APX1_CAEEL
ID APX1_CAEEL Reviewed; 515 AA.
AC P41990; Q9TXN4;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 1.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=Anterior pharynx in excess protein 1;
DE Flags: Precursor;
GN Name=apx-1; ORFNames=K08D9.3;
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 [MRNA], AND FUNCTION.
RC STRAIN=Bristol N2;
RX PubMed=8156602; DOI=10.1016/0092-8674(94)90238-0;
RA Mello C.C., Draper B.W., Priess J.R.;
RT "The maternal genes apx-1 and glp-1 and establishment of dorsal-ventral
RT polarity in the early C. elegans embryo.";
RL Cell 77:95-106(1994).
RN [2]
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 [3]
RP FUNCTION.
RX PubMed=7925031; DOI=10.1242/dev.120.8.2305;
RA Mango S.E., Thorpe C.J., Martin P.R., Chamberlain S.H., Bowerman B.;
RT "Two maternal genes, apx-1 and pie-1, are required to distinguish the fates
RT of equivalent blastomeres in the early Caenorhabditis elegans embryo.";
RL Development 120:2305-2315(1994).
RN [4]
RP FUNCTION, AND MUTAGENESIS OF 188-VAL--VAL-515 AND 402-VAL--VAL-515.
RX PubMed=8575327; DOI=10.1242/dev.121.12.4275;
RA Fitzgerald K., Greenwald I.;
RT "Interchangeability of Caenorhabditis elegans DSL proteins and intrinsic
RT signalling activity of their extracellular domains in vivo.";
RL Development 121:4275-4282(1995).
RN [5]
RP FUNCTION.
RX PubMed=7568229; DOI=10.1073/pnas.92.21.9839;
RA Gao D., Kimble J.;
RT "APX-1 can substitute for its homolog LAG-2 to direct cell interactions
RT throughout Caenorhabditis elegans development.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:9839-9842(1995).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, AND DEVELOPMENTAL STAGE.
RX PubMed=8674418; DOI=10.1242/dev.122.6.1791;
RA Mickey K.M., Mello C.C., Montgomery M.K., Fire A., Priess J.R.;
RT "An inductive interaction in 4-cell stage C. elegans embryos involves APX-1
RT expression in the signalling cell.";
RL Development 122:1791-1798(1996).
RN [7]
RP FUNCTION.
RX PubMed=10903169; DOI=10.1242/dev.127.16.3429;
RA Hermann G.J., Leung B., Priess J.R.;
RT "Left-right asymmetry in C. elegans intestine organogenesis involves a LIN-
RT 12/Notch signaling pathway.";
RL Development 127:3429-3440(2000).
RN [8]
RP FUNCTION, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=14960273; DOI=10.1016/s1534-5807(04)00021-8;
RA Chen N., Greenwald I.;
RT "The lateral signal for LIN-12/Notch in C. elegans vulval development
RT comprises redundant secreted and transmembrane DSL proteins.";
RL Dev. Cell 6:183-192(2004).
RN [9]
RP FUNCTION, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=18036582; DOI=10.1016/j.ydbio.2007.10.027;
RA Foehr M.L., Liu J.;
RT "Dorsoventral patterning of the C. elegans postembryonic mesoderm requires
RT both LIN-12/Notch and TGFbeta signaling.";
RL Dev. Biol. 313:256-266(2008).
RN [10]
RP FUNCTION, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=19502484; DOI=10.1242/dev.034603;
RA Nadarajan S., Govindan J.A., McGovern M., Hubbard E.J., Greenstein D.;
RT "MSP and GLP-1/Notch signaling coordinately regulate actomyosin-dependent
RT cytoplasmic streaming and oocyte growth in C. elegans.";
RL Development 136:2223-2234(2009).
RN [11]
RP FUNCTION, DEVELOPMENTAL STAGE, AND MUTAGENESIS OF GLY-159.
RX PubMed=23539368; DOI=10.7554/elife.00378;
RA Li P., Collins K.M., Koelle M.R., Shen K.;
RT "LIN-12/Notch signaling instructs postsynaptic muscle arm development by
RT regulating UNC-40/DCC and MADD-2 in Caenorhabditis elegans.";
RL Elife 2:e00378-e00378(2013).
RN [12]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=29371032; DOI=10.1016/j.ydbio.2018.01.009;
RA McGovern M., Castaneda P.G., Pekar O., Vallier L.G., Cram E.J.,
RA Hubbard E.J.A.;
RT "The DSL ligand APX-1 is required for normal ovulation in C. elegans.";
RL Dev. Biol. 435:162-169(2018).
CC -!- FUNCTION: Probable ligand for lin-12/Notch and glp-1/Notch receptors
CC and involved in the mediation of Notch signaling (PubMed:14960273,
CC PubMed:7568229, PubMed:8575327). Involved in the lin-12/Notch pathway
CC signaling of cell fate in vulval precursor cells (VPCs), acting
CC redundantly with dsl-1 and lag-2 (PubMed:14960273, PubMed:7568229).
CC Contributes to the establishment of the dorsal-ventral axis in early
CC embryos (PubMed:8156602, PubMed:18036582). Involved in the
CC specification of the blastomere cell ABp fate, probably acting as a
CC signal from the P2 blastomere to the glp-1/Notch receptor on ABp and
CC ABa (PubMed:8156602, PubMed:7925031, PubMed:8674418). Probably acts as
CC a signal, from the secondary vulval epithelial cells and the vulval
CC muscle type 1 (vm1) cells, to activate the lin-12/Notch pathway in type
CC 2 vulval muscle (vm2) cells, contributing to formation of the
CC postsynaptic muscle plasma membrane extensions, known as muscle arms
CC (PubMed:23539368). Required for oocyte growth control, acting
CC redundantly with lag-2, perhaps signaling via the glp-1/Notch pathway
CC (PubMed:19502484). Plays a somatic role in ovulation during adulthood,
CC perhaps via lin-12/Notch signaling (PubMed:29371032). Involved in
CC establishing left-right asymmetry during intestinal organogenesis
CC (PubMed:10903169). {ECO:0000269|PubMed:10903169,
CC ECO:0000269|PubMed:14960273, ECO:0000269|PubMed:18036582,
CC ECO:0000269|PubMed:19502484, ECO:0000269|PubMed:23539368,
CC ECO:0000269|PubMed:29371032, ECO:0000269|PubMed:7568229,
CC ECO:0000269|PubMed:7925031, ECO:0000269|PubMed:8156602,
CC ECO:0000269|PubMed:8575327, ECO:0000269|PubMed:8674418}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:8674418};
CC Single-pass type I membrane protein {ECO:0000255}. Nucleus
CC {ECO:0000269|PubMed:8674418}. Cytoplasm {ECO:0000269|PubMed:8674418}.
CC Note=Nuclear localization of transcripts at 36-cell stage in embryos.
CC {ECO:0000269|PubMed:8674418}.
CC -!- DEVELOPMENTAL STAGE: First expressed in late 2-cell stage embryos at
CC the anterior periphery of the P1 blastomere, where P1 contacts the AB
CC blastomere (at protein level) (PubMed:8674418). Maternally expressed in
CC newly fertilised eggs, and present in all blastomeres between 1-cell
CC and 8-cell stages (PubMed:8674418). After the 8-cell stage, rapidly
CC disappears from all somatic blastomeres, and then expressed in P3
CC blastomere at the 12 cell stage (PubMed:8674418). In 36-cell stage and
CC later embryos, can be detected in one to five unidentified cells
CC (PubMed:8674418). Expressed in the P6.p vulval precursor cell (VPC)
CC during larval L3 stage, coinciding with extension and reflexing of the
CC gonad (PubMed:14960273). Expressed in cells immediately adjacent to
CC ventral mesodermal lineage (M lineage) cells, but not next to dorsal M
CC lineage cells, beginning at the 4-M stage (PubMed:18036582). Expressed
CC in the distal tip cell (DTC) starting in the larval L3 stage
CC (PubMed:19502484). Expressed in the secondary vulval epithelial cells
CC and the non-target vm1 cells at the larval L4 stage (PubMed:23539368).
CC {ECO:0000269|PubMed:14960273, ECO:0000269|PubMed:18036582,
CC ECO:0000269|PubMed:19502484, ECO:0000269|PubMed:23539368,
CC ECO:0000269|PubMed:8674418}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown in the L1 larval stage
CC causes an endomitotic oocyte phenotype; effect not seen if knockdown is
CC targeted to germline, rather than somatic cells (PubMed:29371032).
CC RNAi-mediated knockdown alters ovulation (PubMed:29371032). Spermatheca
CC calcium flux is altered by RNAi-mediated knockdown (PubMed:29371032).
