BIP_MOUSE
ID BIP_MOUSE Reviewed; 655 AA.
AC P20029; O35642; Q3UFF2; Q61630;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 3.
DT 03-AUG-2022, entry version 220.
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 {ECO:0000303|PubMed:7607546};
DE Short=GRP-78 {ECO:0000303|PubMed:7607546};
DE AltName: Full=Binding-immunoglobulin protein {ECO:0000303|PubMed:2895472};
DE Short=BiP {ECO:0000303|PubMed:2895472};
DE AltName: Full=Heat shock protein 70 family protein 5 {ECO:0000305};
DE Short=HSP70 family protein 5 {ECO:0000305};
DE AltName: Full=Heat shock protein family A member 5 {ECO:0000312|MGI:MGI:95835};
DE AltName: Full=Immunoglobulin heavy chain-binding protein {ECO:0000303|PubMed:2895472};
DE Flags: Precursor;
GN Name=Hspa5 {ECO:0000312|MGI:MGI:95835};
GN Synonyms=Grp78 {ECO:0000303|PubMed:7607546};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RX PubMed=2895472; DOI=10.1073/pnas.85.7.2250;
RA Haas I.G., Meo T.;
RT "cDNA cloning of the immunoglobulin heavy chain binding protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 85:2250-2254(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 20-46.
RX PubMed=2559088; DOI=10.1242/jcs.1989.supplement_11.10;
RA Kozutsumi Y., Normington K., Press E., Slaughter C., Sambrook J.,
RA Gething M.J.;
RT "Identification of immunoglobulin heavy chain binding protein as glucose-
RT regulated protein 78 on the basis of amino acid sequence, immunological
RT cross-reactivity, and functional activity.";
RL J. Cell Sci. Suppl. 11:115-137(1989).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=8645260; DOI=10.1006/bbrc.1996.0313;
RA Kajiwara K., Nagawawa H., Shimizu-Nishikawa K., Ookura T., Kimura M.,
RA Sugaya E.;
RT "Molecular characterization of seizure-related genes isolated by
RT differential screening.";
RL Biochem. Biophys. Res. Commun. 219:795-799(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Kidney;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-28.
RC STRAIN=C3B10RF1; TISSUE=Liver;
RX PubMed=7607546; DOI=10.1016/0378-1119(95)00083-i;
RA Tillman J.B., Mote P.L., Walford R.L., Spindler S.R.;
RT "Structure and regulation of the mouse GRP78 (BiP) promoter by glucose and
RT calcium ionophore.";
RL Gene 158:225-229(1995).
RN [7]
RP PROTEIN SEQUENCE OF 20-36.
RC TISSUE=Fibroblast;
RX PubMed=7523108; DOI=10.1002/elps.11501501101;
RA Merrick B.A., Patterson R.M., Wichter L.L., He C., Selkirk J.K.;
RT "Separation and sequencing of familiar and novel murine proteins using
RT preparative two-dimensional gel electrophoresis.";
RL Electrophoresis 15:735-745(1994).
RN [8]
RP PROTEIN SEQUENCE OF 51-75; 140-153; 156-164; 166-182; 187-215; 308-337;
RP 354-368; 449-493; 525-541 AND 623-634, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC STRAIN=C57BL/6J; TISSUE=Brain, and Hippocampus;
RA Lubec G., Kang S.U., Klug S., Friebe K., Yang J.W., Zigmond M.;
RL Submitted (JUL-2007) to UniProtKB.
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 488-655.
RX PubMed=2583523; DOI=10.1016/0378-1119(89)90054-1;
RA Parfett C.L.J., Hofbauer R., Brudzynski K., Edwards D.R., Denhardt D.T.;
RT "Differential screening of a cDNA library with cDNA probes amplified in a
RT heterologous host: isolation of murine GRP78 (BiP) and other serum-
RT regulated low-abundance mRNAs.";
RL Gene 82:291-303(1989).
RN [10]
RP COMPONENT OF A CHAPERONE COMPLEX.
RX PubMed=12475965; DOI=10.1091/mbc.e02-05-0311;
RA Meunier L., Usherwood Y.-K., Chung K.T., Hendershot L.M.;
RT "A subset of chaperones and folding enzymes form multiprotein complexes in
RT endoplasmic reticulum to bind nascent proteins.";
RL Mol. Biol. Cell 13:4456-4469(2002).
