XBP1 (X-box binding protein 1) is a basic-leucine zipper (bZIP) transcription factor and the transcriptional effector of the IRE1 branch of the endoplasmic reticulum (ER) unfolded protein response (UPR). Its mRNA is induced by ATF6 and, under ER stress, is spliced in the cytoplasm by the ER-membrane endoribonuclease IRE1alpha (ERN1), which removes a 26-nucleotide intron; RtcB ligation produces a frameshifted mRNA encoding XBP1s, which carries a C-terminal transactivation domain and nuclear localization signal. Nuclear XBP1s binds UPR elements, ER stress response elements and CRE-like sequences, often as homodimers or heterodimers with ATF6 and other bZIP proteins, and activates transcription of genes for ER chaperones, ER-associated degradation, phospholipid synthesis and ER expansion. The unspliced product XBP1u is a short-lived protein that cotranslationally targets its own mRNA to the ER membrane to facilitate splicing, is cleaved by signal peptide peptidase, and acts as a negative feedback regulator by sequestering XBP1s for proteasomal degradation. Through these activities XBP1 is required for differentiation and function of professional secretory cells, notably plasma cells, and contributes to hepatic lipogenesis, adipogenesis, glucose homeostasis and endothelial proliferation and angiogenesis.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000977 RNA polymerase II transcription regulatory region sequence-specific DNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: XBP1 is a bZIP protein that binds specific cis-regulatory DNA elements (UPRE/ERSE, CRE-like elements, the HTLV-1 21-bp repeat and MHC class II X2 box). Reason: Sequence-specific DNA binding is the defining biochemical activity of the XBP1 bZIP domain and is supported by multiple direct binding assays and by phylogeny (IBA). Supporting Evidence: PMID:8657566 The results indicated that hXBP-1 binds preferably to the CRE-like element GAT-GACGTG(T/G)NNN(A/T)T, wherein the core sequence ACGT is highly conserved file:human/XBP1/XBP1-uniprot.txt Binds the Tax-responsive element (TRE) present in the long terminal repeat (LTR) of T-cell leukemia virus type 1 (HTLV-I) and to the TPA response elements (TRE) file:human/XBP1/XBP1-uniprot.txt [Isoform 2]: Functions as a stress-inducible potent transcriptional activator during endoplasmic reticulum (ER) stress by inducing unfolded protein response (UPR) target genes via binding to the UPR element (UPRE). Up-regulates target genes encoding ER chaperones and ER-associated degradation (ERAD) components |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | ISS GO_REF:0000024 | ACCEPT | Summary: XBP1 is a bZIP protein that binds specific cis-regulatory DNA elements (UPRE/ERSE, CRE-like elements, the HTLV-1 21-bp repeat and MHC class II X2 box). Reason: Sequence-specific DNA binding is the defining biochemical activity of the XBP1 bZIP domain and is supported by multiple direct binding assays and by phylogeny (IBA). Supporting Evidence: PMID:8657566 The results indicated that hXBP-1 binds preferably to the CRE-like element GAT-GACGTG(T/G)NNN(A/T)T, wherein the core sequence ACGT is highly conserved file:human/XBP1/XBP1-uniprot.txt Binds the Tax-responsive element (TRE) present in the long terminal repeat (LTR) of T-cell leukemia virus type 1 (HTLV-I) and to the TPA response elements (TRE) file:human/XBP1/XBP1-uniprot.txt [Isoform 2]: Functions as a stress-inducible potent transcriptional activator during endoplasmic reticulum (ER) stress by inducing unfolded protein response (UPR) target genes via binding to the UPR element (UPRE). Up-regulates target genes encoding ER chaperones and ER-associated degradation (ERAD) components |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IBA GO_REF:0000033 | MODIFY | Summary: XBP1 (notably the spliced XBP1s isoform) is a DNA-binding transcription factor acting at RNA polymerase II promoters. Reason: Core molecular function of XBP1, well supported experimentally and phylogenetically. The evidence shows XBP1 (especially spliced XBP1s) acts as an RNA polymerase II transcriptional activator, so the more specific activator term is proposed. Proposed replacements: DNA-binding transcription activator activity, RNA polymerase II-specific Supporting Evidence: file:human/XBP1/XBP1-uniprot.txt [Isoform 2]: Functions as a stress-inducible potent transcriptional activator during endoplasmic reticulum (ER) stress by inducing unfolded protein response (UPR) target genes via binding to the UPR element (UPRE). Up-regulates target genes encoding ER chaperones and ER-associated degradation (ERAD) components PMID:11779464 Here, we identified the transcription factor XBP1, a target of ATF6, as a mammalian substrate of such an unconventional mRNA splicing system and showed that only the spliced form of XBP1 can activate the UPR efficiently. |
| GO:0000987 cis-regulatory region sequence-specific DNA binding | IDA PMID:2196176 Multiple cDNA clones encoding nuclear proteins that bind to ... | ACCEPT | Summary: XBP1 is a bZIP protein that binds specific cis-regulatory DNA elements (UPRE/ERSE, CRE-like elements, the HTLV-1 21-bp repeat and MHC class II X2 box). Reason: Sequence-specific DNA binding is the defining biochemical activity of the XBP1 bZIP domain and is supported by multiple direct binding assays and by phylogeny (IBA). Supporting Evidence: PMID:2196176 All three proteins, TREB5, TREB7 and TREB36, contained a leucine zipper structure and basic amino acid domain, which are conserved in FOS, JUN and CREB PMID:2196176 The proteins expressed in Escherichia coli bound to the p40tax-dependent enhancer of the 21 bp sequence |
| GO:0001525 angiogenesis | ISS GO_REF:0000024 | MODIFY | Summary: ISS transfer of angiogenesis from mouse Xbp1. Reason: XBP1 promotes angiogenesis indirectly, as a transcriptional regulator downstream of VEGF/IRE1 in endothelial cells; it does not itself perform angiogenesis. The regulatory term (also annotated by IMP) is more accurate. Non-core. Proposed replacements: positive regulation of angiogenesis Supporting Evidence: PMID:25656649 Mechanistically, miR-214 overexpression reduces angiogenesis of HUVECs by targeting XBP1, an important transcription factor of unfolded protein response, and XBP1 silencing decreases HUVECs proliferation and angiogenesis similar to miR-214 overexpression. Furthermore, ectopic expression of XBP1 enhances endothelial cells proliferation and tube formation |
| GO:0001889 liver development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Sequence-similarity transfer from mouse Xbp1 for 'liver development', reflecting a physiological, tissue-specific output of the XBP1 transcriptional program. Reason: Mouse genetic studies place XBP1 in this physiological context, mostly via transcriptional control of secretory, lipogenic or differentiation genes. The transfer to the human ortholog is reasonable, but this is a downstream, context-specific role rather than a core function. Supporting Evidence: file:human/XBP1/XBP1-uniprot.txt Required for cardiac myogenesis and hepatogenesis during embryonic development, and the development of secretory tissues such as exocrine pancreas and salivary gland (By similarity). |
| GO:0002639 positive regulation of immunoglobulin production | IDA PMID:11460154 Plasma cell differentiation requires the transcription facto... | KEEP AS NON CORE | Summary: XBP1-deficient lymphoid chimaeras secrete very little immunoglobulin because plasma cells are absent. Reason: Well supported physiological role in plasma cells; downstream of the core transcription factor function. Supporting Evidence: PMID:11460154 However, they secreted very little immunoglobulin of any isotype and failed to control infection with the B-cell-dependent polyoma virus, because plasma cells were markedly absent. |
| GO:0002639 positive regulation of immunoglobulin production | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Sequence-similarity transfer from mouse Xbp1 for 'positive regulation of immunoglobulin production', reflecting a physiological, tissue-specific output of the XBP1 transcriptional program. Reason: Mouse genetic studies place XBP1 in this physiological context, mostly via transcriptional control of secretory, lipogenic or differentiation genes. The transfer to the human ortholog is reasonable, but this is a downstream, context-specific role rather than a core function. Supporting Evidence: file:human/XBP1/XBP1-uniprot.txt Plays a role in the production of immunoglobulins and interleukin-6 in the presence of stimuli required for plasma cell differentiation (By similarity). |
| GO:0003700 DNA-binding transcription factor activity | IDA PMID:1903538 Human X-box-binding protein 1 is required for the transcript... | MODIFY | Summary: XBP1 (notably the spliced XBP1s isoform) is a DNA-binding transcription factor acting at RNA polymerase II promoters. Reason: Core molecular function of XBP1, well supported experimentally and phylogenetically. The evidence shows XBP1 (especially spliced XBP1s) acts as an RNA polymerase II transcriptional activator, so the more specific activator term is proposed. Proposed replacements: DNA-binding transcription activator activity, RNA polymerase II-specific Supporting Evidence: PMID:1903538 These data suggest that the hXBP-1 c-fos heterodimer is critical for the transcription of a subset of the human class II major histocompatibility complex genes PMID:11779464 Here, we identified the transcription factor XBP1, a target of ATF6, as a mammalian substrate of such an unconventional mRNA splicing system and showed that only the spliced form of XBP1 can activate the UPR efficiently. |
