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'''APH-1''' (anterior pharynx-defective 1) is a [[protein]] [[gene product]] originally identified in the [[Notch pathway|Notch signaling pathway]] in ''[[Caenorhabditis elegans]]'' as a regulator of the cell-surface localization of [[nicastrin]].<ref name="Goutte">Goutte C, Tsunozaki M, Hale VA, Priess JR. (2002). APH-1 is a multipass membrane protein essential for the Notch signaling pathway in Caenorhabditis elegans embryos. ''Proc Natl Acad Sci USA'' 99(2):775-9. {{PMID|11792846}}</ref> 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 protein]]s 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 [[protein folding|misfolded]] form is implicated in the causation of [[Alzheimer's disease]].<ref name="Kaether">Kaether C, Haass C, Steiner H. (2006). Assembly, trafficking and function of gamma-secretase. ''Neurodegener Dis'' 3(4-5):275-83. {{DOI|10.1159/000095267}} {{PMID|17047368}}</ref> 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.<ref name="Luo">Luo WJ, Wang H, Li H, Kim BS, Shah S, Lee HJ, Thinakaran G, Kim TW, Yu G, Xu H. (2003). PEN-2 and APH-1 coordinately regulate proteolytic processing of presenilin 1. ''J Biol Chem'' 278(10):7850-4. {{PMID|12522139}}</ref> APH-1 contains a conserved [[alpha helix]] interaction [[sequence motif|motif]] [[glycine]]-X-X-X-[[glycine]] ([[GxxxG motif|GXXXG]]) that is essential to both assembly of the gamma secretase complex and to the maturation of the components.<ref name="Lee">Lee SF, Shah S, Yu C, Wigley WC, Li H, Lim M, Pedersen K, Han W, Thomas P, Lundkvist J, Hao YH, Yu G. (2004). A conserved GXXXG motif in APH-1 is critical for assembly and activity of the gamma-secretase complex. ''J Biol Chem'' 279(6):4144-52.  {{DOI|10.1074/jbc.M309745200}} {{PMID|14627705}}</ref>
'''APH-1''' (anterior pharynx-defective 1) is a [[protein]] [[gene product]] originally identified in the [[Notch pathway|Notch signaling pathway]] in ''[[Caenorhabditis elegans]]'' as a regulator of the cell-surface localization of [[nicastrin]].<ref name="Goutte">{{cite journal | vauthors = Goutte C, Tsunozaki M, Hale VA, Priess JR | title = APH-1 is a multipass membrane protein essential for the Notch signaling pathway in Caenorhabditis elegans embryos | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 99 | issue = 2 | pages = 775–9 | date = January 2002 | pmid = 11792846 | pmc = 117381 | doi = 10.1073/pnas.022523499 }}</ref> 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 protein]]s 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 [[protein folding|misfolded]] form is implicated in the causation of [[Alzheimer's disease]].<ref name="Kaether">{{cite journal | vauthors = Kaether C, Haass C, Steiner H | title = Assembly, trafficking and function of gamma-secretase | journal = Neuro-Degenerative Diseases | volume = 3 | issue = 4-5 | pages = 275–83 | date = 2006 | pmid = 17047368 | doi = 10.1159/000095267 }}</ref></ref> 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.<ref name="Luo">{{cite journal | vauthors = Luo WJ, Wang H, Li H, Kim BS, Shah S, Lee HJ, Thinakaran G, Kim TW, Yu G, Xu H | title = PEN-2 and APH-1 coordinately regulate proteolytic processing of presenilin 1 | journal = The Journal of Biological Chemistry | volume = 278 | issue = 10 | pages = 7850–4 | date = March 2003 | pmid = 12522139 | doi = 10.1074/jbc.C200648200 }}</ref></ref> APH-1 contains a conserved [[alpha helix]] interaction [[sequence motif|motif]] [[glycine]]-X-X-X-[[glycine]] ([[GxxxG motif|GXXXG]]) that is essential to both assembly of the gamma secretase complex and to the maturation of the components.<ref name="Lee">{{cite journal | vauthors = Lee SF, Shah S, Yu C, Wigley WC, Li H, Lim M, Pedersen K, Han W, Thomas P, Lundkvist J, Hao YH, Yu G | title = A conserved GXXXG motif in APH-1 is critical for assembly and activity of the gamma-secretase complex | journal = The Journal of Biological Chemistry | volume = 279 | issue = 6 | pages = 4144–52 | date = February 2004 | pmid = 14627705 | doi = 10.1074/jbc.M309745200 }}</ref></ref>


==References==
==References==

Latest revision as of 12:37, 9 January 2019

anterior pharynx defective 1 homolog A (C. elegans)
Identifiers
SymbolAPH1A
Entrez51107
HUGO29509
OMIM607629
RefSeqNM_016022
UniProtQ96BI3
Other data
LocusChr. 1 p36.13-q31.3
anterior pharynx defective 1 homolog B (C. elegans)
Identifiers
SymbolAPH1B
Entrez83464
HUGO24080
OMIM607630
RefSeqNM_031301
UniProtQ8WW43
Other data
LocusChr. 15 q22.2

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]</ref> 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]</ref> 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]</ref>

References

  1. ↑ 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. doi:10.1073/pnas.022523499. PMC 117381. PMID 11792846.
  2. ↑ Kaether C, Haass C, Steiner H (2006). "Assembly, trafficking and function of gamma-secretase". Neuro-Degenerative Diseases. 3 (4–5): 275–83. doi:10.1159/000095267. PMID 17047368.
  3. ↑ 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.
  4. ↑ 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


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