Full text data of HSP90B1
HSP90B1
(GRP94, TRA1)
[Confidence: high (present in two of the MS resources)]
Endoplasmin (94 kDa glucose-regulated protein; GRP-94; Heat shock protein 90 kDa beta member 1; Tumor rejection antigen 1; gp96 homolog; Flags: Precursor)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Endoplasmin (94 kDa glucose-regulated protein; GRP-94; Heat shock protein 90 kDa beta member 1; Tumor rejection antigen 1; gp96 homolog; Flags: Precursor)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P14625
ID ENPL_HUMAN Reviewed; 803 AA.
AC P14625; Q96A97;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-APR-1990, sequence version 1.
DT 22-JAN-2014, entry version 167.
DE RecName: Full=Endoplasmin;
DE AltName: Full=94 kDa glucose-regulated protein;
DE Short=GRP-94;
DE AltName: Full=Heat shock protein 90 kDa beta member 1;
DE AltName: Full=Tumor rejection antigen 1;
DE AltName: Full=gp96 homolog;
DE Flags: Precursor;
GN Name=HSP90B1; Synonyms=GRP94, TRA1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF
RP 1-16.
RC TISSUE=Blood;
RX PubMed=2377606; DOI=10.1073/pnas.87.15.5658;
RA Maki R.G., Old L.J., Srivastava P.K.;
RT "Human homologue of murine tumor rejection antigen gp96: 5'-regulatory
RT and coding regions and relationship to stress-induced proteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:5658-5662(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-16.
RC TISSUE=Liver;
RX PubMed=2546060;
RA Chang S.C., Erwin A.E., Lee A.S.;
RT "Glucose-regulated protein (GRP94 and GRP78) genes share common
RT regulatory domains and are coordinately regulated by common trans-
RT acting factors.";
RL Mol. Cell. Biol. 9:2153-2162(1989).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 22-803.
RC TISSUE=Liver;
RA Meng S., Tien P.;
RT "The association of heat shock protein gp96 with HBV-derived peptides
RT in vitro.";
RL Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP PROTEIN SEQUENCE OF 22-39.
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A.,
RA Thomas G.R., Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass
RT spectrometric identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [6]
RP COMPONENT OF A CHAPERONE COMPLEX.
RX PubMed=12475965; DOI=10.1091/mbc.E02-05-0311;
RA Meunier L., Usherwood Y.-K., Chung K.T., Hendershot L.M.;
RT "A subset of chaperones and folding enzymes form multiprotein
RT complexes in endoplasmic reticulum to bind nascent proteins.";
RL Mol. Biol. Cell 13:4456-4469(2002).
RN [7]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY.
RC TISSUE=Melanoma;
RX PubMed=12643545; DOI=10.1021/pr025562r;
RA Basrur V., Yang F., Kushimoto T., Higashimoto Y., Yasumoto K.,
RA Valencia J., Muller J., Vieira W.D., Watabe H., Shabanowitz J.,
RA Hearing V.J., Hunt D.F., Appella E.;
RT "Proteomic analysis of early melanosomes: identification of novel
RT melanosomal proteins.";
RL J. Proteome Res. 2:69-79(2003).
RN [8]
RP GLYCOSYLATION AT ASN-217 AND ASN-445.
RX PubMed=12754519; DOI=10.1038/nbt827;
RA Zhang H., Li X.-J., Martin D.B., Aebersold R.;
RT "Identification and quantification of N-linked glycoproteins using
RT hydrazide chemistry, stable isotope labeling and mass spectrometry.";
RL Nat. Biotechnol. 21:660-666(2003).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [10]
RP INTERACTION WITH CNPY3; TLR4 AND TLR9.
RX PubMed=20865800; DOI=10.1038/ncomms1070;
RA Liu B., Yang Y., Qiu Z., Staron M., Hong F., Li Y., Wu S., Li Y.,
RA Hao B., Bona R., Han D., Li Z.;
RT "Folding of Toll-like receptors by the HSP90 paralogue gp96 requires a
RT substrate-specific cochaperone.";
RL Nat. Commun. 1:79-79(2010).
RN [11]
RP ERRATUM.
RA Liu B., Yang Y., Qiu Z., Staron M., Hong F., Li Y., Wu S., Li Y.,
RA Hao B., Bona R., Han D., Li Z.;
RL Nat. Commun. 3:653-653(2012).
RN [12]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY.
RC TISSUE=Melanoma;
RX PubMed=17081065; DOI=10.1021/pr060363j;
RA Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H.,
RA Mangini N.J., Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R.,
RA Yamagishi S., Shabanowitz J., Hearing V.J., Wu C., Appella E.,
RA Hunt D.F.;
RT "Proteomic and bioinformatic characterization of the biogenesis and
RT function of melanosomes.";
RL J. Proteome Res. 5:3135-3144(2006).
RN [13]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-107, AND MASS
RP SPECTROMETRY.
RC TISSUE=Platelet;
RX PubMed=16263699; DOI=10.1074/mcp.M500324-MCP200;
RA Lewandrowski U., Moebius J., Walter U., Sickmann A.;
RT "Elucidation of N-glycosylation sites on human platelet proteins: a
RT glycoproteomic approach.";
RL Mol. Cell. Proteomics 5:226-233(2006).
RN [14]
RP FUNCTION, AND INTERACTION WITH OS9.
RX PubMed=18264092; DOI=10.1038/ncb1689;
RA Christianson J.C., Shaler T.A., Tyler R.E., Kopito R.R.;
RT "OS-9 and GRP94 deliver mutant alpha1-antitrypsin to the Hrd1-SEL1L
RT ubiquitin ligase complex for ERAD.";
RL Nat. Cell Biol. 10:272-282(2008).
RN [15]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-62; ASN-107; ASN-217 AND
RP ASN-445, AND MASS SPECTROMETRY.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of
RT multiple enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-306, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-306, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [19]
RP INTERACTION WITH METTL23.
RX PubMed=23349634; DOI=10.1371/journal.pgen.1003210;
RA Cloutier P., Lavallee-Adam M., Faubert D., Blanchette M., Coulombe B.;
RT "A newly uncovered group of distantly related lysine
RT methyltransferases preferentially interact with molecular chaperones
RT to regulate their activity.";
RL PLoS Genet. 9:E1003210-E1003210(2013).
CC -!- FUNCTION: Molecular chaperone that functions in the processing and
CC transport of secreted proteins. When associated with CNPY3,
CC required for proper folding of Toll-like receptors (By
CC similarity). Functions in endoplasmic reticulum associated
CC degradation (ERAD). Has ATPase activity.
CC -!- SUBUNIT: Homodimer; disulfide-linked. Component of an EIF2 complex
CC at least composed of CELF1/CUGBP1, CALR, CALR3, EIF2S1, EIF2S2,
CC HSP90B1 and HSPA5 (By similarity). Part of a large chaperone
CC multiprotein complex comprising DNAJB11, HSP90B1, HSPA5, HYOU,
CC PDIA2, PDIA4, PDIA6, PPIB, SDF2L1, UGT1A1 and very small amounts
CC of ERP29, but not, or at very low levels, CALR nor CANX. Interacts
CC with AIMP1; regulates its retention in the endoplasmic reticulum.
