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P14625 (ENPL_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 169. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Endoplasmin
Alternative name(s):
94 kDa glucose-regulated protein
Short name=GRP-94
Heat shock protein 90 kDa beta member 1
Tumor rejection antigen 1
gp96 homolog
Gene names
Name:HSP90B1
Synonyms:GRP94, TRA1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length803 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Molecular chaperone that functions in the processing and transport of secreted proteins. When associated with CNPY3, required for proper folding of Toll-like receptors By similarity. Functions in endoplasmic reticulum associated degradation (ERAD). Has ATPase activity. Ref.14

Subunit structure

Homodimer; disulfide-linked. Component of an EIF2 complex at least composed of CELF1/CUGBP1, CALR, CALR3, EIF2S1, EIF2S2, HSP90B1 and HSPA5 By similarity. Part of a large chaperone multiprotein complex comprising DNAJB11, HSP90B1, HSPA5, HYOU, PDIA2, PDIA4, PDIA6, PPIB, SDF2L1, UGT1A1 and very small amounts of ERP29, but not, or at very low levels, CALR nor CANX. Interacts with AIMP1; regulates its retention in the endoplasmic reticulum. Interacts with OS9. Interacts with CNPY3. This interaction is disrupted in the presence of ATP By similarity. Interacts with TLR4 and TLR9, but not with TLR3. Interacts with MZB1 in a calcium-dependent manner By similarity. Interacts with METTL23. Ref.10 Ref.14 Ref.19

Subcellular location

Endoplasmic reticulum lumen. Melanosome. Note: Identified by mass spectrometry in melanosome fractions from stage I to stage IV. Ref.7 Ref.12

Sequence similarities

Belongs to the heat shock protein 90 family.

Ontologies

Keywords
   Cellular componentEndoplasmic reticulum
   DomainSignal
   LigandATP-binding
Calcium
Nucleotide-binding
   Molecular functionChaperone
   PTMAcetylation
Disulfide bond
Glycoprotein
Phosphoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processER-associated ubiquitin-dependent protein catabolic process

Inferred from mutant phenotype Ref.14. Source: UniProtKB

actin rod assembly

Inferred from direct assay PubMed 19000834. Source: MGI

activation of signaling protein activity involved in unfolded protein response

Traceable author statement. Source: Reactome

cellular response to ATP

Inferred from direct assay PubMed 19000834. Source: MGI

innate immune response

Traceable author statement. Source: Reactome

negative regulation of apoptotic process

Inferred from mutant phenotype PubMed 10497210PubMed 15192333. Source: UniProtKB

protein folding

Inferred from electronic annotation. Source: InterPro

protein transport

Non-traceable author statement PubMed 15845869. Source: UniProtKB

regulation of phosphoprotein phosphatase activity

Inferred from direct assay PubMed 19000834. Source: MGI

response to hypoxia

Inferred from direct assay PubMed 15620698. Source: UniProtKB

sequestering of calcium ion

Non-traceable author statement PubMed 15192333. Source: UniProtKB

toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

   Cellular_componentcytosol

Inferred from direct assay PubMed 9596688. Source: UniProtKB

endocytic vesicle lumen

Traceable author statement. Source: Reactome

endoplasmic reticulum lumen

Inferred from direct assay PubMed 10497210. Source: UniProtKB

endoplasmic reticulum membrane

Inferred from direct assay PubMed 10497210. Source: UniProtKB

extracellular vesicular exosome

Inferred from direct assay PubMed 19199708PubMed 20458337. Source: UniProt

melanosome

Inferred from electronic annotation. Source: UniProtKB-SubCell

midbody

Inferred from direct assay PubMed 15166316. Source: UniProtKB

perinuclear region of cytoplasm

Inferred from direct assay PubMed 10497210. Source: UniProtKB

plasma membrane

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

RNA binding

Inferred from direct assay PubMed 11958450. Source: UniProtKB

calcium ion binding

Traceable author statement PubMed 10497210. Source: UniProtKB

low-density lipoprotein particle receptor binding

Inferred from direct assay PubMed 15082773. Source: MGI

protein phosphatase binding

Inferred from direct assay PubMed 19000834. Source: MGI

virion binding

Inferred from physical interaction PubMed 11958450. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2121 Ref.5
Chain22 – 803782Endoplasmin HAMAP-Rule MF_00505
PRO_0000013598

