PSN2_RAT
ID PSN2_RAT Reviewed; 448 AA.
AC O88777; O08947; O35546;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 15-JUL-1999, sequence version 2.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Presenilin-2;
DE Short=PS-2;
DE EC=3.4.23.-;
DE Contains:
DE RecName: Full=Presenilin-2 NTF subunit;
DE Contains:
DE RecName: Full=Presenilin-2 CTF subunit;
GN Name=Psen2; Synonyms=Ps2, Psnl2;
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 [MRNA].
RC STRAIN=Wistar; TISSUE=Brain;
RA Frentzel S., Abdel A.S., Luebbert H.;
RL Submitted (JUL-1996) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Wistar; TISSUE=Brain;
RX PubMed=9332390; DOI=10.1016/s0378-1119(97)00294-1;
RA Takahashi H., Mercken M., Nakazato Y., Noguchi K., Murayama M., Imahori K.,
RA Takashima A.;
RT "Cloning of cDNA and expression of the gene encoding rat presenilin-2.";
RL Gene 197:383-387(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Wistar; TISSUE=Brain;
RX PubMed=9545577; DOI=10.1016/s0167-4781(97)00219-4;
RA Tanahashi H., Tabira T.;
RT "Cloning of the cDNA encoding rat presenilin-2.";
RL Biochim. Biophys. Acta 1396:259-262(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
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 [5]
RP FUNCTION.
RX PubMed=21285369; DOI=10.1073/pnas.1100735108;
RA Zampese E., Fasolato C., Kipanyula M.J., Bortolozzi M., Pozzan T.,
RA Pizzo P.;
RT "Presenilin 2 modulates endoplasmic reticulum (ER)-mitochondria
RT interactions and Ca2+ cross-talk.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:2777-2782(2011).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Probable catalytic 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). Requires the other members of the gamma-
CC secretase complex to have a protease activity. May play a role in
CC intracellular signaling and gene expression or in linking chromatin to
CC the nuclear membrane. May function in the cytoplasmic partitioning of
CC proteins. The holoprotein functions as a calcium-leak channel that
CC allows the passive movement of calcium from endoplasmic reticulum to
CC cytosol and is involved in calcium homeostasis (By similarity). Is a
CC regulator of mitochondrion-endoplasmic reticulum membrane tethering and
CC modulates calcium ions shuttling between ER and mitochondria
CC (PubMed:21285369). {ECO:0000250|UniProtKB:P49810,
CC ECO:0000269|PubMed:21285369}.
CC -!- SUBUNIT: Homodimer. Component of the gamma-secretase complex, a complex
CC composed of a presenilin homodimer (PSEN1 or PSEN2), nicastrin (NCSTN),
CC APH1 (APH1A or APH1B) and PEN2. Such minimal complex is sufficient for
CC secretase activity, although other components may exist. Interacts with
CC DOCK3. Interacts with HERPUD1, FLNA and FLNB (By similarity).
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000250};
CC Multi-pass membrane protein {ECO:0000250}. Golgi apparatus membrane
CC {ECO:0000250}; Multi-pass membrane protein {ECO:0000250}.
CC -!- DOMAIN: The PAL motif is required for normal active site conformation.
CC {ECO:0000250}.
CC -!- PTM: Phosphorylated on serine residues. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the peptidase A22A family. {ECO:0000305}.
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DR EMBL; X99267; CAA67663.1; -; mRNA.
DR EMBL; D83700; BAA22832.1; -; mRNA.
DR EMBL; AB004454; BAA20406.1; -; mRNA.
DR EMBL; BC078805; AAH78805.1; -; mRNA.
DR RefSeq; NP_112349.2; NM_031087.2.
DR RefSeq; XP_006250467.1; XM_006250405.3.
DR RefSeq; XP_006250469.1; XM_006250407.3.
DR RefSeq; XP_006250470.1; XM_006250408.3.
DR RefSeq; XP_008768099.1; XM_008769877.2.
DR RefSeq; XP_017454428.1; XM_017598939.1.
DR AlphaFoldDB; O88777; -.
DR SMR; O88777; -.
DR STRING; 10116.ENSRNOP00000049605; -.
DR MEROPS; A22.002; -.
DR iPTMnet; O88777; -.
DR PhosphoSitePlus; O88777; -.
DR PaxDb; O88777; -.
DR PRIDE; O88777; -.
DR Ensembl; ENSRNOT00000040203; ENSRNOP00000049605; ENSRNOG00000002879.
DR GeneID; 81751; -.
DR KEGG; rno:81751; -.
DR CTD; 5664; -.
DR RGD; 621060; Psen2.
DR eggNOG; KOG2736; Eukaryota.
DR GeneTree; ENSGT00940000157923; -.
DR InParanoid; O88777; -.
