LE653_CAEEL
ID LE653_CAEEL Reviewed; 812 AA.
AC Q27394; G5ECH8; Q5WRN8;
DT 18-JAN-2017, integrated into UniProtKB/Swiss-Prot.
DT 09-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 139.
DE RecName: Full=Protein let-653 {ECO:0000305};
DE AltName: Full=Lethal protein 653 {ECO:0000312|WormBase:C29E6.1a};
DE Flags: Precursor;
GN Name=let-653 {ECO:0000312|WormBase:C29E6.1a};
GN ORFNames=C29E6.1 {ECO:0000312|WormBase:C29E6.1a};
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|EMBL:CAA62505.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM C), AND FUNCTION.
RC STRAIN=Bristol N2 {ECO:0000312|EMBL:CAA62505.1};
RX PubMed=7476875; DOI=10.1007/bf02191712;
RA Jones S.J.M., Baillie D.L.;
RT "Characterization of the let-653 gene in Caenorhabditis elegans.";
RL Mol. Gen. Genet. 248:719-726(1995).
RN [2] {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 [3] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE,
RP DOMAIN, PROTEOLYTIC CLEAVAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=27482894; DOI=10.1371/journal.pgen.1006205;
RA Gill H.K., Cohen J.D., Ayala-Figueroa J., Forman-Rubinsky R., Poggioli C.,
RA Bickard K., Parry J.M., Pu P., Hall D.H., Sundaram M.V.;
RT "Integrity of narrow epithelial tubes in the C. elegans excretory system
RT requires a transient luminal matrix.";
RL PLoS Genet. 12:E1006205-E1006205(2016).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DOMAIN, PROTEOLYTIC
RP CLEAVAGE, AND MUTAGENESIS OF 54-GLN--ILE-812; 731-ARG--ARG-734 AND
RP 772-PHE--ILE-812.
RX PubMed=33141826; DOI=10.1371/journal.pgen.1009188;
RA Cohen J.D., Bermudez J.G., Good M.C., Sundaram M.V.;
RT "A C. elegans Zona Pellucida domain protein functions via its ZPc domain.";
RL PLoS Genet. 16:e1009188-e1009188(2020).
CC -!- FUNCTION: Required for epithelial tube development and shaping
CC (PubMed:27482894, PubMed:33141826). Involved in the morphogenesis and
CC function of the three unicellular tubes of the excretory system, the
CC canal cell, the duct cell and the pore cell (PubMed:7476875,
CC PubMed:27482894, PubMed:33141826). Also plays a role in cuticle
CC development, alae formation and shaping of the vulval lumen
CC (PubMed:27482894). Required for larval development (PubMed:7476875,
CC PubMed:27482894, PubMed:33141826). {ECO:0000269|PubMed:27482894,
CC ECO:0000269|PubMed:33141826, ECO:0000269|PubMed:7476875}.
CC -!- SUBCELLULAR LOCATION: [Isoform b]: Apical cell membrane
CC {ECO:0000269|PubMed:27482894, ECO:0000269|PubMed:33141826}; Peripheral
CC membrane protein {ECO:0000269|PubMed:27482894,
CC ECO:0000269|PubMed:33141826}; Lumenal side
CC {ECO:0000269|PubMed:27482894, ECO:0000269|PubMed:33141826}. Secreted,
CC extracellular space {ECO:0000269|PubMed:27482894}. Secreted
CC {ECO:0000269|PubMed:27482894, ECO:0000269|PubMed:33141826}.
CC Note=Localizes to fibrils in the vulval luminal space.
CC {ECO:0000269|PubMed:27482894}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=a {ECO:0000312|WormBase:C29E6.1a};
CC IsoId=Q27394-1; Sequence=Displayed;
CC Name=b {ECO:0000312|WormBase:C29E6.1b};
CC IsoId=Q27394-2; Sequence=VSP_058741;
CC Name=c {ECO:0000312|WormBase:C29E6.1c};
CC IsoId=Q27394-3; Sequence=VSP_058742;
CC -!- TISSUE SPECIFICITY: [Isoform b]: Expressed in external cuticle-
CC producing epithelial cells including the epidermis, vulva, rectum,
CC excretory duct and excretory pore. {ECO:0000269|PubMed:27482894,
CC ECO:0000269|PubMed:33141826}.
CC -!- DEVELOPMENTAL STAGE: [Isoform b]: Secreted in the region between the
CC embryo and inner layer of the eggshell. Expressed in excretory canal
CC cells of embryos and at the 1.5-fold stage of embryonic development
CC accumulates in the lumen of the excretory duct and pore. Expression
CC ceases in the lumen of the excretory duct and pore prior to cuticle
CC secretion. Thereafter expressed transiently in the lumen of the
CC excretory duct and pore in the latter phase of each subsequent larval
CC developmental stage. During the molt phase of larval development,
CC accumulates in the space in between the new and old cuticles. During
CC the L4 stage of larval development, accumulates in the vulval lumen.
