DAF8_CAEEL
ID DAF8_CAEEL Reviewed; 546 AA.
AC Q21733;
DT 07-APR-2021, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=Smad protein daf-8 {ECO:0000303|PubMed:20081192};
DE AltName: Full=Abnormal dauer formation protein 8 {ECO:0000312|WormBase:R05D11.1};
GN Name=daf-8 {ECO:0000312|WormBase:R05D11.1};
GN ORFNames=R05D11.1 {ECO:0000312|WormBase:R05D11.1};
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|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 [2] {ECO:0000305}
RP FUNCTION, AND MUTAGENESIS OF GLY-502.
RX PubMed=10625546; DOI=10.1006/dbio.1999.9545;
RA Inoue T., Thomas J.H.;
RT "Targets of TGF-beta signaling in Caenorhabditis elegans dauer formation.";
RL Dev. Biol. 217:192-204(2000).
RN [3] {ECO:0000305}
RP FUNCTION, SUBUNIT, INTERACTION WITH DAF-14 AND DAF-3, SUBCELLULAR LOCATION,
RP TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND MUTAGENESIS OF
RP 52-GLN--THR-546; SER-391; 416-ARG--THR-546 AND GLY-502.
RX PubMed=20081192; DOI=10.1242/dev.043752;
RA Park D., Estevez A., Riddle D.L.;
RT "Antagonistic Smad transcription factors control the dauer/non-dauer switch
RT in C. elegans.";
RL Development 137:477-485(2010).
RN [4] {ECO:0000305}
RP FUNCTION, INTERACTION WITH NHR-69, AND MUTAGENESIS OF 416-ARG--THR-546.
RX PubMed=22359515; DOI=10.1371/journal.pgen.1002519;
RA Park D., Jones K.L., Lee H., Snutch T.P., Taubert S., Riddle D.L.;
RT "Repression of a potassium channel by nuclear hormone receptor and TGF-beta
RT signaling modulates insulin signaling in Caenorhabditis elegans.";
RL PLoS Genet. 8:e1002519-e1002519(2012).
CC -!- FUNCTION: Probably a receptor-regulated SMAD (R-SMAD) that is an
CC intracellular signal transducer and transcriptional modulator activated
CC by TGF-beta-like daf-7 signaling (PubMed:10625546, PubMed:20081192).
CC Plays a role in TGF-beta-like daf-7 signaling in regulating entry into
CC a developmentally arrested larval state known as dauer, in response to
CC harsh environmental conditions; partially redundant with R-SMAD daf-14
CC (PubMed:10625546, PubMed:20081192). Plays a role in inhibiting mitosis
CC and promoting a switch to meiosis in the germ line, perhaps by down-
CC regulating lag-2 transcription in the gonadal distal tip cells (DTCs)
CC (PubMed:20081192). In cooperation with orphan nuclear receptor nhr-69
CC modulates the Insulin/IGF-1-like signaling (IIS) pathway, perhaps by
CC regulating expression of the potassium channel exp-2, which in turn
CC modulates the secretion of the insulin-like peptide daf-28
CC (PubMed:22359515). {ECO:0000269|PubMed:10625546,
CC ECO:0000269|PubMed:20081192, ECO:0000269|PubMed:22359515}.
CC -!- SUBUNIT: Homodimer (Probable). Interacts with R-SMAD daf-14 and co-SMAD
CC daf-3 (PubMed:20081192). Interacts with orphan nuclear receptor nhr-69
CC (PubMed:22359515). {ECO:0000269|PubMed:20081192,
CC ECO:0000269|PubMed:22359515, ECO:0000305|PubMed:20081192}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|RuleBase:RU361195,
CC ECO:0000269|PubMed:20081192}. Nucleus {ECO:0000255|RuleBase:RU361195,
CC ECO:0000269|PubMed:20081192}. Note=Localizes to the nucleus in a TGF-
CC beta-like receptor daf-1 dependent manner.
CC {ECO:0000269|PubMed:20081192}.
CC -!- TISSUE SPECIFICITY: Expressed in the excretory cell and gonadal distal
CC tip cells (DTCs). {ECO:0000269|PubMed:20081192}.
