XBP1_BOVIN
ID XBP1_BOVIN Reviewed; 261 AA.
AC Q3SZZ2;
DT 01-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2005, sequence version 1.
DT 03-AUG-2022, entry version 111.
DE RecName: Full=X-box-binding protein 1 {ECO:0000250|UniProtKB:P17861};
DE Short=XBP-1 {ECO:0000250|UniProtKB:P17861};
DE Contains:
DE RecName: Full=X-box-binding protein 1, cytoplasmic form {ECO:0000250|UniProtKB:P17861};
DE Contains:
DE RecName: Full=X-box-binding protein 1, luminal form {ECO:0000250|UniProtKB:P17861};
GN Name=XBP1 {ECO:0000250|UniProtKB:P17861};
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=Crossbred X Angus; TISSUE=Ileum;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Functions as a transcription factor during endoplasmic
CC reticulum (ER) stress by regulating the unfolded protein response
CC (UPR). Required for cardiac myogenesis and hepatogenesis during
CC embryonic development, and the development of secretory tissues such as
CC exocrine pancreas and salivary gland. Involved in terminal
CC differentiation of B lymphocytes to plasma cells and production of
CC immunoglobulins. Modulates the cellular response to ER stress in a
CC PIK3R-dependent manner. Binds to the cis-acting X box present in the
CC promoter regions of major histocompatibility complex class II genes.
CC Involved in VEGF-induced endothelial cell (EC) proliferation and
CC retinal blood vessel formation during embryonic development but also
CC for angiogenesis in adult tissues under ischemic conditions. Functions
CC also as a major regulator of the UPR in obesity-induced insulin
CC resistance and type 2 diabetes for the management of obesity and
CC diabetes prevention. {ECO:0000250|UniProtKB:O35426,
CC ECO:0000250|UniProtKB:P17861}.
CC -!- FUNCTION: [Isoform 1]: Acts as a weak transcriptional factor. Together
CC with HDAC3, contributes to the activation of NFE2L2-mediated HMOX1
CC transcription factor gene expression in a PI(3)K/mTORC2/Akt-dependent
CC signaling pathway leading to EC survival under disturbed flow/oxidative
CC stress. Binds to the ER stress response element (ERSE) upon ER stress.
CC Binds to the consensus 5'-GATGACGTG[TG]N(3)[AT]T-3' sequence related to
CC cAMP responsive element (CRE)-like sequences. Associates preferentially
CC to the HDAC3 gene promoter region in a static flow-dependent manner.
CC Binds to the CDH5/VE-cadherin gene promoter region.
CC {ECO:0000250|UniProtKB:O35426, ECO:0000250|UniProtKB:P17861}.
CC -!- SUBUNIT: Isoform 1 interacts with HM13. Isoform 1 interacts with
CC RNF139; the interaction induces ubiquitination and degradation of
CC isoform 1. Isoform 1 interacts (via luminal domain) with DERL1; the
CC interaction obviates the need for ectodomain shedding prior HM13/SPP-
CC mediated XBP1 isoform 1 cleavage. Isoform 1 interacts with HDAC3 and
CC AKT1; the interactions occur in endothelial cell (EC) under disturbed
CC flow. Isoform 1 interacts with the oncoprotein FOS. Interacts with
CC SIRT1. {ECO:0000250|UniProtKB:O35426, ECO:0000250|UniProtKB:P17861}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:O35426,
CC ECO:0000250|UniProtKB:P17861}. Endoplasmic reticulum
CC {ECO:0000250|UniProtKB:P17861}. Note=Colocalizes with ERN1 and KDR in
CC the endoplasmic reticulum in endothelial cells in a vascular
CC endothelial growth factor (VEGF)-dependent manner. Colocalizes in the
CC nucleus with SIRT1. {ECO:0000250|UniProtKB:P17861}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Nucleus
CC {ECO:0000250|UniProtKB:P17861}. Cytoplasm
CC {ECO:0000250|UniProtKB:P17861}. Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:P17861}; Single-pass type II membrane protein
CC {ECO:0000250|UniProtKB:P17861}. Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:P17861}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:P17861}. Membrane
CC {ECO:0000250|UniProtKB:P17861}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:P17861}. Note=Shows no preferential localization
CC to either the nucleus or the cytoplasm. Shuttles between the nucleus
CC and the cytoplasm in a CRM1-dependent manner. Localizes predominantly
CC at the endoplasmic reticulum membrane as a membrane-spanning protein;
CC whereas may be only marginally localized on the cytosolic side of the
CC ER membrane as a peripheral membrane. {ECO:0000250|UniProtKB:O35426,
CC ECO:0000250|UniProtKB:P17861}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=1;
CC Comment=Additional isoforms seem to exist. {ECO:0000305};
CC Name=1;
CC IsoId=Q3SZZ2-1; Sequence=Displayed;
CC -!- DOMAIN: Isoform 1 N-terminus domain is necessary for nuclear
CC localization targeting. Isoform 1 C-terminus domain confers
CC localization to the cytoplasm and is sufficient to impose rapid
CC degradation. Isoform 1 N-terminus and C-terminus regions are necessary
CC for DNA-binding and weak transcriptional activity, respectively.
