Q96BI3 · APH1A_HUMAN
- ProteinGamma-secretase subunit APH-1A
- GeneAPH1A
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids265 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Non-catalytic subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (amyloid-beta precursor protein) (PubMed:12297508, PubMed:12522139, PubMed:12679784, PubMed:12763021, PubMed:25043039, PubMed:26280335, PubMed:30598546, PubMed:30630874).
Required for normal gamma-secretase assembly (PubMed:12471034, PubMed:12522139, PubMed:12763021, PubMed:19369254).
The gamma-secretase complex plays a role in Notch and Wnt signaling cascades and regulation of downstream processes via its role in processing key regulatory proteins, and by regulating cytosolic CTNNB1 levels (Probable)
Required for normal gamma-secretase assembly (PubMed:12471034, PubMed:12522139, PubMed:12763021, PubMed:19369254).
The gamma-secretase complex plays a role in Notch and Wnt signaling cascades and regulation of downstream processes via its role in processing key regulatory proteins, and by regulating cytosolic CTNNB1 levels (Probable)
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Keywords
- Biological process
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameGamma-secretase subunit APH-1A
- Short namesAPH-1a
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ96BI3
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
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.
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-2 | Lumenal | ||||
Sequence: MG | ||||||
Transmembrane | 3-23 | Helical; Name=1 | ||||
Sequence: AAVFFGCTFVAFGPAFALFLI | ||||||
Topological domain | 24-31 | Cytoplasmic | ||||
Sequence: TVAGDPLR | ||||||
Transmembrane | 32-52 | Helical; Name=2 | ||||
Sequence: VIILVAGAFFWLVSLLLASVV | ||||||
Topological domain | 53-68 | Lumenal | ||||
Sequence: WFILVHVTDRSDARLQ | ||||||
Transmembrane | 69-89 | Helical; Name=3 | ||||
Sequence: YGLLIFGAAVSVLLQEVFRFA | ||||||
Topological domain | 90-118 | Cytoplasmic | ||||
Sequence: YYKLLKKADEGLASLSEDGRSPISIRQMA | ||||||
Transmembrane | 119-139 | Helical; Name=4 | ||||
Sequence: YVSGLSFGIISGVFSVINILA | ||||||
Topological domain | 140-158 | Lumenal | ||||
Sequence: DALGPGVVGIHGDSPYYFL | ||||||
Transmembrane | 159-179 | Helical; Name=5 | ||||
Sequence: TSAFLTAAIILLHTFWGVVFF | ||||||
Topological domain | 180-186 | Cytoplasmic | ||||
Sequence: DACERRR | ||||||
Transmembrane | 187-207 | Helical; Name=6 | ||||
Sequence: YWALGLVVGSHLLTSGLTFLN | ||||||
Topological domain | 208-213 | Lumenal | ||||
Sequence: PWYEAS | ||||||
Transmembrane | 214-234 | Helical; Name=7 | ||||
Sequence: LLPIYAVTVSMGLWAFITAGG | ||||||
Topological domain | 235-265 | Cytoplasmic | ||||
Sequence: SLRSIQRSLLCRRQEDSRVMVYSALRIPPED |
Keywords
- Cellular component
Disease & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 171 | Impaired gamma-secretease assembly and reduced proteolytic activity of the gamma-secretase complex. | ||||
Sequence: H → A | ||||||
Mutagenesis | 197 | Impaired gamma-secretease assembly and reduced proteolytic activity of the gamma-secretase complex. | ||||
Sequence: H → A |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 204 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000221050 | 1-265 | Gamma-secretase subunit APH-1A | |||
Sequence: MGAAVFFGCTFVAFGPAFALFLITVAGDPLRVIILVAGAFFWLVSLLLASVVWFILVHVTDRSDARLQYGLLIFGAAVSVLLQEVFRFAYYKLLKKADEGLASLSEDGRSPISIRQMAYVSGLSFGIISGVFSVINILADALGPGVVGIHGDSPYYFLTSAFLTAAIILLHTFWGVVFFDACERRRYWALGLVVGSHLLTSGLTFLNPWYEASLLPIYAVTVSMGLWAFITAGGSLRSIQRSLLCRRQEDSRVMVYSALRIPPED |
Proteomic databases
PTM databases
Interaction
Subunit
The functional gamma-secretase complex is composed of at least four polypeptides: a presenilin homodimer (PSEN1 or PSEN2), nicastrin (NCSTN), APH1 (APH1A or APH1B) and PSENEN/PEN2 (PubMed:12297508, PubMed:12740439, PubMed:19369254, PubMed:25043039, PubMed:26280335, PubMed:26623517, PubMed:30598546, PubMed:30630874).
