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humanin (HN, MT-RNR2)
Function:
1) role as a neuroprotective factor against death induced by multiple different types of familial Alzheimer disease genes & beta amyloid in Alzheimer disease
2) induces chemotaxis of mononuclear phagocytes via FPRL1
3) diminishes aggregation fibrillary formation
4) suppresses effect of APP on mononuclear phagocytes
5) competitively inhibits access of FPRL1 to APP
6) prevents translocation of BAX from cytosol to mitochondria
7) interacts with IGFBP3, BAX & TRIM11
8) neuroprotection blocked by genistein (tyrosine kinase inhibitor)
Structure:
- forms homodimer, essential for neuroprotection
- Ser7 & Leu9 ?
- cDNA sequence 99% homologous to 16S mitochondrial ribosomal RNA
Compartment: secreted
Expression:
- expressed in the heart, skeletal muscles, kidney, liver > brain, gastrointestinal tract
- release is regulated by intracellular mechanism
- intracellular level is regulated by TRIM11 through proteasomal pathway
Pathology:
- expressed in AD brain, where it is found in some of the large intact neurons of the occipital lobes & small & round reactive glial cells in the hippocampus
Notes:
- originally identified as neuroprotective against AD related neuronal cell death; found to suppress neuronal cell death induced by three FAD gene proteins:
- amyloid precursor protein & A4 peptide
- presenilin-1
- presenilin-2
General
secreted peptide
Properties
SIZE: MW = 3 kD
entity length = 24 aa
COMPARTMENT: extracellular compartment
MOTIF: neuroprotective {3-19}
Database Correlations
OMIM 606120
UniProt Q8IVG9
References
- UniProt :accession Q8IVG9
- OMIM :accession 606120
- Nishimoto I et al.
Unravelling the role of Humanin.
Trends in Molecular Medicine 10:102-5, 2004
PMID: 15106598