IMP2_CAEEL
ID IMP2_CAEEL Reviewed; 468 AA.
AC P49049;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 1.
DT 03-AUG-2022, entry version 117.
DE RecName: Full=Intramembrane protease 2;
DE EC=3.4.23.- {ECO:0000305|PubMed:29137240};
GN Name=imp-2 {ECO:0000312|WormBase:T05E11.5};
GN ORFNames=T05E11.5 {ECO:0000312|WormBase:T05E11.5};
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 [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 [2]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=15469912; DOI=10.1073/pnas.0406462101;
RA Grigorenko A.P., Moliaka Y.K., Soto M.C., Mello C.C., Rogaev E.I.;
RT "The Caenorhabditis elegans IMPAS gene, imp-2, is essential for development
RT and is functionally distinct from related presenilins.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:14955-14960(2004).
RN [3]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-114, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RX PubMed=15888633; DOI=10.1093/glycob/cwi075;
RA Fan X., She Y.-M., Bagshaw R.D., Callahan J.W., Schachter H., Mahuran D.J.;
RT "Identification of the hydrophobic glycoproteins of Caenorhabditis
RT elegans.";
RL Glycobiology 15:952-964(2005).
RN [4]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-114 AND ASN-123, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=Bristol N2;
RX PubMed=17761667; DOI=10.1074/mcp.m600392-mcp200;
RA Kaji H., Kamiie J., Kawakami H., Kido K., Yamauchi Y., Shinkawa T.,
RA Taoka M., Takahashi N., Isobe T.;
RT "Proteomics reveals N-linked glycoprotein diversity in Caenorhabditis
RT elegans and suggests an atypical translocation mechanism for integral
RT membrane proteins.";
RL Mol. Cell. Proteomics 6:2100-2109(2007).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF
RP GLY-350 AND PRO-417.
RX PubMed=29137240; DOI=10.18632/oncotarget.18299;
RA Grigorenko A.P., Moliaka Y.K., Plotnikova O.V., Smirnov A., Nikishina V.A.,
RA Goltsov A.Y., Gusev F., Andreeva T.V., Nelson O., Bezprozvanny I.,
RA Rogaev E.I.;
RT "Mutational re-modeling of di-aspartyl intramembrane proteases: uncoupling
RT physiologically-relevant activities from those associated with Alzheimer's
RT disease.";
RL Oncotarget 8:82006-82026(2017).
CC -!- FUNCTION: Acts as intramembrane protease (Probable). In larvae,
CC required for the complete shedding of the cuticle during molting,
CC possibly by regulating cholesterol uptake via lrp-1 (PubMed:15469912).
CC Involved in embryonic and larval development (PubMed:15469912,
CC PubMed:29137240). {ECO:0000269|PubMed:15469912,
CC ECO:0000269|PubMed:29137240, ECO:0000305|PubMed:29137240}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Multi-pass membrane
CC protein {ECO:0000255}. Endoplasmic reticulum membrane {ECO:0000305};
CC Multi-pass membrane protein {ECO:0000305}.
CC -!- DOMAIN: The PAL motif is required for normal active site conformation.
CC {ECO:0000250|UniProtKB:P49768}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown results in late stage
CC embryonic and larval lethality, slow growth and pharyngeal pumping,
CC uncoordinated movement, reduced brood size, middle body constriction,
CC and muscle detachment (PubMed:15469912, PubMed:29137240). RNAi-mediated
CC knockdown in L1 larvae causes incomplete cuticle shedding during
CC molting (PubMed:15469912). {ECO:0000269|PubMed:15469912,
CC ECO:0000269|PubMed:29137240}.
CC -!- SIMILARITY: Belongs to the peptidase A22B family. {ECO:0000305}.
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DR EMBL; BX284604; CAA92975.1; -; Genomic_DNA.
DR PIR; T24523; T24523.
DR RefSeq; NP_502079.1; NM_069678.6.
DR AlphaFoldDB; P49049; -.
DR BioGRID; 43112; 16.
DR STRING; 6239.T05E11.5; -.
DR MEROPS; A22.003; -.
DR iPTMnet; P49049; -.
DR EPD; P49049; -.
DR PaxDb; P49049; -.
DR PeptideAtlas; P49049; -.
DR EnsemblMetazoa; T05E11.5.1; T05E11.5.1; WBGene00011481.
DR GeneID; 178013; -.
DR KEGG; cel:CELE_T05E11.5; -.
DR UCSC; T05E11.5; c. elegans.
DR CTD; 178013; -.
