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Q96BI3

- APH1A_HUMAN

UniProt

Q96BI3 - APH1A_HUMAN

Protein

Gamma-secretase subunit APH-1A

Gene

APH1A

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
    • BLAST
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    • History
      Entry version 122 (01 Oct 2014)
      Sequence version 1 (01 Dec 2001)
      Previous versions | rss
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    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

    1. endopeptidase activity Source: Ensembl
    2. protein binding Source: UniProtKB

    GO - Biological processi

    1. amyloid precursor protein catabolic process Source: UniProtKB
    2. apoptotic signaling pathway Source: Reactome
    3. membrane protein ectodomain proteolysis Source: HGNC
    4. membrane protein intracellular domain proteolysis Source: UniProtKB
    5. metanephros development Source: Ensembl
    6. neurotrophin TRK receptor signaling pathway Source: Reactome
    7. Notch receptor processing Source: UniProtKB
    8. Notch signaling pathway Source: Reactome
    9. positive regulation of apoptotic process Source: Reactome
    10. positive regulation of catalytic activity Source: HGNC
    11. protein processing Source: HGNC

    Keywords - Biological processi

    Notch signaling pathway

    Enzyme and pathway databases

    ReactomeiREACT_116022. Nuclear signaling by ERBB4.
    REACT_118614. Activated NOTCH1 Transmits Signal to the Nucleus.
    REACT_118636. Signaling by NOTCH4.
    REACT_118862. Signaling by NOTCH3.
    REACT_13443. Regulated proteolysis of p75NTR.
    REACT_13643. NRIF signals cell death from the nucleus.
    REACT_160205. NOTCH2 Activation and Transmission of Signal to the Nucleus.
    REACT_160243. Constitutive Signaling by NOTCH1 PEST Domain Mutants.
    REACT_160254. Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants.
    SignaLinkiQ96BI3.

    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
    ProteomesiUP000005640: Chromosome 1

    Organism-specific databases

    HGNCiHGNC:29509. APH1A.

    Subcellular locationi

    Endoplasmic reticulum membrane; Multi-pass membrane protein. Golgi apparatusGolgi stack membrane; Multi-pass membrane protein
    Note: Predominantly located in the endoplasmic reticulum and in the cis-Golgi.

    GO - Cellular componenti

    1. endoplasmic reticulum Source: HGNC
    2. endoplasmic reticulum membrane Source: UniProtKB-SubCell
    3. Golgi apparatus Source: HGNC
    4. Golgi cisterna membrane Source: UniProtKB-SubCell
    5. integral component of plasma membrane Source: HGNC
    6. membrane Source: UniProtKB
    7. plasma membrane Source: Reactome

    Keywords - Cellular componenti

    Endoplasmic reticulum, Golgi apparatus, Membrane

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA142672599.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 265265Gamma-secretase subunit APH-1APRO_0000221050Add
    BLAST

    Proteomic databases

    MaxQBiQ96BI3.
    PaxDbiQ96BI3.
    PRIDEiQ96BI3.

    PTM databases

    PhosphoSiteiQ96BI3.

    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

    ArrayExpressiQ96BI3.
    BgeeiQ96BI3.
    CleanExiHS_APH1A.
    GenevestigatoriQ96BI3.

    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. 17 interactions.
    IntActiQ96BI3. 16 interactions.
    STRINGi9606.ENSP00000358105.

    Structurei

    3D structure databases

    ProteinModelPortaliQ96BI3.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 22LumenalSequence Analysis
    Topological domaini24 – 318CytoplasmicSequence Analysis
    Topological domaini53 – 6816LumenalSequence AnalysisAdd
    BLAST
    Topological domaini90 – 11829CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini140 – 15819LumenalSequence AnalysisAdd
    BLAST
    Topological domaini180 – 1867CytoplasmicSequence Analysis
    Topological domaini208 – 2136LumenalSequence Analysis
    Topological domaini235 – 26531CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei3 – 2321Helical; Name=1Sequence AnalysisAdd
    BLAST
    Transmembranei32 – 5221Helical; Name=2Sequence AnalysisAdd
    BLAST
    Transmembranei69 – 8921Helical; Name=3Sequence AnalysisAdd
    BLAST
    Transmembranei119 – 13921Helical; Name=4Sequence AnalysisAdd
    BLAST
    Transmembranei159 – 17921Helical; Name=5Sequence AnalysisAdd
    BLAST
    Transmembranei187 – 20721Helical; Name=6Sequence AnalysisAdd
    BLAST
    Transmembranei214 – 23421Helical; Name=7Sequence AnalysisAdd
    BLAST

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the APH-1 family.Curated

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG300477.
    HOGENOMiHOG000007541.
    HOVERGENiHBG050541.
    InParanoidiQ96BI3.
    KOiK06172.
    OMAiFIAFGPP.
    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. Align

    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

    MGAAVFFGCT FVAFGPAFAL FLITVAGDPL RVIILVAGAF FWLVSLLLAS    50
    VVWFILVHVT DRSDARLQYG LLIFGAAVSV LLQEVFRFAY YKLLKKADEG 100
    LASLSEDGRS PISIRQMAYV SGLSFGIISG VFSVINILAD ALGPGVVGIH 150
    GDSPYYFLTS AFLTAAIILL HTFWGVVFFD ACERRRYWAL GLVVGSHLLT 200
    SGLTFLNPWY EASLLPIYAV TVSMGLWAFI TAGGSLRSIQ RSLLCRRQED 250
    SRVMVYSALR IPPED 265
    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 AAD34072.1 differs from that shown. Reason: Frameshift at position 243.
    The sequence AAN63816.1 differs from that shown. Reason: Frameshift at position 243.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti236 – 2361L → I in AAH01230. (PubMed:15489334)Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei39 – 12082AFFWL…QMAYV → RCSALPTTSCLI in isoform 3. 1 PublicationVSP_045424Add
    BLAST
    Alternative sequencei246 – 2472RR → KD in isoform 2. 5 PublicationsVSP_008355
    Alternative sequencei248 – 26518Missing in isoform 2. 5 PublicationsVSP_008356Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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.2. human. [Q96BI3-1]
    uc001etz.2. human. [Q96BI3-2]
    uc010pbx.2. human.

    Polymorphism databases

    DMDMi37077707.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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 .
    CCDSi CCDS41390.1. [Q96BI3-1 ]
    CCDS41391.1. [Q96BI3-2 ]
    CCDS58025.1. [Q96BI3-3 ]
    RefSeqi NP_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 ]
    UniGenei Hs.108408.
    Hs.735911.

    3D structure databases

    ProteinModelPortali Q96BI3.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 119296. 17 interactions.
    IntActi Q96BI3. 16 interactions.
    STRINGi 9606.ENSP00000358105.

    Chemistry

    BindingDBi Q96BI3.
    ChEMBLi CHEMBL2094135.

    PTM databases

    PhosphoSitei Q96BI3.

    Polymorphism databases

    DMDMi 37077707.

    Proteomic databases

    MaxQBi Q96BI3.
    PaxDbi Q96BI3.
    PRIDEi Q96BI3.

    Protocols and materials databases

    DNASUi 51107.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000360244 ; ENSP00000353380 ; ENSG00000117362 . [Q96BI3-2 ]
    ENST00000369109 ; ENSP00000358105 ; ENSG00000117362 . [Q96BI3-1 ]
    ENST00000414276 ; ENSP00000397473 ; ENSG00000117362 . [Q96BI3-3 ]
    GeneIDi 51107.
    KEGGi hsa:51107.
    UCSCi uc001ety.2. human. [Q96BI3-1 ]
    uc001etz.2. human. [Q96BI3-2 ]
    uc010pbx.2. human.

    Organism-specific databases

    CTDi 51107.
    GeneCardsi GC01M150237.
    HGNCi HGNC:29509. APH1A.
    HPAi CAB037272.
    MIMi 607629. gene.
    neXtProti NX_Q96BI3.
    PharmGKBi PA142672599.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG300477.
    HOGENOMi HOG000007541.
    HOVERGENi HBG050541.
    InParanoidi Q96BI3.
    KOi K06172.
    OMAi FIAFGPP.
    PhylomeDBi Q96BI3.
    TreeFami TF314362.

    Enzyme and pathway databases

    Reactomei REACT_116022. Nuclear signaling by ERBB4.
    REACT_118614. Activated NOTCH1 Transmits Signal to the Nucleus.
    REACT_118636. Signaling by NOTCH4.
    REACT_118862. Signaling by NOTCH3.
    REACT_13443. Regulated proteolysis of p75NTR.
    REACT_13643. NRIF signals cell death from the nucleus.
    REACT_160205. NOTCH2 Activation and Transmission of Signal to the Nucleus.
    REACT_160243. Constitutive Signaling by NOTCH1 PEST Domain Mutants.
    REACT_160254. Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants.
    SignaLinki Q96BI3.

    Miscellaneous databases

    GenomeRNAii 51107.
    NextBioi 53845.
    PROi Q96BI3.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q96BI3.
    Bgeei Q96BI3.
    CleanExi HS_APH1A.
    Genevestigatori Q96BI3.

    Family and domain databases

    InterProi IPR009294. Aph-1.
    [Graphical view ]
    PANTHERi PTHR12889. PTHR12889. 1 hit.
    Pfami PF06105. Aph-1. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Mammalian APH-1 interacts with presenilin and nicastrin and is required for intramembrane proteolysis of amyloid-beta precursor protein and Notch."
      Lee S.-F., Shah S., Li H., Yu C., Han W., Yu G.
      J. Biol. Chem. 277:45013-45019(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, INTERACTION WITH PSEN1; PSEN2 AND NCSTN.
      Tissue: Glioblastoma.
    2. "PSF is essential for gamma-secretase activity and stabilization of presenilin and nicastrin."
      Lee H.-J., Kim T.-W.
      Submitted (MAY-2002) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
    3. "Identification of novel human genes evolutionarily conserved in Caenorhabditis elegans by comparative proteomics."
      Lai C.-H., Chou C.-Y., Ch'ang L.-Y., Liu C.-S., Lin W.-C.
      Genome Res. 10:703-713(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
    4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
    5. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
      Tissue: Retinoblastoma and Thyroid.
    6. "The DNA sequence and biological annotation of human chromosome 1."
      Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.
      , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
      Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    7. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    8. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
      Tissue: Adrenal gland, Brain, Cervix, Eye, Glial tumor and Lung.
    9. "aph-1 and pen-2 are required for Notch pathway signaling, gamma-secretase cleavage of betaAPP, and presenilin protein accumulation."
      Francis R., McGrath G., Zhang J., Ruddy D.A., Sym M., Apfeld J., Nicoll M., Maxwell M., Hai B., Ellis M.C., Parks A.L., Xu W., Li J., Gurney M., Myers R.L., Himes C.S., Hiebsch R., Ruble C., Nye J.S., Curtis D.
      Dev. Cell 3:85-97(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: TISSUE SPECIFICITY.
    10. "PEN-2 and APH-1 coordinately regulate proteolytic processing of presenilin 1."
      Luo W.-J., Wang H., Li H., Kim B.S., Shah S., Lee H.-J., Thinakaran G., Kim T.-W., Yu G., Xu H.
      J. Biol. Chem. 278:7850-7854(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, FUNCTION.
    11. "APH-1 interacts with mature and immature forms of presenilins and nicastrin and may play a role in maturation of presenilin.nicastrin complexes."
      Gu Y., Chen F., Sanjo N., Kawarai T., Hasegawa H., Duthie M., Li W., Ruan X., Luthra A., Mount H.T.J., Tandon A., Fraser P.E., St George-Hyslop P.H.
      J. Biol. Chem. 278:7374-7380(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, INTERACTION WITH PSEN1.
    12. "APH1, PEN2, and nicastrin increase Abeta levels and gamma-secretase activity."
      Marlow L., Canet R.M., Haugabook S.J., Hardy J.A., Lahiri D.K., Sambamurti K.
      Biochem. Biophys. Res. Commun. 305:502-509(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN THE GAMMA-SECRETASE COMPLEX.
    13. "Gamma-secretase is a membrane protein complex comprised of presenilin, nicastrin, Aph-1, and Pen-2."
      Kimberly W.T., LaVoie M.J., Ostaszewski B.L., Ye W., Wolfe M.S., Selkoe D.J.
      Proc. Natl. Acad. Sci. U.S.A. 100:6382-6387(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: COMPONENT OF A GAMMA-SECRETASE COMPLEX WITH PEN2; PSEN1/PSEN2 AND NCSTN.
    14. Cited for: ENZYME ACTIVITY OF A GAMMA-SECRETASE COMPLEX.
    15. "Membrane topology and nicastrin-enhanced endoproteolysis of APH-1, a component of the gamma-secretase complex."
      Fortna R.R., Crystal A.S., Morais V.A., Pijak D.S., Lee V.M., Doms R.W.
      J. Biol. Chem. 279:3685-3693(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, MEMBRANE TOPOLOGY.

    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: October 1, 2014
    This is version 122 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

    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. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3