BIP_YEAST
ID BIP_YEAST Reviewed; 682 AA.
AC P16474; D6VWE9;
DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1990, sequence version 1.
DT 03-AUG-2022, entry version 221.
DE RecName: Full=Endoplasmic reticulum chaperone BiP {ECO:0000305};
DE EC=3.6.4.10 {ECO:0000250|UniProtKB:P11021};
DE AltName: Full=78 kDa glucose-regulated protein homolog {ECO:0000303|PubMed:2661018};
DE Short=GRP-78 {ECO:0000303|PubMed:2661018};
DE AltName: Full=Immunoglobulin heavy chain-binding protein homolog {ECO:0000305};
DE Short=BiP {ECO:0000305};
DE Flags: Precursor;
GN Name=KAR2; Synonyms=GRP78 {ECO:0000303|PubMed:2661018}, SSD1;
GN OrderedLocusNames=YJL034W; ORFNames=J1248;
OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=559292;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND SUBCELLULAR LOCATION.
RX PubMed=2661018; DOI=10.1016/0092-8674(89)90058-5;
RA Rose M.D., Misra L.M., Vogel J.P.;
RT "KAR2, a karyogamy gene, is the yeast homolog of the mammalian BiP/GRP78
RT gene.";
RL Cell 57:1211-1221(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=LL20;
RX PubMed=2105497; DOI=10.1073/pnas.87.3.1159;
RA Nicholson R.C., Williams D.B., Moran L.A.;
RT "An essential member of the HSP70 gene family of Saccharomyces cerevisiae
RT is homologous to immunoglobulin heavy chain binding protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:1159-1163(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2661019; DOI=10.1016/0092-8674(89)90059-7;
RA Normington K., Kohno K., Kozutsumi Y., Gething M.J., Sambrook J.;
RT "S. cerevisiae encodes an essential protein homologous in sequence and
RT function to mammalian BiP.";
RL Cell 57:1223-1236(1989).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=8641269; DOI=10.1002/j.1460-2075.1996.tb00557.x;
RA Galibert F., Alexandraki D., Baur A., Boles E., Chalwatzis N., Chuat J.-C.,
RA Coster F., Cziepluch C., de Haan M., Domdey H., Durand P., Entian K.-D.,
RA Gatius M., Goffeau A., Grivell L.A., Hennemann A., Herbert C.J.,
RA Heumann K., Hilger F., Hollenberg C.P., Huang M.-E., Jacq C.,
RA Jauniaux J.-C., Katsoulou C., Kirchrath L., Kleine K., Kordes E.,
RA Koetter P., Liebl S., Louis E.J., Manus V., Mewes H.-W., Miosga T.,
RA Obermaier B., Perea J., Pohl T.M., Portetelle D., Pujol A., Purnelle B.,
RA Ramezani Rad M., Rasmussen S.W., Rose M., Rossau R.,
RA Schaaff-Gerstenschlaeger I., Smits P.H.M., Scarcez T., Soriano N.,
RA To Van D., Tzermia M., Van Broekhoven A., Vandenbol M., Wedler H.,
RA von Wettstein D., Wambutt R., Zagulski M., Zollner A., Karpfinger-Hartl L.;
RT "Complete nucleotide sequence of Saccharomyces cerevisiae chromosome X.";
RL EMBO J. 15:2031-2049(1996).
RN [5]
RP GENOME REANNOTATION.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=24374639; DOI=10.1534/g3.113.008995;
RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL G3 (Bethesda) 4:389-398(2014).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=14690591; DOI=10.1016/s1097-2765(03)00476-3;
RA Hazbun T.R., Malmstroem L., Anderson S., Graczyk B.J., Fox B., Riffle M.,
RA Sundin B.A., Aranda J.D., McDonald W.H., Chiu C.-H., Snydsman B.E.,
RA Bradley P., Muller E.G.D., Fields S., Baker D., Yates J.R. III, Davis T.N.;
RT "Assigning function to yeast proteins by integration of technologies.";
RL Mol. Cell 12:1353-1365(2003).
RN [7]
RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX PubMed=14562106; DOI=10.1038/nature02046;
RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA O'Shea E.K., Weissman J.S.;
RT "Global analysis of protein expression in yeast.";
RL Nature 425:737-741(2003).
RN [8]
RP FUNCTION, AND INTERACTION WITH EPS1 AND PDI1.
RX PubMed=16002399; DOI=10.1074/jbc.m503377200;
RA Kimura T., Hosoda Y., Sato Y., Kitamura Y., Ikeda T., Horibe T.,
RA Kikuchi M.;
RT "Interactions among yeast protein-disulfide isomerase proteins and
RT endoplasmic reticulum chaperone proteins influence their activities.";
RL J. Biol. Chem. 280:31438-31441(2005).
RN [9]
RP INTERACTION WITH YOS9.
RX PubMed=16873065; DOI=10.1016/j.cell.2006.05.045;
RA Denic V., Quan E.M., Weissman J.S.;
RT "A luminal surveillance complex that selects misfolded glycoproteins for
RT ER-associated degradation.";
RL Cell 126:349-359(2006).
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:0000269|PubMed:16002399}.
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 -!- SUBUNIT: Interacts with EPS1, PDI1 and YOS9.
CC {ECO:0000269|PubMed:16002399, ECO:0000269|PubMed:16873065}.
CC -!- INTERACTION:
CC P16474; P21954: IDP1; NbExp=2; IntAct=EBI-7876, EBI-8898;
CC P16474; Q99220: YOS9; NbExp=2; IntAct=EBI-7876, EBI-34938;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum lumen {ECO:0000255|PROSITE-
CC ProRule:PRU10138, ECO:0000269|PubMed:2661018}.
CC -!- MISCELLANEOUS: Present with 337000 molecules/cell in log phase SD
CC medium. {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the heat shock protein 70 family. {ECO:0000305}.
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DR EMBL; M25064; AAA34714.1; -; Genomic_DNA.
DR EMBL; M25394; AAA34713.1; -; Genomic_DNA.
DR EMBL; M31006; AAA34454.1; -; Genomic_DNA.
DR EMBL; Z49309; CAA89325.1; -; Genomic_DNA.
DR EMBL; BK006943; DAA08765.1; -; Genomic_DNA.
DR PIR; A32366; HHBYK2.
DR RefSeq; NP_012500.3; NM_001181468.3.
DR PDB; 3H0X; X-ray; 1.92 A; A=438-586.
DR PDB; 3QFP; X-ray; 2.26 A; A=43-426.
DR PDB; 3QFU; X-ray; 1.80 A; A=43-426.
DR PDB; 3QML; X-ray; 2.31 A; A/B=43-426.
DR PDBsum; 3H0X; -.
DR PDBsum; 3QFP; -.
DR PDBsum; 3QFU; -.
DR PDBsum; 3QML; -.
DR AlphaFoldDB; P16474; -.
DR SMR; P16474; -.
DR BioGRID; 33726; 674.
DR ComplexPortal; CPX-1280; Luminal surveillance complex.
DR DIP; DIP-2392N; -.
DR IntAct; P16474; 162.
DR MINT; P16474; -.
DR STRING; 4932.YJL034W; -.
DR iPTMnet; P16474; -.
DR SWISS-2DPAGE; P16474; -.
DR MaxQB; P16474; -.
DR PaxDb; P16474; -.
DR PRIDE; P16474; -.
DR EnsemblFungi; YJL034W_mRNA; YJL034W; YJL034W.
DR GeneID; 853418; -.
DR KEGG; sce:YJL034W; -.
DR SGD; S000003571; KAR2.
DR VEuPathDB; FungiDB:YJL034W; -.
DR eggNOG; KOG0100; Eukaryota.
DR GeneTree; ENSGT00940000176233; -.
DR HOGENOM; CLU_005965_7_0_1; -.
DR InParanoid; P16474; -.
DR OMA; AYTKNQD; -.
DR BioCyc; YEAST:G3O-31501-MON; -.
DR EvolutionaryTrace; P16474; -.
DR PRO; PR:P16474; -.
DR Proteomes; UP000002311; Chromosome X.
DR RNAct; P16474; protein.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:SGD.
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:0005789; C:endoplasmic reticulum membrane; IC:ComplexPortal.
DR GO; GO:0034099; C:luminal surveillance complex; IDA:SGD.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IBA:GO_Central.
DR GO; GO:0016887; F:ATP hydrolysis activity; IDA:SGD.
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:0044183; F:protein folding chaperone; IBA:GO_Central.
DR GO; GO:0051082; F:unfolded protein binding; IDA:SGD.
DR GO; GO:0034620; P:cellular response to unfolded protein; IBA:GO_Central.
DR GO; GO:0051085; P:chaperone cofactor-dependent protein refolding; IBA:GO_Central.
DR GO; GO:0002235; P:detection of unfolded protein; IC:ComplexPortal.
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; IGI:SGD.
DR GO; GO:0000742; P:karyogamy involved in conjugation with cellular fusion; IMP:SGD.
DR GO; GO:0031204; P:post-translational protein targeting to membrane, translocation; IDA:SGD.
DR GO; GO:0070972; P:protein localization to endoplasmic reticulum; IMP:SGD.
DR GO; GO:0042026; P:protein refolding; IBA:GO_Central.
DR GO; GO:0006986; P:response to unfolded protein; IMP:SGD.
DR GO; GO:0006616; P:SRP-dependent cotranslational protein targeting to membrane, translocation; IMP:SGD.
DR GO; GO:0030433; P:ubiquitin-dependent ERAD pathway; IMP:SGD.
DR GO; GO:0097466; P:ubiquitin-dependent glycoprotein ERAD pathway; IC:ComplexPortal.
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 3D-structure; ATP-binding; Chaperone; Endoplasmic reticulum; Hydrolase;
KW Nucleotide-binding; Reference proteome; Signal; Stress response.
FT SIGNAL 1..42
FT /evidence="ECO:0000255"
FT CHAIN 43..682
FT /note="Endoplasmic reticulum chaperone BiP"
FT /id="PRO_0000013587"
FT REGION 146..300
FT /note="Nucleotide-binding (NBD)"
FT /evidence="ECO:0000250|UniProtKB:P11021"
FT REGION 420..520
FT /note="Substrate-binding (SBD)"
FT /evidence="ECO:0000250|UniProtKB:P11021"
FT REGION 652..682
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 679..682
FT /note="Prevents secretion from ER"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10138"
FT COMPBIAS 662..682
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 58..61
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P11021"
FT BINDING 117
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P11021"
FT BINDING 247..249
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P11021"
FT BINDING 313..320
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P11021"
FT BINDING 384..387
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P11021"
FT STRAND 53..57
FT /evidence="ECO:0007829|PDB:3QFU"
FT STRAND 59..67
FT /evidence="ECO:0007829|PDB:3QFU"
FT STRAND 72..74
FT /evidence="ECO:0007829|PDB:3QFU"
FT STRAND 82..85
FT /evidence="ECO:0007829|PDB:3QFU"
FT STRAND 88..90
FT /evidence="ECO:0007829|PDB:3QFU"
FT STRAND 95..98
FT /evidence="ECO:0007829|PDB:3QFU"
FT HELIX 99..103
FT /evidence="ECO:0007829|PDB:3QFU"
FT HELIX 105..107
FT /evidence="ECO:0007829|PDB:3QFU"
FT HELIX 109..111
FT /evidence="ECO:0007829|PDB:3QFU"
FT HELIX 116..118
FT /evidence="ECO:0007829|PDB:3QFU"
FT TURN 119..121
FT /evidence="ECO:0007829|PDB:3QFU"
FT HELIX 127..133
FT /evidence="ECO:0007829|PDB:3QFU"
FT STRAND 137..143
FT /evidence="ECO:0007829|PDB:3QFU"
FT STRAND 146..160
