ID   BIP_NEUCR               Reviewed;         661 AA.
AC   P78695; Q7RV55;
DT   15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT   15-MAR-2004, sequence version 3.
DT   27-MAR-2024, entry version 160.
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   Flags: Precursor;
GN   Name=grp78; ORFNames=NCU03982;
OS   Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 /
OS   FGSC 987).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC   Sordariomycetidae; Sordariales; Sordariaceae; Neurospora.
OX   NCBI_TaxID=367110;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=Bd-A / FGSC 1858;
RX   PubMed=9545520; DOI=10.1016/s0167-4781(98)00005-0;
RA   Techel D., Hafker T., Muschner S., Reimann M., Li Y., Monnerjahn C.,
RA   Rensing L.;
RT   "Molecular analysis of a glucose-regulated gene (grp78) of Neurospora
RT   crassa.";
RL   Biochim. Biophys. Acta 1397:21-26(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987;
RX   PubMed=12712197; DOI=10.1038/nature01554;
RA   Galagan J.E., Calvo S.E., Borkovich K.A., Selker E.U., Read N.D.,
RA   Jaffe D.B., FitzHugh W., Ma L.-J., Smirnov S., Purcell S., Rehman B.,
RA   Elkins T., Engels R., Wang S., Nielsen C.B., Butler J., Endrizzi M.,
RA   Qui D., Ianakiev P., Bell-Pedersen D., Nelson M.A., Werner-Washburne M.,
RA   Selitrennikoff C.P., Kinsey J.A., Braun E.L., Zelter A., Schulte U.,
RA   Kothe G.O., Jedd G., Mewes H.-W., Staben C., Marcotte E., Greenberg D.,
RA   Roy A., Foley K., Naylor J., Stange-Thomann N., Barrett R., Gnerre S.,
RA   Kamal M., Kamvysselis M., Mauceli E.W., Bielke C., Rudd S., Frishman D.,
RA   Krystofova S., Rasmussen C., Metzenberg R.L., Perkins D.D., Kroken S.,
RA   Cogoni C., Macino G., Catcheside D.E.A., Li W., Pratt R.J., Osmani S.A.,
RA   DeSouza C.P.C., Glass N.L., Orbach M.J., Berglund J.A., Voelker R.,
RA   Yarden O., Plamann M., Seiler S., Dunlap J.C., Radford A., Aramayo R.,
RA   Natvig D.O., Alex L.A., Mannhaupt G., Ebbole D.J., Freitag M., Paulsen I.,
RA   Sachs M.S., Lander E.S., Nusbaum C., Birren B.W.;
RT   "The genome sequence of the filamentous fungus Neurospora crassa.";
RL   Nature 422:859-868(2003).
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; Y09011; CAA70214.1; -; Genomic_DNA.
DR   EMBL; CM002241; EAA27331.1; -; Genomic_DNA.
DR   PIR; T50464; T50464.
DR   RefSeq; XP_956567.1; XM_951474.3.
DR   AlphaFoldDB; P78695; -.
DR   SMR; P78695; -.
DR   IntAct; P78695; 4.
DR   MINT; P78695; -.
DR   STRING; 367110.P78695; -.
DR   PaxDb; 5141-EFNCRP00000003679; -.
DR   EnsemblFungi; EAA27331; EAA27331; NCU03982.
DR   GeneID; 3872714; -.
DR   KEGG; ncr:NCU03982; -.
DR   VEuPathDB; FungiDB:NCU03982; -.
DR   HOGENOM; CLU_005965_7_0_1; -.
DR   InParanoid; P78695; -.
DR   OMA; AYTKNQD; -.
DR   OrthoDB; 143at2759; -.
DR   Proteomes; UP000001805; Chromosome 5, Linkage Group VI.
DR   GO; GO:0099021; C:cortical endoplasmic reticulum lumen; IEA:EnsemblFungi.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
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:0034099; C:luminal surveillance complex; IEA:EnsemblFungi.
