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P17861

- XBP1_HUMAN

UniProt

P17861 - XBP1_HUMAN

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Protein

X-box-binding protein 1

Gene

XBP1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli

Functioni

Transcription factor essential for hepatocyte growth, the differentiation of plasma cells, the immunoglobulin secretion, and the unfolded protein response (UPR). Acts during endoplasmic reticulum stress (ER) by activating unfolded protein response (UPR) target genes via direct binding to the UPR element (UPRE). Binds DNA preferably to the CRE-like element 5'-GATGACGTG[TG]N3[AT]T-3', and also to some TPA response elements (TRE). Binds to the HLA DR-alpha promoter. Binds to the Tax-responsive element (TRE) of HTLV-I.5 Publications

GO - Molecular functioni

  1. DNA binding Source: ProtInc
  2. sequence-specific DNA binding Source: Ensembl
  3. sequence-specific DNA binding RNA polymerase II transcription factor activity Source: Ensembl
  4. sequence-specific DNA binding transcription factor activity Source: ProtInc

GO - Biological processi

  1. activation of signaling protein activity involved in unfolded protein response Source: Reactome
  2. cellular protein metabolic process Source: Reactome
  3. cellular response to antibiotic Source: Ensembl
  4. endoplasmic reticulum unfolded protein response Source: Reactome
  5. epithelial cell maturation involved in salivary gland development Source: Ensembl
  6. exocrine pancreas development Source: Ensembl
  7. glucose homeostasis Source: Ensembl
  8. immune response Source: ProtInc
  9. positive regulation of endoplasmic reticulum unfolded protein response Source: UniProtKB
  10. positive regulation of proteasomal protein catabolic process Source: Ensembl
  11. positive regulation of transcription from RNA polymerase II promoter Source: Ensembl
  12. response to drug Source: Ensembl
  13. response to electrical stimulus Source: Ensembl
  14. serotonin secretion, neurotransmission Source: Ensembl
Complete GO annotation...

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

ReactomeiREACT_18273. XBP1(S) activates chaperone genes.
REACT_18368. IRE1alpha activates chaperones.
REACT_18423. ATF6-alpha activates chaperone genes.
SignaLinkiP17861.

Names & Taxonomyi

Protein namesi
Recommended name:
X-box-binding protein 1
Short name:
XBP-1
Alternative name(s):
Tax-responsive element-binding protein 5
Gene namesi
Name:XBP1
Synonyms:TREB5, XBP2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 22

Organism-specific databases

HGNCiHGNC:12801. XBP1.

Subcellular locationi

GO - Cellular componenti

  1. nucleoplasm Source: Reactome
  2. nucleus Source: LIFEdb
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

Major affective disorder 7 (MAFD7) [MIM:612371]: A major psychiatric disorder that is characterized by severe mood swings, with fluctuation between two abnormal mood states (manic or major depressive episode). Mania is accompanied by symptoms of euphoria, irritability, or excitation, whereas depression is associated with low mood and decreased motivation and energy.
Note: Disease susceptibility may be associated with variations affecting the gene represented in this entry.

Organism-specific databases

MIMi612371. phenotype.
PharmGKBiPA37400.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 261261X-box-binding protein 1PRO_0000076543Add
BLAST

Proteomic databases

MaxQBiP17861.
PaxDbiP17861.
PRIDEiP17861.

PTM databases

PhosphoSiteiP17861.

Expressioni

Inductioni

Up-regulated by ATF6 via direct binding to the ERSE in response to endoplasmic reticulum stress.1 Publication

Gene expression databases

BgeeiP17861.
CleanExiHS_XBP1.
ExpressionAtlasiP17861. baseline and differential.
GenevestigatoriP17861.

Organism-specific databases

HPAiHPA044305.

Interactioni

Protein-protein interaction databases

BioGridi113331. 25 interactions.
DIPiDIP-41692N.
IntActiP17861. 4 interactions.
MINTiMINT-268152.
STRINGi9606.ENSP00000216037.

Structurei

3D structure databases

ProteinModelPortaliP17861.
SMRiP17861. Positions 62-127.
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
Regioni98 – 13336Leucine-zipperPROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiNOG285368.
GeneTreeiENSGT00390000017751.
HOGENOMiHOG000007671.
HOVERGENiHBG061457.
InParanoidiP17861.
KOiK09027.
OMAiFDHIYTK.
OrthoDBiEOG74BJVQ.
PhylomeDBiP17861.
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]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: P17861-1) [UniParc]FASTAAdd to Basket

