XBP1_CAEEL
ID XBP1_CAEEL Reviewed; 287 AA.
AC G5EE07; Q8WRF0;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 14-DEC-2011, sequence version 1.
DT 03-AUG-2022, entry version 93.
DE RecName: Full=X-box-binding protein 1 {ECO:0000312|WormBase:R74.3};
GN Name=xbp-1 {ECO:0000312|WormBase:R74.3};
GN ORFNames=R74.3 {ECO:0000312|WormBase:R74.3};
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:AAL60200.1, ECO:0000312|EMBL:AAL60201.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, DISRUPTION
RP PHENOTYPE, AND MUTAGENESIS OF 34-GLN--PRO-287.
RX PubMed=11780124; DOI=10.1038/415092a;
RA Calfon M., Zeng H., Urano F., Till J.H., Hubbard S.R., Harding H.P.,
RA Clark S.G., Ron D.;
RT "IRE1 couples endoplasmic reticulum load to secretory capacity by
RT processing the XBP-1 mRNA.";
RL Nature 415:92-96(2002).
RN [2] {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 [3] {ECO:0000305}
RP FUNCTION (ISOFORM 1), AND DISRUPTION PHENOTYPE.
RX PubMed=11779465; DOI=10.1016/s0092-8674(01)00612-2;
RA Shen X., Ellis R.E., Lee K., Liu C.-Y., Yang K., Solomon A., Yoshida H.,
RA Morimoto R., Kurnit D.M., Mori K., Kaufman R.J.;
RT "Complementary signaling pathways regulate the unfolded protein response
RT and are required for C. elegans development.";
RL Cell 107:893-903(2001).
RN [4] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=16184190; DOI=10.1371/journal.pgen.0010037;
RA Shen X., Ellis R.E., Sakaki K., Kaufman R.J.;
RT "Genetic interactions due to constitutive and inducible gene regulation
RT mediated by the unfolded protein response in C. elegans.";
RL PLoS Genet. 1:e37-e37(2005).
RN [5] {ECO:0000305}
RP FUNCTION, AND MUTAGENESIS OF 34-GLN--PRO-287.
RX PubMed=20182512; DOI=10.1038/nature08762;
RA Richardson C.E., Kooistra T., Kim D.H.;
RT "An essential role for XBP-1 in host protection against immune activation
RT in C. elegans.";
RL Nature 463:1092-1095(2010).
RN [6] {ECO:0000305}
RP FUNCTION, AND MUTAGENESIS OF 34-GLN--PRO-287.
RX PubMed=22125500; DOI=10.1371/journal.pgen.1002391;
RA Richardson C.E., Kinkel S., Kim D.H.;
RT "Physiological IRE-1-XBP-1 and PEK-1 signaling in Caenorhabditis elegans
RT larval development and immunity.";
RL PLoS Genet. 7:e1002391-e1002391(2011).
RN [7] {ECO:0000305}
RP FUNCTION (ISOFORM 2), AND MUTAGENESIS OF 34-GLN--PRO-287.
RX PubMed=23791175; DOI=10.1016/j.cell.2013.05.042;
RA Taylor R.C., Dillin A.;
RT "XBP-1 is a cell-nonautonomous regulator of stress resistance and
RT longevity.";
RL Cell 153:1435-1447(2013).
RN [8] {ECO:0000305}
RP INTERACTION WITH UBC-9(ISOFORM 1 AND ISOFORM 2), SUMOYLATED, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=24933177; DOI=10.1016/j.biocel.2014.06.005;
RA Lim Y., Lee D., Kalichamy K., Hong S.E., Michalak M., Ahnn J., Kim D.H.,
RA Lee S.K.;
RT "Sumoylation regulates ER stress response by modulating calreticulin gene
RT expression in XBP-1-dependent mode in Caenorhabditis elegans.";
RL Int. J. Biochem. Cell Biol. 53:399-408(2014).