DR   GO; GO:0016020; C:membrane; IBA:GO_Central.
DR   GO; GO:0031965; C:nuclear membrane; IEA:EnsemblFungi.
DR   GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR   GO; GO:0099020; C:perinuclear endoplasmic reticulum lumen; IEA:EnsemblFungi.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0016887; F:ATP hydrolysis activity; IBA:GO_Central.
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:0044183; F:protein folding chaperone; IBA:GO_Central.
DR   GO; GO:0015450; F:protein-transporting ATPase activity; IEA:EnsemblFungi.
DR   GO; GO:0051082; F:unfolded protein binding; IEA:EnsemblFungi.
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:0070880; P:fungal-type cell wall beta-glucan biosynthetic process; IEA:EnsemblFungi.
DR   GO; GO:0036498; P:IRE1-mediated unfolded protein response; IEA:EnsemblFungi.
DR   GO; GO:0000742; P:karyogamy involved in conjugation with cellular fusion; IEA:EnsemblFungi.
DR   GO; GO:0031204; P:post-translational protein targeting to membrane, translocation; IEA:EnsemblFungi.
DR   GO; GO:0042026; P:protein refolding; IBA:GO_Central.
DR   GO; GO:0006616; P:SRP-dependent cotranslational protein targeting to membrane, translocation; IEA:EnsemblFungi.
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; 3.30.30.30; -; 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   3: Inferred from homology;
KW   ATP-binding; Chaperone; Endoplasmic reticulum; Hydrolase;
KW   Nucleotide-binding; Reference proteome; Signal; Stress response.
FT   SIGNAL          1..32
FT                   /evidence="ECO:0000255"
FT   CHAIN           33..661
FT                   /note="Endoplasmic reticulum chaperone BiP"
FT                   /id="PRO_0000013583"
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   MOTIF           658..661
FT                   /note="Prevents secretion from ER"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10138"
FT   BINDING         47..50
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"
FT   CONFLICT        127
FT                   /note="Y -> N (in Ref. 1; CAA70214)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        527
FT                   /note="T -> N (in Ref. 1; CAA70214)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        538
FT                   /note="D -> E (in Ref. 1; CAA70214)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        617
FT                   /note="N -> ND (in Ref. 1; CAA70214)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   661 AA;  72332 MW;  90963337AF327DEA CRC64;
     MEHRTRSWAL GLSILGFFAL LFSAGFVQQA HANDTEAMGT VIGIDLGTTY SCVGVMQKGK
     VEILVNDQGN RITPSYVAFT DEERLVGDAA KNQAAANPHR TIFDIKRLIG RKFSDKDVQN
     DIKHFPYKVV SKDDKPVVKV EVKGEEKTFT PEEISAMILG KMKETAEGYL GKKVTHAVVT
     VPAYFNDNQR QATKDAGMIA GLNVLRIVNE PTAAAIAYGL DKTGEERQII VYDLGGGTFD
     VSLLSIEQGV FEVLSTAGDT HLGGEDFDQR IINHFAKLFN KKHGVDVTKD AKAMGKLKRE
     AEKAKRTLSS QMSTRIEIEA FYDGKDFSET LTRAKFEELN NDLFKKTLKP VEQVLKDAKV
     SKSEIDDIVL VGGSTRIPKV QALIEEFFNG KKASKGINPD EAVAFGAAVQ AGVLSGEEGT
     EDIVLMDVNP LTLGIETTGG VMTKLIPRNT PIPTRKSQIF STAADNQPVV LIQVYEGERS
     MTKDNNLLGK FELTGIPPAP RGVPQIEVSF ELDANGILKV SAHDKGTGKA ESITITNDKG
     RLTQEEIDRM VAEAEKYAEE DKATRERIEA RNGLENYAFS LKNQVNDEDG LGGKIDEEDK
     ETILDAVKEA QDWLEENAAT ASAEDFDEQK EKLSNVAYPI TSKLYSQGGA GDDEPAGHDE
     L
//