ID ACN1_CAEEL Reviewed; 906 AA.
AC Q18581; Q65ZH6;
DT 30-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 2.
DT 27-MAR-2024, entry version 135.
DE RecName: Full=Inactive angiotensin-converting enzyme-related protein;
DE AltName: Full=ACE-like non-metallopeptidase protein 1;
DE Flags: Precursor;
GN Name=acn-1; ORFNames=C42D8.5;
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], AND ALTERNATIVE SPLICING.
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, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=14559923; DOI=10.1074/jbc.m308858200;
RA Brooks D.R., Appleford P.J., Murray L., Isaac R.E.;
RT "An essential role in molting and morphogenesis of Caenorhabditis elegans
RT for ACN-1, a novel member of the angiotensin-converting enzyme family that
RT lacks a metallopeptidase active site.";
RL J. Biol. Chem. 278:52340-52346(2003).
RN [3]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-159, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC STRAIN=Bristol N2;
RX PubMed=12754521; DOI=10.1038/nbt829;
RA Kaji H., Saito H., Yamauchi Y., Shinkawa T., Taoka M., Hirabayashi J.,
RA Kasai K., Takahashi N., Isobe T.;
RT "Lectin affinity capture, isotope-coded tagging and mass spectrometry to
RT identify N-linked glycoproteins.";
RL Nat. Biotechnol. 21:667-672(2003).
RN [4]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-159 AND ASN-653, 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, AND DISRUPTION PHENOTYPE.
RX PubMed=26918946; DOI=10.1371/journal.pgen.1005866;
RA Kumar S., Dietrich N., Kornfeld K.;
RT "Angiotensin converting enzyme (ACE) inhibitor extends Caenorhabditis
RT elegans life span.";
RL PLoS Genet. 12:E1005866-E1005866(2016).
RN [6]
RP FUNCTION, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=28933985; DOI=10.1080/15384101.2017.1344798;
RA Metheetrairut C., Ahuja Y., Slack F.J.;
RT "acn-1, a C. elegans homologue of ACE, genetically interacts with the let-7
RT microRNA and other heterochronic genes.";
RL Cell Cycle 16:1800-1809(2017).
CC -!- FUNCTION: Inactive as a metallopeptidase, due to a lack of active site
CC residues (PubMed:14559923). Required for larval molting, male tail
CC development, and formation of adult alae (PubMed:14559923). Acts in the
CC heterochronic pathway and plays a role in the developmental timing of
CC postembryonic hypodermal seam cell division and adult alae production
CC (PubMed:28933985). Acts synergistically with apl-1 in let-7 regulated
CC postembryonic cell division events (PubMed:28933985). Might act
CC downstream of the heterochronic protein lin-41 (PubMed:28933985).
CC Negative regulator of lifespan, heat and oxidative stress response and
CC age-related degenerative changes like reduced pharyngeal pumping and
CC decreased body movements (PubMed:26918946). Lifespan restriction is
CC dependent on the forkhead-type transcription factor daf-16
CC (PubMed:26918946). {ECO:0000269|PubMed:14559923,
CC ECO:0000269|PubMed:26918946, ECO:0000269|PubMed:28933985}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=a;
CC IsoId=Q18581-1; Sequence=Displayed;
CC Name=b;
CC IsoId=Q18581-2; Sequence=VSP_015490, VSP_015491;
CC -!- TISSUE SPECIFICITY: Expressed in the hypodermis, in the vulva during
CC organogenesis, and in the ray papillae of the male tail.
CC {ECO:0000269|PubMed:14559923}.
CC -!- DEVELOPMENTAL STAGE: Expressed in embryos and larvae (PubMed:14559923).
CC Expressed in an oscillating expression pattern during larval
CC development, with low expression at the L2 stage, high expression at
CC the L2/L3 transition and low expression at the L3 stage
CC (PubMed:28933985). {ECO:0000269|PubMed:14559923,
CC ECO:0000269|PubMed:28933985}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown results in the extension
CC of mean and maximum lifespan of 21% and 18%, respectively, and
CC increased resistance to oxidative stress caused by paraquat
CC (PubMed:26918946). RNAi-mediated knockdown in a daf-16 mutant
CC background shortens mean and maximum lifespan by 3% and 2%,
CC respectively (PubMed:26918946). RNAi-mediated knockdown in a let-7
CC mutant background partially suppresses the retarded and supernumerary
CC hypodermal seam cell divisions, retarded alae production and
CC postembryonic lethality (PubMed:28933985). Double RNAi-mediated
CC knockdown with apl-1 in a let-7 mutant phenotype leads to complete
CC suppression of the heterochronic seam cell defects (PubMed:28933985).
CC {ECO:0000269|PubMed:26918946, ECO:0000269|PubMed:28933985}.
CC -!- SIMILARITY: Belongs to the peptidase M2 family. {ECO:0000305}.
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DR EMBL; FO080659; CCD65566.1; -; Genomic_DNA.
DR EMBL; FO080659; CCD65567.1; -; Genomic_DNA.
DR PIR; T15792; T15792.
DR RefSeq; NP_001024453.1; NM_001029282.3. [Q18581-1]
DR RefSeq; NP_001024454.1; NM_001029283.3.
DR AlphaFoldDB; Q18581; -.
DR SMR; Q18581; -.
DR BioGRID; 45715; 2.
DR IntAct; Q18581; 1.
DR MINT; Q18581; -.
DR STRING; 6239.C42D8.5a.2; -.
DR GlyCosmos; Q18581; 2 sites, No reported glycans.
DR iPTMnet; Q18581; -.
