CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-005045
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Trifunctional purine biosynthetic protein adenosine-3 
Protein Synonyms/Alias
 Phosphoribosylamine--glycine ligase; Glycinamide ribonucleotide synthetase; GARS; Phosphoribosylglycinamide synthetase; Phosphoribosylformylglycinamidine cyclo-ligase; AIR synthase; AIRS; Phosphoribosyl-aminoimidazole synthetase; Phosphoribosylglycinamide formyltransferase; 5'-phosphoribosylglycinamide transformylase; GAR transformylase; GART 
Gene Name
 GART 
Gene Synonyms/Alias
 PGFT; PRGS 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
20REHTLAWKLAQSHHVubiquitination[1]
28LAQSHHVKQVLVAPGubiquitination[1, 2]
44AGTACSEKISNTAISubiquitination[1]
63TALAQFCKEKKIEFVubiquitination[1]
65LAQFCKEKKIEFVVVubiquitination[1]
66AQFCKEKKIEFVVVGubiquitination[1, 3, 4]
107AAQLESSKRFAKEFMubiquitination[1, 2, 3, 5, 6]
111ESSKRFAKEFMDRHGubiquitination[1, 2, 3]
129AQWKAFTKPEEACSFubiquitination[1]
148DFPALVVKASGLAAGubiquitination[1]
156ASGLAAGKGVIVAKSubiquitination[1, 2, 3, 6]
162GKGVIVAKSKEEACKubiquitination[1, 2]
169KSKEEACKAVQEIMQubiquitination[1]
219MPPAQDHKRLLEGDGubiquitination[1, 3, 6]
249VSNDLLLKIKDTVLQubiquitination[1, 2]
251NDLLLKIKDTVLQRTubiquitination[1, 2, 3, 6]
281YAGIMLTKNGPKVLEubiquitination[3, 6]
285MLTKNGPKVLEFNCRubiquitination[1, 2]
350GYPGDYTKGVEITGFacetylation[7, 8]
350GYPGDYTKGVEITGFubiquitination[1, 2, 3, 6]
375FHAGTALKNGKVVTHubiquitination[1, 2, 3, 6, 9]
378GTALKNGKVVTHGGRubiquitination[1, 3]
404ISALEEAKKGLAAIKubiquitination[1, 3, 6, 9]
405SALEEAKKGLAAIKFubiquitination[1]
411KKGLAAIKFEGAIYRubiquitination[1, 3, 6]
419FEGAIYRKDVGFRAIubiquitination[1]
438QPRSLTYKESGVDIAubiquitination[1, 3, 6]
452AAGNMLVKKIQPLAKubiquitination[1, 10, 11]
453AGNMLVKKIQPLAKAubiquitination[1, 12]
459KKIQPLAKATSRSGCubiquitination[1, 10, 11]
467ATSRSGCKVDLGGFAubiquitination[1]
480FAGLFDLKAAGFKDPubiquitination[1, 10, 11]
485DLKAAGFKDPLLASGubiquitination[1, 3, 6, 10, 11]
499GTDGVGTKLKIAQLCubiquitination[1]
501DGVGTKLKIAQLCNKubiquitination[1]
557AVVAGIAKACGKAGCubiquitination[1]
598GAMERDQKLPHLERIubiquitination[1]
633LVRKIVAKSSLQYSSubiquitination[1]
676VLRSGHVKAFAHITGubiquitination[1]
697IPRVLPEKLGVDLDAubiquitination[1, 3, 6, 10, 11]
743GAVLVVSKEQTEQILubiquitination[1]
757LRDIQQHKEEAWVIGubiquitination[1, 6]
779GSPRVKVKNLIESMQubiquitination[1, 10, 11]
805TNHFSFEKKKARVAVubiquitination[1]
806NHFSFEKKKARVAVLubiquitination[1]
852AAVAGLDKAERAGIPubiquitination[1]
866PTRVINHKLYKNRVEubiquitination[1]
906LSGPFVQKWNGKMLNubiquitination[1]
910FVQKWNGKMLNIHPSubiquitination[1, 10, 11]
1008NGKICWVKEE*****ubiquitination[1]
Reference
 [1] 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]
 [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] 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]
 [4] Proteome-wide identification of ubiquitylation sites by conjugation of engineered lysine-less ubiquitin.
 Oshikawa K, Matsumoto M, Oyamada K, Nakayama KI.
 J Proteome Res. 2012 Feb 3;11(2):796-807. [PMID: 22053931]
 [5] 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]
 [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] 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]
 [8] 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]
 [9] 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]
 [10] 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]
 [11] 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]
 [12] 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] 
Functional Description
  
Sequence Annotation
 DOMAIN 111 318 ATP-grasp.
 NP_BIND 137 199 ATP (By similarity).
 REGION 434 809 AIRS.
 REGION 810 1010 GART.
 REGION 818 820 5'-phosphoribosylglycinamide binding.
 REGION 896 899 10-formyltetrahydrofolate binding.
 REGION 947 951 10-formyltetrahydrofolate binding.
 REGION 977 980 5'-phosphoribosylglycinamide binding.
 ACT_SITE 915 915 Proton donor (By similarity).
 METAL 288 288 Manganese (By similarity).
 METAL 290 290 Manganese (By similarity).
 BINDING 871 871 10-formyltetrahydrofolate.
 BINDING 913 913 10-formyltetrahydrofolate.
 MOD_RES 2 2 N-acetylalanine.
 MOD_RES 350 350 N6-acetyllysine.  
Keyword
 3D-structure; Acetylation; Alternative splicing; ATP-binding; Complete proteome; Ligase; Manganese; Metal-binding; Multifunctional enzyme; Nucleotide-binding; Polymorphism; Purine biosynthesis; Reference proteome; Transferase. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 1010 AA 
Protein Sequence
MAARVLIIGS GGREHTLAWK LAQSHHVKQV LVAPGNAGTA CSEKISNTAI SISDHTALAQ 60
FCKEKKIEFV VVGPEAPLAA GIVGNLRSAG VQCFGPTAEA AQLESSKRFA KEFMDRHGIP 120
TAQWKAFTKP EEACSFILSA DFPALVVKAS GLAAGKGVIV AKSKEEACKA VQEIMQEKAF 180
GAAGETIVIE ELLDGEEVSC LCFTDGKTVA PMPPAQDHKR LLEGDGGPNT GGMGAYCPAP 240
QVSNDLLLKI KDTVLQRTVD GMQQEGTPYT GILYAGIMLT KNGPKVLEFN CRFGDPECQV 300
ILPLLKSDLY EVIQSTLDGL LCTSLPVWLE NHTALTVVMA SKGYPGDYTK GVEITGFPEA 360
QALGLEVFHA GTALKNGKVV THGGRVLAVT AIRENLISAL EEAKKGLAAI KFEGAIYRKD 420
VGFRAIAFLQ QPRSLTYKES GVDIAAGNML VKKIQPLAKA TSRSGCKVDL GGFAGLFDLK 480
AAGFKDPLLA SGTDGVGTKL KIAQLCNKHD TIGQDLVAMC VNDILAQGAE PLFFLDYFSC 540
GKLDLSVTEA VVAGIAKACG KAGCALLGGE TAEMPDMYPP GEYDLAGFAV GAMERDQKLP 600
HLERITEGDV VVGIASSGLH SNGFSLVRKI VAKSSLQYSS PAPDGCGDQT LGDLLLTPTR 660
IYSHSLLPVL RSGHVKAFAH ITGGGLLENI PRVLPEKLGV DLDAQTWRIP RVFSWLQQEG 720
HLSEEEMART FNCGVGAVLV VSKEQTEQIL RDIQQHKEEA WVIGSVVARA EGSPRVKVKN 780
LIESMQINGS VLKNGSLTNH FSFEKKKARV AVLISGTGSN LQALIDSTRE PNSSAQIDIV 840
ISNKAAVAGL DKAERAGIPT RVINHKLYKN RVEFDSAIDL VLEEFSIDIV CLAGFMRILS 900
GPFVQKWNGK MLNIHPSLLP SFKGSNAHEQ ALETGVTVTG CTVHFVAEDV DAGQIILQEA 960
VPVKRGDTVA TLSERVKLAE HKIFPAALQL VASGTVQLGE NGKICWVKEE 1010 
Gene Ontology
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
 GO:0008168; F:methyltransferase activity; IEA:InterPro.
 GO:0004637; F:phosphoribosylamine-glycine ligase activity; IEA:EC.
 GO:0004641; F:phosphoribosylformylglycinamidine cyclo-ligase activity; IEA:EC.
 GO:0004644; F:phosphoribosylglycinamide formyltransferase activity; TAS:ProtInc.
 GO:0006189; P:'de novo' IMP biosynthetic process; IEA:UniProtKB-UniPathway.
 GO:0032259; P:methylation; IEA:GOC.
 GO:0009113; P:purine nucleobase biosynthetic process; IEA:InterPro.
 GO:0006144; P:purine nucleobase metabolic process; TAS:Reactome.
 GO:0009168; P:purine ribonucleoside monophosphate biosynthetic process; TAS:Reactome. 
Interpro
 IPR010918; AIR_synth_C_dom.
 IPR000728; AIR_synth_N_dom.
 IPR011761; ATP-grasp.
 IPR013815; ATP_grasp_subdomain_1.
 IPR013816; ATP_grasp_subdomain_2.
 IPR002376; Formyl_transf_N.
 IPR001555; GART_AS.
 IPR016185; PreATP-grasp_dom.
 IPR020561; PRibGlycinamid_synth_ATP-grasp.
 IPR000115; PRibGlycinamide_synth.
 IPR020560; PRibGlycinamide_synth_C-dom.
 IPR020559; PRibGlycinamide_synth_CS.
 IPR020562; PRibGlycinamide_synth_N.
 IPR004733; PurM_cligase.
 IPR016188; PurM_N-like.
 IPR004607; PurN_trans.
 IPR011054; Rudment_hybrid_motif. 
Pfam
 PF00586; AIRS
 PF02769; AIRS_C
 PF00551; Formyl_trans_N
 PF01071; GARS_A
 PF02843; GARS_C
 PF02844; GARS_N 
SMART
  
PROSITE
 PS50975; ATP_GRASP
 PS00184; GARS
 PS00373; GART 
PRINTS