CREL1_CAEEL
ID CREL1_CAEEL Reviewed; 356 AA.
AC Q19267; A7LPH5;
DT 18-SEP-2019, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Protein disulfide isomerase crld-1 {ECO:0000303|PubMed:30407909};
DE EC=5.3.4.1 {ECO:0000269|PubMed:30407909};
DE AltName: Full=Cysteine-rich with EGF-like domain protein crld-1 {ECO:0000312|WormBase:F09E8.2a};
DE Flags: Precursor;
GN Name=crld-1 {ECO:0000303|PubMed:30407909, ECO:0000312|WormBase:F09E8.2a};
GN ORFNames=F09E8.2 {ECO:0000312|WormBase:F09E8.2a};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
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 [2] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH UNC-29, SUBCELLULAR
RP LOCATION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE, TOPOLOGY, AND
RP MUTAGENESIS OF CYS-30.
RX PubMed=30407909; DOI=10.7554/elife.39649;
RA D'Alessandro M., Richard M., Stigloher C., Gache V., Boulin T.,
RA Richmond J.E., Bessereau J.L.;
RT "CRELD1 is an evolutionarily-conserved maturational enhancer of ionotropic
RT acetylcholine receptors.";
RL Elife 7:0-0(2018).
CC -!- FUNCTION: Protein disulfide isomerase which associates with the unc-29
CC subunit of levamisole-sensitive nicotinic acetylcholine receptors (L-
CC nAChR) to promote L-nAChR assembly in the endoplasmic reticulum at
CC neuromuscular junctions. {ECO:0000269|PubMed:30407909}.
CC -!- FUNCTION: [Isoform a]: Promotes L-nAChR assembly in the endoplasmic
CC reticulum at neuromuscular junctions. {ECO:0000269|PubMed:30407909}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Catalyzes the rearrangement of -S-S- bonds in proteins.;
CC EC=5.3.4.1; Evidence={ECO:0000269|PubMed:30407909};
CC -!- SUBUNIT: Interacts with unc-29. {ECO:0000269|PubMed:30407909}.
CC -!- SUBCELLULAR LOCATION: [Isoform a]: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:30407909}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- SUBCELLULAR LOCATION: [Isoform b]: Endoplasmic reticulum lumen
CC {ECO:0000269|PubMed:30407909}. Note=Ends with a KDEL sequence, which is
CC an endoplasmic reticulum retention signal.
CC {ECO:0000305|PubMed:30407909}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=a {ECO:0000312|WormBase:F09E8.2a};
CC IsoId=Q19267-1; Sequence=Displayed;
CC Name=b {ECO:0000312|WormBase:F09E8.2b};
CC IsoId=Q19267-2; Sequence=VSP_060244, VSP_060245;
CC -!- TISSUE SPECIFICITY: Isoforms a: Widely expressed in tissues including
CC body wall muscles, neurons, pharynx, hypodermis, seam cells, intestine
CC and gonad (PubMed:30407909). Isoform b: Widely expressed in tissues
CC including body wall muscles, neurons, pharynx, hypodermis, seam cells,
CC intestine and gonad (PubMed:30407909). {ECO:0000269|PubMed:30407909}.
CC -!- DISRUPTION PHENOTYPE: Viable, with no defects in coordination
CC (PubMed:30407909). Decreased number of synaptic nicotinic acetylcholine
CC receptors (nAChRs) at neuromuscular junctions (PubMed:30407909).
CC Isoform a: Deletion leads to reduced sensitivity to the nAChR agonist
CC levamisole (PubMed:30407909). Isoform b: Deletion leads to sensitivity
CC to levamisole as in wild-type (PubMed:30407909).
CC {ECO:0000269|PubMed:30407909}.
CC -!- SIMILARITY: Belongs to the CRELD family. {ECO:0000305}.
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DR EMBL; BX284604; CAA98055.1; -; Genomic_DNA.
DR EMBL; BX284604; CAO82025.1; -; Genomic_DNA.
DR PIR; T20656; T20656.
DR RefSeq; NP_001122767.1; NM_001129295.2.
DR RefSeq; NP_502530.1; NM_070129.5. [Q19267-1]
DR AlphaFoldDB; Q19267; -.
DR STRING; 6239.F09E8.2a; -.
DR PaxDb; Q19267; -.
DR PeptideAtlas; Q19267; -.
DR EnsemblMetazoa; F09E8.2a.1; F09E8.2a.1; WBGene00008624. [Q19267-1]
DR EnsemblMetazoa; F09E8.2a.2; F09E8.2a.2; WBGene00008624. [Q19267-1]
DR EnsemblMetazoa; F09E8.2b.1; F09E8.2b.1; WBGene00008624. [Q19267-2]
DR EnsemblMetazoa; F09E8.2b.2; F09E8.2b.2; WBGene00008624. [Q19267-2]
DR GeneID; 178267; -.