CC -!- DEVELOPMENTAL STAGE: Expressed in developing embryos from the pre-comma
CC stage through to hatching (PubMed:20081192). Most highly expressed in
CC larval stage L1 and gradually decreases into adulthood
CC (PubMed:20081192). In larval stages, expressed throughout development
CC in the ventral nerve cord, intestine, gonadal distal tip cells (DTCs)
CC and subsets of head and tail neurons, most strongly in head neurons ASI
CC and ADL (PubMed:20081192). {ECO:0000269|PubMed:20081192}.
CC -!- SIMILARITY: Belongs to the dwarfin/SMAD family.
CC {ECO:0000255|RuleBase:RU361195}.
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DR EMBL; BX284601; CAA99889.1; -; Genomic_DNA.
DR PIR; T23920; T23920.
DR RefSeq; NP_492321.1; NM_059920.3.
DR AlphaFoldDB; Q21733; -.
DR SMR; Q21733; -.
DR STRING; 6239.R05D11.1; -.
DR EPD; Q21733; -.
DR PaxDb; Q21733; -.
DR PeptideAtlas; Q21733; -.
DR EnsemblMetazoa; R05D11.1.1; R05D11.1.1; WBGene00000904.
DR GeneID; 187612; -.
DR KEGG; cel:CELE_R05D11.1; -.
DR UCSC; R05D11.1; c. elegans.
DR CTD; 187612; -.
DR WormBase; R05D11.1; CE06236; WBGene00000904; daf-8.
DR eggNOG; KOG3701; Eukaryota.
DR GeneTree; ENSGT00940000170124; -.
DR HOGENOM; CLU_026736_0_2_1; -.
DR InParanoid; Q21733; -.
DR OMA; YECVEYE; -.
DR OrthoDB; 1319355at2759; -.
DR PhylomeDB; Q21733; -.
DR Reactome; R-CEL-1181150; Signaling by NODAL.
DR Reactome; R-CEL-1502540; Signaling by Activin.
DR Reactome; R-CEL-2173788; Downregulation of TGF-beta receptor signaling.
DR Reactome; R-CEL-2173789; TGF-beta receptor signaling activates SMADs.
DR Reactome; R-CEL-2173795; Downregulation of SMAD2/3:SMAD4 transcriptional activity.
DR Reactome; R-CEL-2173796; SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription.
DR Reactome; R-CEL-5689880; Ub-specific processing proteases.
DR Reactome; R-CEL-8941855; RUNX3 regulates CDKN1A transcription.
DR Reactome; R-CEL-9617828; FOXO-mediated transcription of cell cycle genes.
DR Proteomes; UP000001940; Chromosome I.
DR Bgee; WBGene00000904; Expressed in pharyngeal muscle cell (C elegans) and 3 other tissues.
DR GO; GO:0005829; C:cytosol; IDA:WormBase.
DR GO; GO:0071144; C:heteromeric SMAD protein complex; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IDA:WormBase.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0070411; F:I-SMAD binding; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:WormBase.
DR GO; GO:0009653; P:anatomical structure morphogenesis; IBA:GO_Central.
DR GO; GO:0030509; P:BMP signaling pathway; IBA:GO_Central.
DR GO; GO:0030154; P:cell differentiation; 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:0050829; P:defense response to Gram-negative bacterium; IMP:WormBase.
DR GO; GO:0008340; P:determination of adult lifespan; IMP:WormBase.
DR GO; GO:0061067; P:negative regulation of dauer larval development; IMP:WormBase.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:WormBase.
DR GO; GO:0018991; P:oviposition; IGI:WormBase.
DR GO; GO:0043476; P:pigment accumulation; IGI:WormBase.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:WormBase.
DR GO; GO:0061065; P:regulation of dauer larval development; IMP: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; IBA:GO_Central.
DR Gene3D; 2.60.200.10; -; 1.
DR Gene3D; 3.90.520.10; -; 1.
DR InterPro; IPR013790; Dwarfin.
DR InterPro; IPR003619; MAD_homology1_Dwarfin-type.
DR InterPro; IPR013019; MAD_homology_MH1.
