DBL1_CAEEL
ID DBL1_CAEEL Reviewed; 365 AA.
AC G5EEL5; O76514;
DT 07-APR-2021, integrated into UniProtKB/Swiss-Prot.
DT 14-DEC-2011, sequence version 1.
DT 03-AUG-2022, entry version 91.
DE RecName: Full=Protein dbl-1 {ECO:0000305};
DE AltName: Full=Dpp and BMP-like protein 1 {ECO:0000303|PubMed:9847238};
DE Flags: Precursor;
GN Name=dbl-1 {ECO:0000312|WormBase:T25F10.2};
GN Synonyms=cet-1 {ECO:0000303|PubMed:10021351};
GN ORFNames=T25F10.2 {ECO:0000312|WormBase:T25F10.2};
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:AAC27729.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, DEVELOPMENTAL STAGE, AND MUTAGENESIS
RP OF 314-GLN--ARG-365.
RC STRAIN=Bristol N2 {ECO:0000312|EMBL:AAC27729.1};
RX PubMed=9847238; DOI=10.1242/dev.126.2.241;
RA Suzuki Y., Yandell M.D., Roy P.J., Krishna S., Savage-Dunn C., Ross R.M.,
RA Padgett R.W., Wood W.B.;
RT "A BMP homolog acts as a dose-dependent regulator of body size and male
RT tail patterning in Caenorhabditis elegans.";
RL Development 126:241-250(1999).
RN [2] {ECO:0000312|EMBL:AAC26791.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, DEVELOPMENTAL STAGE, AND DISRUPTION
RP PHENOTYPE.
RC STRAIN=Bristol N2 {ECO:0000312|EMBL:AAC26791.1};
RX PubMed=10021351; DOI=10.1242/dev.126.6.1337;
RA Morita K., Chow K.L., Ueno N.;
RT "Regulation of body length and male tail ray pattern formation of
RT Caenorhabditis elegans by a member of TGF-beta family.";
RL Development 126:1337-1347(1999).
RN [3] {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 [4] {ECO:0000305}
RP FUNCTION.
RX PubMed=12176330; DOI=10.1016/s0960-9822(02)00928-4;
RA Mallo G.V., Kurz C.L., Couillault C., Pujol N., Granjeaud S., Kohara Y.,
RA Ewbank J.J.;
RT "Inducible antibacterial defense system in C. elegans.";
RL Curr. Biol. 12:1209-1214(2002).
RN [5]
RP FUNCTION, AND MUTAGENESIS OF 314-GLN--ARG-365.
RX PubMed=18158917; DOI=10.1016/j.bbrc.2007.12.097;
RA Shim J., Lee J.;
RT "Regulation of rnt-1 expression mediated by the opposing effects of BRO-1
RT and DBL-1 in the nematode Caenorhabditis elegans.";
RL Biochem. Biophys. Res. Commun. 367:130-136(2008).
RN [6] {ECO:0000305}
RP FUNCTION.
RX PubMed=22189608; DOI=10.1017/s0016672311000310;
RA Savage-Dunn C., Yu L., Gill K., Awan M., Fernando T.;
RT "Non-stringent tissue-source requirements for BMP ligand expression in
RT regulation of body size in Caenorhabditis elegans.";
RL Genet. Res. 93:427-432(2011).
RN [7] {ECO:0000305}
RP FUNCTION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF
RP 314-GLN--ARG-365.
RX PubMed=23019581; DOI=10.1073/pnas.1205982109;
RA Zhang X., Zhang Y.;
RT "DBL-1, a TGF-beta, is essential for Caenorhabditis elegans aversive
RT olfactory learning.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:17081-17086(2012).
RN [8] {ECO:0000305}
RP FUNCTION, INTERACTION WITH DRAG-1, AND MUTAGENESIS OF 314-GLN--ARG-365.