CC {ECO:0000269|PubMed:27482894}.
CC -!- DOMAIN: [Isoform b]: The ZP domain is required for localization at the
CC apical cell membrane, secretion and excretory tube and vulval lumen
CC expansion. {ECO:0000269|PubMed:27482894, ECO:0000269|PubMed:33141826}.
CC -!- PTM: [Isoform b]: Cleaved at the C-terminal domain.
CC {ECO:0000269|PubMed:27482894, ECO:0000269|PubMed:33141826}.
CC -!- DISRUPTION PHENOTYPE: Lethal at the larval stage of development.
CC Defects in the development of the excretory system during embryogenesis
CC and the early stages of larval development. Dilated lumens of both the
CC excretory canal cell and excretory duct which become apparent between
CC the early and mid 3-fold stages of embryogenesis and increases in
CC severity as development progresses. Lumen dialation may be as a result
CC of fluid accumulation due to blockage of the lumen. At around the time
CC of hatching, the autocellular junction, which usually seals the
CC excretory pore tube, is absent. Detached excretory duct and pore cells,
CC which usually connects the excretory canal cell to the outside
CC environment for excretion. Irregular morphology of the epidermis and
CC vulva in larvae at the L1 stage of larval development.
CC {ECO:0000269|PubMed:27482894}.
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DR EMBL; X91045; CAA62505.1; -; Genomic_DNA.
DR EMBL; BX284604; CAA96602.2; -; Genomic_DNA.
DR EMBL; BX284604; CAH60755.1; -; Genomic_DNA.
DR EMBL; BX284604; CCD31038.1; -; Genomic_DNA.
DR PIR; T19551; T19551.
DR RefSeq; NP_001021336.2; NM_001026165.4. [Q27394-1]
DR RefSeq; NP_001021337.1; NM_001026166.3. [Q27394-2]
DR RefSeq; NP_001255594.1; NM_001268665.1. [Q27394-3]
DR AlphaFoldDB; Q27394; -.
DR STRING; 6239.C29E6.1a.2; -.
DR EPD; Q27394; -.
DR PaxDb; Q27394; -.
DR EnsemblMetazoa; C29E6.1a.1; C29E6.1a.1; WBGene00002827. [Q27394-1]
DR EnsemblMetazoa; C29E6.1b.1; C29E6.1b.1; WBGene00002827. [Q27394-2]
DR EnsemblMetazoa; C29E6.1c.1; C29E6.1c.1; WBGene00002827. [Q27394-3]
DR GeneID; 178120; -.
DR KEGG; cel:CELE_C29E6.1; -.
DR UCSC; C29E6.1b.1; c. elegans.
DR CTD; 178120; -.
DR WormBase; C29E6.1a; CE40548; WBGene00002827; let-653. [Q27394-1]
DR WormBase; C29E6.1b; CE37323; WBGene00002827; let-653. [Q27394-2]
DR WormBase; C29E6.1c; CE05332; WBGene00002827; let-653. [Q27394-3]
DR eggNOG; ENOG502SMP8; Eukaryota.
DR GeneTree; ENSGT00970000196473; -.
DR InParanoid; Q27394; -.
DR OMA; CHMSKDS; -.
DR OrthoDB; 357404at2759; -.
DR PRO; PR:Q27394; -.
DR Proteomes; UP000001940; Chromosome IV.
DR Bgee; WBGene00002827; Expressed in embryo and 4 other tissues.
DR GO; GO:0098592; C:cytoplasmic side of apical plasma membrane; IDA:UniProtKB.
DR GO; GO:0098591; C:external side of apical plasma membrane; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0099512; C:supramolecular fiber; IDA:UniProtKB.
DR GO; GO:0042302; F:structural constituent of cuticle; IMP:UniProtKB.
DR GO; GO:0009653; P:anatomical structure morphogenesis; IMP:UniProtKB.
DR GO; GO:0035017; P:cuticle pattern formation; IMP:UniProtKB.
DR GO; GO:0048613; P:embryonic ectodermal digestive tract morphogenesis; IMP:UniProtKB.
DR GO; GO:0002064; P:epithelial cell development; IMP:WormBase.
DR GO; GO:1903133; P:negative regulation of tube lumen cavitation; IMP:UniProtKB.
DR GO; GO:1905278; P:positive regulation of epithelial tube formation; IMP:UniProtKB.
DR GO; GO:0040018; P:positive regulation of multicellular organism growth; IMP:UniProtKB.
DR GO; GO:0061063; P:positive regulation of nematode larval development; IMP:UniProtKB.
DR GO; GO:0040026; P:positive regulation of vulval development; IMP:UniProtKB.
DR GO; GO:0035150; P:regulation of tube size; IMP:WormBase.
DR InterPro; IPR003609; Pan_app.
DR InterPro; IPR001507; ZP_dom.
