DAF4_CAEEL
ID DAF4_CAEEL Reviewed; 744 AA.
AC P50488; O45139;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 03-JUL-2003, sequence version 2.
DT 03-AUG-2022, entry version 178.
DE RecName: Full=Cell surface receptor daf-4;
DE EC=2.7.11.30;
DE AltName: Full=Abnormal dauer formation protein 4;
DE Flags: Precursor;
GN Name=daf-4 {ECO:0000312|WormBase:C05D2.1a};
GN ORFNames=C05D2.1 {ECO:0000312|WormBase:C05D2.1a};
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.
RX PubMed=8413626; DOI=10.1038/365644a0;
RA Estevez M., Attisano L., Wrana J.L., Albert P.S., Massague J., Riddle D.L.;
RT "The daf-4 gene encodes a bone morphogenetic protein receptor controlling
RT C. elegans dauer larva development.";
RL Nature 365:644-649(1993).
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, SUBUNIT, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=10887089; DOI=10.1242/dev.127.15.3337;
RA Gunther C.V., Georgi L.L., Riddle D.L.;
RT "A Caenorhabditis elegans type I TGF beta receptor can function in the
RT absence of type II kinase to promote larval development.";
RL Development 127:3337-3347(2000).
RN [4]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-60 AND ASN-134, 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.
RX PubMed=18316030; DOI=10.1016/j.cmet.2008.01.005;
RA You Y.J., Kim J., Raizen D.M., Avery L.;
RT "Insulin, cGMP, and TGF-beta signals regulate food intake and quiescence in
RT C. elegans: a model for satiety.";
RL Cell Metab. 7:249-257(2008).
RN [6]
RP FUNCTION.
RX PubMed=18524955; DOI=10.1073/pnas.0707469105;
RA Hallem E.A., Sternberg P.W.;
RT "Acute carbon dioxide avoidance in Caenorhabditis elegans.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:8038-8043(2008).
RN [7]
RP INTERACTION WITH SMA-10.
RX PubMed=20502686; DOI=10.1371/journal.pgen.1000963;
RA Gumienny T.L., Macneil L., Zimmerman C.M., Wang H., Chin L., Wrana J.L.,
RA Padgett R.W.;
RT "Caenorhabditis elegans SMA-10/LRIG is a conserved transmembrane protein
RT that enhances bone morphogenetic protein signaling.";
RL PLoS Genet. 6:E1000963-E1000963(2010).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX PubMed=21408209; DOI=10.1371/journal.pgen.1002010;
RA Nelson M.D., Zhou E., Kiontke K., Fradin H., Maldonado G., Martin D.,
RA Shah K., Fitch D.H.;
RT "A bow-tie genetic architecture for morphogenesis suggested by a genome-
RT wide RNAi screen in Caenorhabditis elegans.";
RL PLoS Genet. 7:E1002010-E1002010(2011).
CC -!- FUNCTION: Involved in a TGF-beta pathway (PubMed:8413626). May be a
CC receptor for TGF-beta-like ligand daf-7 (PubMed:8413626). Controls the
CC decision of whether or not larvae enter a developmentally arrested
CC state, known as dauer, in response to environmental conditions
CC (PubMed:8413626). Regulates body size and male tail patterning
CC (PubMed:10887089, PubMed:21408209). Involved in regulating entry into
CC quiescence triggered by satiety (PubMed:18316030). Involved in
CC sensitivity to CO2 levels (PubMed:18524955).
CC {ECO:0000269|PubMed:10887089, ECO:0000269|PubMed:18316030,
CC ECO:0000269|PubMed:18524955, ECO:0000269|PubMed:21408209,
CC ECO:0000269|PubMed:8413626}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[receptor-protein] = ADP + H(+) + O-phospho-
CC L-threonyl-[receptor-protein]; Xref=Rhea:RHEA:44880, Rhea:RHEA-
CC COMP:11024, Rhea:RHEA-COMP:11025, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977,
CC ChEBI:CHEBI:456216; EC=2.7.11.30;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[receptor-protein] = ADP + H(+) + O-phospho-L-
CC seryl-[receptor-protein]; Xref=Rhea:RHEA:18673, Rhea:RHEA-COMP:11022,
CC Rhea:RHEA-COMP:11023, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216;
CC EC=2.7.11.30;
CC -!- SUBUNIT: May interact with daf-1 to regulate dauer larva development
CC (PubMed:10887089). Interacts with sma-10 (PubMed:20502686).
