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Protein

X-box-binding protein 1

Gene

XBP1

Organism
Bos taurus (Bovine)
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
Short name:
XBP-1By similarity
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 similarity
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Chromosome 17

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)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 185185CytoplasmicBy similarityAdd
BLAST
Transmembranei186 – 20318Helical; Signal-anchor for type II membrane proteinSequence analysisBy similarityAdd
BLAST
Topological domaini204 – 26158LumenalBy similarityAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Endoplasmic reticulum, Membrane, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 261261X-box-binding protein 1PRO_0000285213Add
BLAST
Chaini1 – 193193X-box-binding protein 1, cytoplasmic formBy similarityPRO_0000432569Add
BLAST
Chaini196 – 26166X-box-binding protein 1, luminal formBy similarityPRO_0000432570Add
BLAST

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)LengthDescriptionGraphical viewFeature identifierActions
Sitei190 – 1912Cleavage; by HM13/SPPBy similarity

Keywords - PTMi

Acetylation, Cleavage on pair of basic residues, Ubl conjugation

Proteomic databases

PaxDbiQ3SZZ2.
PRIDEiQ3SZZ2.

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

STRINGi9913.ENSBTAP00000007835.

Structurei

3D structure databases

ProteinModelPortaliQ3SZZ2.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini70 – 13364bZIPPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni72 – 9423Basic motifPROSITE-ProRule annotationAdd
BLAST
Regioni76 – 9217Nuclear localization signal (NLS)By similarityAdd
BLAST
Regioni98 – 13336Leucine-zipperPROSITE-ProRule annotationAdd
BLAST

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.
GeneTreeiENSGT00390000017751.
HOGENOMiHOG000007671.
HOVERGENiHBG061457.
InParanoidiQ3SZZ2.
KOiK09027.
OMAiNQELRCR.
OrthoDBiEOG74BJVQ.
TreeFamiTF319837.

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: Q3SZZ2-1) [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
MVVVAPAQSP AAGAPKVLLL SGQPAATGGA PAGRALPVMV PGQQGASPEG
60 70 80 90 100
ASGVPPQARK RQRLTHLSPE EKALRRKLKN RVAAQTARDR KKARMSELEQ
110 120 130 140 150
QVVDLEEENQ KLLLENQLLR EKTHGLVVEN QELRQRLGMD ALVTEEEAET
160 170 180 190 200
KGNGAGLVAG SAESAALRLR APLQQVQAQL SPLQNISPWT LMALTLQTLS
210 220 230 240 250
LTSCWAFCST WTQSCSSDVL PQSLPAWSSS QKWTQKDPVP YRPPLLHPWG
260
RHQPSWKPLM N
Length:261
Mass (Da):28,424
Last modified:October 11, 2005 - v1
Checksum:i5F0C4AB640112E78
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC102639 mRNA. Translation: AAI02640.1.
RefSeqiNP_001029899.1. NM_001034727.3. [Q3SZZ2-1]
UniGeneiBt.89117.

Genome annotation databases

EnsembliENSBTAT00000007835; ENSBTAP00000007835; ENSBTAG00000005970. [Q3SZZ2-1]
GeneIDi541236.
KEGGibta:541236.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC102639 mRNA. Translation: AAI02640.1.
RefSeqiNP_001029899.1. NM_001034727.3. [Q3SZZ2-1]
UniGeneiBt.89117.

3D structure databases

ProteinModelPortaliQ3SZZ2.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000007835.

Proteomic databases

PaxDbiQ3SZZ2.
PRIDEiQ3SZZ2.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSBTAT00000007835; ENSBTAP00000007835; ENSBTAG00000005970. [Q3SZZ2-1]
GeneIDi541236.
KEGGibta:541236.

Organism-specific databases

CTDi7494.

Phylogenomic databases

eggNOGiKOG4005. Eukaryota.
ENOG410XSJI. LUCA.
GeneTreeiENSGT00390000017751.
HOGENOMiHOG000007671.
HOVERGENiHBG061457.
InParanoidiQ3SZZ2.
KOiK09027.
OMAiNQELRCR.
OrthoDBiEOG74BJVQ.
TreeFamiTF319837.

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...

Publicationsi

  1. NIH - Mammalian Gene Collection (MGC) project
    Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Strain: Crossbred X Angus.
    Tissue: Ileum.

Entry informationi

Entry nameiXBP1_BOVIN
AccessioniPrimary (citable) accession number: Q3SZZ2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 1, 2007
Last sequence update: October 11, 2005
Last modified: June 8, 2016
This is version 80 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.