ID   BIBH_CAEEL              Reviewed;         657 AA.
AC   P20163; O02085;
DT   01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT   16-AUG-2004, sequence version 2.
DT   04-NOV-2026, entry version 195.
DE   RecName: Full=Endoplasmic reticulum chaperone BiP homolog {ECO:0000305};
DE   AltName: Full=Heat shock 70 kDa protein D;
DE            EC=3.6.4.10 {ECO:0000250|UniProtKB:P11021};
DE   Flags: Precursor;
GN   Name=hsp-4; Synonyms=hsp70d; ORFNames=F43E2.8;
OS   Caenorhabditis elegans.
OC   Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC   Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC   Caenorhabditis.
OX   NCBI_TaxID=6239;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Bristol N2;
RX   PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG   The C. elegans sequencing consortium;
RT   "Genome sequence of the nematode C. elegans: a platform for investigating
RT   biology.";
RL   Science 282:2012-2018(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 370-657.
RX   PubMed=2744444; DOI=10.1139/g89-428;
RA   Heschl M.F.P., Baillie D.L.;
RT   "Identification of a heat-shock pseudogene from Caenorhabditis elegans.";
RL   Genome 32:190-195(1989).
RN   [3]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=15716356; DOI=10.1091/mbc.e04-08-0726;
RA   Poteryaev D., Squirrell J.M., Campbell J.M., White J.G., Spang A.;
RT   "Involvement of the actin cytoskeleton and homotypic membrane fusion in ER
RT   dynamics in Caenorhabditis elegans.";
RL   Mol. Biol. Cell 16:2139-2153(2005).
RN   [4]
RP   X-RAY CRYSTALLOGRAPHY.
RA   Osipiuk J., Duggan E., Gu M., Voisine C., Morimoto R.I., Joachimiak A.;
RT   "X-ray structure of peptide-binding domain of Heat shock 70 kDa protein D
RT   precursor from C.elegans.";
RL   Submitted (JAN-2007) to the PDB data bank.
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). Required for ER dynamics during the first embryonic
CC       cell divisions (PubMed:15716356). Specifically, controls ER transition
CC       into sheet-like structures at the onset of mitosis, possibly by
CC       regulating homotypic membrane fusion (PubMed:15716356).
CC       {ECO:0000250|UniProtKB:P11021, ECO:0000269|PubMed:15716356}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + H2O = ADP + phosphate + H(+); 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:P11021}.
CC   -!- INDUCTION: By endoplasmic reticulum stress.
CC       {ECO:0000250|UniProtKB:P11021}.
CC   -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown prevents the formation of
CC       ER sheet-like structures during mitosis in the 1-cell embryo. ER
CC       accumulates in foci throughout mitosis and partially fails to disperse
CC       at the end of mitosis. {ECO:0000269|PubMed:15716356}.
CC   -!- SIMILARITY: Belongs to the heat shock protein 70 family. {ECO:0000305}.
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DR   EMBL; FO080417; CCD63548.1; -; Genomic_DNA.
DR   EMBL; M28528; AAA28076.1; -; Genomic_DNA.
DR   PIR; T34037; T34037.
DR   RefSeq; NP_001370395.1; NM_001383885.3.
DR   PDB; 2OP6; X-ray; 1.85 A; A=420-568.
DR   AlphaFoldDB; P20163; -.
DR   MDRepo; P20163; -.
DR   SMR; P20163; -.
DR   BioGRID; 39538; 17.
DR   DIP; DIP-26704N; -.
DR   FunCoup; P20163; 2321.
DR   IntAct; P20163; 3.
DR   STRING; 6239.F43E2.8a.2; -.
DR   PaxDb; 6239-F43E2.8a.2; -.
DR   PeptideAtlas; P20163; -.
DR   EnsemblMetazoa; F43E2.8a.1; F43E2.8a.1; WBGene00002008.
DR   EnsemblMetazoa; F43E2.8a.2; F43E2.8a.2; WBGene00002008.
DR   GeneID; 174203; -.
DR   UCSC; F43E2.8.1; c. elegans.
DR   AGR; WB:WBGene00002008; -.
DR   CTD; 174203; -.
DR   WormBase; F43E2.8a; CE07244; WBGene00002008; hsp-4.
DR   eggNOG; KOG0100; Eukaryota.
DR   HOGENOM; CLU_005965_3_0_1; -.
DR   InParanoid; P20163; -.
DR   OMA; ACRGFVN; -.
DR   OrthoDB; 2401965at2759; -.
DR   PhylomeDB; P20163; -.
DR   EvolutionaryTrace; P20163; -.
DR   PRO; PR:P20163; -.
DR   Proteomes; UP000001940; Chromosome II.
DR   Bgee; WBGene00002008; Expressed in adult organism and 4 other cell types or tissues.
DR   ExpressionAtlas; P20163; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0034663; C:endoplasmic reticulum chaperone complex; ISS:WormBase.
DR   GO; GO:0005788; C:endoplasmic reticulum lumen; ISS:UniProtKB.
DR   GO; GO:0016020; C:membrane; IBA:GO_Central.
DR   GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR   GO; GO:0005791; C:rough endoplasmic reticulum; IDA:WormBase.
DR   GO; GO:0005524; F:ATP binding; IEA:InterPro.
DR   GO; GO:0016887; F:ATP hydrolysis activity; ISS:UniProtKB.
DR   GO; GO:0031072; F:heat shock protein binding; IBA:GO_Central.
DR   GO; GO:0044183; F:protein folding chaperone; IBA:GO_Central.
DR   GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:WormBase.
DR   GO; GO:0030968; P:endoplasmic reticulum unfolded protein response; IEP:WormBase.