Regions

Motif800 – 8034Prevents secretion from ER HAMAP-Rule MF_00505

Sites

Binding site1071ATP By similarity
Binding site1491ATP By similarity
Binding site1621ATP By similarity
Binding site1681ATP By similarity
Binding site1991ATP; via amide nitrogen By similarity
Binding site4481ATP By similarity

Amino acid modifications

Modified residue3061Phosphoserine Ref.16 Ref.18
Modified residue4041N6-succinyllysine By similarity
Modified residue4791N6-acetyllysine By similarity
Modified residue6331N6-succinyllysine By similarity
Glycosylation621N-linked (GlcNAc...) Ref.15
Glycosylation1071N-linked (GlcNAc...) Ref.13 Ref.15
Glycosylation2171N-linked (GlcNAc...) Ref.8 Ref.15
Glycosylation4451N-linked (GlcNAc...) Ref.8 Ref.15
Glycosylation4811N-linked (GlcNAc...) Potential
Glycosylation5021N-linked (GlcNAc...) Potential
Disulfide bond138Interchain By similarity

Experimental info

Sequence conflict1881T → S in AAK74072. Ref.4
Sequence conflict4191T → P in AAK74072. Ref.4
Sequence conflict8031L → F in AAK74072. Ref.4

Sequences

Sequence LengthMass (Da)Tools
P14625 [UniParc].

Last modified April 1, 1990. Version 1.
Checksum: 9BF6705A7A2ED0D0

FASTA80392,469
        10         20         30         40         50         60 
MRALWVLGLC CVLLTFGSVR ADDEVDVDGT VEEDLGKSRE GSRTDDEVVQ REEEAIQLDG 

        70         80         90        100        110        120 
LNASQIRELR EKSEKFAFQA EVNRMMKLII NSLYKNKEIF LRELISNASD ALDKIRLISL 

       130        140        150        160        170        180 
TDENALSGNE ELTVKIKCDK EKNLLHVTDT GVGMTREELV KNLGTIAKSG TSEFLNKMTE 

       190        200        210        220        230        240 
AQEDGQSTSE LIGQFGVGFY SAFLVADKVI VTSKHNNDTQ HIWESDSNEF SVIADPRGNT 

       250        260        270        280        290        300 
LGRGTTITLV LKEEASDYLE LDTIKNLVKK YSQFINFPIY VWSSKTETVE EPMEEEEAAK 

       310        320        330        340        350        360 
EEKEESDDEA AVEEEEEEKK PKTKKVEKTV WDWELMNDIK PIWQRPSKEV EEDEYKAFYK 

       370        380        390        400        410        420 
SFSKESDDPM AYIHFTAEGE VTFKSILFVP TSAPRGLFDE YGSKKSDYIK LYVRRVFITD 

       430        440        450        460        470        480 
DFHDMMPKYL NFVKGVVDSD DLPLNVSRET LQQHKLLKVI RKKLVRKTLD MIKKIADDKY 

       490        500        510        520        530        540 
NDTFWKEFGT NIKLGVIEDH SNRTRLAKLL RFQSSHHPTD ITSLDQYVER MKEKQDKIYF 

       550        560        570        580        590        600 
MAGSSRKEAE SSPFVERLLK KGYEVIYLTE PVDEYCIQAL PEFDGKRFQN VAKEGVKFDE 

       610        620        630        640        650        660 
SEKTKESREA VEKEFEPLLN WMKDKALKDK IEKAVVSQRL TESPCALVAS QYGWSGNMER 