| GO:0003700 DNA-binding transcription factor activity | IDA PMID:8657566 The basic domain/leucine zipper protein hXBP-1 preferentiall... | MODIFY | Summary: XBP1 (notably the spliced XBP1s isoform) is a DNA-binding transcription factor acting at RNA polymerase II promoters. Reason: Core molecular function of XBP1, well supported experimentally and phylogenetically. The evidence shows XBP1 (especially spliced XBP1s) acts as an RNA polymerase II transcriptional activator, so the more specific activator term is proposed. Proposed replacements: DNA-binding transcription activator activity, RNA polymerase II-specific Supporting Evidence: PMID:8657566 hXBP-1 can transactivate multimers of the target sequences to which it binds in COS cells, and the level of transactivation directly correlates with the extent of binding as observed in gel retardation experiments. PMID:11779464 Here, we identified the transcription factor XBP1, a target of ATF6, as a mammalian substrate of such an unconventional mRNA splicing system and showed that only the spliced form of XBP1 can activate the UPR efficiently. |
| GO:0003700 DNA-binding transcription factor activity | IEA GO_REF:0000120 | MODIFY | Summary: XBP1 (notably the spliced XBP1s isoform) is a DNA-binding transcription factor acting at RNA polymerase II promoters. Reason: Core molecular function of XBP1, well supported experimentally and phylogenetically. The evidence shows XBP1 (especially spliced XBP1s) acts as an RNA polymerase II transcriptional activator, so the more specific activator term is proposed. Proposed replacements: DNA-binding transcription activator activity, RNA polymerase II-specific Supporting Evidence: file:human/XBP1/XBP1-uniprot.txt [Isoform 2]: Functions as a stress-inducible potent transcriptional activator during endoplasmic reticulum (ER) stress by inducing unfolded protein response (UPR) target genes via binding to the UPR element (UPRE). Up-regulates target genes encoding ER chaperones and ER-associated degradation (ERAD) components PMID:11779464 Here, we identified the transcription factor XBP1, a target of ATF6, as a mammalian substrate of such an unconventional mRNA splicing system and showed that only the spliced form of XBP1 can activate the UPR efficiently. |
| GO:0005515 protein binding | IPI PMID:20102225 Identification of bZIP interaction partners of viral protein... | MODIFY | Summary: Coiled-coil/bZIP interaction arrays detect XBP1 leucine-zipper heterodimerization with other bZIP proteins (ATF6, ATF6B, CREBZF). Reason: Generic protein binding is uninformative; these interactions are bZIP leucine-zipper heterodimers, best captured as protein heterodimerization activity. Proposed replacements: protein heterodimerization activity Supporting Evidence: PMID:20102225 We investigated the interaction specificity of these four viral bZIPs by using coiled-coil arrays to assess self-associations as well as heterointeractions with 33 representative human bZIPs. file:human/XBP1/XBP1-uniprot.txt P17861; P18850: ATF6; NbExp=4 file:human/XBP1/XBP1-uniprot.txt P17861; Q9NS37: CREBZF; NbExp=4 |
| GO:0005515 protein binding | IPI PMID:20102225 Identification of bZIP interaction partners of viral protein... | MODIFY | Summary: Coiled-coil/bZIP interaction arrays detect XBP1 leucine-zipper heterodimerization with other bZIP proteins (ATF6, ATF6B, CREBZF). Reason: Generic protein binding is uninformative; these interactions are bZIP leucine-zipper heterodimers, best captured as protein heterodimerization activity. Proposed replacements: protein heterodimerization activity Supporting Evidence: PMID:20102225 We investigated the interaction specificity of these four viral bZIPs by using coiled-coil arrays to assess self-associations as well as heterointeractions with 33 representative human bZIPs. file:human/XBP1/XBP1-uniprot.txt P17861; P18850: ATF6; NbExp=4 file:human/XBP1/XBP1-uniprot.txt P17861; Q9NS37: CREBZF; NbExp=4 |
| GO:0005515 protein binding | IPI PMID:23661758 Networks of bZIP protein-protein interactions diversified ov... | MODIFY | Summary: Coiled-coil/bZIP interaction arrays detect XBP1 leucine-zipper heterodimerization with other bZIP proteins (ATF6, ATF6B, CREBZF). Reason: Generic protein binding is uninformative; these interactions are bZIP leucine-zipper heterodimers, best captured as protein heterodimerization activity. Proposed replacements: protein heterodimerization activity Supporting Evidence: PMID:23661758 We studied the basic region-leucine zipper (bZIP) transcription factors and quantified bZIP dimerization networks for five metazoan and two single-cell species, measuring interactions in vitro for 2891 protein pairs. file:human/XBP1/XBP1-uniprot.txt P17861; P18850: ATF6; NbExp=4 file:human/XBP1/XBP1-uniprot.txt P17861; Q9NS37: CREBZF; NbExp=4 |
| GO:0005515 protein binding | IPI PMID:23661758 Networks of bZIP protein-protein interactions diversified ov... | MODIFY | Summary: Coiled-coil/bZIP interaction arrays detect XBP1 leucine-zipper heterodimerization with other bZIP proteins (ATF6, ATF6B, CREBZF). Reason: Generic protein binding is uninformative; these interactions are bZIP leucine-zipper heterodimers, best captured as protein heterodimerization activity. Proposed replacements: protein heterodimerization activity Supporting Evidence: PMID:23661758 We studied the basic region-leucine zipper (bZIP) transcription factors and quantified bZIP dimerization networks for five metazoan and two single-cell species, measuring interactions in vitro for 2891 protein pairs. file:human/XBP1/XBP1-uniprot.txt P17861; P18850: ATF6; NbExp=4 file:human/XBP1/XBP1-uniprot.txt P17861; Q9NS37: CREBZF; NbExp=4 |
| GO:0005515 protein binding | IPI PMID:23661758 Networks of bZIP protein-protein interactions diversified ov... | MODIFY | Summary: Coiled-coil/bZIP interaction arrays detect XBP1 leucine-zipper heterodimerization with other bZIP proteins (ATF6, ATF6B, CREBZF). Reason: Generic protein binding is uninformative; these interactions are bZIP leucine-zipper heterodimers, best captured as protein heterodimerization activity. Proposed replacements: protein heterodimerization activity Supporting Evidence: PMID:23661758 We studied the basic region-leucine zipper (bZIP) transcription factors and quantified bZIP dimerization networks for five metazoan and two single-cell species, measuring interactions in vitro for 2891 protein pairs. file:human/XBP1/XBP1-uniprot.txt P17861; P18850: ATF6; NbExp=4 file:human/XBP1/XBP1-uniprot.txt P17861; Q9NS37: CREBZF; NbExp=4 |
| GO:0005515 protein binding | IPI PMID:24670641 XBP1 promotes triple-negative breast cancer by controlling t... | REMOVE | Summary: IPI evidence for interaction with HIF1A. Reason: Generic protein binding is uninformative about XBP1 molecular function; removal does not imply the interaction is false. Supporting Evidence: file:human/XBP1/XBP1-uniprot.txt Functions as a transcription factor during endoplasmic reticulum (ER) stress by regulating the unfolded protein response (UPR). |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: IPI evidence for interaction with UBE2V1 (binary interactome screen). Reason: Generic protein binding is uninformative about XBP1 molecular function; removal does not imply the interaction is false. Supporting Evidence: file:human/XBP1/XBP1-uniprot.txt Functions as a transcription factor during endoplasmic reticulum (ER) stress by regulating the unfolded protein response (UPR). |
| GO:0005634 nucleus | EXP PMID:19394296 Cotranslational targeting of XBP1 protein to the membrane pr... | ACCEPT | Summary: XBP1s carries a nuclear localization signal and acts in the nucleus as a transcription factor; XBP1u shuttles between nucleus and cytoplasm. Reason: Nucleus is the core site of XBP1 transcription factor activity. Supporting Evidence: PMID:19394296 We show that the unspliced XBP1 (XBP1u) mRNA is localized to the membrane, although its product is neither a secretory nor a membrane protein and is released to the cytosol after splicing. |
| GO:0005634 nucleus | EXP PMID:20348923 A regulatory subunit of phosphoinositide 3-kinase increases ... | ACCEPT | Summary: XBP1s carries a nuclear localization signal and acts in the nucleus as a transcription factor; XBP1u shuttles between nucleus and cytoplasm. Reason: Nucleus is the core site of XBP1 transcription factor activity. Supporting Evidence: PMID:20348923 Cell lines with knockout or knockdown of p85alphaalpha show marked alterations in the UPR, including reduced ER stress-dependent accumulation of nuclear XBP-1, decreased induction of UPR target genes and increased rates of apoptosis. |
| GO:0005634 nucleus | EXP PMID:20955178 Regulation of unfolded protein response modulator XBP1s by a... | ACCEPT | Summary: XBP1s carries a nuclear localization signal and acts in the nucleus as a transcription factor; XBP1u shuttles between nucleus and cytoplasm. Reason: Nucleus is the core site of XBP1 transcription factor activity. Supporting Evidence: PMID:20955178 p300 increases the acetylation and protein stability of XBP1s, and enhances its transcriptional activity, whereas SIRT1 deacetylates XBP1s and inhibits its transcriptional activity. |
| GO:0005634 nucleus | EXP PMID:25239945 Signal peptide peptidase functions in ERAD to cleave the unf... | ACCEPT | Summary: XBP1s carries a nuclear localization signal and acts in the nucleus as a transcription factor; XBP1u shuttles between nucleus and cytoplasm. Reason: Nucleus is the core site of XBP1 transcription factor activity. Supporting Evidence: PMID:25239945 Furthermore, we show that XBP1u inhibits the UPR transcription factor XBP1s by targeting it toward proteasomal degradation. |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: XBP1s carries a nuclear localization signal and acts in the nucleus as a transcription factor; XBP1u shuttles between nucleus and cytoplasm. Reason: Nucleus is the core site of XBP1 transcription factor activity. Supporting Evidence: PMID:16461360 The transcription factor protein (p) XBP1 spliced (S), which is translated from mature XBP1 mRNA, contains the nuclear localization signal and the transcriptional activation domain and activates the transcription of target genes, including those encoding ER chaperones in the nucleus. |
