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Protein

Gamma-secretase subunit APH-1A

Gene

APH1A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.3 Publications

GO - Molecular functioni

GO - Biological processi

  • amyloid precursor protein catabolic process Source: UniProtKB
  • ephrin receptor signaling pathway Source: Reactome
  • membrane protein ectodomain proteolysis Source: HGNC
  • membrane protein intracellular domain proteolysis Source: UniProtKB
  • metanephros development Source: Ensembl
  • Notch receptor processing Source: UniProtKB
  • Notch signaling pathway Source: GO_Central
  • positive regulation of apoptotic process Source: Reactome
  • positive regulation of catalytic activity Source: HGNC
  • protein processing Source: HGNC
Complete GO annotation...

Keywords - Biological processi

Notch signaling pathway

Enzyme and pathway databases

BioCyciZFISH:ENSG00000117362-MONOMER.
ReactomeiR-HSA-1251985. Nuclear signaling by ERBB4.
R-HSA-193692. Regulated proteolysis of p75NTR.
R-HSA-1980148. Signaling by NOTCH3.
R-HSA-1980150. Signaling by NOTCH4.
R-HSA-205043. NRIF signals cell death from the nucleus.
R-HSA-2122948. Activated NOTCH1 Transmits Signal to the Nucleus.
R-HSA-2644606. Constitutive Signaling by NOTCH1 PEST Domain Mutants.
R-HSA-2894862. Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants.
R-HSA-2979096. NOTCH2 Activation and Transmission of Signal to the Nucleus.
R-HSA-3928665. EPH-ephrin mediated repulsion of cells.
SignaLinkiQ96BI3.
SIGNORiQ96BI3.

Names & Taxonomyi

Protein namesi
Recommended name:
Gamma-secretase subunit APH-1A
Short name:
APH-1a
Alternative name(s):
Aph-1alpha
Presenilin-stabilization factor
Gene namesi
Name:APH1A
Synonyms:PSF
ORF Names:CGI-78, UNQ579/PRO1141
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:29509. APH1A.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 2LumenalSequence analysis2
Transmembranei3 – 23Helical; Name=1Sequence analysisAdd BLAST21
Topological domaini24 – 31CytoplasmicSequence analysis8
Transmembranei32 – 52Helical; Name=2Sequence analysisAdd BLAST21
Topological domaini53 – 68LumenalSequence analysisAdd BLAST16
Transmembranei69 – 89Helical; Name=3Sequence analysisAdd BLAST21
Topological domaini90 – 118CytoplasmicSequence analysisAdd BLAST29
Transmembranei119 – 139Helical; Name=4Sequence analysisAdd BLAST21
Topological domaini140 – 158LumenalSequence analysisAdd BLAST19
Transmembranei159 – 179Helical; Name=5Sequence analysisAdd BLAST21
Topological domaini180 – 186CytoplasmicSequence analysis7
Transmembranei187 – 207Helical; Name=6Sequence analysisAdd BLAST21
Topological domaini208 – 213LumenalSequence analysis6
Transmembranei214 – 234Helical; Name=7Sequence analysisAdd BLAST21
Topological domaini235 – 265CytoplasmicSequence analysisAdd BLAST31

GO - Cellular componenti

  • endoplasmic reticulum Source: HGNC
  • endoplasmic reticulum membrane Source: UniProtKB-SubCell
  • gamma-secretase complex Source: GO_Central
  • Golgi apparatus Source: HGNC
  • Golgi cisterna membrane Source: UniProtKB-SubCell
  • integral component of plasma membrane Source: HGNC
  • membrane Source: UniProtKB
  • plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Golgi apparatus, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi51107.
OpenTargetsiENSG00000117362.
PharmGKBiPA142672599.

Chemistry databases

ChEMBLiCHEMBL2094135.

Polymorphism and mutation databases

BioMutaiAPH1A.
DMDMi37077707.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002210501 – 265Gamma-secretase subunit APH-1AAdd BLAST265

Proteomic databases

MaxQBiQ96BI3.
PaxDbiQ96BI3.
PeptideAtlasiQ96BI3.
PRIDEiQ96BI3.
TopDownProteomicsiQ96BI3-2. [Q96BI3-2]

PTM databases

iPTMnetiQ96BI3.
PhosphoSitePlusiQ96BI3.
SwissPalmiQ96BI3.

Expressioni

Tissue specificityi

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.1 Publication

Gene expression databases

BgeeiENSG00000117362.
CleanExiHS_APH1A.
ExpressionAtlasiQ96BI3. baseline and differential.
GenevisibleiQ96BI3. HS.

Organism-specific databases

HPAiCAB037272.

Interactioni

Subunit structurei

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.

Binary interactionsi

WithEntry#Exp.IntActNotes
NCSTNQ925423EBI-2606935,EBI-998440

Protein-protein interaction databases

BioGridi119296. 22 interactors.
DIPiDIP-44671N.
IntActiQ96BI3. 16 interactors.
STRINGi9606.ENSP00000358105.

Chemistry databases

BindingDBiQ96BI3.

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5A63electron microscopy3.40C1-265[»]
5FN2electron microscopy4.20C1-265[»]
5FN3electron microscopy4.10C1-265[»]
5FN4electron microscopy4.00C1-265[»]
5FN5electron microscopy4.30C1-265[»]
ProteinModelPortaliQ96BI3.
SMRiQ96BI3.
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.
InParanoidiQ96BI3.
KOiK06172.
OMAiLLHTFWS.
OrthoDBiEOG091G0IH0.
PhylomeDBiQ96BI3.
TreeFamiTF314362.

Family and domain databases

InterProiIPR009294. Aph-1.
[Graphical view]
PANTHERiPTHR12889. PTHR12889. 1 hit.
PfamiPF06105. Aph-1. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q96BI3-1) [UniParc]FASTAAdd to basket
Also known as: L, Aph-alpha1

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 FVAFGPAFAL 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 RSLLCRRQED
260
SRVMVYSALR IPPED
Length:265
Mass (Da):28,996
Last modified:December 1, 2001 - v1
Checksum:i8E37984A1DECC263
GO
Isoform 2 (identifier: Q96BI3-2) [UniParc]FASTAAdd to basket
Also known as: S, Aph-alpha2

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

Show »
Length:247
Mass (Da):26,840
Checksum:i8EECF2236C1EA4A0
GO
Isoform 3 (identifier: Q96BI3-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     39-120: AFFWLVSLLL...PISIRQMAYV → RCSALPTTSCLI

Show »
Length:195
Mass (Da):20,977
Checksum:iA6D104A120AEBFA2
GO

Sequence cautioni

The sequence AAD34072 differs from that shown. Reason: Frameshift at position 243.Curated
The sequence AAN63816 differs from that shown. Reason: Frameshift at position 243.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti236L → I in AAH01230 (PubMed:15489334).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_04542439 – 120AFFWL…QMAYV → RCSALPTTSCLI in isoform 3. 1 PublicationAdd BLAST82
Alternative sequenceiVSP_008355246 – 247RR → KD in isoform 2. 5 Publications2
Alternative sequenceiVSP_008356248 – 265Missing in isoform 2. 5 PublicationsAdd BLAST18

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF508787 mRNA. Translation: AAN63816.1. Frameshift.
AY113698 mRNA. Translation: AAM61955.1.
AY113699 mRNA. Translation: AAM61956.1.
AF151835 mRNA. Translation: AAD34072.1. Frameshift.
AY358951 mRNA. Translation: AAQ89310.1.
AK027879 mRNA. Translation: BAG51389.1.
AK075295 mRNA. Translation: BAC11529.1.
AK298832 mRNA. Translation: BAG60962.1.
AL138795 Genomic DNA. Translation: CAI22811.1.
AL138795 Genomic DNA. Translation: CAI22812.1.
CH471121 Genomic DNA. Translation: EAW53565.1.
CH471121 Genomic DNA. Translation: EAW53566.1.
CH471121 Genomic DNA. Translation: EAW53567.1.
BC001230 mRNA. Translation: AAH01230.1.
BC008732 mRNA. Translation: AAH08732.1.
BC009501 mRNA. Translation: AAH09501.1.
BC015568 mRNA. Translation: AAH15568.1.
BC017699 mRNA. Translation: AAH17699.1.
BC020590 mRNA. Translation: AAH20590.1.
CCDSiCCDS41390.1. [Q96BI3-1]
CCDS41391.1. [Q96BI3-2]
CCDS58025.1. [Q96BI3-3]
RefSeqiNP_001071096.1. NM_001077628.2. [Q96BI3-1]
NP_001230700.1. NM_001243771.1.
NP_001230701.1. NM_001243772.1. [Q96BI3-3]
NP_057106.2. NM_016022.3. [Q96BI3-2]
UniGeneiHs.108408.
Hs.735911.