RN [11]
RP INTERACTION WITH DNAJC1.
RX PubMed=12065409; DOI=10.1093/emboj/cdf315;
RA Dudek J., Volkmer J., Bies C., Guth S., Mueller A., Lerner M., Feick P.,
RA Schaefer K.-H., Morgenstern E., Hennessy F., Blatch G.L., Janoscheck K.,
RA Heim N., Scholtes P., Frien M., Nastainczyk W., Zimmermann R.;
RT "A novel type of co-chaperone mediates transmembrane recruitment of DnaK-
RT like chaperones to ribosomes.";
RL EMBO J. 21:2958-2967(2002).
RN [12]
RP INTERACTION WITH DNAJB9.
RX PubMed=11836248; DOI=10.1074/jbc.m112214200;
RA Shen Y., Meunier L., Hendershot L.M.;
RT "Identification and characterization of a novel endoplasmic reticulum (ER)
RT DnaJ homologue, which stimulates ATPase activity of BiP in vitro and is
RT induced by ER stress.";
RL J. Biol. Chem. 277:15947-15956(2002).
RN [13]
RP FUNCTION, AND INTERACTION WITH DNAJC10.
RX PubMed=12411443; DOI=10.1074/jbc.m206995200;
RA Cunnea P.M., Miranda-Vizuete A., Bertoli G., Simmen T., Damdimopoulos A.E.,
RA Hermann S., Leinonen S., Huikko M.P., Gustafsson J.-A., Sitia R.,
RA Spyrou G.;
RT "ERdj5, an endoplasmic reticulum (ER)-resident protein containing DnaJ and
RT thioredoxin domains, is expressed in secretory cells or following ER
RT stress.";
RL J. Biol. Chem. 278:1059-1066(2003).
RN [14]
RP NITRATION [LARGE SCALE ANALYSIS] AT TYR-161, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=16800626; DOI=10.1021/bi060474w;
RA Sacksteder C.A., Qian W.-J., Knyushko T.V., Wang H., Chin M.H., Lacan G.,
RA Melega W.P., Camp D.G. II, Smith R.D., Smith D.J., Squier T.C.,
RA Bigelow D.J.;
RT "Endogenously nitrated proteins in mouse brain: links to neurodegenerative
RT disease.";
RL Biochemistry 45:8009-8022(2006).
RN [15]
RP IDENTIFICATION IN AN EIF2 COMPLEX WITH EIF2S1; EIF2S2; CELF1; CALR; CALR3
RP AND HSP90B1.
RX PubMed=16931514; DOI=10.1074/jbc.m605701200;
RA Timchenko L.T., Salisbury E., Wang G.-L., Nguyen H., Albrecht J.H.,
RA Hershey J.W., Timchenko N.A.;
RT "Age-specific CUGBP1-eIF2 complex increases translation of CCAAT/enhancer-
RT binding protein beta in old liver.";
RL J. Biol. Chem. 281:32806-32819(2006).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-650, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-644; THR-649 AND SER-650, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [19]
RP INDUCTION.
RX PubMed=20484814; DOI=10.1172/jci42164;
RA Liu M., Spellberg B., Phan Q.T., Fu Y., Fu Y., Lee A.S., Edwards J.E. Jr.,
RA Filler S.G., Ibrahim A.S.;
RT "The endothelial cell receptor GRP78 is required for mucormycosis
RT pathogenesis in diabetic mice.";
RL J. Clin. Invest. 120:1914-1924(2010).
RN [20]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH MX1.
RX PubMed=21992152; DOI=10.1089/jir.2010.0132;
RA Numajiri Haruki A., Naito T., Nishie T., Saito S., Nagata K.;
RT "Interferon-inducible antiviral protein MxA enhances cell death triggered
RT by endoplasmic reticulum stress.";
RL J. Interferon Cytokine Res. 31:847-856(2011).
RN [21]
RP METHYLATION AT LYS-586.
RX PubMed=23921388; DOI=10.1074/jbc.m113.483248;
RA Jakobsson M.E., Moen A., Bousset L., Egge-Jacobsen W., Kernstock S.,
RA Melki R., Falnes P.O.;
RT "Identification and characterization of a novel human methyltransferase
RT modulating Hsp70 function through lysine methylation.";
RL J. Biol. Chem. 288:27752-27763(2013).