| GO:0005634 nucleus | IDA GO_REF:0000054 | ACCEPT | Summary: XBP1s carries a nuclear localization signal and acts in the nucleus as a transcription factor; XBP1u shuttles between nucleus and cytoplasm. Reason: Nucleus is the core site of XBP1 transcription factor activity. Supporting Evidence: PMID:16461360 The transcription factor protein (p) XBP1 spliced (S), which is translated from mature XBP1 mRNA, contains the nuclear localization signal and the transcriptional activation domain and activates the transcription of target genes, including those encoding ER chaperones in the nucleus. |
| GO:0005634 nucleus | IDA PMID:16461360 pXBP1(U) encoded in XBP1 pre-mRNA negatively regulates unfol... | ACCEPT | Summary: XBP1s carries a nuclear localization signal and acts in the nucleus as a transcription factor; XBP1u shuttles between nucleus and cytoplasm. Reason: Nucleus is the core site of XBP1 transcription factor activity. Supporting Evidence: PMID:16461360 The transcription factor protein (p) XBP1 spliced (S), which is translated from mature XBP1 mRNA, contains the nuclear localization signal and the transcriptional activation domain and activates the transcription of target genes, including those encoding ER chaperones in the nucleus. |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: XBP1s carries a nuclear localization signal and acts in the nucleus as a transcription factor; XBP1u shuttles between nucleus and cytoplasm. Reason: Nucleus is the core site of XBP1 transcription factor activity. Supporting Evidence: PMID:16461360 The transcription factor protein (p) XBP1 spliced (S), which is translated from mature XBP1 mRNA, contains the nuclear localization signal and the transcriptional activation domain and activates the transcription of target genes, including those encoding ER chaperones in the nucleus. |
| GO:0005634 nucleus | NAS PMID:23661758 Networks of bZIP protein-protein interactions diversified ov... | ACCEPT | Summary: XBP1s carries a nuclear localization signal and acts in the nucleus as a transcription factor; XBP1u shuttles between nucleus and cytoplasm. Reason: Nucleus is the core site of XBP1 transcription factor activity. Supporting Evidence: PMID:16461360 The transcription factor protein (p) XBP1 spliced (S), which is translated from mature XBP1 mRNA, contains the nuclear localization signal and the transcriptional activation domain and activates the transcription of target genes, including those encoding ER chaperones in the nucleus. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-1791121 | ACCEPT | Summary: XBP1s carries a nuclear localization signal and acts in the nucleus as a transcription factor; XBP1u shuttles between nucleus and cytoplasm. Reason: Nucleus is the core site of XBP1 transcription factor activity. Supporting Evidence: PMID:16461360 The transcription factor protein (p) XBP1 spliced (S), which is translated from mature XBP1 mRNA, contains the nuclear localization signal and the transcriptional activation domain and activates the transcription of target genes, including those encoding ER chaperones in the nucleus. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-381203 | ACCEPT | Summary: XBP1s carries a nuclear localization signal and acts in the nucleus as a transcription factor; XBP1u shuttles between nucleus and cytoplasm. Reason: Nucleus is the core site of XBP1 transcription factor activity. Supporting Evidence: PMID:16461360 The transcription factor protein (p) XBP1 spliced (S), which is translated from mature XBP1 mRNA, contains the nuclear localization signal and the transcriptional activation domain and activates the transcription of target genes, including those encoding ER chaperones in the nucleus. |
| GO:0005737 cytoplasm | EXP PMID:16461360 pXBP1(U) encoded in XBP1 pre-mRNA negatively regulates unfol... | KEEP AS NON CORE | Summary: The unspliced XBP1u protein is largely cytoplasmic (with a nuclear exclusion signal) and sequesters XBP1s in the cytoplasm for degradation. Reason: Correct for the XBP1u isoform and for XBP1s-XBP1u complexes; secondary to the nuclear site of XBP1s activity. Supporting Evidence: PMID:16461360 pXBP1(U) contained the nuclear exclusion signal instead of the transcriptional activation domain and shuttled between the nucleus and the cytoplasm. |
| GO:0005737 cytoplasm | EXP PMID:19394296 Cotranslational targeting of XBP1 protein to the membrane pr... | KEEP AS NON CORE | Summary: The unspliced XBP1u protein is largely cytoplasmic (with a nuclear exclusion signal) and sequesters XBP1s in the cytoplasm for degradation. Reason: Correct for the XBP1u isoform and for XBP1s-XBP1u complexes; secondary to the nuclear site of XBP1s activity. Supporting Evidence: PMID:19394296 We show that the unspliced XBP1 (XBP1u) mRNA is localized to the membrane, although its product is neither a secretory nor a membrane protein and is released to the cytosol after splicing. |
| GO:0005737 cytoplasm | EXP PMID:20348923 A regulatory subunit of phosphoinositide 3-kinase increases ... | KEEP AS NON CORE | Summary: The unspliced XBP1u protein is largely cytoplasmic (with a nuclear exclusion signal) and sequesters XBP1s in the cytoplasm for degradation. Reason: Correct for the XBP1u isoform and for XBP1s-XBP1u complexes; secondary to the nuclear site of XBP1s activity. Supporting Evidence: PMID:16461360 pXBP1(U) contained the nuclear exclusion signal instead of the transcriptional activation domain and shuttled between the nucleus and the cytoplasm. |
| GO:0005737 cytoplasm | EXP PMID:25190803 Unspliced X-box-binding protein 1 (XBP1) protects endothelia... | KEEP AS NON CORE | Summary: The unspliced XBP1u protein is largely cytoplasmic (with a nuclear exclusion signal) and sequesters XBP1s in the cytoplasm for degradation. Reason: Correct for the XBP1u isoform and for XBP1s-XBP1u complexes; secondary to the nuclear site of XBP1s activity. Supporting Evidence: PMID:25190803 In this study, we found that disturbed flow activated anti-oxidative reactions via up-regulating heme oxygenase 1 (HO-1) in an X-box-binding protein 1 (XBP1) and histone deacetylase 3 (HDAC3)-dependent manner. |
| GO:0005737 cytoplasm | EXP PMID:25239945 Signal peptide peptidase functions in ERAD to cleave the unf... | KEEP AS NON CORE | Summary: The unspliced XBP1u protein is largely cytoplasmic (with a nuclear exclusion signal) and sequesters XBP1s in the cytoplasm for degradation. Reason: Correct for the XBP1u isoform and for XBP1s-XBP1u complexes; secondary to the nuclear site of XBP1s activity. Supporting Evidence: PMID:25239945 Furthermore, we show that XBP1u inhibits the UPR transcription factor XBP1s by targeting it toward proteasomal degradation. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: The unspliced XBP1u protein is largely cytoplasmic (with a nuclear exclusion signal) and sequesters XBP1s in the cytoplasm for degradation. Reason: Correct for the XBP1u isoform and for XBP1s-XBP1u complexes; secondary to the nuclear site of XBP1s activity. Supporting Evidence: PMID:16461360 pXBP1(U) contained the nuclear exclusion signal instead of the transcriptional activation domain and shuttled between the nucleus and the cytoplasm. |
| GO:0005737 cytoplasm | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: The unspliced XBP1u protein is largely cytoplasmic (with a nuclear exclusion signal) and sequesters XBP1s in the cytoplasm for degradation. Reason: Correct for the XBP1u isoform and for XBP1s-XBP1u complexes; secondary to the nuclear site of XBP1s activity. Supporting Evidence: PMID:16461360 pXBP1(U) contained the nuclear exclusion signal instead of the transcriptional activation domain and shuttled between the nucleus and the cytoplasm. |
| GO:0005737 cytoplasm | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: The unspliced XBP1u protein is largely cytoplasmic (with a nuclear exclusion signal) and sequesters XBP1s in the cytoplasm for degradation. Reason: Correct for the XBP1u isoform and for XBP1s-XBP1u complexes; secondary to the nuclear site of XBP1s activity. Supporting Evidence: PMID:16461360 pXBP1(U) contained the nuclear exclusion signal instead of the transcriptional activation domain and shuttled between the nucleus and the cytoplasm. |
| GO:0005737 cytoplasm | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: The unspliced XBP1u protein is largely cytoplasmic (with a nuclear exclusion signal) and sequesters XBP1s in the cytoplasm for degradation. Reason: Correct for the XBP1u isoform and for XBP1s-XBP1u complexes; secondary to the nuclear site of XBP1s activity. Supporting Evidence: PMID:16461360 pXBP1(U) contained the nuclear exclusion signal instead of the transcriptional activation domain and shuttled between the nucleus and the cytoplasm. |
| GO:0005783 endoplasmic reticulum | IDA PMID:23529610 Vascular endothelial cell growth-activated XBP1 splicing in ... | KEEP AS NON CORE | Summary: XBP1u is targeted to the ER membrane cotranslationally via a hydrophobic region (a type II transmembrane-like segment), which recruits its own mRNA to IRE1 for splicing; it is cleaved there by signal peptide peptidase. Reason: Membrane/ER association is real for the XBP1u isoform and facilitates XBP1 mRNA splicing, but it is not where the core transcription factor function is exercised. Supporting Evidence: PMID:23529610 We found that vascular endothelial cell growth factor induced the kinase insert domain receptor internalization and interaction through C-terminal domain with the unspliced XBP1 and the inositol requiring enzyme 1 Ξ± in the endoplasmic reticulum |
