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Q8IVG9 (HUNIN_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 66. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Putative humanin peptide
Gene names
Name:MT-RNR2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length24 AA.
Sequence statusComplete.
Protein existenceUncertain

General annotation (Comments)

Function

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. Ref.1 Ref.2 Ref.4 Ref.7 Ref.8

Subunit structure

Interacts with BAX, IGFBP3 and TRIM11. Ref.2 Ref.6 Ref.7

Subcellular location

Secreted. Cytoplasm Ref.1 Ref.6 Ref.7.

Tissue specificity

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. Ref.1 Ref.5 Ref.9

Induction

Release is regulated by intracellular mechanism. The intracellular level is regulated by TRIM11 through proteasome-mediated degradation. Ref.9

Domain

Largely unstructured in aqueous solution. Ref.10

Sequence similarities

Belongs to the humanin family.

Caution

Product of a dubious CDS prediction. The sequence shown is derived from a portion of the mitochondrial MT-RNR2 gene (Ref.5). The existence of this protein sequence in vivo is possibly dubious. No mechanism has been demonstrated for its production and translocation to the cytoplasm and extracellular space. If translated in the mitochondrion rather than the cytoplasm, the usage of the mitochondrial genetic code would lead to the production of a shorter peptide lacking the last three C-terminal residues. An alternative possibility is that the true physiological humanin peptide is encoded by one or more of several nuclear loci apparently derived from MT-RNR2 (Ref.9).

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Peptide1 – 2424Putative humanin peptide
PRO_0000044146

Regions

Region3 – 1917Sufficient for neuroprotective activity
Compositional bias9 – 124Poly-Leu

Experimental info

Mutagenesis1 – 66Missing: No effect on binding to BAX. Ref.2 Ref.7
Mutagenesis1 – 33Missing: Abolishes neuroprotective activity. Ref.4
Mutagenesis1 – 22Missing: No effect on neuroprotective activity.
Mutagenesis31P → A: Abolishes neuroprotective activity. Ref.4
Mutagenesis4 – 63RGF → AGA: Potentiates neuroprotective activity. Ref.2 Ref.4
Mutagenesis61F → A: Abolishes binding to IGFBP3. Ref.2
Mutagenesis81C → A, D, E, F, G, I, L, M, N, Q, S, T, V, W or Y: Abolishes neuroprotective activity. Ref.4 Ref.7
Mutagenesis81C → H: Significantly reduces the neuroprotective activity. Ref.4 Ref.7
Mutagenesis81C → K or R: No effect on the neuroprotective activity. Ref.4 Ref.7
Mutagenesis81C → P: Abolishes neuroprotective activity and interaction with BAX. Ref.4 Ref.7
Mutagenesis91L → A: Abolishes neuroprotective activity. Ref.4 Ref.7
Mutagenesis91L → R: Abolishes binding to BAX. Ref.4 Ref.7
Mutagenesis121L → A: Abolishes neuroprotective activity. Ref.4
Mutagenesis131T → A: Abolishes neuroprotective activity. Ref.4
Mutagenesis141S → A: Abolishes neuroprotective activity. Ref.4
Mutagenesis141S → G: Potentiates neuroprotective activity. Ref.4
Mutagenesis19 – 246Missing: Abolishes neuroprotective activity. Ref.4
Mutagenesis191P → A: Abolishes neuroprotective activity. Ref.4
Mutagenesis20 – 245Missing: No effect on neuroprotective activity. Ref.4

Secondary structure

..... 24
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q8IVG9 [UniParc].