Genome annotation databases

EnsembliENST00000360244; ENSP00000353380; ENSG00000117362. [Q96BI3-2]
ENST00000369109; ENSP00000358105; ENSG00000117362. [Q96BI3-1]
ENST00000414276; ENSP00000397473; ENSG00000117362. [Q96BI3-3]
GeneIDi51107.
KEGGihsa:51107.
UCSCiuc001ety.3. human. [Q96BI3-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF508787 mRNA. Translation: AAN63816.1. Frameshift.
AY113698 mRNA. Translation: AAM61955.1.
AY113699 mRNA. Translation: AAM61956.1.
AF151835 mRNA. Translation: AAD34072.1. Frameshift.
AY358951 mRNA. Translation: AAQ89310.1.
AK027879 mRNA. Translation: BAG51389.1.
AK075295 mRNA. Translation: BAC11529.1.
AK298832 mRNA. Translation: BAG60962.1.
AL138795 Genomic DNA. Translation: CAI22811.1.
AL138795 Genomic DNA. Translation: CAI22812.1.
CH471121 Genomic DNA. Translation: EAW53565.1.
CH471121 Genomic DNA. Translation: EAW53566.1.
CH471121 Genomic DNA. Translation: EAW53567.1.
BC001230 mRNA. Translation: AAH01230.1.
BC008732 mRNA. Translation: AAH08732.1.
BC009501 mRNA. Translation: AAH09501.1.
BC015568 mRNA. Translation: AAH15568.1.
BC017699 mRNA. Translation: AAH17699.1.
BC020590 mRNA. Translation: AAH20590.1.
CCDSiCCDS41390.1. [Q96BI3-1]
CCDS41391.1. [Q96BI3-2]
CCDS58025.1. [Q96BI3-3]
RefSeqiNP_001071096.1. NM_001077628.2. [Q96BI3-1]
NP_001230700.1. NM_001243771.1.
NP_001230701.1. NM_001243772.1. [Q96BI3-3]
NP_057106.2. NM_016022.3. [Q96BI3-2]
UniGeneiHs.108408.
Hs.735911.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5A63electron microscopy3.40C1-265[»]
5FN2electron microscopy4.20C1-265[»]
5FN3electron microscopy4.10C1-265[»]
5FN4electron microscopy4.00C1-265[»]
5FN5electron microscopy4.30C1-265[»]
ProteinModelPortaliQ96BI3.
SMRiQ96BI3.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi119296. 22 interactors.
DIPiDIP-44671N.
IntActiQ96BI3. 16 interactors.
STRINGi9606.ENSP00000358105.

Chemistry databases

BindingDBiQ96BI3.
ChEMBLiCHEMBL2094135.

PTM databases

iPTMnetiQ96BI3.
PhosphoSitePlusiQ96BI3.
SwissPalmiQ96BI3.

Polymorphism and mutation databases

BioMutaiAPH1A.
DMDMi37077707.

Proteomic databases

MaxQBiQ96BI3.
PaxDbiQ96BI3.
PeptideAtlasiQ96BI3.
PRIDEiQ96BI3.
TopDownProteomicsiQ96BI3-2. [Q96BI3-2]

Protocols and materials databases

DNASUi51107.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000360244; ENSP00000353380; ENSG00000117362. [Q96BI3-2]
ENST00000369109; ENSP00000358105; ENSG00000117362. [Q96BI3-1]
ENST00000414276; ENSP00000397473; ENSG00000117362. [Q96BI3-3]
GeneIDi51107.
KEGGihsa:51107.
UCSCiuc001ety.3. human. [Q96BI3-1]

Organism-specific databases

CTDi51107.
DisGeNETi51107.
GeneCardsiAPH1A.
HGNCiHGNC:29509. APH1A.
HPAiCAB037272.
MIMi607629. gene.
neXtProtiNX_Q96BI3.
OpenTargetsiENSG00000117362.
PharmGKBiPA142672599.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3972. Eukaryota.
ENOG4111FIJ. LUCA.
GeneTreeiENSGT00390000002049.
HOGENOMiHOG000007541.
HOVERGENiHBG050541.
InParanoidiQ96BI3.
KOiK06172.
OMAiLLHTFWS.
OrthoDBiEOG091G0IH0.
PhylomeDBiQ96BI3.
TreeFamiTF314362.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000117362-MONOMER.
ReactomeiR-HSA-1251985. Nuclear signaling by ERBB4.
R-HSA-193692. Regulated proteolysis of p75NTR.
R-HSA-1980148. Signaling by NOTCH3.
R-HSA-1980150. Signaling by NOTCH4.
R-HSA-205043. NRIF signals cell death from the nucleus.
R-HSA-2122948. Activated NOTCH1 Transmits Signal to the Nucleus.
R-HSA-2644606. Constitutive Signaling by NOTCH1 PEST Domain Mutants.
R-HSA-2894862. Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants.
R-HSA-2979096. NOTCH2 Activation and Transmission of Signal to the Nucleus.
R-HSA-3928665. EPH-ephrin mediated repulsion of cells.
SignaLinkiQ96BI3.
SIGNORiQ96BI3.

Miscellaneous databases

ChiTaRSiAPH1A. human.
GenomeRNAii51107.
PROiQ96BI3.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000117362.
CleanExiHS_APH1A.
ExpressionAtlasiQ96BI3. baseline and differential.
GenevisibleiQ96BI3. HS.

Family and domain databases

InterProiIPR009294. Aph-1.
[Graphical view]
PANTHERiPTHR12889. PTHR12889. 1 hit.
PfamiPF06105. Aph-1. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiAPH1A_HUMAN
AccessioniPrimary (citable) accession number: Q96BI3
Secondary accession number(s): B4DQK0
, Q5TB22, Q5TB23, Q969R6, Q9BVG0, Q9Y386
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 26, 2003
Last sequence update: December 1, 2001
Last modified: November 2, 2016
This is version 141 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.