CC Interacts with OS9. Interacts with CNPY3. This interaction is
CC disrupted in the presence of ATP (By similarity). Interacts with
CC TLR4 and TLR9, but not with TLR3. Interacts with MZB1 in a
CC calcium-dependent manner (By similarity). Interacts with METTL23.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum lumen. Melanosome.
CC Note=Identified by mass spectrometry in melanosome fractions from
CC stage I to stage IV.
CC -!- SIMILARITY: Belongs to the heat shock protein 90 family.
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DR EMBL; X15187; CAA33261.1; -; mRNA.
DR EMBL; M33716; AAA68201.1; -; Genomic_DNA.
DR EMBL; BC066656; AAH66656.1; -; mRNA.
DR EMBL; M26596; AAA58621.1; -; Genomic_DNA.
DR EMBL; AY040226; AAK74072.1; -; mRNA.
DR PIR; A35954; A35954.
DR RefSeq; NP_003290.1; NM_003299.2.
DR UniGene; Hs.192374; -.
DR ProteinModelPortal; P14625; -.
DR SMR; P14625; 72-755.
DR DIP; DIP-36060N; -.
DR IntAct; P14625; 36.
DR MINT; MINT-210408; -.
DR STRING; 9606.ENSP00000299767; -.
DR BindingDB; P14625; -.
DR ChEMBL; CHEMBL1075323; -.
DR DrugBank; DB00615; Rifabutin.
DR PhosphoSite; P14625; -.
DR DMDM; 119360; -.
DR DOSAC-COBS-2DPAGE; P14625; -.
DR OGP; P14625; -.
DR REPRODUCTION-2DPAGE; IPI00027230; -.
DR PaxDb; P14625; -.
DR PeptideAtlas; P14625; -.
DR PRIDE; P14625; -.
DR DNASU; 7184; -.
DR Ensembl; ENST00000299767; ENSP00000299767; ENSG00000166598.
DR GeneID; 7184; -.
DR KEGG; hsa:7184; -.
DR UCSC; uc001tkb.2; human.
DR CTD; 7184; -.
DR GeneCards; GC12P104324; -.
DR H-InvDB; HIX0056796; -.
DR HGNC; HGNC:12028; HSP90B1.
DR HPA; CAB005224; -.
DR HPA; HPA003901; -.
DR HPA; HPA008424; -.
DR MIM; 191175; gene.
DR neXtProt; NX_P14625; -.
DR PharmGKB; PA36705; -.
DR eggNOG; COG0326; -.
DR HOGENOM; HOG000031988; -.
DR HOVERGEN; HBG007374; -.
DR InParanoid; P14625; -.
DR KO; K09487; -.
DR OMA; HITDTGI; -.
DR OrthoDB; EOG780RM0; -.
DR PhylomeDB; P14625; -.
DR Reactome; REACT_160300; Binding and Uptake of Ligands by Scavenger Receptors.
DR Reactome; REACT_17015; Metabolism of proteins.
DR Reactome; REACT_6900; Immune System.
DR ChiTaRS; HSP90B1; human.
DR GeneWiki; HSP90B1; -.
DR GenomeRNAi; 7184; -.
DR NextBio; 28164; -.
DR PMAP-CutDB; P14625; -.
DR PRO; PR:P14625; -.
DR ArrayExpress; P14625; -.
DR Bgee; P14625; -.
DR CleanEx; HS_HSP90B1; -.
DR Genevestigator; P14625; -.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0071682; C:endocytic vesicle lumen; TAS:Reactome.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0030496; C:midbody; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IEA:Ensembl.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005509; F:calcium ion binding; TAS:UniProtKB.
DR GO; GO:0050750; F:low-density lipoprotein particle receptor binding; IDA:MGI.
DR GO; GO:0019903; F:protein phosphatase binding; IDA:MGI.
DR GO; GO:0003723; F:RNA binding; IDA:UniProtKB.
DR GO; GO:0046790; F:virion binding; IPI:UniProtKB.
DR GO; GO:0031247; P:actin rod assembly; IDA:MGI.
DR GO; GO:0006987; P:activation of signaling protein activity involved in unfolded protein response; TAS:Reactome.
DR GO; GO:0071318; P:cellular response to ATP; IDA:MGI.
DR GO; GO:0030433; P:ER-associated ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
DR GO; GO:0045087; P:innate immune response; TAS:Reactome.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0006457; P:protein folding; IEA:InterPro.
DR GO; GO:0015031; P:protein transport; NAS:UniProtKB.
DR GO; GO:0043666; P:regulation of phosphoprotein phosphatase activity; IDA:MGI.
DR GO; GO:0001666; P:response to hypoxia; IDA:UniProtKB.
DR GO; GO:0051208; P:sequestering of calcium ion; NAS:UniProtKB.
DR GO; GO:0002224; P:toll-like receptor signaling pathway; TAS:Reactome.
DR Gene3D; 3.30.565.10; -; 2.
DR InterPro; IPR015566; Endoplasmin.
DR InterPro; IPR003594; HATPase_ATP-bd.
DR InterPro; IPR019805; Heat_shock_protein_90_CS.
DR InterPro; IPR001404; Hsp90_fam.
DR InterPro; IPR020575; Hsp90_N.
DR InterPro; IPR020568; Ribosomal_S5_D2-typ_fold.
DR PANTHER; PTHR11528; PTHR11528; 1.
DR PANTHER; PTHR11528:SF21; PTHR11528:SF21; 1.
DR Pfam; PF00183; HSP90; 1.
DR PIRSF; PIRSF002583; Hsp90; 1.
DR PRINTS; PR00775; HEATSHOCK90.
DR SMART; SM00387; HATPase_c; 1.
DR SUPFAM; SSF54211; SSF54211; 1.
DR SUPFAM; SSF55874; SSF55874; 2.
DR PROSITE; PS00014; ER_TARGET; 1.
DR PROSITE; PS00298; HSP90; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Calcium; Chaperone; Complete proteome;
KW Direct protein sequencing; Disulfide bond; Endoplasmic reticulum;
KW Glycoprotein; Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Signal.
FT SIGNAL 1 21
FT CHAIN 22 803 Endoplasmin.
FT /FTId=PRO_0000013598.
FT MOTIF 800 803 Prevents secretion from ER.
FT BINDING 107 107 ATP (By similarity).
FT BINDING 149 149 ATP (By similarity).
FT BINDING 162 162 ATP (By similarity).
FT BINDING 168 168 ATP (By similarity).
FT BINDING 199 199 ATP; via amide nitrogen (By similarity).
FT BINDING 448 448 ATP (By similarity).
FT MOD_RES 306 306 Phosphoserine.
FT CARBOHYD 62 62 N-linked (GlcNAc...).
FT CARBOHYD 107 107 N-linked (GlcNAc...).
FT CARBOHYD 217 217 N-linked (GlcNAc...).
FT CARBOHYD 445 445 N-linked (GlcNAc...).
FT CARBOHYD 481 481 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 502 502 N-linked (GlcNAc...) (Potential).
FT DISULFID 138 138 Interchain (By similarity).
FT CONFLICT 188 188 T -> S (in Ref. 4; AAK74072).
