PSN1_CHICK
ID PSN1_CHICK Reviewed; 468 AA.
AC Q4JIM4; Q90X08;
DT 16-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 02-AUG-2005, sequence version 1.
DT 03-AUG-2022, entry version 122.
DE RecName: Full=Presenilin-1;
DE Short=PS-1;
DE EC=3.4.23.-;
DE Contains:
DE RecName: Full=Presenilin-1 NTF subunit;
DE Contains:
DE RecName: Full=Presenilin-1 CTF subunit;
GN Name=PSEN1;
OS Gallus gallus (Chicken).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC Phasianinae; Gallus.
OX NCBI_TaxID=9031;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=B-cell;
RX PubMed=11987239; DOI=10.1006/bcmd.2002.0486;
RA Mirinics Z.K., Calafat J., Udby L., Lovelock J., Kjeldsen L.,
RA Rothermund K., Sisodia S.S., Borregaard N., Corey S.J.;
RT "Identification of the presenilins in hematopoietic cells with localization
RT of presenilin 1 to neutrophil and platelet granules.";
RL Blood Cells Mol. Dis. 28:28-38(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH CDH2, AND SUBCELLULAR
RP LOCATION.
RC TISSUE=Ciliary ganglion;
RX PubMed=16046145; DOI=10.1016/j.mcn.2005.06.005;
RA Rubio M.E., Curcio C., Chauvet N., Bruses J.L.;
RT "Assembly of the N-cadherin complex during synapse formation involves
RT uncoupling of p120-catenin and association with presenilin 1.";
RL Mol. Cell. Neurosci. 30:118-130(2005).
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 (By similarity). Predominantly
CC heterodimer of a N-terminal (NTF) and a C-terminal (CTF)
CC endoproteolytical fragment (By similarity). Interacts with CDH2
CC (PubMed:16046145). {ECO:0000250|UniProtKB:P49768,
CC ECO:0000269|PubMed:16046145}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000305|PubMed:16046145}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P49768}. Golgi apparatus membrane
CC {ECO:0000305|PubMed:16046145}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P49768}. Cytoplasmic granule
CC {ECO:0000250|UniProtKB:P49768}. Cell membrane
CC {ECO:0000305|PubMed:16046145}. Cell projection, axon
CC {ECO:0000269|PubMed:16046145}. Synapse {ECO:0000269|PubMed:16046145}.
CC Cell projection, neuron projection {ECO:0000250|UniProtKB:P49768}.
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}.
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DR EMBL; AY043492; AAK95408.1; -; mRNA.
DR EMBL; DQ084362; AAY85979.1; -; mRNA.
DR RefSeq; NP_989494.2; NM_204163.2.
DR AlphaFoldDB; Q4JIM4; -.
DR SMR; Q4JIM4; -.
DR STRING; 9031.ENSGALP00000031992; -.
DR MEROPS; A22.001; -.
DR PaxDb; Q4JIM4; -.
DR Ensembl; ENSGALT00000032629; ENSGALP00000031992; ENSGALG00000009320.
DR GeneID; 373977; -.
DR KEGG; gga:373977; -.
DR CTD; 5663; -.
DR VEuPathDB; HostDB:geneid_373977; -.
DR eggNOG; KOG2736; Eukaryota.
DR GeneTree; ENSGT00940000158751; -.
DR HOGENOM; CLU_022975_3_0_1; -.
DR InParanoid; Q4JIM4; -.
DR OMA; MYYQDID; -.
DR OrthoDB; 797738at2759; -.
DR PhylomeDB; Q4JIM4; -.
DR TreeFam; TF315040; -.
DR Reactome; R-GGA-1251985; Nuclear signaling by ERBB4.
DR Reactome; R-GGA-3928665; EPH-ephrin mediated repulsion of cells.
DR Reactome; R-GGA-6798695; Neutrophil degranulation.
DR Reactome; R-GGA-9013507; NOTCH3 Activation and Transmission of Signal to the Nucleus.
DR PRO; PR:Q4JIM4; -.
DR Proteomes; UP000000539; Chromosome 5.
DR Bgee; ENSGALG00000009320; Expressed in spermatid and 13 other tissues.
DR ExpressionAtlas; Q4JIM4; baseline and differential.
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:AgBase.
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:AgBase.
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:AgBase.
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:AgBase.
