BIP_XENLA
ID BIP_XENLA Reviewed; 658 AA.
AC Q91883;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 113.
DE RecName: Full=Endoplasmic reticulum chaperone BiP {ECO:0000250|UniProtKB:P11021};
DE EC=3.6.4.10 {ECO:0000250|UniProtKB:P11021};
DE AltName: Full=78 kDa glucose-regulated protein {ECO:0000250|UniProtKB:P11021};
DE Short=GRP-78 {ECO:0000250|UniProtKB:P11021};
DE AltName: Full=Binding-immunoglobulin protein {ECO:0000250|UniProtKB:P11021};
DE Short=BiP {ECO:0000250|UniProtKB:P11021};
DE AltName: Full=Heat shock protein 70 family protein 5 {ECO:0000250|UniProtKB:P11021};
DE Short=HSP70 family protein 5 {ECO:0000250|UniProtKB:P11021};
DE AltName: Full=Heat shock protein family A member 5 {ECO:0000250|UniProtKB:P11021};
DE AltName: Full=Immunoglobulin heavy chain-binding protein {ECO:0000250|UniProtKB:P11021};
DE Flags: Precursor;
GN Name=hspa5 {ECO:0000250|UniProtKB:P11021};
GN Synonyms=grp78 {ECO:0000250|UniProtKB:P11021};
OS Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8702846; DOI=10.1074/jbc.271.34.20895;
RA Beggah A., Mathews P., Beguin P., Geering K.;
RT "Degradation and endoplasmic reticulum retention of unassembled alpha- and
RT beta-subunits of Na,K-ATPase correlate with interaction of BiP.";
RL J. Biol. Chem. 271:20895-20902(1996).
CC -!- FUNCTION: Endoplasmic reticulum chaperone that plays a key role in
CC protein folding and quality control in the endoplasmic reticulum lumen
CC (By similarity). Involved in the correct folding of proteins and
CC degradation of misfolded proteins via its interaction with
CC dnajc10/ERdj5, probably to facilitate the release of dnajc10/ERdj5 from
CC its substrate (By similarity). Acts as a key repressor of the
CC ERN1/IRE1-mediated unfolded protein response (UPR). In the unstressed
CC endoplasmic reticulum, recruited by dnajb9/ERdj4 to the luminal region
CC of ern1/ire1, leading to disrupt the dimerization of ern1/ire1, thereby
CC inactivating ern1/ire1. Accumulation of misfolded protein in the
CC endoplasmic reticulum causes release of hspa5/BiP from ern1/ire1,
CC allowing homodimerization and subsequent activation of ern1/ire1 (By
CC similarity). {ECO:0000250|UniProtKB:G3I8R9,
CC ECO:0000250|UniProtKB:P11021, ECO:0000250|UniProtKB:P20029}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.10;
CC Evidence={ECO:0000250|UniProtKB:G3I8R9};
CC -!- ACTIVITY REGULATION: The chaperone activity is regulated by ATP-induced
CC allosteric coupling of the nucleotide-binding (NBD) and substrate-
CC binding (SBD) domains (By similarity). In the ADP-bound and nucleotide-
CC free (apo) states, the two domains have little interaction (By
CC similarity). In contrast, in the ATP-bound state the two domains are
CC tightly coupled, which results in drastically accelerated kinetics in
CC both binding and release of polypeptide substrates (By similarity). J
CC domain-containing co-chaperones (dnajb9/ERdj4 or dnajc10/ERdj5)
CC stimulate the ATPase activity and are required for efficient substrate
CC recognition by hspa5/BiP. Homooligomerization inactivates participating
CC hspa5/BiP protomers and probably act as reservoirs to store hspa5/BiP
CC molecules when they are not needed by the cell (By similarity).
CC {ECO:0000250|UniProtKB:G3I8R9, ECO:0000250|UniProtKB:P11021}.
CC -!- SUBUNIT: Monomer and homooligomer; homooligomerization via the
CC interdomain linker inactivates the chaperone activity and acts as a
CC storage of hspa5/BiP molecules (By similarity). Interacts with DNAJC10
CC (By similarity). Interacts with dnajb9/ERdj4; leading to recruit
CC hspa5/BiP to ern1/ire1. Interacts with ern1/ire1; interaction takes
CC place following interaction with dnajb9/ERdj4 and leads to inactivate
CC ern1/IRE1 (By similarity). {ECO:0000250|UniProtKB:G3I8R9,
CC ECO:0000250|UniProtKB:P11021, ECO:0000250|UniProtKB:P20029}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum lumen
CC {ECO:0000250|UniProtKB:P11021}.
CC -!- DOMAIN: The interdomain linker regulates the chaperone activity by
CC mediating the formation of homooligomers. Homooligomers are formed by
CC engagement of the interdomain linker of one hspa5/BiP molecule as a
CC typical substrate of an adjacent hspa5/BiP molecule. hspa5/BiP
CC oligomerization inactivates participating hspa5/BiP protomers.
CC hspa5/BiP oligomers probably act as reservoirs to store hspa5/BiP
CC molecules when they are not needed by the cell. When the levels of
CC unfolded proteins rise, cells can rapidly break up these oligomers to
CC make active monomers. {ECO:0000250|UniProtKB:G3I8R9}.
