CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-003869
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 78 kDa glucose-regulated protein 
Protein Synonyms/Alias
 GRP-78; Endoplasmic reticulum lumenal Ca(2+)-binding protein grp78; Heat shock 70 kDa protein 5; Immunoglobulin heavy chain-binding protein; BiP 
Gene Name
 HSPA5 
Gene Synonyms/Alias
 GRP78 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
81RLIGDAAKNQLTSNPacetylation[1]
81RLIGDAAKNQLTSNPubiquitination[2, 3, 4, 5, 6, 7]
96ENTVFDAKRLIGRTWubiquitination[2, 3, 4, 5, 6, 7, 8]
113PSVQQDIKFLPFKVVubiquitination[2, 3, 5, 6, 8, 9, 10]
118DIKFLPFKVVEKKTKacetylation[11]
118DIKFLPFKVVEKKTKubiquitination[2, 3, 5, 6, 9, 10]
122LPFKVVEKKTKPYIQacetylation[11]
122LPFKVVEKKTKPYIQubiquitination[5]
123PFKVVEKKTKPYIQVacetylation[11]
123PFKVVEKKTKPYIQVubiquitination[3]
125KVVEKKTKPYIQVDIacetylation[11]
125KVVEKKTKPYIQVDIubiquitination[2, 3, 5, 6]
138DIGGGQTKTFAPEEIacetylation[11]
138DIGGGQTKTFAPEEIubiquitination[2, 3]
152ISAMVLTKMKETAEAacetylation[11]
152ISAMVLTKMKETAEAubiquitination[2, 3, 5, 6]
154AMVLTKMKETAEAYLacetylation[11]
154AMVLTKMKETAEAYLubiquitination[5]
163TAEAYLGKKVTHAVVubiquitination[2]
164AEAYLGKKVTHAVVTubiquitination[2, 5]
185DAQRQATKDAGTIAGubiquitination[2, 3, 5, 6, 10]
213AIAYGLDKREGEKNIubiquitination[2, 3, 5, 6, 7, 9, 10]
268RVMEHFIKLYKKKTGacetylation[12, 13]
268RVMEHFIKLYKKKTGubiquitination[9, 10]
326SETLTRAKFEELNMDubiquitination[2, 3, 5, 6, 8, 9, 10]
340DLFRSTMKPVQKVLEubiquitination[2]
344STMKPVQKVLEDSDLacetylation[1]
344STMKPVQKVLEDSDLubiquitination[5, 10]
352VLEDSDLKKSDIDEIacetylation[11]
352VLEDSDLKKSDIDEIubiquitination[2]
353LEDSDLKKSDIDEIVacetylation[11]
353LEDSDLKKSDIDEIVubiquitination[2, 5]
370GGSTRIPKIQQLVKEubiquitination[2, 5, 9, 10]
376PKIQQLVKEFFNGKEacetylation[11]
376PKIQQLVKEFFNGKEubiquitination[2, 9, 10]
382VKEFFNGKEPSRGINubiquitination[5]
447NTVVPTKKSQIFSTAubiquitination[5]
464NQPTVTIKVYEGERPubiquitination[2]
523KGTGNKNKITITNDQubiquitination[2, 6, 9, 10]
547RMVNDAEKFAEEDKKacetylation[1]
547RMVNDAEKFAEEDKKubiquitination[2, 9]
573ESYAYSLKNQIGDKEubiquitination[2, 6, 9, 10]
585DKEKLGGKLSSEDKEacetylation[14]
585DKEKLGGKLSSEDKEmethylation[15]
601MEKAVEEKIEWLESHubiquitination[2, 9]
633IVQPIISKLYGSAGPacetylation[11]
Reference
 [1] Proteomic investigations of lysine acetylation identify diverse substrates of mitochondrial deacetylase sirt3.
 Sol EM, Wagner SA, Weinert BT, Kumar A, Kim HS, Deng CX, Choudhary C.
 PLoS One. 2012;7(12):e50545. [PMID: 23236377]
 [2] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [3] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
 [4] Ubiquitin ligase substrate identification through quantitative proteomics at both the protein and peptide levels.
 Lee KA, Hammerle LP, Andrews PS, Stokes MP, Mustelin T, Silva JC, Black RA, Doedens JR.
 J Biol Chem. 2011 Dec 2;286(48):41530-8. [PMID: 21987572]
 [5] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [6] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [7] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [8] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
 [9] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [10] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
 [11] Treatment with panobinostat induces glucose-regulated protein 78 acetylation and endoplasmic reticulum stress in breast cancer cells.
 Rao R, Nalluri S, Kolhe R, Yang Y, Fiskus W, Chen J, Ha K, Buckley KM, Balusu R, Coothankandaswamy V, Joshi A, Atadja P, Bhalla KN.
 Mol Cancer Ther. 2010 Apr;9(4):942-52. [PMID: 20371724]
 [12] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
 [13] Proteomic investigations reveal a role for RNA processing factor THRAP3 in the DNA damage response.
 Beli P, Lukashchuk N, Wagner SA, Weinert BT, Olsen JV, Baskcomb L, Mann M, Jackson SP, Choudhary C.
 Mol Cell. 2012 Apr 27;46(2):212-25. [PMID: 22424773]
 [14] Activation of the unfolded protein response contributes toward the antitumor activity of vorinostat.
