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Protein

X-box-binding protein 1

Gene

Xbp1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

Functions as a transcription factor during endoplasmic reticulum (ER) stress by regulating the unfolded protein response (UPR). Required for cardiac myogenesis and hepatogenesis during embryonic development, and the development of secretory tissues such as exocrine pancreas and salivary gland. Involved in terminal differentiation of B lymphocytes to plasma cells and production of immunoglobulins. Modulates the cellular response to ER stress in a PIK3R-dependent manner. Binds to the cis-acting X box present in the promoter regions of major histocompatibility complex class II genes. Involved in VEGF-induced endothelial cell (EC) proliferation and retinal blood vessel formation during embryonic development but also for angiogenesis in adult tissues under ischemic conditions. Functions also 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
Isoform 1: Acts as a weak transcriptional factor. Together with HDAC3, contributes to the activation of NFE2L2-mediated HMOX1 transcription factor gene expression in a PI3K/mTORC2/Akt-dependent signaling pathway leading to EC survival under disturbed flow/oxidative stress. Binds to the ER stress response element (ERSE) upon ER stress. Binds to the consensus 5'-GATGACGTG[TG]N3[AT]T-3' sequence related to cAMP responsive element (CRE)-like sequences. Associates preferentially to the HDAC3 gene promoter region in a static flow-dependent manner. Binds to the CDH5/VE-cadherin gene promoter region.By similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Activator, Developmental protein

Keywords - Biological processi

Angiogenesis, Apoptosis, Differentiation, Myogenesis, Stress response, Transcription, Transcription regulation, Unfolded protein response

Keywords - Ligandi

DNA-binding

Names & Taxonomyi

Protein namesi
Recommended name:
X-box-binding protein 1By similarity
Alternative name(s):
Hepatocarcinogenesis-related transcription factor
Short name:
HTF
Cleaved into the following 2 chains:
X-box-binding protein 1, cytoplasmic formBy similarity
X-box-binding protein 1, luminal formBy similarity
Gene namesi
Name:Xbp1By similarityImported
Synonyms:Htf
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi1303073. Xbp1.

Subcellular locationi

  • Nucleus By similarity
  • Endoplasmic reticulum By similarity

  • Note: Colocalizes with ERN1 and KDR in the endoplasmic reticulum in endothelial cells in a vascular endothelial growth factor (VEGF)-dependent manner. Colocalizes in the nucleus with SIRT1.By similarity
Isoform 1 :
  • Nucleus By similarity
  • Cytoplasm By similarity
  • Endoplasmic reticulum membrane By similarity; Single-pass type II membrane protein By similarity
  • Endoplasmic reticulum membrane By similarity; Peripheral membrane protein By similarity
  • Membrane By similarity; Peripheral membrane protein By similarity

  • Note: Shows no preferential localization to either the nucleus or the cytoplasm. Shuttles between the nucleus and the cytoplasm in a CRM1-dependent manner. Localizes predominantly at the endoplasmic reticulum membrane as a membrane-spanning protein; whereas may be only marginally localized on the cytosolic side of the ER membrane as a peripheral membrane.By similarity

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 180CytoplasmicCuratedAdd BLAST180
Transmembranei181 – 198Helical; Signal-anchor for type II membrane proteinSequence analysisBy similarityAdd BLAST18
Topological domaini199 – 267LumenalCuratedAdd BLAST69

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Endoplasmic reticulum, Membrane, Nucleus

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL3632453.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000765451 – 267X-box-binding protein 1Add BLAST267
ChainiPRO_00004325711 – 188X-box-binding protein 1, cytoplasmic formBy similarityAdd BLAST188
ChainiPRO_0000432572191 – 267X-box-binding protein 1, luminal formBy similarityAdd BLAST77

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei61PhosphoserineBy similarity1

Post-translational modificationi

Isoform 1 is ubiquitinated, leading to proteasome-mediated degradation in response to ER stress.By similarity
X-box-binding protein 1, cytoplasmic form and luminal form are produced by intramembrane proteolytic cleavage of ER membrane-anchored isoform 1 triggered by HM13/SPP in a DERL1-RNF139-dependent and VCP/p97-independent manner. X-box-binding protein 1, luminal form is ubiquitinated leading to proteasomal degradation.By similarity
Acetylated by EP300; acetylation positively regulates the transcriptional activity of XBP1. Deacetylated by SIRT1; deacetylation negatively regulates the transcriptional activity of XBP1.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei185 – 186Cleavage; by HM13/SPPBy similarity2

Keywords - PTMi

Acetylation, Cleavage on pair of basic residues, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ9R1S4.
PRIDEiQ9R1S4.

PTM databases

PhosphoSitePlusiQ9R1S4.

Expressioni

Gene expression databases

BgeeiENSRNOG00000010298.
GenevisibleiQ9R1S4. RN.