RN [9] {ECO:0000305}
RP FUNCTION(ISOFORM 2), AND MUTAGENESIS OF 34-GLN--PRO-287.
RX PubMed=31315038; DOI=10.1016/j.celrep.2019.06.057;
RA Imanikia S., Sheng M., Castro C., Griffin J.L., Taylor R.C.;
RT "XBP-1 Remodels Lipid Metabolism to Extend Longevity.";
RL Cell Rep. 28:581-589.e4(2019).
RN [10] {ECO:0000305}
RP FUNCTION(ISOFORM 2), AND DISRUPTION PHENOTYPE.
RX PubMed=31303493; DOI=10.1016/j.cub.2019.06.031;
RA Imanikia S., Oezbey N.P., Krueger C., Casanueva M.O., Taylor R.C.;
RT "Neuronal XBP-1 Activates Intestinal Lysosomes to Improve Proteostasis in
RT C. elegans.";
RL Curr. Biol. 29:2322-2338.e7(2019).
RN [11]
RP FUNCTION (ISOFORM 2).
RX PubMed=31570707; DOI=10.1038/s41467-019-12070-3;
RA Waldherr S.M., Strovas T.J., Vadset T.A., Liachko N.F., Kraemer B.C.;
RT "Constitutive XBP-1s-mediated activation of the endoplasmic reticulum
RT unfolded protein response protects against pathological tau.";
RL Nat. Commun. 10:4443-4443(2019).
CC -!- FUNCTION: Required for transcriptional regulation of the unfolded
CC protein response (UPR) in the endoplasmic reticulum (ER) under stressed
CC conditions, acting downstream of ire-1, and also maintaining ER
CC homeostasis via a negative feedback loop, in parallel with ER kinase
CC pek-1 (PubMed:11780124, PubMed:11779465, PubMed:22125500,
CC PubMed:16184190). May also regulate Golgi protein trafficking distal to
CC the ER (PubMed:16184190). Protects the host organism from the
CC detrimental effects of mounting an innate immune response to microbes,
CC such as the Gram-negative bacterium P.aeruginosa, probably by
CC modulating the UPR (PubMed:20182512, PubMed:22125500).
CC {ECO:0000269|PubMed:11779465, ECO:0000269|PubMed:11780124,
CC ECO:0000269|PubMed:20182512, ECO:0000269|PubMed:22125500}.
CC -!- FUNCTION: [Isoform 1]: Plays a role in the unconventional cytoplasmic
CC splicing processing of its own mRNA triggered by the endoplasmic
CC reticulum (ER) transmembrane endoribonuclease ire-1: upon ER stress,
CC the emerging xbp-1 polypeptide chain, as part of a mRNA-ribosome-
CC nascent chain (R-RNC) complex, cotranslationally recruits its own
CC unprocessed mRNA through transient docking to the ER membrane and
CC translational pausing, therefore facilitating efficient ire-1-mediated
CC xbp-1 mRNA isoform 2 production. {ECO:0000250|UniProtKB:P17861}.
CC -!- FUNCTION: [Isoform 2]: Functions as a stress-inducible potent
CC transcriptional activator during endoplasmic reticulum (ER) stress by
CC inducing unfolded protein response (UPR) target genes via binding to
CC the UPR element (UPRE) (By similarity). Plays a role in modulation of
CC the UPR, lipid metabolism, proteostasis, and lifespan (PubMed:23791175,
CC PubMed:31303493, PubMed:31315038. PubMed:31570707). In neurons, rescues
CC stress resistance, increases longevity, and, drives expression of
CC lysosomal genes in the intestine and activates the UPR in distal, non-
CC neuronal cell types through a cell-nonautonomous mechanism
CC (PubMed:23791175, PubMed:31303493, PubMed:31315038). In neurons or
CC intestine, plays a role in protection against proteotoxicity, acting
CC via positive modulation of genes involved in lysosomal function,
CC including lipases and the fatty-acid desaturase fat-6 (PubMed:31303493,
CC PubMed:31315038). Protection against proteotoxicity in neurons is
CC dependent upon the transcription factor atf-6 (PubMed:31570707).