FT /evidence="ECO:0007829|PDB:3QFU"
FT HELIX 162..181
FT /evidence="ECO:0007829|PDB:3QFU"
FT STRAND 187..192
FT /evidence="ECO:0007829|PDB:3QFU"
FT HELIX 198..210
FT /evidence="ECO:0007829|PDB:3QFU"
FT STRAND 214..220
FT /evidence="ECO:0007829|PDB:3QFU"
FT HELIX 221..228
FT /evidence="ECO:0007829|PDB:3QFU"
FT TURN 229..232
FT /evidence="ECO:0007829|PDB:3QFU"
FT STRAND 238..245
FT /evidence="ECO:0007829|PDB:3QFU"
FT STRAND 250..258
FT /evidence="ECO:0007829|PDB:3QFU"
FT STRAND 261..270
FT /evidence="ECO:0007829|PDB:3QFU"
FT HELIX 275..294
FT /evidence="ECO:0007829|PDB:3QFU"
FT HELIX 298..300
FT /evidence="ECO:0007829|PDB:3QML"
FT HELIX 302..318
FT /evidence="ECO:0007829|PDB:3QFU"
FT TURN 319..321
FT /evidence="ECO:0007829|PDB:3QFU"
FT STRAND 323..333
FT /evidence="ECO:0007829|PDB:3QFU"
FT STRAND 336..343
FT /evidence="ECO:0007829|PDB:3QFU"
FT HELIX 344..357
FT /evidence="ECO:0007829|PDB:3QFU"
FT HELIX 359..369
FT /evidence="ECO:0007829|PDB:3QFU"
FT HELIX 373..375
FT /evidence="ECO:0007829|PDB:3QFU"
FT STRAND 378..383
FT /evidence="ECO:0007829|PDB:3QFU"
FT HELIX 384..387
FT /evidence="ECO:0007829|PDB:3QFU"
FT HELIX 389..398
FT /evidence="ECO:0007829|PDB:3QFU"
FT TURN 399..401
FT /evidence="ECO:0007829|PDB:3QFU"
FT TURN 410..412
FT /evidence="ECO:0007829|PDB:3QFU"
FT HELIX 413..425
FT /evidence="ECO:0007829|PDB:3QFU"
FT STRAND 444..448
FT /evidence="ECO:0007829|PDB:3H0X"
FT TURN 449..451
FT /evidence="ECO:0007829|PDB:3H0X"
FT STRAND 452..457
FT /evidence="ECO:0007829|PDB:3H0X"
FT STRAND 462..471
FT /evidence="ECO:0007829|PDB:3H0X"
FT STRAND 481..489
FT /evidence="ECO:0007829|PDB:3H0X"
FT HELIX 493..495
FT /evidence="ECO:0007829|PDB:3H0X"
FT STRAND 496..504
FT /evidence="ECO:0007829|PDB:3H0X"
FT STRAND 517..523
FT /evidence="ECO:0007829|PDB:3H0X"
FT STRAND 527..535
FT /evidence="ECO:0007829|PDB:3H0X"
FT TURN 536..538
FT /evidence="ECO:0007829|PDB:3H0X"
FT STRAND 541..547
FT /evidence="ECO:0007829|PDB:3H0X"
FT HELIX 555..567
FT /evidence="ECO:0007829|PDB:3H0X"
FT HELIX 569..580
FT /evidence="ECO:0007829|PDB:3H0X"
SQ SEQUENCE 682 AA; 74468 MW; A107BD03DF3F30D3 CRC64;
MFFNRLSAGK LLVPLSVVLY ALFVVILPLQ NSFHSSNVLV RGADDVENYG TVIGIDLGTT
YSCVAVMKNG KTEILANEQG NRITPSYVAF TDDERLIGDA AKNQVAANPQ NTIFDIKRLI
GLKYNDRSVQ KDIKHLPFNV VNKDGKPAVE VSVKGEKKVF TPEEISGMIL GKMKQIAEDY
LGTKVTHAVV TVPAYFNDAQ RQATKDAGTI AGLNVLRIVN EPTAAAIAYG LDKSDKEHQI
IVYDLGGGTF DVSLLSIENG VFEVQATSGD THLGGEDFDY KIVRQLIKAF KKKHGIDVSD
NNKALAKLKR EAEKAKRALS SQMSTRIEID SFVDGIDLSE TLTRAKFEEL NLDLFKKTLK
PVEKVLQDSG LEKKDVDDIV LVGGSTRIPK VQQLLESYFD GKKASKGINP DEAVAYGAAV
QAGVLSGEEG VEDIVLLDVN ALTLGIETTG GVMTPLIKRN TAIPTKKSQI FSTAVDNQPT
VMIKVYEGER AMSKDNNLLG KFELTGIPPA PRGVPQIEVT FALDANGILK VSATDKGTGK
SESITITNDK GRLTQEEIDR MVEEAEKFAS EDASIKAKVE SRNKLENYAH SLKNQVNGDL
GEKLEEEDKE TLLDAANDVL EWLDDNFETA IAEDFDEKFE SLSKVAYPIT SKLYGGADGS
GAADYDDEDE DDDGDYFEHD EL