Also known as: XBP-1U

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
MVVVAAAPNP ADGTPKVLLL SGQPASAAGA PAGQALPLMV PAQRGASPEA
60 70 80 90 100
ASGGLPQARK RQRLTHLSPE EKALRRKLKN RVAAQTARDR KKARMSELEQ
110 120 130 140 150
QVVDLEEENQ KLLLENQLLR EKTHGLVVEN QELRQRLGMD ALVAEEEAEA
160 170 180 190 200
KGNEVRPVAG SAESAALRLR APLQQVQAQL SPLQNISPWI LAVLTLQIQS
210 220 230 240 250
LISCWAFWTT WTQSCSSNAL PQSLPAWRSS QRSTQKDPVP YQPPFLCQWG
260
RHQPSWKPLM N
Length:261
Mass (Da):28,695
Last modified:March 1, 2005 - v2
Checksum:iA4EF69EEE0D344A6
GO
Isoform 2 (identifier: P17861-2) [UniParc]FASTAAdd to Basket

Also known as: XBP-1S

The sequence of this isoform differs from the canonical sequence as follows:
     167-261: LRLRAPLQQV...HQPSWKPLMN → GAGPVVTPPE...NELFPQLISV

Note: Potent transcriptional activator. Induced by ERN1 in response to endoplasmic reticulum stress. ENR1 cleaves a 26-bp fragment causing a frameshift of the mRNA transcript.

Show »
Length:376
Mass (Da):40,148
Checksum:i4C1758D7BA055061
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti33 – 353GQA → AR in AAA36031. (PubMed:2321018)Curated
Sequence conflicti130 – 1301N → T in L13850. (PubMed:8349596)Curated
Sequence conflicti196 – 1961L → F in L13850. (PubMed:8349596)Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti12 – 121D → V in a breast cancer sample; somatic mutation. 1 Publication
VAR_035998
Natural varianti232 – 2321R → K in a breast cancer sample; somatic mutation. 1 Publication
VAR_033023

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei167 – 26195LRLRA…KPLMN → GAGPVVTPPEHLPMDSGGID SSDSESDILLGILDNLDPVM FFKCPSPEPASLEELPEVYP EGPSSLPASLSLSVGTSSAK LEAINELIRFDHIYTKPLVL EIPSETESQANVVVKIEEAP LSPSENDHPEFIVSVKEEPV EDDLVPELGISNLLSSSHCP KPSSCLLDAYSDCGYGGSLS PFSDMSSLLGVNHSWEDTFA NELFPQLISV in isoform 2. 1 PublicationVSP_012936Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
M31627 mRNA. Translation: AAA36031.1.
X55543 Genomic DNA. Translation: CAA39149.1.
L13850 Genomic DNA. No translation available.
AB076383 mRNA. Translation: BAB82981.1.
AB076384 mRNA. Translation: BAB82982.1.
CR456611 mRNA. Translation: CAG30497.1.
Z93930 Genomic DNA. Translation: CAB45016.1.
BC000938 mRNA. Translation: AAH00938.1.
BC012841 mRNA. Translation: AAH12841.1.
BC015709 mRNA. Translation: AAH15709.1.
CCDSiCCDS13847.1. [P17861-1]
PIRiA36299.
RefSeqiNP_001073007.1. NM_001079539.1. [P17861-2]
NP_005071.2. NM_005080.3. [P17861-1]
UniGeneiHs.437638.

Genome annotation databases

EnsembliENST00000216037; ENSP00000216037; ENSG00000100219. [P17861-1]
ENST00000344347; ENSP00000343155; ENSG00000100219. [P17861-2]
ENST00000611155; ENSP00000481170; ENSG00000100219. [P17861-2]
GeneIDi7494.
KEGGihsa:7494.
UCSCiuc003aec.3. human. [P17861-2]

Polymorphism databases

DMDMi60416406.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
M31627 mRNA. Translation: AAA36031.1 .
X55543 Genomic DNA. Translation: CAA39149.1 .
L13850 Genomic DNA. No translation available.
AB076383 mRNA. Translation: BAB82981.1 .
AB076384 mRNA. Translation: BAB82982.1 .
CR456611 mRNA. Translation: CAG30497.1 .
Z93930 Genomic DNA. Translation: CAB45016.1 .
BC000938 mRNA. Translation: AAH00938.1 .
BC012841 mRNA. Translation: AAH12841.1 .
BC015709 mRNA. Translation: AAH15709.1 .
CCDSi CCDS13847.1. [P17861-1 ]
PIRi A36299.
RefSeqi NP_001073007.1. NM_001079539.1. [P17861-2 ]
NP_005071.2. NM_005080.3. [P17861-1 ]
UniGenei Hs.437638.

3D structure databases

ProteinModelPortali P17861.
SMRi P17861. Positions 62-127.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 113331. 25 interactions.
DIPi DIP-41692N.
IntActi P17861. 4 interactions.
MINTi MINT-268152.
STRINGi 9606.ENSP00000216037.

Chemistry

BindingDBi P17861.
ChEMBLi CHEMBL1741176.

PTM databases

PhosphoSitei P17861.

Polymorphism databases

DMDMi 60416406.

Proteomic databases

MaxQBi P17861.
PaxDbi P17861.
PRIDEi P17861.

Protocols and materials databases

DNASUi 7494.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000216037 ; ENSP00000216037 ; ENSG00000100219 . [P17861-1 ]
ENST00000344347 ; ENSP00000343155 ; ENSG00000100219 . [P17861-2 ]
ENST00000611155 ; ENSP00000481170 ; ENSG00000100219 . [P17861-2 ]
GeneIDi 7494.
KEGGi hsa:7494.
UCSCi uc003aec.3. human. [P17861-2 ]

Organism-specific databases

CTDi 7494.
GeneCardsi GC22M029190.
HGNCi HGNC:12801. XBP1.
HPAi HPA044305.
MIMi 194355. gene.
612371. phenotype.
neXtProti NX_P17861.
PharmGKBi PA37400.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG285368.
GeneTreei ENSGT00390000017751.
HOGENOMi HOG000007671.
HOVERGENi HBG061457.
InParanoidi P17861.
KOi K09027.
OMAi FDHIYTK.
OrthoDBi EOG74BJVQ.
PhylomeDBi P17861.
TreeFami TF319837.

Enzyme and pathway databases

Reactomei REACT_18273. XBP1(S) activates chaperone genes.
REACT_18368. IRE1alpha activates chaperones.
REACT_18423. ATF6-alpha activates chaperone genes.
SignaLinki P17861.

Miscellaneous databases

GeneWikii XBP1.
GenomeRNAii 7494.
NextBioi 29352.
PROi P17861.
SOURCEi Search...

Gene expression databases

Bgeei P17861.
CleanExi HS_XBP1.
ExpressionAtlasi P17861. baseline and differential.
Genevestigatori P17861.

Family and domain databases

InterProi IPR004827. bZIP.
[Graphical view ]
Pfami PF07716. bZIP_2. 1 hit.
[Graphical view ]
SMARTi SM00338. BRLZ. 1 hit.
[Graphical view ]
PROSITEi PS50217. BZIP. 1 hit.
PS00036. BZIP_BASIC. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "A new member of the leucine zipper class of proteins that binds to the HLA DR alpha promoter."
    Liou H.-C., Boothby M.R., Finn P.W., Davidon R., Nabavi N., Zeleznik-Le N.J., Ting J.P.-Y., Glimcher L.H.
    Science 247:1581-1584(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION.
  2. "Multiple cDNA clones encoding nuclear proteins that bind to the tax-dependent enhancer of HTLV-1: all contain a leucine zipper structure and basic amino acid domain."
    Yoshimura T., Fujisawa J., Yoshida M.
    EMBO J. 9:2537-2542(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION.
  3. "The regulatory gene, hXBP-1, and its target, HLA-DRA, utilize both common and distinct regulatory elements and protein complexes."
    Ponath P.D., Fass D., Liou H.C., Glimcher L.H., Strominger J.L.
    J. Biol. Chem. 268:17074-17082(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION.
  4. "XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress to produce a highly active transcription factor."
    Yoshida H., Matsui T., Yamamoto A., Okada T., Mori K.
    Cell 107:881-891(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), INDUCTION, FUNCTION.
  5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
  6. "The DNA sequence of human chromosome 22."
    Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M.
    , Buck D., Burgess J., Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., Wright H.
    Nature 402:489-495(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  7. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Ovary and Placenta.
  8. "The basic domain/leucine zipper protein hXBP-1 preferentially binds to and transactivates CRE-like sequences containing an ACGT core."
    Clauss I.M., Chu M., Zhao J.-L., Glimcher L.H.
    Nucleic Acids Res. 24:1855-1864(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  9. "Impaired feedback regulation of XBP1 as a genetic risk factor for bipolar disorder."
    Kakiuchi C., Iwamoto K., Ishiwata M., Bundo M., Kasahara T., Kusumi I., Tsujita T., Okazaki Y., Nanko S., Kunugi H., Sasaki T., Kato T.
    Nat. Genet. 35:171-175(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: INVOLVEMENT IN SUSCEPTIBILITY TO MAJOR AFFECTIVE DISORDER TYPE 7.
  10. Cited for: VARIANT [LARGE SCALE ANALYSIS] VAL-12.
  11. "Somatic sequence alterations in twenty-one genes selected by expression profile analysis of breast carcinomas."
    Chanock S.J., Burdett L., Yeager M., Llaca V., Langeroed A., Presswalla S., Kaaresen R., Strausberg R.L., Gerhard D.S., Kristensen V., Perou C.M., Boerresen-Dale A.-L.
    Breast Cancer Res. 9:R5-R5(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT LYS-232.

Entry informationi

Entry nameiXBP1_HUMAN
AccessioniPrimary (citable) accession number: P17861
Secondary accession number(s): Q8WYK6, Q969P1, Q96BD7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1990
Last sequence update: March 1, 2005
Last modified: October 29, 2014
This is version 150 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 22
    Human chromosome 22: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3