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THIO1_CAEEL
ID   THIO1_CAEEL             Reviewed;         115 AA.
AC   Q09433; Q306X0; Q7YZF7;
DT   01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1995, sequence version 1.
DT   03-AUG-2022, entry version 142.
DE   RecName: Full=Thioredoxin-1;
GN   Name=trx-1; ORFNames=B0228.5;
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] (ISOFORMS A AND B), FUNCTION, TISSUE
RP   SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX   PubMed=16387300; DOI=10.1016/j.febslet.2005.12.046;
RA   Miranda-Vizuete A., Gonzalez J.C., Gahmon G., Burghoorn J., Navas P.,
RA   Swoboda P.;
RT   "Lifespan decrease in a Caenorhabditis elegans mutant lacking TRX-1, a
RT   thioredoxin expressed in ASJ sensory neurons.";
RL   FEBS Lett. 580:484-490(2006).
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, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND DISRUPTION
RP   PHENOTYPE.
RX   PubMed=16324156; DOI=10.1111/j.1365-2443.2005.00913.x;
RA   Jee C., Vanoaica L., Lee J., Park B.J., Ahnn J.;
RT   "Thioredoxin is related to life span regulation and oxidative stress
RT   response in Caenorhabditis elegans.";
RL   Genes Cells 10:1203-1210(2005).
RN   [4]
RP   FUNCTION, TISSUE SPECIFICITY, INDUCTION BY DIETARY RESTRICTION, AND
RP   DISRUPTION PHENOTYPE.
RX   PubMed=21334311; DOI=10.1016/j.bbrc.2011.02.079;
RA   Fierro-Gonzalez J.C., Gonzalez-Barrios M., Miranda-Vizuete A., Swoboda P.;
RT   "The thioredoxin TRX-1 regulates adult lifespan extension induced by
RT   dietary restriction in Caenorhabditis elegans.";
RL   Biochem. Biophys. Res. Commun. 406:478-482(2011).
RN   [5]
RP   FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, INDUCTION BY DAUER
RP   FORMATION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF 39-CYS--CYS-42.
RX   PubMed=21304598; DOI=10.1371/journal.pone.0016561;
RA   Fierro-Gonzalez J.C., Cornils A., Alcedo J., Miranda-Vizuete A.,
RA   Swoboda P.;
RT   "The thioredoxin TRX-1 modulates the function of the insulin-like
RT   neuropeptide DAF-28 during dauer formation in Caenorhabditis elegans.";
RL   PLoS ONE 6:E16561-E16561(2011).
RN   [6]
RP   FUNCTION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF CYS-39 AND CYS-73.
RX   PubMed=26920757; DOI=10.1534/genetics.115.185272;
RA   McCallum K.C., Liu B., Fierro-Gonzalez J.C., Swoboda P., Arur S.,
RA   Miranda-Vizuete A., Garsin D.A.;
RT   "TRX-1 Regulates SKN-1 Nuclear Localization Cell Non-autonomously in
RT   Caenorhabditis elegans.";
RL   Genetics 203:387-402(2016).
RN   [7]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=30014846; DOI=10.7554/elife.36833;
RA   Hao Y., Yang W., Ren J., Hall Q., Zhang Y., Kaplan J.M.;
RT   "Thioredoxin shapes the C. elegans sensory response to Pseudomonas produced
RT   nitric oxide.";
RL   Elife 7:0-0(2018).
CC   -!- FUNCTION: Participates in various redox reactions through the
CC       reversible oxidation of its active center dithiol to a disulfide and
CC       catalyzes dithiol-disulfide exchange reactions (PubMed:16324156,
CC       PubMed:16387300). Shown to facilitate the reduction of insulin
CC       disulfide bonds (PubMed:16324156, PubMed:16387300). Might play a role
CC       in the reversible nitrosylation of cysteine residues in target
CC       proteins, and thereby contributing to the response to intracellular
CC       nitric oxide (PubMed:30014846). Shapes the ASJ sensory neuron biphasic
CC       response to nitric oxide (NO) exposure; trans-nitrosylation activity
CC       might inhibit calcium flux to the cytoplasm in ASJ neurons when exposed
CC       to a NO stimulus, whereas de-nitrosylation activity might promote
CC       calcium flux when NO is diminished (PubMed:30014846). By regulating the
CC       NO-induced ASJ sensory neuron activity, mediates the avoidance response
CC       to NO-producing organisms like P.aeruginosa (PubMed:30014846).
CC       Positively regulates life span extension under normal and caloric
CC       restriction conditions, dauer formation and the oxidative stress
CC       response (PubMed:16387300, PubMed:16324156, PubMed:21334311,
CC       PubMed:21304598, PubMed:26920757). Contributes to the down-regulation
CC       of expression of the insulin-like neuropeptide daf-28 in the ASJ
CC       neurons in a redox-independent fashion, thereby promoting dauer
CC       formation (PubMed:21304598). Negatively regulates the nuclear
CC       localization of the intestinal skn-1 transcription factor in a p38 MAPK
CC       pathway-dependent and redox-independent fashion (PubMed:26920757).
