BIP_HUMAN
ID BIP_HUMAN Reviewed; 654 AA.
AC P11021; B0QZ61; Q2EF78; Q9NPF1; Q9UK02;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 11-JUL-2001, sequence version 2.
DT 03-AUG-2022, entry version 242.
DE RecName: Full=Endoplasmic reticulum chaperone BiP {ECO:0000305};
DE EC=3.6.4.10 {ECO:0000269|PubMed:26655470};
DE AltName: Full=78 kDa glucose-regulated protein {ECO:0000303|PubMed:2840249};
DE Short=GRP-78 {ECO:0000303|PubMed:2840249};
DE AltName: Full=Binding-immunoglobulin protein {ECO:0000303|Ref.4};
DE Short=BiP {ECO:0000303|Ref.4};
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|HGNC:HGNC:5238};
DE AltName: Full=Immunoglobulin heavy chain-binding protein {ECO:0000303|Ref.4};
DE Flags: Precursor;
GN Name=HSPA5 {ECO:0000312|HGNC:HGNC:5238};
GN Synonyms=GRP78 {ECO:0000303|PubMed:2840249};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2840249; DOI=10.1089/dna.1988.7.275;
RA Ting J., Lee A.S.;
RT "Human gene encoding the 78,000-dalton glucose-regulated protein and its
RT pseudogene: structure, conservation, and regulation.";
RL DNA 7:275-286(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Cervix carcinoma;
RA Chao C.C.K.;
RL Submitted (DEC-1995) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Fibroblast;
RA Hansen J.J., Nielsen M.N., Jorgensen M.M., Gregersen N., Bolund L.;
RT "Grp78 is involved in the quality control of the LDL-receptor.";
RL Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Bermudez-Fajardo A., Llewellyn D.H., Campbell A.K., Errington R.R.;
RT "Sequence differences between human grp78/BiP isolated from HeLa cells and
RT previously reported human sequences.";
RL Submitted (DEC-1999) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT HIS-543.
RG NIEHS SNPs program;
RL Submitted (JAN-2006) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Muscle;
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 [9]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-25.
RX PubMed=1480470; DOI=10.1093/nar/20.24.6481;
RA Chao C.C.K., Lin-Chao S.;
RT "A direct-repeat sequence of the human BiP gene is required for A23187-
RT mediated inducibility and an inducible nuclear factor binding.";
RL Nucleic Acids Res. 20:6481-6485(1992).
RN [10]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 20-650, AND DISEASE.
RC TISSUE=Articular cartilage;
RX PubMed=11160188; DOI=10.4049/jimmunol.166.3.1492;
RA Corrigall V.M., Bodman-Smith M.D., Fife M.S., Canas B., Myers L.K.,
RA Wooley P., Soh C., Staines N.A., Pappin D.J.C., Berlo S.E., van Eden W.,
RA van Der Zee R., Lanchbury J.S., Panayi G.S.;
RT "The human endoplasmic reticulum molecular chaperone BiP is an autoantigen
RT for rheumatoid arthritis and prevents the induction of experimental
RT arthritis.";
RL J. Immunol. 166:1492-1498(2001).
RN [11]
RP PROTEIN SEQUENCE OF 22-38.
RC TISSUE=Mammary carcinoma;
RX PubMed=9150946; DOI=10.1002/elps.1150180342;
RA Rasmussen R.K., Ji H., Eddes J.S., Moritz R.L., Reid G.E., Simpson R.J.,
RA Dorow D.S.;
RT "Two-dimensional electrophoretic analysis of human breast carcinoma
RT proteins: mapping of proteins that bind to the SH3 domain of mixed lineage
RT kinase MLK2.";
RL Electrophoresis 18:588-598(1997).
RN [12]
RP PROTEIN SEQUENCE OF 19-39, AND FUNCTION.
RX PubMed=2294010; DOI=10.1210/endo-126-1-672;
RA Dana R.C., Welch W.J., Deftos L.J.;
RT "Heat shock proteins bind calcitonin.";
RL Endocrinology 126:672-674(1990).
RN [13]
RP PROTEIN SEQUENCE OF 19-40.
RC TISSUE=Colon carcinoma;
RX PubMed=9150948; DOI=10.1002/elps.1150180344;
RA Ji H., Reid G.E., Moritz R.L., Eddes J.S., Burgess A.W., Simpson R.J.;
RT "A two-dimensional gel database of human colon carcinoma proteins.";
RL Electrophoresis 18:605-613(1997).
RN [14]
RP PROTEIN SEQUENCE OF 61-74; 82-96; 102-113; 124-152; 164-181; 186-214;
RP 307-336; 353-367; 448-464; 475-492; 563-573; 602-617 AND 622-654, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Vishwanath V., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [15]
RP FUNCTION.
RX PubMed=1550958; DOI=10.1091/mbc.3.2.143;
RA Ng D.T., Watowich S.S., Lamb R.A.;
RT "Analysis in vivo of GRP78-BiP/substrate interactions and their role in
RT induction of the GRP78-BiP gene.";
RL Mol. Biol. Cell 3:143-155(1992).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-518, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [18]
RP INTERACTION WITH CCDC88B, SUBCELLULAR LOCATION, AND INDUCTION BY ER STRESS.
RX PubMed=21289099; DOI=10.1091/mbc.e10-08-0724;
RA Matsushita E., Asai N., Enomoto A., Kawamoto Y., Kato T., Mii S., Maeda K.,
RA Shibata R., Hattori S., Hagikura M., Takahashi K., Sokabe M., Murakumo Y.,
RA Murohara T., Takahashi M.;
RT "Protective role of Gipie, a Girdin family protein, in endoplasmic
RT reticulum stress responses in endothelial cells.";
RL Mol. Biol. Cell 22:736-747(2011).
RN [19]
RP PROTEIN SEQUENCE OF 582-596, INTERACTION WITH METTL23, METHYLATION AT
RP LYS-585, MUTAGENESIS OF LYS-585, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=23349634; DOI=10.1371/journal.pgen.1003210;
RA Cloutier P., Lavallee-Adam M., Faubert D., Blanchette M., Coulombe B.;
RT "A newly uncovered group of distantly related lysine methyltransferases
RT preferentially interact with molecular chaperones to regulate their
RT activity.";
RL PLoS Genet. 9:E1003210-E1003210(2013).
RN [20]
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 [21]
RP INTERACTION WITH TRIM21.
RX PubMed=12699405; DOI=10.1046/j.1365-2249.2003.02153.x;
RA Purcell A.W., Todd A., Kinoshita G., Lynch T.A., Keech C.L., Gething M.J.,
RA Gordon T.P.;
RT "Association of stress proteins with autoantigens: a possible mechanism for
RT triggering autoimmunity?";
RL Clin. Exp. Immunol. 132:193-200(2003).
RN [22]
RP 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 [23]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RC TISSUE=Melanoma;
RX PubMed=12643545; DOI=10.1021/pr025562r;
RA Basrur V., Yang F., Kushimoto T., Higashimoto Y., Yasumoto K., Valencia J.,
RA Muller J., Vieira W.D., Watabe H., Shabanowitz J., Hearing V.J., Hunt D.F.,
RA Appella E.;
RT "Proteomic analysis of early melanosomes: identification of novel
RT melanosomal proteins.";
RL J. Proteome Res. 2:69-79(2003).
RN [24]
RP FUNCTION (MICROBIAL INFECTION), AND SUBCELLULAR LOCATION.