RN [22]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-126; LYS-214; LYS-327 AND
RP LYS-354, SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-448, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
RN [23]
RP INTERACTION WITH CCDC47.
RX PubMed=25009997; DOI=10.1016/j.ydbio.2014.06.024;
RA Yamamoto S., Yamazaki T., Komazaki S., Yamashita T., Osaki M.,
RA Matsubayashi M., Kidoya H., Takakura N., Yamazaki D., Kakizawa S.;
RT "Contribution of calumin to embryogenesis through participation in the
RT endoplasmic reticulum-associated degradation activity.";
RL Dev. Biol. 393:33-43(2014).
RN [24]
RP INDUCTION.
RX PubMed=27159390; DOI=10.1172/jci82744;
RA Gebremariam T., Lin L., Liu M., Kontoyiannis D.P., French S.,
RA Edwards J.E. Jr., Filler S.G., Ibrahim A.S.;
RT "Bicarbonate correction of ketoacidosis alters host-pathogen interactions
RT and alleviates mucormycosis.";
RL J. Clin. Invest. 126:2280-2294(2016).
RN [25]
RP INTERACTION WITH ILDR2.
RX PubMed=33863978; DOI=10.1038/s41598-021-87884-7;
RA Watanabe K., Nakayama K., Ohta S., Matsumoto A., Tsuda H., Iwamoto S.;
RT "ILDR2 stabilization is regulated by its interaction with GRP78.";
RL Sci. Rep. 11:8414-8414(2021).
CC -!- FUNCTION: Endoplasmic reticulum chaperone that plays a key role in
CC protein folding and quality control in the endoplasmic reticulum lumen
CC (PubMed:12411443, PubMed:12475965). Involved in the correct folding of
CC proteins and degradation of misfolded proteins via its interaction with
CC DNAJC10/ERdj5, probably to facilitate the release of DNAJC10/ERdj5 from
CC its substrate (PubMed:12411443). Acts as a key repressor of the
CC ERN1/IRE1-mediated unfolded protein response (UPR) (By similarity). In
CC the unstressed endoplasmic reticulum, recruited by DNAJB9/ERdj4 to the
CC luminal region of ERN1/IRE1, leading to disrupt the dimerization of
CC ERN1/IRE1, thereby inactivating ERN1/IRE1 (By similarity). Accumulation
CC of misfolded protein in the endoplasmic reticulum causes release of
CC HSPA5/BiP from ERN1/IRE1, allowing homodimerization and subsequent
CC activation of ERN1/IRE1 (By similarity). Plays an auxiliary role in
CC post-translational transport of small presecretory proteins across
CC endoplasmic reticulum (ER). May function as an allosteric modulator for
CC SEC61 channel-forming translocon complex, likely cooperating with SEC62
CC to enable the productive insertion of these precursors into SEC61
CC channel. Appears to specifically regulate translocation of precursors
CC having inhibitory residues in their mature region that weaken channel
CC gating. May also play a role in apoptosis and cell proliferation (By
CC similarity). {ECO:0000250|UniProtKB:G3I8R9,
CC ECO:0000250|UniProtKB:P11021, ECO:0000269|PubMed:12411443,
CC ECO:0000269|PubMed:12475965}.
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 DNAJC1
CC (via J domain) (PubMed:12065409). Component of an EIF2 complex at least
CC composed of CELF1/CUGBP1, CALR, CALR3, EIF2S1, EIF2S2, HSP90B1 and
CC HSPA5 (PubMed:16931514). Part of a large chaperone multiprotein complex
CC comprising DNAJB11, HSP90B1, HSPA5, HYOU, PDIA2, PDIA4, PDIA6, PPIB,
CC SDF2L1, UGGT1 and very small amounts of ERP29, but not, or at very low
CC levels, CALR nor CANX (PubMed:12475965). Interacts with TMEM132A and
CC TRIM21 (By similarity). May form a complex with ERLEC1, OS9, SEL1L and
CC SYVN1 (By similarity). Interacts with DNAJC10 (PubMed:12411443).