FT CONFLICT 419 419 T -> P (in Ref. 4; AAK74072).
FT CONFLICT 803 803 L -> F (in Ref. 4; AAK74072).
SQ SEQUENCE 803 AA; 92469 MW; 9BF6705A7A2ED0D0 CRC64;
MRALWVLGLC CVLLTFGSVR ADDEVDVDGT VEEDLGKSRE GSRTDDEVVQ REEEAIQLDG
LNASQIRELR EKSEKFAFQA EVNRMMKLII NSLYKNKEIF LRELISNASD ALDKIRLISL
TDENALSGNE ELTVKIKCDK EKNLLHVTDT GVGMTREELV KNLGTIAKSG TSEFLNKMTE
AQEDGQSTSE LIGQFGVGFY SAFLVADKVI VTSKHNNDTQ HIWESDSNEF SVIADPRGNT
LGRGTTITLV LKEEASDYLE LDTIKNLVKK YSQFINFPIY VWSSKTETVE EPMEEEEAAK
EEKEESDDEA AVEEEEEEKK PKTKKVEKTV WDWELMNDIK PIWQRPSKEV EEDEYKAFYK
SFSKESDDPM AYIHFTAEGE VTFKSILFVP TSAPRGLFDE YGSKKSDYIK LYVRRVFITD
DFHDMMPKYL NFVKGVVDSD DLPLNVSRET LQQHKLLKVI RKKLVRKTLD MIKKIADDKY
NDTFWKEFGT NIKLGVIEDH SNRTRLAKLL RFQSSHHPTD ITSLDQYVER MKEKQDKIYF
MAGSSRKEAE SSPFVERLLK KGYEVIYLTE PVDEYCIQAL PEFDGKRFQN VAKEGVKFDE
SEKTKESREA VEKEFEPLLN WMKDKALKDK IEKAVVSQRL TESPCALVAS QYGWSGNMER
IMKAQAYQTG KDISTNYYAS QKKTFEINPR HPLIRDMLRR IKEDEDDKTV LDLAVVLFET
ATLRSGYLLP DTKAYGDRIE RMLRLSLNID PDAKVEEEPE EEPEETAEDT TEDTEQDEDE
EMDVGTDEEE ETAKESTAEK DEL
//
ID ENPL_HUMAN Reviewed; 803 AA.
AC P14625; Q96A97;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-APR-1990, sequence version 1.
DT 22-JAN-2014, entry version 167.
DE RecName: Full=Endoplasmin;
DE AltName: Full=94 kDa glucose-regulated protein;
DE Short=GRP-94;
DE AltName: Full=Heat shock protein 90 kDa beta member 1;
DE AltName: Full=Tumor rejection antigen 1;
DE AltName: Full=gp96 homolog;
DE Flags: Precursor;
GN Name=HSP90B1; Synonyms=GRP94, TRA1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF
RP 1-16.
RC TISSUE=Blood;
RX PubMed=2377606; DOI=10.1073/pnas.87.15.5658;
RA Maki R.G., Old L.J., Srivastava P.K.;
RT "Human homologue of murine tumor rejection antigen gp96: 5'-regulatory
RT and coding regions and relationship to stress-induced proteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:5658-5662(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-16.
RC TISSUE=Liver;
RX PubMed=2546060;
RA Chang S.C., Erwin A.E., Lee A.S.;
RT "Glucose-regulated protein (GRP94 and GRP78) genes share common
RT regulatory domains and are coordinately regulated by common trans-
RT acting factors.";
RL Mol. Cell. Biol. 9:2153-2162(1989).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 22-803.
RC TISSUE=Liver;
RA Meng S., Tien P.;
RT "The association of heat shock protein gp96 with HBV-derived peptides
RT in vitro.";
RL Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP PROTEIN SEQUENCE OF 22-39.
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A.,
RA Thomas G.R., Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass
RT spectrometric identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [6]
RP COMPONENT OF A CHAPERONE COMPLEX.
RX PubMed=12475965; DOI=10.1091/mbc.E02-05-0311;
RA Meunier L., Usherwood Y.-K., Chung K.T., Hendershot L.M.;
RT "A subset of chaperones and folding enzymes form multiprotein
RT complexes in endoplasmic reticulum to bind nascent proteins.";
RL Mol. Biol. Cell 13:4456-4469(2002).
RN [7]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY.
RC TISSUE=Melanoma;
RX PubMed=12643545; DOI=10.1021/pr025562r;
RA Basrur V., Yang F., Kushimoto T., Higashimoto Y., Yasumoto K.,
RA Valencia J., Muller J., Vieira W.D., Watabe H., Shabanowitz J.,
RA Hearing V.J., Hunt D.F., Appella E.;
RT "Proteomic analysis of early melanosomes: identification of novel
RT melanosomal proteins.";
RL J. Proteome Res. 2:69-79(2003).
RN [8]
RP GLYCOSYLATION AT ASN-217 AND ASN-445.
RX PubMed=12754519; DOI=10.1038/nbt827;
RA Zhang H., Li X.-J., Martin D.B., Aebersold R.;
RT "Identification and quantification of N-linked glycoproteins using
RT hydrazide chemistry, stable isotope labeling and mass spectrometry.";
RL Nat. Biotechnol. 21:660-666(2003).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [10]
RP INTERACTION WITH CNPY3; TLR4 AND TLR9.
RX PubMed=20865800; DOI=10.1038/ncomms1070;
RA Liu B., Yang Y., Qiu Z., Staron M., Hong F., Li Y., Wu S., Li Y.,
RA Hao B., Bona R., Han D., Li Z.;
RT "Folding of Toll-like receptors by the HSP90 paralogue gp96 requires a
RT substrate-specific cochaperone.";
RL Nat. Commun. 1:79-79(2010).
RN [11]
RP ERRATUM.
RA Liu B., Yang Y., Qiu Z., Staron M., Hong F., Li Y., Wu S., Li Y.,
RA Hao B., Bona R., Han D., Li Z.;
RL Nat. Commun. 3:653-653(2012).
RN [12]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY.
RC TISSUE=Melanoma;
RX PubMed=17081065; DOI=10.1021/pr060363j;
RA Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H.,
RA Mangini N.J., Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R.,
RA Yamagishi S., Shabanowitz J., Hearing V.J., Wu C., Appella E.,
RA Hunt D.F.;
RT "Proteomic and bioinformatic characterization of the biogenesis and
RT function of melanosomes.";
RL J. Proteome Res. 5:3135-3144(2006).
RN [13]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-107, AND MASS
RP SPECTROMETRY.
RC TISSUE=Platelet;
RX PubMed=16263699; DOI=10.1074/mcp.M500324-MCP200;
RA Lewandrowski U., Moebius J., Walter U., Sickmann A.;
RT "Elucidation of N-glycosylation sites on human platelet proteins: a
RT glycoproteomic approach.";
RL Mol. Cell. Proteomics 5:226-233(2006).
RN [14]
RP FUNCTION, AND INTERACTION WITH OS9.
RX PubMed=18264092; DOI=10.1038/ncb1689;
RA Christianson J.C., Shaler T.A., Tyler R.E., Kopito R.R.;
RT "OS-9 and GRP94 deliver mutant alpha1-antitrypsin to the Hrd1-SEL1L
RT ubiquitin ligase complex for ERAD.";
RL Nat. Cell Biol. 10:272-282(2008).