Last modified March 1, 2003. Version 1.
Checksum: 08B9A778EC13B971

FASTA242,687
        10         20 
MAPRGFSCLL LLTSEIDLPV KRRA 

« Hide

References

« Hide 'large scale' references
[1]"A rescue factor abolishing neuronal cell death by a wide spectrum of familial Alzheimer's disease genes and Abeta."
Hashimoto Y., Niikura T., Tajima H., Yasukawa T., Sudo H., Ito Y., Kita Y., Kawasumi M., Kouyama K., Doyu M., Sobue G., Koide T., Tsuji S., Lang J., Kurokawa K., Nashimoto I.
Proc. Natl. Acad. Sci. U.S.A. 98:6336-6341(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
Tissue: Brain.
[2]"Interaction between the Alzheimer's survival peptide humanin and insulin-like growth factor-binding protein 3 regulates cell survival and apoptosis."
Ikonen M., Liu B., Hashimoto Y., Ma L., Lee K.W., Niikura T., Nishimoto I., Cohen P.
Proc. Natl. Acad. Sci. U.S.A. 100:13042-13047(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH IGFBP3, MUTAGENESIS OF PHE-6.
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]"Detailed characterization of neuroprotection by a rescue factor humanin against various Alzheimer's disease-relevant insults."
Hashimoto Y., Niikura T., Ito Y., Sudo H., Hata M., Arakawa E., Abe Y., Kita Y., Nishimoto I.
J. Neurosci. 21:9235-9245(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF 1-MET-ALA-2; 1-MET--PRO-3; PRO-3; 4-ARG--MET-6; CYS-8; LEU-9; LEU-12; THR-13; SER-14; PRO-19; 19-PRO--ALA-24 AND 20-VAL--ALA-24.
[5]"Evidence for in vivo production of Humanin peptide, a neuroprotective factor against Alzheimer's disease-related insults."
Tajima H., Niikura T., Hashimoto Y., Ito Y., Kita Y., Terashita K., Yamazaki K., Koto A., Aiso S., Nishimoto I.
Neurosci. Lett. 324:227-231(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: EVIDENCE OF IN VIVO EXPRESSION, TISSUE SPECIFICITY.
Tissue: Brain.
[6]"A tripartite motif protein TRIM11 binds and destabilizes Humanin, a neuroprotective peptide against Alzheimer's disease-relevant insults."
Niikura T., Hashimoto Y., Tajima H., Ishizaka M., Yamagishi Y., Kawasumi M., Nawa M., Terashita K., Aiso S., Nishimoto I.
Eur. J. Neurosci. 17:1150-1158(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TRIM11, SUBCELLULAR LOCATION.
[7]"Humanin peptide suppresses apoptosis by interfering with Bax activation."
Guo B., Zhai D., Cabezas E., Welsh K., Nouraini S., Satterthwait A.C., Reed J.C.
Nature 423:456-461(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH BAX, SUBCELLULAR LOCATION, MUTAGENESIS OF 1-MET--PHE-6; 18-LEU--ALA-24; CYS-8 AND LEU-9.
[8]"Humanin, a newly identified neuroprotective factor, uses the G protein-coupled formylpeptide receptor-like-1 as a functional receptor."
Ying G., Iribarren P., Zhou Y., Gong W., Zhang N., Yu Z.-X., Le Y., Cui Y., Wang J.M.
J. Immunol. 172:7078-7085(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[9]"Evidence for potential functionality of nuclearly-encoded humanin isoforms."
Bodzioch M., Lapicka-Bodzioch K., Zapala B., Kamysz W., Kiec-Wilk B., Dembinska-Kiec A.
Genomics 94:247-256(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, INDUCTION.
[10]"Solution structure of humanin, a peptide against Alzheimer's disease-related neurotoxicity."
Benaki D., Zikos C., Evangelou A., Livaniou E., Vlassi M., Mikros E., Pelecanou M.
Biochem. Biophys. Res. Commun. 329:152-160(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR, DOMAIN.
[11]"Solution structure of Ser14Gly-humanin, a potent rescue factor against neuronal cell death in Alzheimer's disease."
Benaki D., Zikos C., Evangelou A., Livaniou E., Vlassi M., Mikros E., Pelecanou M.
Biochem. Biophys. Res. Commun. 349:634-642(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF MUTANT GLY-14.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AY029066 mRNA. Translation: AAK50430.1.
BE899497 mRNA. No translation available.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1Y32NMR-A1-24[»]
2GD3NMR-A1-24[»]
ProteinModelPortalQ8IVG9.
SMRQ8IVG9. Positions 1-26.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

MINTMINT-265682.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Organism-specific databases

GeneCardsGCMTP001674.
HGNCHGNC:7471. MT-RNR2.
MIM606120. gene.
neXtProtNX_Q8IVG9.
GenAtlasSearch...

Phylogenomic databases

PhylomeDBQ8IVG9.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.

Gene expression databases

GenevestigatorQ8IVG9.

Family and domain databases

InterProIPR028139. Humanin.
[Graphical view]
PfamPF15040. Humanin. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ8IVG9.
NextBio35541109.
PROQ8IVG9.
SOURCESearch...

Entry information

Entry nameHUNIN_HUMAN
AccessionPrimary (citable) accession number: Q8IVG9
Entry history
Integrated into UniProtKB/Swiss-Prot: September 27, 2004
Last sequence update: March 1, 2003
Last modified: April 16, 2014
This is version 66 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot