PSN2_BOVIN
ID PSN2_BOVIN Reviewed; 449 AA.
AC Q9XT96; Q2KI10;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2006, sequence version 2.
DT 03-AUG-2022, entry version 157.
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 Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RA Sahara N., Shirasawa T., Mori H.;
RT "Molecular cloning of bovine presenilin 2 gene.";
RL Submitted (DEC-1997) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Heart ventricle;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (JAN-2006) 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 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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF038937; AAD39024.1; -; mRNA.
DR EMBL; BC112811; AAI12812.1; -; mRNA.
DR RefSeq; NP_776865.2; NM_174440.4.
DR RefSeq; XP_005216851.1; XM_005216794.3.
DR RefSeq; XP_010811413.1; XM_010813111.2.
DR RefSeq; XP_010811414.1; XM_010813112.2.
DR RefSeq; XP_010811415.1; XM_010813113.2.
DR RefSeq; XP_010811416.1; XM_010813114.2.
DR AlphaFoldDB; Q9XT96; -.
DR SMR; Q9XT96; -.
DR STRING; 9913.ENSBTAP00000017565; -.
DR MEROPS; A22.002; -.
DR PaxDb; Q9XT96; -.
DR PRIDE; Q9XT96; -.
DR Ensembl; ENSBTAT00000017565; ENSBTAP00000017565; ENSBTAG00000013197.
DR Ensembl; ENSBTAT00000072821; ENSBTAP00000057595; ENSBTAG00000013197.
DR GeneID; 282010; -.
DR KEGG; bta:282010; -.
DR CTD; 5664; -.
DR VEuPathDB; HostDB:ENSBTAG00000013197; -.
DR VGNC; VGNC:33435; PSEN2.
DR eggNOG; KOG2736; Eukaryota.
DR GeneTree; ENSGT00940000157923; -.
DR HOGENOM; CLU_022975_3_1_1; -.
DR InParanoid; Q9XT96; -.
DR OMA; YEARPVN; -.
DR OrthoDB; 797738at2759; -.
DR TreeFam; TF315040; -.
DR Proteomes; UP000009136; Chromosome 16.
DR Bgee; ENSBTAG00000013197; Expressed in thyroid gland and 104 other tissues.
DR ExpressionAtlas; Q9XT96; baseline and differential.
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; IEA:Ensembl.
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:0070765; C:gamma-secretase complex; IEA:Ensembl.
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:0000776; C:kinetochore; IEA:Ensembl.
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:0005637; C:nuclear inner membrane; IEA:Ensembl.
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:0034205; P:amyloid-beta formation; IEA:Ensembl.
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:0043085; P:positive regulation of catalytic activity; IEA:Ensembl.
DR GO; GO:0016485; P:protein processing; IEA:Ensembl.
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 2: Evidence at transcript level;
KW Endoplasmic reticulum; Golgi apparatus; Hydrolase; Membrane;
KW Notch signaling pathway; Phosphoprotein; Protease; Reference proteome;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..298
FT /note="Presenilin-2 NTF subunit"
FT /evidence="ECO:0000250"
FT /id="PRO_0000025601"
FT CHAIN 299..449
FT /note="Presenilin-2 CTF subunit"
FT /evidence="ECO:0000250"
FT /id="PRO_0000025602"
FT TOPO_DOM 1..88
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 89..109
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 110..139
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 140..160
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 161..167
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 168..188
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 189..201
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 202..222
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 223..224
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 225..245
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 246..250
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 251..271
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 272..362
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 363..383
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 384..389
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 390..410
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 411..414
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT INTRAMEM 415..435
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 436..449
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 1..71
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 415..417
FT /note="PAL"
FT ACT_SITE 264
FT /evidence="ECO:0000250"
FT ACT_SITE 367
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"
FT CONFLICT 381
FT /note="T -> M (in Ref. 1; AAD39024)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 449 AA; 50271 MW; 63080D05B70C1A6A CRC64;
MLTFMASDSE EEVCDERTSL MSAESPTPRS CQDGRQGLED GESAAQWRSQ ESEEDHEEED
PDRYVCSGVP GRPPGLEEEL TLKYGAKHVI MLFVPVTLCM IVVVATIKSV RFYTEKNGQL
IYTPFSEDTP SVGQRLLNSV LNTLIMISVI VTMTIFLVVL YKYRCYKFIH GWLIMSSLML
LFLFTYIYLG EVLKTYNVAM DYPTLFLTVW NFGAVGMVCI HWKGPLVLQQ AYLIMISALM
ALVFIKYLPE WSAWVILGAI SVYDLVAVLC PKGPLRMLVE TAQERNEPIF PALIYSSAMV
WTVGMAKLDP SSQGALQLPY DPEMEEDSYD SFGEPSYPDV FEPPLPGYPG EELEEEEERG
VKLGLGDFIF YSVLVGKAAA TGSGDWNTTL ACFVAILIGL CLTLLLLAVF KKALPALPIS
ITFGLIFYFS TDNLVRPFMD TLASHQLYI