RN [15]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-62; ASN-107; ASN-217 AND
RP ASN-445, AND MASS SPECTROMETRY.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of
RT multiple enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-306, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-306, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [19]
RP INTERACTION WITH METTL23.
RX PubMed=23349634; DOI=10.1371/journal.pgen.1003210;
RA Cloutier P., Lavallee-Adam M., Faubert D., Blanchette M., Coulombe B.;
RT "A newly uncovered group of distantly related lysine
RT methyltransferases preferentially interact with molecular chaperones
RT to regulate their activity.";
RL PLoS Genet. 9:E1003210-E1003210(2013).
CC -!- FUNCTION: Molecular chaperone that functions in the processing and
CC transport of secreted proteins. When associated with CNPY3,
CC required for proper folding of Toll-like receptors (By
CC similarity). Functions in endoplasmic reticulum associated
CC degradation (ERAD). Has ATPase activity.
CC -!- SUBUNIT: Homodimer; disulfide-linked. Component of an EIF2 complex
CC at least composed of CELF1/CUGBP1, CALR, CALR3, EIF2S1, EIF2S2,
CC HSP90B1 and HSPA5 (By similarity). Part of a large chaperone
CC multiprotein complex comprising DNAJB11, HSP90B1, HSPA5, HYOU,
CC PDIA2, PDIA4, PDIA6, PPIB, SDF2L1, UGT1A1 and very small amounts
CC of ERP29, but not, or at very low levels, CALR nor CANX. Interacts
CC with AIMP1; regulates its retention in the endoplasmic reticulum.
CC Interacts with OS9. Interacts with CNPY3. This interaction is
CC disrupted in the presence of ATP (By similarity). Interacts with
CC TLR4 and TLR9, but not with TLR3. Interacts with MZB1 in a
CC calcium-dependent manner (By similarity). Interacts with METTL23.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum lumen. Melanosome.
CC Note=Identified by mass spectrometry in melanosome fractions from
CC stage I to stage IV.
CC -!- SIMILARITY: Belongs to the heat shock protein 90 family.
CC -----------------------------------------------------------------------
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DR EMBL; X15187; CAA33261.1; -; mRNA.
DR EMBL; M33716; AAA68201.1; -; Genomic_DNA.
DR EMBL; BC066656; AAH66656.1; -; mRNA.
DR EMBL; M26596; AAA58621.1; -; Genomic_DNA.
DR EMBL; AY040226; AAK74072.1; -; mRNA.
DR PIR; A35954; A35954.
DR RefSeq; NP_003290.1; NM_003299.2.
DR UniGene; Hs.192374; -.
DR ProteinModelPortal; P14625; -.
DR SMR; P14625; 72-755.
DR DIP; DIP-36060N; -.
DR IntAct; P14625; 36.
DR MINT; MINT-210408; -.
DR STRING; 9606.ENSP00000299767; -.
DR BindingDB; P14625; -.
DR ChEMBL; CHEMBL1075323; -.
DR DrugBank; DB00615; Rifabutin.
DR PhosphoSite; P14625; -.
DR DMDM; 119360; -.
DR DOSAC-COBS-2DPAGE; P14625; -.
DR OGP; P14625; -.
DR REPRODUCTION-2DPAGE; IPI00027230; -.
DR PaxDb; P14625; -.
DR PeptideAtlas; P14625; -.
DR PRIDE; P14625; -.
DR DNASU; 7184; -.
DR Ensembl; ENST00000299767; ENSP00000299767; ENSG00000166598.
DR GeneID; 7184; -.
DR KEGG; hsa:7184; -.
DR UCSC; uc001tkb.2; human.
DR CTD; 7184; -.
DR GeneCards; GC12P104324; -.
DR H-InvDB; HIX0056796; -.
DR HGNC; HGNC:12028; HSP90B1.
DR HPA; CAB005224; -.
DR HPA; HPA003901; -.
DR HPA; HPA008424; -.
DR MIM; 191175; gene.
DR neXtProt; NX_P14625; -.
DR PharmGKB; PA36705; -.
DR eggNOG; COG0326; -.
DR HOGENOM; HOG000031988; -.
DR HOVERGEN; HBG007374; -.
DR InParanoid; P14625; -.
DR KO; K09487; -.
DR OMA; HITDTGI; -.
DR OrthoDB; EOG780RM0; -.
DR PhylomeDB; P14625; -.
DR Reactome; REACT_160300; Binding and Uptake of Ligands by Scavenger Receptors.
DR Reactome; REACT_17015; Metabolism of proteins.
DR Reactome; REACT_6900; Immune System.
DR ChiTaRS; HSP90B1; human.
DR GeneWiki; HSP90B1; -.
DR GenomeRNAi; 7184; -.
DR NextBio; 28164; -.
DR PMAP-CutDB; P14625; -.
DR PRO; PR:P14625; -.
DR ArrayExpress; P14625; -.
DR Bgee; P14625; -.
DR CleanEx; HS_HSP90B1; -.
DR Genevestigator; P14625; -.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0071682; C:endocytic vesicle lumen; TAS:Reactome.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0030496; C:midbody; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IEA:Ensembl.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005509; F:calcium ion binding; TAS:UniProtKB.
DR GO; GO:0050750; F:low-density lipoprotein particle receptor binding; IDA:MGI.
DR GO; GO:0019903; F:protein phosphatase binding; IDA:MGI.
DR GO; GO:0003723; F:RNA binding; IDA:UniProtKB.
DR GO; GO:0046790; F:virion binding; IPI:UniProtKB.
DR GO; GO:0031247; P:actin rod assembly; IDA:MGI.
DR GO; GO:0006987; P:activation of signaling protein activity involved in unfolded protein response; TAS:Reactome.
DR GO; GO:0071318; P:cellular response to ATP; IDA:MGI.
DR GO; GO:0030433; P:ER-associated ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
DR GO; GO:0045087; P:innate immune response; TAS:Reactome.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0006457; P:protein folding; IEA:InterPro.
DR GO; GO:0015031; P:protein transport; NAS:UniProtKB.
DR GO; GO:0043666; P:regulation of phosphoprotein phosphatase activity; IDA:MGI.
DR GO; GO:0001666; P:response to hypoxia; IDA:UniProtKB.
DR GO; GO:0051208; P:sequestering of calcium ion; NAS:UniProtKB.
DR GO; GO:0002224; P:toll-like receptor signaling pathway; TAS:Reactome.
DR Gene3D; 3.30.565.10; -; 2.
DR InterPro; IPR015566; Endoplasmin.
DR InterPro; IPR003594; HATPase_ATP-bd.
DR InterPro; IPR019805; Heat_shock_protein_90_CS.
DR InterPro; IPR001404; Hsp90_fam.
DR InterPro; IPR020575; Hsp90_N.
DR InterPro; IPR020568; Ribosomal_S5_D2-typ_fold.
DR PANTHER; PTHR11528; PTHR11528; 1.
DR PANTHER; PTHR11528:SF21; PTHR11528:SF21; 1.
