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Q8WW43

- APH1B_HUMAN

UniProt

Q8WW43 - APH1B_HUMAN

Protein

Gamma-secretase subunit APH-1B

Gene

APH1B

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 109 (01 Oct 2014)
      Sequence version 3 (15 Mar 2005)
      Previous versions | rss
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    Functioni

    Probable 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. Probably present in a minority of gamma-secretase complexes compared to APH1A.1 Publication

    GO - Molecular functioni

    1. peptidase activity Source: MGI
    2. protein binding Source: UniProtKB

    GO - Biological processi

    1. apoptotic signaling pathway Source: Reactome
    2. membrane protein intracellular domain proteolysis Source: Reactome
    3. neurotrophin TRK receptor signaling pathway Source: Reactome
    4. Notch receptor processing Source: Reactome
    5. Notch signaling pathway Source: Reactome
    6. positive regulation of apoptotic process Source: Reactome
    7. positive regulation of catalytic activity Source: InterPro
    8. protein processing Source: MGI

    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.
    SignaLinkiQ8WW43.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Gamma-secretase subunit APH-1B
    Short name:
    APH-1b
    Alternative name(s):
    Aph-1beta
    Presenilin-stabilization factor-like
    Gene namesi
    Name:APH1B
    Synonyms:PSFL
    ORF Names:UNQ688/PRO1328
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 15

    Organism-specific databases

    HGNCiHGNC:24080. APH1B.

    Subcellular locationi

    GO - Cellular componenti

    1. integral component of membrane Source: MGI
    2. plasma membrane Source: Reactome
    3. transport vesicle Source: LIFEdb

    Keywords - Cellular componenti

    Membrane

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA142672600.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 257257Gamma-secretase subunit APH-1BPRO_0000221052Add
    BLAST

    Proteomic databases

    PaxDbiQ8WW43.
    PRIDEiQ8WW43.

    PTM databases

    PhosphoSiteiQ8WW43.

    Expressioni

    Tissue specificityi

    Weakly or not expressed in leukocytes, lung, placenta, small intestine, liver, kidney, spleen thymus, colon, skeletal muscle, heart and brain.1 Publication

    Gene expression databases

    ArrayExpressiQ8WW43.
    BgeeiQ8WW43.
    CleanExiHS_APH1B.
    GenevestigatoriQ8WW43.

    Interactioni

    Subunit structurei

    Probable 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 By similarity. Interacts with PSEN1 and PSEN2.By similarity1 Publication

    Protein-protein interaction databases

    BioGridi123659. 5 interactions.
    IntActiQ8WW43. 1 interaction.
    MINTiMINT-4721718.
    STRINGi9606.ENSP00000261879.

    Structurei

    3D structure databases

    ProteinModelPortaliQ8WW43.
    ModBaseiSearch...
    MobiDBiSearch...

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei5 – 2521Helical; Name=1Sequence AnalysisAdd
    BLAST
    Transmembranei32 – 5221Helical; Name=2Sequence AnalysisAdd
    BLAST
    Transmembranei71 – 9121Helical; Name=3Sequence AnalysisAdd
    BLAST
    Transmembranei115 – 13521Helical; Name=4Sequence AnalysisAdd
    BLAST
    Transmembranei158 – 17821Helical; Name=5Sequence AnalysisAdd
    BLAST
    Transmembranei186 – 20621Helical; Name=6Sequence AnalysisAdd
    BLAST
    Transmembranei213 – 23321Helical; 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.
    InParanoidiQ8WW43.
    KOiK06172.
    OMAiFRFGYYK.
    PhylomeDBiQ8WW43.
    TreeFamiTF314362.

    Family and domain databases

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

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q8WW43-1) [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

    MTAAVFFGCA FIAFGPALAL YVFTIATEPL RIIFLIAGAF FWLVSLLISS    50
    LVWFMARVII DNKDGPTQKY LLIFGAFVSV YIQEMFRFAY YKLLKKASEG 100
    LKSINPGETA PSMRLLAYVS GLGFGIMSGV FSFVNTLSDS LGPGTVGIHG 150
    DSPQFFLYSA FMTLVIILLH VFWGIVFFDG CEKKKWGILL IVLLTHLLVS 200
    AQTFISSYYG INLASAFIIL VLMGTWAFLA AGGSCRSLKL CLLCQDKNFL 250
    LYNQRSR 257
    Length:257
    Mass (Da):28,460
    Last modified:March 15, 2005 - v3
    Checksum:iA7A0C0076E20990A
    GO
    Isoform 2 (identifier: Q8WW43-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         119-159: Missing.

    Note: Expressed at low levels in most tissues.