RX PubMed=24004951; DOI=10.1242/dev.099838;
RA Tian C., Shi H., Xiong S., Hu F., Xiong W.C., Liu J.;
RT "The neogenin/DCC homolog UNC-40 promotes BMP signaling via the RGM protein
RT DRAG-1 in C. elegans.";
RL Development 140:4070-4080(2013).
RN [9] {ECO:0000305}
RP FUNCTION.
RX PubMed=24690231; DOI=10.1016/j.ydbio.2014.03.015;
RA Ramakrishnan K., Ray P., Okkema P.G.;
RT "CEH-28 activates dbl-1 expression and TGF-beta signaling in the C. elegans
RT M4 neuron.";
RL Dev. Biol. 390:149-159(2014).
RN [10] {ECO:0000305}
RP FUNCTION, AND MUTAGENESIS OF 314-GLN--ARG-365.
RX PubMed=29162682; DOI=10.1534/g3.117.300416;
RA Clark J.F., Meade M., Ranepura G., Hall D.H., Savage-Dunn C.;
RT "Caenorhabditis elegans DBL-1/BMP Regulates Lipid Accumulation via
RT Interaction with Insulin Signaling.";
RL G3 (Bethesda) 8:343-351(2018).
CC -!- FUNCTION: Ligand for the serine/threonine-protein kinase receptor type-
CC 1 sma-6 which activates a TGF-beta-like signaling pathway
CC (PubMed:24004951). Multifunctional protein that is involved in body
CC size, male ectodermal patterning, innate immunity, lipid metabolism and
CC neural plasticity (PubMed:10021351, PubMed:9847238, PubMed:12176330,
CC PubMed:29162682, PubMed:23019581). Dose-dependent regulator of body
CC size, probably influencing the sizes of some or all cells rather than
CC their number (PubMed:10021351, PubMed:9847238, PubMed:22189608). Plays
CC a role in patterning of male-specific genital sensilla (simple sense
CC organs), known as rays, and mating-associated structures, spicules
CC (PubMed:10021351, PubMed:9847238). Plays a protective role in response
CC to infection by the Gram-negative bacterium S.marcescens, by activating
CC expression of genes involved in innate immunity (PubMed:12176330).
CC Regulator of lipid homeostasis, acting non cell-autonomously in the
CC hypodermis; partly dependent on the Insulin/IGF-1-like signaling (IIS)
CC mediated pathway (PubMed:29162682). Required for aversive olfactory
CC learning of pathogenic bacteria in adults (PubMed:23019581). Involved
CC in gland cell morphology, possibly via activation of a Smad-independent
CC TGF-beta signaling pathway (PubMed:24690231). Required to oppose the
CC autoregulation of expression of Runt-related transcription factor rnt-
CC 1. {ECO:0000269|PubMed:10021351, ECO:0000269|PubMed:12176330,
CC ECO:0000269|PubMed:18158917, ECO:0000269|PubMed:22189608,
CC ECO:0000269|PubMed:23019581, ECO:0000269|PubMed:24004951,
CC ECO:0000269|PubMed:24690231, ECO:0000269|PubMed:29162682,
CC ECO:0000269|PubMed:9847238}.
CC -!- SUBUNIT: Homodimer; disulfide-linked (By similarity). Interacts with
CC drag-1 (PubMed:24004951). {ECO:0000250|UniProtKB:P61812,
CC ECO:0000269|PubMed:24004951}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Expressed in embryos just prior to hatching and
CC remains constant in most cells throughout the larval and adult stages
CC (PubMed:9847238). Expressed by AVA command interneurons
CC (PubMed:23019581). {ECO:0000269|PubMed:23019581,
CC ECO:0000269|PubMed:9847238}.
CC -!- DEVELOPMENTAL STAGE: Expressed in L4 larval stage primarily in neurons,
CC including ventral cord neurons DA, DB, VA and VB; the lateral excretory
CC canal associated CAN cells; and anterior neurons AVK, DVA, I5, M1, M2,
CC M4 and M5. {ECO:0000269|PubMed:10021351, ECO:0000269|PubMed:9847238}.
