P17861 (XBP1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
X-box-binding protein 1
Short name=XBP-1

Alternative name(s):
Tax-responsive element-binding protein 5

Gene names

Name:	XBP1
Synonyms:	TREB5, XBP2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	261 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	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. Ref.1 Ref.2 Ref.3 Ref.4 Ref.8
Subcellular location	Nucleus.
Induction	Up-regulated by ATF6 via direct binding to the ERSE in response to endoplasmic reticulum stress. Ref.4
Involvement in disease	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.
Sequence similarities	Belongs to the bZIP family. Contains 1 bZIP (basic-leucine zipper) domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	DNA-binding
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	activation of signaling protein activity involved in unfolded protein response Traceable author statement. Source: Reactome epithelial cell maturation involved in salivary gland development Inferred from electronic annotation. Source: Compara exocrine pancreas development Inferred from electronic annotation. Source: Compara immune response Traceable author statement PubMed 1718857. Source: ProtInc positive regulation of endoplasmic reticulum unfolded protein response Inferred from mutant phenotype PubMed 16645094. Source: UniProtKB response to drug Inferred from electronic annotation. Source: Compara response to electrical stimulus Inferred from electronic annotation. Source: Compara serotonin secretion, neurotransmission Inferred from electronic annotation. Source: Compara transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara
Cellular_component	nucleoplasm Traceable author statement. Source: Reactome
Molecular_function	DNA binding Traceable author statement PubMed 1718857. Source: ProtInc sequence-specific DNA binding Inferred from electronic annotation. Source: Compara sequence-specific DNA binding transcription factor activity Traceable author statement PubMed 1718857Ref.1. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P17861-1)

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.

Isoform 2 (identifier: P17861-2)

