ID   BIP_APLCA               Reviewed;         667 AA.
AC   Q16956;
DT   15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1996, sequence version 1.
DT   27-MAR-2024, entry version 99.
DE   RecName: Full=Endoplasmic reticulum chaperone BiP {ECO:0000305};
DE            EC=3.6.4.10 {ECO:0000250|UniProtKB:P11021};
DE   AltName: Full=Immunoglobulin heavy chain-binding protein homolog {ECO:0000305};
DE            Short=BiP {ECO:0000305};
DE   AltName: Full=Protein 1603 {ECO:0000303|PubMed:1360013};
DE   Flags: Precursor;
OS   Aplysia californica (California sea hare).
OC   Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda;
OC   Heterobranchia; Euthyneura; Tectipleura; Aplysiida; Aplysioidea;
OC   Aplysiidae; Aplysia.
OX   NCBI_TaxID=6500;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 368-382.
RX   PubMed=1360013; DOI=10.1083/jcb.119.5.1069;
RA   Kuhl D., Kennedy T., Barzilai A., Kandel E.;
RT   "Long-term sensitization training in Aplysia leads to an increase in the
RT   expression of BiP, the major protein chaperon of the ER.";
RL   J. Cell Biol. 119:1069-1076(1992).
CC   -!- FUNCTION: Probably plays a role in facilitating the assembly of
CC       multimeric protein complexes inside the ER. Is required for secretory
CC       polypeptide translocation. May physically associate with SEC63 protein
CC       in the endoplasmic reticulum and this interaction may be regulated by
CC       ATP hydrolysis. {ECO:0000250|UniProtKB:P16474}.
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:P11021};
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. In the ADP-bound and nucleotide-free (apo)
CC       states, the two domains have little interaction. In contrast, in the
CC       ATP-bound state the two domains are tightly coupled, which results in
CC       drastically accelerated kinetics in both binding and release of
CC       polypeptide substrates. J domain-containing co-chaperones stimulate the
CC       ATPase activity and are required for efficient substrate recognition.
CC       {ECO:0000250|UniProtKB:P11021}.
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum lumen
CC       {ECO:0000250|UniProtKB:P16474, ECO:0000255|PROSITE-ProRule:PRU10138}.
CC   -!- SIMILARITY: Belongs to the heat shock protein 70 family. {ECO:0000305}.
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DR   EMBL; Z15041; CAA78759.1; -; mRNA.
DR   PIR; D44261; D44261.
DR   PIR; S24782; S24782.
DR   RefSeq; NP_001191581.1; NM_001204652.1.
DR   AlphaFoldDB; Q16956; -.
DR   SMR; Q16956; -.
DR   EnsemblMetazoa; NM_001204652.1; NP_001191581.1; LOC100533358.
DR   GeneID; 100533358; -.
DR   OrthoDB; 143at2759; -.
DR   Proteomes; UP000694888; Unplaced.
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; IEA:RHEA.
DR   GO; GO:0140662; F:ATP-dependent protein folding chaperone; IEA:InterPro.
DR   CDD; cd10241; HSPA5-like_NBD; 1.
DR   Gene3D; 1.20.1270.10; -; 1.
DR   Gene3D; 3.30.420.40; -; 2.
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:SF144; ENDOPLASMIC RETICULUM CHAPERONE BIP; 1.
DR   PANTHER; PTHR19375; HEAT SHOCK PROTEIN 70KDA; 1.
DR   Pfam; PF00012; HSP70; 1.
DR   PRINTS; PR00301; HEATSHOCK70.
DR   SUPFAM; SSF53067; Actin-like ATPase domain; 2.
DR   SUPFAM; SSF100934; Heat shock protein 70kD (HSP70), C-terminal subdomain; 1.
DR   SUPFAM; SSF100920; Heat shock protein 70kD (HSP70), peptide-binding domain; 1.
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; Direct protein sequencing; Endoplasmic reticulum;
KW   Hydrolase; Nucleotide-binding; Signal.
FT   SIGNAL          1..22
FT                   /evidence="ECO:0000255"
FT   CHAIN           23..667
FT                   /note="Endoplasmic reticulum chaperone BiP"
FT                   /id="PRO_0000013572"
FT   REGION          135..289
FT                   /note="Nucleotide-binding (NBD)"
FT                   /evidence="ECO:0000250|UniProtKB:P11021"
FT   REGION          409..509
FT                   /note="Substrate-binding (SBD)"
FT                   /evidence="ECO:0000250|UniProtKB:P11021"
FT   REGION          641..667
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           664..667
FT                   /note="Prevents secretion from ER"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10138"
FT   BINDING         46..49
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P11021"
FT   BINDING         106
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P11021"
FT   BINDING         236..238
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P11021"
FT   BINDING         302..309
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P11021"
FT   BINDING         373..376
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P11021"
SQ   SEQUENCE   667 AA;  73698 MW;  A59EC27AF188141D CRC64;
     MDRFTPFFLL VILFSSNLLV RADGDEEDEG DKKKSEVGTV IGIDLGTTYS CVGVFKNGRV
     DIIANDQGNR ITPSYVAFTA DGERLIGDAA KNQLTSNPEN TIFDVKRLIG RTFDDKSVQH
     DIKFYPFKVT NANNKPHIQA ATGEGDRSFA PEEISAMVLS KMRDIAEEYL GKKITNAVVT
     VPAYFNDAQR QATKDAGTIA GLNVMRIINE PTAAAIAYGL DKKEGEKNIL VFDLGGGTFD
     VSLLTIDNGV FEVVSTNGDT HLGGEDFDQR VMEHFIKLYK KKKGKDIRKD NRAVQKLRRE
     VEKAKRALSS AHQVRLEIES FFDGEDFSES LTRAKFEELN MDLFRSTMKP VKQVLEDADL
     KTDDIDEIVL VGGSTRIPKV QQLVKEYFNG KEPSRGINPD EAVAYGAAVQ AGVLSGEEDT
     GDLVLLDVNP LTMGIETVGG VMTKLIPRNT VIPTKKSQIF STAADNQPTV TIQVYEGERS
     MTKDNHLLGK FDLTGIPPAP RGVPQIEVTF EIDVNGILKV TAEDKGTGSK NQIVIQNDQN
     RLSPEDIERM INDAEKYADE DKKVKEKVDA KNELESYAYS LKNQIGDKEK LGAKLSDEDK
     EKITEAVDEA IKWLESNAEA ESEAFNEKKT ELEGIVQPIM TKLYEQSGGA PPPSGEEESE
     EAEKDEL
//