CC Interacts with DNAJB9/ERdj4; leading to recruit HSPA5/BiP to ERN1/IRE1
CC (PubMed:11836248). Interacts with ERN1/IRE1; interaction takes place
CC following interaction with DNAJB9/ERdj4 and leads to inactivate
CC ERN1/IRE1 (By similarity). Interacts with MX1 (PubMed:21992152).
CC Interacts with METTL23 (By similarity). Interacts with CEMIP; the
CC interaction induces calcium leakage from the endoplasmic reticulum and
CC cell migration (By similarity). Interacts with PCSK4 form; the
CC interaction takes place in the endoplasmic reticulum (By similarity).
CC Interacts with CIPC (By similarity). Interacts with CCDC88B (via C-
CC terminus); the interaction opposes ERN1-mediated JNK activation,
CC protecting against apoptosis (By similarity). Interacts with INPP5K;
CC necessary for INPP5K localization at the endoplasmic reticulum (By
CC similarity). Interacts with MANF; the interaction is direct (By
CC similarity). Interacts with LOXL2; leading to activate the ERN1/IRE1-
CC XBP1 pathway of the unfolded protein response (By similarity).
CC Interacts with CLU under stressed condition; interaction increases CLU
CC protein stability; facilitates its retrotranslocation and
CC redistribution to the mitochondria; cooperatively suppress stress-
CC induced apoptosis by stabilizing mitochondrial membrane integrity (By
CC similarity). Interacts with CCDC47 (PubMed:25009997). Interacts with
CC CLN3 (By similarity). Interacts with KIAA1324; may regulate the
CC function of HSPA5 in apoptosis and cell proliferation. Interacts with
CC CASP7 (By similarity). Interacts with ILDR2; the interaction stabilizes
CC ILDR2 expression (PubMed:33863978). {ECO:0000250|UniProtKB:G3I8R9,
CC ECO:0000250|UniProtKB:P11021, ECO:0000269|PubMed:11836248,
CC ECO:0000269|PubMed:12065409, ECO:0000269|PubMed:12411443,
CC ECO:0000269|PubMed:12475965, ECO:0000269|PubMed:16931514,
CC ECO:0000269|PubMed:21992152, ECO:0000269|PubMed:25009997,
CC ECO:0000269|PubMed:33863978}.
CC -!- INTERACTION:
CC P20029; O35451: Atf6b; NbExp=2; IntAct=EBI-772325, EBI-8361741;
CC P20029; Q99KV1: Dnajb11; NbExp=4; IntAct=EBI-772325, EBI-8328260;
CC P20029; O75460: ERN1; Xeno; NbExp=2; IntAct=EBI-772325, EBI-371750;
CC P20029; P00441: SOD1; Xeno; NbExp=7; IntAct=EBI-772325, EBI-990792;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum lumen {ECO:0000255|PROSITE-
CC ProRule:PRU10138, ECO:0000269|PubMed:21992152}. Melanosome
CC {ECO:0000250|UniProtKB:P11021}. Cytoplasm
CC {ECO:0000269|PubMed:21992152}. 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 -!- INDUCTION: Induced in sinus, lung and brain tissue in response to 3-
CC hydroxybutyric acid (BHB)-induced acidosis (PubMed:27159390). Induced
CC in sinus, lung and brain tissue following intraperitoneal injection of
CC streptozotocin to produce a mouse model of diabetic ketoacidosis (DKA)
CC (PubMed:20484814). {ECO:0000269|PubMed:20484814,
CC ECO:0000269|PubMed:27159390}.
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 -!- PTM: In unstressed cells, AMPylation at Thr-519 by FICD inactivates the
CC chaperome activity: AMPylated form is locked in a relatively inert
CC state and only weakly stimulated by J domain-containing proteins. In
CC response to endoplasmic reticulum stress, de-AMPylation by the same
CC protein, FICD, restores the chaperone activity.
CC {ECO:0000250|UniProtKB:G3I8R9}.
CC -!- SIMILARITY: Belongs to the heat shock protein 70 family. {ECO:0000305}.
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DR EMBL; AJ002387; CAA05361.1; -; mRNA.
DR EMBL; M19351; AAA37315.1; -; mRNA.
DR EMBL; D78645; BAA11462.1; -; mRNA.
DR EMBL; AK076079; BAC36166.1; -; mRNA.
DR EMBL; AK146647; BAE27328.1; -; mRNA.
DR EMBL; AK148539; BAE28609.1; -; mRNA.
DR EMBL; AK151647; BAE30576.1; -; mRNA.
DR EMBL; AK152020; BAE30882.1; -; mRNA.
DR EMBL; AK166739; BAE38982.1; -; mRNA.
DR EMBL; AK169034; BAE40825.1; -; mRNA.
DR EMBL; BC050927; AAH50927.1; -; mRNA.
DR EMBL; U16277; AAA76734.1; -; Genomic_DNA.
DR EMBL; M30779; AAA37742.1; -; mRNA.
DR CCDS; CCDS15950.1; -.
DR PIR; A37048; A37048.
DR RefSeq; NP_001156906.1; NM_001163434.1.
DR RefSeq; NP_071705.3; NM_022310.3.
DR AlphaFoldDB; P20029; -.
DR SMR; P20029; -.
DR BioGRID; 200078; 98.
DR CORUM; P20029; -.
DR DIP; DIP-32341N; -.
DR IntAct; P20029; 36.
DR MINT; P20029; -.
DR STRING; 10090.ENSMUSP00000097747; -.
DR CarbonylDB; P20029; -.
DR iPTMnet; P20029; -.
DR PhosphoSitePlus; P20029; -.
DR SwissPalm; P20029; -.
DR COMPLUYEAST-2DPAGE; P20029; -.
DR REPRODUCTION-2DPAGE; IPI00319992; -.
DR REPRODUCTION-2DPAGE; P20029; -.
DR SWISS-2DPAGE; P20029; -.
DR UCD-2DPAGE; P20029; -.
DR CPTAC; non-CPTAC-3387; -.
DR CPTAC; non-CPTAC-3388; -.
DR EPD; P20029; -.
DR jPOST; P20029; -.
DR MaxQB; P20029; -.
DR PaxDb; P20029; -.
DR PeptideAtlas; P20029; -.
DR PRIDE; P20029; -.
DR ProteomicsDB; 273615; -.
DR TopDownProteomics; P20029; -.
DR Antibodypedia; 3926; 1771 antibodies from 49 providers.
DR DNASU; 14828; -.
DR Ensembl; ENSMUST00000028222; ENSMUSP00000028222; ENSMUSG00000026864.
DR Ensembl; ENSMUST00000100171; ENSMUSP00000097747; ENSMUSG00000026864.
DR GeneID; 14828; -.
DR KEGG; mmu:14828; -.
DR UCSC; uc008jis.2; mouse.
DR CTD; 3309; -.
DR MGI; MGI:95835; Hspa5.
DR VEuPathDB; HostDB:ENSMUSG00000026864; -.
DR eggNOG; KOG0100; Eukaryota.
DR GeneTree; ENSGT00940000154787; -.
DR HOGENOM; CLU_005965_3_0_1; -.
DR InParanoid; P20029; -.
DR OMA; AYTKNQD; -.
DR OrthoDB; 288077at2759; -.
DR PhylomeDB; P20029; -.
DR TreeFam; TF105044; -.
DR Reactome; R-MMU-3371453; Regulation of HSF1-mediated heat shock response.
DR Reactome; R-MMU-983170; Antigen Presentation: Folding, assembly and peptide loading of class I MHC.
DR BioGRID-ORCS; 14828; 29 hits in 69 CRISPR screens.
DR ChiTaRS; Hspa5; mouse.
DR PRO; PR:P20029; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; P20029; protein.
DR Bgee; ENSMUSG00000026864; Expressed in prostate gland ventral lobe and 262 other tissues.
DR ExpressionAtlas; P20029; baseline and differential.
DR Genevisible; P20029; MM.
DR GO; GO:0009986; C:cell surface; IDA:MGI.
DR GO; GO:0008180; C:COP9 signalosome; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:ParkinsonsUK-UCL.
DR GO; GO:0034663; C:endoplasmic reticulum chaperone complex; IDA:ParkinsonsUK-UCL.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; IDA:BHF-UCL.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:MGI.
DR GO; GO:0005793; C:endoplasmic reticulum-Golgi intermediate compartment; IDA:MGI.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; ISO:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; ISO:MGI.
DR GO; GO:0030496; C:midbody; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:0043209; C:myelin sheath; HDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0005790; C:smooth endoplasmic reticulum; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; ISO:MGI.
