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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. 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) 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.  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">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>


==References==
==References==
{{reflist|2}}
<references />


==External links==
==External links==
* {{MeshName|APH-1+protein,+human}}
* {{MeshName|APH-1+protein,+human}}
{{protein-stub}}


[[Category:Alzheimer's disease]]
[[Category:Alzheimer's disease]]
[[Category:Proteins]]
[[Category:Proteins]]
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Revision as of 14:21, 22 May 2017

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] 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]

References

  1. ↑ 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
  2. ↑ 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
  3. ↑ 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
  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. (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

External links


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