XBP1 X-box binding protein 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: XBP1provided by HGNC
Official Full Name: X-box binding protein 1provided by HGNC
Primary source: HGNC:HGNC:12801
See related: Ensembl:ENSG00000100219 MIM:194355; AllianceGenome:HGNC:12801
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: XBP2; TREB5; XBP-1; TREB-5
Summary: This gene encodes a transcription factor that regulates MHC class II genes by binding to a promoter element referred to as an X box. This gene product is a bZIP protein, which was also identified as a cellular transcription factor that binds to an enhancer in the promoter of the T cell leukemia virus type 1 promoter. It may increase expression of viral proteins by acting as the DNA binding partner of a viral transactivator. It has been found that upon accumulation of unfolded proteins in the endoplasmic reticulum (ER), the mRNA of this gene is processed to an active form by an unconventional splicing mechanism that is mediated by the endonuclease inositol-requiring enzyme 1 (IRE1). The resulting loss of 26 nt from the spliced mRNA causes a frame-shift and an isoform XBP1(S), which is the functionally active transcription factor. The isoform encoded by the unspliced mRNA, XBP1(U), is constitutively expressed, and thought to function as a negative feedback regulator of XBP1(S), which shuts off transcription of target genes during the recovery phase of ER stress. A pseudogene of XBP1 has been identified and localized to chromosome 5. [provided by RefSeq, Jul 2008]
Expression: Ubiquitous expression in salivary gland (RPKM 196.1), urinary bladder (RPKM 191.7) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 22q12.1; 22q12

Exon count:: 7

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	22	NC_000022.11 (28794560..28800569, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	22	NC_060946.1 (29255848..29261869, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	22	NC_000022.10 (29190548..29196557, complement)

Chromosome 22 - NC_000022.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Expression and Clinical Significance of IRE1-XBP1s, p62, and Caspase-3 in Colorectal Cancer Patients.
Title: Expression and Clinical Significance of IRE1-XBP1s, p62, and Caspase-3 in Colorectal Cancer Patients.
Innate IRE1alpha-XBP1 activation by viral single-stranded RNA and its influence on lung cytokine production during SARS-CoV-2 pneumonia.
Title: Innate IRE1α-XBP1 activation by viral single-stranded RNA and its influence on lung cytokine production during SARS-CoV-2 pneumonia.
miRNA-378 Is Downregulated by XBP1 and Inhibits Growth and Migration of Luminal Breast Cancer Cells.
Title: miRNA-378 Is Downregulated by XBP1 and Inhibits Growth and Migration of Luminal Breast Cancer Cells.
The Role of XBP1 in bone metabolism.
Title: The Role of XBP1 in bone metabolism.
Novel XBP1s-independent function of IRE1 RNase in HIF-1alpha-mediated glycolysis upregulation in human macrophages upon stimulation with LPS or saturated fatty acid.
Title: Novel XBP1s-independent function of IRE1 RNase in HIF-1α-mediated glycolysis upregulation in human macrophages upon stimulation with LPS or saturated fatty acid.
The unfolded protein response components IRE1alpha and XBP1 promote human coronavirus infection.
Title: The unfolded protein response components IRE1α and XBP1 promote human coronavirus infection.
Endoplasmic reticulum stress-triggered ferroptosis via the XBP1-Hrd1-Nrf2 pathway induces EMT progression in diabetic nephropathy.
Title: Endoplasmic reticulum stress-triggered ferroptosis via the XBP1-Hrd1-Nrf2 pathway induces EMT progression in diabetic nephropathy.
Single-cell RNA sequencing reveals XBP1-SLC38A2 axis as a metabolic regulator in cytotoxic T lymphocytes in multiple myeloma.
Title: Single-cell RNA sequencing reveals XBP1-SLC38A2 axis as a metabolic regulator in cytotoxic T lymphocytes in multiple myeloma.
XBP1s acts as a transcription factor of IRE1alpha and promotes proliferation of colon cancer cells.
Title: XBP1s acts as a transcription factor of IRE1α and promotes proliferation of colon cancer cells.
Enhanced IRE1alpha Phosphorylation/Oligomerization-Triggered XBP1 Splicing Contributes to Parkin-Mediated Prevention of SH-SY5Y Cell Death under Nitrosative Stress.
Title: Enhanced IRE1α Phosphorylation/Oligomerization-Triggered XBP1 Splicing Contributes to Parkin-Mediated Prevention of SH-SY5Y Cell Death under Nitrosative Stress.