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:0019899; F:enzyme binding; ISO:MGI.
DR GO; GO:0031072; F:heat shock protein binding; IBA:GO_Central.
DR GO; GO:0051787; F:misfolded protein binding; IDA:BHF-UCL.
DR GO; GO:0019904; F:protein domain specific binding; ISO:MGI.
DR GO; GO:0044183; F:protein folding chaperone; IDA:MGI.
DR GO; GO:0043022; F:ribosome binding; IDA:MGI.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI.
DR GO; GO:0051082; F:unfolded protein binding; ISO:MGI.
DR GO; GO:0071236; P:cellular response to antibiotic; IEA:Ensembl.
DR GO; GO:0071277; P:cellular response to calcium ion; IEA:Ensembl.
DR GO; GO:0071320; P:cellular response to cAMP; IEA:Ensembl.
DR GO; GO:0071480; P:cellular response to gamma radiation; IEA:Ensembl.
DR GO; GO:0042149; P:cellular response to glucose starvation; ISO:MGI.
DR GO; GO:0071353; P:cellular response to interleukin-4; IDA:MGI.
DR GO; GO:0071287; P:cellular response to manganese ion; IEA:Ensembl.
DR GO; GO:1990090; P:cellular response to nerve growth factor stimulus; IEA:Ensembl.
DR GO; GO:0034620; P:cellular response to unfolded protein; IBA:GO_Central.
DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0021680; P:cerebellar Purkinje cell layer development; IMP:BHF-UCL.
DR GO; GO:0021589; P:cerebellum structural organization; IMP:BHF-UCL.
DR GO; GO:0051085; P:chaperone cofactor-dependent protein refolding; IBA:GO_Central.
DR GO; GO:0030968; P:endoplasmic reticulum unfolded protein response; IMP:BHF-UCL.
DR GO; GO:0006983; P:ER overload response; IDA:MGI.
DR GO; GO:0001554; P:luteolysis; IEA:Ensembl.
DR GO; GO:0035437; P:maintenance of protein localization in endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:MGI.
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; IGI:MGI.
DR GO; GO:0051402; P:neuron apoptotic process; IEA:Ensembl.
DR GO; GO:0030182; P:neuron differentiation; IEA:Ensembl.
DR GO; GO:0030335; P:positive regulation of cell migration; ISS:UniProtKB.
DR GO; GO:0040019; P:positive regulation of embryonic development; TAS:BHF-UCL.
DR GO; GO:0010976; P:positive regulation of neuron projection development; ISO:MGI.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; IMP:BHF-UCL.
DR GO; GO:0031204; P:post-translational protein targeting to membrane, translocation; ISS:UniProtKB.
DR GO; GO:0042026; P:protein refolding; IBA:GO_Central.
DR GO; GO:0051603; P:proteolysis involved in protein catabolic process; IDA:BHF-UCL.
DR GO; GO:0042220; P:response to cocaine; IEA:Ensembl.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; ISO:MGI.
DR GO; GO:1904313; P:response to methamphetamine hydrochloride; IEA:Ensembl.
DR GO; GO:0097501; P:stress response to metal ion; IEA:Ensembl.
DR GO; GO:1901998; P:toxin transport; IMP:MGI.
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 Acetylation; ATP-binding; Chaperone; Cytoplasm; Direct protein sequencing;
KW Endoplasmic reticulum; Hydrolase; Isopeptide bond; Methylation; Nitration;
KW Nucleotide-binding; Phosphoprotein; Reference proteome; Signal;
KW Ubl conjugation.
