PSN2_MICMU
ID PSN2_MICMU Reviewed; 445 AA.
AC P79801;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 03-AUG-2022, entry version 108.
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;
DE Flags: Fragment;
GN Name=PSEN2; Synonyms=PS2, PSNL2;
OS Microcebus murinus (Gray mouse lemur) (Lemur murinus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Strepsirrhini; Lemuriformes;
OC Cheirogaleidae; Microcebus.
OX NCBI_TaxID=30608;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RX PubMed=10069575; DOI=10.1006/nbdi.1998.0205;
RA Calenda A., Mestre-Frances N., Czech C., Pradier L., Petter A., Perret M.,
RA Bons N., Bellis M.;
RT "Cloning of the presenilin 2 cDNA and its distribution in brain of the
RT primate, Microcebus murinus: coexpression with betaAPP and Tau proteins.";
RL Neurobiol. Dis. 5:323-333(1998).
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}.
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DR EMBL; Y10140; CAA71228.1; -; mRNA.
DR AlphaFoldDB; P79801; -.
DR SMR; P79801; -.
DR MEROPS; A22.002; -.
DR Proteomes; UP000694394; 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; Parkinsonism; Phosphoprotein; Protease;
KW Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..297
FT /note="Presenilin-2 NTF subunit"
FT /evidence="ECO:0000250"
FT /id="PRO_0000025605"
FT CHAIN 298..445
FT /note="Presenilin-2 CTF subunit"
FT /evidence="ECO:0000250"
FT /id="PRO_0000025606"
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..271
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 272..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..445
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 1..76
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 MOD_RES 52
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q61144"
FT NON_TER 445
SQ SEQUENCE 445 AA; 49475 MW; 0A01A7646659E052 CRC64;
MLTFMASDSE EEVCDERTSL MSAESPSPRS CQEGGQGPED GDSTAQWRIQ DSEEDGEEDP
DRYVSSGVPG RPPGPEEELT LKYGAKHVIM LSVPVTLCMI VVVATIKSVR FYTEKNGQLI
YTPFTEDTPS VSQRLLNSVL NTLIMISVIV VMTIFLVVLY KYRCYKFIHG WLIMSSLMLL
FLFTYIYLGE VLKTYNVAMD YPTLVLTVWN FGAVGMVCIH WKGPLMLQQA YLIAISALMA
LVFIKYLPEW SAWVILGAIS VYDLVAVLCP KGPLRMLVET AQERNEPIFP ALIYSSAMVW
TVGMAKLDPS SQGALQLPYD PEMEEDSYDS LGEPSYPEVF EAPLPGYPGE ELEEEEERGV
KLGLGDFIFY SVLVGKAAAT GSGDWNTTLA CFVAILIGLC LTLLLLAVFK KALPALPISI
TFGLVFYFST DNLVRPFMDT LAYHQ
