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Protein

Gamma-secretase subunit APH-1A

Gene

Aph1a

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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:15634781, PubMed:19369254). Required for normal gamma-secretase assembly (PubMed:15634781, 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).Curated2 Publications

GO - Molecular functioni

  • endopeptidase activity Source: MGI
  • peptidase activity Source: MGI

GO - Biological processi

Keywordsi

Biological processNotch signaling pathway

Enzyme and pathway databases

ReactomeiR-MMU-1251985 Nuclear signaling by ERBB4
R-MMU-193692 Regulated proteolysis of p75NTR
R-MMU-1980150 Signaling by NOTCH4
R-MMU-205043 NRIF signals cell death from the nucleus
R-MMU-3928665 EPH-ephrin mediated repulsion of cells
R-MMU-9013507 NOTCH3 Activation and Transmission of Signal to the Nucleus
R-MMU-9017802 Noncanonical activation of NOTCH3

Protein family/group databases

TCDBi9.B.47.1.1 the Gama-secretase (Gama-secretase) family

Names & Taxonomyi

Protein namesi
Recommended name:
Gamma-secretase subunit APH-1A
Short name:
APH-1a
Alternative name(s):
Aph-1alpha
Gene namesi
Name:Aph1a
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 3

Organism-specific databases

MGIiMGI:2385110 Aph1a

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 2LumenalBy similarity2
Transmembranei3 – 23Helical; Name=1By similarityAdd BLAST21
Topological domaini24 – 31CytoplasmicBy similarity8
Transmembranei32 – 52Helical; Name=2By similarityAdd BLAST21
Topological domaini53 – 68LumenalBy similarityAdd BLAST16
Transmembranei69 – 89Helical; Name=3By similarityAdd BLAST21
Topological domaini90 – 118CytoplasmicBy similarityAdd BLAST29
Transmembranei119 – 139Helical; Name=4By similarityAdd BLAST21
Topological domaini140 – 158LumenalBy similarityAdd BLAST19
Transmembranei159 – 179Helical; Name=5By similarityAdd BLAST21
Topological domaini180 – 186CytoplasmicBy similarity7
Transmembranei187 – 207Helical; Name=6By similarityAdd BLAST21
Topological domaini208 – 213LumenalBy similarity6
Transmembranei214 – 234Helical; Name=7By similarityAdd BLAST21
Topological domaini235 – 265CytoplasmicBy similarityAdd BLAST31

Keywords - Cellular componenti

Endoplasmic reticulum, Golgi apparatus, Membrane

Pathology & Biotechi

Disruption phenotypei

Full embryonic lethality. No live homozygous embryos are present after 11 dpc.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002210511 – 265Gamma-secretase subunit APH-1AAdd BLAST265

Proteomic databases

PaxDbiQ8BVF7
PRIDEiQ8BVF7

PTM databases

iPTMnetiQ8BVF7
PhosphoSitePlusiQ8BVF7

Expressioni

Gene expression databases

BgeeiENSMUSG00000015750
ExpressionAtlasiQ8BVF7 baseline and differential
GenevisibleiQ8BVF7 MM

Interactioni

Subunit structurei

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 PEN2.2 Publications

Protein-protein interaction databases

BioGridi230528, 14 interactors
CORUMiQ8BVF7
IntActiQ8BVF7, 1 interactor
MINTiQ8BVF7
STRINGi10090.ENSMUSP00000058846

Structurei

3D structure databases

ProteinModelPortaliQ8BVF7
SMRiQ8BVF7
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the APH-1 family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3972 Eukaryota
ENOG4111FIJ LUCA
GeneTreeiENSGT00390000002049
HOGENOMiHOG000007541
HOVERGENiHBG050541
InParanoidiQ8BVF7
KOiK06172
OMAiWSVIFFN
OrthoDBiEOG091G0IH0
PhylomeDBiQ8BVF7
TreeFamiTF314362

Family and domain databases

InterProiView protein in InterPro
IPR009294 Aph-1
PANTHERiPTHR12889 PTHR12889, 1 hit
PfamiView protein in Pfam
PF06105 Aph-1, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8BVF7-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MGAAVFFGCT FVAFGPAFSL FLITVAGDPL RVIILVAGAF FWLVSLLLAS
60 70 80 90 100
VVWFILVHVT DRSDARLQYG LLIFGAAVSV LLQEVFRFAY YKLLKKADEG
110 120 130 140 150
LASLSEDGRS PISIRQMAYV SGLSFGIISG VFSVINILAD ALGPGVVGIH
160 170 180 190 200
GDSPYYFLTS AFLTAAIILL HTFWGVVFFD ACERRRYWAL GLVVGSHLLT
210 220 230 240 250
SGLTFLNPWY EASLLPIYAV TVSMGLWAFI TAGGSLRSIQ RSLSCRRQED
260
SRVMVYSALR IPPED
Length:265
Mass (Da):28,986
Last modified:September 26, 2003 - v2
Checksum:i1E37922A1DFAA92C
GO
Isoform 2 (identifier: Q8BVF7-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     246-247: RR → KD
     248-265: Missing.

Show »
Length:247
Mass (Da):26,830
Checksum:i47C86078DE8D7262
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_008357246 – 247RR → KD in isoform 2. 2 Publications2
Alternative sequenceiVSP_008358248 – 265Missing in isoform 2. 2 PublicationsAdd BLAST18

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC012406 mRNA Translation: AAH12406.1
BC024111 mRNA Translation: AAH24111.1
AK078343 mRNA Translation: BAC37228.1
CCDSiCCDS17624.1 [Q8BVF7-2]
CCDS50999.1 [Q8BVF7-1]
RefSeqiNP_666216.1, NM_146104.3 [Q8BVF7-2]
NP_666246.1, NM_146134.2 [Q8BVF7-1]
UniGeneiMm.306954
Mm.337825
Mm.486756

Genome annotation databases

EnsembliENSMUST00000015894; ENSMUSP00000015894; ENSMUSG00000015750 [Q8BVF7-2]
ENSMUST00000056710; ENSMUSP00000058846; ENSMUSG00000015750 [Q8BVF7-1]
GeneIDi226548
KEGGimmu:226548
UCSCiuc008qlq.2 mouse [Q8BVF7-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiAPH1A_MOUSE
AccessioniPrimary (citable) accession number: Q8BVF7
Secondary accession number(s): Q8R1T3, Q91VL5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 26, 2003
Last sequence update: September 26, 2003
Last modified: May 23, 2018
This is version 140 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

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