RX PubMed=15098107; DOI=10.1007/s00705-003-0263-x;
RA Jindadamrongwech S., Thepparit C., Smith D.R.;
RT "Identification of GRP 78 (BiP) as a liver cell expressed receptor element
RT for dengue virus serotype 2.";
RL Arch. Virol. 149:915-927(2004).
RN [25]
RP INTERACTION WITH CLN3.
RX PubMed=18621045; DOI=10.1016/j.yexcr.2008.06.016;
RA Uusi-Rauva K., Luiro K., Tanhuanpaeae K., Kopra O., Martin-Vasallo P.,
RA Kyttaelae A., Jalanko A.;
RT "Novel interactions of CLN3 protein link Batten disease to dysregulation of
RT fodrin-Na+, K+ ATPase complex.";
RL Exp. Cell Res. 314:2895-2905(2008).
RN [26]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RC TISSUE=Melanoma;
RX PubMed=17081065; DOI=10.1021/pr060363j;
RA Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H., Mangini N.J.,
RA Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R., Yamagishi S.,
RA Shabanowitz J., Hearing V.J., Wu C., Appella E., Hunt D.F.;
RT "Proteomic and bioinformatic characterization of the biogenesis and
RT function of melanosomes.";
RL J. Proteome Res. 5:3135-3144(2006).
RN [27]
RP INTERACTION WITH ERLEC1; OS9; SEL1L AND SYVN1.
RX PubMed=18502753; DOI=10.1074/jbc.m709336200;
RA Hosokawa N., Wada I., Nagasawa K., Moriyama T., Okawa K., Nagata K.;
RT "Human XTP3-B forms an endoplasmic reticulum quality control scaffold with
RT the HRD1-SEL1L ubiquitin ligase complex and BiP.";
RL J. Biol. Chem. 283:20914-20924(2008).
RN [28]
RP INTERACTION WITH ERLEC1; OS9; SEL1L AND SYVN1.
RX PubMed=18264092; DOI=10.1038/ncb1689;
RA Christianson J.C., Shaler T.A., Tyler R.E., Kopito R.R.;
RT "OS-9 and GRP94 deliver mutant alpha1-antitrypsin to the Hrd1-SEL1L
RT ubiquitin ligase complex for ERAD.";
RL Nat. Cell Biol. 10:272-282(2008).
RN [29]
RP FUNCTION.
RX PubMed=19538957; DOI=10.1016/j.yexcr.2009.06.009;
RA Oikawa D., Kimata Y., Kohno K., Iwawaki T.;
RT "Activation of mammalian IRE1alpha upon ER stress depends on dissociation
RT of BiP rather than on direct interaction with unfolded proteins.";
RL Exp. Cell Res. 315:2496-2504(2009).
RN [30]
RP FUNCTION (MICROBIAL INFECTION), SUBCELLULAR LOCATION, INDUCTION, AND
RP BIOTECHNOLOGY.
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 [31]
RP INTERACTION WITH PCSK4, AND SUBCELLULAR LOCATION.
RX PubMed=21080038; DOI=10.1007/s11010-010-0635-y;
RA Gyamera-Acheampong C., Sirois F., Denis N.J., Mishra P., Figeys D.,
RA Basak A., Mbikay M.;
RT "The precursor to the germ cell-specific PCSK4 proteinase is inefficiently
RT activated in transfected somatic cells: evidence of interaction with the
RT BiP chaperone.";
RL Mol. Cell. Biochem. 348:43-52(2011).
RN [32]
RP INTERACTION WITH MANF.
RX PubMed=22637475; DOI=10.1074/jbc.m112.356345;
RA Glembotski C.C., Thuerauf D.J., Huang C., Vekich J.A., Gottlieb R.A.,
RA Doroudgar S.;
RT "Mesencephalic astrocyte-derived neurotrophic factor protects the heart
RT from ischemic damage and is selectively secreted upon sarco/endoplasmic
RT reticulum calcium depletion.";
RL J. Biol. Chem. 287:25893-25904(2012).
RN [33]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22905912; DOI=10.1021/pr300539b;
RA Rosenow A., Noben J.P., Jocken J., Kallendrusch S., Fischer-Posovszky P.,
RA Mariman E.C., Renes J.;
RT "Resveratrol-induced changes of the human adipocyte secretion profile.";
RL J. Proteome Res. 11:4733-4743(2012).
RN [34]
RP METHYLATION AT LYS-585, AND MUTAGENESIS OF LYS-585.
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 [35]
RP FUNCTION, INTERACTION WITH CEMIP, AND SUBCELLULAR LOCATION.
RX PubMed=23990668; DOI=10.1093/jnci/djt224;
RA Evensen N.A., Kuscu C., Nguyen H.L., Zarrabi K., Dufour A., Kadam P.,
RA Hu Y.J., Pulkoski-Gross A., Bahou W.F., Zucker S., Cao J.;
RT "Unraveling the role of KIAA1199, a novel endoplasmic reticulum protein, in
RT cancer cell migration.";
RL J. Natl. Cancer Inst. 105:1402-1416(2013).
RN [36]
RP FUNCTION, AND INTERACTION WITH DNAJC10.
RX PubMed=23769672; DOI=10.1016/j.molcel.2013.05.014;
RA Oka O.B., Pringle M.A., Schopp I.M., Braakman I., Bulleid N.J.;
RT "ERdj5 is the ER reductase that catalyzes the removal of non-native
RT disulfides and correct folding of the LDL receptor.";
RL Mol. Cell 50:793-804(2013).
RN [37]
RP INTERACTION WITH CLU, SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=22689054; DOI=10.1038/onc.2012.212;
RA Li N., Zoubeidi A., Beraldi E., Gleave M.E.;
RT "GRP78 regulates clusterin stability, retrotranslocation and mitochondrial
RT localization under ER stress in prostate cancer.";
RL Oncogene 32:1933-1942(2013).
RN [38]
RP FUNCTION (MICROBIAL INFECTION), INTERACTION WITH R.DELEMAR COTH2 AND COTH3
RP (MICROBIAL INFECTION), AND SUBCELLULAR LOCATION.
RX PubMed=24355926; DOI=10.1172/jci71349;
RA Gebremariam T., Liu M., Luo G., Bruno V., Phan Q.T., Waring A.J.,
RA Edwards J.E. Jr., Filler S.G., Yeaman M.R., Ibrahim A.S.;
RT "CotH3 mediates fungal invasion of host cells during mucormycosis.";
RL J. Clin. Invest. 124:237-250(2014).
RN [39]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-518, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [40]
RP METHYLATION [LARGE SCALE ANALYSIS] AT LYS-585 AND LYS-591, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Colon carcinoma;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
RN [41]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-352, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25218447; DOI=10.1038/nsmb.2890;
RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M.,
RA Vertegaal A.C.;
RT "Uncovering global SUMOylation signaling networks in a site-specific
RT manner.";
RL Nat. Struct. Mol. Biol. 21:927-936(2014).
RN [42]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-352 AND LYS-353, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25114211; DOI=10.1073/pnas.1413825111;
RA Impens F., Radoshevich L., Cossart P., Ribet D.;
RT "Mapping of SUMO sites and analysis of SUMOylation changes induced by
RT external stimuli.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:12432-12437(2014).
RN [43]
RP FUNCTION, INTERACTION WITH CASP7 AND KIAA1324, AND REGION.
RX PubMed=26045166; DOI=10.1158/0008-5472.can-14-3751;
RA Kang J.M., Park S., Kim S.J., Kim H., Lee B., Kim J., Park J., Kim S.T.,
RA Yang H.K., Kim W.H., Kim S.J.;
RT "KIAA1324 Suppresses Gastric Cancer Progression by Inhibiting the
RT Oncoprotein GRP78.";
RL Cancer Res. 75:3087-3097(2015).
RN [44]
RP AMPYLATION.
RX PubMed=25601083; DOI=10.1074/jbc.m114.618348;
RA Sanyal A., Chen A.J., Nakayasu E.S., Lazar C.S., Zbornik E.A., Worby C.A.,
RA Koller A., Mattoo S.;
RT "A novel link between Fic (filamentation induced by cAMP)-mediated
RT adenylylation/AMPylation and the unfolded protein response.";
RL J. Biol. Chem. 290:8482-8499(2015).
RN [45]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-352, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25755297; DOI=10.1074/mcp.o114.044792;
RA Xiao Z., Chang J.G., Hendriks I.A., Sigurdsson J.O., Olsen J.V.,
RA Vertegaal A.C.;
RT "System-wide analysis of SUMOylation dynamics in response to replication
RT stress reveals novel small ubiquitin-like modified target proteins and
RT acceptor lysines relevant for genome stability.";
RL Mol. Cell. Proteomics 14:1419-1434(2015).
RN [46]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [47]
RP INTERACTION WITH CIPC.
RX PubMed=26657846; DOI=10.1016/j.bbrc.2015.11.117;
RA Matsunaga R., Nishino T., Yokoyama A., Nakashima A., Kikkawa U.,
RA Konishi H.;
RT "Versatile function of the circadian protein CIPC as a regulator of Erk
RT activation.";
RL Biochem. Biophys. Res. Commun. 469:377-383(2016).
RN [48]
RP INTERACTION WITH INPP5K.
RX PubMed=26940976; DOI=10.1111/gtc.12353;
RA Ijuin T., Hatano N., Takenawa T.;
RT "Glucose-regulated protein 78 (GRP78) binds directly to PIP3 phosphatase
RT SKIP and determines its localization.";
RL Genes Cells 21:457-465(2016).
RN [49]
RP SUBCELLULAR LOCATION, AND 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 [50]
RP REVIEW.
RX PubMed=28286085; DOI=10.1016/j.gene.2017.03.005;
RA Wang J., Lee J., Liem D., Ping P.;
RT "HSPA5 Gene encoding Hsp70 chaperone BiP in the endoplasmic reticulum.";
RL Gene 618:14-23(2017).
RN [51]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-352, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [52]
RP FUNCTION, INTERACTION WITH LOXL2, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=28332555; DOI=10.1038/srep44988;
RA Cuevas E.P., Eraso P., Mazon M.J., Santos V., Moreno-Bueno G., Cano A.,
RA Portillo F.;
RT "LOXL2 drives epithelial-mesenchymal transition via activation of IRE1-XBP1
RT signalling pathway.";
RL Sci. Rep. 7:44988-44988(2017).
RN [53]
RP FUNCTION (MICROBIAL INFECTION), INTERACTION WITH JAPANESE ENCEPHALITIS
RP VIRUS ENVELOPE PROTEIN E (MICROBIAL INFECTION), AND SUBCELLULAR LOCATION.
RX PubMed=28053106; DOI=10.1128/jvi.02274-16;
RA Nain M., Mukherjee S., Karmakar S.P., Paton A.W., Paton J.C., Abdin M.Z.,
RA Basu A., Kalia M., Vrati S.;
RT "GRP78 Is an Important Host Factor for Japanese Encephalitis Virus Entry
RT and Replication in Mammalian Cells.";
RL J. Virol. 91:0-0(2017).
RN [54]
RP FUNCTION.
RX PubMed=29719251; DOI=10.1016/j.celrep.2018.03.122;
RA Hassdenteufel S., Johnson N., Paton A.W., Paton J.C., High S.,
RA Zimmermann R.;
RT "Chaperone-Mediated Sec61 Channel Gating during ER Import of Small
RT Precursor Proteins Overcomes Sec61 Inhibitor-Reinforced Energy Barrier.";
RL Cell Rep. 23:1373-1386(2018).
RN [55]
RP SUBCELLULAR LOCATION.
RX PubMed=29497057; DOI=10.1038/s41467-018-03355-0;
RA Bai M., Vozdek R., Hnizda A., Jiang C., Wang B., Kuchar L., Li T.,
RA Zhang Y., Wood C., Feng L., Dang Y., Ma D.K.;
RT "Conserved roles of C. elegans and human MANFs in sulfatide binding and
RT cytoprotection.";
RL Nat. Commun. 9:897-897(2018).
RN [56]
RP FUNCTION (MICROBIAL INFECTION), INTERACTION WITH R.DELEMAR COTH3 (MICROBIAL
RP INFECTION), AND INDUCTION.
RX PubMed=32487760; DOI=10.1128/mbio.01087-20;
RA Alqarihi A., Gebremariam T., Gu Y., Swidergall M., Alkhazraji S.,
RA Soliman S.S.M., Bruno V.M., Edwards J.E. Jr., Filler S.G., Uppuluri P.,
RA Ibrahim A.S.;
RT "GRP78 and Integrins Play Different Roles in Host Cell Invasion during
RT Mucormycosis.";
RL MBio 11:e01087-e01087(2020).
RN [57]
RP FUNCTION (MICROBIAL INFECTION), INTERACTION WITH ZIKA VIRUS ENVELOPE
RP PROTEIN E (MICROBIAL INFECTION), AND SUBCELLULAR LOCATION.
RX PubMed=33432092; DOI=10.1038/s41598-020-79803-z;
RA Khongwichit S., Sornjai W., Jitobaom K., Greenwood M., Greenwood M.P.,
RA Hitakarun A., Wikan N., Murphy D., Smith D.R.;
RT "A functional interaction between GRP78 and Zika virus E protein.";
RL Sci. Rep. 11:393-393(2021).
RN [58]
RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 26-410.
RX PubMed=20072699; DOI=10.1371/journal.pone.0008625;
RA Wisniewska M., Karlberg T., Lehtio L., Johansson I., Kotenyova T.,
RA Moche M., Schuler H.;
RT "Crystal structures of the ATPase domains of four human Hsp70 isoforms:
RT HSPA1L/Hsp70-hom, HSPA2/Hsp70-2, HSPA6/Hsp70B', and HSPA5/BiP/GRP78.";
RL PLoS ONE 5:E8625-E8625(2010).
RN [59]
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 26-407 IN COMPLEXES WITH ATP
RP ANALOG.
RX PubMed=21526763; DOI=10.1021/jm101625x;
RA Macias A.T., Williamson D.S., Allen N., Borgognoni J., Clay A., Daniels Z.,
RA Dokurno P., Drysdale M.J., Francis G.L., Graham C.J., Howes R.,
RA Matassova N., Murray J.B., Parsons R., Shaw T., Surgenor A.E., Terry L.,
RA Wang Y., Wood M., Massey A.J.;
RT "Adenosine-derived inhibitors of 78 kDa glucose regulated protein (Grp78)
RT ATPase: insights into isoform selectivity.";
RL J. Med. Chem. 54:4034-4041(2011).
RN [60] {ECO:0007744|PDB:5E84, ECO:0007744|PDB:5E85, ECO:0007744|PDB:5E86}
RP X-RAY CRYSTALLOGRAPHY (2.57 ANGSTROMS) OF 418-637 IN COMPLEX WITH ATP,
RP CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND MUTAGENESIS OF THR-229.