CC       {ECO:0000269|PubMed:16324156, ECO:0000269|PubMed:16387300,
CC       ECO:0000269|PubMed:21304598, ECO:0000269|PubMed:21334311,
CC       ECO:0000269|PubMed:26920757, ECO:0000269|PubMed:30014846}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=a;
CC         IsoId=Q09433-1; Sequence=Displayed;
CC       Name=b;
CC         IsoId=Q09433-2; Sequence=VSP_019285;
CC   -!- TISSUE SPECIFICITY: Expressed in ASJ and ASI ciliated sensory neurons
CC       (PubMed:16387300, PubMed:21304598, PubMed:16324156, PubMed:21334311).
CC       Expressed in the intestine (at protein level) (PubMed:16324156).
CC       {ECO:0000269|PubMed:16324156, ECO:0000269|PubMed:16387300,
CC       ECO:0000269|PubMed:21304598, ECO:0000269|PubMed:21334311}.
CC   -!- DEVELOPMENTAL STAGE: Expressed in larval stages L2 and L3 and increased
CC       expression during dauer stage (PubMed:21304598). Expressed in adult
CC       animals with increased expression in 10-day-old animals
CC       (PubMed:16324156). {ECO:0000269|PubMed:16324156,
CC       ECO:0000269|PubMed:21304598}.
CC   -!- INDUCTION: Up-regulated in response to dietary restriction and during
CC       dauer formation. {ECO:0000269|PubMed:21304598,
CC       ECO:0000269|PubMed:21334311}.
CC   -!- DISRUPTION PHENOTYPE: Increased nitric oxide-evoked calcium flux to
CC       cytoplasm in ASJ sensory neurons (PubMed:30014846). Decreased avoidance
CC       of P.aeruginosa (PubMed:30014846). Decrease in lifespan
CC       (PubMed:16387300, PubMed:16324156). Suppression of lifespan extension
CC       induced by dietary deprivation or in an eat-2(ad1116) mutant background
CC       and partial suppression in a daf-2(e1370) mutant background
CC       (PubMed:21334311). Enhancement of the constitutive dauer formation
CC       phenotype in a daf-11(ks67), daf-11(m47), daf-11(sa195), daf-7(e1372),
CC       daf-1(e1287) or daf-8(e1393) mutant background at 15 degrees Celsius
CC       (PubMed:21304598). Suppression of the constitutive dauer formation
CC       phenotype in a daf-11(sa195), daf-28(tm2308) or daf-28(sa191) mutant
CC       background at 25 degrees Celsius (PubMed:21304598). Failure in down-
CC       regulation of daf-28 expression during dauer stage (PubMed:21304598).
CC       Decreased survival when facing oxidative stress upon exposure to sodium
CC       arsenite or paraquat (PubMed:26920757, PubMed:16324156). Increased
CC       localization of skn-1 to the nuclei of intestinal cells
CC       (PubMed:26920757). Suppression of skn-1 nuclear localization in a nsy-
CC       1(ok593), sek-1(km4) or pmk-1(km25) mutant background
CC       (PubMed:26920757). {ECO:0000269|PubMed:16324156,
CC       ECO:0000269|PubMed:16387300, ECO:0000269|PubMed:21304598,
CC       ECO:0000269|PubMed:21334311, ECO:0000269|PubMed:26920757,
CC       ECO:0000269|PubMed:30014846}.
CC   -!- SIMILARITY: Belongs to the thioredoxin family. {ECO:0000305}.
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DR   EMBL; DQ241299; ABB45863.1; -; mRNA.
DR   EMBL; DQ241300; ABB45864.1; -; mRNA.
DR   EMBL; FO080130; CCD61448.1; -; Genomic_DNA.
DR   EMBL; FO080130; CCD61449.1; -; Genomic_DNA.
DR   PIR; T29044; T29044.
DR   RefSeq; NP_001021885.1; NM_001026714.3. [Q09433-1]
DR   RefSeq; NP_001021886.1; NM_001026715.4. [Q09433-2]
DR   AlphaFoldDB; Q09433; -.
DR   SMR; Q09433; -.
DR   STRING; 6239.B0228.5a; -.
DR   EPD; Q09433; -.
DR   PaxDb; Q09433; -.
DR   PeptideAtlas; Q09433; -.
DR   PRIDE; Q09433; -.
DR   EnsemblMetazoa; B0228.5a.1; B0228.5a.1; WBGene00015062. [Q09433-1]
DR   EnsemblMetazoa; B0228.5b.1; B0228.5b.1; WBGene00015062. [Q09433-2]
DR   GeneID; 181863; -.