DR Pfam; PF00183; HSP90; 1.
DR PIRSF; PIRSF002583; Hsp90; 1.
DR PRINTS; PR00775; HEATSHOCK90.
DR SMART; SM00387; HATPase_c; 1.
DR SUPFAM; SSF54211; SSF54211; 1.
DR SUPFAM; SSF55874; SSF55874; 2.
DR PROSITE; PS00014; ER_TARGET; 1.
DR PROSITE; PS00298; HSP90; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Calcium; Chaperone; Complete proteome;
KW Direct protein sequencing; Disulfide bond; Endoplasmic reticulum;
KW Glycoprotein; Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Signal.
FT SIGNAL 1 21
FT CHAIN 22 803 Endoplasmin.
FT /FTId=PRO_0000013598.
FT MOTIF 800 803 Prevents secretion from ER.
FT BINDING 107 107 ATP (By similarity).
FT BINDING 149 149 ATP (By similarity).
FT BINDING 162 162 ATP (By similarity).
FT BINDING 168 168 ATP (By similarity).
FT BINDING 199 199 ATP; via amide nitrogen (By similarity).
FT BINDING 448 448 ATP (By similarity).
FT MOD_RES 306 306 Phosphoserine.
FT CARBOHYD 62 62 N-linked (GlcNAc...).
FT CARBOHYD 107 107 N-linked (GlcNAc...).
FT CARBOHYD 217 217 N-linked (GlcNAc...).
FT CARBOHYD 445 445 N-linked (GlcNAc...).
FT CARBOHYD 481 481 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 502 502 N-linked (GlcNAc...) (Potential).
FT DISULFID 138 138 Interchain (By similarity).
FT CONFLICT 188 188 T -> S (in Ref. 4; AAK74072).
FT CONFLICT 419 419 T -> P (in Ref. 4; AAK74072).
FT CONFLICT 803 803 L -> F (in Ref. 4; AAK74072).
SQ SEQUENCE 803 AA; 92469 MW; 9BF6705A7A2ED0D0 CRC64;
MRALWVLGLC CVLLTFGSVR ADDEVDVDGT VEEDLGKSRE GSRTDDEVVQ REEEAIQLDG
LNASQIRELR EKSEKFAFQA EVNRMMKLII NSLYKNKEIF LRELISNASD ALDKIRLISL
TDENALSGNE ELTVKIKCDK EKNLLHVTDT GVGMTREELV KNLGTIAKSG TSEFLNKMTE
AQEDGQSTSE LIGQFGVGFY SAFLVADKVI VTSKHNNDTQ HIWESDSNEF SVIADPRGNT
LGRGTTITLV LKEEASDYLE LDTIKNLVKK YSQFINFPIY VWSSKTETVE EPMEEEEAAK
EEKEESDDEA AVEEEEEEKK PKTKKVEKTV WDWELMNDIK PIWQRPSKEV EEDEYKAFYK
SFSKESDDPM AYIHFTAEGE VTFKSILFVP TSAPRGLFDE YGSKKSDYIK LYVRRVFITD
DFHDMMPKYL NFVKGVVDSD DLPLNVSRET LQQHKLLKVI RKKLVRKTLD MIKKIADDKY
NDTFWKEFGT NIKLGVIEDH SNRTRLAKLL RFQSSHHPTD ITSLDQYVER MKEKQDKIYF
MAGSSRKEAE SSPFVERLLK KGYEVIYLTE PVDEYCIQAL PEFDGKRFQN VAKEGVKFDE
SEKTKESREA VEKEFEPLLN WMKDKALKDK IEKAVVSQRL TESPCALVAS QYGWSGNMER
IMKAQAYQTG KDISTNYYAS QKKTFEINPR HPLIRDMLRR IKEDEDDKTV LDLAVVLFET
ATLRSGYLLP DTKAYGDRIE RMLRLSLNID PDAKVEEEPE EEPEETAEDT TEDTEQDEDE
EMDVGTDEEE ETAKESTAEK DEL
//
MIM
191175
*RECORD*
*FIELD* NO
191175
*FIELD* TI
*191175 HEAT-SHOCK PROTEIN, 90-KD, BETA, 1; HSP90B1
;;TUMOR REJECTION ANTIGEN 1;;
TRA1;;
read moreSTRESS-INDUCIBLE TUMOR REJECTION ANTIGEN GP96;;
GLUCOSE-REGULATED PROTEIN, 94-KD; GRP94
*FIELD* TX
DESCRIPTION
HSP90 proteins are highly conserved molecular chaperones that have key
roles in signal transduction, protein folding, protein degradation, and
morphologic evolution. HSP90 proteins normally associate with other
cochaperones and play important roles in folding newly synthesized
proteins or stabilizing and refolding denatured proteins after stress.
HSP90B1 is an endoplasmic reticulum HSP90 protein. Other HSP90 proteins
are found in cytosol (see HSP90AA1; 140571) and mitochondria (TRAP1;
606219) (Chen et al., 2005).
CLONING
By screening a human teratocarcinoma cDNA library with mouse gp96, Maki
et al. (1990) isolated a cDNA encoding TRA1, which they called GP96. The
803-amino acid protein, which is 96% homologous to the mouse sequence,
contains a 21-amino acid signal peptide and 5 potential N-linked
glycosylation sites. Northern blot analysis detected a 2.8-kb GP96
transcript in all tumor cell lines tested. Southern blot analysis
suggested the presence 3 or 4 GP96-related genes per haploid genome.
By database analysis, Chen et al. (2005) identified full-length HSP90B1
and several variants. Like other HSP90 proteins, the 803-amino acid
HSP90B1 protein has a highly conserved N-terminal domain, a charged
domain, a middle domain involved in ATPase activity, a second charged
domain, and a C-terminal domain. It also has an incomplete 4-helical
cytokine motif, a gln-rich region, and a signal peptide.
GENE FUNCTION
Using a mouse system, Binder et al. (2000) determined that the receptor
for GP96 is CD91 (A2MR, or LRP1; 107770) and that A2M (103950), a
protein found in blood, inhibits GP96 binding to CD91.
Schild and Rammensee (2000) stated that GP96 has multiple functions,
including chaperoning peptides to MHC class I molecules of dendritic
cells and other antigen-presenting cells, as well as inducing dendritic
cells to express costimulatory molecules such as B7 (CD80; 112203) and
to produce cytokines IL12 (see 161560) and TNFA (191160).
Using a mutagenesis screen, Randow and Seed (2001) identified a murine
pre-B cell line that was unresponsive to lipopolysaccharide and
deficient in Gp96. Lack of Gp96 was compatible with survival even under
stress conditions and resulted in defective formation of a subset of
surface receptors and retention of intracellular Toll-like receptors
(TLRs), leading to unresponsiveness to microbial stimuli. Reintroduction
of Gp96 restored surface expression of Tlr1 (601194), Tlr2 (603028), and
Tlr4 (603030). Randow and Seed (2001) concluded that GP96 is required
for maturation of a narrow set of client proteins and that it forms
stable associations with these proteins.
Rivoltini et al. (2003) showed that GP96 derived from metastatic human
melanoma or colon carcinomas could present antigenic peptides to CD8
(see 186910)-positive T cells both in vivo and in vitro.