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:0042982; P:amyloid precursor protein metabolic process; ISS:UniProtKB.
DR GO; GO:0034205; P:amyloid-beta formation; ISS:UniProtKB.
DR GO; GO:0050435; P:amyloid-beta metabolic process; IBA:GO_Central.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0006816; P:calcium ion transport; IBA:GO_Central.
DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR GO; GO:0006509; P:membrane protein ectodomain proteolysis; ISS:AgBase.
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; ISS:AgBase.
DR GO; GO:0016485; P:protein processing; ISS:AgBase.
DR GO; GO:0060828; P:regulation of canonical Wnt signaling pathway; ISS:UniProtKB.
DR GO; GO:0042325; P:regulation of phosphorylation; ISS:AgBase.
DR GO; GO:0051563; P:smooth endoplasmic reticulum calcium ion homeostasis; IBA:GO_Central.
DR Gene3D; 1.10.472.100; -; 1.
DR InterPro; IPR002031; Pept_A22A_PS1.
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 PRINTS; PR01073; PRESENILIN1.
DR SMART; SM00730; PSN; 1.
PE 1: Evidence at protein level;
KW Apoptosis; Cell adhesion; Cell membrane; Cell projection;
KW Endoplasmic reticulum; Golgi apparatus; Hydrolase; Membrane;
KW Notch signaling pathway; Phosphoprotein; Protease; Reference proteome;
KW Synapse; Transmembrane; Transmembrane helix.
FT CHAIN 1..299
FT /note="Presenilin-1 NTF subunit"
FT /id="PRO_0000236063"
FT CHAIN 300..468
FT /note="Presenilin-1 CTF subunit"
FT /id="PRO_0000236064"
FT TOPO_DOM 1..83
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TRANSMEM 84..104
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TOPO_DOM 105..133
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TRANSMEM 134..154
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TOPO_DOM 155..167
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TRANSMEM 168..190
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TOPO_DOM 191..195
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TRANSMEM 196..217
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TOPO_DOM 218..221
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TRANSMEM 222..242
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TOPO_DOM 243..249
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TRANSMEM 250..273
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TOPO_DOM 274..381
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TRANSMEM 382..402
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TOPO_DOM 403..408
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TRANSMEM 409..429
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TOPO_DOM 430..433
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TRANSMEM 434..454
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TOPO_DOM 455..468
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT REGION 1..66
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 289..291
FT /note="Important for cleavage of target proteins"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT REGION 306..378
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 378..382
FT /note="Important for cleavage of target proteins"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT REGION 433..435
FT /note="Important for cleavage of target proteins"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT MOTIF 434..436
FT /note="PAL"
FT /evidence="ECO:0000305"
FT COMPBIAS 1..27
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 28..48
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 49..63
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 313..351
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 258
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT ACT_SITE 386
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT SITE 292..293
FT /note="Cleavage; alternate"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT SITE 293..294
FT /note="Cleavage; alternate"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT SITE 299..300
FT /note="Cleavage"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT SITE 346..347
FT /note="Cleavage; by caspase"
FT /evidence="ECO:0000250|UniProtKB:P49768"
SQ SEQUENCE 468 AA; 52831 MW; 9671E8B06A9C07CF CRC64;
MTELSAHLPQ FQHGQMTENF PDNHLSNTND NSERRRHDNS ERRRNDNPGS ETNGQPQNNI
QQVVDQDEEE DEELTLKYGA KHVIMLFVPV TLCMVVVVAT IKSVSFYTRK DGQLIYTPFT
EETDTIGQRA LNSILNAAIM ISVIIVMTIL LVVLYKYRCY KVIHGWLIIS SLLLLFFFSF
IYLGEVFKTY NVAMDYITVA LIIWNFGVVG MICIHWKGPL RLQQAYLIMI SALMALVFIK
YLPEWTAWLI LAVISVYDLV AVLCPKGPLR MLVETAQERN ETLFPALIYS STMVWLVNMA
EEDPEGQRKA SKNSTYDKQA PANQSQNEDA EADDGGFSQE WQQQRDNRIG PIESTPESRA
AVQALPSNSQ TSEDPEERGV KLGLGDFIFY SVLVGKASAT ASGDWNTTLA CFVAILIGLC
LTLLLLAIFK KALPALPISI TFGLVFYFAT DNLVQPFMDQ LAFHQFYI
