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Protein

Humanin

Gene

MT-RNR2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Plays a role as a neuroprotective factor. Protects against death induced by multiple different familial Alzheimer disease genes and beta amyloid proteins in Alzheimer disease. Suppresses apoptosis by binding to BAX and preventing the translocation of BAX from the cytosol to mitochondria. Binds to IGFBP3 and specifically blocks IGFBP3-induced cell death Induces chemotaxis of mononuclear phagocytes via FPR2. Reduces the aggregation and fibrillary formation by suppressing the effect of APP on mononuclear phagocytes and acts by competitively inhibiting the access of FPRL1 to APP.5 Publications

GO - Molecular functioni

  • receptor antagonist activity Source: UniProtKB
  • receptor binding Source: UniProtKB

GO - Biological processi

  • apoptotic process Source: UniProtKB-KW
  • cellular iron ion homeostasis Source: UniProtKB
  • leukocyte chemotaxis Source: UniProtKB
  • negative regulation of apoptotic process Source: UniProtKB
Complete GO annotation...

Keywords - Biological processi

Apoptosis

Enzyme and pathway databases

ReactomeiR-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.

Names & Taxonomyi

Protein namesi
Recommended name:
HumaninCurated
Alternative name(s):
Humanin mitochondrial1 Publication
Short name:
HNM1 Publication
Gene namesi
Name:MT-RNR2Imported
Synonyms:HN1 Publication
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Unplaced

Organism-specific databases

HGNCiHGNC:7471. MT-RNR2.

Subcellular locationi

GO - Cellular componenti

  • extracellular region Source: UniProtKB
  • mitochondrion Source: UniProtKB
  • perinuclear region of cytoplasm Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi1 – 66Missing : No effect on binding to BAX. 1 Publication
Mutagenesisi1 – 33Missing : Abolishes neuroprotective activity. 1 Publication
Mutagenesisi1 – 22Missing : No effect on neuroprotective activity. 1 Publication
Mutagenesisi3 – 31P → A: Abolishes neuroprotective activity. 1 Publication
Mutagenesisi4 – 63RGF → AGA: Potentiates neuroprotective activity. 1 Publication
Mutagenesisi6 – 61F → A: Abolishes binding to IGFBP3. 1 Publication
Mutagenesisi8 – 81C → A, D, E, F, G, I, L, M, N, Q, S, T, V, W or Y: Abolishes neuroprotective activity. 2 Publications
Mutagenesisi8 – 81C → H: Significantly reduces the neuroprotective activity. 2 Publications
Mutagenesisi8 – 81C → K or R: No effect on the neuroprotective activity. 2 Publications
Mutagenesisi8 – 81C → P: Abolishes neuroprotective activity and interaction with BAX. 2 Publications
Mutagenesisi9 – 91L → A: Abolishes neuroprotective activity. 2 Publications
Mutagenesisi9 – 91L → R: Abolishes binding to BAX. 2 Publications
Mutagenesisi12 – 121L → A: Abolishes neuroprotective activity. 1 Publication
Mutagenesisi13 – 131T → A: Abolishes neuroprotective activity. 1 Publication
Mutagenesisi14 – 141S → A: Abolishes neuroprotective activity. 1 Publication
Mutagenesisi14 – 141S → G: Potentiates neuroprotective activity. 1 Publication
Mutagenesisi19 – 246Missing : Abolishes neuroprotective activity. 1 Publication
Mutagenesisi19 – 191P → A: Abolishes neuroprotective activity. 1 Publication
Mutagenesisi20 – 245Missing : No effect on neuroprotective activity. 1 Publication

Organism-specific databases

Orphaneti155. Familial isolated hypertrophic cardiomyopathy.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 2424HumaninPRO_0000044146Add
BLAST

Proteomic databases

PaxDbiQ8IVG9.

Expressioni

Tissue specificityi

Expressed in the heart, skeletal muscles, kidney and liver. Lesser but significant expression is observed in the brain and the gastrointestinal tract. Expressed in the AD brain, where it is found in some of the large intact neurons of the occipital lobes and small and round reactive glial cells in the hippocampus.3 Publications

Inductioni

Release is regulated by intracellular mechanism. The intracellular level is regulated by TRIM11 through proteasome-mediated degradation.1 Publication

Interactioni

Subunit structurei

Interacts with BAX, IGFBP3 and TRIM11.3 Publications

GO - Molecular functioni

  • receptor antagonist activity Source: UniProtKB
  • receptor binding Source: UniProtKB

Protein-protein interaction databases

MINTiMINT-265682.
STRINGi9606.ENSP00000468991.

Structurei

Secondary structure

1
24
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi4 – 1512Combined sources
Beta strandi18 – 214Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1Y32NMR-A1-24[»]
2GD3NMR-A1-24[»]
ProteinModelPortaliQ8IVG9.
SMRiQ8IVG9. Positions 1-26.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ8IVG9.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni3 – 1917Sufficient for neuroprotective activityAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi9 – 124Poly-Leu

Domaini

Largely unstructured in aqueous solution.1 Publication

Sequence similaritiesi

Belongs to the humanin family.Curated

Phylogenomic databases

PhylomeDBiQ8IVG9.

Family and domain databases

InterProiIPR028139. Humanin.
[Graphical view]
PfamiPF15040. Humanin. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q8IVG9-1 [UniParc]FASTAAdd to basket

« Hide

        10         20 
MAPRGFSCLL LLTSEIDLPV KRRA
Length:24
Mass (Da):2,687
Last modified:March 1, 2003 - v1
Checksum:i08B9A778EC13B971
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY029066 mRNA. Translation: AAK50430.1.
BE899497 mRNA. No translation available.

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
EntryMethodResolution (Å)ChainPositionsPDBsum
1Y32NMR-A1-24[»]
2GD3NMR-A1-24[»]
ProteinModelPortaliQ8IVG9.
SMRiQ8IVG9. Positions 1-26.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

MINTiMINT-265682.
STRINGi9606.ENSP00000468991.

Proteomic databases

PaxDbiQ8IVG9.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Organism-specific databases

GeneCardsiMT-RNR2.
HGNCiHGNC:7471. MT-RNR2.
MIMi606120. gene.
neXtProtiNX_Q8IVG9.
Orphaneti155. Familial isolated hypertrophic cardiomyopathy.
GenAtlasiSearch...

Phylogenomic databases

PhylomeDBiQ8IVG9.

Enzyme and pathway databases

ReactomeiR-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.

Miscellaneous databases

EvolutionaryTraceiQ8IVG9.
PROiQ8IVG9.
SOURCEiSearch...

Family and domain databases

InterProiIPR028139. Humanin.
[Graphical view]
PfamiPF15040. Humanin. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiHUNIN_HUMAN
AccessioniPrimary (citable) accession number: Q8IVG9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 27, 2004
Last sequence update: March 1, 2003
Last modified: July 6, 2016
This is version 83 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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

Caution

The humanin peptide described here has been shown to be biologically active but is the product of a mitochondrial gene, MT-RNR2 (PubMed:12009529). If translation of the mRNA occurs in the mitochondrion rather than in the cytoplasm, then the usage of the mitochondrial genetic code would lead to the production of a shorter peptide lacking the last three C-terminal residues. The mechanisms allowing the production and the secretion of humanin remaining unclear, the possibility exist that the physiologically active humanin peptide is encoded by one of the related genes present in the nuclear genome (PubMed:19477263).2 Publications

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.