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Aliases for APH1A Gene

Aliases for APH1A Gene

  • APH1A Gamma Secretase Subunit 2 3
  • Presenilin-Stabilization Factor 3 4
  • Aph-1alpha 3 4
  • APH-1A 3 4
  • Anterior Pharynx Defective 1 Homolog A (C. Elegans) 2
  • Anterior Pharynx Defective 1 Homolog A 3
  • Gamma-Secretase Subunit APH-1A 3
  • 6530402N02Rik 3
  • CGI-78 3
  • APH-1 3
  • PSF 4

External Ids for APH1A Gene

Summaries for APH1A Gene

Entrez Gene Summary for APH1A Gene

  • This gene encodes a component of the gamma secretase complex that cleaves integral membrane proteins such as Notch receptors and beta-amyloid precursor protein. The gamma secretase complex contains this gene product, or the paralogous anterior pharynx defective 1 homolog B (APH1B), along with the presenilin, nicastrin, and presenilin enhancer-2 proteins. The precise function of this seven-transmembrane-domain protein is unknown though it is suspected of facilitating the association of nicastrin and presenilin in the gamma secretase complex as well as interacting with substrates of the gamma secretase complex prior to their proteolytic processing. Polymorphisms in a promoter region of this gene have been associated with an increased risk for developing sporadic Alzheimer's disease. Alternative splicing results in multiple protein-coding and non-protein-coding transcript variants. [provided by RefSeq, Aug 2011]

GeneCards Summary for APH1A Gene

APH1A (APH1A Gamma Secretase Subunit) is a Protein Coding gene. Among its related pathways are PI-3K cascade and Signaling by FGFR. GO annotations related to this gene include endopeptidase activity. An important paralog of this gene is APH1B.

UniProtKB/Swiss-Prot for APH1A Gene

  • 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.

No data available for Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for APH1A Gene

Genomics for APH1A Gene

Genomic Location for APH1A Gene

Start:
150,265,399 bp from pter
End:
150,269,580 bp from pter
Size:
4,182 bases
Orientation:
Minus strand

Genomic View for APH1A Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for APH1A Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for APH1A Gene

Regulatory Elements for APH1A Gene

Proteins for APH1A Gene

  • Protein details for APH1A Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q96BI3-APH1A_HUMAN
    Recommended name:
    Gamma-secretase subunit APH-1A
    Protein Accession:
    Q96BI3
    Secondary Accessions:
    • B4DQK0
    • Q5TB22
    • Q5TB23
    • Q969R6
    • Q9BVG0
    • Q9Y386

    Protein attributes for APH1A Gene

    Size:
    265 amino acids
    Molecular mass:
    28996 Da
    Quaternary structure:
    • Component of the gamma-secretase complex, a complex composed of a presenilin homodimer (PSEN1 or PSEN2), nicastrin (NCSTN), APH1 (APH1A or APH1B) and PEN2. Such minimal complex is sufficient for secretase activity, although other components may exist
    SequenceCaution:
    • Sequence=AAD34072.1; Type=Frameshift; Positions=243; Evidence={ECO:0000305}; Sequence=AAN63816.1; Type=Frameshift; Positions=243; Evidence={ECO:0000305};

    Alternative splice isoforms for APH1A Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for APH1A Gene

Proteomics data for APH1A Gene at MOPED

Post-translational modifications for APH1A Gene

  • Modification sites at PhosphoSitePlus
  • Ubiquitination at Lys92

Other Protein References for APH1A Gene

No data available for DME Specific Peptides for APH1A Gene

Domains for APH1A Gene

Protein Domains for APH1A Gene

InterPro:
Blocks:
ProtoNet:

UniProtKB/Swiss-Prot:

APH1A_HUMAN
Family:
  • Belongs to the APH-1 family.:
    • Q96BI3
genes like me logo Genes that share domains with APH1A: view

No data available for Gene Families for APH1A Gene

Function for APH1A Gene

Molecular function for APH1A Gene

UniProtKB/Swiss-Prot 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.