CC {ECO:0000250|UniProtKB:O35426, ECO:0000250|UniProtKB:P17861}.
CC -!- PTM: Isoform 1 is ubiquitinated, leading to proteasome-mediated
CC degradation in response to ER stress. {ECO:0000250|UniProtKB:O35426,
CC ECO:0000250|UniProtKB:P17861}.
CC -!- PTM: X-box-binding protein 1, cytoplasmic form and luminal form are
CC produced by intramembrane proteolytic cleavage of ER membrane-anchored
CC isoform 1 triggered by HM13/SPP in a DERL1-RNF139-dependent and
CC VCP/p97-independent manner. X-box-binding protein 1, luminal form is
CC ubiquitinated leading to proteasomal degradation.
CC {ECO:0000250|UniProtKB:P17861}.
CC -!- PTM: Acetylated by EP300; acetylation positively regulates the
CC transcriptional activity of XBP1. Deacetylated by SIRT1; deacetylation
CC negatively regulates the transcriptional activity of XBP1.
CC {ECO:0000250|UniProtKB:O35426, ECO:0000250|UniProtKB:P17861}.
CC -!- SIMILARITY: Belongs to the bZIP family. {ECO:0000305}.
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DR EMBL; BC102639; AAI02640.1; -; mRNA.
DR RefSeq; NP_001029899.1; NM_001034727.3. [Q3SZZ2-1]
DR AlphaFoldDB; Q3SZZ2; -.
DR SMR; Q3SZZ2; -.
DR STRING; 9913.ENSBTAP00000007835; -.
DR PaxDb; Q3SZZ2; -.
DR PRIDE; Q3SZZ2; -.
DR GeneID; 541236; -.
DR KEGG; bta:541236; -.
DR CTD; 7494; -.
DR eggNOG; KOG4005; Eukaryota.
DR HOGENOM; CLU_093516_0_0_1; -.
DR InParanoid; Q3SZZ2; -.
DR OrthoDB; 1269901at2759; -.
DR TreeFam; TF319837; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0031490; F:chromatin DNA binding; ISS:UniProtKB.
DR GO; GO:0000987; F:cis-regulatory region sequence-specific DNA binding; ISS:UniProtKB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISS:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0046982; F:protein heterodimerization activity; ISS:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISS:UniProtKB.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; ISS:UniProtKB.
DR GO; GO:0060612; P:adipose tissue development; ISS:UniProtKB.
DR GO; GO:0001525; P:angiogenesis; ISS:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0071230; P:cellular response to amino acid stimulus; ISS:UniProtKB.
DR GO; GO:0071498; P:cellular response to fluid shear stress; ISS:UniProtKB.
DR GO; GO:0042149; P:cellular response to glucose starvation; ISS:UniProtKB.
DR GO; GO:0071353; P:cellular response to interleukin-4; ISS:UniProtKB.
DR GO; GO:0071499; P:cellular response to laminar fluid shear stress; ISS:UniProtKB.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; ISS:UniProtKB.
DR GO; GO:0071375; P:cellular response to peptide hormone stimulus; ISS:UniProtKB.
DR GO; GO:0035356; P:cellular triglyceride homeostasis; ISS:UniProtKB.
DR GO; GO:0042632; P:cholesterol homeostasis; ISS:UniProtKB.
DR GO; GO:0001935; P:endothelial cell proliferation; ISS:UniProtKB.
DR GO; GO:0055089; P:fatty acid homeostasis; ISS:UniProtKB.