RX PubMed=26655470; DOI=10.1016/j.str.2015.10.012;
RA Yang J., Nune M., Zong Y., Zhou L., Liu Q.;
RT "Close and allosteric opening of the polypeptide-binding site in a human
RT Hsp70 chaperone BiP.";
RL Structure 23:2191-2203(2015).
CC -!- FUNCTION: Endoplasmic reticulum chaperone that plays a key role in
CC protein folding and quality control in the endoplasmic reticulum lumen
CC (PubMed:2294010, PubMed:23769672, PubMed:23990668, PubMed:28332555).
CC Involved in the correct folding of proteins and degradation of
CC misfolded proteins via its interaction with DNAJC10/ERdj5, probably to
CC facilitate the release of DNAJC10/ERdj5 from its substrate (By
CC similarity). Acts as a key repressor of the ERN1/IRE1-mediated unfolded
CC protein response (UPR) (PubMed:1550958, PubMed:19538957). In the
CC 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
CC (PubMed:26045166). {ECO:0000250|UniProtKB:G3I8R9,
CC ECO:0000250|UniProtKB:P20029, ECO:0000269|PubMed:1550958,
CC ECO:0000269|PubMed:19538957, ECO:0000269|PubMed:2294010,
CC ECO:0000269|PubMed:23769672, ECO:0000269|PubMed:23990668,
CC ECO:0000269|PubMed:26045166, ECO:0000269|PubMed:28332555,
CC ECO:0000269|PubMed:29719251}.
CC -!- FUNCTION: (Microbial infection) Plays an important role in viral
CC binding to the host cell membrane and entry for several flaviruses such
CC as Dengue virus, Zika virus and Japanese encephalitis virus
CC (PubMed:33432092, PubMed:15098107, PubMed:28053106). Acts as a
CC component of the cellular receptor for Dengue virus serotype 2/DENV-2
CC on human liver cells (PubMed:15098107). {ECO:0000269|PubMed:15098107,
CC ECO:0000269|PubMed:28053106, ECO:0000269|PubMed:33432092}.
CC -!- FUNCTION: (Microbial infection) Acts as a receptor for CotH proteins
CC expressed by fungi of the order mucorales, the causative agent of
CC mucormycosis, which plays an important role in epithelial cell invasion
CC by the fungi (PubMed:24355926, PubMed:20484814, PubMed:32487760). Acts
CC as a receptor for R.delemar CotH3 in nasal epithelial cells, which may
CC be an early step in rhinoorbital/cerebral mucormycosis (RCM) disease
CC progression (PubMed:32487760). {ECO:0000269|PubMed:20484814,
CC ECO:0000269|PubMed:24355926, ECO:0000269|PubMed:32487760}.
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:0000269|PubMed:26655470};
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 (PubMed:26655470). In
CC contrast, in the ATP-bound state the two domains are tightly coupled,
CC which results in drastically accelerated kinetics in both binding and
CC release of polypeptide substrates (PubMed:26655470). J domain-
CC containing co-chaperones (DNAJB9/ERdj4 or DNAJC10/ERdj5) stimulate the
CC ATPase activity and are required for efficient substrate recognition by
CC HSPA5/BiP (By similarity). Homooligomerization inactivates
CC participating HSPA5/BiP protomers and probably act as reservoirs to
CC store HSPA5/BiP molecules when they are not needed by the cell (By
CC similarity). {ECO:0000250|UniProtKB:G3I8R9,
CC ECO:0000269|PubMed:26655470, ECO:0000303|PubMed:28286085}.
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) (By similarity). Component of an EIF2 complex at least
CC composed of CELF1/CUGBP1, CALR, CALR3, EIF2S1, EIF2S2, HSP90B1 and
CC HSPA5 (By similarity). 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 (By similarity). Interacts with TMEM132A and
CC TRIM21 (PubMed:12699405). May form a complex with ERLEC1, OS9, SEL1L
CC and SYVN1 (PubMed:18264092,PubMed:18502753). Interacts with DNAJC10
CC (PubMed:12411443, PubMed:23769672). Interacts with DNAJB9/ERdj4;
CC leading to recruit HSPA5/BiP to ERN1/IRE1 (By similarity). Interacts
CC with ERN1/IRE1; interaction takes place following interaction with
CC DNAJB9/ERdj4 and leads to inactivate ERN1/IRE1 (By similarity).
CC Interacts with MX1 (By similarity). Interacts with METTL23
CC (PubMed:23349634). Interacts with CEMIP; the interaction induces
CC calcium leakage from the endoplasmic reticulum and cell migration
CC (PubMed:23990668). Interacts with PCSK4 form; the interaction takes
CC place in the endoplasmic reticulum (PubMed:21080038). Interacts with
CC CIPC (PubMed:26657846). Interacts with CCDC88B (via C-terminus); the
CC interaction opposes ERN1-mediated JNK activation, protecting against
CC apoptosis (PubMed:21289099). Interacts with INPP5K; necessary for
CC INPP5K localization at the endoplasmic reticulum (PubMed:26940976).
CC Interacts with MANF; the interaction is direct (PubMed:22637475).
CC Interacts with LOXL2; leading to activate the ERN1/IRE1-XBP1 pathway of
CC the unfolded protein response (PubMed:28332555). Interacts with CLU
CC under stressed condition; interaction increases CLU protein stability;
CC facilitates its retrotranslocation and redistribution to the
CC mitochondria; cooperatively suppress stress-induced apoptosis by
CC stabilizing mitochondrial membrane integrity (PubMed:22689054).
CC Interacts with CCDC47 (By similarity). Interacts with CLN3 (Probable).
CC Interacts with KIAA1324; may regulate the function of HSPA5 in
CC apoptosis and cell proliferation (PubMed:26045166). Interacts with
CC CASP7 (PubMed:26045166). Interacts with ILDR2; the interaction
CC stabilizes ILDR2 expression (By similarity).
CC {ECO:0000250|UniProtKB:G3I8R9, ECO:0000250|UniProtKB:P20029,
CC ECO:0000269|PubMed:12411443, ECO:0000269|PubMed:12699405,
CC ECO:0000269|PubMed:18264092, ECO:0000269|PubMed:18502753,
CC ECO:0000269|PubMed:21080038, ECO:0000269|PubMed:21289099,
CC ECO:0000269|PubMed:22637475, ECO:0000269|PubMed:22689054,
CC ECO:0000269|PubMed:23349634, ECO:0000269|PubMed:23769672,
CC ECO:0000269|PubMed:23990668, ECO:0000269|PubMed:26045166,
CC ECO:0000269|PubMed:26657846, ECO:0000269|PubMed:26940976,
CC ECO:0000269|PubMed:28332555, ECO:0000305|PubMed:18621045}.
CC -!- SUBUNIT: (Microbial infection) Interacts with Japanese encephalitis
CC virus envelope protein E. {ECO:0000269|PubMed:28053106}.
CC -!- SUBUNIT: (Microbial infection) Interacts with R.delemar invasin CotH3
CC on the surface of nasal epithelial cells (PubMed:32487760,
CC PubMed:24355926). Interacts with R.delemar invasin CotH2
CC (PubMed:24355926). {ECO:0000269|PubMed:24355926,
CC ECO:0000269|PubMed:32487760}.