| GO:0005783 endoplasmic reticulum | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: XBP1u is targeted to the ER membrane cotranslationally via a hydrophobic region (a type II transmembrane-like segment), which recruits its own mRNA to IRE1 for splicing; it is cleaved there by signal peptide peptidase. Reason: Membrane/ER association is real for the XBP1u isoform and facilitates XBP1 mRNA splicing, but it is not where the core transcription factor function is exercised. Supporting Evidence: PMID:25239945 Cleavage occurs within a so far unrecognized type II transmembrane domain, which renders XBP1u as an SPP substrate through specific sequence features. file:human/XBP1/XBP1-uniprot.txt upon ER stress, the emerging XBP1 polypeptide chain, as part of a mRNA-ribosome-nascent chain (R-RNC) complex, cotranslationally recruits its own unprocessed mRNA through transient docking to the ER membrane |
| GO:0005789 endoplasmic reticulum membrane | EXP PMID:25239945 Signal peptide peptidase functions in ERAD to cleave the unf... | KEEP AS NON CORE | Summary: XBP1u is targeted to the ER membrane cotranslationally via a hydrophobic region (a type II transmembrane-like segment), which recruits its own mRNA to IRE1 for splicing; it is cleaved there by signal peptide peptidase. Reason: Membrane/ER association is real for the XBP1u isoform and facilitates XBP1 mRNA splicing, but it is not where the core transcription factor function is exercised. Supporting Evidence: PMID:25239945 Cleavage occurs within a so far unrecognized type II transmembrane domain, which renders XBP1u as an SPP substrate through specific sequence features. file:human/XBP1/XBP1-uniprot.txt upon ER stress, the emerging XBP1 polypeptide chain, as part of a mRNA-ribosome-nascent chain (R-RNC) complex, cotranslationally recruits its own unprocessed mRNA through transient docking to the ER membrane |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: XBP1u is targeted to the ER membrane cotranslationally via a hydrophobic region (a type II transmembrane-like segment), which recruits its own mRNA to IRE1 for splicing; it is cleaved there by signal peptide peptidase. Reason: Membrane/ER association is real for the XBP1u isoform and facilitates XBP1 mRNA splicing, but it is not where the core transcription factor function is exercised. Supporting Evidence: PMID:25239945 Cleavage occurs within a so far unrecognized type II transmembrane domain, which renders XBP1u as an SPP substrate through specific sequence features. file:human/XBP1/XBP1-uniprot.txt upon ER stress, the emerging XBP1 polypeptide chain, as part of a mRNA-ribosome-nascent chain (R-RNC) complex, cotranslationally recruits its own unprocessed mRNA through transient docking to the ER membrane |
| GO:0005789 endoplasmic reticulum membrane | NAS PMID:25239945 Signal peptide peptidase functions in ERAD to cleave the unf... | KEEP AS NON CORE | Summary: XBP1u is targeted to the ER membrane cotranslationally via a hydrophobic region (a type II transmembrane-like segment), which recruits its own mRNA to IRE1 for splicing; it is cleaved there by signal peptide peptidase. Reason: Membrane/ER association is real for the XBP1u isoform and facilitates XBP1 mRNA splicing, but it is not where the core transcription factor function is exercised. Supporting Evidence: PMID:25239945 Cleavage occurs within a so far unrecognized type II transmembrane domain, which renders XBP1u as an SPP substrate through specific sequence features. file:human/XBP1/XBP1-uniprot.txt upon ER stress, the emerging XBP1 polypeptide chain, as part of a mRNA-ribosome-nascent chain (R-RNC) complex, cotranslationally recruits its own unprocessed mRNA through transient docking to the ER membrane |
| GO:0006355 regulation of DNA-templated transcription | IEA GO_REF:0000002 | ACCEPT | Summary: XBP1s activates Pol II transcription of UPR target genes (ER chaperones, ERAD components, lipid synthesis genes). Reason: Core biological role of the XBP1 transcription factor. Supporting Evidence: file:human/XBP1/XBP1-uniprot.txt [Isoform 2]: Functions as a stress-inducible potent transcriptional activator during endoplasmic reticulum (ER) stress by inducing unfolded protein response (UPR) target genes via binding to the UPR element (UPRE). Up-regulates target genes encoding ER chaperones and ER-associated degradation (ERAD) components |
| GO:0006357 regulation of transcription by RNA polymerase II | NAS PMID:23661758 Networks of bZIP protein-protein interactions diversified ov... | ACCEPT | Summary: XBP1s activates Pol II transcription of UPR target genes (ER chaperones, ERAD components, lipid synthesis genes). Reason: Core biological role of the XBP1 transcription factor. Supporting Evidence: PMID:23661758 We studied the basic region-leucine zipper (bZIP) transcription factors and quantified bZIP dimerization networks for five metazoan and two single-cell species, measuring interactions in vitro for 2891 protein pairs. |
| GO:0006366 transcription by RNA polymerase II | ISS GO_REF:0000024 | MODIFY | Summary: ISS transfer of transcription by RNA polymerase II. Reason: XBP1 is a sequence-specific activator, so the regulatory term positive regulation of transcription by RNA polymerase II better describes its role than the core transcription process itself. Proposed replacements: positive regulation of transcription by RNA polymerase II Supporting Evidence: file:human/XBP1/XBP1-uniprot.txt [Isoform 2]: Functions as a stress-inducible potent transcriptional activator during endoplasmic reticulum (ER) stress by inducing unfolded protein response (UPR) target genes via binding to the UPR element (UPRE). Up-regulates target genes encoding ER chaperones and ER-associated degradation (ERAD) components |
| GO:0006511 ubiquitin-dependent protein catabolic process | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: ISS transfer of ubiquitin-dependent protein catabolic process from mouse Xbp1. Reason: XBP1 promotes proteasomal degradation of partners (XBP1u targeting XBP1s; XBP1s promoting FOXO1 degradation) but does not itself carry out ubiquitin-dependent catabolism; at most a regulatory role. Supporting Evidence: file:human/XBP1/XBP1-uniprot.txt Functions as a negative feed-back regulator of the potent transcription factor XBP1 isoform 2 protein levels through proteasome-mediated degradation file:human/XBP1/XBP1-uniprot.txt Also improves glucose homeostasis in an ER stress- and/or insulin-independent manner through both binding and proteasome-induced degradation of the transcription factor FOXO1 |
| GO:0006633 fatty acid biosynthetic process | TAS PMID:22013210 The unfolded protein response: integrating stress signals th... | MARK AS OVER ANNOTATED | Summary: TAS from a review: XBP1 regulates lipid synthesis genes. Reason: XBP1 regulates expression of lipogenic and phospholipid synthesis genes; it is not an enzyme of fatty acid biosynthesis. A positive regulation term would be appropriate. Supporting Evidence: file:human/XBP1/XBP1-uniprot.txt Controls the induction of de novo fatty acid synthesis in hepatocytes by regulating the expression of a subset of lipogenic genes in an ER stress- and UPR-independent manner |
| GO:0006955 immune response | TAS PMID:22013210 The unfolded protein response: integrating stress signals th... | MARK AS OVER ANNOTATED | Summary: TAS from a review linking XBP1 to immunity (plasma cell differentiation, cytokine production). Reason: Too general; the supported immune roles (plasma cell differentiation, immunoglobulin and IL-6 production) are already captured by specific terms. Supporting Evidence: PMID:11460154 Here we report that the transcription factor XBP-1 is required for the generation of plasma cells. |
| GO:0008284 positive regulation of cell population proliferation | IDA PMID:25656649 MicroRNA-214 Is Upregulated in Heart Failure Patients and Su... | KEEP AS NON CORE | Summary: In HUVECs, XBP1 silencing decreased proliferation and angiogenesis, and ectopic XBP1 enhanced proliferation and tube formation (PMID:25656649). Reason: Supported cell-type-specific outputs of the XBP1 transcriptional program in endothelial cells; not core. Supporting Evidence: PMID:25656649 Mechanistically, miR-214 overexpression reduces angiogenesis of HUVECs by targeting XBP1, an important transcription factor of unfolded protein response, and XBP1 silencing decreases HUVECs proliferation and angiogenesis similar to miR-214 overexpression. Furthermore, ectopic expression of XBP1 enhances endothelial cells proliferation and tube formation |
| GO:0008284 positive regulation of cell population proliferation | IGI PMID:25656649 MicroRNA-214 Is Upregulated in Heart Failure Patients and Su... | KEEP AS NON CORE | Summary: In HUVECs, XBP1 silencing decreased proliferation and angiogenesis, and ectopic XBP1 enhanced proliferation and tube formation (PMID:25656649). Reason: Supported cell-type-specific outputs of the XBP1 transcriptional program in endothelial cells; not core. Supporting Evidence: PMID:25656649 Mechanistically, miR-214 overexpression reduces angiogenesis of HUVECs by targeting XBP1, an important transcription factor of unfolded protein response, and XBP1 silencing decreases HUVECs proliferation and angiogenesis similar to miR-214 overexpression. Furthermore, ectopic expression of XBP1 enhances endothelial cells proliferation and tube formation |