CC RNAi-mediated knockdown, on a lag-2 mutant background, induces the
CC presence of 1-2 extra mesodermal lineage (M lineage)-derived
CC coelomocytes (PubMed:18036582). RNAi-mediated knockdown on a lin-15
CC mutant background, causes adjacent vulval precursor cells (VPCs) to
CC adopt altered cell fate (PubMed:14960273). On a lag-2 mutant
CC background, RNAi-mediated knockdown causes germ cells to display
CC nuclear morphology consistent with meiotic prophase or gametogenesis in
CC adult hermaphrodites (PubMed:19502484). RNAi-mediated knockdown, when
CC combined with RNAi-mediated knockdown of lag-2, on a dsl-1 mutant
CC background, causes adjacent vulval precursor cells (VPCs) to adopt
CC altered cell fate; phenotype exacerbated on double mutant lin-15;dsl-1
CC background (PubMed:14960273). {ECO:0000269|PubMed:14960273,
CC ECO:0000269|PubMed:18036582, ECO:0000269|PubMed:19502484,
CC ECO:0000269|PubMed:29371032}.
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DR EMBL; U07628; AAA17738.1; -; mRNA.
DR EMBL; FO081608; CCD72794.1; -; Genomic_DNA.
DR PIR; D88991; D88991.
DR RefSeq; NP_503882.2; NM_071481.4.
DR AlphaFoldDB; P41990; -.
DR BioGRID; 43815; 1.
DR IntAct; P41990; 1.
DR STRING; 6239.K08D9.3; -.
DR PaxDb; P41990; -.
DR EnsemblMetazoa; K08D9.3a.1; K08D9.3a.1; WBGene00000168.
DR GeneID; 178759; -.
DR KEGG; cel:CELE_K08D9.3; -.
DR UCSC; K08D9.3; c. elegans.
DR CTD; 178759; -.
DR WormBase; K08D9.3a; CE30819; WBGene00000168; apx-1.
DR eggNOG; KOG1217; Eukaryota.
DR GeneTree; ENSGT00970000196457; -.
DR HOGENOM; CLU_533452_0_0_1; -.
DR InParanoid; P41990; -.
DR OMA; TVCANFE; -.
DR OrthoDB; 511040at2759; -.
DR PhylomeDB; P41990; -.
DR Reactome; R-CEL-1912420; Pre-NOTCH Processing in Golgi.
DR Reactome; R-CEL-9013700; NOTCH4 Activation and Transmission of Signal to the Nucleus.
DR Reactome; R-CEL-9604323; Negative regulation of NOTCH4 signaling.
DR SignaLink; P41990; -.
DR PRO; PR:P41990; -.
DR Proteomes; UP000001940; Chromosome V.
DR Bgee; WBGene00000168; Expressed in somatic blastomere (C elegans) and 20 other tissues.
DR ExpressionAtlas; P41990; baseline and differential.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005112; F:Notch binding; IBA:GO_Central.
DR GO; GO:0008595; P:anterior/posterior axis specification, embryo; NAS:UniProtKB.
DR GO; GO:0030154; P:cell differentiation; NAS:UniProtKB.
DR GO; GO:0048858; P:cell projection morphogenesis; IMP:UniProtKB.
DR GO; GO:0009880; P:embryonic pattern specification; IMP:WormBase.
DR GO; GO:0031129; P:inductive cell-cell signaling; IMP:UniProtKB.
DR GO; GO:0046331; P:lateral inhibition; IGI:WormBase.
DR GO; GO:0016331; P:morphogenesis of embryonic epithelium; IMP:WormBase.
DR GO; GO:0007219; P:Notch signaling pathway; IEA:UniProtKB-KW.
DR GO; GO:1905936; P:regulation of germ cell proliferation; IGI:UniProtKB.
DR GO; GO:0040028; P:regulation of vulval development; IGI:WormBase.
DR InterPro; IPR001774; DSL.
DR InterPro; IPR000742; EGF-like_dom.
DR Pfam; PF01414; DSL; 1.
DR Pfam; PF00008; EGF; 1.
DR SMART; SM00051; DSL; 1.
DR SMART; SM00181; EGF; 4.
DR PROSITE; PS51051; DSL; 1.
DR PROSITE; PS00022; EGF_1; 4.
DR PROSITE; PS01186; EGF_2; 3.
