PSN1_XENLA
ID PSN1_XENLA Reviewed; 433 AA.
AC O12976; Q6DD65;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 1.
DT 03-AUG-2022, entry version 108.
DE RecName: Full=Presenilin-1;
DE Short=PS-1;
DE EC=3.4.23.-;
DE AltName: Full=Presenilin alpha;
DE Short=PS-alpha;
GN Name=psen1;
OS Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RC TISSUE=Brain;
RX PubMed=9070286; DOI=10.1006/bbrc.1996.6043;
RA Tsujimura A., Yasojima K., Hashimoto-Gotoh T.;
RT "Cloning of Xenopus presenilin-alpha and -beta cDNAs and their differential
RT expression in oogenesis and embryogenesis.";
RL Biochem. Biophys. Res. Commun. 231:392-396(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Embryo;
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: 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 presence of the other members of
CC the gamma-secretase complex for protease activity. Plays a role in
CC Notch and Wnt signaling cascades and regulation of downstream processes
CC via its role in processing key regulatory proteins.
CC {ECO:0000250|UniProtKB:P49768}.
CC -!- SUBUNIT: Homodimer. The functional gamma-secretase complex is composed
CC of at least four polypeptides: a presenilin homodimer (PSEN1 or PSEN2),
CC nicastrin (NCSTN), APH1 (APH1A or APH1B) and PEN2. Such minimal complex
CC is sufficient for secretase activity. {ECO:0000250|UniProtKB:P49768}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:P49768}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P49768}. Golgi apparatus membrane
CC {ECO:0000250|UniProtKB:P49768}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P49768}. Cytoplasmic granule
CC {ECO:0000250|UniProtKB:P49768}. Cell membrane
CC {ECO:0000250|UniProtKB:P49768}. Cell projection, axon
CC {ECO:0000250|UniProtKB:Q4JIM4}. Synapse {ECO:0000250|UniProtKB:Q4JIM4}.
CC Cell projection, neuron projection {ECO:0000250|UniProtKB:P49768}.
CC -!- TISSUE SPECIFICITY: Highest expression in ovaries and to a lesser
CC extent in testis, intestine, kidney, brain, eye and lung. Weak
CC expression in liver and heart. Present in trace amounts in skeletal
CC muscle. {ECO:0000269|PubMed:9070286}.
CC -!- DEVELOPMENTAL STAGE: Abundant in early stages of oogenesis. The
CC expression is rapidly reduced between meiotic maturation and
CC fertilization stages. {ECO:0000269|PubMed:9070286}.
CC -!- DOMAIN: The PAL motif is required for normal active site conformation.
CC {ECO:0000250|UniProtKB:P49768}.
CC -!- DOMAIN: Substrates, such as NOTCH1 and APP peptides, are bound between
CC PSEN1 transmembrane domains and via the first lumenal loop and the
CC cytoplasmic loop between the sixth and seventh transmembrane domains.
CC Substrate binding causes a conformation change and formation of an
CC intermolecular antiparallel beta-sheet between PSEN1 and its
CC substrates. {ECO:0000250|UniProtKB:P49768}.
CC -!- PTM: Heterogeneous proteolytic processing generates N-terminal (NTF)
CC and C-terminal (CTF) fragments of approximately 35 and 20 kDa,
CC respectively. During apoptosis, the C-terminal fragment (CTF) is
CC further cleaved by a caspase. {ECO:0000250|UniProtKB:P49768}.
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; D84427; BAA19570.1; -; mRNA.
DR EMBL; BC077762; AAH77762.1; -; mRNA.
DR PIR; JC5390; JC5390.
DR RefSeq; NP_001084023.1; NM_001090554.2.
DR RefSeq; XP_018084271.1; XM_018228782.1.
DR RefSeq; XP_018084272.1; XM_018228783.1.
DR RefSeq; XP_018084273.1; XM_018228784.1.
DR RefSeq; XP_018084274.1; XM_018228785.1.
DR AlphaFoldDB; O12976; -.
DR SMR; O12976; -.
DR IntAct; O12976; 1.
DR MEROPS; A22.001; -.
DR DNASU; 399258; -.
DR GeneID; 399258; -.
DR KEGG; xla:399258; -.
DR CTD; 399258; -.
DR Xenbase; XB-GENE-481920; psen1.L.
DR OMA; MQPVADP; -.
DR OrthoDB; 797738at2759; -.
