UniProtKB - Q8IVG9 (HUNIN_HUMAN)
Humanin
MT-RNR2
Functioni
Plays a role as a neuroprotective factor (PubMed:11371646, PubMed:11717357, PubMed:12860203, PubMed:19386761, PubMed:12787071, PubMed:12154011).
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:12860203, PubMed:19386761, PubMed:12787071, PubMed:12154011).
Mediates its neuroprotective effect by interacting with a receptor complex composed of IL6ST/GP130, IL27RA/WSX1 and CNTFR (PubMed:19386761).
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).
26 PublicationsCaution
GO - Molecular functioni
- G protein-coupled receptor binding Source: UniProtKB
- identical protein binding Source: UniProtKB
- protein self-association Source: UniProtKB
- receptor antagonist activity Source: UniProtKB
- signaling receptor binding Source: UniProtKB
GO - Biological processi
- apoptotic process Source: UniProtKB-KW
- cellular iron ion homeostasis Source: UniProtKB
- cellular response to amyloid-beta Source: UniProtKB
- leukocyte chemotaxis Source: UniProtKB
- mitochondrion organization Source: UniProtKB
- negative regulation of amyloid fibril formation Source: UniProtKB
- negative regulation of apoptotic process Source: UniProtKB
- negative regulation of execution phase of apoptosis Source: GO_Central
- negative regulation of inflammatory response Source: UniProtKB
- negative regulation of interleukin-18 production Source: UniProtKB
- negative regulation of interleukin-1 production Source: UniProtKB
- negative regulation of neuroinflammatory response Source: UniProtKB
- negative regulation of neuron apoptotic process Source: UniProtKB
- negative regulation of neuron death Source: UniProtKB
- negative regulation of NLRP3 inflammasome complex assembly Source: UniProtKB
- negative regulation of response to oxidative stress Source: UniProtKB
- supramolecular fiber organization Source: UniProtKB
Keywordsi
Biological process | Apoptosis |
Enzyme and pathway databases
PathwayCommonsi | Q8IVG9 |
Reactomei | R-HSA-416476, G alpha (q) signalling events R-HSA-418594, G alpha (i) signalling events R-HSA-444473, Formyl peptide receptors bind formyl peptides and many other ligands |
SignaLinki | Q8IVG9 |
Names & Taxonomyi
Protein namesi | Recommended name: Humanin1 PublicationAlternative name(s): Humanin mitochondrial1 Publication Short name: HNM1 Publication |
Gene namesi | |
Encoded oni | Mitochondrion |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:7471, MT-RNR2 |
MIMi | 606120, gene |
neXtProti | NX_Q8IVG9 |
Subcellular locationi
Nucleus
- Nucleus 1 Publication
Cytoplasm and Cytosol
- Cytoplasm 5 Publications
Mitochondrion
- Mitochondrion 2 Publications
Extracellular region or secreted
- Secreted 4 Publications
Other locations
- flagellum 2 Publications
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).3 Publications
Extracellular region or secreted
- extracellular region Source: UniProtKB
- extracellular space Source: UniProtKB
Mitochondrion
- mitochondrion Source: UniProtKB
Nucleus
- nucleus Source: UniProtKB
Other locations
- cytoplasm Source: UniProtKB
- perinuclear region of cytoplasm Source: UniProtKB
- sperm flagellum Source: UniProtKB
- sperm midpiece Source: UniProtKB
Keywords - Cellular componenti
Cell projection, Cilium, Cytoplasm, Flagellum, Mitochondrion, Nucleus, SecretedPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 1 – 6 | Missing : No effect on binding to BAX. 1 Publication | 6 | |
Mutagenesisi | 1 – 3 | Missing : Abolishes neuroprotective activity. 1 Publication | 3 | |
Mutagenesisi | 1 – 2 | Missing : No effect on neuroprotective activity. 1 Publication | 2 | |
Mutagenesisi | 3 | P → A: Abolishes neuroprotective activity. 2 Publications | 1 | |
Mutagenesisi | 4 – 6 | RGF → AGA: Potentiates neuroprotective activity. 1 Publication | 3 | |
Mutagenesisi | 6 | F → A: Abolishes binding to IGFBP3 and increases insulin sensitivity. 2 Publications | 1 | |
Mutagenesisi | 7 | S → A: Abolishes neuroprotective activity and dimerization. No effect on insulin sensitivity. 3 Publications | 1 | |
Mutagenesisi | 8 | 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. 5 Publications | 1 | |
Mutagenesisi | 8 | C → D, E, F, G, I, L, M, N, Q, S, T, V, W or Y: Abolishes neuroprotective activity. 2 Publications | 1 | |
Mutagenesisi | 8 | C → H: Significantly reduces neuroprotective activity. 2 Publications | 1 | |
Mutagenesisi | 8 | C → K or R: No effect on neuroprotective activity. 2 Publications | 1 | |
Mutagenesisi | 8 | 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. 4 Publications | 1 | |
Mutagenesisi | 9 | L → A: Abolishes neuroprotective activity and dimerization. 3 Publications | 1 | |
Mutagenesisi | 9 | L → R: Abolishes binding to BAX. Abolishes secretion. 4 Publications | 1 | |
Mutagenesisi | 10 | L → D: Abolishes secretion. 1 Publication | 1 | |
Mutagenesisi | 10 | L → R: Abolishes secretion. 1 Publication | 1 | |
Mutagenesisi | 11 | L → R: Abolishes secretion. 1 Publication | 1 | |
Mutagenesisi | 12 | L → A: Abolishes neuroprotective activity. 2 Publications | 1 | |
Mutagenesisi | 13 | T → A: Abolishes neuroprotective activity. 2 Publications | 1 | |
Mutagenesisi | 14 | S → A, R, W, E or P: Abolishes neuroprotective activity. 3 Publications | 1 | |
Mutagenesisi | 14 | 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. 7 Publications | 1 | |
Mutagenesisi | 19 – 24 | Missing : Abolishes neuroprotective activity. 1 Publication | 6 | |
Mutagenesisi | 19 | P → A: Abolishes neuroprotective activity. 2 Publications | 1 | |
Mutagenesisi | 19 | P → R: Abolishes secretion. 1 Publication | 1 | |
Mutagenesisi | 20 – 24 | Missing : No effect on neuroprotective activity. 1 Publication | 5 | |
Mutagenesisi | 20 | V → R: Abolishes secretion. 1 Publication | 1 |
Organism-specific databases
Orphaneti | 155, NON RARE IN EUROPE: Familial isolated hypertrophic cardiomyopathy |
Miscellaneous databases
Pharosi | Q8IVG9, Tdark |
Genetic variation databases
BioMutai | HGNC:7471 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000044146 | 1 – 24 | HumaninAdd BLAST | 24 |
Proteomic databases
PRIDEi | Q8IVG9 |
PTM databases
iPTMneti | Q8IVG9 |
PhosphoSitePlusi | Q8IVG9 |
Expressioni
Tissue specificityi
Developmental stagei
Inductioni
Interactioni
Subunit structurei
Homodimer (PubMed:12787071, PubMed:12860203).
Interacts with amyloid-beta protein 42 (Abeta42); the interaction prevents Abeta42 fibril formation (PubMed:28282805).
Interacts with BAX; forms fibers with BAX which results in BAX conformational changes and sequestering of BAX into the fibers, preventing BAX activation (PubMed:12732850, PubMed:31690630).
Interacts with both full-length BID and cleaved BID p15; forms fibers with BID which results in BID conformational changes and sequestering of BID into the fibers, preventing BID activation (PubMed:15661737, PubMed:33106313).
Interacts with BIM isoform BimEL but not with BIM isoforms BimL or BimS; the interaction prevents BIM-induced apoptosis (PubMed:15661735).
Interacts with IGFBP3; competes with importin KPNB1 for binding to IGFBP3, blocking IGFBP3 nuclear import (PubMed:14561895, PubMed:19623253, PubMed:26216267).
Interacts with TRIM11 (PubMed:12670303).
Interacts with MPP8 (PubMed:23532874).