CC -!- SIMILARITY: Belongs to the heat shock protein 70 family. {ECO:0000305}.
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DR EMBL; U62807; AAB08760.1; -; mRNA.
DR RefSeq; NP_001081462.1; NM_001087993.1.
DR AlphaFoldDB; Q91883; -.
DR SMR; Q91883; -.
DR BioGRID; 99189; 1.
DR PRIDE; Q91883; -.
DR DNASU; 397850; -.
DR GeneID; 397850; -.
DR KEGG; xla:397850; -.
DR CTD; 397850; -.
DR Xenbase; XB-GENE-17331987; hspa5.L.
DR Proteomes; UP000186698; Chromosome 8L.
DR Bgee; 397850; Expressed in zone of skin and 19 other tissues.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; ISS:UniProtKB.
DR GO; GO:0140662; F:ATP-dependent protein folding chaperone; IEA:InterPro.
DR GO; GO:1903895; P:negative regulation of IRE1-mediated unfolded protein response; ISS:UniProtKB.
DR GO; GO:0031333; P:negative regulation of protein-containing complex assembly; ISS:UniProtKB.
DR CDD; cd10241; HSPA5-like_NBD; 1.
DR Gene3D; 1.20.1270.10; -; 1.
DR Gene3D; 2.60.34.10; -; 1.
DR InterPro; IPR043129; ATPase_NBD.
DR InterPro; IPR042050; BIP_NBD.
DR InterPro; IPR018181; Heat_shock_70_CS.
DR InterPro; IPR029048; HSP70_C_sf.
DR InterPro; IPR029047; HSP70_peptide-bd_sf.
DR InterPro; IPR013126; Hsp_70_fam.
DR PANTHER; PTHR19375; PTHR19375; 1.
DR Pfam; PF00012; HSP70; 1.
DR SUPFAM; SSF100920; SSF100920; 1.
DR SUPFAM; SSF100934; SSF100934; 1.
DR SUPFAM; SSF53067; SSF53067; 2.
DR PROSITE; PS00014; ER_TARGET; 1.
DR PROSITE; PS00297; HSP70_1; 1.
DR PROSITE; PS00329; HSP70_2; 1.
DR PROSITE; PS01036; HSP70_3; 1.
PE 2: Evidence at transcript level;
KW ATP-binding; Chaperone; Endoplasmic reticulum; Hydrolase;
KW Nucleotide-binding; Reference proteome; Signal.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..658
FT /note="Endoplasmic reticulum chaperone BiP"
FT /id="PRO_0000013571"
FT REGION 127..281
FT /note="Nucleotide-binding (NBD)"
FT /evidence="ECO:0000250|UniProtKB:P11021"
FT REGION 410..420
FT /note="Interdomain linker"
FT /evidence="ECO:0000250|UniProtKB:G3I8R9"
FT REGION 421..501
FT /note="Substrate-binding (SBD)"
FT /evidence="ECO:0000250|UniProtKB:P11021"
FT REGION 634..658
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 655..658
FT /note="Prevents secretion from ER"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10138"
FT BINDING 38..41
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P11021"
FT BINDING 98
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P11021"
FT BINDING 228..230
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P11021"
FT BINDING 294..301
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P11021"
FT BINDING 365..368
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P11021"
SQ SEQUENCE 658 AA; 72635 MW; 43E1468F532E80CF CRC64;
MVTMKLFALV LLVSASVFAS DDDDKKDDIG TVVGIDLGTT YSCVGVFKNG RVEIIANDQG
NRITPSYVAF TPEGERLIGD AAKNQLTSNP ENTVFDAKRL IGRTWNDPSV QQDIKYLPFK
VIEKKTKPYI EVDIGDQMKT FAPEEISAMV LVKMKETAEA YLGRKVTHAV VTVPAYFNDA
QRQATKDAGT IAGLNVMRII NEPTAAAIAY GLDKKEGEKN ILVFDLGGGT FDVSLLTIDN
GVFEVVATNG DTHLGGEDFD QRVMEHFIKL YKKKTGKDVR ADKRAVQKLR REVEKAKRAL
SAQHQSRIEI ESFFEGEDFS ETLTRAKFEE LNMDLFRSTM KPVQKVLDDS DLKKSDIDEI
VLVGGSTRIP KIQQLVKELF NGKEPSRGIN PDEAVAYGAA VQAGVLSGDQ DTGDLVLLDV
CPLTLGIETV GGVMTKLIPR NTVVPTKKSQ IFSTASDNQP TVTIKVYEGE RPLTKDNHLL
GTFDLTGIPP APRGVPQIEV TFEIDVNGIL RVTAEDKGTG NKNKITITND QNRLTPEEIE
RMVTDAEKFA EEDKKLKERI DTRNELESYA YSLKNQIGDK EKLGGKLSSE DKETIEKAVE
EKIEWLESHQ DADIEDFKAK KKELEEIVQP IVGKLYGGAG APPPEGAEGA EETEKDEL
