PSN_CAEEL
ID PSN_CAEEL Reviewed; 444 AA.
AC P52166; Q20076; Q9U9C7;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 27-MAY-2002, sequence version 2.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=Presenilin sel-12;
DE AltName: Full=Suppressor/enhancer of lin-12 protein 12;
GN Name=sel-12 {ECO:0000312|WormBase:F35H12.3};
GN ORFNames=F35H12.3 {ECO:0000312|WormBase:F35H12.3};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND MUTAGENESIS OF CYS-60.
RC STRAIN=Bristol N2;
RX PubMed=7566091; DOI=10.1038/377351a0;
RA Levitan D., Greenwald I.;
RT "Facilitation of lin-12-mediated signalling by sel-12, a Caenorhabditis
RT elegans S182 Alzheimer's disease gene.";
RL Nature 377:351-354(1995).
RN [2]
RP SEQUENCE REVISION TO 84-85.
RA Levitan D.;
RL Submitted (JAN-1996) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND TISSUE SPECIFICITY.
RC STRAIN=Bristol N2;
RX PubMed=10917532; DOI=10.1038/35018575;
RA Wittenburg N., Eimer S., Lakowski B., Roehrig S., Rudolph C.,
RA Baumeister R.;
RT "Presenilin is required for proper morphology and function of neurons in C.
RT elegans.";
RL Nature 406:306-309(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [5]
RP INTERACTION WITH SEL-10.
RX PubMed=9861048; DOI=10.1073/pnas.95.26.15787;
RA Wu G., Hubbard E.J.A., Kitajewski J.K., Greenwald I.;
RT "Evidence for functional and physical association between Caenorhabditis
RT elegans SEL-10, a Cdc4p-related protein, and SEL-12 presenilin.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:15787-15791(1998).
RN [6]
RP FUNCTION, AND MUTAGENESIS OF CYS-60.
RX PubMed=12413907; DOI=10.1006/dbio.2002.0782;
RA Eimer S., Donhauser R., Baumeister R.;
RT "The Caenorhabditis elegans presenilin sel-12 is required for mesodermal
RT patterning and muscle function.";
RL Dev. Biol. 251:178-192(2002).
RN [7]
RP DEVELOPMENTAL STAGE.
RX PubMed=12668626; DOI=10.1242/dev.00429;
RA Lakowski B., Eimer S., Goebel C., Boettcher A., Wagler B., Baumeister R.;
RT "Two suppressors of sel-12 encode C2H2 zinc-finger proteins that regulate
RT presenilin transcription in Caenorhabditis elegans.";
RL Development 130:2117-2128(2003).
RN [8]
RP FUNCTION, AND MUTAGENESIS OF 134-TRP--TYR-444.
RX PubMed=27661254; DOI=10.7554/elife.17218;
RA McClatchey S.T., Wang Z., Linden L.M., Hastie E.L., Wang L., Shen W.,
RA Chen A., Chi Q., Sherwood D.R.;
RT "Boundary cells restrict dystroglycan trafficking to control basement
RT membrane sliding during tissue remodeling.";
RL Elife 5:0-0(2016).
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 (lin-12 or glp-1).
CC Provides the major presenilin function compared to hop-1 and spe-4.
CC Required cell-autonomously for correct neurite connectivity of the AIY
CC cholinergic interneurons and their correct functioning in thermotaxis.
CC Required for mesodermal patterning of muscle function. Promotes
CC basement membrane gap formation during tissue remodeling
CC (PubMed:27661254). {ECO:0000269|PubMed:10917532,
CC ECO:0000269|PubMed:12413907, ECO:0000269|PubMed:27661254}.
CC -!- SUBUNIT: Homodimer. Component of the gamma-secretase complex, a complex
CC probably composed of the presenilin homodimer (sel-12, hop-1 or spe-4),
CC nicastrin (aph-2), aph-1 and pen-2 (Probable). Interacts with sel-10
CC (PubMed:9861048). {ECO:0000269|PubMed:9861048, ECO:0000305}.
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 -!- TISSUE SPECIFICITY: Expressed in most neurons.
CC {ECO:0000269|PubMed:10917532}.
CC -!- DEVELOPMENTAL STAGE: Expressed both maternally and zygotically.
CC Ubiquitously expressed throughout the development and in the adult.
CC {ECO:0000269|PubMed:12668626}.
CC -!- DOMAIN: The PAL motif is required for normal active site conformation.
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the peptidase A22A family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA85511.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; U35660; AAA85511.1; ALT_FRAME; mRNA.
DR EMBL; AF171064; AAD50991.1; -; mRNA.
DR EMBL; BX284606; CCD70617.1; -; Genomic_DNA.
DR RefSeq; NP_508175.1; NM_075774.5.
DR AlphaFoldDB; P52166; -.
DR SMR; P52166; -.
DR BioGRID; 45394; 57.
DR STRING; 6239.F35H12.3; -.
DR MEROPS; A22.009; -.
DR EPD; P52166; -.
DR PaxDb; P52166; -.
DR EnsemblMetazoa; F35H12.3.1; F35H12.3.1; WBGene00004769.
DR GeneID; 180441; -.
DR KEGG; cel:CELE_F35H12.3; -.