CC {ECO:0000250|UniProtKB:P17861, ECO:0000269|PubMed:23791175,
CC ECO:0000269|PubMed:31303493, ECO:0000269|PubMed:31315038}.
CC -!- SUBUNIT: [Isoform 1]: Interacts with SUMO-conjugating enzyme ubc-9; the
CC interaction is direct. {ECO:0000269|PubMed:24933177}.
CC -!- SUBUNIT: [Isoform 2]: Interacts with SUMO-conjugating enzyme ubc-9; the
CC interaction is direct. {ECO:0000269|PubMed:24933177}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00978}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1 {ECO:0000312|EMBL:AAL60200.1}; Synonyms=xbp-1u
CC {ECO:0000303|PubMed:22125500}, unspliced xbp-1
CC {ECO:0000303|PubMed:22125500};
CC IsoId=G5EE07-1; Sequence=Displayed;
CC Name=2 {ECO:0000312|EMBL:AAL60201.1}; Synonyms=xbp-1s
CC {ECO:0000303|PubMed:22125500}, spliced xbp-1
CC {ECO:0000303|PubMed:22125500};
CC IsoId=G5EE07-2; Sequence=VSP_061350;
CC -!- PTM: [Isoform 2]: Sumoylated (PubMed:24933177). Sumoylation may
CC negatively modulate the transcription of genes involved in the ER-
CC stress-response (PubMed:24933177). {ECO:0000269|PubMed:24933177}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown inhibits induction of
CC expression of the endoplasmic reticulum chaperone BiP homolog hsp-4 and
CC heat shock protein hsp-3 during the unfolded protein response (UPR)
CC (PubMed:11780124, PubMed:11779465). Larval development is normal, but
CC in a pek-1 genetic background, causes arrested development at or prior
CC to the L2 larval stage (PubMed:11779465). Abolishes crt-1 promoter
CC activity (PubMed:24933177). Reduces lifespan, perhaps acting
CC independently of macroautophagy (PubMed:31303493). In combination with
CC RNAi-mediated knockdown of atf-6, causes lethality early in larval
CC development (PubMed:16184190). Intestine-specific RNAi-mediated
CC knockdown prevents up-regulation of several lysosomal transcripts
CC (PubMed:31303493). {ECO:0000269|PubMed:11779465,
CC ECO:0000269|PubMed:11780124, ECO:0000269|PubMed:24933177,
CC ECO:0000269|PubMed:31303493}.
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DR EMBL; AF443190; AAL60200.1; -; mRNA.
DR EMBL; AF443191; AAL60201.1; -; mRNA.
DR EMBL; BX284603; CAL63999.1; -; Genomic_DNA.
DR RefSeq; NP_001076646.1; NM_001083177.3.
DR AlphaFoldDB; G5EE07; -.
DR SMR; G5EE07; -.
DR IntAct; G5EE07; 4.
DR EnsemblMetazoa; R74.3.1; R74.3.1; WBGene00006959. [G5EE07-1]
DR EnsemblMetazoa; R74.3.2; R74.3.2; WBGene00006959. [G5EE07-1]
DR GeneID; 175541; -.
DR KEGG; cel:CELE_R74.3; -.
DR CTD; 175541; -.
DR WormBase; R74.3; CE40514; WBGene00006959; xbp-1.
DR GeneTree; ENSGT00940000168780; -.
DR HOGENOM; CLU_708281_0_0_1; -.
DR Proteomes; UP000001940; Chromosome III.
DR Bgee; WBGene00006959; Expressed in pharyngeal muscle cell (C elegans) and 4 other tissues.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IEA:InterPro.
