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 02-SEP-2026, entry version 196. 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=L-threonyl-[receptor-protein] + ATP = O-phospho-L-threonyl- CC [receptor-protein] + ADP + H(+); 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=L-seryl-[receptor-protein] + ATP = O-phospho-L-seryl- CC [receptor-protein] + ADP + H(+); Xref=Rhea:RHEA:18673, Rhea:RHEA- CC COMP:11022, Rhea:RHEA-COMP:11023, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, CC ChEBI:CHEBI:456216; 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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_065810.8. DR AlphaFoldDB; P50488; -. DR SMR; P50488; -. DR BioGRID; 41009; 19. DR FunCoup; P50488; 1612. DR IntAct; P50488; 14. DR MINT; P50488; -. DR STRING; 6239.C05D2.1a.2; -. DR GlyCosmos; P50488; 3 sites, No reported glycans. DR iPTMnet; P50488; -. DR PaxDb; 6239-C05D2.1a.2; -. DR PeptideAtlas; 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 AGR; WB:WBGene00000900; -. DR CTD; 175781; -. DR WormBase; C05D2.1a; CE16827; WBGene00000900; daf-4. DR eggNOG; KOG3653; Eukaryota. DR InParanoid; P50488; -. DR OMA; AMDVYSM; -. DR OrthoDB; 547665at2759; -. DR BRENDA; 2.7.10.2; 1045. DR SignaLink; P50488; -. DR PRO; PR:P50488; -. DR Proteomes; UP000001940; Chromosome III. DR Bgee; WBGene00000900; Expressed in larva and 4 other cell types or tissues. DR ExpressionAtlas; P50488; baseline and differential. DR GO; GO:0005886; C:plasma membrane; IDA:WormBase. DR GO; GO:0043235; C:signaling receptor complex; IBA:GO_Central. DR GO; GO:0005524; F:ATP binding; IEA:InterPro. DR GO; GO:0036122; F:BMP binding; IPI:WormBase. DR GO; GO:0005024; F:transforming growth factor beta receptor activity; IBA:GO_Central. DR GO; GO:0004675; F:transmembrane receptor protein serine/threonine kinase activity; ISS:WormBase. DR GO; GO:0030509; P:BMP signaling pathway; IBA:GO_Central. 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:0018991; P:egg-laying behavior; 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: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: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 CDD; cd23617; TFP_LU_ECD_Daf4; 1. DR FunFam; 1.10.510.10:FF:000487; Anti-Muellerian hormone type-2 receptor; 1. DR FunFam; 3.30.200.20:FF:000958; Receptor protein serine/threonine kinase; 1. DR Gene3D; 3.30.200.20; Phosphorylase Kinase, domain 1; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. 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:SF100; RECEPTOR PROTEIN SERINE_THREONINE KINASE; 1. DR PANTHER; PTHR23255; TRANSFORMING GROWTH FACTOR-BETA RECEPTOR TYPE I AND II; 1. DR Pfam; PF00069; Pkinase; 1. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR SUPFAM; SSF57302; Snake toxin-like; 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 620..639 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 731..744 FT /note="Low complexity" 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 //