CC -!- SUBUNIT: (Microbial infection) Interacts with Zika virus envelope
CC protein E. {ECO:0000269|PubMed:33432092}.
CC -!- INTERACTION:
CC P11021; Q9BYF1: ACE2; NbExp=6; IntAct=EBI-354921, EBI-7730807;
CC P11021; P05067: APP; NbExp=3; IntAct=EBI-354921, EBI-77613;
CC P11021; P18850: ATF6; NbExp=2; IntAct=EBI-354921, EBI-852157;
CC P11021; Q9ULD4-2: BRPF3; NbExp=3; IntAct=EBI-354921, EBI-23662416;
CC P11021; Q6E0U4: DMKN; NbExp=3; IntAct=EBI-354921, EBI-7943171;
CC P11021; Q9UBS4: DNAJB11; NbExp=4; IntAct=EBI-354921, EBI-713113;
CC P11021; Q9NZJ5: EIF2AK3; NbExp=4; IntAct=EBI-354921, EBI-766076;
CC P11021; O75460: ERN1; NbExp=3; IntAct=EBI-354921, EBI-371750;
CC P11021; O75460-1: ERN1; NbExp=4; IntAct=EBI-354921, EBI-15600828;
CC P11021; P62993: GRB2; NbExp=4; IntAct=EBI-354921, EBI-401755;
CC P11021; Q15486: GUSBP1; NbExp=3; IntAct=EBI-354921, EBI-712457;
CC P11021; P14625: HSP90B1; NbExp=2; IntAct=EBI-354921, EBI-359129;
CC P11021; Q9Y4L1: HYOU1; NbExp=2; IntAct=EBI-354921, EBI-1054186;
CC P11021; Q96IZ0: PAWR; NbExp=8; IntAct=EBI-354921, EBI-595869;
CC P11021; Q15084: PDIA6; NbExp=2; IntAct=EBI-354921, EBI-1043087;
CC P11021; P04049: RAF1; NbExp=5; IntAct=EBI-354921, EBI-365996;
CC P11021; P61619: SEC61A1; NbExp=3; IntAct=EBI-354921, EBI-358919;
CC P11021; Q9H173: SIL1; NbExp=9; IntAct=EBI-354921, EBI-2840325;
CC P11021; Q9UHI5: SLC7A8; NbExp=3; IntAct=EBI-354921, EBI-13292283;
CC P11021; Q13573: SNW1; NbExp=5; IntAct=EBI-354921, EBI-632715;
CC P11021; Q6PF05: TTC23L; NbExp=3; IntAct=EBI-354921, EBI-8656864;
CC P11021; Q13404: UBE2V1; NbExp=3; IntAct=EBI-354921, EBI-1050671;
CC P11021; Q6T424; NbExp=3; IntAct=EBI-354921, EBI-7888150;
CC P11021; Q9QXT0: Cnpy2; Xeno; NbExp=2; IntAct=EBI-354921, EBI-8321111;
CC P11021; Q91YW3: Dnajc3; Xeno; NbExp=2; IntAct=EBI-354921, EBI-8381770;
CC P11021; Q9Z2B5: Eif2ak3; Xeno; NbExp=2; IntAct=EBI-354921, EBI-1226344;
CC P11021; Q62627: Pawr; Xeno; NbExp=4; IntAct=EBI-354921, EBI-1187240;
CC P11021; K0BRG7: S; Xeno; NbExp=9; IntAct=EBI-354921, EBI-16040613;
CC P11021; P0DTC2: S; Xeno; NbExp=8; IntAct=EBI-354921, EBI-25474821;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum lumen
CC {ECO:0000269|PubMed:21080038, ECO:0000269|PubMed:21289099,
CC ECO:0000269|PubMed:23990668, ECO:0000269|PubMed:29497057}. Melanosome
CC {ECO:0000269|PubMed:12643545}. Cytoplasm
CC {ECO:0000250|UniProtKB:P20029}. Cell surface
CC {ECO:0000269|PubMed:15098107, ECO:0000269|PubMed:20484814,
CC ECO:0000269|PubMed:24355926, ECO:0000269|PubMed:27159390,
CC ECO:0000269|PubMed:28053106, ECO:0000269|PubMed:33432092}.
CC Note=Identified by mass spectrometry in melanosome fractions from stage
CC I to stage IV (PubMed:12643545). Localizes to the cell surface of
CC epithelial cells in response to high levels of free iron
CC (PubMed:20484814, PubMed:24355926, PubMed:27159390).
CC {ECO:0000269|PubMed:12643545, ECO:0000269|PubMed:20484814,
CC ECO:0000269|PubMed:24355926, ECO:0000269|PubMed:27159390}.
CC -!- INDUCTION: By endoplasmic reticulum stress (PubMed:21289099). Induced
CC in nasal epithelial cells by high free iron levels (PubMed:32487760,
CC PubMed:20484814, PubMed:27159390). Induced in nasal epithelial cells in
CC high glucose (PubMed:32487760, PubMed:20484814, PubMed:27159390).
CC Induced in nasal epithelial cells by 3-hydroxybutyric acid (BHB)
CC (PubMed:32487760, PubMed:27159390). {ECO:0000269|PubMed:20484814,
CC ECO:0000269|PubMed:21289099, ECO:0000269|PubMed:27159390,
CC ECO:0000269|PubMed:32487760}.
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: AMPylated by FICD (PubMed:25601083). In unstressed cells,
CC AMPylation at Thr-518 by FICD inactivates the chaperome activity:
CC AMPylated form is locked in a relatively inert state and only weakly
CC stimulated by J domain-containing proteins (By similarity). In response
CC to endoplasmic reticulum stress, de-AMPylation by the same protein,
CC FICD, restores the chaperone activity (By similarity).
CC {ECO:0000250|UniProtKB:G3I8R9, ECO:0000269|PubMed:25601083}.
CC -!- DISEASE: Note=Autoantigen in rheumatoid arthritis.
CC {ECO:0000269|PubMed:11160188}.
CC -!- BIOTECHNOLOGY: Antibodies against the protein protects endothelial
CC cells from invasion by the fungus R.delemar, a causative agent of
CC mucormycosis, and could thus potentially be used to treat mucormycosis
CC disease (PubMed:20484814). Antibodies against the protein also protect
CC a diabetic ketoacidosis mouse model against mucormycosis
CC (PubMed:20484814). {ECO:0000269|PubMed:20484814}.
CC -!- SIMILARITY: Belongs to the heat shock protein 70 family. {ECO:0000305}.
CC -!- CAUTION: AMPylation was initially reported to take place at Ser-365 and
CC Thr-366 in vitro, and promote activation of HSPA5/BiP
CC (PubMed:25601083). However, it was later shown that AMPylation takes
CC place at Thr-518 and leads to inactivation of HSPA5/BiP.
CC {ECO:0000250|UniProtKB:G3I8R9, ECO:0000269|PubMed:25601083}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/hspa5/";
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/HSPA5ID40876ch9q33.html";
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DR EMBL; M19645; AAA52614.1; -; Genomic_DNA.
DR EMBL; X87949; CAA61201.1; -; mRNA.
DR EMBL; AJ271729; CAB71335.1; -; mRNA.
DR EMBL; AF216292; AAF42836.1; -; mRNA.
DR EMBL; DQ385847; ABD04090.1; -; Genomic_DNA.
DR EMBL; AL354710; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471090; EAW87620.1; -; Genomic_DNA.
DR EMBL; BC020235; AAH20235.1; -; mRNA.
