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Q9NZ42

- PEN2_HUMAN

UniProt

Q9NZ42 - PEN2_HUMAN

Protein

Gamma-secretase subunit PEN-2

Gene

PSENEN

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

    Essential subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (beta-amyloid precursor protein). Probably represents the last step of maturation of gamma-secretase, facilitating endoproteolysis of presenilin and conferring gamma-secretase activity.2 Publications

    GO - Molecular functioni

    1. protein binding Source: IntAct

    GO - Biological processi

    1. amyloid precursor protein catabolic process Source: HGNC
    2. apoptotic signaling pathway Source: Reactome
    3. membrane protein ectodomain proteolysis Source: HGNC
    4. membrane protein intracellular domain proteolysis Source: Reactome
    5. neurotrophin TRK receptor signaling pathway Source: Reactome
    6. Notch receptor processing Source: HGNC
    7. Notch signaling pathway Source: Reactome
    8. positive regulation of apoptotic process Source: Reactome
    9. positive regulation of catalytic activity Source: HGNC
    10. 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.
    SignaLinkiQ9NZ42.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Gamma-secretase subunit PEN-2
    Alternative name(s):
    Presenilin enhancer protein 2
    Gene namesi
    Name:PSENEN
    Synonyms:PEN2
    ORF Names:MDS033
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 19

    Organism-specific databases

    HGNCiHGNC:30100. PSENEN.

    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. plasma membrane Source: Reactome

    Keywords - Cellular componenti

    Endoplasmic reticulum, Golgi apparatus, Membrane

    Pathology & Biotechi

    Involvement in diseasei

    Acne inversa, familial, 2 (ACNINV2) [MIM:613736]: A chronic relapsing inflammatory disease of the hair follicles characterized by recurrent draining sinuses, painful skin abscesses, and disfiguring scars. Manifestations typically appear after puberty.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi10 – 101E → S: Induces a N-linked glycosylation on N-8. 1 Publication
    Mutagenesisi46 – 461A → N: No effect. 1 Publication
    Mutagenesisi93 – 931S → N: Induces a N-linked glycosylation. 1 Publication

    Organism-specific databases

    MIMi613736. phenotype.
    Orphaneti387. Hidradenitis suppurativa.
    PharmGKBiPA142671122.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 101101Gamma-secretase subunit PEN-2PRO_0000190900Add
    BLAST

    Proteomic databases

    MaxQBiQ9NZ42.
    PaxDbiQ9NZ42.
    PRIDEiQ9NZ42.

    PTM databases

    PhosphoSiteiQ9NZ42.

    Expressioni

    Tissue specificityi

    Widely expressed. Expressed in leukocytes, lung, placenta, small intestine, liver, kidney, spleen thymus, skeletal muscle, heart and brain.2 Publications

    Gene expression databases

    BgeeiQ9NZ42.
    CleanExiHS_PSENEN.
    GenevestigatoriQ9NZ42.

    Organism-specific databases

    HPAiCAB013471.
    HPA047435.

    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 PSENEN/PEN2. Such minimal complex is sufficient for secretase activity, although other components may exist.

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    FTLP027924EBI-998468,EBI-713279
    NCSTNQ925423EBI-998468,EBI-998440
    TMED10P497553EBI-998468,EBI-998422

    Protein-protein interaction databases

    BioGridi120953. 7 interactions.
    IntActiQ9NZ42. 6 interactions.
    MINTiMINT-5207259.
    STRINGi9606.ENSP00000222266.

    Structurei

    3D structure databases

    ProteinModelPortaliQ9NZ42.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 1717LumenalSequence AnalysisAdd
    BLAST
    Topological domaini39 – 6022CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini82 – 10120LumenalSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei18 – 3821HelicalSequence AnalysisAdd
    BLAST
    Transmembranei61 – 8121HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the PEN-2 family.Curated

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG279333.
    HOGENOMiHOG000006914.
    HOVERGENiHBG045628.
    InParanoidiQ9NZ42.
    KOiK06170.
    OMAiQTILLEC.
    OrthoDBiEOG7ZSHW4.
    PhylomeDBiQ9NZ42.

    Family and domain databases

    InterProiIPR019379. Gamma_Secretase_Asp_P_PEN2.
    [Graphical view]
    PfamiPF10251. PEN-2. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q9NZ42-1 [UniParc]FASTAAdd to Basket

    « Hide

    MNLERVSNEE KLNLCRKYYL GGFAFLPFLW LVNIFWFFRE AFLVPAYTEQ    50
    SQIKGYVWRS AVGFLFWVIV LTSWITIFQI YRPRWGALGD YLSFTIPLGT 100
    P 101
    Length:101
    Mass (Da):12,029
    Last modified:October 1, 2000 - v1
    Checksum:iFDBA4D299488EA02
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF220053 mRNA. Translation: AAF67646.1.
    AK312233 mRNA. Translation: BAG35166.1.
    BC009575 mRNA. Translation: AAH09575.1.
    CCDSiCCDS12474.1.
    RefSeqiNP_001268461.1. NM_001281532.1.
    NP_758844.1. NM_172341.2.
    UniGeneiHs.534465.

    Genome annotation databases

    EnsembliENST00000222266; ENSP00000222266; ENSG00000205155.
    ENST00000587708; ENSP00000468411; ENSG00000205155.
    GeneIDi55851.
    KEGGihsa:55851.
    UCSCiuc002obi.1. human.

    Polymorphism databases

    DMDMi37081820.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF220053 mRNA. Translation: AAF67646.1 .
    AK312233 mRNA. Translation: BAG35166.1 .
    BC009575 mRNA. Translation: AAH09575.1 .
    CCDSi CCDS12474.1.
    RefSeqi NP_001268461.1. NM_001281532.1.
    NP_758844.1. NM_172341.2.
    UniGenei Hs.534465.

    3D structure databases

    ProteinModelPortali Q9NZ42.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 120953. 7 interactions.
    IntActi Q9NZ42. 6 interactions.
    MINTi MINT-5207259.
    STRINGi 9606.ENSP00000222266.

    Chemistry

    BindingDBi Q9NZ42.
    ChEMBLi CHEMBL2094135.

    PTM databases

    PhosphoSitei Q9NZ42.

    Polymorphism databases

    DMDMi 37081820.

    Proteomic databases

    MaxQBi Q9NZ42.
    PaxDbi Q9NZ42.
    PRIDEi Q9NZ42.

    Protocols and materials databases

    DNASUi 55851.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000222266 ; ENSP00000222266 ; ENSG00000205155 .
    ENST00000587708 ; ENSP00000468411 ; ENSG00000205155 .
    GeneIDi 55851.
    KEGGi hsa:55851.
    UCSCi uc002obi.1. human.

    Organism-specific databases

    CTDi 55851.
    GeneCardsi GC19P036236.
    H-InvDB HIX0080122.
    HGNCi HGNC:30100. PSENEN.
    HPAi CAB013471.
    HPA047435.
    MIMi 607632. gene.
    613736. phenotype.
    neXtProti NX_Q9NZ42.
    Orphaneti 387. Hidradenitis suppurativa.
    PharmGKBi PA142671122.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG279333.
    HOGENOMi HOG000006914.
    HOVERGENi HBG045628.
    InParanoidi Q9NZ42.
    KOi K06170.
    OMAi QTILLEC.
    OrthoDBi EOG7ZSHW4.
    PhylomeDBi Q9NZ42.

    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 Q9NZ42.

    Miscellaneous databases

    ChiTaRSi PSENEN. human.
    GenomeRNAii 55851.
    NextBioi 61115.
    PROi Q9NZ42.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q9NZ42.
    CleanExi HS_PSENEN.
    Genevestigatori Q9NZ42.

    Family and domain databases

    InterProi IPR019379. Gamma_Secretase_Asp_P_PEN2.
    [Graphical view ]
    Pfami PF10251. PEN-2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Novel genes expressed in hematopoietic stem/progenitor cells from myelodysplastic syndrome patients."
      Zhao M., Gu J., Li N., Peng Y., Han Z., Chen Z.
      Submitted (DEC-1999) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Hematopoietic stem cell.
    2. "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].
      Tissue: Uterus.
    3. "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].
      Tissue: Brain.
    4. "PEN-2 is an integral component of the gamma-secretase complex required for coordinated expression of presenilin and nicastrin."
      Steiner H., Winkler E., Edbauer D., Prokop S., Basset G., Yamasaki A., Kostka M., Haass C.
      J. Biol. Chem. 277:39062-39065(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH NCSTN; PSEN1 AND PSEN2.
    5. "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.
    6. "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.
    7. Cited for: MEMBRANE TOPOLOGY, SUBCELLULAR LOCATION, MUTAGENESIS OF GLU-10; ALA-46 AND SER-93.
    8. "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.
    9. "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, COMPONENT OF A GAMMA-SECRETASE COMPLEX WITH APH1A; PSEN1/PSEN2 AND NCSTN.
    10. Cited for: ENZYME ACTIVITY OF A GAMMA-SECRETASE COMPLEX.
    11. "Gamma-secretase gene mutations in familial acne inversa."
      Wang B., Yang W., Wen W., Sun J., Su B., Liu B., Ma D., Lv D., Wen Y., Qu T., Chen M., Sun M., Shen Y., Zhang X.
      Science 330:1065-1065(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: INVOLVEMENT IN ACNINV2.

    Entry informationi

    Entry nameiPEN2_HUMAN
    AccessioniPrimary (citable) accession number: Q9NZ42
    Secondary accession number(s): B2R5L9
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: September 26, 2003
    Last sequence update: October 1, 2000
    Last modified: October 1, 2014
    This is version 116 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 19
      Human chromosome 19: 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