DR   KEGG; cel:CELE_B0228.5; -.
DR   UCSC; B0228.5b; c. elegans. [Q09433-1]
DR   CTD; 181863; -.
DR   WormBase; B0228.5a; CE01745; WBGene00015062; trx-1. [Q09433-1]
DR   WormBase; B0228.5b; CE34629; WBGene00015062; trx-1. [Q09433-2]
DR   eggNOG; KOG0907; Eukaryota.
DR   HOGENOM; CLU_090389_14_6_1; -.
DR   InParanoid; Q09433; -.
DR   OMA; HAMADKF; -.
DR   OrthoDB; 1482186at2759; -.
DR   PhylomeDB; Q09433; -.
DR   PRO; PR:Q09433; -.
DR   Proteomes; UP000001940; Chromosome II.
DR   Bgee; WBGene00015062; Expressed in pharyngeal muscle cell (C elegans) and 3 other tissues.
DR   GO; GO:0030424; C:axon; IDA:WormBase.
DR   GO; GO:0005737; C:cytoplasm; IDA:WormBase.
DR   GO; GO:0030425; C:dendrite; IDA:WormBase.
DR   GO; GO:0043025; C:neuronal cell body; IDA:WormBase.
DR   GO; GO:0097730; C:non-motile cilium; IDA:WormBase.
DR   GO; GO:0005634; C:nucleus; IDA:WormBase.
DR   GO; GO:0015035; F:protein-disulfide reductase activity; IDA:WormBase.
DR   GO; GO:0008340; P:determination of adult lifespan; IMP:WormBase.
DR   InterPro; IPR005746; Thioredoxin.
DR   InterPro; IPR036249; Thioredoxin-like_sf.
DR   InterPro; IPR017937; Thioredoxin_CS.
DR   InterPro; IPR013766; Thioredoxin_domain.
DR   Pfam; PF00085; Thioredoxin; 1.
DR   PIRSF; PIRSF000077; Thioredoxin; 1.
DR   SUPFAM; SSF52833; SSF52833; 1.
DR   PROSITE; PS00194; THIOREDOXIN_1; 1.
DR   PROSITE; PS51352; THIOREDOXIN_2; 1.
PE   1: Evidence at protein level;
KW   Alternative splicing; Disulfide bond; Electron transport;
KW   Redox-active center; Reference proteome; Transport.
FT   CHAIN           1..115
FT                   /note="Thioredoxin-1"
FT                   /id="PRO_0000120027"
FT   DOMAIN          2..114
FT                   /note="Thioredoxin"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00691"
FT   ACT_SITE        39
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000250|UniProtKB:P29445"
FT   ACT_SITE        42
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000250|UniProtKB:P29445"
FT   SITE            33
FT                   /note="Deprotonates C-terminal active site Cys"
FT                   /evidence="ECO:0000250"
FT   SITE            40
FT                   /note="Contributes to redox potential value"
FT                   /evidence="ECO:0000250"
FT   SITE            41
FT                   /note="Contributes to redox potential value"
FT                   /evidence="ECO:0000250"
FT   DISULFID        39..42
FT                   /note="Redox-active"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00691"
FT   VAR_SEQ         2..15
FT                   /note="LKRCNFKNQVKYFQ -> SLTKEPILELADM (in isoform b)"
FT                   /evidence="ECO:0000303|PubMed:16387300"
FT                   /id="VSP_019285"
FT   MUTAGEN         39..42
FT                   /note="CGPC->SGPS: No change in suppression of the
FT                   constitutive dauer formation phenotype in a daf-28(sa191)
FT                   mutant background. No impact on skn-1 nuclear
FT                   localization."
FT                   /evidence="ECO:0000269|PubMed:21304598,
FT                   ECO:0000269|PubMed:26920757"
FT   MUTAGEN         39
FT                   /note="C->S: In nu517; abolishes the calcium flux to the
FT                   cytoplasm in the ASJ sensory neurons in response to the
FT                   removal of a nitric oxide stimulus. No defect in
FT                   P.aeruginosa avoidance."
FT                   /evidence="ECO:0000269|PubMed:30014846"
FT   MUTAGEN         73
FT                   /note="C->S: Elimination of the nitric oxide-evoked calcium
FT                   flux to the cytoplasm in ASJ sensory neurons. Defect in
FT                   avoidance of P.aeruginosa."
FT                   /evidence="ECO:0000269|PubMed:30014846"
SQ   SEQUENCE   115 AA;  13323 MW;  073F51A3EA97AD4B CRC64;
     MLKRCNFKNQ VKYFQSDFEQ LIRQHPEKII ILDFYATWCG PCKAIAPLYK ELATTHKGII
     FCKVDVDEAE DLCSKYDVKM MPTFIFTKNG DAIEALEGCV EDELRQKVLE HVSAQ
 
 
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