Paris et al. (2005) found that GRP94 was upregulated in endothelial
cells by hypoxia, and they identified 3 hypoxia-responsive elements
(HRE) in the GRP94 promoter. Competition experiments demonstrated that
HIF1 (see 603348) bound to the GRP94 HREs with high affinity.
Using a ligand overlay approach, Cabanes et al. (2005) identified GP96
as a receptor for a Listeria monocytogenes virulence factor, Vip. The
GP96-Vip interaction was critical for viral entry into mammalian cells
and for infection in vivo.
By coimmunoprecipitation, mass spectrum analysis, and fluorescence
microscopy, Na et al. (2008) identified GP96 as a human colonocyte
membrane binding protein for Clostridium dificile toxin A (Txa), a
mediator of antibiotic-associated colitis. They also showed that GP96
mediated Txa translocation to the cytoplasm.
BIOCHEMICAL FEATURES
Dollins et al. (2007) reported the crystal structures of near
full-length canine Grp94, which is 98.5% identical to human GRP94, in
complex with the nonhydrolyzable ATP analog AMPPNP at 2.4-angstrom
resolution and with ADP at 2.45-angstrom resolution. The structures
showed that, in contrast with models of cytosolic Hsp90 action, Grp94
was conformationally insensitive to the identity of the bound
nucleotide, adopting a twisted V conformation that precluded N-terminal
domain dimerization. However, kinetic data demonstrated that Grp94
possessed ATP hydrolysis activity, although its rate was 5- to 25-fold
slower than that of yeast Hsp82, a cytosolic Hsp90 chaperone. These
experiments also revealed a regulatory role for the Grp94-specific
pre-N-terminal domain. Using a set of Grp94/Hsp82 chimeras, Dollins et
al. (2007) showed that the catalytic differences between Grp94 and Hsp82
could be ascribed entirely to their N-terminal domains.
GENE STRUCTURE
Chen et al. (2005) determined that the HSP90B1 gene contains 18 exons.
MAPPING
Maki et al. (1991) used a human GP96 cDNA fragment to probe Southern
blots of human-mouse somatic cell hybrid panels. Two bands mapped to
chromosome 12 and were derived from different parts of 1 GP96 coding
gene, while a third band mapped to chromosome 15 and corresponded to a
GP96 pseudogene. A second pseudogene that mapped to chromosome 1 was
identified. By in situ hybridization, Maki et al. (1991) showed that the
expressed gene maps to 12q24.2-q24.3, while the 2 pseudogenes
(designated TRAP1 and TRAP2) map to chromosome 15q25-q26 and 1p22,
respectively. The homologous coding sequence in the mouse (Tra-1) maps
to chromosome 10.
By genomic sequence analysis, Chen et al. (2005) mapped the HSP90B1 gene
to chromosome 12q23.3. They identified HSP90B pseudogenes on chromosomes
15q26.3 (HSP90B2P) and 1p22.1 (HSP90B3P).
NOMENCLATURE
Chen et al. (2005) provided a revised nomenclature system for the HSP90
gene family. Under this system, the root HSP90A indicates cytosolic
HSP90, HSP90B indicates endoplasmic reticulum HSP90, and TRAP indicates
mitochondrial HSP90. HSP90A was divided into 2 classes, with HSP90AA
representing conventional HSP90-alpha, and HSP90AB representing
HSP90-beta. The number following the root/class represents the gene in
that class, and a 'P' at the end indicates a putative pseudogene.
ANIMAL MODEL
Yang et al. (2007) generated macrophage-specific gp96-deficient mice.
Gp96-deficient macrophages showed normal responses to
activation-inducing cytokines, but they failed to respond to ligands of
cell surface and intracellular TLRs, thereby creating conditional and
cell-specific TLR-deficient mice. These mice were resistant to endotoxic
shock and highly susceptible to Listeria monocytogenes.
Coimmunoprecipitation experiments revealed that Tlr4 and Tlr9 (605474)
primarily interacted with a highly glycosylated, 110-kD form of gp96.
Yang et al. (2007) concluded that gp96 is the master chaperone for TLRs
and that macrophages, but not other myeloid cells, are the primary
source of proinflammatory cytokines after endotoxin and Listeria
challenges.
Wanderling et al. (2007) found that Grp94 -/- mice did not survive
beyond day 7 of gestation. Grp94 -/- embryonic stem cells differentiated
into cells representing mesoderm, endoderm, and ectoderm germ layers,
but they did not differentiate into cardiac, smooth, or skeletal muscle.
Grp94 -/- cells were deficient in secretion of Igf2 (147470), and their
defect could be complemented by exogenous Igf1 (147440) or Igf2.
Wanderling et al. (2007) concluded that IGF2 is a developmentally
important protein whose production depends on GRP94 activity.
*FIELD* RF
1. Binder, R. J.; Han, D. K.; Srivastava, P. K.: CD91: a receptor
for heat shock protein gp96. Nature Immun. 1: 151-155, 2000.
2. Cabanes, D.; Sousa, S.; Cebria, A.; Lecuit, M.; Garcia-del Portillo,
F.; Cossart, P.: Gp96 is a receptor for a novel Listeria monocytogenes
virulence factor, Vip, a surface protein. EMBO J. 24: 2827-2838,
2005.
3. Chen, B.; Piel, W. H.; Gui, L.; Bruford, E.; Monteiro, A.: The
HSP90 family of genes in the human genome: insights into their divergence
and evolution. Genomics 86: 627-637, 2005.
4. Dollins, D. E.; Warren, J. J.; Immormino, R. M.; Gewirth, D. T.
: Structures of GRP94-nucleotide complexes reveal mechanistic differences
between the hsp90 chaperones. Molec. Cell 28: 41-56, 2007.
5. Maki, R. G.; Eddy, R. L.; Byers, M. G.; Shows, T. B.; Srivastava,
P. K.: Localization of genes for the stress-inducible tumor rejection
antigen gp96. (Abstract) Cytogenet. Cell Genet. 58: 1978 only, 1991.
6. Maki, R. G.; Old, L. J.; Srivastava, P. K.: Human homologue of
murine tumor rejection antigen gp96: 5-prime-regulatory and coding
regions and relationship to stress-induced proteins. Proc. Nat. Acad.
Sci. 87: 5658-5662, 1990.
7. Na, X.; Kim, H.; Moyer, M. P.; Pothoulakis, C.; LaMont, J. T.:
gp96 is a human colonocyte plasma membrane binding protein for Clostridium
difficile toxin A. Infect. Immun. 76: 2862-2871, 2008.
8. Paris, S.; Denis, H.; Delaive, E.; Dieu, M.; Dumont, V.; Ninane,
N.; Raes, M.; Michiels, C.: Up-regulation of 94-kDa glucose-regulated
protein by hypoxia-inducible factor-1 in human endothelial cells in
response to hypoxia. FEBS Lett. 579: 105-114, 2005.
9. Randow, F.; Seed, B.: Endoplasmic reticulum chaperone gp96 is
required for innate immunity but not cell viability. Nature Cell
Biol. 3: 891-896, 2001.