DR GO; GO:0050829; P:defense response to Gram-negative bacterium; IMP:UniProtKB.
DR GO; GO:0008340; P:determination of adult lifespan; IMP:UniProtKB.
DR GO; GO:0055088; P:lipid homeostasis; IMP:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR GO; GO:0006990; P:positive regulation of transcription from RNA polymerase II promoter involved in unfolded protein response; IMP:WormBase.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; IMP:UniProtKB.
DR GO; GO:0009408; P:response to heat; IGI:UniProtKB.
DR GO; GO:0035966; P:response to topologically incorrect protein; IMP:UniProtKB.
DR InterPro; IPR004827; bZIP.
DR InterPro; IPR046347; bZIP_sf.
DR Pfam; PF07716; bZIP_2; 1.
DR SMART; SM00338; BRLZ; 1.
DR SUPFAM; SSF57959; SSF57959; 1.
DR PROSITE; PS50217; BZIP; 1.
DR PROSITE; PS00036; BZIP_BASIC; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; DNA-binding; Nucleus; Reference proteome;
KW Transcription; Transcription regulation; Ubl conjugation.
FT CHAIN 1..287
FT /note="X-box-binding protein 1"
FT /id="PRO_0000454499"
FT DOMAIN 61..117
FT /note="bZIP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 63..88
FT /note="Basic motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 63..87
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 89..117
FT /note="Leucine-zipper"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT VAR_SEQ 175..287
FT /note="AFINEPQQWEQARSTSINNNISNQLRRMDSKKNNTISVDMYLTIISILCNHM
FT DRNKKMDTSNKSSNISRAQAESSIDSLLATLRKEQTVMQRLVQADPCTHLQKRVKHFRR
FT IP -> VGTGPIHLHQQQHQQPTPSYGFQEEQHNQCGYVSNYHLDSMQPHGSQQEDGHL
FT EQILEHLKSPSGEFDRFVAGYIEEGADGYAASCSSGSMYTSSETRETLSPNSLACPRR
FT (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_061350"
FT MUTAGEN 34..287
FT /note="Missing: In zc12; strongly blocks hsp-4 mRNA
FT induction. Severely attenuates larval development and
FT growth, and causes disruption of ER homeostasis, when
FT exposed to Gram-negative bacterium P.aeruginosa PA14; this
FT effect is abrogated in a pmk-1 mutant background. Disrupts
FT ER homeostasis and larval development, in the absence of
FT pathogenic bacteria, when combined with RNAi-mediated
FT knockdown of vhp-1, in a pmk-1-dependent manner. Increases
FT constitutive ire-1 splicing activity, in a smg-2 mutant
FT background. Positively modulates pek-1-mediated
FT phosphorylation of the alpha subunit of eukaryotic
FT translation-initiation factor 2 (eIF2alpha). Increases
FT longevity by oleic acid (OA) dietary supplementation."
FT /evidence="ECO:0000269|PubMed:11780124,
FT ECO:0000269|PubMed:20182512, ECO:0000269|PubMed:22125500,
FT ECO:0000269|PubMed:23791175, ECO:0000269|PubMed:31315038"
SQ SEQUENCE 287 AA; 33326 MW; 7AAA7B4C4F1E9CAD CRC64;
MSNYPKRIYV LPARHVAAPQ PQRMAPKRAL PTEQVVAQLL GDDMGPSGPR KRERLNHLSQ
EEKMDRRKLK NRVAAQNARD KKKERSAKIE DVMRDLVEEN RRLRAENERL RRQNKNLMNQ
QNESVMYMEE NNENLMNSND ACIYQNVVYE EEVVGEVAPV VVVGGEDRRA FESAAFINEP
QQWEQARSTS INNNISNQLR RMDSKKNNTI SVDMYLTIIS ILCNHMDRNK KMDTSNKSSN
ISRAQAESSI DSLLATLRKE QTVMQRLVQA DPCTHLQKRV KHFRRIP