FT SIGNAL 1..19
FT /evidence="ECO:0000269|PubMed:2559088,
FT ECO:0000269|PubMed:7523108"
FT CHAIN 20..655
FT /note="Endoplasmic reticulum chaperone BiP"
FT /id="PRO_0000013568"
FT REGION 1..81
FT /note="Required for interaction with KIAA1324"
FT /evidence="ECO:0000250|UniProtKB:P11021"
FT REGION 126..281
FT /note="Nucleotide-binding (NBD)"
FT /evidence="ECO:0000250|UniProtKB:P11021"
FT REGION 410..420
FT /note="Interdomain linker"
FT /evidence="ECO:0000250|UniProtKB:G3I8R9"
FT REGION 421..501
FT /note="Substrate-binding (SBD)"
FT /evidence="ECO:0000250|UniProtKB:P11021"
FT REGION 632..655
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 652..655
FT /note="Prevents secretion from ER"
FT BINDING 37..40
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P11021"
FT BINDING 97
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P11021"
FT BINDING 228..230
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P11021"
FT BINDING 294..301
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P11021"
FT BINDING 365..368
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P11021"
FT MOD_RES 87
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P06761"
FT MOD_RES 126
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 161
FT /note="3'-nitrotyrosine"
FT /evidence="ECO:0007744|PubMed:16800626"
FT MOD_RES 214
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 272
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P0DMV8"
FT MOD_RES 327
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 354
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 448
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 493
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:P0DMV8"
FT MOD_RES 519
FT /note="O-AMP-threonine; alternate"
FT /evidence="ECO:0000250|UniProtKB:G3I8R9"
FT MOD_RES 519
FT /note="Phosphothreonine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P11021"
FT MOD_RES 586
FT /note="N6,N6,N6-trimethyllysine; by METTL21A; in vitro"
FT /evidence="ECO:0000269|PubMed:23921388"
FT MOD_RES 586
FT /note="N6,N6-dimethyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P11021"
FT MOD_RES 586
FT /note="N6-methyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P11021"
FT MOD_RES 592
FT /note="N6-methyllysine"
FT /evidence="ECO:0000250|UniProtKB:P11021"
FT MOD_RES 644
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 649
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 650
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT CROSSLNK 353
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P11021"
FT CROSSLNK 354
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1); alternate"
FT /evidence="ECO:0000250|UniProtKB:P11021"
FT CONFLICT 43
FT /note="V -> F (in Ref. 3; BAA11462)"
FT /evidence="ECO:0000305"
FT CONFLICT 245
FT /note="V -> W (in Ref. 3; BAA11462)"
FT /evidence="ECO:0000305"
FT CONFLICT 329
FT /note="E -> G (in Ref. 3; BAA11462)"
FT /evidence="ECO:0000305"
FT CONFLICT 361
FT /note="V -> A (in Ref. 3; BAA11462)"
FT /evidence="ECO:0000305"
FT CONFLICT 474
FT /note="T -> R (in Ref. 1; CAA05361)"
FT /evidence="ECO:0000305"
FT CONFLICT 591
FT /note="D -> G (in Ref. 9; AAA37742)"
FT /evidence="ECO:0000305"
FT CONFLICT 596
FT /note="E -> K (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 655 AA; 72422 MW; AFB795D15E20FAC2 CRC64;
MMKFTVVAAA LLLLGAVRAE EEDKKEDVGT VVGIDLGTTY SCVGVFKNGR VEIIANDQGN
RITPSYVAFT PEGERLIGDA AKNQLTSNPE NTVFDAKRLI GRTWNDPSVQ QDIKFLPFKV
VEKKTKPYIQ VDIGGGQTKT FAPEEISAMV LTKMKETAEA YLGKKVTHAV VTVPAYFNDA
QRQATKDAGT IAGLNVMRII NEPTAAAIAY GLDKREGEKN ILVFDLGGGT FDVSLLTIDN
GVFEVVATNG DTHLGGEDFD QRVMEHFIKL YKKKTGKDVR KDNRAVQKLR REVEKAKRAL
SSQHQARIEI ESFFEGEDFS ETLTRAKFEE LNMDLFRSTM KPVQKVLEDS DLKKSDIDEI
VLVGGSTRIP KIQQLVKEFF NGKEPSRGIN PDEAVAYGAA VQAGVLSGDQ DTGDLVLLDV
CPLTLGIETV GGVMTKLIPR NTVVPTKKSQ IFSTASDNQP TVTIKVYEGE RPLTKDNHLL
GTFDLTGIPP APRGVPQIEV TFEIDVNGIL RVTAEDKGTG NKNKITITND QNRLTPEEIE
RMVNDAEKFA EEDKKLKERI DTRNELESYA YSLKNQIGDK EKLGGKLSSE DKETMEKAVE
EKIEWLESHQ DADIEDFKAK KKELEEIVQP IISKLYGSGG PPPTGEEDTS EKDEL
