AEX5_CAEEL
ID AEX5_CAEEL Reviewed; 537 AA.
AC P91863;
DT 12-APR-2017, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 2.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=Endoprotease aex-5 {ECO:0000305};
DE EC=3.4.21.- {ECO:0000303|PubMed:16945111};
DE AltName: Full=Subtilisin-like protease {ECO:0000255|PROSITE-ProRule:PRU10080};
DE Flags: Precursor;
GN Name=aex-5 {ECO:0000303|PubMed:2323555, ECO:0000312|WormBase:F32A7.6};
GN Synonyms=kpc-3 {ECO:0000312|WormBase:F32A7.6};
GN ORFNames=F32A7.6 {ECO:0000312|WormBase:F32A7.6};
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, AND MUTAGENESIS OF CYS-443.
RX PubMed=2323555; DOI=10.1093/genetics/124.4.855;
RA Thomas J.H.;
RT "Genetic analysis of defecation in Caenorhabditis elegans.";
RL Genetics 124:855-872(1990).
RN [3] {ECO:0000305}
RP FUNCTION, AND MUTAGENESIS OF CYS-443.
RX PubMed=11804572; DOI=10.1016/s0896-6273(01)00587-6;
RA Doi M., Iwasaki K.;
RT "Regulation of retrograde signaling at neuromuscular junctions by the novel
RT C2 domain protein AEX-1.";
RL Neuron 33:249-259(2002).
RN [4] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF CYS-443.
RX PubMed=16945111; DOI=10.1111/j.1471-4159.2006.04014.x;
RA Husson S.J., Clynen E., Baggerman G., Janssen T., Schoofs L.;
RT "Defective processing of neuropeptide precursors in Caenorhabditis elegans
RT lacking proprotein convertase 2 (KPC-2/EGL-3): mutant analysis by mass
RT spectrometry.";
RL J. Neurochem. 98:1999-2012(2006).
RN [5] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF
RP CYS-443.
RX PubMed=18852466; DOI=10.1073/pnas.0803617105;
RA Mahoney T.R., Luo S., Round E.K., Brauner M., Gottschalk A., Thomas J.H.,
RA Nonet M.L.;
RT "Intestinal signaling to GABAergic neurons regulates a rhythmic behavior in
RT Caenorhabditis elegans.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:16350-16355(2008).
RN [6] {ECO:0000305}
RP FUNCTION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF GLY-184; GLY-405 AND
RP CYS-443.
RX PubMed=25849533; DOI=10.1371/journal.pone.0124515;
RA Sheng M., Hosseinzadeh A., Muralidharan S.V., Gaur R., Selstam E., Tuck S.;
RT "Aberrant fat metabolism in Caenorhabditis elegans mutants with defects in
RT the defecation motor program.";
RL PLoS ONE 10:E0124515-E0124515(2015).
CC -!- FUNCTION: Probable serine endoprotease which cleaves preproteins at
CC paired basic amino acids (PubMed:16945111). May process FMRFamide-like
CC (flp) and neuropeptide-like protein (nlp) neuropeptides
CC (PubMed:16945111). In muscles, involved in neuronal retrograde
CC signaling by regulating presynaptic activity and localization of
CC synaptic vesicle fusion protein unc-13 at the neuromuscular junction
CC (NMJ) (PubMed:11804572). Acts in the intestine to regulate anterior
CC body muscle contractions (aBOC) and the expulsion steps during the
CC defecation motor program (DMP) (PubMed:2323555, PubMed:11804572,
CC PubMed:18852466, PubMed:25849533). Probably by regulating DMP, required
CC for fatty acid uptake by intestinal cells and therefore regulates the
CC levels of triglycerides in the intestine (PubMed:25849533). Plays a
CC role in locomotion (PubMed:11804572). {ECO:0000269|PubMed:11804572,
CC ECO:0000269|PubMed:16945111, ECO:0000269|PubMed:18852466,
CC ECO:0000269|PubMed:2323555, ECO:0000269|PubMed:25849533}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:18852466}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown causes a reduction in
CC fatty acid uptake (PubMed:25849533). RNAi-mediated knockdown in the
CC intestine causes a severe defect in the expulsion step of the
CC defecation cycle (PubMed:18852466). {ECO:0000269|PubMed:18852466,
CC ECO:0000269|PubMed:25849533}.
