Gamma-secretase subunit APH-1A

Details

Name
Gamma-secretase subunit APH-1A
Synonyms
  • APH-1a
  • Aph-1alpha
  • Presenilin-stabilization factor
  • PSF
Gene Name
APH1A
Organism
Humans
Amino acid sequence
>lcl|BSEQ0006653|Gamma-secretase subunit APH-1A
MGAAVFFGCTFVAFGPAFALFLITVAGDPLRVIILVAGAFFWLVSLLLASVVWFILVHVT
DRSDARLQYGLLIFGAAVSVLLQEVFRFAYYKLLKKADEGLASLSEDGRSPISIRQMAYV
SGLSFGIISGVFSVINILADALGPGVVGIHGDSPYYFLTSAFLTAAIILLHTFWGVVFFD
ACERRRYWALGLVVGSHLLTSGLTFLNPWYEASLLPIYAVTVSMGLWAFITAGGSLRSIQ
RSLLCRRQEDSRVMVYSALRIPPED
Number of residues
265
Molecular Weight
28995.7
Theoretical pI
8.05
GO Classification
Functions
endopeptidase activity
Processes
amyloid precursor protein catabolic process / apoptotic signaling pathway / axon guidance / ephrin receptor signaling pathway / membrane protein ectodomain proteolysis / membrane protein intracellular domain proteolysis / metanephros development / neurotrophin TRK receptor signaling pathway / Notch receptor processing / Notch signaling pathway / positive regulation of apoptotic process / positive regulation of catalytic activity / protein processing
Components
endoplasmic reticulum / endoplasmic reticulum membrane / Golgi apparatus / Golgi cisterna membrane / integral component of plasma membrane / membrane / plasma membrane
General Function
Endopeptidase activity
Specific Function
Essential subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral proteins such as Notch receptors and APP (beta-amyloid precursor protein). It probably represents a stabilizing cofactor for the presenilin homodimer that promotes the formation of a stable complex.
Pfam Domain Function
Transmembrane Regions
3-23 32-52 69-89 119-139 159-179 187-207 214-234
Cellular Location
Endoplasmic reticulum membrane
Gene sequence
>lcl|BSEQ0012388|Gamma-secretase subunit APH-1A (APH1A)
ATGGGGGCTGCGGTGTTTTTCGGCTGCACTTTCGTCGCGTTCGGCCCGGCCTTCGCGCTT
TTCTTGATCACTGTGGCTGGGGACCCGCTTCGCGTTATCATCCTGGTCGCAGGGGCATTT
TTCTGGCTGGTCTCCCTGCTCCTGGCCTCTGTGGTCTGGTTCATCTTGGTCCATGTGACC
GACCGGTCAGATGCCCGGCTCCAGTACGGCCTCCTGATTTTTGGTGCTGCTGTCTCTGTC
CTTCTACAGGAGGTGTTCCGCTTTGCCTACTACAAGCTGCTTAAGAAGGCAGATGAGGGG
TTAGCATCGCTGAGTGAGGACGGAAGATCACCCATCTCCATCCGCCAGATGGCCTATGTT
TCTGGTCTCTCCTTCGGTATCATCAGTGGTGTCTTCTCTGTTATCAATATTTTGGCTGAT
GCACTTGGGCCAGGTGTGGTTGGGATCCATGGAGACTCACCCTATTACTTCCTGACTTCA
GCCTTTCTGACAGCAGCCATTATCCTGCTCCATACCTTTTGGGGAGTTGTGTTCTTTGAT
GCCTGTGAGAGGAGACGGTACTGGGCTTTGGGCCTGGTGGTTGGGAGTCACCTACTGACA
TCGGGACTGACATTCCTGAACCCCTGGTATGAGGCCAGCCTGCTGCCCATCTATGCAGTC
ACTGTTTCCATGGGGCTCTGGGCCTTCATCACAGCTGGAGGGTCCCTCCGAAGTATTCAG
CGCAGCCTCTTGTGCCGACGGCAGGAGGACAGTCGGGTGATGGTGTATTCTGCCCTGCGC
ATCCCACCCGAGGACTGA
Chromosome Location
1
Locus
1p36.13-q31.3
External Identifiers
ResourceLink
UniProtKB IDQ96BI3
UniProtKB Entry NameAPH1A_HUMAN
GenBank Gene IDAF508787
GenAtlas IDAPH1A
HGNC IDHGNC:29509
General References
  1. Lee SF, Shah S, Li H, Yu C, Han W, Yu G: Mammalian APH-1 interacts with presenilin and nicastrin and is required for intramembrane proteolysis of amyloid-beta precursor protein and Notch. J Biol Chem. 2002 Nov 22;277(47):45013-9. Epub 2002 Sep 23. [Article]
  2. Lai CH, Chou CY, Ch'ang LY, Liu CS, Lin W: Identification of novel human genes evolutionarily conserved in Caenorhabditis elegans by comparative proteomics. Genome Res. 2000 May;10(5):703-13. [Article]
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  7. Francis R, McGrath G, Zhang J, Ruddy DA, Sym M, Apfeld J, Nicoll M, Maxwell M, Hai B, Ellis MC, Parks AL, Xu W, Li J, Gurney M, Myers RL, Himes CS, Hiebsch R, Ruble C, Nye JS, Curtis D: aph-1 and pen-2 are required for Notch pathway signaling, gamma-secretase cleavage of betaAPP, and presenilin protein accumulation. Dev Cell. 2002 Jul;3(1):85-97. [Article]
  8. Luo WJ, Wang H, Li H, Kim BS, Shah S, Lee HJ, Thinakaran G, Kim TW, Yu G, Xu H: PEN-2 and APH-1 coordinately regulate proteolytic processing of presenilin 1. J Biol Chem. 2003 Mar 7;278(10):7850-4. Epub 2003 Jan 8. [Article]
  9. Gu Y, Chen F, Sanjo N, Kawarai T, Hasegawa H, Duthie M, Li W, Ruan X, Luthra A, Mount HT, Tandon A, Fraser PE, St George-Hyslop P: APH-1 interacts with mature and immature forms of presenilins and nicastrin and may play a role in maturation of presenilin.nicastrin complexes. J Biol Chem. 2003 Feb 28;278(9):7374-80. Epub 2002 Dec 5. [Article]
  10. Marlow L, Canet RM, Haugabook SJ, Hardy JA, Lahiri DK, Sambamurti K: APH1, PEN2, and Nicastrin increase Abeta levels and gamma-secretase activity. Biochem Biophys Res Commun. 2003 Jun 6;305(3):502-9. [Article]
  11. Kimberly WT, LaVoie MJ, Ostaszewski BL, Ye W, Wolfe MS, Selkoe DJ: Gamma-secretase is a membrane protein complex comprised of presenilin, nicastrin, Aph-1, and Pen-2. Proc Natl Acad Sci U S A. 2003 May 27;100(11):6382-7. Epub 2003 May 9. [Article]
  12. Edbauer D, Winkler E, Regula JT, Pesold B, Steiner H, Haass C: Reconstitution of gamma-secretase activity. Nat Cell Biol. 2003 May;5(5):486-8. [Article]
  13. Fortna RR, Crystal AS, Morais VA, Pijak DS, Lee VM, Doms RW: Membrane topology and nicastrin-enhanced endoproteolysis of APH-1, a component of the gamma-secretase complex. J Biol Chem. 2004 Jan 30;279(5):3685-93. Epub 2003 Oct 30. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB05171E-2012investigationalunknownDetails
DB12852MK-0752investigationalunknowninhibitorDetails