CC {ECO:0000269|PubMed:10887089, ECO:0000269|PubMed:20502686}.
CC -!- INTERACTION:
CC P50488; P46561: atp-2; NbExp=2; IntAct=EBI-296172, EBI-316294;
CC P50488; O45799: scrm-1; NbExp=2; IntAct=EBI-296172, EBI-312683;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:21408209};
CC Single-pass type I membrane protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Pharynx, intestine, hypodermis and body wall
CC muscles in L1 through to adult stages. Also expressed in head neurons,
CC ventral cord and tail neurons. Subset of head neurons show coexpression
CC with daf-1 when dauer/nondauer decision is made.
CC {ECO:0000269|PubMed:10887089}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown disrupts tail tip
CC morphogenesis resulting in retention of the pointed larval tail tip in
CC adult males (also known as the Lep phenotype).
CC {ECO:0000269|PubMed:21408209}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. TKL Ser/Thr
CC protein kinase family. TGFB receptor subfamily. {ECO:0000305}.
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DR EMBL; L23110; AAA03544.1; -; mRNA.
DR EMBL; BX284603; CCD63118.1; -; Genomic_DNA.
DR PIR; D88462; D88462.
DR PIR; S38279; S38279.
DR RefSeq; NP_498211.1; NM_065810.5.
DR AlphaFoldDB; P50488; -.
DR SMR; P50488; -.
DR BioGRID; 41009; 19.
DR IntAct; P50488; 14.
DR MINT; P50488; -.
DR STRING; 6239.C05D2.1a; -.
DR iPTMnet; P50488; -.
DR EPD; P50488; -.
DR PaxDb; P50488; -.
DR PeptideAtlas; P50488; -.
DR PRIDE; P50488; -.
DR EnsemblMetazoa; C05D2.1a.1; C05D2.1a.1; WBGene00000900.
DR GeneID; 175781; -.
DR KEGG; cel:CELE_C05D2.1; -.
DR UCSC; C05D2.1a.1; c. elegans.
DR CTD; 175781; -.
DR WormBase; C05D2.1a; CE16827; WBGene00000900; daf-4.
DR eggNOG; KOG3653; Eukaryota.
DR InParanoid; P50488; -.
DR OMA; KAMDVYS; -.
DR OrthoDB; 390511at2759; -.
DR BRENDA; 2.7.10.2; 1045.
DR Reactome; R-CEL-201451; Signaling by BMP.
DR Reactome; R-CEL-2173788; Downregulation of TGF-beta receptor signaling.
DR Reactome; R-CEL-2173789; TGF-beta receptor signaling activates SMADs.
DR SignaLink; P50488; -.
DR PRO; PR:P50488; -.
DR Proteomes; UP000001940; Chromosome III.
DR Bgee; WBGene00000900; Expressed in larva and 4 other tissues.
DR ExpressionAtlas; P50488; baseline and differential.
DR GO; GO:0048179; C:activin receptor complex; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:WormBase.
DR GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR GO; GO:0048185; F:activin binding; IBA:GO_Central.
DR GO; GO:0017002; F:activin receptor activity; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0036122; F:BMP binding; IPI:WormBase.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:0004675; F:transmembrane receptor protein serine/threonine kinase activity; ISS:WormBase.
DR GO; GO:0032924; P:activin receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0030509; P:BMP signaling pathway; IC:WormBase.
DR GO; GO:0071363; P:cellular response to growth factor stimulus; IBA:GO_Central.
DR GO; GO:0043053; P:dauer entry; IGI:UniProtKB.
DR GO; GO:0040024; P:dauer larval development; IMP:WormBase.
DR GO; GO:0050832; P:defense response to fungus; IMP:WormBase.
DR GO; GO:0008340; P:determination of adult lifespan; IMP:WormBase.
DR GO; GO:0045087; P:innate immune response; IMP:WormBase.
DR GO; GO:0030536; P:larval feeding behavior; IMP:UniProtKB.