DR OMA; YEARPVN; -.
DR OrthoDB; 797738at2759; -.
DR PhylomeDB; O88777; -.
DR TreeFam; TF315040; -.
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:O88777; -.
DR Proteomes; UP000002494; Chromosome 13.
DR Bgee; ENSRNOG00000002879; Expressed in liver and 19 other tissues.
DR Genevisible; O88777; RN.
DR GO; GO:0016324; C:apical plasma membrane; IBA:GO_Central.
DR GO; GO:0005938; C:cell cortex; IBA:GO_Central.
DR GO; GO:0009986; C:cell surface; IBA:GO_Central.
DR GO; GO:0005813; C:centrosome; ISO:RGD.
DR GO; GO:0036064; C:ciliary basal body; ISO:RGD.
DR GO; GO:0035253; C:ciliary rootlet; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; ISO:RGD.
DR GO; GO:0043198; C:dendritic shaft; IBA:GO_Central.
DR GO; GO:0005769; C:early endosome; IDA:RGD.
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; ISO:RGD.
DR GO; GO:0005794; C:Golgi apparatus; ISO:RGD.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0030426; C:growth cone; IBA:GO_Central.
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:0000776; C:kinetochore; ISO:RGD.
DR GO; GO:0005765; C:lysosomal membrane; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; ISO:RGD.
DR GO; GO:0045121; C:membrane raft; IBA:GO_Central.
DR GO; GO:0005743; C:mitochondrial inner membrane; IBA:GO_Central.
DR GO; GO:0031594; C:neuromuscular junction; IBA:GO_Central.
DR GO; GO:0043025; C:neuronal cell body; ISO:RGD.
DR GO; GO:0005637; C:nuclear inner membrane; ISO:RGD.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR GO; GO:0032991; C:protein-containing complex; ISO:RGD.
DR GO; GO:0097060; C:synaptic membrane; IDA:RGD.
DR GO; GO:0008021; C:synaptic vesicle; IDA:RGD.
DR GO; GO:0030018; C:Z disc; ISO:RGD.
DR GO; GO:0042500; F:aspartic endopeptidase activity, intramembrane cleaving; ISO:RGD.
DR GO; GO:0004175; F:endopeptidase activity; ISO:RGD.
DR GO; GO:0042987; P:amyloid precursor protein catabolic process; ISO:RGD.
DR GO; GO:0034205; P:amyloid-beta formation; ISO:RGD.
DR GO; GO:0050435; P:amyloid-beta metabolic process; ISO:RGD.
DR GO; GO:0048854; P:brain morphogenesis; ISO:RGD.
DR GO; GO:0006816; P:calcium ion transport; ISO:RGD.
DR GO; GO:0060048; P:cardiac muscle contraction; ISO:RGD.
DR GO; GO:0001708; P:cell fate specification; ISO:RGD.
DR GO; GO:0021904; P:dorsal/ventral neural tube patterning; ISO:RGD.
DR GO; GO:0030326; P:embryonic limb morphogenesis; ISO:RGD.
DR GO; GO:0032469; P:endoplasmic reticulum calcium ion homeostasis; ISO:RGD.
DR GO; GO:0030900; P:forebrain development; ISO:RGD.
DR GO; GO:0001942; P:hair follicle development; ISO:RGD.
DR GO; GO:0002244; P:hematopoietic progenitor cell differentiation; ISO:RGD.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR GO; GO:0007611; P:learning or memory; ISO:RGD.
DR GO; GO:0040011; P:locomotion; ISO:RGD.
DR GO; GO:0048286; P:lung alveolus development; ISO:RGD.
DR GO; GO:0006509; P:membrane protein ectodomain proteolysis; ISO:RGD.
DR GO; GO:0007613; P:memory; ISO:RGD.
DR GO; GO:1990456; P:mitochondrion-endoplasmic reticulum membrane tethering; ISO:RGD.
DR GO; GO:0002573; P:myeloid leukocyte differentiation; ISO:RGD.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IBA:GO_Central.
DR GO; GO:2001234; P:negative regulation of apoptotic signaling pathway; ISO:RGD.
DR GO; GO:0007175; P:negative regulation of epidermal growth factor-activated receptor activity; ISO:RGD.
DR GO; GO:0001933; P:negative regulation of protein phosphorylation; ISO:RGD.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:2000059; P:negative regulation of ubiquitin-dependent protein catabolic process; ISO:RGD.
DR GO; GO:0051444; P:negative regulation of ubiquitin-protein transferase activity; ISO:RGD.
DR GO; GO:0150076; P:neuroinflammatory response; ISO:RGD.
DR GO; GO:0070050; P:neuron cellular homeostasis; ISO:RGD.
DR GO; GO:0007220; P:Notch receptor processing; IBA:GO_Central.
