PSN1_DANRE
ID PSN1_DANRE Reviewed; 456 AA.
AC Q9W6T7;
DT 26-SEP-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 130.
DE RecName: Full=Presenilin-1;
DE Short=PS-1;
DE Short=Zf-PS1;
DE EC=3.4.23.- {ECO:0000269|PubMed:10521267};
GN Name=psen1;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, PROTEOLYTIC
RP CLEAVAGE, MUTAGENESIS OF ASP-374, AND ACTIVE SITE.
RX PubMed=10521267; DOI=10.1021/bi991453n;
RA Leimer U., Lun K., Romig H., Walter J., Gruenberg J., Brand M., Haass C.;
RT "Zebrafish (Danio rerio) presenilin promotes aberrant amyloid beta-peptide
RT production and requires a critical aspartate residue for its function in
RT amyloidogenesis.";
RL Biochemistry 38:13602-13609(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Embryo;
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (JUL-2003) 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) (PubMed:10521267). Requires the presence of the
CC other members of the gamma-secretase complex for protease activity.
CC Plays a role in Notch and Wnt signaling cascades and regulation of
CC downstream processes via its role in processing key regulatory proteins
CC (By similarity). {ECO:0000250|UniProtKB:P49768,
CC ECO:0000269|PubMed:10521267}.
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 -!- DEVELOPMENTAL STAGE: Expressed both maternally and zygotically.
CC Ubiquitously expressed during embryogenesis.
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: Cleaved, probably through autocleavage.
CC {ECO:0000269|PubMed:10521267}.
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 -!- SEQUENCE CAUTION:
CC Sequence=AAH54639.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AJ132931; CAB40386.1; -; mRNA.
DR EMBL; BC054639; AAH54639.1; ALT_INIT; mRNA.
DR RefSeq; NP_571099.1; NM_131024.1.
DR AlphaFoldDB; Q9W6T7; -.
DR SMR; Q9W6T7; -.
DR IntAct; Q9W6T7; 1.
DR STRING; 7955.ENSDARP00000030180; -.
DR MEROPS; A22.001; -.
DR PaxDb; Q9W6T7; -.
DR GeneID; 30221; -.
DR KEGG; dre:30221; -.
DR CTD; 5663; -.
DR ZFIN; ZDB-GENE-991119-4; psen1.
DR eggNOG; KOG2736; Eukaryota.
DR InParanoid; Q9W6T7; -.
DR PhylomeDB; Q9W6T7; -.
DR Reactome; R-DRE-1251985; Nuclear signaling by ERBB4.
DR Reactome; R-DRE-193692; Regulated proteolysis of p75NTR.
DR Reactome; R-DRE-205043; NRIF signals cell death from the nucleus.
DR Reactome; R-DRE-3928665; EPH-ephrin mediated repulsion of cells.
DR Reactome; R-DRE-6798695; Neutrophil degranulation.
DR PRO; PR:Q9W6T7; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Unplaced.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
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: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:0030426; C:growth cone; IBA:GO_Central.
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:0031224; C:intrinsic component of membrane; IDA:ZFIN.
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:0005739; C:mitochondrion; ISS:UniProtKB.
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:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0005790; C:smooth endoplasmic reticulum; IEA:GOC.
DR GO; GO:0030018; C:Z disc; IBA:GO_Central.
DR GO; GO:0042500; F:aspartic endopeptidase activity, intramembrane cleaving; ISS:UniProtKB.
DR GO; GO:0008013; F:beta-catenin binding; IBA:GO_Central.
DR GO; GO:0045296; F:cadherin binding; IBA:GO_Central.
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; IDA:ZFIN.
DR GO; GO:0050435; P:amyloid-beta metabolic process; IBA:GO_Central.
DR GO; GO:0007420; P:brain development; IMP:ZFIN.
DR GO; GO:0006816; P:calcium ion transport; IBA:GO_Central.
DR GO; GO:0060070; P:canonical Wnt signaling pathway; IMP:ZFIN.
DR GO; GO:0001946; P:lymphangiogenesis; IMP:ZFIN.
