P14625 (ENPL_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

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	803 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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. Ref.10 Ref.14
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 component	Endoplasmic reticulum
Domain	Signal
Ligand	ATP-binding Calcium Nucleotide-binding
Molecular function	Chaperone
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	ER-associated 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
Cellular_component	cytosol Inferred from direct assay PubMed 9596688. Source: UniProtKB endoplasmic reticulum lumen Inferred from direct assay PubMed 10497210. Source: UniProtKB endoplasmic reticulum membrane Inferred from direct assay PubMed 10497210. Source: UniProtKB 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 part Inferred from electronic annotation. Source: Compara
Molecular_function	ATP 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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 21	21	Ref.5
	Chain	22 – 803	782	Endoplasmin		PRO_0000013598
Regions
	Motif	800 – 803	4	Prevents secretion from ER
Sites
	Binding site	107	1	ATP By similarity
	Binding site	149	1	ATP By similarity
	Binding site	162	1	ATP By similarity
	Binding site	168	1	ATP By similarity
	Binding site	199	1	ATP; via amide nitrogen By similarity
	Binding site	448	1	ATP By similarity
Amino acid modifications
	Modified residue	306	1	Phosphoserine Ref.16 Ref.18
	Glycosylation	62	1	N-linked (GlcNAc...) Ref.15
	Glycosylation	107	1	N-linked (GlcNAc...) Ref.13 Ref.15
	Glycosylation	217	1	N-linked (GlcNAc...) Ref.8 Ref.15
	Glycosylation	445	1	N-linked (GlcNAc...) Ref.8 Ref.15
	Glycosylation	481	1	N-linked (GlcNAc...) Potential
	Glycosylation	502	1	N-linked (GlcNAc...) Potential
	Disulfide bond	138		Interchain By similarity
Experimental info
	Sequence conflict	188	1	T → S in AAK74072. Ref.4
	Sequence conflict	419	1	T → P in AAK74072. Ref.4
	Sequence conflict	803	1	L → F in AAK74072. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	P14625 [UniParc]. Last modified April 1, 1990. Version 1. Checksum: 9BF6705A7A2ED0D0	FASTA	803	92,469
	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

References

	« Hide 'large scale' referencesShow '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], MASS SPECTROMETRY. 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], MASS SPECTROMETRY. 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, MASS SPECTROMETRY. 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, MASS SPECTROMETRY. 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, MASS SPECTROMETRY. 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, MASS SPECTROMETRY.
+	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.
IPI	IPI00027230.
PIR	A35954.
RefSeq	NP_003290.1. NM_003299.2.
UniGene	Hs.192374.
3D structure databases
ProteinModelPortal	P14625.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-36060N.
IntAct	P14625. 32 interactions.
MINT	MINT-210408.
STRING	9606.ENSP00000299767.
PTM databases
PhosphoSite	P14625.
Polymorphism databases
DMDM	119360.
2D gel databases
DOSAC-COBS-2DPAGE	P14625.
OGP	P14625.
REPRODUCTION-2DPAGE	IPI00027230.
Proteomic databases
PaxDb	P14625.
PeptideAtlas	P14625.
PRIDE	P14625.
Protocols and materials databases
DNASU	7184.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000299767; ENSP00000299767; ENSG00000166598.
GeneID	7184.
KEGG	hsa:7184.
UCSC	uc001tkb.1. human.
Organism-specific databases
CTD	7184.
GeneCards	GC12P104324.
H-InvDB	HIX0056796.
HGNC	HGNC:12028. HSP90B1.
HPA	CAB005224. HPA003901. HPA008424.
MIM	191175. gene.
neXtProt	NX_P14625.
PharmGKB	PA36705.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0326.
HOGENOM	HOG000031988.
HOVERGEN	HBG007374.
InParanoid	P14625.
KO	K09487.
OMA	HITDTGI.
PhylomeDB	P14625.
Enzyme and pathway databases
Pathway_Interaction_DB	il6_7pathway. IL6-mediated signaling events.
Reactome	REACT_116125. Disease. REACT_6900. Immune System.
Gene expression databases
ArrayExpress	P14625.
Bgee	P14625.
CleanEx	HS_HSP90B1.
Genevestigator	P14625.
GermOnline	ENSG00000166598. Homo sapiens.
Family and domain databases
Gene3D	3.30.565.10. 2 hits.
InterPro	IPR003594. HATPase_ATP-bd. IPR019805. Heat_shock_protein_90_CS. IPR001404. Hsp90. IPR020575. Hsp90_N. IPR020568. Ribosomal_S5_D2-typ_fold. [Graphical view]
PANTHER	PTHR11528. PTHR11528. 1 hit.
Pfam	PF00183. HSP90. 1 hit. [Graphical view]
PIRSF	PIRSF002583. Hsp90. 1 hit.
PRINTS	PR00775. HEATSHOCK90.
SMART	SM00387. HATPase_c. 1 hit. [Graphical view]
SUPFAM	SSF55874. ATP_bd_ATPase. 1 hit. SSF54211. Ribosomal_S5_D2-typ_fold. 1 hit.
PROSITE	PS00014. ER_TARGET. 1 hit. PS00298. HSP90. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	P14625.
ChEMBL	CHEMBL1075323.
ChiTaRS	HSP90B1. human.
DrugBank	DB00615. Rifabutin.
GenomeRNAi	7184.
NextBio	28164.
PMAP-CutDB	P14625.
SOURCE	Search...

Entry information

Entry name

ENPL_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 160 of the entry and version 1 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.