| GO:0010832 negative regulation of myotube differentiation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Sequence-similarity transfer from mouse Xbp1 for 'negative regulation of myotube differentiation', reflecting a physiological, tissue-specific output of the XBP1 transcriptional program. Reason: Mouse genetic studies place XBP1 in this physiological context, mostly via transcriptional control of secretory, lipogenic or differentiation genes. The transfer to the human ortholog is reasonable, but this is a downstream, context-specific role rather than a core function. Supporting Evidence: file:human/XBP1/XBP1-uniprot.txt Required for cardiac myogenesis and hepatogenesis during embryonic development, and the development of secretory tissues such as exocrine pancreas and salivary gland (By similarity). |
| GO:0016020 membrane | EXP PMID:19394296 Cotranslational targeting of XBP1 protein to the membrane pr... | KEEP AS NON CORE | Summary: XBP1u is targeted to the ER membrane cotranslationally via a hydrophobic region (a type II transmembrane-like segment), which recruits its own mRNA to IRE1 for splicing; it is cleaved there by signal peptide peptidase. Reason: Membrane/ER association is real for the XBP1u isoform and facilitates XBP1 mRNA splicing, but it is not where the core transcription factor function is exercised. Supporting Evidence: PMID:19394296 We show that the unspliced XBP1 (XBP1u) mRNA is localized to the membrane, although its product is neither a secretory nor a membrane protein and is released to the cytosol after splicing. |
| GO:0016020 membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: XBP1u is targeted to the ER membrane cotranslationally via a hydrophobic region (a type II transmembrane-like segment), which recruits its own mRNA to IRE1 for splicing; it is cleaved there by signal peptide peptidase. Reason: Membrane/ER association is real for the XBP1u isoform and facilitates XBP1 mRNA splicing, but it is not where the core transcription factor function is exercised. Supporting Evidence: PMID:25239945 Cleavage occurs within a so far unrecognized type II transmembrane domain, which renders XBP1u as an SPP substrate through specific sequence features. file:human/XBP1/XBP1-uniprot.txt upon ER stress, the emerging XBP1 polypeptide chain, as part of a mRNA-ribosome-nascent chain (R-RNC) complex, cotranslationally recruits its own unprocessed mRNA through transient docking to the ER membrane |
| GO:0030335 positive regulation of cell migration | IDA PMID:25656649 MicroRNA-214 Is Upregulated in Heart Failure Patients and Su... | KEEP AS NON CORE | Summary: In HUVECs, XBP1 silencing decreased proliferation and angiogenesis, and ectopic XBP1 enhanced proliferation and tube formation (PMID:25656649). Reason: Supported cell-type-specific outputs of the XBP1 transcriptional program in endothelial cells; not core. Supporting Evidence: PMID:25656649 Mechanistically, miR-214 overexpression reduces angiogenesis of HUVECs by targeting XBP1, an important transcription factor of unfolded protein response, and XBP1 silencing decreases HUVECs proliferation and angiogenesis similar to miR-214 overexpression. Furthermore, ectopic expression of XBP1 enhances endothelial cells proliferation and tube formation |
| GO:0030968 endoplasmic reticulum unfolded protein response | IDA PMID:31387940 BIK ubiquitination by the E3 ligase Cul5-ASB11 determines ce... | ACCEPT | Summary: XBP1s is the transcriptional effector of the IRE1 branch of the ER unfolded protein response. Reason: Core biological process for XBP1. Supporting Evidence: PMID:31387940 ER stress leads to the activation of ASB11 by XBP1s during the adaptive phase of the unfolded protein response PMID:11779464 Here, we identified the transcription factor XBP1, a target of ATF6, as a mammalian substrate of such an unconventional mRNA splicing system and showed that only the spliced form of XBP1 can activate the UPR efficiently. |
| GO:0030968 endoplasmic reticulum unfolded protein response | IEA GO_REF:0000117 | ACCEPT | Summary: XBP1s is the transcriptional effector of the IRE1 branch of the ER unfolded protein response. Reason: Core biological process for XBP1. Supporting Evidence: file:human/XBP1/XBP1-uniprot.txt Functions as a transcription factor during endoplasmic reticulum (ER) stress by regulating the unfolded protein response (UPR). PMID:11779464 Here, we identified the transcription factor XBP1, a target of ATF6, as a mammalian substrate of such an unconventional mRNA splicing system and showed that only the spliced form of XBP1 can activate the UPR efficiently. |
| GO:0030968 endoplasmic reticulum unfolded protein response | ISS GO_REF:0000024 | ACCEPT | Summary: XBP1s is the transcriptional effector of the IRE1 branch of the ER unfolded protein response. Reason: Core biological process for XBP1. Supporting Evidence: file:human/XBP1/XBP1-uniprot.txt Functions as a transcription factor during endoplasmic reticulum (ER) stress by regulating the unfolded protein response (UPR). PMID:11779464 Here, we identified the transcription factor XBP1, a target of ATF6, as a mammalian substrate of such an unconventional mRNA splicing system and showed that only the spliced form of XBP1 can activate the UPR efficiently. |
| GO:0030968 endoplasmic reticulum unfolded protein response | ISS GO_REF:0000024 | ACCEPT | Summary: XBP1s is the transcriptional effector of the IRE1 branch of the ER unfolded protein response. Reason: Core biological process for XBP1. Supporting Evidence: file:human/XBP1/XBP1-uniprot.txt Functions as a transcription factor during endoplasmic reticulum (ER) stress by regulating the unfolded protein response (UPR). PMID:11779464 Here, we identified the transcription factor XBP1, a target of ATF6, as a mammalian substrate of such an unconventional mRNA splicing system and showed that only the spliced form of XBP1 can activate the UPR efficiently. |
| GO:0031670 cellular response to nutrient | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Sequence-similarity transfer from mouse Xbp1 for 'cellular response to nutrient', reflecting a physiological, tissue-specific output of the XBP1 transcriptional program. Reason: Mouse genetic studies place XBP1 in this physiological context, mostly via transcriptional control of secretory, lipogenic or differentiation genes. The transfer to the human ortholog is reasonable, but this is a downstream, context-specific role rather than a core function. Supporting Evidence: file:human/XBP1/XBP1-uniprot.txt Controls the induction of de novo fatty acid synthesis in hepatocytes by regulating the expression of a subset of lipogenic genes in an ER stress- and UPR-independent manner |
| GO:0032755 positive regulation of interleukin-6 production | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Sequence-similarity transfer from mouse Xbp1 for 'positive regulation of interleukin-6 production', reflecting a physiological, tissue-specific output of the XBP1 transcriptional program. Reason: Mouse genetic studies place XBP1 in this physiological context, mostly via transcriptional control of secretory, lipogenic or differentiation genes. The transfer to the human ortholog is reasonable, but this is a downstream, context-specific role rather than a core function. Supporting Evidence: file:human/XBP1/XBP1-uniprot.txt Plays a role in the production of immunoglobulins and interleukin-6 in the presence of stimuli required for plasma cell differentiation (By similarity). |
| GO:0032869 cellular response to insulin stimulus | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Sequence-similarity transfer from mouse Xbp1 for 'cellular response to insulin stimulus', reflecting a physiological, tissue-specific output of the XBP1 transcriptional program. Reason: Mouse genetic studies place XBP1 in this physiological context, mostly via transcriptional control of secretory, lipogenic or differentiation genes. The transfer to the human ortholog is reasonable, but this is a downstream, context-specific role rather than a core function. Supporting Evidence: file:human/XBP1/XBP1-uniprot.txt Also functions as a major regulator of the UPR in obesity-induced insulin resistance and type 2 diabetes for the management of obesity and diabetes prevention (By similarity). |
| GO:0034976 response to endoplasmic reticulum stress | TAS PMID:22013210 The unfolded protein response: integrating stress signals th... | ACCEPT | Summary: XBP1s is the transcriptional effector of the IRE1 branch of the ER unfolded protein response. Reason: Core biological process for XBP1. Supporting Evidence: PMID:22013210 Inositol-requiring transmembrane kinase/endonuclease-1 (IRE1Ξ±), the most conserved UPR stress sensor, functions as an endoribonuclease that processes the mRNA of the transcription factor X-box binding protein-1 (XBP1). PMID:11779464 Here, we identified the transcription factor XBP1, a target of ATF6, as a mammalian substrate of such an unconventional mRNA splicing system and showed that only the spliced form of XBP1 can activate the UPR efficiently. |
| GO:0035356 intracellular triglyceride homeostasis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Sequence-similarity transfer from mouse Xbp1 for 'intracellular triglyceride homeostasis', reflecting a physiological, tissue-specific output of the XBP1 transcriptional program. Reason: Mouse genetic studies place XBP1 in this physiological context, mostly via transcriptional control of secretory, lipogenic or differentiation genes. The transfer to the human ortholog is reasonable, but this is a downstream, context-specific role rather than a core function. Supporting Evidence: file:human/XBP1/XBP1-uniprot.txt Controls the induction of de novo fatty acid synthesis in hepatocytes by regulating the expression of a subset of lipogenic genes in an ER stress- and UPR-independent manner |