DR PROSITE; PS50026; EGF_3; 4.
PE 1: Evidence at protein level;
KW Cell membrane; Cytoplasm; Developmental protein; Differentiation;
KW Disulfide bond; EGF-like domain; Glycoprotein; Membrane;
KW Notch signaling pathway; Nucleus; Reference proteome; Repeat; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..26
FT /evidence="ECO:0000255"
FT CHAIN 27..515
FT /note="Anterior pharynx in excess protein 1"
FT /id="PRO_0000007480"
FT TOPO_DOM 27..392
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 393..413
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 414..515
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 130..172
FT /note="DSL"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00377"
FT DOMAIN 173..205
FT /note="EGF-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 203..238
FT /note="EGF-like 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 240..280
FT /note="EGF-like 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 284..322
FT /note="EGF-like 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 325..349
FT /note="EGF-like 5; incomplete"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REGION 427..452
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 466..494
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 123
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 200
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 132..141
FT /evidence="ECO:0000250"
FT DISULFID 145..155
FT /evidence="ECO:0000250"
FT DISULFID 163..172
FT /evidence="ECO:0000250"
FT DISULFID 177..187
FT /evidence="ECO:0000250"
FT DISULFID 181..193
FT /evidence="ECO:0000250"
FT DISULFID 195..204
FT /evidence="ECO:0000250"
FT DISULFID 213..218
FT /evidence="ECO:0000250"
FT DISULFID 228..237
FT /evidence="ECO:0000250"
FT DISULFID 244..256
FT /evidence="ECO:0000250"
FT DISULFID 250..268
FT /evidence="ECO:0000250"
FT DISULFID 270..279
FT /evidence="ECO:0000250"
FT DISULFID 288..300
FT /evidence="ECO:0000250"
FT DISULFID 294..310
FT /evidence="ECO:0000250"
FT DISULFID 312..321
FT /evidence="ECO:0000250"
FT MUTAGEN 159
FT /note="G->E: In wy755; egg-laying defect due to, at least
FT in part, the absence of muscle plasma membrane extensions,
FT known as muscle arms, on type 2 vulval muscles (vm2)."
FT /evidence="ECO:0000269|PubMed:23539368"
FT MUTAGEN 188..515
FT /note="Missing: Causes abnormal proximal proliferation in
FT the germline and / or tumorous germline phenotypes."
FT /evidence="ECO:0000269|PubMed:8575327"
FT MUTAGEN 402..515
FT /note="Missing: On lag-2 mutant background, typical mutant
FT phenotype absent; however, on the same mutant background,
FT activates lin-12 in the vulval precursor cells (VPCs)
FT causing formation of ectopic vulvae, and / or activates
FT glp-1, causing tumorous germline phenotype. On a glp-1
FT mutant background, hermaphrodites may have tumorous
FT germlines at the permissive temperature (15 degrees
FT Celsius) but, after shifting to the restrictive temperature
FT (25 degrees Celsius), the germ cells enter meiosis."
FT /evidence="ECO:0000269|PubMed:8575327"
SQ SEQUENCE 515 AA; 55818 MW; F41192A5268C24D9 CRC64;
MTNFSSLLTT IFLCIISSAT GSGTIELLIS SPQTVLVEPT VCANFECAAP DDLSLARKVQ
RRVPLRFGTG QYHGEARERI DLHLKIIEPT SNEILALQHH RPAADTEWNS DAPIVIETSR
GFNVTVQLRN LCSSNYHGKR CNRYCIANAK LHWECSTHGV RRCSAGWSGE DCSNPICAGG
CSNRGRCVAP NQCSCADGFN GTRCEQCLPR AGCVNGDCVN ETPNTCKCRD GFIGDRCDID
IKICSLEKPC ANGGICSIDS SSSTGYKCHC PFEFVGSQCK TPLSKVRCSA EHVCKNGGAC
ISMDDTNIQC KCRRGFSGKF CEIGNHGDCS AMRCSAGETC QISGDFAICV ENDELLLTTN
KPAETTKSVE KWREPRKTAN DEQASDELQL RLIAAICVLF SVCVIGLALV SFFFYMHSFS
KWKHPSSQQA GGSTILPTTT SIPMSTTSSG TGSPVYKVCI IDSEHRGNAP GSSSDSEPDH
HCPPPHRHSP PPAYSSLVLY KKVPMAADDE SSFRV
