PEN2_RAT
ID PEN2_RAT Reviewed; 101 AA.
AC Q6QI68;
DT 08-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 102.
DE RecName: Full=Gamma-secretase subunit PEN-2;
DE AltName: Full=Liver regeneration-related protein LRRGT00140;
DE AltName: Full=Presenilin enhancer protein 2;
GN Name=Psenen;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Xu C.S., Zhang L., Chang C.F., Han H.P., Wang G.P., Chai L.Q., Yuan J.Y.,
RA Yang K.J., Zhao L.F., Ma H., Wang L., Wang S.F., Xing X.K., Shen G.M.,
RA Shi J.B., Rahman S., Wang Q.N., Zhang J.B.;
RT "Liver regeneration after PH.";
RL Submitted (FEB-2004) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Spleen;
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).
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). The gamma-secretase complex plays a role in
CC Notch and Wnt signaling cascades and regulation of downstream processes
CC via its role in processing key regulatory proteins, and by regulating
CC cytosolic CTNNB1 levels. PSENEN modulates both endoproteolysis of
CC presenilin and gamma-secretase activity.
CC {ECO:0000250|UniProtKB:Q9NZ42}.
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:0000250|UniProtKB:Q9NZ42}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q9NZ42}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q9NZ42}. Golgi apparatus, Golgi stack membrane
CC {ECO:0000250|UniProtKB:Q9NZ42}; 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:0000250|UniProtKB:Q9NZ42}.
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; AY539891; AAS66231.1; -; mRNA.
DR EMBL; BC100104; AAI00105.1; -; mRNA.
DR RefSeq; NP_001008764.1; NM_001008764.2.
DR RefSeq; XP_006228832.1; XM_006228770.3.
DR AlphaFoldDB; Q6QI68; -.
DR SMR; Q6QI68; -.
DR BioGRID; 253977; 1.
DR IntAct; Q6QI68; 1.
DR STRING; 10116.ENSRNOP00000028438; -.
DR PhosphoSitePlus; Q6QI68; -.
DR PaxDb; Q6QI68; -.
DR Ensembl; ENSRNOT00000028438; ENSRNOP00000028438; ENSRNOG00000020941.
DR GeneID; 292788; -.
DR KEGG; rno:292788; -.
DR CTD; 55851; -.
DR RGD; 1312037; Psenen.
DR eggNOG; KOG3402; Eukaryota.
DR GeneTree; ENSGT00390000016319; -.
DR HOGENOM; CLU_124142_2_0_1; -.
DR InParanoid; Q6QI68; -.
DR OMA; WYFRAGF; -.
DR OrthoDB; 1517974at2759; -.
DR PhylomeDB; Q6QI68; -.
DR TreeFam; TF313116; -.
DR Reactome; R-RNO-1251985; Nuclear signaling by ERBB4.
DR Reactome; R-RNO-193692; Regulated proteolysis of p75NTR.
DR Reactome; R-RNO-205043; NRIF signals cell death from the nucleus.
DR Reactome; R-RNO-3928665; EPH-ephrin mediated repulsion of cells.
DR Reactome; R-RNO-9013507; NOTCH3 Activation and Transmission of Signal to the Nucleus.
DR Reactome; R-RNO-9017802; Noncanonical activation of NOTCH3.
DR PRO; PR:Q6QI68; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Bgee; ENSRNOG00000020941; Expressed in stomach and 20 other tissues.
DR Genevisible; Q6QI68; RN.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:RGD.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0070765; C:gamma-secretase complex; ISS:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; ISO:RGD.
DR GO; GO:0032580; C:Golgi cisterna membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; ISS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; ISO:RGD.
DR GO; GO:0099056; C:integral component of presynaptic membrane; IDA:SynGO.
DR GO; GO:0005739; C:mitochondrion; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0061133; F:endopeptidase activator activity; ISO:RGD.
DR GO; GO:0019899; F:enzyme binding; ISO:RGD.
DR GO; GO:0042987; P:amyloid precursor protein catabolic process; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0031293; P:membrane protein intracellular domain proteolysis; ISO:RGD.
DR GO; GO:0007220; P:Notch receptor processing; ISO:RGD.
DR GO; GO:0007219; P:Notch signaling pathway; IEA:UniProtKB-KW.
DR GO; GO:0043085; P:positive regulation of catalytic activity; ISO:RGD.
DR GO; GO:0010950; P:positive regulation of endopeptidase activity; ISO:RGD.
DR GO; GO:0016485; P:protein processing; ISO:RGD.
DR InterPro; IPR019379; Gamma_Secretase_Asp_P_PEN2.
DR PANTHER; PTHR16318; PTHR16318; 1.
DR Pfam; PF10251; PEN-2; 1.
PE 3: Inferred from homology;
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_0000327207"
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; 12021 MW; FDBA771384E58E1B CRC64;
MNLERVSNEE KLNLCRKYYL GGFAFLPFLW LVNIFWFFKE AFFAPAYTEQ SQIKGYVWRS
AVGFLFWVIV LTTWITIFQI YRPRWGALGD YLSFTIPLGT P
