Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q9NZ42 (PEN2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 114. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Gamma-secretase subunit PEN-2
Alternative name(s):
Presenilin enhancer protein 2
Gene names
Name:PSENEN
Synonyms:PEN2
ORF Names:MDS033
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length101 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.6 Ref.8

Subunit structure

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.

Subcellular location

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. Ref.6 Ref.7

Tissue specificity

Widely expressed. Expressed in leukocytes, lung, placenta, small intestine, liver, kidney, spleen thymus, skeletal muscle, heart and brain. Ref.5 Ref.9

Involvement in disease

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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.11

Sequence similarities

Belongs to the PEN-2 family.

Ontologies

Keywords
   Biological processNotch signaling pathway
   Cellular componentEndoplasmic reticulum
Golgi apparatus
Membrane
   DomainTransmembrane
Transmembrane helix
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processNotch receptor processing

Traceable author statement PubMed 15274632. Source: HGNC

Notch signaling pathway

Traceable author statement. Source: Reactome

amyloid precursor protein catabolic process

Traceable author statement PubMed 15274632. Source: HGNC

apoptotic signaling pathway

Traceable author statement. Source: Reactome

membrane protein ectodomain proteolysis

Inferred from direct assay PubMed 15274632. Source: HGNC

membrane protein intracellular domain proteolysis

Traceable author statement. Source: Reactome

neurotrophin TRK receptor signaling pathway

Traceable author statement. Source: Reactome

positive regulation of apoptotic process

Traceable author statement. Source: Reactome

positive regulation of catalytic activity

Inferred from direct assay PubMed 15274632. Source: HGNC

protein processing

Inferred from direct assay PubMed 15274632. Source: HGNC

   Cellular_componentGolgi apparatus

Inferred from direct assay PubMed 15274632. Source: HGNC

Golgi cisterna membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

endoplasmic reticulum

Inferred from direct assay PubMed 15274632. Source: HGNC

endoplasmic reticulum membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

integral component of plasma membrane

Inferred from direct assay PubMed 15274632. Source: HGNC

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functionprotein binding

Inferred from physical interaction PubMed 16641999PubMed 18201567PubMed 23685131. Source: IntAct

Complete GO annotation...

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 101101Gamma-secretase subunit PEN-2
PRO_0000190900

Regions

Topological domain1 – 1717Lumenal Potential
Transmembrane18 – 3821Helical; Potential
Topological domain39 – 6022Cytoplasmic Potential
Transmembrane61 – 8121Helical; Potential
Topological domain82 – 10120Lumenal Potential

Experimental info

Mutagenesis101E → S: Induces a N-linked glycosylation on N-8. Ref.7
Mutagenesis461A → N: No effect. Ref.7
Mutagenesis931S → N: Induces a N-linked glycosylation. Ref.7

Sequences

Sequence LengthMass (Da)Tools
Q9NZ42 [UniParc].

Last modified October 1, 2000. Version 1.
Checksum: FDBA4D299488EA02

FASTA10112,029
        10         20         30         40         50         60 
MNLERVSNEE KLNLCRKYYL GGFAFLPFLW LVNIFWFFRE AFLVPAYTEQ SQIKGYVWRS 

        70         80         90        100 
AVGFLFWVIV LTSWITIFQI YRPRWGALGD YLSFTIPLGT P 

« Hide

References

« Hide 'large scale' references
[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. expand/collapse author list , 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]"Membrane topology of gamma-secretase component PEN-2."
Crystal A.S., Morais V.A., Pierson T.C., Pijak D.S., Carlin D., Lee V.M., Doms R.W.
J. Biol. Chem. 278:20117-20123(2003) [PubMed] [Europe PMC] [Abstract]
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]"Reconstitution of gamma-secretase activity."
Edbauer D., Winkler E., Regula J.T., Pesold B., Steiner H., Haass C.
Nat. Cell Biol. 5:486-488(2003) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF220053 mRNA. Translation: AAF67646.1.
AK312233 mRNA. Translation: BAG35166.1.
BC009575 mRNA. Translation: AAH09575.1.
CCDSCCDS12474.1.
RefSeqNP_001268461.1. NM_001281532.1.
NP_758844.1. NM_172341.2.
UniGeneHs.534465.

3D structure databases

ProteinModelPortalQ9NZ42.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid120953. 7 interactions.
IntActQ9NZ42. 6 interactions.
MINTMINT-5207259.
STRING9606.ENSP00000222266.

Chemistry

BindingDBQ9NZ42.
ChEMBLCHEMBL2094135.

PTM databases

PhosphoSiteQ9NZ42.

Polymorphism databases

DMDM37081820.

Proteomic databases

MaxQBQ9NZ42.
PaxDbQ9NZ42.
PRIDEQ9NZ42.

Protocols and materials databases

DNASU55851.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000222266; ENSP00000222266; ENSG00000205155.
ENST00000587708; ENSP00000468411; ENSG00000205155.
GeneID55851.
KEGGhsa:55851.
UCSCuc002obi.1. human.

Organism-specific databases

CTD55851.
GeneCardsGC19P036236.
H-InvDBHIX0080122.
HGNCHGNC:30100. PSENEN.
HPACAB013471.
HPA047435.
MIM607632. gene.
613736. phenotype.
neXtProtNX_Q9NZ42.
Orphanet387. Hidradenitis suppurativa.
PharmGKBPA142671122.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG279333.
HOGENOMHOG000006914.
HOVERGENHBG045628.
InParanoidQ9NZ42.
KOK06170.
OMAQTILLEC.
OrthoDBEOG7ZSHW4.
PhylomeDBQ9NZ42.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_116125. Disease.
REACT_691. A third proteolytic cleavage releases NICD.
SignaLinkQ9NZ42.

Gene expression databases

BgeeQ9NZ42.
CleanExHS_PSENEN.
GenevestigatorQ9NZ42.

Family and domain databases

InterProIPR019379. Gamma_Secretase_Asp_P_PEN2.
[Graphical view]
PfamPF10251. PEN-2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSPSENEN. human.
GenomeRNAi55851.
NextBio61115.
PROQ9NZ42.
SOURCESearch...

Entry information

Entry namePEN2_HUMAN
AccessionPrimary (citable) accession number: Q9NZ42
Secondary accession number(s): B2R5L9
Entry history
Integrated into UniProtKB/Swiss-Prot: September 26, 2003
Last sequence update: October 1, 2000
Last modified: July 9, 2014
This is version 114 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM