CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-007481
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Glycine--tRNA ligase 
Protein Synonyms/Alias
 Diadenosine tetraphosphate synthetase; AP-4-A synthetase; Glycyl-tRNA synthetase; GlyRS 
Gene Name
 GARS 
Gene Synonyms/Alias
  
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
82GDLVRKLKEDKAPQVubiquitination[1, 2, 3, 4]
93APQVDVDKAVAELKAacetylation[5]
93APQVDVDKAVAELKAubiquitination[1, 6]
99DKAVAELKARKRVLEacetylation[4, 5, 7]
99DKAVAELKARKRVLEubiquitination[1, 3, 4, 6, 8]
108RKRVLEAKELALQPKacetylation[4, 5]
108RKRVLEAKELALQPKubiquitination[1, 3, 4, 6, 8, 9, 10]
115KELALQPKDDIVDRAubiquitination[3]
123DDIVDRAKMEDTLKRubiquitination[3]
129AKMEDTLKRRFFYDQubiquitination[3, 4]
197KTSGHVDKFADFMVKubiquitination[1, 2, 3, 4, 6, 8, 9, 10]
204KFADFMVKDVKNGECacetylation[5, 7, 11]
204KFADFMVKDVKNGECubiquitination[1, 3, 4, 8]
207DFMVKDVKNGECFRAubiquitination[3, 4]
219FRADHLLKAHLQKLMacetylation[5, 7, 11]
219FRADHLLKAHLQKLMubiquitination[3]
224LLKAHLQKLMSDKKCacetylation[5]
309QGIFLNFKRLLEFNQubiquitination[3, 6, 8, 12]
318LLEFNQGKLPFAAAQubiquitination[1, 2, 3, 4, 8, 9, 10]
379HLYLYSAKAQVSGQSubiquitination[1, 3, 4, 6, 9, 10]
419RIYLYLTKVGISPDKubiquitination[1, 3, 4, 6, 8, 9, 10]
426KVGISPDKLRFRQHMubiquitination[2, 3]
484KVPLVAEKPLKEPKTacetylation[5]
487LVAEKPLKEPKTVNVubiquitination[3, 4]
501VVQFEPSKGAIGKAYacetylation[5, 7, 11]
501VVQFEPSKGAIGKAYubiquitination[1, 3, 4, 8]
506PSKGAIGKAYKKDAKubiquitination[3]
547FTIETEGKTFQLTKDubiquitination[1, 6]
553GKTFQLTKDMINVKRubiquitination[6]
563INVKRFQKTLYVEEVubiquitination[1, 3, 8, 9, 10]
646TRHGVSHKVDDSSGSubiquitination[1, 3, 4, 12]
733FEGQETGKKETIEE*acetylation[5]
733FEGQETGKKETIEE*ubiquitination[1, 3, 8]
734EGQETGKKETIEE**ubiquitination[1, 3]
Reference
 [1] 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]
 [2] 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]
 [3] 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]
 [4] 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]
 [5] 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]
 [6] 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]
 [7] 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]
 [8] 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]
 [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] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [11] 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]
 [12] 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] 
Functional Description
 Catalyzes the attachment of glycine to tRNA(Gly). Is also able produce diadenosine tetraphosphate (Ap4A), a universal pleiotropic signaling molecule needed for cell regulation pathways, by direct condensation of 2 ATPs. 
Sequence Annotation
 DOMAIN 63 119 WHEP-TRS.
 NP_BIND 331 333 ATP.
 NP_BIND 341 346 ATP.
 NP_BIND 457 458 ATP.
 NP_BIND 580 583 ATP.
 REGION 346 350 Substrate binding.
 REGION 576 580 Substrate binding.
 BINDING 213 213 Substrate.
 BINDING 299 299 Substrate.
 BINDING 435 435 Substrate; via carbonyl oxygen.
 MOD_RES 204 204 N6-acetyllysine.
