Aph1b aph1 homolog B, gamma secretase subunit [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Aph1bprovided by MGI
Official Full Name: aph1 homolog B, gamma secretase subunitprovided by MGI
Primary source: MGI:MGI:3522097
See related: Ensembl:ENSMUSG00000032375 AllianceGenome:MGI:3522097
Gene type: protein coding
RefSeq status: PROVISIONAL
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: APH-1b; aph-1beta
Summary: Predicted to enable endopeptidase activator activity and protein-macromolecule adaptor activity. Acts upstream of or within several processes, including amyloid-beta formation; chemical synaptic transmission; and prepulse inhibition. Part of gamma-secretase complex. Is expressed in several structures, including nervous system. Human ortholog(s) of this gene implicated in coronary artery disease. Orthologous to human APH1B (aph-1 homolog B, gamma-secretase subunit). [provided by Alliance of Genome Resources, Dec 2024]
Expression: Ubiquitous expression in CNS E18 (RPKM 5.1), whole brain E14.5 (RPKM 4.7) and 28 other tissues See more
Orthologs: human all
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Genomic context

Location:: 9 C; 9 36.12 cM

Exon count:: 7

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	9	NC_000075.7 (66682484..66704671, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	9	NC_000075.6 (66775202..66797345, complement)

Chromosome 9 - NC_000075.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

We propose a model that identifies critical TMDs of Aph-1 for associations with Nct and PS for the stepwise assembly of gamma-secretase components.
Title: Specific domains in anterior pharynx-defective 1 determine its intramembrane interactions with nicastrin and presenilin.
Loss of Aph1B is associated with memory deficit.
Title: Deletion of the γ-secretase subunits Aph1B/C impairs memory and worsens the deficits of knock-in mice modeling the Alzheimer-like familial Danish dementia.
Prostaglandin I2 accumulation in neuronal cells activates PKA/CREB and JNK/c-Jun signaling pathways by phosphorylation, which results in APH-1alpha/1beta expression.
Title: Prostaglandin I2 upregulates the expression of anterior pharynx-defective-1α and anterior pharynx-defective-1β in amyloid precursor protein/presenilin 1 transgenic mice.
Abeta oligomers in the cerebrospinal fluid (CSF) further promoted the expression of APH-1alpha/-1beta (by >2.5-fold), which enhances the gamma-cleavage of APP and Abeta deposition during AD progression
Title: By suppressing the expression of anterior pharynx-defective-1α and -1β and inhibiting the aggregation of β-amyloid protein, magnesium ions inhibit the cognitive decline of amyloid precursor protein/presenilin 1 transgenic mice.
analysis of hippocampal circuitry via Aph1b-gamma-secretase/neuregulin 1 signalling
Title: Cell autonomous regulation of hippocampal circuitry via Aph1b-γ-secretase/neuregulin 1 signalling.
Upregulation of PS1/gamma-secretase activity may be a risk factor for late onset sporadic Alzheimer's disease.
Title: Increased expression of PS1 is sufficient to elevate the level and activity of γ-secretase in vivo.
study shows gamma-secretase complexes containing different Aph1 subunits have heterogeneous properties; inactivation of Aph1B gamma-secretase in an Alzheimer disease model led to improvement of disease-relevant features without Notch-related side effects
Title: gamma-Secretase heterogeneity in the Aph1 subunit: relevance for Alzheimer's disease.
the Aph1B/C-gamma-secretase complex is expressed in brain areas relevant to schizophrenia pathogenesis and that Aph1B/C deficiency causes pharmacological and behavioral abnormalities that can be reversed by antipsychotic drugs
Title: Deficiency of Aph1B/C-gamma-secretase disturbs Nrg1 cleavage and sensorimotor gating that can be reversed with antipsychotic treatment.

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Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Endonuclease-mediated (1)
Targeted (1) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables endopeptidase activator activity	ISO Inferred from Sequence Orthology more info
enables protein-macromolecule adaptor activity	IBA Inferred from Biological aspect of Ancestor more info
enables protein-macromolecule adaptor activity	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
involved_in Notch receptor processing	IBA Inferred from Biological aspect of Ancestor more info
involved_in Notch receptor processing	ISO Inferred from Sequence Orthology more info
involved_in Notch receptor processing	NAS Non-traceable Author Statement more info	PubMed
involved_in Notch signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in Notch signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in amyloid precursor protein catabolic process	ISO Inferred from Sequence Orthology more info
involved_in amyloid precursor protein catabolic process	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within amyloid-beta formation	IGI Inferred from Genetic Interaction more info	PubMed
involved_in amyloid-beta formation	ISO Inferred from Sequence Orthology more info
involved_in locomotory behavior	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within membrane protein ectodomain proteolysis	IGI Inferred from Genetic Interaction more info	PubMed
involved_in membrane protein intracellular domain proteolysis	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of endopeptidase activity	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within prepulse inhibition	IGI Inferred from Genetic Interaction more info	PubMed
involved_in protein processing	IBA Inferred from Biological aspect of Ancestor more info
involved_in protein processing	IEA Inferred from Electronic Annotation more info
involved_in protein processing	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within short-term memory	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within synaptic transmission, dopaminergic	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within synaptic transmission, glutamatergic	IGI Inferred from Genetic Interaction more info	PubMed

Component	Evidence Code	Pubs
located_in Golgi membrane	NAS Non-traceable Author Statement more info	PubMed
is_active_in endoplasmic reticulum	IBA Inferred from Biological aspect of Ancestor more info
located_in endoplasmic reticulum	NAS Non-traceable Author Statement more info	PubMed
part_of gamma-secretase complex	IBA Inferred from Biological aspect of Ancestor more info
part_of gamma-secretase complex	IDA Inferred from Direct Assay more info	PubMed
part_of gamma-secretase complex	IGI Inferred from Genetic Interaction more info	PubMed
part_of gamma-secretase complex	ISO Inferred from Sequence Orthology more info
part_of gamma-secretase complex	ISS Inferred from Sequence or Structural Similarity more info
located_in plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in plasma membrane	TAS Traceable Author Statement more info
located_in synapse	IEA Inferred from Electronic Annotation more info
located_in transport vesicle	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: gamma-secretase subunit APH-1B

Names: APH1B homolog; anterior pharynx defective 1b homolog; anterior pharynx defective 1c homolog

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_177583.4 → NP_808251.1 gamma-secretase subunit APH-1B

See identical proteins and their annotated locations for NP_808251.1

Status: PROVISIONAL

Source sequence(s)

AC134429, AC142504

Consensus CDS

CCDS23307.1

UniProtKB/Swiss-Prot

Q3U3B5, Q8C7N7, Q8CEC9

UniProtKB/TrEMBL

F8WHK7

Related

ENSMUSP00000034934.9, ENSMUST00000034934.15

Conserved Domains (1) summary

pfam06105
Location:2 → 232

Aph-1; Aph-1 protein

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCm39 C57BL/6J

Genomic

NC_000075.7 Reference GRCm39 C57BL/6J

Range

66682484..66704671 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006510922.5 → XP_006510985.1 gamma-secretase subunit APH-1B isoform X1

Conserved Domains (1) summary

pfam06105
Location:3 → 279

Aph-1; Aph-1 protein