NCLN_CAEEL
ID NCLN_CAEEL Reviewed; 563 AA.
AC A5JYX8; O18033;
DT 13-NOV-2019, integrated into UniProtKB/Swiss-Prot.
DT 26-JUN-2007, sequence version 1.
DT 03-AUG-2022, entry version 102.
DE RecName: Full=Nicalin {ECO:0000255|PIRNR:PIRNR011018};
DE AltName: Full=Inactive aminopeptidase nra-2 {ECO:0000305};
DE AltName: Full=Nicotinic receptor-associated protein 2 {ECO:0000303|PubMed:19609303};
DE Flags: Precursor;
GN Name=nra-2 {ECO:0000303|PubMed:15990870, ECO:0000312|WormBase:T05F1.1b};
GN ORFNames=T05F1.1 {ECO:0000312|WormBase:T05F1.1b};
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, INTERACTION WITH NICOTINIC ACETYLCHOLINE RECEPTOR, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=15990870; DOI=10.1038/sj.emboj.7600741;
RA Gottschalk A., Almedom R.B., Schedletzky T., Anderson S.D., Yates J.R. III,
RA Schafer W.R.;
RT "Identification and characterization of novel nicotinic receptor-associated
RT proteins in Caenorhabditis elegans.";
RL EMBO J. 24:2566-2578(2005).
RN [3] {ECO:0000305}
RP FUNCTION, INTERACTION WITH NRA-4, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=19609303; DOI=10.1038/emboj.2009.204;
RA Almedom R.B., Liewald J.F., Hernando G., Schultheis C., Rayes D., Pan J.,
RA Schedletzky T., Hutter H., Bouzat C., Gottschalk A.;
RT "An ER-resident membrane protein complex regulates nicotinic acetylcholine
RT receptor subunit composition at the synapse.";
RL EMBO J. 28:2636-2649(2009).
RN [4] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=24567339; DOI=10.1074/jbc.m113.533695;
RA Kamat S., Yeola S., Zhang W., Bianchi L., Driscoll M.;
RT "NRA-2, a nicalin homolog, regulates neuronal death by controlling surface
RT localization of toxic Caenorhabditis elegans DEG/ENaC channels.";
RL J. Biol. Chem. 289:11916-11926(2014).
CC -!- FUNCTION: Involved in the recognition and selection of protein
CC complexes to exit the endoplasmic reticulum (ER) (PubMed:19609303,
CC PubMed:24567339). In muscles, regulates levamisole-sensitive nicotinic
CC acetylcholine receptor (L-AChR) subunit composition, possibly by
CC allowing only specific L-AChR subunit combinations to exit the ER
CC (PubMed:19609303). Specifically, may promote the inclusion of alpha
CC subunits unc-38 and unc-29 into L-AChR (PubMed:19609303). Regulates L-
CC AChR sensitivity to agonists such as nicotine and levamisole at neuro-
CC muscular junctions (PubMed:15990870, PubMed:19609303). In touch
CC neurons, may prevent ER exit of incorrectly folded mec-4-mec-10 ion
CC channel (PubMed:24567339). {ECO:0000269|PubMed:15990870,
CC ECO:0000269|PubMed:19609303, ECO:0000269|PubMed:24567339}.
CC -!- SUBUNIT: May interact with the levamisole-sensitive nicotinic
CC acetylcholine receptor (L-AChR) (PubMed:15990870). May interact with
CC nra-4 in the ER (PubMed:19609303). {ECO:0000269|PubMed:15990870,
CC ECO:0000269|PubMed:19609303}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:19609303}; Single-pass type I membrane protein
CC {ECO:0000255}. Note=During the assembly of acetylcholine receptor in
CC muscles, colocalizes with L-AChR component unc-29 in the ER.
CC {ECO:0000269|PubMed:19609303}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=b {ECO:0000312|WormBase:T05F1.1b};
CC IsoId=A5JYX8-1; Sequence=Displayed;
CC Name=a {ECO:0000312|WormBase:T05F1.1a};
CC IsoId=A5JYX8-2; Sequence=VSP_060399, VSP_060400;
CC -!- TISSUE SPECIFICITY: Expressed in body wall, pharyngeal, and vulval
CC muscles, excretory canal cell, head and motor neurons, and vulval
CC epithelium. {ECO:0000269|PubMed:19609303}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown causes a moderate
CC resistance to nicotine-induced paralysis (PubMed:15990870). RNAi-
CC mediated knockdown in neurons in a hyperactive mec-10 (A673V) mutant
CC background increases touch neuron (TRN) cell death (PubMed:24567339).
CC {ECO:0000269|PubMed:15990870, ECO:0000269|PubMed:24567339}.
CC -!- SIMILARITY: Belongs to the nicastrin family.
CC {ECO:0000255|PIRNR:PIRNR011018}.