 MOD_RES 453 453 Phosphotyrosine (By similarity).
 MOD_RES 501 501 N6-acetyllysine.  
Keyword
 3D-structure; Acetylation; Aminoacyl-tRNA synthetase; ATP-binding; Charcot-Marie-Tooth disease; Complete proteome; Cytoplasm; Disease mutation; Ligase; Mitochondrion; Neurodegeneration; Neuropathy; Nucleotide-binding; Phosphoprotein; Protein biosynthesis; Reference proteome. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 739 AA 
Protein Sequence
MPSPRPVLLR GARAALLLLL PPRLLARPSL LLRRSLSAAS CPPISLPAAA SRSSMDGAGA 60
EEVLAPLRLA VRQQGDLVRK LKEDKAPQVD VDKAVAELKA RKRVLEAKEL ALQPKDDIVD 120
RAKMEDTLKR RFFYDQAFAI YGGVSGLYDF GPVGCALKNN IIQTWRQHFI QEEQILEIDC 180
TMLTPEPVLK TSGHVDKFAD FMVKDVKNGE CFRADHLLKA HLQKLMSDKK CSVEKKSEME 240
SVLAQLDNYG QQELADLFVN YNVKSPITGN DLSPPVSFNL MFKTFIGPGG NMPGYLRPET 300
AQGIFLNFKR LLEFNQGKLP FAAAQIGNSF RNEISPRSGL IRVREFTMAE IEHFVDPSEK 360
DHPKFQNVAD LHLYLYSAKA QVSGQSARKM RLGDAVEQGV INNTVLGYFI GRIYLYLTKV 420
GISPDKLRFR QHMENEMAHY ACDCWDAESK TSYGWIEIVG CADRSCYDLS CHARATKVPL 480
VAEKPLKEPK TVNVVQFEPS KGAIGKAYKK DAKLVMEYLA ICDECYITEM EMLLNEKGEF 540
TIETEGKTFQ LTKDMINVKR FQKTLYVEEV VPNVIEPSFG LGRIMYTVFE HTFHVREGDE 600
QRTFFSFPAV VAPFKCSVLP LSQNQEFMPF VKELSEALTR HGVSHKVDDS SGSIGRRYAR 660
TDEIGVAFGV TIDFDTVNKT PHTATLRDRD SMRQIRAEIS ELPSIVQDLA NGNITWADVE 720
ARYPLFEGQE TGKKETIEE 739 
Gene Ontology
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0005759; C:mitochondrial matrix; TAS:Reactome.
 GO:0030141; C:secretory granule; IEA:Compara.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0004820; F:glycine-tRNA ligase activity; IDA:UniProtKB.
 GO:0046983; F:protein dimerization activity; IDA:UniProtKB.
 GO:0008219; P:cell death; IEA:UniProtKB-KW.
 GO:0015966; P:diadenosine tetraphosphate biosynthetic process; IDA:UniProtKB.
 GO:0006426; P:glycyl-tRNA aminoacylation; IEA:InterPro.
 GO:0006418; P:tRNA aminoacylation for protein translation; TAS:Reactome. 
Interpro
 IPR002314; aa-tRNA-synt_IIb_cons-dom.
 IPR006195; aa-tRNA-synth_II.
 IPR004154; Anticodon-bd.
 IPR027031; Gly-tRNA_synthase/POLG2.
 IPR009068; S15_NS1_RNA-bd.
 IPR002315; tRNA-synt_gly.
 IPR000738; WHEP-TRS. 
Pfam
 PF03129; HGTP_anticodon
 PF00587; tRNA-synt_2b
 PF00458; WHEP-TRS 
SMART
 SM00991; WHEP-TRS 
PROSITE
 PS50862; AA_TRNA_LIGASE_II
 PS00762; WHEP_TRS_1
 PS51185; WHEP_TRS_2 
PRINTS
 PR01043; TRNASYNTHGLY.