BIP_CHICK
ID BIP_CHICK Reviewed; 652 AA.
AC Q90593;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 150.
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 Gallus gallus (Chicken).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC Phasianinae; Gallus.
OX NCBI_TaxID=9031;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2841586; DOI=10.1128/mcb.8.7.2675-2680.1988;
RA Stoeckle M.Y., Sugano S., Hampe A., Vashishtha A., Pellman D., Hanafusa H.;
RT "78-kilodalton glucose-regulated protein is induced in Rous sarcoma virus-
RT transformed cells independently of glucose deprivation.";
RL Mol. Cell. Biol. 8:2675-2680(1988).
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). May also play a role in apoptosis and cell proliferation
CC (By 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 -!- INTERACTION:
CC Q90593; Q8AYS8: KCNMA1; NbExp=3; IntAct=EBI-1635886, EBI-1635766;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum lumen
CC {ECO:0000250|UniProtKB:P11021}. Melanosome
CC {ECO:0000250|UniProtKB:P11021}. Cytoplasm
CC {ECO:0000250|UniProtKB:P20029}. Cell surface. Note=Identified by mass
CC spectrometry in melanosome fractions from stage I to stage IV (By
CC similarity). Localizes to the cell surface in epithelial cells; high
CC levels of free iron promotes cell surface localization (By similarity).
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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; M27260; AAA48785.1; -; mRNA.
DR PIR; I50242; I50242.
DR RefSeq; NP_990822.1; NM_205491.1.
DR AlphaFoldDB; Q90593; -.
DR SMR; Q90593; -.
DR BioGRID; 676734; 3.
DR IntAct; Q90593; 1.
DR STRING; 9031.ENSGALP00000001474; -.
DR PaxDb; Q90593; -.
DR PRIDE; Q90593; -.
DR Ensembl; ENSGALT00000001476; ENSGALP00000001474; ENSGALG00000001000.
DR GeneID; 396487; -.
DR KEGG; gga:396487; -.
DR CTD; 3309; -.
DR VEuPathDB; HostDB:geneid_396487; -.
DR eggNOG; KOG0100; Eukaryota.
DR GeneTree; ENSGT00940000154787; -.
DR HOGENOM; CLU_005965_7_2_1; -.
DR InParanoid; Q90593; -.
DR OMA; AYTKNQD; -.
DR OrthoDB; 288077at2759; -.
DR PhylomeDB; Q90593; -.
DR TreeFam; TF105044; -.
DR Reactome; R-GGA-983170; Antigen Presentation: Folding, assembly and peptide loading of class I MHC.
DR PRO; PR:Q90593; -.
DR Proteomes; UP000000539; Chromosome 17.
DR Bgee; ENSGALG00000001000; Expressed in spermatocyte and 13 other tissues.
DR GO; GO:0009986; C:cell surface; IEA:UniProtKB-SubCell.
DR GO; GO:0008180; C:COP9 signalosome; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0034663; C:endoplasmic reticulum chaperone complex; IBA:GO_Central.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; IBA:GO_Central.
DR GO; GO:0005793; C:endoplasmic reticulum-Golgi intermediate compartment; IEA:Ensembl.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; IEA:Ensembl.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0030496; C:midbody; IEA:Ensembl.
DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IEA:Ensembl.
DR GO; GO:0005524; F:ATP binding; IBA:GO_Central.
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:0031072; F:heat shock protein binding; IBA:GO_Central.
DR GO; GO:0051787; F:misfolded protein binding; IBA:GO_Central.
DR GO; GO:0019904; F:protein domain specific binding; IEA:Ensembl.
DR GO; GO:0044183; F:protein folding chaperone; IBA:GO_Central.
DR GO; GO:0043022; F:ribosome binding; IEA:Ensembl.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IEA:Ensembl.
DR GO; GO:0051082; F:unfolded protein binding; IBA:GO_Central.
DR GO; GO:0042149; P:cellular response to glucose starvation; IEA:Ensembl.
DR GO; GO:0071353; P:cellular response to interleukin-4; IEA:Ensembl.
DR GO; GO:0034620; P:cellular response to unfolded protein; IBA:GO_Central.
DR GO; GO:0021680; P:cerebellar Purkinje cell layer development; IEA:Ensembl.
DR GO; GO:0021589; P:cerebellum structural organization; IEA:Ensembl.
DR GO; GO:0051085; P:chaperone cofactor-dependent protein refolding; IBA:GO_Central.
DR GO; GO:0030968; P:endoplasmic reticulum unfolded protein response; IBA:GO_Central.
DR GO; GO:0006983; P:ER overload response; IEA:Ensembl.
DR GO; GO:0035437; P:maintenance of protein localization in endoplasmic reticulum; IEA:Ensembl.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IEA:Ensembl.
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 GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0030335; P:positive regulation of cell migration; IEA:Ensembl.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; IEA:Ensembl.
DR GO; GO:0031204; P:post-translational protein targeting to membrane, translocation; IEA:Ensembl.
DR GO; GO:0042026; P:protein refolding; IBA:GO_Central.
DR GO; GO:1901998; P:toxin transport; IEA:Ensembl.
DR GO; GO:0030433; P:ubiquitin-dependent ERAD pathway; IBA:GO_Central.
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 1: Evidence at protein level;
KW ATP-binding; Chaperone; Cytoplasm; Endoplasmic reticulum; Hydrolase;
KW Nucleotide-binding; Reference proteome; Signal.
FT SIGNAL 1..16
FT /evidence="ECO:0000255"
FT CHAIN 17..652
FT /note="Endoplasmic reticulum chaperone BiP"
FT /id="PRO_0000013570"
FT REGION 123..278
FT /note="Nucleotide-binding (NBD)"
FT /evidence="ECO:0000250|UniProtKB:P11021"
FT REGION 407..417
FT /note="Interdomain linker"
FT /evidence="ECO:0000250|UniProtKB:G3I8R9"
FT REGION 418..498
FT /note="Substrate-binding (SBD)"
FT /evidence="ECO:0000250|UniProtKB:P11021"
FT REGION 630..652
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 649..652
FT /note="Prevents secretion from ER"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10138"
FT BINDING 34..37
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P11021"
FT BINDING 94
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P11021"
FT BINDING 225..227
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P11021"
FT BINDING 291..298
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P11021"
FT BINDING 362..365
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P11021"
SQ SEQUENCE 652 AA; 72019 MW; 4E4BB58A3EEFAF6F CRC64;
MRHLLLALLL LGGARADDEE KKEDVGTVVG IDLGTTYSCV GVFKNGRVEI IANDQGNRIT
PSYVAFTPEG ERLIGDAAKN QLTSNPENTV FDAKRLIGRT WNDPSVQQDI KYLPFKVVEK
KAKPHIQVDV GGGQTKTFAP EEISAMVLTK MKETAEAYLG KKVTHAVVTV PAYFNDAQRQ
ATKDAGTIAG LNVMRIINEP TAAAIAYGLD KREGEKNILV FDLGGGTFDV SLLTIDNGVF
EVVATNGDTH LGGEDFDQRV MEHFIKLYKK KTGKDVRKDN RAVQKLRREV EKAKRALSSQ
HQARIEIESF FEGEDFSETL TRAKFEELNM DLFRSTMKPV QKVLEDSDLK KSDIDEIVLV
GGSTRIPKIQ QLVKEFFNGK EPSRGINPDE AVAYGAAVQA GVLSGDQDTG DLVLLDVCPL
TLGIETVGGV MTKLIPRNTV VPTKKSQIFS TASDNQPTVT IKVYEGERPL TKDNHLLGTF
DLTGIPPAPR GVPQIEVTFE IDVNGILRVT AEDKGTGNKN KITITNDQNR LTPEEIERMV
NDAEKFAEED KKLKERIDAR NELESYAYSL KNQIGDKEKL GGKLSSEDKE TIEKAVEEKI
EWLESHQDAD IEDFKSKKKE LEEVVQPIVS KLYGSAGPPP TGEEEAAEKD EL
