LET4_CAEEL
ID LET4_CAEEL Reviewed; 773 AA.
AC Q93373;
DT 29-MAY-2013, integrated into UniProtKB/Swiss-Prot.
DT 16-DEC-2008, sequence version 2.
DT 03-AUG-2022, entry version 139.
DE RecName: Full=Leucine-rich repeat-containing protein let-4;
DE AltName: Full=Lethal protein 4;
DE Flags: Precursor;
GN Name=let-4; Synonyms=sym-5; ORFNames=C44H4.2;
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1] {ECO:0000305, ECO:0000312|EMBL:AEZ55699.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RC STRAIN=Bristol N2 {ECO:0000269|PubMed:22278925};
RX PubMed=22278925; DOI=10.1242/dev.075135;
RA Mancuso V.P., Parry J.M., Storer L., Poggioli C., Nguyen K.C., Hall D.H.,
RA Sundaram M.V.;
RT "Extracellular leucine-rich repeat proteins are required to organize the
RT apical extracellular matrix and maintain epithelial junction integrity in
RT C. elegans.";
RL Development 139:979-990(2012).
RN [2] {ECO:0000312|EMBL:CAB01864.2}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|EMBL:CAB01864.2};
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).
CC -!- FUNCTION: Required for apical extracellular matrix organization and
CC epithelial junction maintenance. {ECO:0000269|PubMed:22278925}.
CC -!- SUBCELLULAR LOCATION: Apical cell membrane
CC {ECO:0000269|PubMed:22278925}; Single-pass type I membrane protein
CC {ECO:0000269|PubMed:22278925}. Note=In the excretory canal cell at the
CC 1.5-fold embryonic stage, localized uniformly at the cell membrane.
CC {ECO:0000255, ECO:0000269|PubMed:22278925}.
CC -!- TISSUE SPECIFICITY: In L1 larvae, expressed in a subset of epithelial
CC cells including epidermal, vulval and rectal cells and the excretory
CC duct and pore. Absent from internal epithelia such as the gut and
CC pharyngeal tubes. Transiently expressed in the excretory canal cell at
CC the 1.5-fold embryonic stage but no longer visible in this cell at
CC hatching. {ECO:0000269|PubMed:22278925}.
CC -!- DEVELOPMENTAL STAGE: Expression begins around the ventral closure stage
CC of embryogenesis, continues throughout larval development and decreases
CC in adulthood. {ECO:0000269|PubMed:22278925}.
CC -!- DISRUPTION PHENOTYPE: Highly lethal at L1 larval stage due to excretory
CC defects. A small percentage of mutants die as embryos and a very small
CC number survive to adulthood and are fertile but have defects in
CC locomotion and egg-laying. There is no maternal effect on lethality.
CC {ECO:0000269|PubMed:22278925}.
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DR EMBL; JQ292907; AEZ55699.1; -; mRNA.
DR EMBL; Z79598; CAB01864.2; -; Genomic_DNA.
DR RefSeq; NP_510425.2; NM_078024.3.
DR AlphaFoldDB; Q93373; -.
DR SMR; Q93373; -.
DR STRING; 6239.C44H4.2; -.
DR EPD; Q93373; -.
DR PaxDb; Q93373; -.
DR PeptideAtlas; Q93373; -.
DR EnsemblMetazoa; C44H4.2.1; C44H4.2.1; WBGene00002282.
DR GeneID; 181554; -.
DR KEGG; cel:CELE_C44H4.2; -.
DR CTD; 181554; -.
DR WormBase; C44H4.2; CE43213; WBGene00002282; let-4.
DR eggNOG; KOG0619; Eukaryota.
DR HOGENOM; CLU_358724_0_0_1; -.
DR InParanoid; Q93373; -.
DR OMA; LCISKHR; -.
DR OrthoDB; 448516at2759; -.
DR PhylomeDB; Q93373; -.
DR PRO; PR:Q93373; -.
DR Proteomes; UP000001940; Chromosome X.
DR Bgee; WBGene00002282; Expressed in embryo and 3 other tissues.
DR GO; GO:0045177; C:apical part of cell; IDA:WormBase.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0009792; P:embryo development ending in birth or egg hatching; IMP:WormBase.
DR GO; GO:0002064; P:epithelial cell development; IMP:WormBase.
DR GO; GO:0002119; P:nematode larval development; IMP:WormBase.
DR GO; GO:1905710; P:positive regulation of membrane permeability; IMP:UniProtKB.