10. Rivoltini, L.; Castelli, C.; Carrabba, M.; Mazzaferro, V.; Pilla,
L.; Huber, V.; Coppa, J.; Gallino, G.; Scheibenbogen, C.; Squarcina,
P.; Cova, A.; Camerini, R.; Lewis, J. J.; Srivastava, P. K.; Parmiani,
G.: Human tumor-derived heat shock protein 96 mediates in vitro activation
and in vivo expansion of melanoma- and colon carcinoma-specific T
cells. J. Immun. 171: 3467-3474, 2003.
11. Schild, H.; Rammensee, H.-G.: gp96: the immune system's Swiss
army knife. Nature Immun. 1: 100-101, 2000.
12. Wanderling, S.; Simen, B. B.; Ostrovsky, O.; Ahmed, N. T.; Vogen,
S. M.; Gidalevitz, T.; Argon, Y.: GRP94 is essential for mesoderm
induction and muscle development because it regulates insulin-like
growth factor secretion. Molec. Biol. Cell 18: 3764-3775, 2007.
13. Yang, Y.; Liu, B.; Dai, J.; Srivastava, P. K.; Zammit, D. J.;
Lefrancois, L.; Li, Z.: Heat shock protein gp96 is a master chaperone
for Toll-like receptors and is important in the innate function of
macrophages. Immunity 26: 215-226, 2007.
*FIELD* CN
Matthew B. Gross - updated: 9/3/2008
Paul J. Converse - updated: 8/22/2008
Matthew B. Gross - updated: 8/12/2008
Paul J. Converse - updated: 8/7/2007
Paul J. Converse - updated: 9/18/2000
*FIELD* CD
Victor A. McKusick: 10/11/1991
*FIELD* ED
carol: 05/08/2009
mgross: 9/3/2008
terry: 8/22/2008
mgross: 8/12/2008
mgross: 8/23/2007
terry: 8/7/2007
mgross: 7/31/2003
mgross: 9/18/2000
dkim: 7/16/1998
supermim: 3/16/1992
carol: 2/23/1992
carol: 10/11/1991
*RECORD*
*FIELD* NO
191175
*FIELD* TI
*191175 HEAT-SHOCK PROTEIN, 90-KD, BETA, 1; HSP90B1
;;TUMOR REJECTION ANTIGEN 1;;
TRA1;;
read moreSTRESS-INDUCIBLE TUMOR REJECTION ANTIGEN GP96;;
GLUCOSE-REGULATED PROTEIN, 94-KD; GRP94
*FIELD* TX
DESCRIPTION
HSP90 proteins are highly conserved molecular chaperones that have key
roles in signal transduction, protein folding, protein degradation, and
morphologic evolution. HSP90 proteins normally associate with other
cochaperones and play important roles in folding newly synthesized
proteins or stabilizing and refolding denatured proteins after stress.
HSP90B1 is an endoplasmic reticulum HSP90 protein. Other HSP90 proteins
are found in cytosol (see HSP90AA1; 140571) and mitochondria (TRAP1;
606219) (Chen et al., 2005).
CLONING
By screening a human teratocarcinoma cDNA library with mouse gp96, Maki
et al. (1990) isolated a cDNA encoding TRA1, which they called GP96. The
803-amino acid protein, which is 96% homologous to the mouse sequence,
contains a 21-amino acid signal peptide and 5 potential N-linked
glycosylation sites. Northern blot analysis detected a 2.8-kb GP96
transcript in all tumor cell lines tested. Southern blot analysis
suggested the presence 3 or 4 GP96-related genes per haploid genome.
By database analysis, Chen et al. (2005) identified full-length HSP90B1
and several variants. Like other HSP90 proteins, the 803-amino acid
HSP90B1 protein has a highly conserved N-terminal domain, a charged
domain, a middle domain involved in ATPase activity, a second charged
domain, and a C-terminal domain. It also has an incomplete 4-helical
cytokine motif, a gln-rich region, and a signal peptide.
GENE FUNCTION
Using a mouse system, Binder et al. (2000) determined that the receptor
for GP96 is CD91 (A2MR, or LRP1; 107770) and that A2M (103950), a
protein found in blood, inhibits GP96 binding to CD91.
Schild and Rammensee (2000) stated that GP96 has multiple functions,
including chaperoning peptides to MHC class I molecules of dendritic
cells and other antigen-presenting cells, as well as inducing dendritic
cells to express costimulatory molecules such as B7 (CD80; 112203) and
to produce cytokines IL12 (see 161560) and TNFA (191160).
Using a mutagenesis screen, Randow and Seed (2001) identified a murine
pre-B cell line that was unresponsive to lipopolysaccharide and
deficient in Gp96. Lack of Gp96 was compatible with survival even under
stress conditions and resulted in defective formation of a subset of
surface receptors and retention of intracellular Toll-like receptors
(TLRs), leading to unresponsiveness to microbial stimuli. Reintroduction
of Gp96 restored surface expression of Tlr1 (601194), Tlr2 (603028), and
Tlr4 (603030). Randow and Seed (2001) concluded that GP96 is required
for maturation of a narrow set of client proteins and that it forms
stable associations with these proteins.
Rivoltini et al. (2003) showed that GP96 derived from metastatic human
melanoma or colon carcinomas could present antigenic peptides to CD8
(see 186910)-positive T cells both in vivo and in vitro.
Paris et al. (2005) found that GRP94 was upregulated in endothelial
cells by hypoxia, and they identified 3 hypoxia-responsive elements
(HRE) in the GRP94 promoter. Competition experiments demonstrated that
HIF1 (see 603348) bound to the GRP94 HREs with high affinity.
Using a ligand overlay approach, Cabanes et al. (2005) identified GP96
as a receptor for a Listeria monocytogenes virulence factor, Vip. The
GP96-Vip interaction was critical for viral entry into mammalian cells
and for infection in vivo.
By coimmunoprecipitation, mass spectrum analysis, and fluorescence
microscopy, Na et al. (2008) identified GP96 as a human colonocyte
membrane binding protein for Clostridium dificile toxin A (Txa), a
mediator of antibiotic-associated colitis. They also showed that GP96
mediated Txa translocation to the cytoplasm.
BIOCHEMICAL FEATURES
Dollins et al. (2007) reported the crystal structures of near
full-length canine Grp94, which is 98.5% identical to human GRP94, in
complex with the nonhydrolyzable ATP analog AMPPNP at 2.4-angstrom
resolution and with ADP at 2.45-angstrom resolution. The structures
showed that, in contrast with models of cytosolic Hsp90 action, Grp94
was conformationally insensitive to the identity of the bound
nucleotide, adopting a twisted V conformation that precluded N-terminal
domain dimerization. However, kinetic data demonstrated that Grp94
possessed ATP hydrolysis activity, although its rate was 5- to 25-fold
slower than that of yeast Hsp82, a cytosolic Hsp90 chaperone. These
experiments also revealed a regulatory role for the Grp94-specific
pre-N-terminal domain. Using a set of Grp94/Hsp82 chimeras, Dollins et
al. (2007) showed that the catalytic differences between Grp94 and Hsp82
could be ascribed entirely to their N-terminal domains.
GENE STRUCTURE
Chen et al. (2005) determined that the HSP90B1 gene contains 18 exons.