DR Proteomes; UP000186698; Chromosome 8L.
DR Bgee; 399258; Expressed in testis and 19 other tissues.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0030424; C:axon; IEA:UniProtKB-SubCell.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0070765; C:gamma-secretase complex; ISS:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; ISS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0045202; C:synapse; IEA:UniProtKB-SubCell.
DR GO; GO:0042500; F:aspartic endopeptidase activity, intramembrane cleaving; ISS:UniProtKB.
DR GO; GO:0042982; P:amyloid precursor protein metabolic process; ISS:UniProtKB.
DR GO; GO:0034205; P:amyloid-beta formation; ISS:UniProtKB.
DR GO; GO:0006509; P:membrane protein ectodomain proteolysis; ISS:UniProtKB.
DR GO; GO:0007219; P:Notch signaling pathway; IEA:UniProtKB-KW.
DR GO; GO:0043085; P:positive regulation of catalytic activity; ISS:UniProtKB.
DR GO; GO:0016485; P:protein processing; ISS:UniProtKB.
DR GO; GO:0060828; P:regulation of canonical Wnt signaling pathway; ISS:UniProtKB.
DR Gene3D; 1.10.472.100; -; 1.
DR InterPro; IPR001108; Peptidase_A22A.
DR InterPro; IPR006639; Preselin/SPP.
DR InterPro; IPR042524; Presenilin_C.
DR PANTHER; PTHR10202; PTHR10202; 1.
DR Pfam; PF01080; Presenilin; 1.
DR PRINTS; PR01072; PRESENILIN.
DR SMART; SM00730; PSN; 1.
PE 2: Evidence at transcript level;
KW Cell membrane; Cell projection; Endoplasmic reticulum; Glycoprotein;
KW Golgi apparatus; Hydrolase; Membrane; Notch signaling pathway;
KW Phosphoprotein; Protease; Reference proteome; Synapse; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..433
FT /note="Presenilin-1"
FT /id="PRO_0000073898"
FT TOPO_DOM 1..48
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TRANSMEM 49..69
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TOPO_DOM 70..98
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TRANSMEM 99..119
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TOPO_DOM 120..132
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TRANSMEM 133..155
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TOPO_DOM 156..160
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TRANSMEM 161..182
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TOPO_DOM 183..186
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TRANSMEM 187..207
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TOPO_DOM 208..214
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TRANSMEM 215..238
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TOPO_DOM 239..346
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TRANSMEM 347..367
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TOPO_DOM 368..373
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TRANSMEM 374..394
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TOPO_DOM 395..398
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TRANSMEM 399..419
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TOPO_DOM 420..433
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT REGION 1..31
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 254..256
FT /note="Important for cleavage of target proteins"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT REGION 273..307
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 343..347
FT /note="Important for cleavage of target proteins"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT REGION 398..400
FT /note="Important for cleavage of target proteins"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT MOTIF 399..401
FT /note="PAL"
FT /evidence="ECO:0000305"
FT COMPBIAS 11..28
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 273..300
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 223
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT ACT_SITE 351
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT SITE 257..258
FT /note="Cleavage; alternate"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT SITE 258..259
FT /note="Cleavage; alternate"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT SITE 264..265
FT /note="Cleavage"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT CARBOHYD 371
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 433 AA; 48301 MW; 71CCEE3F6BB9C0AF CRC64;
MNDTSERRSN ENSESQSNGQ TQSSSQQVLE QDEEEDEELT LKYGAKHVIM LFVPVTLCMV
VVVATIKSVS FYTRFDGQLI YTPFTEDTES VGQRALNSIL NATIMISVII VMTILLVVLY
KYRCYKVIHG WLIISSLLLL FFFSYIYLGE VFKTYNVAVD YITLALLIWN FGVVGMICIH
WKGPLLLQQA YLIMISALMA LVFIKYLPEW TTWLILAVIS VYDLVAVLSP KGPLRMLVET
AQERNETLFP ALIYSSTMIW LVNMADGDPG LKQSASTKTY NTQAPTAHPR SDSAASDDNG
GFDTTWEDHR NAQIGPINST PESRVAVQAL PSNSPPSEDP EERGVKLGLG DFIFYSVLVG
KASATASGDW NTTLACFVAI LIGLCLTLLL LAIFKKALPA LPISITFGLV FYFATDYLVQ
PFMDQLAFHQ FYI
