Q9NZ42 (PEN2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Gamma-secretase subunit PEN-2

Alternative name(s):
Presenilin enhancer protein 2

Gene names

Name:	PSENEN
Synonyms:	PEN2
ORF Names:	MDS033

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	101 AA.
Sequence status	Complete.
Protein existence	Evidence 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 apparatus › Golgi 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	Familial acne inversa 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 process	Notch signaling pathway
Cellular component	Endoplasmic reticulum Golgi apparatus Membrane
Domain	Transmembrane Transmembrane helix
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Notch 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 process 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 nerve growth factor receptor signaling pathway 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_component	Golgi 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 to plasma membrane Inferred from direct assay PubMed 15274632. Source: HGNC
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
TMED10	P49755	3	EBI-998468,EBI-998422

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 101	101	Gamma-secretase subunit PEN-2		PRO_0000190900
Regions
	Topological domain	1 – 17	17	Lumenal Potential
	Transmembrane	18 – 38	21	Helical; Potential
	Topological domain	39 – 60	22	Cytoplasmic Potential
	Transmembrane	61 – 81	21	Helical; Potential
	Topological domain	82 – 101	20	Lumenal Potential
Experimental info
	Mutagenesis	10	1	E → S: Induces a N-linked glycosylation on N-8. Ref.7
	Mutagenesis	46	1	A → N: No effect. Ref.7
	Mutagenesis	93	1	S → N: Induces a N-linked glycosylation. Ref.7

Sequences

	Sequence		Length	Mass (Da)
	Q9NZ42 [UniParc]. Last modified October 1, 2000. Version 1. Checksum: FDBA4D299488EA02	FASTA	101	12,029
	10 20 30 40 50 60 MNLERVSNEE KLNLCRKYYL GGFAFLPFLW LVNIFWFFRE AFLVPAYTEQ SQIKGYVWRS 70 80 90 100 AVGFLFWVIV LTSWITIFQI YRPRWGALGD YLSFTIPLGT P

References

	« Hide 'large scale' referencesShow '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. , 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.
IPI	IPI00020516.
RefSeq	NP_758844.1. NM_172341.1.
UniGene	Hs.534465.
3D structure databases
ProteinModelPortal	Q9NZ42.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9NZ42. 3 interactions.
MINT	MINT-5207259.
STRING	9606.ENSP00000222266.
PTM databases
PhosphoSite	Q9NZ42.
Polymorphism databases
DMDM	37081820.
Proteomic databases
PaxDb	Q9NZ42.
PRIDE	Q9NZ42.
Protocols and materials databases
DNASU	55851.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000222266; ENSP00000222266; ENSG00000205155. ENST00000587708; ENSP00000468411; ENSG00000205155.
GeneID	55851.
KEGG	hsa:55851.
UCSC	uc002obi.1. human.
Organism-specific databases
CTD	55851.
GeneCards	GC19P036236.
H-InvDB	HIX0080122.
HGNC	HGNC:30100. PSENEN.
HPA	CAB013471.
MIM	607632. gene. 613736. phenotype.
neXtProt	NX_Q9NZ42.
Orphanet	387. Hidradenitis suppurativa.
PharmGKB	PA142671122.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG279333.
HOGENOM	HOG000006914.
HOVERGEN	HBG045628.
InParanoid	Q9NZ42.
KO	K06170.
OMA	WGATADY.
OrthoDB	EOG483D63.
Enzyme and pathway databases
Pathway_Interaction_DB	p75ntrpathway. p75(NTR)-mediated signaling. ps1pathway. Presenilin action in Notch and Wnt signaling. syndecan_3_pathway. Syndecan-3-mediated signaling events.
Reactome	REACT_111102. Signal Transduction. REACT_691. A third proteolytic cleavage releases NICD.
Gene expression databases
Bgee	Q9NZ42.
CleanEx	HS_PSENEN.
Genevestigator	Q9NZ42.
GermOnline	ENSG00000205155. Homo sapiens.
Family and domain databases
InterPro	IPR019379. Gamma_Secretase_Asp_P_PEN2. [Graphical view]
Pfam	PF10251. PEN-2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	Q9NZ42.
ChEMBL	CHEMBL2374.
ChiTaRS	PSENEN. human.
GenomeRNAi	55851.
NextBio	61115.
SOURCE	Search...

Entry information

Entry name

PEN2_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 102 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.