 Kahali S, Sarcar B, Fang B, Williams ES, Koomen JM, Tofilon PJ, Chinnaiyan P.
 Neoplasia. 2010 Jan;12(1):80-6. [PMID: 20072656]
 [15] Mass spectrometry-based identification and characterisation of lysine and arginine methylation in the human proteome.
 Bremang M, Cuomo A, Agresta AM, Stugiewicz M, Spadotto V, Bonaldi T.
 Mol Biosyst. 2013 Jul 30;9(9):2231-47. [PMID: 23748837] 
Functional Description
 Probably plays a role in facilitating the assembly of multimeric protein complexes inside the ER. 
Sequence Annotation
 MOTIF 651 654 Prevents secretion from ER.
 MOD_RES 160 160 Nitrated tyrosine (By similarity).
 MOD_RES 166 166 Phosphothreonine (By similarity).
 MOD_RES 518 518 Phosphothreonine.
 MOD_RES 571 571 Phosphoserine (By similarity).
 MOD_RES 585 585 N6,N6,N6-trimethyllysine; by METTL21A; in  
Keyword
 3D-structure; ATP-binding; Complete proteome; Cytoplasm; Direct protein sequencing; Endoplasmic reticulum; Methylation; Nitration; Nucleotide-binding; Phosphoprotein; Polymorphism; Reference proteome; Signal. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 654 AA 
Protein Sequence
MKLSLVAAML LLLSAARAEE EDKKEDVGTV VGIDLGTTYS CVGVFKNGRV EIIANDQGNR 60
ITPSYVAFTP EGERLIGDAA KNQLTSNPEN TVFDAKRLIG RTWNDPSVQQ DIKFLPFKVV 120
EKKTKPYIQV DIGGGQTKTF APEEISAMVL TKMKETAEAY LGKKVTHAVV TVPAYFNDAQ 180
RQATKDAGTI AGLNVMRIIN EPTAAAIAYG LDKREGEKNI LVFDLGGGTF DVSLLTIDNG 240
VFEVVATNGD THLGGEDFDQ RVMEHFIKLY KKKTGKDVRK DNRAVQKLRR EVEKAKRALS 300
SQHQARIEIE SFYEGEDFSE TLTRAKFEEL NMDLFRSTMK PVQKVLEDSD LKKSDIDEIV 360
LVGGSTRIPK IQQLVKEFFN GKEPSRGINP DEAVAYGAAV QAGVLSGDQD TGDLVLLDVC 420
PLTLGIETVG GVMTKLIPRN TVVPTKKSQI FSTASDNQPT VTIKVYEGER PLTKDNHLLG 480
TFDLTGIPPA PRGVPQIEVT FEIDVNGILR VTAEDKGTGN KNKITITNDQ NRLTPEEIER 540
MVNDAEKFAE EDKKLKERID TRNELESYAY SLKNQIGDKE KLGGKLSSED KETMEKAVEE 600
KIEWLESHQD ADIEDFKAKK KELEEIVQPI ISKLYGSAGP PPTGEEDTAE KDEL 654 
Gene Ontology
 GO:0009986; C:cell surface; IDA:UniProtKB.
 GO:0034663; C:endoplasmic reticulum chaperone complex; IDA:UniProtKB.
 GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
 GO:0005793; C:endoplasmic reticulum-Golgi intermediate compartment; IDA:UniProtKB.
 GO:0030176; C:integral to endoplasmic reticulum membrane; IDA:BHF-UCL.
 GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
 GO:0030496; C:midbody; IDA:UniProtKB.
 GO:0005634; C:nucleus; IMP:UniProtKB.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0016887; F:ATPase activity; ISS:UniProtKB.
 GO:0005509; F:calcium ion binding; TAS:UniProtKB.
 GO:0051087; F:chaperone binding; TAS:BHF-UCL.
 GO:0051787; F:misfolded protein binding; IDA:UniProtKB.
 GO:0030674; F:protein binding, bridging; NAS:UniProtKB.
 GO:0043022; F:ribosome binding; IEA:Compara.
 GO:0051082; F:unfolded protein binding; TAS:UniProtKB.
 GO:0006987; P:activation of signaling protein activity involved in unfolded protein response; TAS:Reactome.
 GO:0042149; P:cellular response to glucose starvation; IDA:UniProtKB.
 GO:0021680; P:cerebellar Purkinje cell layer development; IEA:Compara.
 GO:0021589; P:cerebellum structural organization; IEA:Compara.
 GO:0006983; P:ER overload response; IEA:Compara.
 GO:0030433; P:ER-associated protein catabolic process; TAS:BHF-UCL.
 GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
 GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; IEA:Compara.
 GO:0030168; P:platelet activation; TAS:Reactome.
 GO:0002576; P:platelet degranulation; TAS:Reactome.
 GO:0031398; P:positive regulation of protein ubiquitination; IEA:Compara.
 GO:0060904; P:regulation of protein folding in endoplasmic reticulum; TAS:BHF-UCL. 
Interpro
 IPR018181; Heat_shock_70_CS.
 IPR013126; Hsp_70_fam. 
Pfam
 PF00012; HSP70 
SMART
  
PROSITE
 PS00014; ER_TARGET
 PS00297; HSP70_1
 PS00329; HSP70_2
 PS01036; HSP70_3 
PRINTS
 PR00301; HEATSHOCK70.