PEN2_MOUSE
ID PEN2_MOUSE Reviewed; 101 AA.
AC Q9CQR7;
DT 26-SEP-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=Gamma-secretase subunit PEN-2;
DE AltName: Full=Presenilin enhancer protein 2;
GN Name=Psenen; Synonyms=Pen2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Kidney, Pancreas, and Testis;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain, and Colon;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP SUBCELLULAR LOCATION, FUNCTION, AND SUBUNIT.
RX PubMed=12522139; DOI=10.1074/jbc.c200648200;
RA Luo W.-J., Wang H., Li H., Kim B.S., Shah S., Lee H.-J., Thinakaran G.,
RA Kim T.-W., Yu G., Xu H.;
RT "PEN-2 and APH-1 coordinately regulate proteolytic processing of presenilin
RT 1.";
RL J. Biol. Chem. 278:7850-7854(2003).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Kidney, and Lung;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP FUNCTION, AND SUBUNIT.
RX PubMed=24941111; DOI=10.1021/bi500489j;
RA Holmes O., Paturi S., Selkoe D.J., Wolfe M.S.;
RT "Pen-2 is essential for gamma-secretase complex stability and trafficking
RT but partially dispensable for endoproteolysis.";
RL Biochemistry 53:4393-4406(2014).
CC -!- FUNCTION: Essential subunit of the gamma-secretase complex, an
CC endoprotease complex that catalyzes the intramembrane cleavage of
CC integral membrane proteins such as Notch receptors and APP (amyloid-
CC beta precursor protein) (PubMed:12522139, PubMed:24941111). The gamma-
CC secretase complex plays a role in Notch and Wnt signaling cascades and
CC regulation of downstream processes via its role in processing key
CC regulatory proteins, and by regulating cytosolic CTNNB1 levels
CC (Probable). PSENEN modulates both endoproteolysis of presenilin and
CC gamma-secretase activity (PubMed:12522139, PubMed:24941111).
CC {ECO:0000269|PubMed:12522139, ECO:0000269|PubMed:24941111,
CC ECO:0000305}.
CC -!- SUBUNIT: The functional gamma-secretase complex is composed of at least
CC four polypeptides: a presenilin homodimer (PSEN1 or PSEN2), nicastrin
CC (NCSTN), APH1 (APH1A or APH1B) and PSENEN.
CC {ECO:0000269|PubMed:12522139, ECO:0000269|PubMed:24941111}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:12522139}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q9NZ42}. Golgi apparatus, Golgi stack membrane
CC {ECO:0000269|PubMed:12522139}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q9NZ42}. Cell membrane
CC {ECO:0000250|UniProtKB:Q9NZ42}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q9NZ42}. Membrane
CC {ECO:0000250|UniProtKB:Q9NZ42}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q9NZ42}. Note=Predominantly located in the
CC endoplasmic reticulum and in the cis-Golgi.
CC {ECO:0000269|PubMed:12522139}.
CC -!- SIMILARITY: Belongs to the PEN-2 family. {ECO:0000305}.
CC -!- CAUTION: 3D-structure analysis of the human homolog indicates that the
CC membrane topology differs from the predictions. Contrary to
CC predictions, the N-terminus contains two short helices that dip into
CC the membrane, but do not cross it. The C-terminus contains the single
CC transmembrane helix. This gives rise to a topology where the N-terminus
CC is cytoplasmic and the C-terminus is lumenal. {ECO:0000305}.
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DR EMBL; AK002440; BAB22102.1; -; mRNA.
DR EMBL; AK006284; BAB24503.1; -; mRNA.
DR EMBL; AK007621; BAB25141.1; -; mRNA.
DR EMBL; BC024347; AAH24347.1; -; mRNA.
DR EMBL; BC081443; AAH81443.1; -; mRNA.
DR CCDS; CCDS21099.1; -.
DR RefSeq; NP_079774.1; NM_025498.2.
DR AlphaFoldDB; Q9CQR7; -.
DR SMR; Q9CQR7; -.
DR BioGRID; 211397; 2.
DR ComplexPortal; CPX-4234; Gamma-secretase complex, Aph1a-Psen1 variant.
DR ComplexPortal; CPX-4235; Gamma-secretase complex, Aph1b-Psen1 variant.
DR ComplexPortal; CPX-4236; Gamma-secretase complex, Aph1a-Psen2 variant.
DR ComplexPortal; CPX-4237; Gamma-secretase complex, Aph1b-Psen2 variant.
DR CORUM; Q9CQR7; -.
DR DIP; DIP-36333N; -.
DR IntAct; Q9CQR7; 5.
DR STRING; 10090.ENSMUSP00000044682; -.
DR TCDB; 4.G.1.1.1; the Gama-secretase (Gama-secretase) family.
DR iPTMnet; Q9CQR7; -.
DR PhosphoSitePlus; Q9CQR7; -.