       670        680        690        700        710        720 
IMKAQAYQTG KDISTNYYAS QKKTFEINPR HPLIRDMLRR IKEDEDDKTV LDLAVVLFET 

       730        740        750        760        770        780 
ATLRSGYLLP DTKAYGDRIE RMLRLSLNID PDAKVEEEPE EEPEETAEDT TEDTEQDEDE 

       790        800 
EMDVGTDEEE ETAKESTAEK DEL 

« Hide

References

« Hide 'large scale' references
[1]"Human homologue of murine tumor rejection antigen gp96: 5'-regulatory and coding regions and relationship to stress-induced proteins."
Maki R.G., Old L.J., Srivastava P.K.
Proc. Natl. Acad. Sci. U.S.A. 87:5658-5662(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-16.
Tissue: Blood.
[2]"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].
Tissue: Skin.
[3]"Glucose-regulated protein (GRP94 and GRP78) genes share common regulatory domains and are coordinately regulated by common trans-acting factors."
Chang S.C., Erwin A.E., Lee A.S.
Mol. Cell. Biol. 9:2153-2162(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-16.
Tissue: Liver.
[4]"The association of heat shock protein gp96 with HBV-derived peptides in vitro."
Meng S., Tien P.
Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 22-803.
Tissue: Liver.
[5]"Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides."
Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R., Vandekerckhove J.
Nat. Biotechnol. 21:566-569(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 22-39.
Tissue: Platelet.
[6]"A subset of chaperones and folding enzymes form multiprotein complexes in endoplasmic reticulum to bind nascent proteins."
Meunier L., Usherwood Y.-K., Chung K.T., Hendershot L.M.
Mol. Biol. Cell 13:4456-4469(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: COMPONENT OF A CHAPERONE COMPLEX.
[7]"Proteomic analysis of early melanosomes: identification of novel melanosomal proteins."
Basrur V., Yang F., Kushimoto T., Higashimoto Y., Yasumoto K., Valencia J., Muller J., Vieira W.D., Watabe H., Shabanowitz J., Hearing V.J., Hunt D.F., Appella E.
J. Proteome Res. 2:69-79(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
Tissue: Melanoma.
[8]"Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry."
Zhang H., Li X.-J., Martin D.B., Aebersold R.
Nat. Biotechnol. 21:660-666(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION AT ASN-217 AND ASN-445.
[9]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[10]"Folding of Toll-like receptors by the HSP90 paralogue gp96 requires a substrate-specific cochaperone."
Liu B., Yang Y., Qiu Z., Staron M., Hong F., Li Y., Wu S., Li Y., Hao B., Bona R., Han D., Li Z.
Nat. Commun. 1:79-79(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CNPY3; TLR4 AND TLR9.
[11]Erratum
Liu B., Yang Y., Qiu Z., Staron M., Hong F., Li Y., Wu S., Li Y., Hao B., Bona R., Han D., Li Z.
Nat. Commun. 3:653-653(2012)
[12]"Proteomic and bioinformatic characterization of the biogenesis and function of melanosomes."
Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H., Mangini N.J., Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R., Yamagishi S., Shabanowitz J., Hearing V.J., Wu C., Appella E., Hunt D.F.
J. Proteome Res. 5:3135-3144(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
Tissue: Melanoma.
[13]"Elucidation of N-glycosylation sites on human platelet proteins: a glycoproteomic approach."
Lewandrowski U., Moebius J., Walter U., Sickmann A.
Mol. Cell. Proteomics 5:226-233(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-107.
Tissue: Platelet.
[14]"OS-9 and GRP94 deliver mutant alpha1-antitrypsin to the Hrd1-SEL1L ubiquitin ligase complex for ERAD."
Christianson J.C., Shaler T.A., Tyler R.E., Kopito R.R.
Nat. Cell Biol. 10:272-282(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH OS9.
[15]"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.
J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-62; ASN-107; ASN-217 AND ASN-445.
Tissue: Liver.
[16]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-306, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[17]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[18]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-306, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[19]"A newly uncovered group of distantly related lysine methyltransferases preferentially interact with molecular chaperones to regulate their activity."
Cloutier P., Lavallee-Adam M., Faubert D., Blanchette M., Coulombe B.
PLoS Genet. 9:E1003210-E1003210(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH METTL23.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X15187 mRNA. Translation: CAA33261.1.
M33716 Genomic DNA. Translation: AAA68201.1.
BC066656 mRNA. Translation: AAH66656.1.
M26596 Genomic DNA. Translation: AAA58621.1.
AY040226 mRNA. Translation: AAK74072.1.
PIRA35954.
RefSeqNP_003290.1. NM_003299.2.
UniGeneHs.192374.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4NH9X-ray2.77A69-337[»]
ProteinModelPortalP14625.
SMRP14625. Positions 72-755.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid113036. 81 interactions.
DIPDIP-36060N.
IntActP14625. 40 interactions.
MINTMINT-210408.
STRING9606.ENSP00000299767.