Gene Ontology (GO) - Molecular Function for APH1A Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004175 endopeptidase activity IEA --
GO:0005515 protein binding IPI 12297508
genes like me logo Genes that share ontologies with APH1A: view
genes like me logo Genes that share phenotypes with APH1A: view

Animal Models for APH1A Gene

MGI Knock Outs for APH1A:

miRNA for APH1A Gene

miRTarBase miRNAs that target APH1A

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targeting and HOMER Transcription for APH1A Gene

Localization for APH1A Gene

Subcellular locations from UniProtKB/Swiss-Prot for APH1A Gene

Endoplasmic reticulum membrane; Multi-pass membrane protein. Golgi apparatus, Golgi stack membrane; Multi-pass membrane protein. Note=Predominantly located in the endoplasmic reticulum and in the cis-Golgi.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for APH1A Gene COMPARTMENTS Subcellular localization image for APH1A gene
Compartment Confidence
endoplasmic reticulum 5
golgi apparatus 5
plasma membrane 4

Gene Ontology (GO) - Cellular Components for APH1A Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005783 endoplasmic reticulum IDA 15274632
GO:0005789 endoplasmic reticulum membrane IEA --
GO:0005794 Golgi apparatus IDA 15274632
GO:0005886 plasma membrane TAS --
GO:0005887 integral component of plasma membrane IDA 15274632
genes like me logo Genes that share ontologies with APH1A: view

Pathways for APH1A Gene

genes like me logo Genes that share pathways with APH1A: view

Gene Ontology (GO) - Biological Process for APH1A Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001656 metanephros development IEA --
GO:0006509 membrane protein ectodomain proteolysis IDA 15274632
GO:0007219 Notch signaling pathway TAS --
GO:0007220 Notch receptor processing TAS 15274632
GO:0007411 axon guidance TAS --
genes like me logo Genes that share ontologies with APH1A: view

Compounds for APH1A Gene

(17) ApexBio Compounds for APH1A Gene

Compound Action Cas Number
Begacestat gamma-secretase inhibitor [769169-27-9]
BMS 299897 Orally active, potent gamma-secretase inhibitor. [290315-45-6]
BMS-708163 (Avagacestat) potent, selective an [1146699-66-2]
Compound W Inhibitor of gamma-secretase. [173550-33-9]
DAPT (GSI-IX) potent and specific inhibitor of gamma-secretase. [208255-80-5]
E 2012 potent gamma-secretase modulator. [870843-42-8]
Flurizan inhibits gamma-secretase activity. [51543-40-9]
JLK 6 Inhibitor of gamma-secretase. [62252-26-0]
L-685,458 Potent and selective gamma-secretase Inhibitor [292632-98-5]
LY3039478 potent Notch inhibitor [1421438-81-4]
LY-411575 selective, cell permeable, small molecule gamma secretase inhibitor. [209984-57-6]
MK-0752 potent gamma secretase inhibitor [471905-41-6]
MRK 560 gamma-secretase Inhibitor
PF-03084014 novel gamma-secretase inhibitor [865773-15-5]
RO4929097 small-molecule inhibitor of gamma secretase [847925-91-1]
Semagacestat (LY450139) azepine class gamma-secretase [425386-60-3]
YO-01027 (Dibenzazepine, DBZ) potent inhibitor of gamma-secretaseproteins. [209984-56-5]
genes like me logo Genes that share compounds with APH1A: view

Transcripts for APH1A Gene

Unigene Clusters for APH1A Gene

Anterior pharynx defective 1 homolog A (C. elegans):
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for APH1A Gene

ExUns: 1a · 1b ^ 2a · 2b ^ 3a · 3b ^ 4a · 4b ^ 5a · 5b · 5c · 5d ^ 6a · 6b · 6c ^ 7
SP1: - - - - -
SP2: - - -
SP3: - -
SP4: - - - - -
SP5: -
SP6: -

Relevant External Links for APH1A Gene

GeneLoc Exon Structure for
APH1A
ECgene alternative splicing isoforms for
APH1A

Expression for APH1A Gene

mRNA expression in normal human tissues for APH1A Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, MOPED, and MaxQB for APH1A Gene

SOURCE GeneReport for Unigene cluster for APH1A Gene Hs.108408

mRNA Expression by UniProt/SwissProt for APH1A Gene

Q96BI3-APH1A_HUMAN
Tissue specificity: Widely expressed. Expressed in leukocytes, lung, placenta, small intestine, liver, kidney, spleen thymus, skeletal muscle, heart and brain. Isoform 1 and isoform 2 are nearly expressed at the same level.
genes like me logo Genes that share expressions with APH1A: view

