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Protein

Endoplasmic reticulum chaperone BiP

Gene

hspa5

Organism
Xenopus laevis (African clawed frog)
Status
Reviewed-Annotation score: -Experimental evidence at transcript leveli

Functioni

Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen (By similarity). Involved in the correct folding of proteins and degradation of misfolded proteins via its interaction with dnajc10/ERdj5, probably to facilitate the release of dnajc10/ERdj5 from its substrate (By similarity). Acts as a key repressor of the ERN1/IRE1-mediated unfolded protein response (UPR). In the unstressed endoplasmic reticulum, recruited by dnajb9/ERdj4 to the luminal region of ern1/ire1, leading to disrupt the dimerization of ern1/ire1, thereby inactivating ern1/ire1. Accumulation of misfolded protein in the endoplasmic reticulum causes release of hspa5/BiP from ern1/ire1, allowing homodimerization and subsequent activation of ern1/ire1 (By similarity).By similarity

Catalytic activityi

ATP + H2O = ADP + phosphate.By similarity

Activity regulationi

The chaperone activity is regulated by ATP-induced allosteric coupling of the nucleotide-binding (NBD) and substrate-binding (SBD) domains (By similarity). In the ADP-bound and nucleotide-free (apo) states, the two domains have little interaction (By similarity). In contrast, in the ATP-bound state the two domains are tightly coupled, which results in drastically accelerated kinetics in both binding and release of polypeptide substrates (By similarity). J domain-containing co-chaperones (dnajb9/ERdj4 or dnajc10/ERdj5) stimulate the ATPase activity and are required for efficient substrate recognition by hspa5/BiP. Homooligomerization inactivates participating hspa5/BiP protomers and probably act as reservoirs to store hspa5/BiP molecules when they are not needed by the cell (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei98ATPBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi38 – 41ATPBy similarity4
Nucleotide bindingi228 – 230ATPBy similarity3
Nucleotide bindingi294 – 301ATPBy similarity8
Nucleotide bindingi365 – 368ATPBy similarity4

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionChaperone, Hydrolase
LigandATP-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Endoplasmic reticulum chaperone BiPBy similarity (EC:3.6.4.10By similarity)
Alternative name(s):
78 kDa glucose-regulated proteinBy similarity
Short name:
GRP-78By similarity
Binding-immunoglobulin proteinBy similarity
Short name:
BiPBy similarity
Heat shock protein 70 family protein 5By similarity
Short name:
HSP70 family protein 5By similarity
Heat shock protein family A member 5By similarity
Immunoglobulin heavy chain-binding proteinBy similarity
Gene namesi
Name:hspa5By similarity
Synonyms:grp78By similarity
OrganismiXenopus laevis (African clawed frog)
Taxonomic identifieri8355 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiAmphibiaBatrachiaAnuraPipoideaPipidaeXenopodinaeXenopusXenopus

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Endoplasmic reticulum

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 19Sequence analysisAdd BLAST19
ChainiPRO_000001357120 – 658Endoplasmic reticulum chaperone BiPAdd BLAST639

Proteomic databases

PRIDEiQ91883

Interactioni

Subunit structurei

Monomer and homooligomer; homooligomerization via the interdomain linker inactivates the chaperone activity and acts as a storage of hspa5/BiP molecules (By similarity). Interacts with DNAJC10 (By similarity). Interacts with dnajb9/ERdj4; leading to recruit hspa5/BiP to ern1/ire1. Interacts with ern1/ire1; interaction takes place following interaction with dnajb9/ERdj4 and leads to inactivate ern1/IRE1 (By similarity).By similarity

Structurei

3D structure databases

ProteinModelPortaliQ91883
SMRiQ91883
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni127 – 281Nucleotide-binding (NBD)By similarityAdd BLAST155
Regioni410 – 420Interdomain linkerBy similarityAdd BLAST11
Regioni421 – 501Substrate-binding (SBD)By similarityAdd BLAST81

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi655 – 658Prevents secretion from ERPROSITE-ProRule annotation4

Domaini

The interdomain linker regulates the chaperone activity by mediating the formation of homooligomers. Homooligomers are formed by engagement of the interdomain linker of one hspa5/BiP molecule as a typical substrate of an adjacent hspa5/BiP molecule. hspa5/BiP oligomerization inactivates participating hspa5/BiP protomers. hspa5/BiP oligomers probably act as reservoirs to store hspa5/BiP molecules when they are not needed by the cell. When the levels of unfolded proteins rise, cells can rapidly break up these oligomers to make active monomers.By similarity

Sequence similaritiesi

Belongs to the heat shock protein 70 family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

