PSN2_PONAB
ID PSN2_PONAB Reviewed; 448 AA.
AC Q5RCN9;
DT 14-OCT-2008, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 75.
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 Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
RG The German cDNA consortium;
RL Submitted (NOV-2004) 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: Interacts with DOCK3 (By similarity). Homodimer. Component of
CC the gamma-secretase complex, a complex composed of a presenilin
CC homodimer (PSEN1 or PSEN2), nicastrin (NCSTN), APH1 (APH1A or APH1B)
CC and PEN2. Such minimal complex is sufficient for secretase activity,
CC although other components may exist. Interacts with HERPUD1, FLNA, FLNB
CC and PARL (By similarity). {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; CR858231; CAH90468.1; -; mRNA.
DR RefSeq; NP_001125243.1; NM_001131771.1.
DR AlphaFoldDB; Q5RCN9; -.
DR SMR; Q5RCN9; -.
DR STRING; 9601.ENSPPYP00000000158; -.
DR MEROPS; A22.002; -.
DR GeneID; 100172138; -.
DR KEGG; pon:100172138; -.
DR CTD; 5664; -.
DR eggNOG; KOG2736; Eukaryota.
DR InParanoid; Q5RCN9; -.
DR OrthoDB; 797738at2759; -.
DR Proteomes; UP000001595; Unplaced.
DR GO; GO:0071944; C:cell periphery; IEA:UniProt.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0042500; F:aspartic endopeptidase activity, intramembrane cleaving; IEA:InterPro.
DR GO; GO:0042987; P:amyloid precursor protein catabolic process; IEA:InterPro.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR GO; GO:1990456; P:mitochondrion-endoplasmic reticulum membrane tethering; ISS:UniProtKB.
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 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..297
FT /note="Presenilin-2 NTF subunit"
FT /evidence="ECO:0000250"
FT /id="PRO_0000351651"
FT CHAIN 298..448
FT /note="Presenilin-2 CTF subunit"
FT /evidence="ECO:0000250"
FT /id="PRO_0000351652"
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 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"
SQ SEQUENCE 448 AA; 50126 MW; 91CA6E7F0BA7C0E5 CRC64;
MLTFMASDSE EEVCDERTSL MSAESPTPRS CQEGRQGPED GENTAQWRSQ ENEEDGEEDP
DRYICSGVPG RPPGLEEELT LKYGAKHVIM LFVPVTLCMI VVVATIKSVR FYTEKNGQLI
YTPFTEDTPS VGQRLLNSVL NTLIMISVIV AMTIFLVVLY KYRCYKFIHG WLIMSSLMLL
FLFTYIYLGE VLKTYNVAMD YPTLLLTVWN FGAVGMVCIH WKGPLVLQQA YLIMISALMA
LVFIKYLPEW SAWVILGAIS VYDLVAVLCP KGPLRMLVET AQERNEPIFP ALIYSSAMVW
TVGMAKLDPS SQGALQLPYD PEMEEDSYDS FGEPSYPEVF EPPLTGYPGE ELEEEEERGV
KLGLGDFIFY SVLVGKAAAT GSGDWNTTLA CFVAILIGLC LTLLLLAVFK KALPALPISI
TFGLIFYFST DNLVRPFMDT LASHQLYI
