; /note="P->R: Abolishes secretion."; /evidence="ECO:0000269|PubMed:12860203"; MUTAGEN 20..24; /note="Missing: No effect on neuroprotective activity."; /evidence="ECO:0000269|PubMed:11717357"; MUTAGEN 20; /note="V->R: Abolishes secretion."; /evidence="ECO:0000269|PubMed:12860203
uniprot
proteins
protein_family
Humanin family
uniprot
proteins
pubmed
11371646
uniprot
proteins
pubmed
11717357
uniprot
proteins
pubmed
12009529
uniprot
proteins
pubmed
12154011
uniprot
proteins
pubmed
12670303
uniprot
proteins
pubmed
12732850
uniprot
proteins
pubmed
12787071
uniprot
proteins
pubmed
12860203
uniprot
proteins
pubmed
14561895
uniprot
proteins
pubmed
15153530
uniprot
proteins
pubmed
15465011
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15661735
uniprot
proteins
pubmed
15661737
uniprot
proteins
pubmed
15721287
uniprot
proteins
pubmed
16005025
uniprot
proteins
pubmed
16945331
uniprot
proteins
pubmed
19386761
uniprot
proteins
pubmed
19477263
uniprot
proteins
pubmed
19623253
uniprot
proteins
pubmed
19952275
uniprot
proteins
pubmed
20542501
uniprot
proteins
pubmed
23277413
uniprot
proteins
pubmed
23532874
uniprot
proteins
pubmed
25138702
uniprot
proteins
pubmed
26216267
uniprot
proteins
pubmed
26990160
uniprot
proteins
pubmed
27349871
uniprot
proteins
pubmed
27384491
uniprot
proteins
pubmed
27783653
uniprot
proteins
pubmed
28282805
uniprot
proteins
pubmed
29432738
uniprot
proteins
pubmed
30029058
uniprot
proteins
pubmed
30920769
uniprot
proteins
pubmed
31690630
uniprot
proteins
pubmed
32923762
uniprot
proteins
pubmed
33106313
uniprot
proteins
sequence_length
24
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:11371646, ECO:0000269|PubMed:12860203, ECO:0000269|PubMed:19623253, ECO:0000269|PubMed:26990160}. Cytoplasm {ECO:0000269|PubMed:11371646, ECO:0000269|PubMed:12670303, ECO:0000269|PubMed:15661737, ECO:0000269|PubMed:20542501, ECO:0000269|PubMed:26990160}. Cell projection, cilium, flagellum {ECO:0000269|PubMed:20542501, ECO:0000269|PubMed:30920769}. Nucleus {ECO:0000269|PubMed:20542501}. Mitochondrion {ECO:0000269|PubMed:20542501, ECO:0000269|PubMed:26990160}. Note=Localizes to the sperm flagellum where it is highly concentrated in the midpiece (PubMed:20542501, PubMed:30920769). Detected in the cytoplasm and nucleus of spermatocytes and spermatids (PubMed:20542501). Also detected in sperm mitochondria (PubMed:20542501). In retinal pigment epithelium cells, detected in cytoplasm and mitochondria (PubMed:26990160). {ECO:0000269|PubMed:20542501, ECO:0000269|PubMed:26990160, ECO:0000269|PubMed:30920769}.
uniprot
proteins