DR UCSC; F09E8.2b; c. elegans.
DR CTD; 178267; -.
DR WormBase; F09E8.2a; CE05579; WBGene00008624; crld-1. [Q19267-1]
DR WormBase; F09E8.2b; CE41378; WBGene00008624; crld-1. [Q19267-2]
DR eggNOG; KOG4260; Eukaryota.
DR HOGENOM; CLU_038974_1_0_1; -.
DR InParanoid; Q19267; -.
DR OMA; CDANYYA; -.
DR OrthoDB; 883628at2759; -.
DR PhylomeDB; Q19267; -.
DR PRO; PR:Q19267; -.
DR Proteomes; UP000001940; Chromosome IV.
DR Bgee; WBGene00008624; Expressed in pharyngeal muscle cell (C elegans) and 4 other tissues.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; IEA:UniProtKB-SubCell.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0003756; F:protein disulfide isomerase activity; IEA:UniProtKB-EC.
DR InterPro; IPR021852; DUF3456.
DR InterPro; IPR001881; EGF-like_Ca-bd_dom.
DR InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR000152; EGF-type_Asp/Asn_hydroxyl_site.
DR InterPro; IPR018097; EGF_Ca-bd_CS.
DR InterPro; IPR009030; Growth_fac_rcpt_cys_sf.
DR InterPro; IPR002049; LE_dom.
DR Pfam; PF11938; DUF3456; 2.
DR Pfam; PF07645; EGF_CA; 1.
DR SMART; SM00181; EGF; 3.
DR SMART; SM00179; EGF_CA; 1.
DR SUPFAM; SSF57184; SSF57184; 1.
DR PROSITE; PS00010; ASX_HYDROXYL; 1.
DR PROSITE; PS00022; EGF_1; 1.
DR PROSITE; PS01186; EGF_2; 1.
DR PROSITE; PS50026; EGF_3; 2.
DR PROSITE; PS01187; EGF_CA; 1.
DR PROSITE; PS01248; EGF_LAM_1; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Calcium; Disulfide bond; EGF-like domain;
KW Endoplasmic reticulum; Glycoprotein; Isomerase; Membrane;
KW Redox-active center; Reference proteome; Repeat; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..17
FT /evidence="ECO:0000255"
FT CHAIN 18..356
FT /note="Protein disulfide isomerase crld-1"
FT /evidence="ECO:0000255"
FT /id="PRO_5004187109"
FT TOPO_DOM 18..299
FT /note="Lumenal"
FT /evidence="ECO:0000305|PubMed:30407909"
FT TRANSMEM 300..317
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 318..321
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:30407909"
FT TRANSMEM 322..341
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 342..356
FT /note="Lumenal"
FT /evidence="ECO:0000305|PubMed:30407909"
FT DOMAIN 150..188
FT /note="EGF-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 241..282
FT /note="EGF-like 2; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT MOTIF 27..30
FT /note="CXXC"
FT /evidence="ECO:0000305|PubMed:30407909"
FT CARBOHYD 122
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 247
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT DISULFID 27..30
FT /note="Redox-active"
FT /evidence="ECO:0000305|PubMed:30407909"
FT DISULFID 158..176
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 178..187
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 245..258
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 251..267
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 269..281
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT VAR_SEQ 288..310
FT /note="SPDRPFMPIDQQLKLIAFSSLII -> LKATEQQAHEDEDGDDDDEKDEL
FT (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_060244"
FT VAR_SEQ 311..356
FT /note="Missing (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_060245"
FT MUTAGEN 30
FT /note="C->A: In kr302; substrate-trapping mutant. Reduced
FT sensitivity to the nicotinic acetylcholine receptor (nAChR)
FT agonist levamisole."
FT /evidence="ECO:0000269|PubMed:30407909"
SQ SEQUENCE 356 AA; 39790 MW; EFF82577DE334F57 CRC64;
MSRILLLLAV LIGATSQKEV TIKNEKCRTC NFLVSTFDEG LKKTARHHFA GGDTAWEEKN
LGKYKTSETR LIEVLEGVCK KSSLPNMDNF MGIAEIEFKC STQLEKHEET IEEFYYNQQH
NNMSNWLCVE QLKLCCPDGH FGKNCEQCPG LSEKADVCFG KGSCHGDGSR EGSGKCKCET
GYTGNLCRYC DIEYFEESRT VQGVVCKKCH EGCLGVCSSE SSKGCSKCKN GWKLTEEGCA
DVNECQNESA CTKEHEICVN TVGSFKCECK EGYKKDDEQN CQFDVEASPD RPFMPIDQQL
KLIAFSSLII IITFVVWHGS PVLYVLTGIT IVALILVDLY VNPDTIPDEA KRFLGY