DR InterPro; IPR017855; SMAD-like_dom_sf.
DR InterPro; IPR001132; SMAD_dom_Dwarfin-type.
DR InterPro; IPR008984; SMAD_FHA_dom_sf.
DR InterPro; IPR036578; SMAD_MH1_sf.
DR PANTHER; PTHR13703; PTHR13703; 1.
DR Pfam; PF03165; MH1; 1.
DR Pfam; PF03166; MH2; 1.
DR SMART; SM00523; DWA; 1.
DR SMART; SM00524; DWB; 1.
DR SUPFAM; SSF49879; SSF49879; 1.
DR SUPFAM; SSF56366; SSF56366; 1.
DR PROSITE; PS51075; MH1; 1.
DR PROSITE; PS51076; MH2; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; DNA-binding; Metal-binding; Nucleus; Reference proteome;
KW Transcription; Transcription regulation; Zinc.
FT CHAIN 1..546
FT /note="Smad protein daf-8"
FT /id="PRO_0000452404"
FT DOMAIN 16..137
FT /note="MH1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00438"
FT DOMAIN 349..546
FT /note="MH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00439"
FT REGION 234..268
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 292..317
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 52..546
FT /note="Missing: In sa343; constitutive dauer formation at
FT 25 degrees Celsius."
FT /evidence="ECO:0000269|PubMed:20081192"
FT MUTAGEN 391
FT /note="S->L: In e1393; constitutive dauer formation at 25
FT degrees Celsius."
FT /evidence="ECO:0000269|PubMed:20081192"
FT MUTAGEN 416..546
FT /note="Missing: In m85; constitutive dauer formation at 25
FT degrees Celsius. In the ovaries, the germ line mitotic zone
FT at the distal end is significantly extended, with an
FT increased number of metaphase and telophase cells. Reduces
FT interaction between daf-3 and daf-14. On an nhr-69 mutant
FT background, has defects in dauer entry and exit, and
FT impaired Insulin/IGF-1-like signaling (IIS). Reduces
FT binding of nhr-69 to the promoter, and up-regulates
FT expression, of the potassium channel gene exp-2."
FT /evidence="ECO:0000269|PubMed:20081192,
FT ECO:0000269|PubMed:22359515"
FT MUTAGEN 502
FT /note="G->E: In sa234; constitutive dauer formation at 25
FT degrees Celsius."
FT /evidence="ECO:0000269|PubMed:10625546,
FT ECO:0000269|PubMed:20081192"
FT MUTAGEN 502
FT /note="G->R: In m121; constitutive dauer formation at 25
FT degrees Celsius."
FT /evidence="ECO:0000269|PubMed:20081192"
SQ SEQUENCE 546 AA; 61972 MW; 28027F78EE9B5B16 CRC64;
MDDFPSPEPT DPRLEAMAQK VLEETIITEG DGTIYWALKV TRLLSRVAKK HQCFEAFYDA
VIKGDPKTRC CPAHNEKLIG NFGRAIMCVL RAFRFPVIRY ESQVKSILTC RHAFNSHSRN
VCLNPYHYRW VELPTCQVPP IIVNKELDYG EPPIRTEDAL DDWNQKDLKE EQVVASWDVP
NVTMRGDEIK LLYDRYAAEN GDFQYMNYGN FGSFDGSPCS STTMSLGSSF ASLLQQSNRQ
DDEEPGYYRS GLSSPASHAA SPREFIPNGN DTISLDQEMM DDSEVSDIMH SENFSSENNG
NRKPTYADGR PITPIEPRPL YRSSALELGD LSRQAGIYEC VEYEESPSWL KLIYYEEGTM
IGEKADVEGH HCLIDGFTAS RTDSETRSRF SLGWYNNPNR SPQTAEVRGL IGKGVRFYLL
AGEVYVENLC NIPVFVQSIG ANMKNGFQLN TVSKLPPTGT MKVFDMRLFS KQLRTAAEKT
YQDVYCLSRM CTVRVSFCKG WGEHYRRSTV LRSPVWFQAH LNNPMHWVDS VLTCMGAPPR
ICSSRT
