78 kDa glucose-regulated protein

Details

Name
78 kDa glucose-regulated protein
Synonyms
  • BiP
  • Endoplasmic reticulum lumenal Ca(2+)-binding protein grp78
  • GRP-78
  • GRP78
  • Heat shock 70 kDa protein 5
  • Immunoglobulin heavy chain-binding protein
Gene Name
HSPA5
Organism
Humans
Amino acid sequence
>lcl|BSEQ0019062|78 kDa glucose-regulated protein
MKLSLVAAMLLLLSAARAEEEDKKEDVGTVVGIDLGTTYSCVGVFKNGRVEIIANDQGNR
ITPSYVAFTPEGERLIGDAAKNQLTSNPENTVFDAKRLIGRTWNDPSVQQDIKFLPFKVV
EKKTKPYIQVDIGGGQTKTFAPEEISAMVLTKMKETAEAYLGKKVTHAVVTVPAYFNDAQ
RQATKDAGTIAGLNVMRIINEPTAAAIAYGLDKREGEKNILVFDLGGGTFDVSLLTIDNG
VFEVVATNGDTHLGGEDFDQRVMEHFIKLYKKKTGKDVRKDNRAVQKLRREVEKAKRALS
SQHQARIEIESFYEGEDFSETLTRAKFEELNMDLFRSTMKPVQKVLEDSDLKKSDIDEIV
LVGGSTRIPKIQQLVKEFFNGKEPSRGINPDEAVAYGAAVQAGVLSGDQDTGDLVLLDVC
PLTLGIETVGGVMTKLIPRNTVVPTKKSQIFSTASDNQPTVTIKVYEGERPLTKDNHLLG
TFDLTGIPPAPRGVPQIEVTFEIDVNGILRVTAEDKGTGNKNKITITNDQNRLTPEEIER
MVNDAEKFAEEDKKLKERIDTRNELESYAYSLKNQIGDKEKLGGKLSSEDKETMEKAVEE
KIEWLESHQDADIEDFKAKKKELEEIVQPIISKLYGSAGPPPTGEEDTAEKDEL
Number of residues
654
Molecular Weight
72332.425
Theoretical pI
4.8
GO Classification
Functions
ATP binding / ATPase activity / calcium ion binding / chaperone binding / enzyme binding / glycoprotein binding / misfolded protein binding / protein domain specific binding / ribosome binding / ubiquitin protein ligase binding / unfolded protein binding
Processes
activation of signaling protein activity involved in unfolded protein response / ATF6-mediated unfolded protein response / blood coagulation / cellular protein metabolic process / cellular response to antibiotic / cellular response to glucose starvation / cellular response to interleukin-4 / cerebellar Purkinje cell layer development / cerebellum structural organization / endoplasmic reticulum unfolded protein response / ER overload response / ER-associated ubiquitin-dependent protein catabolic process / IRE1-mediated unfolded protein response / maintenance of protein localization in endoplasmic reticulum / negative regulation of apoptotic process / negative regulation of protein homodimerization activity / negative regulation of transforming growth factor beta receptor signaling pathway / PERK-mediated unfolded protein response / platelet activation / platelet degranulation / positive regulation of cell migration / positive regulation of protein ubiquitination / positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress / protein folding in endoplasmic reticulum / regulation of ATF6-mediated unfolded protein response / regulation of IRE1-mediated unfolded protein response / regulation of PERK-mediated unfolded protein response / regulation of protein folding in endoplasmic reticulum / substantia nigra development / toxin transport
Components
cell surface / endoplasmic reticulum / endoplasmic reticulum chaperone complex / endoplasmic reticulum lumen / endoplasmic reticulum membrane / endoplasmic reticulum-Golgi intermediate compartment / extracellular exosome / focal adhesion / integral component of endoplasmic reticulum membrane / melanosome / membrane / midbody / mitochondrion / myelin sheath / nucleus / plasma membrane / smooth endoplasmic reticulum
General Function
Unfolded protein binding
Specific Function
Probably plays a role in facilitating the assembly of multimeric protein complexes inside the endoplasmic reticulum. Involved in the correct folding of proteins and degradation of misfolded proteins via its interaction with DNAJC10, probably to facilitate the release of DNAJC10 from its substrate.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Endoplasmic reticulum lumen
Gene sequence
>lcl|BSEQ0019063|78 kDa glucose-regulated protein (HSPA5)
ATGAAGCTCTCCCTGGTGGCCGCGATGCTGCTGCTGCTCAGCGCGGCGCGGGCCGAGGAG
GAGGACAAGAAGGAGGACGTGGGCACGGTGGTCGGCATCGACCTGGGGACCACCTACTCC
TGCGTCGGCGTGTTCAAGAACGGCCGCGTGGAGATCATCGCCAACGATCAGGGCAACCGC
ATCACGCCGTCCTATGTCGCCTTCACTCCTGAAGGGGAACGTCTGATTGGCGATGCCGCC
AAGAACCAGCTCACCTCCAACCCCGAGAACACGGTCTTTGACGCCAAGCGGCTCATCGGC
CGCACGTGGAATGACCCGTCTGTGCAGCAGGACATCAAGTTCTTGCCGTTCAAGGTGGTT
GAAAAGAAAACTAAACCATACATTCAAGTTGATATTGGAGGTGGGCAAACAAAGACATTT
GCTCCTGAAGAAATTTCTGCCATGGTTCTCACTAAAATGAAAGAAACCGCTGAGGCTTAT
TTGGGAAAGAAGGTTACCCATGCAGTTGTTACTGTACCAGCCTATTTTAATGATGCCCAA
CGCCAAGCAACCAAAGACGCTGGAACTATTGCTGGCCTAAATGTTATGAGGATCATCAAC
GAGCCTACGGCAGCTGCTATTGCTTATGGCCTGGATAAGAGGGAGGGGGAGAAGAACATC
CTGGTGTTTGACCTGGGTGGCGGAACCTTCGATGTGTCTCTTCTCACCATTGACAATGGT
GTCTTCGAAGTTGTGGCCACTAATGGAGATACTCATCTGGGTGGAGAAGACTTTGACCAG
CGTGTCATGGAACACTTCATCAAACTGTACAAAAAGAAGACGGGCAAAGATGTCAGGAAA
GACAATAGAGCTGTGCAGAAACTCCGGCGCGAGGTAGAAAAGGCCAAACGGGCCCTGTCT
TCTCAGCATCAAGCAAGAATTGAAATTGAGTCCTTCTATGAAGGAGAAGACTTTTCTGAG
ACCCTGACTCGGGCCAAATTTGAAGAGCTCAACATGGATCTGTTCCGGTCTACTATGAAG
CCCGTCCAGAAAGTGTTGGAAGATTCTGATTTGAAGAAGTCTGATATTGATGAAATTGTT
CTTGTTGGTGGCTCGACTCGAATTCCAAAGATTCAGCAACTGGTTAAAGAGTTCTTCAAT
GGCAAGGAACCATCCCGTGGCATAAACCCAGATGAAGCTGTAGCGTATGGTGCTGCTGTC
CAGGCTGGTGTGCTCTCTGGTGATCAAGATACAGGTGACCTGGTACTGCTTGATGTATGT
CCCCTTACACTTGGTATTGAAACTGTGGGAGGTGTCATGACCAAACTGATTCCAAGGAAC
ACAGTGGTGCCTACCAAGAAGTCTCAGATCTTTTCTACAGCTTCTGATAATCAACCAACT
GTTACAATCAAGGTCTATGAAGGTGAAAGACCCCTGACAAAAGACAATCATCTTCTGGGT
ACATTTGATCTGACTGGAATTCCTCCTGCTCCTCGTGGGGTCCCACAGATTGAAGTCACC
TTTGAGATAGATGTGAATGGTATTCTTCGAGTGACAGCTGAAGACAAGGGTACAGGGAAC
AAAAATAAGATCACAATCACCAATGACCAGAATCGCCTGACACCTGAAGAAATCGAAAGG
ATGGTTAATGATGCTGAGAAGTTTGCTGAGGAAGACAAAAAGCTCAAGGAGCGCATTGAT
ACTAGAAATGAGTTGGAAAGCTATGCCTATTCTCTAAAGAATCAGATTGGAGATAAAGAA
AAGCTGGGAGGTAAACTTTCCTCTGAAGATAAGGAGACCATGGAAAAAGCTGTAGAAGAA
AAGATTGAATGGCTGGAAAGCCACCAAGATGCTGACATTGAAGACTTCAAAGCTAAGAAG
AAGGAACTGGAAGAAATTGTTCAACCAATTATCAGCAAACTCTATGGAAGTGCAGGCCCT
CCCCCAACTGGTGAAGAGGATACAGCAGAAAAAGATGAGTTGTAG
Chromosome Location
9
Locus
9q33-q34.1
External Identifiers
ResourceLink
UniProtKB IDP11021
UniProtKB Entry NameGRP78_HUMAN
GenBank Protein ID386758
GenBank Gene IDM19645
GenAtlas IDHSPA5
HGNC IDHGNC:5238
General References
  1. Ting J, Lee AS: Human gene encoding the 78,000-dalton glucose-regulated protein and its pseudogene: structure, conservation, and regulation. DNA. 1988 May;7(4):275-86. [PubMed:2840249]
  2. Humphray SJ, Oliver K, Hunt AR, Plumb RW, Loveland JE, Howe KL, Andrews TD, Searle S, Hunt SE, Scott CE, Jones MC, Ainscough R, Almeida JP, Ambrose KD, Ashwell RI, Babbage AK, Babbage S, Bagguley CL, Bailey J, Banerjee R, Barker DJ, Barlow KF, Bates K, Beasley H, Beasley O, Bird CP, Bray-Allen S, Brown AJ, Brown JY, Burford D, Burrill W, Burton J, Carder C, Carter NP, Chapman JC, Chen Y, Clarke G, Clark SY, Clee CM, Clegg S, Collier RE, Corby N, Crosier M, Cummings AT, Davies J, Dhami P, Dunn M, Dutta I, Dyer LW, Earthrowl ME, Faulkner L, Fleming CJ, Frankish A, Frankland JA, French L, Fricker DG, Garner P, Garnett J, Ghori J, Gilbert JG, Glison C, Grafham DV, Gribble S, Griffiths C, Griffiths-Jones S, Grocock R, Guy J, Hall RE, Hammond S, Harley JL, Harrison ES, Hart EA, Heath PD, Henderson CD, Hopkins BL, Howard PJ, Howden PJ, Huckle E, Johnson C, Johnson D, Joy AA, Kay M, Keenan S, Kershaw JK, Kimberley AM, King A, Knights A, Laird GK, Langford C, Lawlor S, Leongamornlert DA, Leversha M, Lloyd C, Lloyd DM, Lovell J, Martin S, Mashreghi-Mohammadi M, Matthews L, McLaren S, McLay KE, McMurray A, Milne S, Nickerson T, Nisbett J, Nordsiek G, Pearce AV, Peck AI, Porter KM, Pandian R, Pelan S, Phillimore B, Povey S, Ramsey Y, Rand V, Scharfe M, Sehra HK, Shownkeen R, Sims SK, Skuce CD, Smith M, Steward CA, Swarbreck D, Sycamore N, Tester J, Thorpe A, Tracey A, Tromans A, Thomas DW, Wall M, Wallis JM, West AP, Whitehead SL, Willey DL, Williams SA, Wilming L, Wray PW, Young L, Ashurst JL, Coulson A, Blocker H, Durbin R, Sulston JE, Hubbard T, Jackson MJ, Bentley DR, Beck S, Rogers J, Dunham I: DNA sequence and analysis of human chromosome 9. Nature. 2004 May 27;429(6990):369-74. [PubMed:15164053]
  3. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334]
  4. Chao CC, Lin-Chao S: A direct-repeat sequence of the human BiP gene is required for A23187-mediated inducibility and an inducible nuclear factor binding. Nucleic Acids Res. 1992 Dec 25;20(24):6481-5. [PubMed:1480470]
  5. Corrigall VM, Bodman-Smith MD, Fife MS, Canas B, Myers LK, Wooley P, Soh C, Staines NA, Pappin DJ, Berlo SE, van Eden W, van Der Zee R, Lanchbury JS, Panayi GS: The human endoplasmic reticulum molecular chaperone BiP is an autoantigen for rheumatoid arthritis and prevents the induction of experimental arthritis. J Immunol. 2001 Feb 1;166(3):1492-8. [PubMed:11160188]
  6. Rasmussen RK, Ji H, Eddes JS, Moritz RL, Reid GE, Simpson RJ, Dorow DS: Two-dimensional electrophoretic analysis of human breast carcinoma proteins: mapping of proteins that bind to the SH3 domain of mixed lineage kinase MLK2. Electrophoresis. 1997 Mar-Apr;18(3-4):588-98. [PubMed:9150946]
  7. Dana RC, Welch WJ, Deftos LJ: Heat shock proteins bind calcitonin. Endocrinology. 1990 Jan;126(1):672-4. [PubMed:2294010]
  8. Ji H, Reid GE, Moritz RL, Eddes JS, Burgess AW, Simpson RJ: A two-dimensional gel database of human colon carcinoma proteins. Electrophoresis. 1997 Mar-Apr;18(3-4):605-13. [PubMed:9150948]
  9. Cloutier P, Lavallee-Adam M, Faubert D, Blanchette M, Coulombe B: A newly uncovered group of distantly related lysine methyltransferases preferentially interact with molecular chaperones to regulate their activity. PLoS Genet. 2013;9(1):e1003210. doi: 10.1371/journal.pgen.1003210. Epub 2013 Jan 17. [PubMed:23349634]
  10. Meunier L, Usherwood YK, Chung KT, Hendershot LM: A subset of chaperones and folding enzymes form multiprotein complexes in endoplasmic reticulum to bind nascent proteins. Mol Biol Cell. 2002 Dec;13(12):4456-69. [PubMed:12475965]
  11. Purcell AW, Todd A, Kinoshita G, Lynch TA, Keech CL, Gething MJ, Gordon TP: Association of stress proteins with autoantigens: a possible mechanism for triggering autoimmunity? Clin Exp Immunol. 2003 May;132(2):193-200. [PubMed:12699405]
  12. Cunnea PM, Miranda-Vizuete A, Bertoli G, Simmen T, Damdimopoulos AE, Hermann S, Leinonen S, Huikko MP, Gustafsson JA, Sitia R, Spyrou G: ERdj5, an endoplasmic reticulum (ER)-resident protein containing DnaJ and thioredoxin domains, is expressed in secretory cells or following ER stress. J Biol Chem. 2003 Jan 10;278(2):1059-66. Epub 2002 Oct 30. [PubMed:12411443]
  13. Basrur V, Yang F, Kushimoto T, Higashimoto Y, Yasumoto K, Valencia J, Muller J, Vieira WD, Watabe H, Shabanowitz J, Hearing VJ, Hunt DF, Appella E: Proteomic analysis of early melanosomes: identification of novel melanosomal proteins. J Proteome Res. 2003 Jan-Feb;2(1):69-79. [PubMed:12643545]
  14. Chi A, Valencia JC, Hu ZZ, Watabe H, Yamaguchi H, Mangini NJ, Huang H, Canfield VA, Cheng KC, Yang F, Abe R, Yamagishi S, Shabanowitz J, Hearing VJ, Wu C, Appella E, Hunt DF: Proteomic and bioinformatic characterization of the biogenesis and function of melanosomes. J Proteome Res. 2006 Nov;5(11):3135-44. [PubMed:17081065]
  15. Hosokawa N, Wada I, Nagasawa K, Moriyama T, Okawa K, Nagata K: Human XTP3-B forms an endoplasmic reticulum quality control scaffold with the HRD1-SEL1L ubiquitin ligase complex and BiP. J Biol Chem. 2008 Jul 25;283(30):20914-24. doi: 10.1074/jbc.M709336200. Epub 2008 May 23. [PubMed:18502753]
  16. Christianson JC, Shaler TA, Tyler RE, Kopito RR: OS-9 and GRP94 deliver mutant alpha1-antitrypsin to the Hrd1-SEL1L ubiquitin ligase complex for ERAD. Nat Cell Biol. 2008 Mar;10(3):272-82. doi: 10.1038/ncb1689. Epub 2008 Feb 10. [PubMed:18264092]
  17. Olsen JV, Vermeulen M, Santamaria A, Kumar C, Miller ML, Jensen LJ, Gnad F, Cox J, Jensen TS, Nigg EA, Brunak S, Mann M: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal. 2010 Jan 12;3(104):ra3. doi: 10.1126/scisignal.2000475. [PubMed:20068231]
  18. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [PubMed:21269460]