CC -!- DISRUPTION PHENOTYPE: Reduced body size (PubMed:10021351).
CC Abnormalities in the male tail (PubMed:10021351). Disrupted aversive
CC learning (PubMed:23019581). {ECO:0000269|PubMed:10021351,
CC ECO:0000269|PubMed:23019581}.
CC -!- SIMILARITY: Belongs to the TGF-beta family.
CC {ECO:0000255|RuleBase:RU000354}.
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DR EMBL; AF074395; AAC26791.1; -; mRNA.
DR EMBL; AF004395; AAC27729.1; -; mRNA.
DR EMBL; BX284605; CCD74236.1; -; Genomic_DNA.
DR PIR; T29518; T29518.
DR PIR; T43286; T43286.
DR RefSeq; NP_504709.1; NM_072308.5.
DR AlphaFoldDB; G5EEL5; -.
DR SMR; G5EEL5; -.
DR STRING; 6239.T25F10.2.1; -.
DR PaxDb; G5EEL5; -.
DR EnsemblMetazoa; T25F10.2.1; T25F10.2.1; WBGene00000936.
DR GeneID; 179068; -.
DR KEGG; cel:CELE_T25F10.2; -.
DR CTD; 179068; -.
DR WormBase; T25F10.2; CE26386; WBGene00000936; dbl-1.
DR eggNOG; KOG3900; Eukaryota.
DR GeneTree; ENSGT00940000160223; -.
DR HOGENOM; CLU_020515_3_0_1; -.
DR InParanoid; G5EEL5; -.
DR OMA; SIYFFED; -.
DR OrthoDB; 962484at2759; -.
DR PhylomeDB; G5EEL5; -.
DR Reactome; R-CEL-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR Reactome; R-CEL-8957275; Post-translational protein phosphorylation.
DR SignaLink; G5EEL5; -.
DR Proteomes; UP000001940; Chromosome V.
DR Bgee; WBGene00000936; Expressed in larva and 3 other tissues.
DR GO; GO:0005615; C:extracellular space; ISS:WormBase.
DR GO; GO:0070700; F:BMP receptor binding; ISS:WormBase.
DR GO; GO:0005125; F:cytokine activity; IBA:GO_Central.
DR GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR GO; GO:0030509; P:BMP signaling pathway; ISS:WormBase.
DR GO; GO:0050832; P:defense response to fungus; IMP:WormBase.
DR GO; GO:0050829; P:defense response to Gram-negative bacterium; IMP:WormBase.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IMP:WormBase.
DR GO; GO:0045087; P:innate immune response; IMP:WormBase.
DR GO; GO:0002119; P:nematode larval development; IMP:WormBase.
DR GO; GO:0045138; P:nematode male tail tip morphogenesis; IMP:WormBase.
DR GO; GO:0045793; P:positive regulation of cell size; IMP:WormBase.
DR GO; GO:0032877; P:positive regulation of DNA endoreduplication; IMP:WormBase.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:UniProtKB.
DR GO; GO:0040018; P:positive regulation of multicellular organism growth; IMP:WormBase.
DR GO; GO:0046622; P:positive regulation of organ growth; IMP:WormBase.
DR GO; GO:0010862; P:positive regulation of pathway-restricted SMAD protein phosphorylation; IBA:GO_Central.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:WormBase.
DR GO; GO:0030511; P:positive regulation of transforming growth factor beta receptor signaling pathway; IGI:UniProtKB.
DR GO; GO:0022604; P:regulation of cell morphogenesis; IMP:WormBase.
DR GO; GO:0010468; P:regulation of gene expression; IMP:UniProtKB.
DR GO; GO:0019216; P:regulation of lipid metabolic process; IMP:UniProtKB.
DR GO; GO:0042661; P:regulation of mesodermal cell fate specification; IGI:UniProtKB.
DR GO; GO:0060395; P:SMAD protein signal transduction; IBA:GO_Central.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:1901048; P:transforming growth factor beta receptor signaling pathway involved in regulation of multicellular organism growth; IMP:UniProtKB.