13 PublicationsBinary interactionsi
Q8IVG9
With | #Exp. | IntAct |
---|---|---|
Amyloid-beta protein 42 (PRO_0000000092) | 4 | EBI-8643752,EBI-821758 |
BAX [Q07812] | 5 | EBI-8643752,EBI-516580 |
IGFBP3 [P17936] | 7 | EBI-8643752,EBI-715709 |
GO - Molecular functioni
- G protein-coupled receptor binding Source: UniProtKB
- identical protein binding Source: UniProtKB
- protein self-association Source: UniProtKB
- receptor antagonist activity Source: UniProtKB
- signaling receptor binding Source: UniProtKB
Protein-protein interaction databases
IntActi | Q8IVG9, 3 interactors |
MINTi | Q8IVG9 |
Structurei
Secondary structure
3D structure databases
AlphaFoldDBi | Q8IVG9 |
BMRBi | Q8IVG9 |
SMRi | Q8IVG9 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q8IVG9 |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 12 | Sufficient to interact with BID and BIM and to suppress BID and BIM activity2 PublicationsAdd BLAST | 12 | |
Regioni | 3 – 19 | Sufficient for neuroprotective activityAdd BLAST | 17 | |
Regioni | 5 – 12 | Sufficient to interact with MPP81 Publication | 8 | |
Regioni | 9 – 11 | Required for secretion1 Publication | 3 | |
Regioni | 19 – 20 | Required for secretion1 Publication | 2 |
Domaini
Sequence similaritiesi
Phylogenomic databases
PhylomeDBi | Q8IVG9 |
Family and domain databases
CDDi | cd20245, humanin, 1 hit |
DisProti | DP02267 |
InterProi | View protein in InterPro IPR028139, Humanin |
PANTHERi | PTHR33895, PTHR33895, 1 hit |
Pfami | View protein in Pfam PF15040, Humanin, 1 hit |
i Sequence
Sequence statusi: Complete.
Mass spectrometryi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AY029066 mRNA Translation: AAK50430.1 BE899497 mRNA No translation available. |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AY029066 mRNA Translation: AAK50430.1 BE899497 mRNA No translation available. |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1Y32 | NMR | - | A | 1-24 | [»] | |
2GD3 | NMR | - | A | 1-24 | [»] | |
5GIW | NMR | - | X | 1-24 | [»] | |
AlphaFoldDBi | Q8IVG9 | |||||
BMRBi | Q8IVG9 | |||||
SMRi | Q8IVG9 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
IntActi | Q8IVG9, 3 interactors |
MINTi | Q8IVG9 |
PTM databases
iPTMneti | Q8IVG9 |
PhosphoSitePlusi | Q8IVG9 |
Genetic variation databases
BioMutai | HGNC:7471 |
Proteomic databases
PRIDEi | Q8IVG9 |
Organism-specific databases
GeneCardsi | MT-RNR2 |
HGNCi | HGNC:7471, MT-RNR2 |
MIMi | 606120, gene |
neXtProti | NX_Q8IVG9 |
Orphaneti | 155, NON RARE IN EUROPE: Familial isolated hypertrophic cardiomyopathy |
GenAtlasi | Search... |
Phylogenomic databases
PhylomeDBi | Q8IVG9 |
Enzyme and pathway databases
PathwayCommonsi | Q8IVG9 |
Reactomei | R-HSA-416476, G alpha (q) signalling events R-HSA-418594, G alpha (i) signalling events R-HSA-444473, Formyl peptide receptors bind formyl peptides and many other ligands |
SignaLinki | Q8IVG9 |
Miscellaneous databases
ChiTaRSi | MT-RNR2, human |
EvolutionaryTracei | Q8IVG9 |
Pharosi | Q8IVG9, Tdark |
PROi | PR:Q8IVG9 |
SOURCEi | Search... |
Family and domain databases
CDDi | cd20245, humanin, 1 hit |
DisProti | DP02267 |
InterProi | View protein in InterPro IPR028139, Humanin |
PANTHERi | PTHR33895, PTHR33895, 1 hit |
Pfami | View protein in Pfam PF15040, Humanin, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | HUNIN_HUMAN | |
Accessioni | Q8IVG9Primary (citable) accession number: Q8IVG9 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | September 27, 2004 |
Last sequence update: | March 1, 2003 | |
Last modified: | May 25, 2022 | |
This is version 113 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families