    Show »
    Length:216
    Mass (Da):24,282
    Checksum:i73F52F010DD3ECBA
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti27 – 271T → I in AAQ89061. (PubMed:12975309)Curated
    Sequence conflicti83 – 831Q → R in AAN63817. 1 PublicationCurated
    Sequence conflicti83 – 831Q → R in CAB66606. (PubMed:11230166)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti217 – 2171F → L.
    Corresponds to variant rs1047552 [ dbSNP | Ensembl ].
    VAR_048315

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei119 – 15941Missing in isoform 2. 1 PublicationVSP_042945Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF508794 mRNA. Translation: AAN63817.1.
    AB189172 mRNA. Translation: BAD95573.1.
    AL136671 mRNA. Translation: CAB66606.1.
    AY358698 mRNA. Translation: AAQ89061.1.
    AK291204 mRNA. Translation: BAF83893.1.
    AC016207 Genomic DNA. No translation available.
    CH471082 Genomic DNA. Translation: EAW77645.1.
    BC020905 mRNA. Translation: AAH20905.1.
    CCDSiCCDS10184.1. [Q8WW43-1]
    CCDS45276.1. [Q8WW43-2]
    RefSeqiNP_001139118.1. NM_001145646.1. [Q8WW43-2]
    NP_112591.2. NM_031301.3. [Q8WW43-1]
    UniGeneiHs.511703.

    Genome annotation databases

    EnsembliENST00000261879; ENSP00000261879; ENSG00000138613. [Q8WW43-1]
    ENST00000380343; ENSP00000369700; ENSG00000138613. [Q8WW43-2]
    GeneIDi83464.
    KEGGihsa:83464.
    UCSCiuc002ama.3. human. [Q8WW43-1]
    uc002amb.3. human. [Q8WW43-2]

    Polymorphism databases

    DMDMi61252592.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF508794 mRNA. Translation: AAN63817.1 .
    AB189172 mRNA. Translation: BAD95573.1 .
    AL136671 mRNA. Translation: CAB66606.1 .
    AY358698 mRNA. Translation: AAQ89061.1 .
    AK291204 mRNA. Translation: BAF83893.1 .
    AC016207 Genomic DNA. No translation available.
    CH471082 Genomic DNA. Translation: EAW77645.1 .
    BC020905 mRNA. Translation: AAH20905.1 .
    CCDSi CCDS10184.1. [Q8WW43-1 ]
    CCDS45276.1. [Q8WW43-2 ]
    RefSeqi NP_001139118.1. NM_001145646.1. [Q8WW43-2 ]
    NP_112591.2. NM_031301.3. [Q8WW43-1 ]
    UniGenei Hs.511703.

    3D structure databases

    ProteinModelPortali Q8WW43.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 123659. 5 interactions.
    IntActi Q8WW43. 1 interaction.
    MINTi MINT-4721718.
    STRINGi 9606.ENSP00000261879.

    Chemistry

    BindingDBi Q8WW43.
    ChEMBLi CHEMBL2094135.

    PTM databases

    PhosphoSitei Q8WW43.

    Polymorphism databases

    DMDMi 61252592.

    Proteomic databases

    PaxDbi Q8WW43.
    PRIDEi Q8WW43.

    Protocols and materials databases

    DNASUi 83464.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000261879 ; ENSP00000261879 ; ENSG00000138613 . [Q8WW43-1 ]
    ENST00000380343 ; ENSP00000369700 ; ENSG00000138613 . [Q8WW43-2 ]
    GeneIDi 83464.
    KEGGi hsa:83464.
    UCSCi uc002ama.3. human. [Q8WW43-1 ]
    uc002amb.3. human. [Q8WW43-2 ]

    Organism-specific databases

    CTDi 83464.
    GeneCardsi GC15P064873.
    HGNCi HGNC:24080. APH1B.
    MIMi 607630. gene.
    neXtProti NX_Q8WW43.
    PharmGKBi PA142672600.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG300477.
    HOGENOMi HOG000007541.
    HOVERGENi HBG050541.
    InParanoidi Q8WW43.
    KOi K06172.
    OMAi FRFGYYK.
    PhylomeDBi Q8WW43.
    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 Q8WW43.

    Miscellaneous databases

    GenomeRNAii 83464.
    NextBioi 72393.
    PROi Q8WW43.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q8WW43.
    Bgeei Q8WW43.
    CleanExi HS_APH1B.
    Genevestigatori Q8WW43.

    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. "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] (ISOFORM 1).
    2. "Identification and characterization of a novel human APH-1b splice variant lacking exon 4."
      Saito S., Takahashi-Sasaki N., Araki W.
      Biochem. Biophys. Res. Commun. 330:1068-1072(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), ALTERNATIVE SPLICING.
    3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
      Tissue: Brain.
    4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    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] (ISOFORM 1).
    6. "Analysis of the DNA sequence and duplication history of human chromosome 15."
      Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., Abouelleil A.
      , Arachchi H.M., Baradarani L., Birditt B., Bloom S., Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.
      Nature 440:671-675(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] (ISOFORM 1).
      Tissue: Placenta.
    9. "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: FUNCTION, INTERACTION WITH PSEN1 AND PSEN2.
      Tissue: Glioblastoma.
    10. "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: TISSUE SPECIFICITY.

    Entry informationi

    Entry nameiAPH1B_HUMAN
    AccessioniPrimary (citable) accession number: Q8WW43
    Secondary accession number(s): A8K589
    , Q564N3, Q6UWQ1, Q9H0S0
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: September 26, 2003
    Last sequence update: March 15, 2005
    Last modified: October 1, 2014
    This is version 109 of the entry and version 3 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 15
      Human chromosome 15: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3