| GO:0035470 positive regulation of vascular wound healing | IDA PMID:25656649 MicroRNA-214 Is Upregulated in Heart Failure Patients and Su... | KEEP AS NON CORE | Summary: In HUVECs, XBP1 silencing decreased proliferation and angiogenesis, and ectopic XBP1 enhanced proliferation and tube formation (PMID:25656649). Reason: Supported cell-type-specific outputs of the XBP1 transcriptional program in endothelial cells; not core. Supporting Evidence: PMID:25656649 Mechanistically, miR-214 overexpression reduces angiogenesis of HUVECs by targeting XBP1, an important transcription factor of unfolded protein response, and XBP1 silencing decreases HUVECs proliferation and angiogenesis similar to miR-214 overexpression. Furthermore, ectopic expression of XBP1 enhances endothelial cells proliferation and tube formation |
| GO:0036498 IRE1-mediated unfolded protein response | TAS PMID:22013210 The unfolded protein response: integrating stress signals th... | ACCEPT | Summary: XBP1s is the transcriptional effector of the IRE1 branch of the ER unfolded protein response. Reason: Core biological process for XBP1. Supporting Evidence: PMID:22013210 Inositol-requiring transmembrane kinase/endonuclease-1 (IRE1Ξ±), the most conserved UPR stress sensor, functions as an endoribonuclease that processes the mRNA of the transcription factor X-box binding protein-1 (XBP1). PMID:11779464 Here, we identified the transcription factor XBP1, a target of ATF6, as a mammalian substrate of such an unconventional mRNA splicing system and showed that only the spliced form of XBP1 can activate the UPR efficiently. |
| GO:0036498 IRE1-mediated unfolded protein response | TAS PMID:22934019 The endoplasmic reticulum stress response in aging and age-r... | ACCEPT | Summary: XBP1s is the transcriptional effector of the IRE1 branch of the ER unfolded protein response. Reason: Core biological process for XBP1. Supporting Evidence: PMID:22934019 The UPR is characterized by the induction of chaperones, degradation of misfolded proteins and attenuation of protein translation. PMID:11779464 Here, we identified the transcription factor XBP1, a target of ATF6, as a mammalian substrate of such an unconventional mRNA splicing system and showed that only the spliced form of XBP1 can activate the UPR efficiently. |
| GO:0036500 ATF6-mediated unfolded protein response | NAS PMID:32046286 Sledgehammer to Scalpel: Broad Challenges to the Heart and O... | KEEP AS NON CORE | Summary: XBP1 is transcriptionally induced by ATF6 and heterodimerizes with ATF6 to induce ERAD components. Reason: XBP1 participates with ATF6 in UPR target induction, but its principal role is in the IRE1 branch; the cited review is mainly about ATF6. Supporting Evidence: PMID:17765680 ATF6alpha heterodimerizes with XBP1 for the induction of ER-associated degradation components PMID:11779464 Here, we identified the transcription factor XBP1, a target of ATF6, as a mammalian substrate of such an unconventional mRNA splicing system and showed that only the spliced form of XBP1 can activate the UPR efficiently. PMID:32046286 This generates a fragment of ATF6Ξ± that translocates to the nucleus, where it regulates numerous genes that restore ER protein-folding capacity but is degraded soon after. |
| GO:0036503 ERAD quality control pathway | NAS PMID:17765680 Transcriptional induction of mammalian ER quality control pr... | MODIFY | Summary: ATF6alpha heterodimerizes with XBP1 to induce ERAD components (PMID:17765680). Reason: XBP1 transcriptionally upregulates ERAD components rather than executing ERAD; the regulatory term is accurate. Proposed replacements: positive regulation of ERAD pathway Supporting Evidence: PMID:17765680 ATF6alpha heterodimerizes with XBP1 for the induction of ER-associated degradation components file:human/XBP1/XBP1-uniprot.txt [Isoform 2]: Functions as a stress-inducible potent transcriptional activator during endoplasmic reticulum (ER) stress by inducing unfolded protein response (UPR) target genes via binding to the UPR element (UPRE). Up-regulates target genes encoding ER chaperones and ER-associated degradation (ERAD) components |
| GO:0042149 cellular response to glucose starvation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Sequence-similarity transfer from mouse Xbp1 for 'cellular response to glucose starvation', reflecting a physiological, tissue-specific output of the XBP1 transcriptional program. Reason: Mouse genetic studies place XBP1 in this physiological context, mostly via transcriptional control of secretory, lipogenic or differentiation genes. The transfer to the human ortholog is reasonable, but this is a downstream, context-specific role rather than a core function. Supporting Evidence: file:human/XBP1/XBP1-uniprot.txt Functions as a transcription factor during endoplasmic reticulum (ER) stress by regulating the unfolded protein response (UPR). |
| GO:0042632 cholesterol homeostasis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Sequence-similarity transfer from mouse Xbp1 for 'cholesterol homeostasis', reflecting a physiological, tissue-specific output of the XBP1 transcriptional program. Reason: Mouse genetic studies place XBP1 in this physiological context, mostly via transcriptional control of secretory, lipogenic or differentiation genes. The transfer to the human ortholog is reasonable, but this is a downstream, context-specific role rather than a core function. Supporting Evidence: file:human/XBP1/XBP1-uniprot.txt Controls the induction of de novo fatty acid synthesis in hepatocytes by regulating the expression of a subset of lipogenic genes in an ER stress- and UPR-independent manner |
| GO:0042802 identical protein binding | IPI PMID:20102225 Identification of bZIP interaction partners of viral protein... | MODIFY | Summary: bZIP interaction arrays show XBP1 self-association via its leucine zipper. Reason: Self-association of the bZIP leucine zipper is homodimerization; the specific term is more informative. Proposed replacements: protein homodimerization activity Supporting Evidence: PMID:20102225 We investigated the interaction specificity of these four viral bZIPs by using coiled-coil arrays to assess self-associations as well as heterointeractions with 33 representative human bZIPs. |
| GO:0042802 identical protein binding | IPI PMID:23661758 Networks of bZIP protein-protein interactions diversified ov... | MODIFY | Summary: bZIP interaction arrays show XBP1 self-association via its leucine zipper. Reason: Self-association of the bZIP leucine zipper is homodimerization; the specific term is more informative. Proposed replacements: protein homodimerization activity Supporting Evidence: PMID:23661758 We studied the basic region-leucine zipper (bZIP) transcription factors and quantified bZIP dimerization networks for five metazoan and two single-cell species, measuring interactions in vitro for 2891 protein pairs. |
| GO:0043066 negative regulation of apoptotic process | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: XBP1s promotes cell survival under ER stress (e.g. protecting dopaminergic cells from PD-related insults). Reason: Supported pro-survival output of the adaptive UPR transcriptional program; downstream rather than core. Supporting Evidence: PMID:20348923 Cell lines with knockout or knockdown of p85alphaalpha show marked alterations in the UPR, including reduced ER stress-dependent accumulation of nuclear XBP-1, decreased induction of UPR target genes and increased rates of apoptosis. PMID:20955178 p300 increases the acetylation and protein stability of XBP1s, and enhances its transcriptional activity, whereas SIRT1 deacetylates XBP1s and inhibits its transcriptional activity. |
| GO:0043066 negative regulation of apoptotic process | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: XBP1s promotes cell survival under ER stress (e.g. protecting dopaminergic cells from PD-related insults). Reason: Supported pro-survival output of the adaptive UPR transcriptional program; downstream rather than core. Supporting Evidence: PMID:20348923 Cell lines with knockout or knockdown of p85alphaalpha show marked alterations in the UPR, including reduced ER stress-dependent accumulation of nuclear XBP-1, decreased induction of UPR target genes and increased rates of apoptosis. PMID:20955178 p300 increases the acetylation and protein stability of XBP1s, and enhances its transcriptional activity, whereas SIRT1 deacetylates XBP1s and inhibits its transcriptional activity. |
| GO:0043565 sequence-specific DNA binding | IEA GO_REF:0000117 | ACCEPT | Summary: XBP1 is a bZIP protein that binds specific cis-regulatory DNA elements (UPRE/ERSE, CRE-like elements, the HTLV-1 21-bp repeat and MHC class II X2 box). Reason: Sequence-specific DNA binding is the defining biochemical activity of the XBP1 bZIP domain and is supported by multiple direct binding assays and by phylogeny (IBA). Supporting Evidence: PMID:8657566 The results indicated that hXBP-1 binds preferably to the CRE-like element GAT-GACGTG(T/G)NNN(A/T)T, wherein the core sequence ACGT is highly conserved file:human/XBP1/XBP1-uniprot.txt Binds the Tax-responsive element (TRE) present in the long terminal repeat (LTR) of T-cell leukemia virus type 1 (HTLV-I) and to the TPA response elements (TRE) file:human/XBP1/XBP1-uniprot.txt [Isoform 2]: Functions as a stress-inducible potent transcriptional activator during endoplasmic reticulum (ER) stress by inducing unfolded protein response (UPR) target genes via binding to the UPR element (UPRE). Up-regulates target genes encoding ER chaperones and ER-associated degradation (ERAD) components |