DR MaxQB; Q9CQR7; -.
DR PaxDb; Q9CQR7; -.
DR PeptideAtlas; Q9CQR7; -.
DR PRIDE; Q9CQR7; -.
DR ProteomicsDB; 287913; -.
DR TopDownProteomics; Q9CQR7; -.
DR DNASU; 66340; -.
DR Ensembl; ENSMUST00000043898; ENSMUSP00000044682; ENSMUSG00000036835.
DR Ensembl; ENSMUST00000207747; ENSMUSP00000146675; ENSMUSG00000036835.
DR GeneID; 66340; -.
DR KEGG; mmu:66340; -.
DR UCSC; uc009gez.1; mouse.
DR CTD; 55851; -.
DR MGI; MGI:1913590; Psenen.
DR VEuPathDB; HostDB:ENSMUSG00000036835; -.
DR eggNOG; KOG3402; Eukaryota.
DR GeneTree; ENSGT00390000016319; -.
DR HOGENOM; CLU_124142_2_0_1; -.
DR InParanoid; Q9CQR7; -.
DR OMA; WYFRAGF; -.
DR OrthoDB; 1517974at2759; -.
DR PhylomeDB; Q9CQR7; -.
DR TreeFam; TF313116; -.
DR Reactome; R-MMU-1251985; Nuclear signaling by ERBB4.
DR Reactome; R-MMU-193692; Regulated proteolysis of p75NTR.
DR Reactome; R-MMU-205043; NRIF signals cell death from the nucleus.
DR Reactome; R-MMU-3928665; EPH-ephrin mediated repulsion of cells.
DR Reactome; R-MMU-9013507; NOTCH3 Activation and Transmission of Signal to the Nucleus.
DR Reactome; R-MMU-9017802; Noncanonical activation of NOTCH3.
DR BioGRID-ORCS; 66340; 10 hits in 72 CRISPR screens.
DR ChiTaRS; Psenen; mouse.
DR PRO; PR:Q9CQR7; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q9CQR7; protein.
DR Bgee; ENSMUSG00000036835; Expressed in primary oocyte and 59 other tissues.
DR ExpressionAtlas; Q9CQR7; baseline and differential.
DR Genevisible; Q9CQR7; MM.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:HGNC-UCL.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IC:ComplexPortal.
DR GO; GO:0070765; C:gamma-secretase complex; IDA:MGI.
DR GO; GO:0005794; C:Golgi apparatus; ISS:HGNC-UCL.
DR GO; GO:0032580; C:Golgi cisterna membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0000139; C:Golgi membrane; IC:ComplexPortal.
DR GO; GO:0016021; C:integral component of membrane; ISS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:HGNC-UCL.
DR GO; GO:0099056; C:integral component of presynaptic membrane; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0061133; F:endopeptidase activator activity; IMP:ARUK-UCL.
DR GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR GO; GO:0042987; P:amyloid precursor protein catabolic process; ISO:MGI.
DR GO; GO:0042982; P:amyloid precursor protein metabolic process; ISS:UniProtKB.
DR GO; GO:0034205; P:amyloid-beta formation; ISS:UniProtKB.
DR GO; GO:0006509; P:membrane protein ectodomain proteolysis; ISS:HGNC-UCL.
DR GO; GO:0031293; P:membrane protein intracellular domain proteolysis; ISO:MGI.
DR GO; GO:0007220; P:Notch receptor processing; IMP:MGI.
DR GO; GO:0007219; P:Notch signaling pathway; IEA:UniProtKB-KW.
DR GO; GO:0043085; P:positive regulation of catalytic activity; ISS:HGNC-UCL.
DR GO; GO:0010950; P:positive regulation of endopeptidase activity; IMP:UniProtKB.
DR GO; GO:0016485; P:protein processing; IMP:UniProtKB.
DR InterPro; IPR019379; Gamma_Secretase_Asp_P_PEN2.
DR PANTHER; PTHR16318; PTHR16318; 1.
DR Pfam; PF10251; PEN-2; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Endoplasmic reticulum; Golgi apparatus; Membrane;
KW Notch signaling pathway; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..101
FT /note="Gamma-secretase subunit PEN-2"
FT /id="PRO_0000190901"
FT TOPO_DOM 1..17
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9NZ42"
FT INTRAMEM 18..36
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q9NZ42"
FT TOPO_DOM 37..57
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9NZ42"
FT TRANSMEM 58..78
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q9NZ42"
FT TOPO_DOM 79..101
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:Q9NZ42"
SQ SEQUENCE 101 AA; 11999 MW; 6596CA2984FBCC59 CRC64;
MNLERVSNEE KLNLCRKYYL GGFAFLPFLW LVNIFWFFRE AFLAPAYTEQ SQIKGYVWRS
AVGFLFWVII LATWITIFQI YRPRWGALGD YLSFTIPLGT P