HOVERGENiHBG051845
KOiK09490

Family and domain databases

Gene3Di1.20.1270.10, 1 hit
2.60.34.10, 1 hit
InterProiView protein in InterPro
IPR018181 Heat_shock_70_CS
IPR029048 HSP70_C_sf
IPR029047 HSP70_peptide-bd_sf
IPR013126 Hsp_70_fam
PANTHERiPTHR19375 PTHR19375, 1 hit
PfamiView protein in Pfam
PF00012 HSP70, 1 hit
PRINTSiPR00301 HEATSHOCK70
SUPFAMiSSF100920 SSF100920, 1 hit
SSF100934 SSF100934, 1 hit
PROSITEiView protein in PROSITE
PS00014 ER_TARGET, 1 hit
PS00297 HSP70_1, 1 hit
PS00329 HSP70_2, 1 hit
PS01036 HSP70_3, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q91883-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MVTMKLFALV LLVSASVFAS DDDDKKDDIG TVVGIDLGTT YSCVGVFKNG
60 70 80 90 100
RVEIIANDQG NRITPSYVAF TPEGERLIGD AAKNQLTSNP ENTVFDAKRL
110 120 130 140 150
IGRTWNDPSV QQDIKYLPFK VIEKKTKPYI EVDIGDQMKT FAPEEISAMV
160 170 180 190 200
LVKMKETAEA YLGRKVTHAV VTVPAYFNDA QRQATKDAGT IAGLNVMRII
210 220 230 240 250
NEPTAAAIAY GLDKKEGEKN ILVFDLGGGT FDVSLLTIDN GVFEVVATNG
260 270 280 290 300
DTHLGGEDFD QRVMEHFIKL YKKKTGKDVR ADKRAVQKLR REVEKAKRAL
310 320 330 340 350
SAQHQSRIEI ESFFEGEDFS ETLTRAKFEE LNMDLFRSTM KPVQKVLDDS
360 370 380 390 400
DLKKSDIDEI VLVGGSTRIP KIQQLVKELF NGKEPSRGIN PDEAVAYGAA
410 420 430 440 450
VQAGVLSGDQ DTGDLVLLDV CPLTLGIETV GGVMTKLIPR NTVVPTKKSQ
460 470 480 490 500
IFSTASDNQP TVTIKVYEGE RPLTKDNHLL GTFDLTGIPP APRGVPQIEV
510 520 530 540 550
TFEIDVNGIL RVTAEDKGTG NKNKITITND QNRLTPEEIE RMVTDAEKFA
560 570 580 590 600
EEDKKLKERI DTRNELESYA YSLKNQIGDK EKLGGKLSSE DKETIEKAVE
610 620 630 640 650
EKIEWLESHQ DADIEDFKAK KKELEEIVQP IVGKLYGGAG APPPEGAEGA

EETEKDEL
Length:658
Mass (Da):72,635
Last modified:November 1, 1996 - v1
Checksum:i43E1468F532E80CF
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U62807 mRNA Translation: AAB08760.1
RefSeqiNP_001081462.1, NM_001087993.1
UniGeneiXl.3204
Xl.85442

Genome annotation databases

GeneIDi397850
KEGGixla:397850

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U62807 mRNA Translation: AAB08760.1
RefSeqiNP_001081462.1, NM_001087993.1
UniGeneiXl.3204
Xl.85442

3D structure databases

ProteinModelPortaliQ91883
SMRiQ91883
ModBaseiSearch...
MobiDBiSearch...

Proteomic databases

PRIDEiQ91883

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi397850
KEGGixla:397850

Organism-specific databases

CTDi397850

Phylogenomic databases

HOVERGENiHBG051845
KOiK09490

Family and domain databases

Gene3Di1.20.1270.10, 1 hit
2.60.34.10, 1 hit
InterProiView protein in InterPro
IPR018181 Heat_shock_70_CS
IPR029048 HSP70_C_sf
IPR029047 HSP70_peptide-bd_sf
IPR013126 Hsp_70_fam
PANTHERiPTHR19375 PTHR19375, 1 hit
PfamiView protein in Pfam
PF00012 HSP70, 1 hit
PRINTSiPR00301 HEATSHOCK70
SUPFAMiSSF100920 SSF100920, 1 hit
SSF100934 SSF100934, 1 hit
PROSITEiView protein in PROSITE
PS00014 ER_TARGET, 1 hit
PS00297 HSP70_1, 1 hit
PS00329 HSP70_2, 1 hit
PS01036 HSP70_3, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiBIP_XENLA
AccessioniPrimary (citable) accession number: Q91883
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: November 1, 1996
Last modified: October 10, 2018
This is version 97 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Documents

  1. SIMILARITY comments
    Index of protein domains and families
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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