| GO:0045348 positive regulation of MHC class II biosynthetic process | IMP PMID:1903538 Human X-box-binding protein 1 is required for the transcript... | KEEP AS NON CORE | Summary: Antisense XBP1 represses HLA-DR/DP surface expression and HLA-DRA promoter activity (PMID:1903538). Reason: Historical, supported role at MHC class II X2 boxes; peripheral to the UPR function. Supporting Evidence: PMID:1903538 Transient transfection of a mammalian expression vector with the hXBP-1 cDNA inserted in the antisense orientation represses the surface expression of HLA-DR and HLA-DP in Raji cells. PMID:1903538 These data suggest that the hXBP-1 c-fos heterodimer is critical for the transcription of a subset of the human class II major histocompatibility complex genes |
| GO:0045579 positive regulation of B cell differentiation | IDA PMID:11460154 Plasma cell differentiation requires the transcription facto... | KEEP AS NON CORE | Summary: XBP1 is required for, and when introduced initiates, plasma-cell differentiation of B cells (PMID:11460154). Reason: Well established physiological role of XBP1 in terminal B cell differentiation, executed through its transcription factor activity; non-core relative to the UPR TF function. Supporting Evidence: PMID:11460154 Here we report that the transcription factor XBP-1 is required for the generation of plasma cells. PMID:11460154 XBP-1 is the only transcription factor known to be selectively and specifically required for the terminal differentiation of B lymphocytes to plasma cells. |
| GO:0045582 positive regulation of T cell differentiation | IDA PMID:11460154 Plasma cell differentiation requires the transcription facto... | UNDECIDED | Summary: The cited paper (PMID:11460154) concerns XBP1 in plasma-cell differentiation; the cached abstract does not describe T cell differentiation. Reason: The full text is not available to verify the T cell claim, and the abstract emphasizes the selective requirement of XBP1 in the B-lineage. Cannot be adjudicated from the available evidence. Supporting Evidence: PMID:11460154 XBP-1 is the only transcription factor known to be selectively and specifically required for the terminal differentiation of B lymphocytes to plasma cells. |
| GO:0045600 positive regulation of fat cell differentiation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Sequence-similarity transfer from mouse Xbp1 for 'positive regulation of fat cell differentiation', reflecting a physiological, tissue-specific output of the XBP1 transcriptional program. Reason: Mouse genetic studies place XBP1 in this physiological context, mostly via transcriptional control of secretory, lipogenic or differentiation genes. The transfer to the human ortholog is reasonable, but this is a downstream, context-specific role rather than a core function. Supporting Evidence: file:human/XBP1/XBP1-uniprot.txt Involved in adipocyte differentiation by regulating lipogenic gene expression during lactation. |
| GO:0045766 positive regulation of angiogenesis | IMP PMID:25656649 MicroRNA-214 Is Upregulated in Heart Failure Patients and Su... | KEEP AS NON CORE | Summary: In HUVECs, XBP1 silencing decreased proliferation and angiogenesis, and ectopic XBP1 enhanced proliferation and tube formation (PMID:25656649). Reason: Supported cell-type-specific outputs of the XBP1 transcriptional program in endothelial cells; not core. Supporting Evidence: PMID:25656649 Mechanistically, miR-214 overexpression reduces angiogenesis of HUVECs by targeting XBP1, an important transcription factor of unfolded protein response, and XBP1 silencing decreases HUVECs proliferation and angiogenesis similar to miR-214 overexpression. Furthermore, ectopic expression of XBP1 enhances endothelial cells proliferation and tube formation |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:8657566 The basic domain/leucine zipper protein hXBP-1 preferentiall... | ACCEPT | Summary: XBP1s activates Pol II transcription of UPR target genes (ER chaperones, ERAD components, lipid synthesis genes). Reason: Core biological role of the XBP1 transcription factor. Supporting Evidence: PMID:8657566 hXBP-1 can transactivate multimers of the target sequences to which it binds in COS cells, and the level of transactivation directly correlates with the extent of binding as observed in gel retardation experiments. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:1903538 Human X-box-binding protein 1 is required for the transcript... | ACCEPT | Summary: XBP1s activates Pol II transcription of UPR target genes (ER chaperones, ERAD components, lipid synthesis genes). Reason: Core biological role of the XBP1 transcription factor. Supporting Evidence: PMID:1903538 These data suggest that the hXBP-1 c-fos heterodimer is critical for the transcription of a subset of the human class II major histocompatibility complex genes PMID:1903538 Transient transfection of a mammalian expression vector with the hXBP-1 cDNA inserted in the antisense orientation represses the surface expression of HLA-DR and HLA-DP in Raji cells. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | ISS GO_REF:0000024 | ACCEPT | Summary: XBP1s activates Pol II transcription of UPR target genes (ER chaperones, ERAD components, lipid synthesis genes). Reason: Core biological role of the XBP1 transcription factor. Supporting Evidence: file:human/XBP1/XBP1-uniprot.txt [Isoform 2]: Functions as a stress-inducible potent transcriptional activator during endoplasmic reticulum (ER) stress by inducing unfolded protein response (UPR) target genes via binding to the UPR element (UPRE). Up-regulates target genes encoding ER chaperones and ER-associated degradation (ERAD) components |
| GO:0046982 protein heterodimerization activity | IDA PMID:1903538 Human X-box-binding protein 1 is required for the transcript... | ACCEPT | Summary: hXBP-1 forms a stable heterodimer with c-Fos (PMID:1903538). Reason: bZIP heterodimerization (with Fos, ATF6 and others) is a genuine aspect of XBP1 molecular function that affects target specificity. Supporting Evidence: PMID:1903538 Moreover, hXBP-1 is shown to form a stable heterodimer with the product of the c-fos protooncogene. |
| GO:0048666 neuron development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Sequence-similarity transfer from mouse Xbp1 for 'neuron development', reflecting a physiological, tissue-specific output of the XBP1 transcriptional program. Reason: Mouse genetic studies place XBP1 in this physiological context, mostly via transcriptional control of secretory, lipogenic or differentiation genes. The transfer to the human ortholog is reasonable, but this is a downstream, context-specific role rather than a core function. Supporting Evidence: file:human/XBP1/XBP1-uniprot.txt Plays a role in the survival of both dopaminergic neurons of the substantia nigra pars compacta (SNpc), by maintaining protein homeostasis and of myeloma cells. |
| GO:0055089 fatty acid homeostasis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Sequence-similarity transfer from mouse Xbp1 for 'fatty acid homeostasis', reflecting a physiological, tissue-specific output of the XBP1 transcriptional program. Reason: Mouse genetic studies place XBP1 in this physiological context, mostly via transcriptional control of secretory, lipogenic or differentiation genes. The transfer to the human ortholog is reasonable, but this is a downstream, context-specific role rather than a core function. Supporting Evidence: file:human/XBP1/XBP1-uniprot.txt Controls the induction of de novo fatty acid synthesis in hepatocytes by regulating the expression of a subset of lipogenic genes in an ER stress- and UPR-independent manner |
| GO:0055092 sterol homeostasis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Sequence-similarity transfer from mouse Xbp1 for 'sterol homeostasis', reflecting a physiological, tissue-specific output of the XBP1 transcriptional program. Reason: Mouse genetic studies place XBP1 in this physiological context, mostly via transcriptional control of secretory, lipogenic or differentiation genes. The transfer to the human ortholog is reasonable, but this is a downstream, context-specific role rather than a core function. Supporting Evidence: file:human/XBP1/XBP1-uniprot.txt Controls the induction of de novo fatty acid synthesis in hepatocytes by regulating the expression of a subset of lipogenic genes in an ER stress- and UPR-independent manner |
| GO:0060612 adipose tissue development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Sequence-similarity transfer from mouse Xbp1 for 'adipose tissue development', reflecting a physiological, tissue-specific output of the XBP1 transcriptional program. Reason: Mouse genetic studies place XBP1 in this physiological context, mostly via transcriptional control of secretory, lipogenic or differentiation genes. The transfer to the human ortholog is reasonable, but this is a downstream, context-specific role rather than a core function. Supporting Evidence: file:human/XBP1/XBP1-uniprot.txt Involved in adipocyte differentiation by regulating lipogenic gene expression during lactation. |
| GO:0071222 cellular response to lipopolysaccharide | IDA PMID:11460154 Plasma cell differentiation requires the transcription facto... | KEEP AS NON CORE | Summary: XBP1 transcripts are rapidly upregulated by plasma-cell-inducing stimuli such as LPS (PMID:11460154). Reason: Induction by LPS reflects B-cell differentiation context; non-core. Supporting Evidence: PMID:11460154 XBP-1 transcripts were rapidly upregulated in vitro by stimuli that induce plasma-cell differentiation |
| GO:0071230 cellular response to amino acid stimulus | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Sequence-similarity transfer from mouse Xbp1 for 'cellular response to amino acid stimulus', reflecting a physiological, tissue-specific output of the XBP1 transcriptional program. Reason: Mouse genetic studies place XBP1 in this physiological context, mostly via transcriptional control of secretory, lipogenic or differentiation genes. The transfer to the human ortholog is reasonable, but this is a downstream, context-specific role rather than a core function. Supporting Evidence: file:human/XBP1/XBP1-uniprot.txt Also functions as a major regulator of the UPR in obesity-induced insulin resistance and type 2 diabetes for the management of obesity and diabetes prevention (By similarity). |