DR EPD; Q18581; -.
DR PaxDb; 6239-C42D8-5a; -.
DR PeptideAtlas; Q18581; -.
DR EnsemblMetazoa; C42D8.5.1; C42D8.5.1; WBGene00000039. [Q18581-1]
DR GeneID; 180780; -.
DR KEGG; cel:CELE_C42D8.5; -.
DR UCSC; C42D8.5b.1; c. elegans. [Q18581-1]
DR AGR; WB:WBGene00000039; -.
DR WormBase; C42D8.5a; CE30627; WBGene00000039; acn-1. [Q18581-1]
DR WormBase; C42D8.5b; CE37212; WBGene00000039; acn-1. [Q18581-2]
DR eggNOG; KOG3690; Eukaryota.
DR GeneTree; ENSGT00940000158077; -.
DR HOGENOM; CLU_011699_0_0_1; -.
DR InParanoid; Q18581; -.
DR OMA; FTVIHHE; -.
DR OrthoDB; 2898149at2759; -.
DR PhylomeDB; Q18581; -.
DR Reactome; R-CEL-2022377; Metabolism of Angiotensinogen to Angiotensins.
DR PRO; PR:Q18581; -.
DR Proteomes; UP000001940; Chromosome X.
DR Bgee; WBGene00000039; Expressed in embryo and 3 other cell types or tissues.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0008237; F:metallopeptidase activity; IBA:GO_Central.
DR GO; GO:0042395; P:ecdysis, collagen and cuticulin-based cuticle; IMP:WormBase.
DR GO; GO:0045138; P:nematode male tail tip morphogenesis; IMP:WormBase.
DR GO; GO:0045026; P:plasma membrane fusion; IMP:WormBase.
DR CDD; cd06461; M2_ACE; 1.
DR InterPro; IPR001548; Peptidase_M2.
DR PANTHER; PTHR10514; ANGIOTENSIN-CONVERTING ENZYME; 1.
DR PANTHER; PTHR10514:SF27; ANGIOTENSIN-CONVERTING ENZYME; 1.
DR Pfam; PF01401; Peptidase_M2; 1.
DR PRINTS; PR00791; PEPDIPTASEA.
DR SUPFAM; SSF55486; Metalloproteases ('zincins'), catalytic domain; 1.
DR PROSITE; PS52011; PEPTIDASE_M2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Developmental protein; Disulfide bond; Glycoprotein;
KW Reference proteome; Signal.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..906
FT /note="Inactive angiotensin-converting enzyme-related
FT protein"
FT /id="PRO_0000028567"
FT DOMAIN 175..765
FT /note="Peptidase M2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01355"
FT REGION 28..95
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 862..882
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 28..43
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 69..85
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 159
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:12754521,
FT ECO:0000269|PubMed:17761667"
FT CARBOHYD 653
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:17761667"
FT DISULFID 289..297
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01355"
FT VAR_SEQ 160..197
FT /note="SSNYWKTDNLQAPGSIKDEEKLRSWLAGYEAEAIKVLR -> LTLNHFSSTT
FT SHSSTGSAIPMKSIRLLLDGTEKELHSLCS (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_015490"
FT VAR_SEQ 198..773
FT /note="Missing (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_015491"
SQ SEQUENCE 906 AA; 100725 MW; 50B3CD37EA62CBD3 CRC64;
MKFHILLLLL VGACLPVFTQ EIKPKPELLP ADEAPKDPEA VFSEGEPFEL TDALDTPKNG
SVPVPEPEPK PEPEPEPEPK PEPEPSPTPE PEPAIKFDNI ESEDYGDVAE TAASTQPDEL
NTEVIEQLVD TFLNTGSIAS NKTNKGPVFA NPVAQALVNS SNYWKTDNLQ APGSIKDEEK
LRSWLAGYEA EAIKVLREVA LSGWRYFNDA SPSLKLALDE AENVLTMFVR STSMQAKQFD
MASVTDEKVM RQLGYVSFEG MSALAPSRFA DYSQAQAALN RDSKDSTICD KDVPPPCALQ
KIDMDSIFRN EKDASRLQHL WVSYVTAIAK SKPSYNNIIT ISNEGAKLNG FANGGAMWRS
AFDMSSKVHK AEFDLNKQID KIYSTIQPFY QLLHAYMRRQ LAGIYSNPVG LSKDGPIPAH
LFGSLDGGDW SAHYEQTKPF EEESETPEAM LSAFNTQNYT TKKMFVTAYR YFKSAGFPHL
PKSYWTSSIF ARVWSKDMIC HPAAALDMRA PNDFRVKACA QLGEPDFEQA HSLLVQTYYQ
YLYKDQSLLF REQASPVITD AIANAFAHLS TNPHYLYSQK LVPSEHLDIK DSVIINKLYK
ESLESFTKLP FTIAADNWRY ELFDGTVPKN KLNDRWWEIR NKYEGVRSPQ PYNTSNLDAL
IHNSVSQVHS PATRTLISYV LKFQILKALC PEGTILSEGC ILSEDTTEKL RETMKLGSSI
TWLKALEMIS GKGELDAQPL LEYYEPLINW LRNTNEIDQV VVGWDGEGTP FTVEEIPKTR
QPGDGGNGLP SEDRVAFPGG ECVNGQECLL DSHCNGTICV CNDGLYTLEI GNTFNCVPGN
PADSGFGDGK GGLVIGLFNN EVTTPEPSAE PEPTAKTTTK MPPRVRAATS PFSLYLTVLL
IIYFAL
//
