Reviewed, UniProtKB/Swiss-Prot P17861 (XBP1_HUMAN)

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)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	261 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
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	Genetic variations in XBP1 could be associated with susceptibility to major affective disorder type 7 (MAFD7) [MIM:612371]. Major affective disorders represent a class of mental disorders characterized by a disturbance in mood as their predominant feature.
Sequence similarities	Belongs to the bZIP family. Contains 1 bZIP domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	DNA-binding
Gene Ontology (GO)
Biological process	immune response Traceable author statement. Source: ProtInc regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW transcription Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	nucleus Inferred from direct assay. Source: LIFEdb
Molecular function	protein dimerization activity Inferred from electronic annotation. Source: InterPro sequence-specific DNA binding Inferred from electronic annotation. Source: InterPro transcription factor activity Ref.1 Traceable author statement. 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	98 – 126	29	Leucine-zipper
	DNA binding	72 – 94	23	Basic motif
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 Ref.3
	Sequence conflict	196	1	L → F 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). 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: 2321018] [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: 2196176] [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: 8349596] [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: 11779464] [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:RESEARCH84.1-RESEARCH84.11(2004) [PubMed: 15461802] [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: 10591208] [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: 15489334] [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: 8657566] [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: 12949534] [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: 16959974] [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: 17224074] [Abstract] Cited for: VARIANT LYS-232.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	M31627 mRNA. Translation: AAA36031.1. X55543 Genomic DNA. Translation: CAA39149.1. L13850 Unassigned 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. NP_005071.2.
UniGene	Hs.437638
3D structure databases
HSSP	HSSP built from PDB template 1JNM based on UniProtKB P05412.
ModBase	Search...
Proteomic databases
PRIDE	P17861.
Genome annotation databases
Ensembl	ENSG00000100219. Homo sapiens. [Contig view]
GeneID	7494.
KEGG	hsa:7494.
Organism-specific databases
GeneCards	GC22M027515.
H-InvDB	HIX0016344.
HGNC	HGNC:12801. XBP1.
MIM	194355. gene. 612371. phenotype.
PharmGKB	PA36241.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	P17861.
OMA	P17861. PFSDMSS.
Enzyme and pathway databases
Pathway_Interaction_DB	hnf3apathway. FOXA1 transcription factor network.
Gene expression databases
ArrayExpress	P17861.
Bgee	P17861.
CleanEx	HS_XBP1.
GermOnline	ENSG00000100219. Homo sapiens.
Family and domain databases
InterPro	IPR011700. bZIP_2. IPR004827. TF_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 Resources
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:	June 16, 2009
This is version 93 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)