DR Pfam; PF00024; PAN_1; 1.
DR SMART; SM00473; PAN_AP; 2.
DR SMART; SM00241; ZP; 1.
DR PROSITE; PS50948; PAN; 2.
DR PROSITE; PS51034; ZP_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Cleavage on pair of basic residues;
KW Developmental protein; Disulfide bond; Glycoprotein; Membrane;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..812
FT /note="Protein let-653"
FT /evidence="ECO:0000305"
FT /id="PRO_5004203492"
FT DOMAIN 26..116
FT /note="Apple 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00315"
FT DOMAIN 123..209
FT /note="Apple 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00315"
FT DOMAIN 221..725
FT /note="ZP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00375"
FT REGION 375..461
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 494..584
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 172
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 211
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 272
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 771
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT DISULFID 26..116
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00315"
FT DISULFID 53..88
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00315"
FT DISULFID 57..72
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00315"
FT DISULFID 123..209
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00315"
FT DISULFID 154..178
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00315"
FT DISULFID 158..166
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00315"
FT VAR_SEQ 334..493
FT /note="RNKAMEASAHALFELLSKTGDDEALQNTFPLPLTTTTEVIRQVTTTTKKPST
FT TTSTKKLTTTTTTTPKPSQKPTTTTTKSPVVITTTTKTSPKPTTSPSTTTSTTTSTTIP
FT PSTTTRKPANPRRSTIMSATSKVAIIVGKDSSFARARLFTTKHPSTQKI -> S (in
FT isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_058741"
FT VAR_SEQ 374..493
FT /note="RQVTTTTKKPSTTTSTKKLTTTTTTTPKPSQKPTTTTTKSPVVITTTTKTSP
FT KPTTSPSTTTSTTTSTTIPPSTTTRKPANPRRSTIMSATSKVAIIVGKDSSFARARLFT
FT TKHPSTQKI -> S (in isoform c)"
FT /evidence="ECO:0000305"
FT /id="VSP_058742"
FT MUTAGEN 54..812
FT /note="Missing: In cs178; Lethal at the larval stage of
FT development due to discontinuities in the excretory duct
FT tube lumen that prevent fluid excretion."
FT /evidence="ECO:0000269|PubMed:33141826"
FT MUTAGEN 731..734
FT /note="RYRR->AYAA: Abolishes cleavage of the C-terminal
FT domain. Does not impair localization and localizes to the
FT apical membrane of the vulva and the excretory duct lumen
FT in embryos, as wild-type. Partially rescues the excretory
FT duct defects in the let-653 cs178 mutant."
FT /evidence="ECO:0000269|PubMed:33141826"
FT MUTAGEN 772..812
FT /note="Missing: Not secreted. Does not rescue excretory
FT duct defects in the let-653 cs178 mutant."
FT /evidence="ECO:0000269|PubMed:33141826"
SQ SEQUENCE 812 AA; 89480 MW; 0E491EC768A43C60 CRC64;
MRHPLISLLL LIAFYSTSSE AFVPKCNSFY VRWPRVRLNF KAVAEARLSL KGCQSACSLG
EDPVSPGKQL ECAAVNHQAS PDGFSHLCAV FQPHQLQNVD GYVEADDRFT FYWKYCLPST
RKCSGEYAFT YLSDRYMDQK SVIKWTTKAN LEECLSDCLD EKSFECRSIS FNRTDGGCHM
SKDSQISRPE AIRLNNNPNY RIDYYENNCY NLSESFTFKH ECRDNGISVS VKSRLPYTGA
IYGLYDFFTC RTEPKEATEF DHFFPYQTVS KNCSDSIKYK GNEMVLEVVL STDGIEPLYF
ITPEDLTYQA KCPISGVKAK DPANTKSSAH LDNRNKAMEA SAHALFELLS KTGDDEALQN
TFPLPLTTTT EVIRQVTTTT KKPSTTTSTK KLTTTTTTTP KPSQKPTTTT TKSPVVITTT
TKTSPKPTTS PSTTTSTTTS TTIPPSTTTR KPANPRRSTI MSATSKVAII VGKDSSFARA
RLFTTKHPST QKIDVPTTTV QTSTTVPTTP SKTTATTTTT PKPTTTETAT TSSSTTTVTT
QKPTTVTSTT TLPSTTASTT TKTTTSTPTS PQTTTTHVGA PASSVASVAH DGSTLAGKPK
VPVIFDIFHN GQPVEAVVVG TKISLSFRPH YPIPPEYVDV RGCQVEPIDP KYEWEHEPLF
IIRDGCPADG VGLVCPPTHS EFGAKVSVEA FRYQTTGQVQ YSCLVRICPF APCPKNTCDD
VEGCDSSYMH RYRRELSLED IKKALEANPE LASQFGISPS AFARNPSKSK NFTSVVEEQQ
RIALGGDYLV RRRLIVVNSE DQLRYYVRTG NI