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.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 261	261	X-box-binding protein 1		PRO_0000076543
Regions
	Domain	70 – 133	64	bZIP
	Region	72 – 94	23	Basic motif By similarity
	Region	98 – 133	36	Leucine-zipper By similarity
Natural variations
	Alternative sequence	167 – 261	95	LRLRA…KPLMN → GAGPVVTPPEHLPMDSGGID SSDSESDILLGILDNLDPVM FFKCPSPEPASLEELPEVYP EGPSSLPASLSLSVGTSSAK LEAINELIRFDHIYTKPLVL EIPSETESQANVVVKIEEAP LSPSENDHPEFIVSVKEEPV EDDLVPELGISNLLSSSHCP KPSSCLLDAYSDCGYGGSLS PFSDMSSLLGVNHSWEDTFA NELFPQLISV in isoform 2.		VSP_012936
	Natural variant	12	1	D → V in a breast cancer sample; somatic mutation. Ref.10		VAR_035998
	Natural variant	232	1	R → K in a breast cancer sample; somatic mutation. Ref.11		VAR_033023
Experimental info
	Sequence conflict	33 – 35	3	GQA → AR in AAA36031. Ref.1
	Sequence conflict	130	1	N → T in L13850. Ref.3
	Sequence conflict	196	1	L → F in L13850. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (XBP-1U) [UniParc]. Last modified March 1, 2005. Version 2. Checksum: A4EF69EEE0D344A6	FASTA	261	28,695
	10 20 30 40 50 60 MVVVAAAPNP ADGTPKVLLL SGQPASAAGA PAGQALPLMV PAQRGASPEA ASGGLPQARK 70 80 90 100 110 120 RQRLTHLSPE EKALRRKLKN RVAAQTARDR KKARMSELEQ QVVDLEEENQ KLLLENQLLR 130 140 150 160 170 180 EKTHGLVVEN QELRQRLGMD ALVAEEEAEA KGNEVRPVAG SAESAALRLR APLQQVQAQL 190 200 210 220 230 240 SPLQNISPWI LAVLTLQIQS LISCWAFWTT WTQSCSSNAL PQSLPAWRSS QRSTQKDPVP 250 260 YQPPFLCQWG RHQPSWKPLM N
	Isoform 2 (XBP-1S) [UniParc]. Checksum: 4C1758D7BA055061	FASTA	376	40,148
	10 20 30 40 50 60 MVVVAAAPNP ADGTPKVLLL SGQPASAAGA PAGQALPLMV PAQRGASPEA ASGGLPQARK 70 80 90 100 110 120 RQRLTHLSPE EKALRRKLKN RVAAQTARDR KKARMSELEQ QVVDLEEENQ KLLLENQLLR 130 140 150 160 170 180 EKTHGLVVEN QELRQRLGMD ALVAEEEAEA KGNEVRPVAG SAESAAGAGP VVTPPEHLPM 190 200 210 220 230 240 DSGGIDSSDS ESDILLGILD NLDPVMFFKC PSPEPASLEE LPEVYPEGPS SLPASLSLSV 250 260 270 280 290 300 GTSSAKLEAI NELIRFDHIY TKPLVLEIPS ETESQANVVV KIEEAPLSPS ENDHPEFIVS 310 320 330 340 350 360 VKEEPVEDDL VPELGISNLL SSSHCPKPSS CLLDAYSDCG YGGSLSPFSD MSSLLGVNHS 370 WEDTFANELF PQLISV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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]	"A genome annotation-driven approach to cloning the human ORFeome." Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A., Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J., Beare D.M., Dunham I. Genome Biol. 5:R84.1-R84.11(2004) [PubMed] [Europe PMC] [Abstract] 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]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract] 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.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	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.
IPI	IPI00056479. IPI00411953.
PIR	A36299.
RefSeq	NP_001073007.1. NM_001079539.1. NP_005071.2. NM_005080.3.
UniGene	Hs.437638.
3D structure databases
ProteinModelPortal	P17861.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-268152.
STRING	9606.ENSP00000216037.
PTM databases
PhosphoSite	P17861.
Polymorphism databases
DMDM	60416406.
Proteomic databases
PaxDb	P17861.
PRIDE	P17861.
Protocols and materials databases
DNASU	7494.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000216037; ENSP00000216037; ENSG00000100219. ENST00000344347; ENSP00000343155; ENSG00000100219.
GeneID	7494.
KEGG	hsa:7494.
UCSC	uc003aec.3. human.
Organism-specific databases
CTD	7494.
GeneCards	GC22M029190.
HGNC	HGNC:12801. XBP1.
HPA	HPA044305.
MIM	194355. gene. 612371. phenotype.
neXtProt	NX_P17861.
PharmGKB	PA37400.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG285368.
HOGENOM	HOG000007671.
HOVERGEN	HBG061457.
KO	K09027.
OMA	FDHIYTK.
OrthoDB	EOG4BK54X.
Enzyme and pathway databases
Pathway_Interaction_DB	hnf3apathway. FOXA1 transcription factor network.
Reactome	REACT_116125. Disease.
Gene expression databases
ArrayExpress	P17861.
Bgee	P17861.
CleanEx	HS_XBP1.
Genevestigator	P17861.
GermOnline	ENSG00000100219. Homo sapiens.
Family and domain databases
InterPro	IPR004827. bZIP. [Graphical view]
Pfam	PF07716. bZIP_2. 1 hit. [Graphical view]
SMART	SM00338. BRLZ. 1 hit. [Graphical view]
PROSITE	PS50217. BZIP. 1 hit. PS00036. BZIP_BASIC. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	P17861.
ChEMBL	CHEMBL1741176.
GenomeRNAi	7494.
NextBio	29352.
SOURCE	Search...

Entry information

Entry name

XBP1_HUMAN

Accession

Primary (citable) accession number: P17861
Secondary accession number(s): Q8WYK6, Q969P1, Q96BD7

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1990
Last sequence update:	March 1, 2005
Last modified:	May 1, 2013
This is version 134 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.