DR GO; GO:0030318; P:melanocyte differentiation; IMP:ZFIN.
DR GO; GO:0006509; P:membrane protein ectodomain proteolysis; 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; IDA:ZFIN.
DR GO; GO:0071632; P:optomotor response; IMP:ZFIN.
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 GO; GO:0052548; P:regulation of endopeptidase activity; IDA:ZFIN.
DR GO; GO:0001666; P:response to hypoxia; IDA:ZFIN.
DR GO; GO:0051563; P:smooth endoplasmic reticulum calcium ion homeostasis; IBA:GO_Central.
DR GO; GO:0061053; P:somite development; IMP:ZFIN.
DR GO; GO:0036269; P:swimming behavior; IMP:ZFIN.
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; 2.
DR PRINTS; PR01072; PRESENILIN.
DR SMART; SM00730; PSN; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Cell projection; Endoplasmic reticulum; Golgi apparatus;
KW Hydrolase; Membrane; Notch signaling pathway; Protease; Reference proteome;
KW Synapse; Transmembrane; Transmembrane helix.
FT CHAIN 1..456
FT /note="Presenilin-1"
FT /id="PRO_0000073897"
FT TOPO_DOM 1..70
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TRANSMEM 71..91
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TOPO_DOM 92..121
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TRANSMEM 122..142
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TOPO_DOM 143..155
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TRANSMEM 156..178
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TOPO_DOM 179..183
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TRANSMEM 184..205
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TOPO_DOM 206..209
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TRANSMEM 210..230
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TOPO_DOM 231..237
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TRANSMEM 238..261
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TOPO_DOM 262..369
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TRANSMEM 370..390
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TOPO_DOM 391..396
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TRANSMEM 397..417
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TOPO_DOM 418..421
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TRANSMEM 422..442
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TOPO_DOM 443..456
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT REGION 9..56
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 277..279
FT /note="Important for cleavage of target proteins"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT REGION 332..365
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 366..370
FT /note="Important for cleavage of target proteins"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT REGION 421..423
FT /note="Important for cleavage of target proteins"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT MOTIF 422..424
FT /note="PAL"
FT /evidence="ECO:0000305"
FT COMPBIAS 9..38
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 333..347
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 246
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT ACT_SITE 374
FT /evidence="ECO:0000305|PubMed:10521267"
FT SITE 280..281
FT /note="Cleavage; alternate"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT SITE 281..282
FT /note="Cleavage; alternate"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT SITE 287..288
FT /note="Cleavage"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT MUTAGEN 374
FT /note="D->A: Abolishes its endoproteolysis. Probably loss
FT of function."
FT /evidence="ECO:0000269|PubMed:10521267"
FT CONFLICT 308
FT /note="Missing (in Ref. 2; AAH54639)"
FT /evidence="ECO:0000305"
FT CONFLICT 317
FT /note="A -> P (in Ref. 2; AAH54639)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 456 AA; 50981 MW; B90C42280C874F8D CRC64;
MADLVQNAAN NVLNDGMDTS RHTSSTAAPP SRNEVELNGQ PPTAPPPQVV TDSEEDEDEE
LTLKYGAKHV IMLFIPVTLC MVVVVATIKS VSFYTQKDGQ QLIYTPFRED TETVGQRALH
SMLNAIIMIS VIVVMTLVLV VLYKYRCYKV IQAWLFFSNL LLLFFFSLIY LGEVFKTYNV
AMDYFTLALI IWNFGVVGMI CIHWKGPLRL QQAYLIMISA LMALVFIKYL PEWTAWLILA
AISVYDLLAV LCPKGPLRIL VETAQERNEA IFPALIYSST MVWLFNMADS AETRNNSSHP
VPQQENQVVA MAPTAQAEDD GGFTPAWVDH QQHQLGPMQS TEESRRQIQE MPSARPPPPA
DDDEERGVKL GLGDFIFYSM LVGKASATAS GDWNTTLACF VAILIGLCLT LLLLAIFKKA
LPALPISITF GLVFYFATDN LVRPFMDQLA VHQFYI