Orthologs for APH1A Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for APH1A Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia APH1A 36
  • 99.75 (n)
  • 100 (a)
APH1A 37
  • 100 (a)
OneToOne
cow
(Bos Taurus)
Mammalia APH1A 36
  • 95.93 (n)
  • 98.37 (a)
APH1A 37
  • 98 (a)
OneToOne
dog
(Canis familiaris)
Mammalia APH1 36
  • 96.73 (n)
  • 99.25 (a)
APH1A 37
  • 99 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Aph1a 36
  • 94.72 (n)
  • 99.25 (a)
Aph1a 16
Aph1a 37
  • 99 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia APH1A 37
  • 89 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Aph1a 36
  • 93.36 (n)
  • 98.78 (a)
chicken
(Gallus gallus)
Aves APH1A 37
  • 78 (a)
OneToOne
LOC431243 36
  • 72.96 (n)
  • 78.11 (a)
lizard
(Anolis carolinensis)
Reptilia APH1A 37
  • 78 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia aph1a 36
  • 67.61 (n)
  • 72.87 (a)
Str.2748 36
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.2866 36
zebrafish
(Danio rerio)
Actinopterygii APH1A 37
  • 62 (a)
OneToOne
aph1b 36
  • 65.19 (n)
  • 63.86 (a)
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP009816 36
  • 52.18 (n)
  • 47.26 (a)
fruit fly
(Drosophila melanogaster)
Insecta aph-1 36
  • 54.69 (n)
  • 49.35 (a)
aph-1 37
  • 48 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea aph-1 36
  • 43.55 (n)
  • 37.19 (a)
aph-1 37
  • 24 (a)
OneToMany
thale cress
(Arabidopsis thaliana)
eudicotyledons AT2G31440 36
  • 46.53 (n)
  • 29.21 (a)
rice
(Oryza sativa)
Liliopsida Os02g0272600 36
  • 48.35 (n)
  • 32.67 (a)
sea squirt
(Ciona savignyi)
Ascidiacea CSA.7022 37
  • 43 (a)
OneToMany
Species with no ortholog for APH1A:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • platypus (Ornithorhynchus anatinus)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for APH1A Gene

ENSEMBL:
Gene Tree for APH1A (if available)
TreeFam:
Gene Tree for APH1A (if available)

Paralogs for APH1A Gene

Paralogs for APH1A Gene

Selected SIMAP similar genes for APH1A Gene using alignment to 2 proteins:

genes like me logo Genes that share paralogs with APH1A: view

Variants for APH1A Gene

Sequence variations from dbSNP and Humsavar for APH1A Gene

SNP ID Clin Chr 01 pos Sequence Context AA Info Type MAF
rs1132746 -- 150,268,105(-) TCTCC(C/T)TGCTC reference, synonymous-codon, intron-variant, nc-transcript-variant
rs2275778 -- 150,267,078(+) ACCAG(G/T)CCCGA reference, synonymous-codon, nc-transcript-variant
rs2275780 -- 150,268,830(+) GAAGG(G/T)GGGTG utr-variant-5-prime, nc-transcript-variant
rs3754048 -- 150,269,789(-) GCCAC(C/G)GCGCT upstream-variant-2KB
rs9658936 -- 150,266,588(+) GCCCA(A/G)AGCCC reference, synonymous-codon, nc-transcript-variant

Structural Variations from Database of Genomic Variants (DGV) for APH1A Gene

Variant ID Type Subtype PubMed ID
nsv872415 CNV Loss 21882294

Relevant External Links for APH1A Gene

HapMap Linkage Disequilibrium report
APH1A
Human Gene Mutation Database (HGMD)
APH1A

Disorders for APH1A Gene

(1) University of Copenhagen DISEASES for APH1A Gene

Relevant External Links for APH1A

Genetic Association Database (GAD)
APH1A
Human Genome Epidemiology (HuGE) Navigator
APH1A
genes like me logo Genes that share disorders with APH1A: view

No data available for UniProtKB/Swiss-Prot for APH1A Gene

Publications for APH1A Gene

  1. APH1, PEN2, and nicastrin increase Abeta levels and gamma-secretase activity. (PMID: 12763021) Marlow L. … Sambamurti K. (Biochem. Biophys. Res. Commun. 2003) 3 4 23
  2. Identification of novel human genes evolutionarily conserved in Caenorhabditis elegans by comparative proteomics. (PMID: 10810093) Lai C.-H. … Lin W.-C. (Genome Res. 2000) 2 3 4
  3. aph-1 and pen-2 are required for Notch pathway signaling, gamma- secretase cleavage of betaAPP, and presenilin protein accumulation. (PMID: 12110170) Francis R. … Curtis D. (Dev. Cell 2002) 2 3 4
  4. Mammalian APH-1 interacts with presenilin and nicastrin and is required for intramembrane proteolysis of amyloid-beta precursor protein and Notch. (PMID: 12297508) Lee S.-F. … Yu G. (J. Biol. Chem. 2002) 3 4
  5. APH-1 interacts with mature and immature forms of presenilins and nicastrin and may play a role in maturation of presenilin.nicastrin complexes. (PMID: 12471034) Gu Y. … St George-Hyslop P.H. (J. Biol. Chem. 2003) 3 4

Products for APH1A Gene

Sources for APH1A Gene

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