DR Gene3D; 2.10.90.10; -; 1.
DR InterPro; IPR029034; Cystine-knot_cytokine.
DR InterPro; IPR001839; TGF-b_C.
DR InterPro; IPR001111; TGF-b_propeptide.
DR InterPro; IPR015615; TGF-beta-rel.
DR InterPro; IPR017948; TGFb_CS.
DR PANTHER; PTHR11848; PTHR11848; 1.
DR Pfam; PF00019; TGF_beta; 1.
DR Pfam; PF00688; TGFb_propeptide; 1.
DR SMART; SM00204; TGFB; 1.
DR SUPFAM; SSF57501; SSF57501; 1.
DR PROSITE; PS00250; TGF_BETA_1; 1.
DR PROSITE; PS51362; TGF_BETA_2; 1.
PE 1: Evidence at protein level;
KW Developmental protein; Disulfide bond; Glycoprotein; Growth factor;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1..42
FT /evidence="ECO:0000255"
FT PROPEP 43..244
FT /evidence="ECO:0000255"
FT /id="PRO_0000452181"
FT CHAIN 245..365
FT /note="Protein dbl-1"
FT /evidence="ECO:0000255"
FT /id="PRO_0000452182"
FT REGION 231..259
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 110
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 143
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 167
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 306
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT DISULFID 264..330
FT /evidence="ECO:0000250|UniProtKB:P61812"
FT DISULFID 293..362
FT /evidence="ECO:0000250|UniProtKB:P61812"
FT DISULFID 297..364
FT /evidence="ECO:0000250|UniProtKB:P61812"
FT DISULFID 329
FT /note="Interchain"
FT /evidence="ECO:0000250|UniProtKB:P61812"
FT MUTAGEN 314..365
FT /note="Missing: In wk70; reduced body size in
FT hermaphrodites, probably due to abnormal postembryonic
FT growth, but without embryonic or larval lethality. Fusions
FT of male-specific genital sensilla (simple sense organs)
FT known as rays. Decrease in lipid levels at the L4 larval
FT stage. Disrupted aversive learning. Expression of Runt-
FT related transcription factor rnt-1 is abolished, when
FT combined with RNAi-mediated knockdown of CBF beta homolog
FT bro-1. Hatched larvae show considerably lower expression of
FT rnt-1, but normal levels in embryos."
FT /evidence="ECO:0000269|PubMed:18158917,
FT ECO:0000269|PubMed:23019581, ECO:0000269|PubMed:24004951,
FT ECO:0000269|PubMed:29162682, ECO:0000269|PubMed:9847238"
FT CONFLICT 199
FT /note="I -> T (in Ref. 2; AAC26791)"
FT /evidence="ECO:0000305"
FT CONFLICT 212..215
FT /note="YARA -> TRGS (in Ref. 2; AAC26791)"
FT /evidence="ECO:0000305"
FT CONFLICT 238
FT /note="A -> R (in Ref. 2; AAC26791)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 365 AA; 41769 MW; 937BFF3459F02C7E CRC64;
MNDSVRTTTT ISSTKSLVHS FQLSAILHLF LLISFTPMSA AADQHASHAT RRGLLRKLGL
EHVPVQTGPS IDVPQHMWDI YDDDNDVDWV RHYYPKEIIE DNEGFLLSYN LSLAARNAHN
EEVTKATLKL RLRRNNKARR SGNISIYFFE DDINNDRFQI ESRSVDNLTE WIDFDVTAAF
LRRTNRISFF IDLPEDVEIE ETQSSSLSSL PYARAQSAPL IVFSDLSEPS SVRRKRSAQT
GNSERKNRKK GRKHHNTEAE SNLCRRTDFY VDFDDLNWQD WIMAPKGYDA YQCQGSCPNP
MPAQLNATNH AIIQSLLHSL RPDEVPPPCC VPTETSPLSI LYMDVDKVIV IREYADMRVE
SCGCR