MAPPING
Maki et al. (1991) used a human GP96 cDNA fragment to probe Southern
blots of human-mouse somatic cell hybrid panels. Two bands mapped to
chromosome 12 and were derived from different parts of 1 GP96 coding
gene, while a third band mapped to chromosome 15 and corresponded to a
GP96 pseudogene. A second pseudogene that mapped to chromosome 1 was
identified. By in situ hybridization, Maki et al. (1991) showed that the
expressed gene maps to 12q24.2-q24.3, while the 2 pseudogenes
(designated TRAP1 and TRAP2) map to chromosome 15q25-q26 and 1p22,
respectively. The homologous coding sequence in the mouse (Tra-1) maps
to chromosome 10.
By genomic sequence analysis, Chen et al. (2005) mapped the HSP90B1 gene
to chromosome 12q23.3. They identified HSP90B pseudogenes on chromosomes
15q26.3 (HSP90B2P) and 1p22.1 (HSP90B3P).
NOMENCLATURE
Chen et al. (2005) provided a revised nomenclature system for the HSP90
gene family. Under this system, the root HSP90A indicates cytosolic
HSP90, HSP90B indicates endoplasmic reticulum HSP90, and TRAP indicates
mitochondrial HSP90. HSP90A was divided into 2 classes, with HSP90AA
representing conventional HSP90-alpha, and HSP90AB representing
HSP90-beta. The number following the root/class represents the gene in
that class, and a 'P' at the end indicates a putative pseudogene.
ANIMAL MODEL
Yang et al. (2007) generated macrophage-specific gp96-deficient mice.
Gp96-deficient macrophages showed normal responses to
activation-inducing cytokines, but they failed to respond to ligands of
cell surface and intracellular TLRs, thereby creating conditional and
cell-specific TLR-deficient mice. These mice were resistant to endotoxic
shock and highly susceptible to Listeria monocytogenes.
Coimmunoprecipitation experiments revealed that Tlr4 and Tlr9 (605474)
primarily interacted with a highly glycosylated, 110-kD form of gp96.
Yang et al. (2007) concluded that gp96 is the master chaperone for TLRs
and that macrophages, but not other myeloid cells, are the primary
source of proinflammatory cytokines after endotoxin and Listeria
challenges.
Wanderling et al. (2007) found that Grp94 -/- mice did not survive
beyond day 7 of gestation. Grp94 -/- embryonic stem cells differentiated
into cells representing mesoderm, endoderm, and ectoderm germ layers,
but they did not differentiate into cardiac, smooth, or skeletal muscle.
Grp94 -/- cells were deficient in secretion of Igf2 (147470), and their
defect could be complemented by exogenous Igf1 (147440) or Igf2.
Wanderling et al. (2007) concluded that IGF2 is a developmentally
important protein whose production depends on GRP94 activity.
*FIELD* RF
1. Binder, R. J.; Han, D. K.; Srivastava, P. K.: CD91: a receptor
for heat shock protein gp96. Nature Immun. 1: 151-155, 2000.
2. Cabanes, D.; Sousa, S.; Cebria, A.; Lecuit, M.; Garcia-del Portillo,
F.; Cossart, P.: Gp96 is a receptor for a novel Listeria monocytogenes
virulence factor, Vip, a surface protein. EMBO J. 24: 2827-2838,
2005.
3. Chen, B.; Piel, W. H.; Gui, L.; Bruford, E.; Monteiro, A.: The
HSP90 family of genes in the human genome: insights into their divergence
and evolution. Genomics 86: 627-637, 2005.
4. Dollins, D. E.; Warren, J. J.; Immormino, R. M.; Gewirth, D. T.
: Structures of GRP94-nucleotide complexes reveal mechanistic differences
between the hsp90 chaperones. Molec. Cell 28: 41-56, 2007.
5. Maki, R. G.; Eddy, R. L.; Byers, M. G.; Shows, T. B.; Srivastava,
P. K.: Localization of genes for the stress-inducible tumor rejection
antigen gp96. (Abstract) Cytogenet. Cell Genet. 58: 1978 only, 1991.
6. Maki, R. G.; Old, L. J.; Srivastava, P. K.: Human homologue of
murine tumor rejection antigen gp96: 5-prime-regulatory and coding
regions and relationship to stress-induced proteins. Proc. Nat. Acad.
Sci. 87: 5658-5662, 1990.
7. Na, X.; Kim, H.; Moyer, M. P.; Pothoulakis, C.; LaMont, J. T.:
gp96 is a human colonocyte plasma membrane binding protein for Clostridium
difficile toxin A. Infect. Immun. 76: 2862-2871, 2008.
8. Paris, S.; Denis, H.; Delaive, E.; Dieu, M.; Dumont, V.; Ninane,
N.; Raes, M.; Michiels, C.: Up-regulation of 94-kDa glucose-regulated
protein by hypoxia-inducible factor-1 in human endothelial cells in
response to hypoxia. FEBS Lett. 579: 105-114, 2005.
9. Randow, F.; Seed, B.: Endoplasmic reticulum chaperone gp96 is
required for innate immunity but not cell viability. Nature Cell
Biol. 3: 891-896, 2001.
10. Rivoltini, L.; Castelli, C.; Carrabba, M.; Mazzaferro, V.; Pilla,
L.; Huber, V.; Coppa, J.; Gallino, G.; Scheibenbogen, C.; Squarcina,
P.; Cova, A.; Camerini, R.; Lewis, J. J.; Srivastava, P. K.; Parmiani,
G.: Human tumor-derived heat shock protein 96 mediates in vitro activation
and in vivo expansion of melanoma- and colon carcinoma-specific T
cells. J. Immun. 171: 3467-3474, 2003.
11. Schild, H.; Rammensee, H.-G.: gp96: the immune system's Swiss
army knife. Nature Immun. 1: 100-101, 2000.
12. Wanderling, S.; Simen, B. B.; Ostrovsky, O.; Ahmed, N. T.; Vogen,
S. M.; Gidalevitz, T.; Argon, Y.: GRP94 is essential for mesoderm
induction and muscle development because it regulates insulin-like
growth factor secretion. Molec. Biol. Cell 18: 3764-3775, 2007.
13. Yang, Y.; Liu, B.; Dai, J.; Srivastava, P. K.; Zammit, D. J.;
Lefrancois, L.; Li, Z.: Heat shock protein gp96 is a master chaperone
for Toll-like receptors and is important in the innate function of
macrophages. Immunity 26: 215-226, 2007.
*FIELD* CN
Matthew B. Gross - updated: 9/3/2008
Paul J. Converse - updated: 8/22/2008
Matthew B. Gross - updated: 8/12/2008
Paul J. Converse - updated: 8/7/2007
Paul J. Converse - updated: 9/18/2000
*FIELD* CD
Victor A. McKusick: 10/11/1991
*FIELD* ED
carol: 05/08/2009
mgross: 9/3/2008
terry: 8/22/2008
mgross: 8/12/2008
mgross: 8/23/2007
terry: 8/7/2007
mgross: 7/31/2003
mgross: 9/18/2000
dkim: 7/16/1998
supermim: 3/16/1992
carol: 2/23/1992
carol: 10/11/1991