CC -!- SIMILARITY: Belongs to the peptidase S8 family. Furin subfamily.
CC {ECO:0000305}.
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DR EMBL; BX284601; CAB05501.2; -; Genomic_DNA.
DR PIR; T21624; T21624.
DR RefSeq; NP_493594.1; NM_061193.5.
DR AlphaFoldDB; P91863; -.
DR SMR; P91863; -.
DR STRING; 6239.F32A7.6; -.
DR MEROPS; S08.132; -.
DR PaxDb; P91863; -.
DR EnsemblMetazoa; F32A7.6.1; F32A7.6.1; WBGene00000088.
DR GeneID; 173358; -.
DR KEGG; cel:CELE_F32A7.6; -.
DR CTD; 173358; -.
DR WormBase; F32A7.6; CE28554; WBGene00000088; aex-5.
DR eggNOG; KOG3525; Eukaryota.
DR HOGENOM; CLU_002976_4_4_1; -.
DR InParanoid; P91863; -.
DR OMA; QRDIQHL; -.
DR OrthoDB; 308083at2759; -.
DR PhylomeDB; P91863; -.
DR PRO; PR:P91863; -.
DR Proteomes; UP000001940; Chromosome I.
DR Bgee; WBGene00000088; Expressed in larva and 3 other tissues.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0030173; C:integral component of Golgi membrane; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005802; C:trans-Golgi network; IBA:GO_Central.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IMP:UniProtKB.
DR GO; GO:0030421; P:defecation; IMP:WormBase.
DR GO; GO:0010877; P:lipid transport involved in lipid storage; IMP:UniProtKB.
DR GO; GO:0040011; P:locomotion; IMP:WormBase.
DR GO; GO:0061837; P:neuropeptide processing; IMP:UniProtKB.
DR GO; GO:2000294; P:positive regulation of defecation; IMP:UniProtKB.
DR GO; GO:2000748; P:positive regulation of defecation rhythm; IMP:UniProtKB.
DR GO; GO:1904731; P:positive regulation of intestinal lipid absorption; IMP:UniProtKB.
DR GO; GO:0040017; P:positive regulation of locomotion; IGI:UniProtKB.
DR GO; GO:0045887; P:positive regulation of synaptic assembly at neuromuscular junction; IGI:UniProtKB.
DR GO; GO:1905885; P:positive regulation of triglyceride transport; IMP:UniProtKB.
DR GO; GO:0035418; P:protein localization to synapse; IMP:WormBase.
DR GO; GO:0016485; P:protein processing; IBA:GO_Central.
DR GO; GO:2000292; P:regulation of defecation; IGI:UniProtKB.
DR CDD; cd04059; Peptidases_S8_Protein_convertases_Kexins_Furin-like; 1.
DR Gene3D; 3.40.50.200; -; 1.
DR InterPro; IPR008979; Galactose-bd-like_sf.
DR InterPro; IPR034182; Kexin/furin.
DR InterPro; IPR002884; P_dom.
DR InterPro; IPR000209; Peptidase_S8/S53_dom.
DR InterPro; IPR036852; Peptidase_S8/S53_dom_sf.
DR InterPro; IPR023827; Peptidase_S8_Asp-AS.
DR InterPro; IPR022398; Peptidase_S8_His-AS.
DR InterPro; IPR015500; Peptidase_S8_subtilisin-rel.
DR Pfam; PF01483; P_proprotein; 1.
DR Pfam; PF00082; Peptidase_S8; 1.
DR PRINTS; PR00723; SUBTILISIN.
DR SUPFAM; SSF49785; SSF49785; 1.
DR SUPFAM; SSF52743; SSF52743; 1.
DR PROSITE; PS51829; P_HOMO_B; 1.
DR PROSITE; PS51892; SUBTILASE; 1.
DR PROSITE; PS00136; SUBTILASE_ASP; 1.
DR PROSITE; PS00137; SUBTILASE_HIS; 1.
PE 1: Evidence at protein level;
KW Cleavage on pair of basic residues; Disulfide bond; Glycoprotein;
KW Hydrolase; Protease; Reference proteome; Secreted; Serine protease; Signal;
KW Zymogen.
FT SIGNAL 1..17
FT /evidence="ECO:0000255"
FT PROPEP 18..99
FT /evidence="ECO:0000255"
FT /id="PRO_0000439454"
FT CHAIN 100..537
FT /note="Endoprotease aex-5"
FT /evidence="ECO:0000255"
FT /id="PRO_5004161816"
FT DOMAIN 111..413
FT /note="Peptidase S8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT DOMAIN 407..537
FT /note="P/Homo B"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01173"
FT ACT_SITE 139
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT ACT_SITE 178
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT ACT_SITE 346
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT CARBOHYD 129
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 380
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT DISULFID 286..316
FT /evidence="ECO:0000250|UniProtKB:P23188"
FT MUTAGEN 184
FT /note="G->E: In sv76; intestinal lipid droplets are smaller
FT and their number is reduced. Reduced uptake and
FT accumulation of triglycerides in the intestine."
FT /evidence="ECO:0000269|PubMed:25849533"
FT MUTAGEN 405
FT /note="G->S: In sv75; intestinal lipid droplets are smaller
FT and their number is reduced. Reduced uptake and
FT accumulation of triglycerides in the intestine."
FT /evidence="ECO:0000269|PubMed:25849533"
FT MUTAGEN 443
FT /note="C->W: In sa23; loss of production of several nlp and
FT flp neuropeptides. Reduced enrichment of unc-13 at
FT presynaptic active sites of neuromuscular junctions.
FT Mutants are constipated due to a defect in body wall muscle
FT and intestinal contractions and have a slightly longer
FT defecation cycle. Reduced uptake and accumulation of
FT triglycerides in the intestine. Mild body thrashing."
FT /evidence="ECO:0000269|PubMed:11804572,
FT ECO:0000269|PubMed:16945111, ECO:0000269|PubMed:18852466,
FT ECO:0000269|PubMed:2323555, ECO:0000269|PubMed:25849533"
SQ SEQUENCE 537 AA; 58705 MW; 8160A7B53EF2D386 CRC64;
MKLIFLLLLF GVSPIVCQDF EDGVFLAKIT SIDEHDARKI GRRFGFEAQW KLQSYTDVYV
GRRLRRRKRG IEDEIVAEMM LSQQVQFIEK LQGFRRYKRA PMTNKGYPVH VWNLTPSLYI
REAWEDGFNA SRVTVAVVDD GVDIKHVDLK SAFSPRVSFD FVRFGDLPTP KNSKEFEHGT
QCAGLVAMEG QQCGLGVGHG ATLGAIKLLG QDFLNDALEG DALAFQKDLI DIYSVSWGPK
DDGKSAEKPA KFTEEAIKNG ALHGRNGKGN IFVWASGNGG VNGDNCAYDG YVSNEYTLSF
GVIDASGAPA AYGEGCSSVL AAVSGGDAMI QTTGLESTCS SISGSSASAA IASGIISLVL
DANPTLSQRD IQHLIARTSN ASAIRDVELY ENSAGLNFHP KVGFGLLNAQ KLVVMAATWE
NVAPQVTCEK MNLANGIIDN SDCDVTKVER VIVSGSIIHP HRGQVQIRLE SPRGTISELL
PLRPKDTSRD LLDWNFVSVN FFGENSRGIW KLHVTSEEDD VDFRVEMKMF KVVGTMS