DR GO; GO:0007219; P:Notch signaling pathway; ISO:RGD.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:RGD.
DR GO; GO:0043085; P:positive regulation of catalytic activity; ISO:RGD.
DR GO; GO:0050820; P:positive regulation of coagulation; ISO:RGD.
DR GO; GO:1902043; P:positive regulation of extrinsic apoptotic signaling pathway via death domain receptors; ISO:RGD.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; ISO:RGD.
DR GO; GO:0001921; P:positive regulation of receptor recycling; ISO:RGD.
DR GO; GO:0051604; P:protein maturation; ISO:RGD.
DR GO; GO:0016485; P:protein processing; ISO:RGD.
DR GO; GO:0015031; P:protein transport; ISO:RGD.
DR GO; GO:0110097; P:regulation of calcium import into the mitochondrion; ISO:RGD.
DR GO; GO:0007176; P:regulation of epidermal growth factor-activated receptor activity; ISO:RGD.
DR GO; GO:0043393; P:regulation of protein binding; ISO:RGD.
DR GO; GO:0048167; P:regulation of synaptic plasticity; ISO:RGD.
DR GO; GO:0001666; P:response to hypoxia; IEP:RGD.
DR GO; GO:0043589; P:skin morphogenesis; ISO:RGD.
DR GO; GO:0001756; P:somitogenesis; ISO:RGD.
DR GO; GO:0002286; P:T cell activation involved in immune response; ISO:RGD.
DR GO; GO:0050852; P:T cell receptor signaling pathway; ISO:RGD.
DR GO; GO:0048538; P:thymus development; ISO:RGD.
DR Gene3D; 1.10.472.100; -; 1.
DR InterPro; IPR001493; Pept_A22A_PS2.
DR InterPro; IPR001108; Peptidase_A22A.
DR InterPro; IPR006639; Preselin/SPP.
DR InterPro; IPR042524; Presenilin_C.
DR PANTHER; PTHR10202; PTHR10202; 1.
DR Pfam; PF01080; Presenilin; 2.
DR PRINTS; PR01072; PRESENILIN.
DR PRINTS; PR01074; PRESENILIN2.
DR SMART; SM00730; PSN; 1.
PE 1: Evidence at protein level;
KW Endoplasmic reticulum; Golgi apparatus; Hydrolase; Membrane;
KW Notch signaling pathway; Phosphoprotein; Protease; Reference proteome;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..297
FT /note="Presenilin-2 NTF subunit"
FT /evidence="ECO:0000250"
FT /id="PRO_0000025609"
FT CHAIN 298..448
FT /note="Presenilin-2 CTF subunit"
FT /evidence="ECO:0000250"
FT /id="PRO_0000025610"
FT TOPO_DOM 1..87
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 88..106
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 107..138
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 139..159
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 160..166
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 167..187
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 188..200
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 201..221
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 222..223
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 224..244
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 245..249
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 250..270
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 271..358
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 359..379
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 380..388
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 389..409
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 410..413
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT INTRAMEM 414..434
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 435..448
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 1..62
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 414..416
FT /note="PAL"
FT COMPBIAS 20..45
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 263
FT /evidence="ECO:0000250"
FT ACT_SITE 366
FT /evidence="ECO:0000250"
FT MOD_RES 22
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P49810"
FT MOD_RES 25
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P49810"
FT MOD_RES 30
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q61144"
FT CONFLICT 7
FT /note="S -> T (in Ref. 1; CAA67663)"
FT /evidence="ECO:0000305"
FT CONFLICT 86..87
FT /note="KH -> ND (in Ref. 3; BAA20406)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 448 AA; 50051 MW; 299A7C416405046C CRC64;
MLTFMASDSE EEVCDERTSL MSAESPTSRS CQDSRPGPED GENTAQWRSQ ENEDDCEEDP
DHYACSGVPG RPSGLEEELT LKYGAKHVIM LFVPVTLCMI VVVATIKSVR FYTEKNGQLI
YTPFTEDTPS VGQRLLNSVL NTLIMISVIV VMTIFLVVLY KYRCYKFIHG WLIMSSLMLL
FLFTYIYLGE VFKTYNVAMD YPTLFLAVWN FGAVGMVCIH WKGPLVLQQA YLIVISALMA
LVFIKYLPEW SAWVILGAIS VYDLVAVLCP KGPLRMLVET AQERNEPIFP ALIYSSAMVW
TVGMAKLDPS SQGALQLPYD PEMEEDSYDS FGEPSYPEAF EAPQPGYPGE EPEEEEERGV
KLGLGDFIFY SVLVGKAAAT GNGDWSTTLA CFIAILIGLC LTLLLLAVFK KALPALPISI
TFGLIFYFST DNLVRPFMDT LASHQLYI