DR WormBase; T05E11.5; CE06364; WBGene00011481; imp-2.
DR eggNOG; KOG2443; Eukaryota.
DR GeneTree; ENSGT00940000156478; -.
DR HOGENOM; CLU_023799_0_2_1; -.
DR InParanoid; P49049; -.
DR OMA; RHWITNN; -.
DR OrthoDB; 1087991at2759; -.
DR PhylomeDB; P49049; -.
DR PRO; PR:P49049; -.
DR Proteomes; UP000001940; Chromosome IV.
DR Bgee; WBGene00011481; Expressed in germ line (C elegans) and 4 other tissues.
DR GO; GO:0071458; C:integral component of cytoplasmic side of endoplasmic reticulum membrane; IBA:GO_Central.
DR GO; GO:0071556; C:integral component of lumenal side of endoplasmic reticulum membrane; IBA:GO_Central.
DR GO; GO:0042500; F:aspartic endopeptidase activity, intramembrane cleaving; IDA:UniProtKB.
DR GO; GO:0042395; P:ecdysis, collagen and cuticulin-based cuticle; IMP:UniProtKB.
DR GO; GO:0033619; P:membrane protein proteolysis; IBA:GO_Central.
DR GO; GO:0040019; P:positive regulation of embryonic development; IMP:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IDA:UniProtKB.
DR GO; GO:0061062; P:regulation of nematode larval development; IMP:UniProtKB.
DR GO; GO:0006465; P:signal peptide processing; IBA:GO_Central.
DR InterPro; IPR007369; Peptidase_A22B_SPP.
DR InterPro; IPR006639; Preselin/SPP.
DR PANTHER; PTHR12174; PTHR12174; 1.
DR Pfam; PF04258; Peptidase_A22B; 1.
DR SMART; SM00730; PSN; 1.
PE 1: Evidence at protein level;
KW Endoplasmic reticulum; Glycoprotein; Hydrolase; Membrane; Protease;
KW Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..468
FT /note="Intramembrane protease 2"
FT /id="PRO_0000073914"
FT TOPO_DOM 1..22
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 23..43
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 44..70
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 71..91
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 92..168
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 169..189
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 190..247
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 248..265
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 266..267
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 268..284
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 285..296
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 297..317
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 318..343
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 344..364
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 365..388
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 389..409
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 410..415
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 416..436
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 437..468
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT MOTIF 417..419
FT /note="PAL"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT ACT_SITE 306
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT ACT_SITE 353
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT CARBOHYD 14
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 114
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:15888633,
FT ECO:0000269|PubMed:17761667"
FT CARBOHYD 123
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:17761667"
FT MUTAGEN 350
FT /note="G->A: Slight reduction in progeny number."
FT /evidence="ECO:0000269|PubMed:29137240"
FT MUTAGEN 350
FT /note="G->K: Embryonic or larval lethality. The few
FT surviving adults are uncoordinated and have severely
FT reduced fertility."
FT /evidence="ECO:0000269|PubMed:29137240"
FT MUTAGEN 417
FT /note="P->A: Slight reduction in progeny number."
FT /evidence="ECO:0000269|PubMed:29137240"
FT MUTAGEN 417
FT /note="P->L: Embryonic or larval lethality. The few
FT surviving adults are uncoordinated and have severely
FT reduced fertility."
FT /evidence="ECO:0000269|PubMed:29137240"
SQ SEQUENCE 468 AA; 52794 MW; 00DFFACB679AA5F8 CRC64;
MAEAATEIPP TASNVTVFTF EEQATSSLAL YGMSILCIII GSIRSAQYIR TNIDKKRLIE
GSITMREARK FPISASLVLF GLYLFFKPAA ERFLWVARVF QILRVPEEYV QKINSTIISY
TANTTTTGPS EPFLLRLASR IPQERVPEAI QNAATYAYTN LPTIQKAECM QLLTFLICFE
GVNAFASLLK PFVTAFLKKM PLVPSFLRFN APYLFSLKKG NKEMEEGDIE DAKKKETEYL
FKIDFDRYDI IALLMCSPIL ISHLLKRHWI TNNIIGVSFS ILGIERLHLA SFKAGSLLLV
GLFFYDIFWV FGTDVMTSVA KGIDAPILLQ FPQDIYRNGI MEASKHSMLG LGDIVIPGIF
IALLRRFDYR VVQTTAESKA PQGSLKGRYY FVVTVVAYMA GLFITMAVMH HFKAAQPALL
YLVPCCLFVP LLLAVIRGEL SALWNYDESR HVDNEENRKK VDSGKKNN
