Q8IVG9 (HUNIN_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Putative humanin peptide

Gene names

Name:

MT-RNR2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	24 AA.
Sequence status	Complete.
Protein existence	Uncertain

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).

Ontologies

Keywords
Biological process	Apoptosis
Cellular component	Cytoplasm Secreted
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW cellular iron ion homeostasis Non-traceable author statement PubMed 15567815. Source: UniProtKB leukocyte chemotaxis Inferred from direct assay Ref.8. Source: UniProtKB negative regulation of apoptotic process Inferred from direct assay PubMed 11327724PubMed 15661735PubMed 15661737. Source: UniProtKB
Cellular_component	extracellular region Inferred from direct assay Ref.1. Source: UniProtKB mitochondrion Inferred from direct assay PubMed 15567815. Source: UniProtKB perinuclear region of cytoplasm Inferred from direct assay PubMed 15619032. Source: UniProtKB
Molecular_function	receptor antagonist activity Inferred from direct assay Ref.8. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Peptide

1 – 24

24

Putative humanin peptide

PRO_0000044146

Regions

Region

3 – 19

17

Sufficient for neuroprotective activity

Compositional bias

9 – 12

4

Poly-Leu

Experimental info

Mutagenesis

1 – 6

6

Missing: No effect on binding to BAX. Ref.2 Ref.7

Mutagenesis

1 – 3

3

Missing: Abolishes neuroprotective activity. Ref.4

Mutagenesis

1 – 2

2

Missing: No effect on neuroprotective activity.

Mutagenesis

3

1

P → A: Abolishes neuroprotective activity. Ref.4

Mutagenesis

4 – 6

3

RGF → AGA: Potentiates neuroprotective activity. Ref.2 Ref.4

Mutagenesis

6

1

F → A: Abolishes binding to IGFBP3. Ref.2

Mutagenesis

8

1

C → A, D, E, F, G, I, L, M, N, Q, S, T, V, W or Y: Abolishes neuroprotective activity. Ref.4 Ref.7

Mutagenesis

8

1

C → H: Significantly reduces the neuroprotective activity. Ref.4 Ref.7

Mutagenesis

8

1

C → K or R: No effect on the neuroprotective activity. Ref.4 Ref.7

Mutagenesis

8

1

C → P: Abolishes neuroprotective activity and interaction with BAX. Ref.4 Ref.7

Mutagenesis

9

1

L → A: Abolishes neuroprotective activity. Ref.4 Ref.7

Mutagenesis

9

1

L → R: Abolishes binding to BAX. Ref.4 Ref.7

Mutagenesis

12

1

L → A: Abolishes neuroprotective activity. Ref.4

Mutagenesis

13

1

T → A: Abolishes neuroprotective activity. Ref.4

Mutagenesis

14

1

S → A: Abolishes neuroprotective activity. Ref.4

Mutagenesis

14

1

S → G: Potentiates neuroprotective activity. Ref.4

Mutagenesis

19 – 24

6

Missing: Abolishes neuroprotective activity. Ref.4

Mutagenesis

19

1

P → A: Abolishes neuroprotective activity. Ref.4

Mutagenesis

20 – 24

5

Missing: No effect on neuroprotective activity. Ref.4

Secondary structure

1

.

.

.

.

.

24

Helix Strand Turn

Details...

Helix

4 – 15

12

Beta strand

18 – 21

4

Sequences

	Sequence		Length	Mass (Da)
	Q8IVG9 [UniParc]. Last modified March 1, 2003. Version 1. Checksum: 08B9A778EC13B971	FASTA	24	2,687
	10 20 MAPRGFSCLL LLTSEIDLPV KRRA

References

	« Hide 'large scale' referencesShow '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.

IPI

IPI00383412.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1Y32	NMR	-	A	1-24	[»]
2GD3	NMR	-	A	1-24	[»]

ProteinModelPortal

Q8IVG9.

ModBase

Search...

Protein-protein interaction databases

MINT

MINT-265682.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Organism-specific databases

GeneCards

GCMTP001674.

HGNC

HGNC:7471. MT-RNR2.

MIM

606120. gene.

neXtProt

NX_Q8IVG9.

GenAtlas

Search...

Enzyme and pathway databases

Reactome

REACT_111102. Signal Transduction.

Gene expression databases

Genevestigator

Q8IVG9.

Family and domain databases

ProtoNet

Search...

Other

EvolutionaryTrace

Q8IVG9.

NextBio

35541109.

SOURCE

Search...

Entry information

Entry name

HUNIN_HUMAN

Accession

Primary (citable) accession number: Q8IVG9

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 27, 2004
Last sequence update:	March 1, 2003
Last modified:	May 1, 2013
This is version 60 of the entry and version 1 of the sequence. [Complete history]

Entry status

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.