DR EMBL; X59969; CAA42595.1; -; Genomic_DNA.
DR EMBL; AF188611; AAF13605.1; ALT_SEQ; mRNA.
DR CCDS; CCDS6863.1; -.
DR PIR; A29821; A29821.
DR RefSeq; NP_005338.1; NM_005347.4.
DR PDB; 3IUC; X-ray; 2.40 A; A/C=26-410.
DR PDB; 3LDL; X-ray; 2.30 A; A/B=26-407.
DR PDB; 3LDN; X-ray; 2.20 A; A/B=26-407.
DR PDB; 3LDO; X-ray; 1.95 A; A/B=26-407.
DR PDB; 3LDP; X-ray; 2.20 A; A/B=26-407.
DR PDB; 5E84; X-ray; 2.99 A; A/B/C/D/E/F=25-633.
DR PDB; 5E85; X-ray; 2.57 A; A=418-637.
DR PDB; 5E86; X-ray; 2.68 A; A=418-637.
DR PDB; 5EVZ; X-ray; 1.85 A; A/B=26-407.
DR PDB; 5EX5; X-ray; 1.90 A; A/B=26-407.
DR PDB; 5EXW; X-ray; 1.90 A; A/B=26-407.
DR PDB; 5EY4; X-ray; 1.86 A; A/B=26-407.
DR PDB; 5F0X; X-ray; 1.60 A; A/B=26-407.
DR PDB; 5F1X; X-ray; 1.90 A; A/B=26-407.
DR PDB; 5F2R; X-ray; 2.15 A; A/B=26-407.
DR PDB; 6ASY; X-ray; 1.85 A; A/B=25-633.
DR PDB; 6CZ1; X-ray; 1.68 A; A/B=26-407.
DR PDB; 6DFM; X-ray; 2.14 A; A/B=26-407.
DR PDB; 6DFO; X-ray; 2.54 A; A/B=26-407.
DR PDB; 6DO2; X-ray; 1.70 A; A/B=26-407.
DR PDB; 6DWS; X-ray; 1.90 A; A/B=26-407.
DR PDB; 6ZMD; X-ray; 2.64 A; A=28-549.
DR PDB; 7N1R; X-ray; 2.03 A; A/B=25-633.
DR PDBsum; 3IUC; -.
DR PDBsum; 3LDL; -.
DR PDBsum; 3LDN; -.
DR PDBsum; 3LDO; -.
DR PDBsum; 3LDP; -.
DR PDBsum; 5E84; -.
DR PDBsum; 5E85; -.
DR PDBsum; 5E86; -.
DR PDBsum; 5EVZ; -.
DR PDBsum; 5EX5; -.
DR PDBsum; 5EXW; -.
DR PDBsum; 5EY4; -.
DR PDBsum; 5F0X; -.
DR PDBsum; 5F1X; -.
DR PDBsum; 5F2R; -.
DR PDBsum; 6ASY; -.
DR PDBsum; 6CZ1; -.
DR PDBsum; 6DFM; -.
DR PDBsum; 6DFO; -.
DR PDBsum; 6DO2; -.
DR PDBsum; 6DWS; -.
DR PDBsum; 6ZMD; -.
DR PDBsum; 7N1R; -.
DR AlphaFoldDB; P11021; -.
DR SMR; P11021; -.
DR BioGRID; 109541; 1228.
DR CORUM; P11021; -.
DR DIP; DIP-33189N; -.
DR ELM; P11021; -.
DR IntAct; P11021; 418.
DR MINT; P11021; -.
DR STRING; 9606.ENSP00000324173; -.
DR BindingDB; P11021; -.
DR ChEMBL; CHEMBL1781865; -.
DR DrugBank; DB00945; Acetylsalicylic acid.
DR DrugBank; DB00025; Antihemophilic factor, human recombinant.
DR DrugBank; DB09130; Copper.
DR DrugBank; DB13998; Lonoctocog alfa.
DR DrugBank; DB13999; Moroctocog alfa.
DR TCDB; 1.A.33.1.5; the cation channel-forming heat shock protein-70 (hsp70) family.
DR GlyGen; P11021; 2 sites, 1 O-linked glycan (1 site).
DR iPTMnet; P11021; -.
DR MetOSite; P11021; -.
DR PhosphoSitePlus; P11021; -.
DR SwissPalm; P11021; -.
DR BioMuta; HSPA5; -.
DR DMDM; 14916999; -.
DR DOSAC-COBS-2DPAGE; P11021; -.
DR OGP; P11021; -.
DR REPRODUCTION-2DPAGE; P11021; -.
DR SWISS-2DPAGE; P11021; -.
DR UCD-2DPAGE; P11021; -.
DR CPTAC; CPTAC-524; -.
DR CPTAC; CPTAC-525; -.
DR CPTAC; non-CPTAC-2616; -.
DR EPD; P11021; -.
DR jPOST; P11021; -.
DR MassIVE; P11021; -.
DR PaxDb; P11021; -.
DR PeptideAtlas; P11021; -.
DR PRIDE; P11021; -.
DR ProteomicsDB; 52688; -.
DR TopDownProteomics; P11021; -.
DR ABCD; P11021; 16 sequenced antibodies.
DR Antibodypedia; 3926; 1771 antibodies from 49 providers.
DR DNASU; 3309; -.
DR Ensembl; ENST00000324460.7; ENSP00000324173.6; ENSG00000044574.9.
DR GeneID; 3309; -.
DR KEGG; hsa:3309; -.
DR MANE-Select; ENST00000324460.7; ENSP00000324173.6; NM_005347.5; NP_005338.1.
DR CTD; 3309; -.
DR DisGeNET; 3309; -.
DR GeneCards; HSPA5; -.
DR HGNC; HGNC:5238; HSPA5.
DR HPA; ENSG00000044574; Low tissue specificity.
DR MIM; 138120; gene.
DR neXtProt; NX_P11021; -.
DR OpenTargets; ENSG00000044574; -.
DR PharmGKB; PA29504; -.
DR VEuPathDB; HostDB:ENSG00000044574; -.
DR eggNOG; KOG0100; Eukaryota.
DR GeneTree; ENSGT00940000154787; -.
DR HOGENOM; CLU_005965_3_0_1; -.
DR InParanoid; P11021; -.
DR OMA; AYTKNQD; -.
DR OrthoDB; 288077at2759; -.
DR PhylomeDB; P11021; -.
DR TreeFam; TF105044; -.
DR PathwayCommons; P11021; -.
DR Reactome; R-HSA-114608; Platelet degranulation.
DR Reactome; R-HSA-3371453; Regulation of HSF1-mediated heat shock response.
DR Reactome; R-HSA-381033; ATF6 (ATF6-alpha) activates chaperones.
DR Reactome; R-HSA-381042; PERK regulates gene expression.
DR Reactome; R-HSA-381070; IRE1alpha activates chaperones.
DR Reactome; R-HSA-381183; ATF6 (ATF6-alpha) activates chaperone genes.
DR Reactome; R-HSA-983170; Antigen Presentation: Folding, assembly and peptide loading of class I MHC.
DR SignaLink; P11021; -.
DR SIGNOR; P11021; -.
DR BioGRID-ORCS; 3309; 662 hits in 1083 CRISPR screens.
DR ChiTaRS; HSPA5; human.
DR EvolutionaryTrace; P11021; -.
DR GeneWiki; Binding_immunoglobulin_protein; -.