| GO:0071332 cellular response to fructose stimulus | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Sequence-similarity transfer from mouse Xbp1 for 'cellular response to fructose stimulus', reflecting a physiological, tissue-specific output of the XBP1 transcriptional program. Reason: Mouse genetic studies place XBP1 in this physiological context, mostly via transcriptional control of secretory, lipogenic or differentiation genes. The transfer to the human ortholog is reasonable, but this is a downstream, context-specific role rather than a core function. Supporting Evidence: file:human/XBP1/XBP1-uniprot.txt Increases insulin sensitivity in the liver as a response to a high carbohydrate diet, resulting in improved glucose tolerance. |
| GO:0071333 cellular response to glucose stimulus | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Sequence-similarity transfer from mouse Xbp1 for 'cellular response to glucose stimulus', reflecting a physiological, tissue-specific output of the XBP1 transcriptional program. Reason: Mouse genetic studies place XBP1 in this physiological context, mostly via transcriptional control of secretory, lipogenic or differentiation genes. The transfer to the human ortholog is reasonable, but this is a downstream, context-specific role rather than a core function. Supporting Evidence: file:human/XBP1/XBP1-uniprot.txt Increases insulin sensitivity in the liver as a response to a high carbohydrate diet, resulting in improved glucose tolerance. |
| GO:0071353 cellular response to interleukin-4 | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Sequence-similarity transfer from mouse Xbp1 for 'cellular response to interleukin-4', reflecting a physiological, tissue-specific output of the XBP1 transcriptional program. Reason: Mouse genetic studies place XBP1 in this physiological context, mostly via transcriptional control of secretory, lipogenic or differentiation genes. The transfer to the human ortholog is reasonable, but this is a downstream, context-specific role rather than a core function. Supporting Evidence: file:human/XBP1/XBP1-uniprot.txt Plays a role in the production of immunoglobulins and interleukin-6 in the presence of stimuli required for plasma cell differentiation (By similarity). |
| GO:0071375 cellular response to peptide hormone stimulus | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Sequence-similarity transfer from mouse Xbp1 for 'cellular response to peptide hormone stimulus', reflecting a physiological, tissue-specific output of the XBP1 transcriptional program. Reason: Mouse genetic studies place XBP1 in this physiological context, mostly via transcriptional control of secretory, lipogenic or differentiation genes. The transfer to the human ortholog is reasonable, but this is a downstream, context-specific role rather than a core function. Supporting Evidence: file:human/XBP1/XBP1-uniprot.txt Also functions as a major regulator of the UPR in obesity-induced insulin resistance and type 2 diabetes for the management of obesity and diabetes prevention (By similarity). |
| GO:0090575 RNA polymerase II transcription regulator complex | IPI PMID:23661758 Networks of bZIP protein-protein interactions diversified ov... | ACCEPT | Summary: XBP1 forms bZIP dimers with other bZIP transcription factors. Reason: bZIP dimers bound at Pol II promoters are transcription regulator complexes. Supporting Evidence: PMID:23661758 We studied the basic region-leucine zipper (bZIP) transcription factors and quantified bZIP dimerization networks for five metazoan and two single-cell species, measuring interactions in vitro for 2891 protein pairs. PMID:17765680 ATF6alpha heterodimerizes with XBP1 for the induction of ER-associated degradation components |
| GO:1900100 positive regulation of plasma cell differentiation | IDA PMID:11460154 Plasma cell differentiation requires the transcription facto... | ACCEPT | Summary: XBP1 is required for, and when introduced initiates, plasma-cell differentiation of B cells (PMID:11460154). Reason: XBP1 is the transcription factor selectively required for terminal B-cell differentiation into plasma cells, a defining physiological role that it executes through its transcriptional activation of secretory-capacity genes. Supporting Evidence: PMID:11460154 Here we report that the transcription factor XBP-1 is required for the generation of plasma cells. PMID:11460154 XBP-1 is the only transcription factor known to be selectively and specifically required for the terminal differentiation of B lymphocytes to plasma cells. |
| GO:1902236 negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway | IDA PMID:19135031 Protective effect against Parkinson's disease-related insult... | KEEP AS NON CORE | Summary: XBP1s promotes cell survival under ER stress (e.g. protecting dopaminergic cells from PD-related insults). Reason: Supported pro-survival output of the adaptive UPR transcriptional program; downstream rather than core. Supporting Evidence: PMID:19135031 The exogenous expression of the active-form XBP1 (XBP1s) protein had protective effects against cell death induced by 1-methyl-4-phenylpyridinium (MPP+) and proteasome inhibitors. |
| GO:1903489 positive regulation of lactation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Sequence-similarity transfer from mouse Xbp1 for 'positive regulation of lactation', reflecting a physiological, tissue-specific output of the XBP1 transcriptional program. Reason: Mouse genetic studies place XBP1 in this physiological context, mostly via transcriptional control of secretory, lipogenic or differentiation genes. The transfer to the human ortholog is reasonable, but this is a downstream, context-specific role rather than a core function. Supporting Evidence: file:human/XBP1/XBP1-uniprot.txt Involved in adipocyte differentiation by regulating lipogenic gene expression during lactation. |
| GO:1990418 response to insulin-like growth factor stimulus | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Sequence-similarity transfer from mouse Xbp1 for 'response to insulin-like growth factor stimulus', reflecting a physiological, tissue-specific output of the XBP1 transcriptional program. Reason: Mouse genetic studies place XBP1 in this physiological context, mostly via transcriptional control of secretory, lipogenic or differentiation genes. The transfer to the human ortholog is reasonable, but this is a downstream, context-specific role rather than a core function. Supporting Evidence: file:human/XBP1/XBP1-uniprot.txt Also functions as a major regulator of the UPR in obesity-induced insulin resistance and type 2 diabetes for the management of obesity and diabetes prevention (By similarity). |
| GO:1990837 sequence-specific double-stranded DNA binding | IDA PMID:28473536 Impact of cytosine methylation on DNA binding specificities ... | ACCEPT | Summary: XBP1 is a bZIP protein that binds specific cis-regulatory DNA elements (UPRE/ERSE, CRE-like elements, the HTLV-1 21-bp repeat and MHC class II X2 box). Reason: Sequence-specific DNA binding is the defining biochemical activity of the XBP1 bZIP domain and is supported by multiple direct binding assays and by phylogeny (IBA). Supporting Evidence: PMID:8657566 The results indicated that hXBP-1 binds preferably to the CRE-like element GAT-GACGTG(T/G)NNN(A/T)T, wherein the core sequence ACGT is highly conserved file:human/XBP1/XBP1-uniprot.txt Binds the Tax-responsive element (TRE) present in the long terminal repeat (LTR) of T-cell leukemia virus type 1 (HTLV-I) and to the TPA response elements (TRE) file:human/XBP1/XBP1-uniprot.txt [Isoform 2]: Functions as a stress-inducible potent transcriptional activator during endoplasmic reticulum (ER) stress by inducing unfolded protein response (UPR) target genes via binding to the UPR element (UPRE). Up-regulates target genes encoding ER chaperones and ER-associated degradation (ERAD) components |
| GO:2000347 positive regulation of hepatocyte proliferation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Sequence-similarity transfer from mouse Xbp1 for 'positive regulation of hepatocyte proliferation', reflecting a physiological, tissue-specific output of the XBP1 transcriptional program. Reason: Mouse genetic studies place XBP1 in this physiological context, mostly via transcriptional control of secretory, lipogenic or differentiation genes. The transfer to the human ortholog is reasonable, but this is a downstream, context-specific role rather than a core function. Supporting Evidence: file:human/XBP1/XBP1-uniprot.txt Required for cardiac myogenesis and hepatogenesis during embryonic development, and the development of secretory tissues such as exocrine pancreas and salivary gland (By similarity). |
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Download this section (compressed HTML)Q: To what extent do XBP1s homodimers versus ATF6-XBP1 heterodimers account for target selectivity among UPRE, ERSE and ERSE-II elements in human cells?
Q: Is the XBP1u-mediated negative feedback on XBP1s physiologically important in human secretory tissues, and does it depend on SPP-mediated cleavage?
Q: Which XBP1-dependent metabolic programs (hepatic lipogenesis, FOXO1 degradation) are independent of ER stress in human cells?
Experiment: CUT&RUN for XBP1s in human plasma cells and hepatocytes, with and without ATF6 knockout, to resolve homodimer versus heterodimer target sets.
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