  19. Rosenow A, Noben JP, Jocken J, Kallendrusch S, Fischer-Posovszky P, Mariman EC, Renes J: Resveratrol-induced changes of the human adipocyte secretion profile. J Proteome Res. 2012 Sep 7;11(9):4733-43. doi: 10.1021/pr300539b. Epub 2012 Aug 27. [PubMed:22905912]
  20. Jakobsson ME, Moen A, Bousset L, Egge-Jacobsen W, Kernstock S, Melki R, Falnes PO: Identification and characterization of a novel human methyltransferase modulating Hsp70 protein function through lysine methylation. J Biol Chem. 2013 Sep 27;288(39):27752-63. doi: 10.1074/jbc.M113.483248. Epub 2013 Aug 6. [PubMed:23921388]
  21. Evensen NA, Kuscu C, Nguyen HL, Zarrabi K, Dufour A, Kadam P, Hu YJ, Pulkoski-Gross A, Bahou WF, Zucker S, Cao J: Unraveling the role of KIAA1199, a novel endoplasmic reticulum protein, in cancer cell migration. J Natl Cancer Inst. 2013 Sep 18;105(18):1402-16. doi: 10.1093/jnci/djt224. Epub 2013 Aug 29. [PubMed:23990668]
  22. Oka OB, Pringle MA, Schopp IM, Braakman I, Bulleid NJ: ERdj5 is the ER reductase that catalyzes the removal of non-native disulfides and correct folding of the LDL receptor. Mol Cell. 2013 Jun 27;50(6):793-804. doi: 10.1016/j.molcel.2013.05.014. Epub 2013 Jun 13. [PubMed:23769672]
  23. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [PubMed:24275569]
  24. Hendriks IA, D'Souza RC, Yang B, Verlaan-de Vries M, Mann M, Vertegaal AC: Uncovering global SUMOylation signaling networks in a site-specific manner. Nat Struct Mol Biol. 2014 Oct;21(10):927-36. doi: 10.1038/nsmb.2890. Epub 2014 Sep 14. [PubMed:25218447]
  25. Vaca Jacome AS, Rabilloud T, Schaeffer-Reiss C, Rompais M, Ayoub D, Lane L, Bairoch A, Van Dorsselaer A, Carapito C: N-terminome analysis of the human mitochondrial proteome. Proteomics. 2015 Jul;15(14):2519-24. doi: 10.1002/pmic.201400617. Epub 2015 Jun 8. [PubMed:25944712]
  26. Wisniewska M, Karlberg T, Lehtio L, Johansson I, Kotenyova T, Moche M, Schuler H: Crystal structures of the ATPase domains of four human Hsp70 isoforms: HSPA1L/Hsp70-hom, HSPA2/Hsp70-2, HSPA6/Hsp70B', and HSPA5/BiP/GRP78. PLoS One. 2010 Jan 11;5(1):e8625. doi: 10.1371/journal.pone.0008625. [PubMed:20072699]
  27. Macias AT, Williamson DS, Allen N, Borgognoni J, Clay A, Daniels Z, Dokurno P, Drysdale MJ, Francis GL, Graham CJ, Howes R, Matassova N, Murray JB, Parsons R, Shaw T, Surgenor AE, Terry L, Wang Y, Wood M, Massey AJ: Adenosine-derived inhibitors of 78 kDa glucose regulated protein (Grp78) ATPase: insights into isoform selectivity. J Med Chem. 2011 Jun 23;54(12):4034-41. doi: 10.1021/jm101625x. Epub 2011 May 20. [PubMed:21526763]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00025Antihemophilic factor, human recombinantapproved, investigationalunknownchaperoneDetails
DB00945Acetylsalicylic acidapproved, vet_approvedunknownbindingDetails
DB09130Copperapproved, investigationalunknownDetails
DB13998Lonoctocog alfaapproved, investigationalunknownchaperoneDetails
DB13999Moroctocog alfaapprovedunknownchaperoneDetails