Binary interactions
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Sequence & Isoforms
- Sequence statusComplete
This entry describes 3 isoforms produced by Alternative splicing.
Q96BI3-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- SynonymsL, Aph-alpha1
- Length265
- Mass (Da)28,996
- Last updated2001-12-01 v1
- Checksum8E37984A1DECC263
Q96BI3-2
- Name2
- SynonymsS, Aph-alpha2
Q96BI3-3
- Name3
- Differences from canonical
- 39-120: AFFWLVSLLLASVVWFILVHVTDRSDARLQYGLLIFGAAVSVLLQEVFRFAYYKLLKKADEGLASLSEDGRSPISIRQMAYV → RCSALPTTSCLI
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
Q5TB21 | Q5TB21_HUMAN | APH1A | 150 |
Sequence caution
Features
Showing features for alternative sequence, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_045424 | 39-120 | in isoform 3 | |||
Sequence: AFFWLVSLLLASVVWFILVHVTDRSDARLQYGLLIFGAAVSVLLQEVFRFAYYKLLKKADEGLASLSEDGRSPISIRQMAYV → RCSALPTTSCLI | ||||||
Sequence conflict | 236 | in Ref. 8; AAH01230 | ||||
Sequence: L → I | ||||||
Alternative sequence | VSP_008355 | 246-247 | in isoform 2 | |||
Sequence: RR → KD | ||||||
Alternative sequence | VSP_008356 | 248-265 | in isoform 2 | |||
Sequence: Missing |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF508787 EMBL· GenBank· DDBJ | AAN63816.1 EMBL· GenBank· DDBJ | mRNA | Frameshift | |
AY113698 EMBL· GenBank· DDBJ | AAM61955.1 EMBL· GenBank· DDBJ | mRNA | ||
AY113699 EMBL· GenBank· DDBJ | AAM61956.1 EMBL· GenBank· DDBJ | mRNA | ||
AF151835 EMBL· GenBank· DDBJ | AAD34072.1 EMBL· GenBank· DDBJ | mRNA | Frameshift | |
AY358951 EMBL· GenBank· DDBJ | AAQ89310.1 EMBL· GenBank· DDBJ | mRNA | ||
AK027879 EMBL· GenBank· DDBJ | BAG51389.1 EMBL· GenBank· DDBJ | mRNA | ||
AK075295 EMBL· GenBank· DDBJ | BAC11529.1 EMBL· GenBank· DDBJ | mRNA | ||
AK298832 EMBL· GenBank· DDBJ | BAG60962.1 EMBL· GenBank· DDBJ | mRNA | ||
AL138795 EMBL· GenBank· DDBJ | CAI22811.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AL138795 EMBL· GenBank· DDBJ | CAI22812.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471121 EMBL· GenBank· DDBJ | EAW53565.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471121 EMBL· GenBank· DDBJ | EAW53566.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471121 EMBL· GenBank· DDBJ | EAW53567.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC001230 EMBL· GenBank· DDBJ | AAH01230.1 EMBL· GenBank· DDBJ | mRNA | ||
BC008732 EMBL· GenBank· DDBJ | AAH08732.1 EMBL· GenBank· DDBJ | mRNA | ||
BC009501 EMBL· GenBank· DDBJ | AAH09501.1 EMBL· GenBank· DDBJ | mRNA | ||
BC015568 EMBL· GenBank· DDBJ | AAH15568.1 EMBL· GenBank· DDBJ | mRNA | ||
BC017699 EMBL· GenBank· DDBJ | AAH17699.1 EMBL· GenBank· DDBJ | mRNA | ||
BC020590 EMBL· GenBank· DDBJ | AAH20590.1 EMBL· GenBank· DDBJ | mRNA |