DR UCSC; F35H12.3; c. elegans.
DR CTD; 180441; -.
DR WormBase; F35H12.3; CE24946; WBGene00004769; sel-12.
DR eggNOG; KOG2736; Eukaryota.
DR GeneTree; ENSGT00940000174002; -.
DR HOGENOM; CLU_022975_3_0_1; -.
DR InParanoid; P52166; -.
DR OMA; MQPVADP; -.
DR OrthoDB; 797738at2759; -.
DR PhylomeDB; P52166; -.
DR Reactome; R-CEL-1251985; Nuclear signaling by ERBB4.
DR Reactome; R-CEL-6798695; Neutrophil degranulation.
DR SignaLink; P52166; -.
DR PRO; PR:P52166; -.
DR Proteomes; UP000001940; Chromosome X.
DR Bgee; WBGene00004769; Expressed in pharyngeal muscle cell (C elegans) and 4 other tissues.
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:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0070765; C:gamma-secretase complex; ISS:WormBase.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0030426; C:growth cone; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
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: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; IDA:WormBase.
DR GO; GO:0030018; C:Z disc; IBA:GO_Central.
DR GO; GO:0004190; F:aspartic-type endopeptidase activity; IEA:InterPro.
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:0050435; P:amyloid-beta metabolic process; IBA:GO_Central.
DR GO; GO:0045176; P:apical protein localization; IDA:WormBase.
DR GO; GO:0006816; P:calcium ion transport; IBA:GO_Central.
DR GO; GO:0001708; P:cell fate specification; IMP:WormBase.
DR GO; GO:0048858; P:cell projection morphogenesis; IMP:UniProtKB.
DR GO; GO:0016048; P:detection of temperature stimulus; IMP:UniProtKB.
DR GO; GO:0006509; P:membrane protein ectodomain proteolysis; IBA:GO_Central.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IBA:GO_Central.
DR GO; GO:0007399; P:nervous system development; IMP:UniProtKB.
DR GO; GO:0007220; P:Notch receptor processing; IBA:GO_Central.
DR GO; GO:0007219; P:Notch signaling pathway; NAS:UniProtKB.
DR GO; GO:0018991; P:oviposition; IMP:WormBase.
DR GO; GO:0045747; P:positive regulation of Notch signaling pathway; IGI:WormBase.
DR GO; GO:0048563; P:post-embryonic animal organ morphogenesis; IMP:WormBase.
DR GO; GO:0016485; P:protein processing; IEA:InterPro.
DR GO; GO:0110011; P:regulation of basement membrane organization; IMP:UniProtKB.
DR GO; GO:0017015; P:regulation of transforming growth factor beta receptor signaling pathway; IGI:WormBase.
DR Gene3D; 1.10.472.100; -; 1.
DR InterPro; IPR001686; Pept_A22A_Ceel.
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; PR01075; PRESENILNSEL.
DR SMART; SM00730; PSN; 1.
PE 1: Evidence at protein level;
KW Endoplasmic reticulum; Golgi apparatus; Membrane; Notch signaling pathway;
KW Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..444
FT /note="Presenilin sel-12"
FT /id="PRO_0000073903"
FT TOPO_DOM 1..45
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 46..66
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 67..101
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 102..122
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 123..130
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 131..151
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 152..163
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 164..184
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 185..189
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 190..210
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 211..212
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 213..233
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 234..359
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 360..380
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 381..384
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 385..405
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 406..413
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT INTRAMEM 414..434
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 435..444
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 275..331
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 410..412
FT /note="PAL"
FT COMPBIAS 275..296
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 313..331
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 226
FT /evidence="ECO:0000250"
FT ACT_SITE 364
FT /evidence="ECO:0000250"
FT MUTAGEN 60
FT /note="C->S: In ar131; egg-laying-defective."
FT /evidence="ECO:0000269|PubMed:12413907,
FT ECO:0000269|PubMed:7566091"
FT MUTAGEN 134..444
FT /note="Missing: In ty11; reduces the size of the openings
FT in the basement membranes that underlie epithelial cells."
FT /evidence="ECO:0000269|PubMed:27661254"
SQ SEQUENCE 444 AA; 50034 MW; 37ADBC124E16429C CRC64;
MPSTRRQQEG GGADAETHTV YGTNLITNRN SQEDENVVEE AELKYGASHV IHLFVPVSLC
MALVVFTMNT ITFYSQNNGR HLLYTPFVRE TDSIVEKGLM SLGNALVMLC VVVLMTVLLI
VFYKYKFYKL IHGWLIVSSF LLLFLFTTIY VQEVLKSFDV SPSALLVLFG LGNYGVLGMM
CIHWKGPLRL QQFYLITMSA LMALVFIKYL PEWTVWFVLF VISVWDLVAV LTPKGPLRYL
VETAQERNEP IFPALIYSSG VIYPYVLVTA VENTTDPREP TSSDSNTSTA FPGEASCSSE
TPKRPKVKRI PQKVQIESNT TASTTQNSGV RVERELAAER PTVQDANFHR HEEEERGVKL
GLGDFIFYSV LLGKASSYFD WNTTIACYVA ILIGLCFTLV LLAVFKRALP ALPISIFSGL
IFYFCTRWII TPFVTQVSQK CLLY