Submit: New GeneRIF Correction See all GeneRIFs (277)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Major affective disorder 7 MedGen: C2700438 OMIM: 612371 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
Genome-wide association analyses of esophageal squamous cell carcinoma in Chinese identify multiple susceptibility loci and gene-environment interactions. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study identifies multiple susceptibility loci for pancreatic cancer. EBI GWAS Catalog EBI GWAS CatalogPubMed
Joint analysis of three genome-wide association studies of esophageal squamous cell carcinoma in Chinese populations. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	HIV-1 Env gp120 upregulates XBP-1 in SVGA cells, human fetal astrocytes, and the prefrontal cortex of gp120 transgenic mice	PubMed
Tat	tat	Neurons exposed to HIV-1 Tat induces calcium loss from the endoplasmic reticulum via ryanodine receptor (RyR) and increases the phosphorylated levels of PERK, eIF2a, and XBP1	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

STS-M31627 (e-PCR)
- UniSTS:65864

DXS9738 (e-PCR)
- UniSTS:79461

D22S1031 (e-PCR)
- UniSTS:50803

RH103903 (e-PCR)
- UniSTS:98228

RH27882 (e-PCR)
- UniSTS:89567

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables DNA binding	TAS Traceable Author Statement more info	PubMed
enables DNA-binding transcription factor activity	IDA Inferred from Direct Assay more info	PubMed
enables DNA-binding transcription factor activity, RNA polymerase II-specific	IBA Inferred from Biological aspect of Ancestor more info
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding	ISS Inferred from Sequence or Structural Similarity more info
enables RNA polymerase II transcription regulatory region sequence-specific DNA binding	IBA Inferred from Biological aspect of Ancestor more info
enables cis-regulatory region sequence-specific DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein heterodimerization activity	IDA Inferred from Direct Assay more info	PubMed
enables sequence-specific double-stranded DNA binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in ATF6-mediated unfolded protein response	NAS Non-traceable Author Statement more info	PubMed
involved_in ERAD pathway	NAS Non-traceable Author Statement more info	PubMed
involved_in IRE1-mediated unfolded protein response	TAS Traceable Author Statement more info	PubMed
involved_in adipose tissue development	ISS Inferred from Sequence or Structural Similarity more info
involved_in angiogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in autophagy	IEA Inferred from Electronic Annotation more info
involved_in cellular response to amino acid stimulus	ISS Inferred from Sequence or Structural Similarity more info
involved_in cellular response to fructose stimulus	ISS Inferred from Sequence or Structural Similarity more info
involved_in cellular response to glucose starvation	ISS Inferred from Sequence or Structural Similarity more info
involved_in cellular response to glucose stimulus	ISS Inferred from Sequence or Structural Similarity more info
involved_in cellular response to insulin stimulus	ISS Inferred from Sequence or Structural Similarity more info
involved_in cellular response to interleukin-4	ISS Inferred from Sequence or Structural Similarity more info
involved_in cellular response to lipopolysaccharide	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to nutrient	ISS Inferred from Sequence or Structural Similarity more info
involved_in cellular response to peptide hormone stimulus	ISS Inferred from Sequence or Structural Similarity more info
involved_in cholesterol homeostasis	ISS Inferred from Sequence or Structural Similarity more info
involved_in endoplasmic reticulum unfolded protein response	ISS Inferred from Sequence or Structural Similarity more info
involved_in fatty acid biosynthetic process	TAS Traceable Author Statement more info	PubMed
involved_in fatty acid homeostasis	ISS Inferred from Sequence or Structural Similarity more info
involved_in immune response	TAS Traceable Author Statement more info	PubMed
involved_in intracellular triglyceride homeostasis	ISS Inferred from Sequence or Structural Similarity more info
involved_in liver development	ISS Inferred from Sequence or Structural Similarity more info
involved_in muscle organ development	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of apoptotic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of myotube differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in neuron development	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of B cell differentiation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of MHC class II biosynthetic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of T cell differentiation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of angiogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of cell migration	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of cell population proliferation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of cell population proliferation	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of endoplasmic reticulum unfolded protein response	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of fat cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of hepatocyte proliferation	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of immunoglobulin production	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of immunoglobulin production	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of interleukin-6 production	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of lactation	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of plasma cell differentiation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of vascular wound healing	IDA Inferred from Direct Assay more info	PubMed
involved_in protein transport	IEA Inferred from Electronic Annotation more info
involved_in regulation of transcription by RNA polymerase II	NAS Non-traceable Author Statement more info	PubMed
involved_in response to endoplasmic reticulum stress	TAS Traceable Author Statement more info	PubMed
involved_in response to insulin-like growth factor stimulus	ISS Inferred from Sequence or Structural Similarity more info
involved_in sterol homeostasis	ISS Inferred from Sequence or Structural Similarity more info
involved_in transcription by RNA polymerase II	ISS Inferred from Sequence or Structural Similarity more info
involved_in ubiquitin-dependent protein catabolic process	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
part_of RNA polymerase II transcription regulator complex	IPI Inferred from Physical Interaction more info	PubMed
located_in cytoplasm	ISS Inferred from Sequence or Structural Similarity more info
located_in endoplasmic reticulum	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum membrane	IEA Inferred from Electronic Annotation more info
located_in nucleoplasm	TAS Traceable Author Statement more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IDA Inferred from Direct Assay more info
located_in nucleus	NAS Non-traceable Author Statement more info	PubMed