DR GO; GO:0001889; P:liver development; ISS:UniProtKB.
DR GO; GO:0007517; P:muscle organ development; IEA:UniProtKB-KW.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0045579; P:positive regulation of B cell differentiation; ISS:UniProtKB.
DR GO; GO:0045600; P:positive regulation of fat cell differentiation; ISS:UniProtKB.
DR GO; GO:2000347; P:positive regulation of hepatocyte proliferation; ISS:UniProtKB.
DR GO; GO:0002639; P:positive regulation of immunoglobulin production; ISS:UniProtKB.
DR GO; GO:1903489; P:positive regulation of lactation; ISS:UniProtKB.
DR GO; GO:0045348; P:positive regulation of MHC class II biosynthetic process; ISS:UniProtKB.
DR GO; GO:1900100; P:positive regulation of plasma cell differentiation; ISS:UniProtKB.
DR GO; GO:0045582; P:positive regulation of T cell differentiation; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0006990; P:positive regulation of transcription from RNA polymerase II promoter involved in unfolded protein response; ISS:UniProtKB.
DR GO; GO:0031648; P:protein destabilization; ISS:UniProtKB.
DR GO; GO:0010506; P:regulation of autophagy; ISS:UniProtKB.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; ISS:UniProtKB.
DR GO; GO:1990418; P:response to insulin-like growth factor stimulus; ISS:UniProtKB.
DR GO; GO:0055092; P:sterol homeostasis; ISS:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR InterPro; IPR004827; bZIP.
DR InterPro; IPR046347; bZIP_sf.
DR Pfam; PF07716; bZIP_2; 1.
DR SMART; SM00338; BRLZ; 1.
DR SUPFAM; SSF57959; SSF57959; 1.
DR PROSITE; PS50217; BZIP; 1.
DR PROSITE; PS00036; BZIP_BASIC; 1.
PE 2: Evidence at transcript level;
KW Acetylation; Activator; Alternative splicing; Angiogenesis; Apoptosis;
KW Cleavage on pair of basic residues; Cytoplasm; Developmental protein;
KW Differentiation; DNA-binding; Endoplasmic reticulum; Membrane; Myogenesis;
KW Nucleus; Phosphoprotein; Reference proteome; Signal-anchor;
KW Stress response; Transcription; Transcription regulation; Transmembrane;
KW Transmembrane helix; Ubl conjugation; Unfolded protein response.
FT CHAIN 1..261
FT /note="X-box-binding protein 1"
FT /id="PRO_0000285213"
FT CHAIN 1..193
FT /note="X-box-binding protein 1, cytoplasmic form"
FT /evidence="ECO:0000250|UniProtKB:P17861"
FT /id="PRO_0000432569"
FT CHAIN 196..261
FT /note="X-box-binding protein 1, luminal form"
FT /evidence="ECO:0000250|UniProtKB:P17861"
FT /id="PRO_0000432570"
FT TOPO_DOM 1..185
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P17861"
FT TRANSMEM 186..203
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000250|UniProtKB:P17861, ECO:0000255"
FT TOPO_DOM 204..261
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P17861"
FT DOMAIN 70..133
FT /note="bZIP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 27..65
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 72..94
FT /note="Basic motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 76..92
FT /note="Nuclear localization signal (NLS)"
FT /evidence="ECO:0000250|UniProtKB:P17861"
FT REGION 98..133
FT /note="Leucine-zipper"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT SITE 190..191
FT /note="Cleavage; by HM13/SPP"
FT /evidence="ECO:0000250|UniProtKB:P17861"
FT MOD_RES 47
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P17861"
FT MOD_RES 68
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P17861"
SQ SEQUENCE 261 AA; 28424 MW; 5F0C4AB640112E78 CRC64;
MVVVAPAQSP AAGAPKVLLL SGQPAATGGA PAGRALPVMV PGQQGASPEG ASGVPPQARK
RQRLTHLSPE EKALRRKLKN RVAAQTARDR KKARMSELEQ QVVDLEEENQ KLLLENQLLR
EKTHGLVVEN QELRQRLGMD ALVTEEEAET KGNGAGLVAG SAESAALRLR APLQQVQAQL
SPLQNISPWT LMALTLQTLS LTSCWAFCST WTQSCSSDVL PQSLPAWSSS QKWTQKDPVP
YRPPLLHPWG RHQPSWKPLM N