DR GO; GO:0035150; P:regulation of tube size; IMP:WormBase.
DR Gene3D; 3.80.10.10; -; 3.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR003591; Leu-rich_rpt_typical-subtyp.
DR InterPro; IPR032675; LRR_dom_sf.
DR Pfam; PF13855; LRR_8; 4.
DR SMART; SM00369; LRR_TYP; 14.
DR PROSITE; PS51450; LRR; 14.
PE 2: Evidence at transcript level;
KW Cell membrane; Leucine-rich repeat; Membrane; Reference proteome; Repeat;
KW Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..773
FT /note="Leucine-rich repeat-containing protein let-4"
FT /evidence="ECO:0000255"
FT /id="PRO_0000422395"
FT TOPO_DOM 21..689
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 690..710
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 711..773
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REPEAT 61..84
FT /note="LRR 1"
FT /evidence="ECO:0000255"
FT REPEAT 85..107
FT /note="LRR 2"
FT /evidence="ECO:0000255"
FT REPEAT 109..132
FT /note="LRR 3"
FT /evidence="ECO:0000255"
FT REPEAT 133..157
FT /note="LRR 4"
FT /evidence="ECO:0000255"
FT REPEAT 159..181
FT /note="LRR 5"
FT /evidence="ECO:0000255"
FT REPEAT 183..206
FT /note="LRR 6"
FT /evidence="ECO:0000255"
FT REPEAT 207..230
FT /note="LRR 7"
FT /evidence="ECO:0000255"
FT REPEAT 231..254
FT /note="LRR 8"
FT /evidence="ECO:0000255"
FT REPEAT 256..278
FT /note="LRR 9"
FT /evidence="ECO:0000255"
FT REPEAT 279..302
FT /note="LRR 10"
FT /evidence="ECO:0000255"
FT REPEAT 303..326
FT /note="LRR 11"
FT /evidence="ECO:0000255"
FT REPEAT 328..349
FT /note="LRR 12"
FT /evidence="ECO:0000255"
FT REPEAT 350..373
FT /note="LRR 13"
FT /evidence="ECO:0000255"
FT REPEAT 375..397
FT /note="LRR 14"
FT /evidence="ECO:0000255"
FT REPEAT 399..421
FT /note="LRR 15"
FT /evidence="ECO:0000255"
FT REPEAT 486..516
FT /note="LRR 16"
FT /evidence="ECO:0000255"
SQ SEQUENCE 773 AA; 85297 MW; 5B1CF58516E91F78 CRC64;
MRLLLCLLLF STLLINSTNA CPGVITQACF CSEVHSGIVL DCSNSSASGI LQIIRTNQAQ
VGLIQSLTMN QAELVELPPN FFSGLFIRRL DLSQNKIKKI DDAAFAGINP VLEEVVLNHN
LIEKVPAAAL AGLPNLLRLD LSNNSIVEIQ EQEIFPNLNK LYDINLGSNK IFSIHTSTFQ
NVKNSIQTIN LGHNNMTAVP SSAIRGLKQL QSLHLHKNRI EQLDALNFLN LPVLNLLNLA
GNQIHELNRQ AFLNVPSLRY LYLSGNKITK LTAYQFQTFE QLEMLDLTNN EIGAIPANSL
SGLKQLRQLY LAHNKISNIS SNAFTNSSIV VLVLSSNELK TLTAGIISGL PNLQQVSFRD
NQIKTINRNA FYDAASLVML DLAKNQLTEI APTTFLAQLN LLLVDLSENK LPKTPYSAFN
SRVGTVLLKE NPLVCTENLH MLQQGTGVYV RDSPDIICGR KPTPKPEPVL VPIVTDSLIS
TQRPALVQIP KMQIHRNVHT TTGDQAPQIP SGAFQQIDLG KSRSLPRGHS RFILDKPSTR
EQSVEPTEEL TPIQPIILPS REDEIRQSSM EAGTSQESVE ATSQKIPSTT DIIDRPNVVL
PFPVPFLKRG PNLSESKKVE STDMPSTSQV FHTLPPSILI EPGSTPKVAQ PSTEANIKSE
HIDEFALASS NSNEPTLQPR LEKSFFTTTI IFICVGTAVI VLVVVIAGLC ISKHRQLQFE
NTYSDSSAAR TSEYISTQYR QNSLRGTGGR VGRFEESPAW IYNPGSSYCN YYK