APH-1 (anterior pharynx-defective 1) is a protein gene product originally identified in the Notch signaling pathway in Caenorhabditis elegans as a regulator of the cell-surface localization of nicastrin.[1] APH-1 homologs in other organisms, including humans, have since been identified as components of the gamma secretase complex along with the catalytic subunit presenilin and the regulatory subunits nicastrin and PEN-2. The gamma-secretase complex is a multimeric protease responsible for the intramembrane proteolysis of transmembrane proteins such as the Notch protein and amyloid precursor protein (APP). Gamma-secretase cleavage of APP is one of two proteolytic steps required to generate the peptide known as amyloid beta, whose misfolded form is implicated in the causation of Alzheimer's disease.[2] All of the components of the gamma-secretase complex undergo extensive post-translational modification, especially proteolytic activation; APH-1 and PEN-2 are regarded as regulators of the maturation process of the catalytic component presenilin.[3] APH-1 contains a conserved alpha helix interaction motif glycine-X-X-X-glycine (GXXXG) that is essential to both assembly of the gamma secretase complex and to the maturation of the components.[4]
| anterior pharynx defective 1 homolog A (C. elegans) | |||||||
|---|---|---|---|---|---|---|---|
| Identifiers | |||||||
| Symbol | APH1A | ||||||
| NCBI gene | 51107 | ||||||
| HGNC | 29509 | ||||||
| OMIM | 607629 | ||||||
| RefSeq | NM_016022 | ||||||
| UniProt | Q96BI3 | ||||||
| Other data | |||||||
| Locus | Chr. 1 p36.13-q31.3 | ||||||
| |||||||
| anterior pharynx defective 1 homolog B (C. elegans) | |||||||
|---|---|---|---|---|---|---|---|
| Identifiers | |||||||
| Symbol | APH1B | ||||||
| NCBI gene | 83464 | ||||||
| HGNC | 24080 | ||||||
| OMIM | 607630 | ||||||
| RefSeq | NM_031301 | ||||||
| UniProt | Q8WW43 | ||||||
| Other data | |||||||
| Locus | Chr. 15 q22.2 | ||||||
| |||||||
References
edit- ^ Goutte C, Tsunozaki M, Hale VA, Priess JR (January 2002). "APH-1 is a multipass membrane protein essential for the Notch signaling pathway in Caenorhabditis elegans embryos". Proceedings of the National Academy of Sciences of the United States of America. 99 (2): 775–9. Bibcode:2002PNAS...99..775G. doi:10.1073/pnas.022523499. PMC 117381. PMID 11792846.
- ^ Kaether C, Haass C, Steiner H (2006). "Assembly, trafficking and function of gamma-secretase" (PDF). Neuro-Degenerative Diseases. 3 (4–5): 275–83. doi:10.1159/000095267. PMID 17047368. S2CID 17324271.
- ^ Luo WJ, Wang H, Li H, Kim BS, Shah S, Lee HJ, Thinakaran G, Kim TW, Yu G, Xu H (March 2003). "PEN-2 and APH-1 coordinately regulate proteolytic processing of presenilin 1". The Journal of Biological Chemistry. 278 (10): 7850–4. doi:10.1074/jbc.C200648200. PMID 12522139.
- ^ Lee SF, Shah S, Yu C, Wigley WC, Li H, Lim M, Pedersen K, Han W, Thomas P, Lundkvist J, Hao YH, Yu G (February 2004). "A conserved GXXXG motif in APH-1 is critical for assembly and activity of the gamma-secretase complex". The Journal of Biological Chemistry. 279 (6): 4144–52. doi:10.1074/jbc.M309745200. PMID 14627705.
External links
edit- APH-1+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
 | This article on a gene on human chromosome 15 is a stub. You can help Wikipedia by expanding it. |