General protein information

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Preferred Names: X-box-binding protein 1

Names: tax-responsive element-binding protein 5

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_012266.1 RefSeqGene

Range

5001..11013

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001079539.2 → NP_001073007.1 X-box-binding protein 1 isoform XBP1(S)

See identical proteins and their annotated locations for NP_001073007.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks a 26 nt segment in the CDS compared to variant 1, that causes a frameshift. The resulting isoform, XBP1(S), has the same N-terminus, but a longer and distinct C-terminus compared to isoform XBP1(U). Isoform XBP1(S) functions as a transcription factor.

Source sequence(s)

AB076383, AB076384, BC015709, BI545390

UniProtKB/Swiss-Prot

P17861

Related

ENSP00000343155.5, ENST00000344347.6

Conserved Domains (1) summary

cd14691
Location:70 → 126

bZIP_XBP1; Basic leucine zipper (bZIP) domain of X-box binding protein 1 (XBP1) and similar proteins: a DNA-binding and dimerization domain
NM_001393999.1 → NP_001380928.1 X-box-binding protein 1 isoform 3

Status: REVIEWED

Source sequence(s)

Z93930

Conserved Domains (1) summary

cd14691
Location:26 → 76

bZIP_XBP1; Basic leucine zipper (bZIP) domain of X-box binding protein 1 (XBP1) and similar proteins: a DNA-binding and dimerization domain
NM_001394000.1 → NP_001380929.1 X-box-binding protein 1 isoform 4

Status: REVIEWED

Source sequence(s)

Z93930

Consensus CDS

CCDS93142.1

UniProtKB/TrEMBL

B1AHH1

Related

ENSP00000384295.3, ENST00000405219.7

Conserved Domains (1) summary

cd14691
Location:26 → 76

bZIP_XBP1; Basic leucine zipper (bZIP) domain of X-box binding protein 1 (XBP1) and similar proteins: a DNA-binding and dimerization domain
NM_005080.4 → NP_005071.2 X-box-binding protein 1 isoform XBP1(U)

See identical proteins and their annotated locations for NP_005071.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript but encodes the shorter isoform, XBP1(U).

Source sequence(s)

Z93930

Consensus CDS

CCDS13847.1

UniProtKB/Swiss-Prot

P17861, Q8WYK6, Q969P1, Q96BD7

UniProtKB/TrEMBL

A8K823

Related

ENSP00000216037.6, ENST00000216037.10

Conserved Domains (1) summary

cd14691
Location:70 → 126

bZIP_XBP1; Basic leucine zipper (bZIP) domain of X-box binding protein 1 (XBP1) and similar proteins: a DNA-binding and dimerization domain