CC -!- CAUTION: Although it contains a putative aminopeptidase domain, the
CC critical residues for Zn(2+) binding and thus for catalytic activity
CC are not conserved suggesting that nra-2 lacks peptidase activity.
CC {ECO:0000305|PubMed:19609303}.
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; BX284601; CAB04692.1; -; Genomic_DNA.
DR EMBL; BX284601; CAN86915.1; -; Genomic_DNA.
DR PIR; T24538; T24538.
DR RefSeq; NP_001122514.1; NM_001129042.2. [A5JYX8-1]
DR RefSeq; NP_492553.1; NM_060152.4. [A5JYX8-2]
DR AlphaFoldDB; A5JYX8; -.
DR SMR; A5JYX8; -.
DR IntAct; A5JYX8; 1.
DR MINT; A5JYX8; -.
DR STRING; 6239.T05F1.1b; -.
DR EPD; A5JYX8; -.
DR PaxDb; A5JYX8; -.
DR PeptideAtlas; A5JYX8; -.
DR EnsemblMetazoa; T05F1.1a.1; T05F1.1a.1; WBGene00011488. [A5JYX8-2]
DR EnsemblMetazoa; T05F1.1b.1; T05F1.1b.1; WBGene00011488. [A5JYX8-1]
DR GeneID; 172803; -.
DR KEGG; cel:CELE_T05F1.1; -.
DR UCSC; T05F1.1b; c. elegans.
DR CTD; 172803; -.
DR WormBase; T05F1.1a; CE13267; WBGene00011488; nra-2. [A5JYX8-2]
DR WormBase; T05F1.1b; CE41012; WBGene00011488; nra-2. [A5JYX8-1]
DR eggNOG; KOG2526; Eukaryota.
DR GeneTree; ENSGT00500000044945; -.
DR HOGENOM; CLU_034102_2_0_1; -.
DR InParanoid; A5JYX8; -.
DR OMA; RMHQYDL; -.
DR OrthoDB; 424149at2759; -.
DR PhylomeDB; A5JYX8; -.
DR PRO; PR:A5JYX8; -.
DR Proteomes; UP000001940; Chromosome I.
DR Bgee; WBGene00011488; Expressed in germ line (C elegans) and 4 other tissues.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:WormBase.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0065003; P:protein-containing complex assembly; IMP:UniProtKB.
DR GO; GO:0090313; P:regulation of protein targeting to membrane; IMP:UniProtKB.
DR GO; GO:0009966; P:regulation of signal transduction; IBA:GO_Central.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR InterPro; IPR016574; Nicalin.
DR PANTHER; PTHR31826; PTHR31826; 1.
DR PIRSF; PIRSF011018; Nicalin; 1.
DR PROSITE; PS00018; EF_HAND_1; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Endoplasmic reticulum; Glycoprotein; Membrane;
KW Reference proteome; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..29
FT /evidence="ECO:0000255"
FT CHAIN 30..563
FT /note="Nicalin"
FT /evidence="ECO:0000255"
FT /id="PRO_5002683601"
FT TOPO_DOM 30..522
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 523..543
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 544..563
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT CARBOHYD 232
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT VAR_SEQ 301..303
FT /note="Missing (in isoform a)"
FT /evidence="ECO:0000305"
FT /id="VSP_060399"
FT VAR_SEQ 345..348
FT /note="KYFS -> N (in isoform a)"
FT /evidence="ECO:0000305"
FT /id="VSP_060400"
SQ SEQUENCE 563 AA; 61872 MW; 57887C9DCF452638 CRC64;
MQDEIIDFFR SPALLFYMTL MLTICVVNGS QQVGEVVETE FHAYRLHQYE ISGNIYGCKN
YRVSYEAVSL GARTLRRTMV TTWRDLLTTD VDDMWALSTG AVLIFIPDNL DELNDIDRKA
FIDLEAKLLS AKTDLAVYVA PFNDDAVSIL HDVNTRSEKA PTALQHLLQS LSGNTISITS
SDQSPELPPS YKPLNIVGRL SSGDRAAPTI AFVAHYDTQS AVPGVSPGAD SNGSGIVALL
ELLAVLSKFY DSPSTRPPYN ILFIWTAAGK LNYQGTRHWI DEYQKGFDSA DYAKSGLSRK
GFSDDRVDLA ICIEAIGRKT GGFFMHAGKT PSENSVAAQL LRRLKYFSSI SPKKNIELVT
KKISLTTVSA WEHEKFNIKR MPAITLSTLP SPSDPARNSI LDLPSALDED ELIDNIRLIG
EAVLGYILDL PESGPSSDSR VKSEATMLSK DAVDKQRVHH FIRQFASRPR PVGDQRATES
ITSNLASVAA GYGNVFKSAV TITDAKAFGV TQNRLVAERV KPAVFELVIA AGVFTYLSAF
YYIATHSQNT IEGTVAAIRK SIF