Chemistry

BindingDBP14625.
ChEMBLCHEMBL1075323.
DrugBankDB00615. Rifabutin.

PTM databases

PhosphoSiteP14625.

Polymorphism databases

DMDM119360.

2D gel databases

DOSAC-COBS-2DPAGEP14625.
OGPP14625.
REPRODUCTION-2DPAGEIPI00027230.

Proteomic databases

PaxDbP14625.
PeptideAtlasP14625.
PRIDEP14625.

Protocols and materials databases

DNASU7184.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000299767; ENSP00000299767; ENSG00000166598.
GeneID7184.
KEGGhsa:7184.
UCSCuc001tkb.2. human.

Organism-specific databases

CTD7184.
GeneCardsGC12P104324.
H-InvDBHIX0056796.
HGNCHGNC:12028. HSP90B1.
HPACAB005224.
HPA003901.
HPA008424.
MIM191175. gene.
neXtProtNX_P14625.
PharmGKBPA36705.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0326.
HOGENOMHOG000031988.
HOVERGENHBG007374.
InParanoidP14625.
KOK09487.
OMAHITDTGI.
OrthoDBEOG780RM0.
PhylomeDBP14625.
TreeFamTF105969.

Enzyme and pathway databases

ReactomeREACT_160300. Binding and Uptake of Ligands by Scavenger Receptors.
REACT_17015. Metabolism of proteins.
REACT_6900. Immune System.

Gene expression databases

ArrayExpressP14625.
BgeeP14625.
CleanExHS_HSP90B1.
GenevestigatorP14625.

Family and domain databases

Gene3D3.30.565.10. 2 hits.
HAMAPMF_00505. HSP90.
InterProIPR015566. Endoplasmin.
IPR003594. HATPase_ATP-bd.
IPR019805. Heat_shock_protein_90_CS.
IPR001404. Hsp90_fam.
IPR020575. Hsp90_N.
IPR020568. Ribosomal_S5_D2-typ_fold.
[Graphical view]
PANTHERPTHR11528. PTHR11528. 1 hit.
PTHR11528:SF21. PTHR11528:SF21. 1 hit.
PfamPF00183. HSP90. 1 hit.
[Graphical view]
PIRSFPIRSF002583. Hsp90. 1 hit.
PRINTSPR00775. HEATSHOCK90.
SMARTSM00387. HATPase_c. 1 hit.
[Graphical view]
SUPFAMSSF54211. SSF54211. 1 hit.
SSF55874. SSF55874. 2 hits.
PROSITEPS00014. ER_TARGET. 1 hit.
PS00298. HSP90. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSHSP90B1. human.
GeneWikiHSP90B1.
GenomeRNAi7184.
NextBio28164.
PMAP-CutDBP14625.
PROP14625.
SOURCESearch...

Entry information

Entry nameENPL_HUMAN
AccessionPrimary (citable) accession number: P14625
Secondary accession number(s): Q96A97
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: April 1, 1990
Last modified: March 19, 2014
This is version 169 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM