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Q9NZ42

- PEN2_HUMAN

UniProt

Q9NZ42 - PEN2_HUMAN

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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

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 - 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
Complete GO annotation...

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. Golgi apparatus Source: HGNC
  3. integral component of plasma membrane Source: HGNC
  4. plasma membrane Source: Reactome
Complete GO annotation...

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.
ExpressionAtlasiQ9NZ42. baseline.
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. 8 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.
GeneTreeiENSGT00390000016319.
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

        10         20         30         40         50
MNLERVSNEE KLNLCRKYYL GGFAFLPFLW LVNIFWFFRE AFLVPAYTEQ
60 70 80 90 100
SQIKGYVWRS AVGFLFWVIV LTSWITIFQI YRPRWGALGD YLSFTIPLGT

P
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. 8 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.
GeneTreei ENSGT00390000016319.
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.
ExpressionAtlasi Q9NZ42. baseline.
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

« Hide 'large scale' publications
  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 29, 2014
This is version 117 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