Interactioni

Subunit structurei

Isoform 1 interacts with HM13. Isoform 1 interacts with RNF139; the interaction induces ubiquitination and degradation of isoform 1. Isoform 1 interacts (via luminal domain) with DERL1; the interaction obviates the need for ectodomain shedding prior HM13/SPP-mediated XBP1 isoform 1 cleavage. Isoform 1 interacts with HDAC3 and AKT1; the interactions occur in endothelial cell (EC) under disturbed flow. Isoform 1 interacts with the oncoprotein FOS. Interacts with SIRT1.By similarity

GO - Molecular functioni

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000014044.

Structurei

3D structure databases

ProteinModelPortaliQ9R1S4.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini63 – 126bZIPPROSITE-ProRule annotationAdd BLAST64

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni65 – 87Basic motifPROSITE-ProRule annotationAdd BLAST23
Regioni69 – 85Nuclear localization signal (NLS)By similarityAdd BLAST17
Regioni91 – 126Leucine-zipperPROSITE-ProRule annotationAdd BLAST36

Domaini

Isoform 1 N-terminus domain is necessary for nuclear localization targeting. Isoform 1 C-terminus domain confers localization to the cytoplasm and is sufficient to impose rapid degradation. Isoform 1 N-terminus and C-terminus regions are necessary for DNA-binding and weak transcriptional activity, respectively.By similarity

Sequence similaritiesi

Belongs to the bZIP family.Curated
Contains 1 bZIP (basic-leucine zipper) domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG4005. Eukaryota.
ENOG410XSJI. LUCA.
HOVERGENiHBG061457.
InParanoidiQ9R1S4.
KOiK09027.
OrthoDBiEOG091G0T4E.

Family and domain databases

InterProiIPR004827. bZIP.
[Graphical view]
PfamiPF07716. bZIP_2. 1 hit.
[Graphical view]
SMARTiSM00338. BRLZ. 1 hit.
[Graphical view]
PROSITEiPS50217. BZIP. 1 hit.
PS00036. BZIP_BASIC. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 1 isoform i produced by alternative splicing. AlignAdd to basket

Note: Additional isoforms seem to exist.Curated
Isoform 1 (identifier: Q9R1S4-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MVVVAAAPSA ASAAPKVLLL SGQPASGGRA LPLMVPGPRA AGSEASGTPQ
60 70 80 90 100
ARKRQRLTHL SPEEKALRRK LKNRVAAQTA RDRKKARMSE LEQQVVDLEE
110 120 130 140 150
ENQKLQLENQ LLREKTHGLV IENQELRTRL GMNALVTEEV SEAESKGNGV
160 170 180 190 200
RLVAGSAESA ALRLRAPLQQ VQAQLSPPQN IFPWILTLLP LQILSLISFW
210 220 230 240 250
AFWTSWTLSC FSNVLPQSLL IWRNSQRSTQ KDLVPYQPPF LCQWGPHQPS
260
WKPLMNSFVL TMYTPSL
Length:267
Mass (Da):29,665
Last modified:May 1, 2000 - v1
Checksum:iB5A58F1D3FAA10B4
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB030238 Genomic DNA. Translation: BAA82600.1.
BC079450 mRNA. Translation: AAH79450.1.
PIRiJC4857.
RefSeqiNP_001004210.1. NM_001004210.2. [Q9R1S4-1]
NP_001258660.1. NM_001271731.1.
UniGeneiRn.101044.

Genome annotation databases

GeneIDi289754.
KEGGirno:289754.
UCSCiRGD:1303073. rat. [Q9R1S4-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB030238 Genomic DNA. Translation: BAA82600.1.
BC079450 mRNA. Translation: AAH79450.1.
PIRiJC4857.
RefSeqiNP_001004210.1. NM_001004210.2. [Q9R1S4-1]
NP_001258660.1. NM_001271731.1.
UniGeneiRn.101044.

3D structure databases

ProteinModelPortaliQ9R1S4.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000014044.

Chemistry databases

ChEMBLiCHEMBL3632453.

PTM databases

PhosphoSitePlusiQ9R1S4.

Proteomic databases

PaxDbiQ9R1S4.
PRIDEiQ9R1S4.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi289754.
KEGGirno:289754.
UCSCiRGD:1303073. rat. [Q9R1S4-1]

Organism-specific databases

CTDi7494.
RGDi1303073. Xbp1.

Phylogenomic databases

eggNOGiKOG4005. Eukaryota.
ENOG410XSJI. LUCA.
HOVERGENiHBG061457.
InParanoidiQ9R1S4.
KOiK09027.
OrthoDBiEOG091G0T4E.

Miscellaneous databases

PROiQ9R1S4.

Gene expression databases

BgeeiENSRNOG00000010298.
GenevisibleiQ9R1S4. RN.

Family and domain databases

InterProiIPR004827. bZIP.
[Graphical view]
PfamiPF07716. bZIP_2. 1 hit.
[Graphical view]
SMARTiSM00338. BRLZ. 1 hit.
[Graphical view]
PROSITEiPS50217. BZIP. 1 hit.
PS00036. BZIP_BASIC. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiXBP1_RAT
AccessioniPrimary (citable) accession number: Q9R1S4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 1, 2005
Last sequence update: May 1, 2000
Last modified: November 30, 2016
This is version 97 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.