DR   GO; GO:0036503; P:ERAD pathway; IBA:GO_Central.
DR   GO; GO:0042026; P:protein refolding; IBA:GO_Central.
DR   CDD; cd10241; ASKHA_NBD_HSP70_BiP; 1.
DR   FunFam; 3.90.640.10:FF:000153; Endoplasmic reticulum chaperone BiP; 1.
DR   FunFam; 2.60.34.10:FF:000002; Heat shock 70 kDa; 1.
DR   FunFam; 3.30.420.40:FF:000172; Heat shock 70 kDa protein; 1.
DR   FunFam; 1.20.1270.10:FF:000016; Heat shock protein 70; 1.
DR   FunFam; 3.30.420.40:FF:000026; Heat shock protein 70; 1.
DR   Gene3D; 1.20.1270.10; -; 1.
DR   Gene3D; 3.30.420.40; -; 2.
DR   Gene3D; 3.90.640.10; Actin, Chain A, domain 4; 1.
DR   Gene3D; 2.60.34.10; Substrate Binding Domain Of DNAk, Chain A, domain 1; 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   NCBIfam; NF001413; dnaK; 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   3D-structure; ATP-binding; Chaperone; Endoplasmic reticulum; Hydrolase;
KW   Nucleotide-binding; Reference proteome; Signal; Stress response.
FT   SIGNAL          1..17
FT                   /evidence="ECO:0000255"
FT   CHAIN           18..657
FT                   /note="Endoplasmic reticulum chaperone BiP homolog"
FT                   /id="PRO_0000013542"
FT   REGION          128..282
FT                   /note="Nucleotide-binding (NBD)"
FT                   /evidence="ECO:0000250|UniProtKB:P11021"
FT   REGION          402..502
FT                   /note="Substrate-binding (SBD)"
FT                   /evidence="ECO:0000250|UniProtKB:P11021"
FT   REGION          607..657
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           654..657
FT                   /note="Prevents secretion from ER"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10138"
FT   COMPBIAS        616..626
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        646..657
FT                   /note="Acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         38..41
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P11021"
FT   BINDING         99
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P11021"
FT   BINDING         229..231
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P11021"
FT   BINDING         295..302
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P11021"
FT   BINDING         366..369
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P11021"
FT   CONFLICT        454
FT                   /note="S -> P (in Ref. 2; AAA28076)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        574
FT                   /note="M -> I (in Ref. 2; AAA28076)"
FT                   /evidence="ECO:0000305"
FT   STRAND          426..430
FT                   /evidence="ECO:0007829|PDB:2OP6"
FT   TURN            431..433
FT                   /evidence="ECO:0007829|PDB:2OP6"
FT   STRAND          434..439
FT                   /evidence="ECO:0007829|PDB:2OP6"
FT   STRAND          444..457
FT                   /evidence="ECO:0007829|PDB:2OP6"
FT   STRAND          463..471
FT                   /evidence="ECO:0007829|PDB:2OP6"
FT   HELIX           475..477
FT                   /evidence="ECO:0007829|PDB:2OP6"
FT   STRAND          478..486
FT                   /evidence="ECO:0007829|PDB:2OP6"
FT   STRAND          499..505
FT                   /evidence="ECO:0007829|PDB:2OP6"
FT   STRAND          511..517
FT                   /evidence="ECO:0007829|PDB:2OP6"
FT   TURN            518..520
FT                   /evidence="ECO:0007829|PDB:2OP6"
FT   STRAND          523..528
FT                   /evidence="ECO:0007829|PDB:2OP6"
FT   STRAND          530..533
FT                   /evidence="ECO:0007829|PDB:2OP6"
FT   HELIX           537..549
FT                   /evidence="ECO:0007829|PDB:2OP6"
FT   HELIX           551..560
FT                   /evidence="ECO:0007829|PDB:2OP6"
FT   STRAND          565..567
FT                   /evidence="ECO:0007829|PDB:2OP6"
SQ   SEQUENCE   657 AA;  72288 MW;  0C046D3EF1B5592F CRC64;
     MKVFSLILIA FVANAYCDEG ASTEKEEKMG TIIGIDLGTT YSCVGVFKNG RVEIIANDQG
     NRITPSYVAF SGDQGERLIG DAAKNQLTIN PENTIFDAKR LIGRFYNEKT VQQDIKHWPF
     KIVDKSNKPN VEVKVGSETK QFTPEEVSAM VLTKMKQIAE SYLGHEVKNA VVTVPAYFND
     AQKQATKDAG SIAGLNVVRI INEPTAAAIA YGLDKKDGER NILVFDLGGG TFDVSLLTID
     SGVFEVLATN GDTHLGGEDF DQRVMEYFIK LYKKKSGKDL RKDNRAVQKL RREVEKAKRA
     LSTQHQTKIE IESLFDGEDF SETLTRAKFE ELNMDLFRAT LKPVQKVLED ADMKKTDVHE
     IVLVGGSTRI PKVQQLIKDY FNGKEPSRGI NPDEAVAYGA AVQAGVIGGV ENTGDVVLLD
     VNPLTLGIET VGGVMTKLIG RNTVIPTKKS QVFSTAADSQ SAVSIVIYEG ERPMVMDNHK
     LGNFDVTGIP PAPRGVPQIE VTFEIDVNGI LHVSAEDKGT GNKNKLTITN DHNRLSPEDI
     ERMINDADKF AADDQAQKEK VESRNELEAY AYQMKTQIAD KEKLGGKLTD EDKVSIESAV
     ERAIEWLGSN QDASTEENKE QKKELESVVQ PIVSKLYSAG GQGEQASEEP SEDHDEL
//