PSN2_PIG
ID PSN2_PIG Reviewed; 448 AA.
AC Q0MS45;
DT 25-NOV-2008, integrated into UniProtKB/Swiss-Prot.
DT 19-SEP-2006, sequence version 1.
DT 03-AUG-2022, entry version 106.
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;
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Brain, Liver, and Lymphocyte;
RX PubMed=17854491; DOI=10.1186/1471-2202-8-72;
RA Madsen L.B., Thomsen B., Larsen K., Bendixen C., Holm I.E., Fredholm M.,
RA Joergensen A.L., Nielsen A.L.;
RT "Molecular characterization and temporal expression profiling of
RT presenilins in the developing porcine brain.";
RL BMC Neurosci. 8:72-72(2007).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Wang G.;
RL Submitted (NOV-2007) to the EMBL/GenBank/DDBJ databases.
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. Is a regulator of
CC mitochondrion-endoplasmic reticulum membrane tethering and modulates
CC calcium ions shuttling between ER and mitochondria.
CC {ECO:0000250|UniProtKB:P49810}.
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, FLNB and PARL (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 -!- TISSUE SPECIFICITY: Detected in the embryonic brain in frontal cortex
CC (at protein level). Expressed in the developing brain: frontal cortex,
CC cerebellum, hippocampus, basal ganglia and brain stem. Localized mainly
CC in neuronal cells and astrocytes. {ECO:0000269|PubMed:17854491}.
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; DQ853415; ABI15722.1; -; mRNA.
DR EMBL; EU287432; ABX84376.1; -; mRNA.
DR RefSeq; NP_001072134.1; NM_001078666.1.
DR RefSeq; XP_005668005.1; XM_005667948.2.
DR RefSeq; XP_005668006.1; XM_005667949.2.
DR RefSeq; XP_013835506.1; XM_013980052.1.
DR RefSeq; XP_013835507.1; XM_013980053.1.
DR RefSeq; XP_013835508.1; XM_013980054.1.
DR RefSeq; XP_013835509.1; XM_013980055.1.
DR RefSeq; XP_013835510.1; XM_013980056.1.
DR AlphaFoldDB; Q0MS45; -.
DR SMR; Q0MS45; -.
DR STRING; 9823.ENSSSCP00000011578; -.
DR MEROPS; A22.002; -.
DR PaxDb; Q0MS45; -.
DR PRIDE; Q0MS45; -.
DR Ensembl; ENSSSCT00005016750; ENSSSCP00005009992; ENSSSCG00005010874.
DR Ensembl; ENSSSCT00070016557; ENSSSCP00070013711; ENSSSCG00070008508.
DR Ensembl; ENSSSCT00070016560; ENSSSCP00070013714; ENSSSCG00070008508.
DR GeneID; 780410; -.
DR KEGG; ssc:780410; -.
DR CTD; 5664; -.
DR eggNOG; KOG2736; Eukaryota.
DR HOGENOM; CLU_022975_3_1_1; -.
DR InParanoid; Q0MS45; -.
DR TreeFam; TF315040; -.
DR Reactome; R-SSC-1251985; Nuclear signaling by ERBB4.
DR Reactome; R-SSC-193692; Regulated proteolysis of p75NTR.
DR Reactome; R-SSC-3928665; EPH-ephrin mediated repulsion of cells.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Chromosome 10.
DR Genevisible; Q0MS45; SS.
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:0035253; C:ciliary rootlet; IBA:GO_Central.
DR GO; GO:0043198; C:dendritic shaft; IBA:GO_Central.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
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; IBA:GO_Central.
DR GO; GO:0005765; C:lysosomal membrane; IBA:GO_Central.
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; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IBA:GO_Central.
DR GO; GO:0030018; C:Z disc; IBA:GO_Central.
DR GO; GO:0042500; F:aspartic endopeptidase activity, intramembrane cleaving; IEA:InterPro.
DR GO; GO:0004175; F:endopeptidase activity; IBA:GO_Central.
DR GO; GO:0042987; P:amyloid precursor protein catabolic process; IBA:GO_Central.
DR GO; GO:0050435; P:amyloid-beta metabolic process; IBA:GO_Central.
DR GO; GO:0006816; P:calcium ion transport; IBA:GO_Central.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR GO; GO:0006509; P:membrane protein ectodomain proteolysis; IBA:GO_Central.
DR GO; GO:1990456; P:mitochondrion-endoplasmic reticulum membrane tethering; ISS:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IBA:GO_Central.
DR GO; GO:0007220; P:Notch receptor processing; IBA:GO_Central.
DR GO; GO:0007219; P:Notch signaling pathway; IEA:UniProtKB-KW.
DR GO; GO:0016485; P:protein processing; IEA:InterPro.
DR GO; GO:0110097; P:regulation of calcium import into the mitochondrion; ISS:UniProtKB.
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_0000354669"
FT CHAIN 298..448
FT /note="Presenilin-2 CTF subunit"
FT /evidence="ECO:0000250"
FT /id="PRO_0000354670"
FT TOPO_DOM 1..87
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 88..108
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 109..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..361
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 362..382
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 383..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..70
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 414..416
FT /note="PAL"
FT COMPBIAS 46..64
FT /note="Basic and acidic 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 MOD_RES 52
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q61144"
SQ SEQUENCE 448 AA; 50138 MW; 734999D64407A86D CRC64;
MLTFMASDSE EEVCDERTSL MSAESPTPRS CQEGRQGLED GESAAQWRSQ DSEEDHEEDP
DRYVCSGVPG RPPGLEEELT LKYGAKHVIM LFVPVTLCMI VVVATIKSVR FYTEKNGQLI
YTPFTEDTPS VGQRLLNSVL NTLIMISVIV VMTIFLVVLY KYRCYKFIHG WLITSSLMLL
FLFTYIYLGE VLKTYNVAMD YPTLFLTVWN FGAVGMVCIH WKGPLVLQQA YLIMISALMA
LVFIKYLPEW SAWVILGAIS VYDLVAVLCP KGPLRMLVET AQERNEPIFP ALIYSSAMVW
TVGMAKLDPS SQGALQLPYD PEMEEDSYDS FGEPSYPEVF EPPLPGYPGE ELEEEEERGV
KLGLGDFIFY SVLVGKAAAT GSGDWNTTLA CFVAILIGLC LTLLLLAVFK KALPALPISI
TFGLIFYFST DNLVRPFMDT LASHQLYI