DR GenomeRNAi; 3309; -.
DR Pharos; P11021; Tchem.
DR PRO; PR:P11021; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; P11021; protein.
DR Bgee; ENSG00000044574; Expressed in vena cava and 212 other tissues.
DR ExpressionAtlas; P11021; baseline and differential.
DR Genevisible; P11021; HS.
DR GO; GO:0009986; C:cell surface; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:MGI.
DR GO; GO:0034663; C:endoplasmic reticulum chaperone complex; IDA:UniProtKB.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0005793; C:endoplasmic reticulum-Golgi intermediate compartment; IDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005925; C:focal adhesion; HDA:UniProtKB.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; IDA:BHF-UCL.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:UniProtKB.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0030496; C:midbody; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IMP:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IEA:Ensembl.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0005790; C:smooth endoplasmic reticulum; IEA:Ensembl.
DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR GO; GO:0016887; F:ATP hydrolysis activity; IDA:AgBase.
DR GO; GO:0140662; F:ATP-dependent protein folding chaperone; IEA:InterPro.
DR GO; GO:0045296; F:cadherin binding; HDA:BHF-UCL.
DR GO; GO:0005509; F:calcium ion binding; TAS:UniProtKB.
DR GO; GO:0051087; F:chaperone binding; TAS:BHF-UCL.
DR GO; GO:0019899; F:enzyme binding; IPI:BHF-UCL.
DR GO; GO:0031072; F:heat shock protein binding; IBA:GO_Central.
DR GO; GO:0051787; F:misfolded protein binding; IDA:UniProtKB.
DR GO; GO:0019904; F:protein domain specific binding; IPI:UniProtKB.
DR GO; GO:0044183; F:protein folding chaperone; IBA:GO_Central.
DR GO; GO:0043022; F:ribosome binding; IEA:Ensembl.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB.
DR GO; GO:0051082; F:unfolded protein binding; IBA:GO_Central.
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; IDA:UniProtKB.
DR GO; GO:0071353; P:cellular response to interleukin-4; IEA:Ensembl.
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; IEA:Ensembl.
DR GO; GO:0021589; P:cerebellum structural organization; IEA:Ensembl.
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:0006983; P:ER overload response; IEA:Ensembl.
DR GO; GO:0001554; P:luteolysis; IEA:Ensembl.
DR GO; GO:0035437; P:maintenance of protein localization in endoplasmic reticulum; IMP:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
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; IEA:Ensembl.
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; IMP:UniProtKB.
DR GO; GO:0010976; P:positive regulation of neuron projection development; IEA:Ensembl.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; IEA:Ensembl.
DR GO; GO:1990440; P:positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress; TAS:ParkinsonsUK-UCL.
DR GO; GO:0031204; P:post-translational protein targeting to membrane, translocation; IMP:UniProtKB.
DR GO; GO:0034975; P:protein folding in endoplasmic reticulum; TAS:ParkinsonsUK-UCL.
DR GO; GO:0042026; P:protein refolding; IBA:GO_Central.
DR GO; GO:1903891; P:regulation of ATF6-mediated unfolded protein response; TAS:ParkinsonsUK-UCL.
DR GO; GO:1903894; P:regulation of IRE1-mediated unfolded protein response; TAS:ParkinsonsUK-UCL.
DR GO; GO:1903897; P:regulation of PERK-mediated unfolded protein response; TAS:ParkinsonsUK-UCL.
DR GO; GO:0060904; P:regulation of protein folding in endoplasmic reticulum; TAS:BHF-UCL.
DR GO; GO:0042220; P:response to cocaine; IEA:Ensembl.
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:0021762; P:substantia nigra development; HEP:UniProtKB.
DR GO; GO:1901998; P:toxin transport; IEA:Ensembl.
DR GO; GO:0030433; P:ubiquitin-dependent ERAD pathway; IBA:GO_Central.
DR CDD; cd10241; HSPA5-like_NBD; 1.
DR DisProt; DP01938; -.
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; Acetylation; ATP-binding; Chaperone; Cytoplasm;
KW Direct protein sequencing; Endoplasmic reticulum; Host-virus interaction;
KW Hydrolase; Isopeptide bond; Methylation; Nitration; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Signal; Ubl conjugation.
FT SIGNAL 1..18
FT /evidence="ECO:0000269|PubMed:2294010,
FT ECO:0000269|PubMed:9150948"
FT CHAIN 19..654
FT /note="Endoplasmic reticulum chaperone BiP"
FT /id="PRO_0000013566"
FT REGION 1..80
FT /note="Required for interaction with KIAA1324"
FT /evidence="ECO:0000269|PubMed:26045166"
FT REGION 125..280
FT /note="Nucleotide-binding (NBD)"
FT /evidence="ECO:0000303|PubMed:28286085"
FT REGION 409..419
FT /note="Interdomain linker"
FT /evidence="ECO:0000250|UniProtKB:G3I8R9"
FT REGION 420..500
FT /note="Substrate-binding (SBD)"
FT /evidence="ECO:0000303|PubMed:28286085"
FT REGION 633..654
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 651..654
FT /note="Prevents secretion from ER"
FT /evidence="ECO:0000255"
FT BINDING 36..39
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:21526763"
FT BINDING 96
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:21526763"
FT BINDING 227..229
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:21526763"
FT BINDING 293..300
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:21526763"
FT BINDING 364..367
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:21526763"
FT MOD_RES 86
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P06761"
FT MOD_RES 125
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P20029"
FT MOD_RES 160
FT /note="3'-nitrotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P20029"
FT MOD_RES 213
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P20029"
FT MOD_RES 271
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P0DMV8"
FT MOD_RES 326
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P20029"
FT MOD_RES 353
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P20029"
FT MOD_RES 447
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P20029"
FT MOD_RES 492
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:P0DMV8"
FT MOD_RES 518
FT /note="O-AMP-threonine; alternate"
FT /evidence="ECO:0000250|UniProtKB:G3I8R9"
FT MOD_RES 518
FT /note="Phosphothreonine; alternate"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 585
FT /note="N6,N6,N6-trimethyllysine; by METTL21A; in vitro"
FT /evidence="ECO:0000269|PubMed:23349634,
FT ECO:0000269|PubMed:23921388, ECO:0007744|PubMed:24129315"
FT MOD_RES 585
FT /note="N6,N6-dimethyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 585
FT /note="N6-methyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 591
FT /note="N6-methyllysine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 643
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P20029"
FT MOD_RES 648
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P20029"
FT CROSSLNK 352
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25114211,
FT ECO:0007744|PubMed:25218447, ECO:0007744|PubMed:25755297,
FT ECO:0007744|PubMed:28112733"
FT CROSSLNK 353
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1); alternate"
FT /evidence="ECO:0007744|PubMed:25114211"
FT VARIANT 543
FT /note="N -> H (in dbSNP:rs35356639)"
FT /evidence="ECO:0000269|Ref.5"
FT /id="VAR_025815"
FT MUTAGEN 229
FT /note="T->A: Impaired ATPase activity."
FT /evidence="ECO:0000269|PubMed:26655470"
FT MUTAGEN 585
FT /note="K->R: Complete loss of in vitro methylation by
FT METTL21A."
FT /evidence="ECO:0000269|PubMed:23349634,
FT ECO:0000269|PubMed:23921388"
FT CONFLICT 297
FT /note="Missing (in Ref. 1; AAA52614 and 2; CAA61201)"
FT /evidence="ECO:0000305"
FT CONFLICT 418
FT /note="D -> H (in Ref. 1; AAA52614 and 2; CAA61201)"
FT /evidence="ECO:0000305"
FT CONFLICT 439
FT /note="R -> S (in Ref. 1; AAA52614 and 2; CAA61201)"
FT /evidence="ECO:0000305"
FT CONFLICT 447
FT /note="K -> N (in Ref. 1; AAA52614 and 2; CAA61201)"
FT /evidence="ECO:0000305"
FT STRAND 31..34
FT /evidence="ECO:0007829|PDB:5F0X"
FT STRAND 37..45
FT /evidence="ECO:0007829|PDB:5F0X"
FT STRAND 47..52
FT /evidence="ECO:0007829|PDB:5F0X"
FT STRAND 60..63
FT /evidence="ECO:0007829|PDB:5F0X"
FT STRAND 66..68
FT /evidence="ECO:0007829|PDB:5F0X"
FT STRAND 74..76
FT /evidence="ECO:0007829|PDB:5F0X"
FT HELIX 78..82
FT /evidence="ECO:0007829|PDB:5F0X"
FT HELIX 84..86
FT /evidence="ECO:0007829|PDB:6ASY"
FT HELIX 88..90
FT /evidence="ECO:0007829|PDB:5F0X"
FT STRAND 91..93
FT /evidence="ECO:0007829|PDB:6ASY"
FT HELIX 95..97
FT /evidence="ECO:0007829|PDB:5F0X"
FT TURN 98..100
FT /evidence="ECO:0007829|PDB:5F0X"
FT HELIX 106..114
FT /evidence="ECO:0007829|PDB:5F0X"
FT STRAND 116..122
FT /evidence="ECO:0007829|PDB:5F0X"
FT STRAND 125..131
FT /evidence="ECO:0007829|PDB:5F0X"
FT STRAND 137..140
FT /evidence="ECO:0007829|PDB:5F0X"
FT HELIX 142..161
FT /evidence="ECO:0007829|PDB:5F0X"
FT STRAND 167..172
FT /evidence="ECO:0007829|PDB:5F0X"
FT HELIX 178..190
FT /evidence="ECO:0007829|PDB:5F0X"
FT STRAND 194..200
FT /evidence="ECO:0007829|PDB:5F0X"
FT HELIX 201..208
FT /evidence="ECO:0007829|PDB:5F0X"
FT TURN 209..212
FT /evidence="ECO:0007829|PDB:5F0X"
FT STRAND 215..225
FT /evidence="ECO:0007829|PDB:5F0X"
FT STRAND 230..238
FT /evidence="ECO:0007829|PDB:5F0X"
FT STRAND 241..250
FT /evidence="ECO:0007829|PDB:5F0X"
FT HELIX 255..274
FT /evidence="ECO:0007829|PDB:5F0X"
FT HELIX 278..280
FT /evidence="ECO:0007829|PDB:5F0X"
FT HELIX 282..298
FT /evidence="ECO:0007829|PDB:5F0X"
FT TURN 299..301
FT /evidence="ECO:0007829|PDB:5F0X"
FT STRAND 302..313
FT /evidence="ECO:0007829|PDB:5F0X"
FT STRAND 316..323
FT /evidence="ECO:0007829|PDB:5F0X"
FT HELIX 324..337
FT /evidence="ECO:0007829|PDB:5F0X"
FT HELIX 339..348
FT /evidence="ECO:0007829|PDB:5F0X"
FT HELIX 353..355
FT /evidence="ECO:0007829|PDB:5F0X"
FT STRAND 358..363
FT /evidence="ECO:0007829|PDB:5F0X"
FT HELIX 364..367
FT /evidence="ECO:0007829|PDB:5F0X"
FT HELIX 369..378
FT /evidence="ECO:0007829|PDB:5F0X"
FT TURN 379..381
FT /evidence="ECO:0007829|PDB:5F0X"
FT TURN 390..392
FT /evidence="ECO:0007829|PDB:5F0X"
FT HELIX 393..405
FT /evidence="ECO:0007829|PDB:5F0X"
FT STRAND 415..419
FT /evidence="ECO:0007829|PDB:6ASY"
FT STRAND 424..428
FT /evidence="ECO:0007829|PDB:6ASY"
FT TURN 429..431
FT /evidence="ECO:0007829|PDB:5E85"
FT STRAND 433..437
FT /evidence="ECO:0007829|PDB:6ASY"
FT STRAND 442..451
FT /evidence="ECO:0007829|PDB:6ASY"
FT STRAND 461..468
FT /evidence="ECO:0007829|PDB:6ASY"
FT HELIX 473..475
FT /evidence="ECO:0007829|PDB:6ASY"
FT STRAND 476..484
FT /evidence="ECO:0007829|PDB:6ASY"
FT STRAND 491..493
FT /evidence="ECO:0007829|PDB:6ASY"
FT STRAND 497..503
FT /evidence="ECO:0007829|PDB:6ASY"
FT STRAND 509..515
FT /evidence="ECO:0007829|PDB:6ASY"
FT TURN 516..518
FT /evidence="ECO:0007829|PDB:6ASY"
FT STRAND 524..526
FT /evidence="ECO:0007829|PDB:7N1R"
FT TURN 529..531
FT /evidence="ECO:0007829|PDB:7N1R"
FT HELIX 535..576
FT /evidence="ECO:0007829|PDB:6ASY"
FT TURN 579..581
FT /evidence="ECO:0007829|PDB:6ASY"
FT HELIX 582..585
FT /evidence="ECO:0007829|PDB:6ASY"
FT HELIX 588..607
FT /evidence="ECO:0007829|PDB:6ASY"
FT HELIX 613..631
FT /evidence="ECO:0007829|PDB:6ASY"
SQ SEQUENCE 654 AA; 72333 MW; 59B7D8D85BC32A00 CRC64;
MKLSLVAAML LLLSAARAEE EDKKEDVGTV VGIDLGTTYS CVGVFKNGRV EIIANDQGNR
ITPSYVAFTP EGERLIGDAA KNQLTSNPEN TVFDAKRLIG RTWNDPSVQQ DIKFLPFKVV
EKKTKPYIQV DIGGGQTKTF APEEISAMVL TKMKETAEAY LGKKVTHAVV TVPAYFNDAQ
RQATKDAGTI AGLNVMRIIN EPTAAAIAYG LDKREGEKNI LVFDLGGGTF DVSLLTIDNG
VFEVVATNGD THLGGEDFDQ RVMEHFIKLY KKKTGKDVRK DNRAVQKLRR EVEKAKRALS
SQHQARIEIE SFYEGEDFSE TLTRAKFEEL NMDLFRSTMK PVQKVLEDSD LKKSDIDEIV
LVGGSTRIPK IQQLVKEFFN GKEPSRGINP DEAVAYGAAV QAGVLSGDQD TGDLVLLDVC
PLTLGIETVG GVMTKLIPRN TVVPTKKSQI FSTASDNQPT VTIKVYEGER PLTKDNHLLG
TFDLTGIPPA PRGVPQIEVT FEIDVNGILR VTAEDKGTGN KNKITITNDQ NRLTPEEIER
MVNDAEKFAE EDKKLKERID TRNELESYAY SLKNQIGDKE KLGGKLSSED KETMEKAVEE
KIEWLESHQD ADIEDFKAKK KELEEIVQPI ISKLYGSAGP PPTGEEDTAE KDEL