DR GO; GO:0030514; P:negative regulation of BMP signaling pathway; IMP:WormBase.
DR GO; GO:0061067; P:negative regulation of dauer larval development; IMP:WormBase.
DR GO; GO:0002119; P:nematode larval development; IMP:WormBase.
DR GO; GO:0018991; P:oviposition; IMP:WormBase.
DR GO; GO:0030513; P:positive regulation of BMP signaling pathway; IMP:WormBase.
DR GO; GO:0040018; P:positive regulation of multicellular organism growth; IMP:WormBase.
DR GO; GO:0110039; P:positive regulation of nematode male tail tip morphogenesis; IMP:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:WormBase.
DR GO; GO:0006468; P:protein phosphorylation; IBA:GO_Central.
DR GO; GO:0022604; P:regulation of cell morphogenesis; IMP:WormBase.
DR GO; GO:0061065; P:regulation of dauer larval development; IMP:UniProtKB.
DR GO; GO:1903998; P:regulation of eating behavior; IMP:UniProtKB.
DR GO; GO:0042661; P:regulation of mesodermal cell fate specification; IGI:UniProtKB.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR InterPro; IPR045860; Snake_toxin-like_sf.
DR InterPro; IPR000333; TGFB_receptor.
DR PANTHER; PTHR23255; PTHR23255; 1.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR SUPFAM; SSF57302; SSF57302; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cell membrane; Developmental protein; Glycoprotein; Kinase;
KW Membrane; Nucleotide-binding; Receptor; Reference proteome;
KW Serine/threonine-protein kinase; Signal; Transferase; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..31
FT /evidence="ECO:0000255"
FT CHAIN 32..744
FT /note="Cell surface receptor daf-4"
FT /id="PRO_0000024431"
FT TOPO_DOM 48..253
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 254..274
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 275..744
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 306..603
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 605..686
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 724..744
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 622..643
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 655..669
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 729..744
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 440
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 312..320
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 338
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT CARBOHYD 60
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:17761667"
FT CARBOHYD 134
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:17761667"
FT CARBOHYD 165
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 374
FT /note="A -> P (in Ref. 1; AAA03544)"
FT /evidence="ECO:0000305"
FT CONFLICT 545
FT /note="L -> R (in Ref. 1; AAA03544)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 744 AA; 84410 MW; 33C087871FD81AF0 CRC64;
MNQKGTVRLK ALVLICLPLF LIATPVPVAV TEDDRQDRIE SEAAEKEWAN TLVSKVAQSN
GTGTIKVSAP AKPTLRRMDN EEDEVISIEC VYYDEMECEK SGDCEITKKT CYSEAHLKAV
GCLAVFGLPT QEINSTEPYL KVDKPQYKSL GCMPYQHADS MNCENESSCR QGRSFRGGIG
MCCCSTNNCN MPDLIEMVNP SLKKDSDNSA LLWASTPSNM DLESLDKFPF YWIIIIALSV
ILCIALLILA YVGWKFQQNK KEEIKKQQKI KFDMEKTDAL EAGNVPLVEP EEEMIEMVET
PKELPITDFQ LISKGRFGKV FKAQYTPDSG EKRLVAVKKL NEFQKASFLA EKRIFDELNE
YPKWYKSIVE FVCAEKIGDE YWIVTEFHER LSLYELLKNN VISITSANRI IMSMIDGLQF
LHDDRPYFFG HPKKPIIHRD IKSKNILVKS DMTTCIADFG LARIYSYDIE QSDLLGQVGT
KRYMSPEMLE GATEFTPTAF KAMDVYSMGL VMWEVISRTK LHQTDEPPNY QMPFQVIGFD
PTIGLMRNYV VSKKERPQWR DEIIKHEYMS LLKKVTEEMW DPEACARITA GCAFARVWNH
IMSSPDSSEG YHSGSSMKNR GVDDVEQSEK PEGIEEMQHY HASSPSKRQH PSPNPFFDSC
PPPPPIPVIL ENGGILQPDN AEPEPEELPD LPIVEKIYDI ATNMLFSREE LDLMNAQRQV
EYEAGADTRA STPTPSGTFG TFTT
