CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-008163
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Alanine--tRNA ligase, cytoplasmic 
Protein Synonyms/Alias
 Alanyl-tRNA synthetase; AlaRS; Renal carcinoma antigen NY-REN-42 
Gene Name
 AARS 
Gene Synonyms/Alias
  
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
19QRFIDFFKRNEHTYVacetylation[1]
19QRFIDFFKRNEHTYVubiquitination[2, 3, 4, 5]
81KCIRAGGKHNDLDDVubiquitination[6]
231READGILKPLPKKSIacetylation[7]
231READGILKPLPKKSIubiquitination[8, 9]
282GARPYTGKVGAEDADubiquitination[4]
338AVRYAHEKLNASRGFubiquitination[4, 9]
366DAFPELKKDPDMVKDacetylation[9]
384EEEVQFLKTLSRGRRubiquitination[2, 3, 5, 6, 10]
558VDDSSEDKTEFTVKNacetylation[7]
564DKTEFTVKNAQVRGGubiquitination[4, 6, 9, 10]
625VLGEADQKGSLVAPDubiquitination[4, 6, 10, 11]
641LRFDFTAKGAMSTQQubiquitination[4]
650AMSTQQIKKAEEIANubiquitination[4]
651MSTQQIKKAEEIANEubiquitination[4]
677DCPLAAAKAIQGLRAubiquitination[2, 4, 5, 8, 11]
747VTEEAIAKGIRRIVAubiquitination[4, 6, 8, 10]
762VTGAEAQKALRKAESubiquitination[2, 3, 4, 5, 11]
772RKAESLKKCLSVMEAubiquitination[4]
789KAQTAPNKDVQREIAubiquitination[4]
820DELRETLKSLKKVMDubiquitination[2, 5, 10]
846KRVLEKTKQFIDSNPubiquitination[4, 6, 10]
876KALNEALKLFKMHSPacetylation[1, 7, 12]
876KALNEALKLFKMHSPubiquitination[2, 4, 5]
915NAANRGLKASEWVQQubiquitination[10]
930VSGLMDGKGGGKDVSubiquitination[4, 6, 10]
934MDGKGGGKDVSAQATubiquitination[4, 6]
943VSAQATGKNVGCLQEubiquitination[4]
Reference
 [1] 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]
 [2] 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]
 [3] 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]
 [4] 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]
 [5] 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]
 [6] 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]
 [7] 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]
 [8] 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]
 [9] 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]
 [10] 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]
 [11] 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]
 [12] 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] 
Functional Description
 Catalyzes the attachment of alanine to tRNA(Ala) in a two-step reaction: alanine is first activated by ATP to form Ala- AMP and then transferred to the acceptor end of tRNA(Ala). Also edits incorrectly charged tRNA(Ala) via its editing domain (By similarity). 
Sequence Annotation
 METAL 605 605 Zinc (Potential).
 METAL 609 609 Zinc (Potential).
 METAL 723 723 Zinc (Potential).
 METAL 727 727 Zinc (Potential).
 MOD_RES 1 1 N-acetylmethionine.
 MOD_RES 19 19 N6-acetyllysine.
 MOD_RES 399 399 Phosphoserine.
 MOD_RES 555 555 Phosphoserine.
 MOD_RES 876 876 N6-acetyllysine.  
Keyword
 Acetylation; Aminoacyl-tRNA synthetase; ATP-binding; Charcot-Marie-Tooth disease; Complete proteome; Cytoplasm; Direct protein sequencing; Disease mutation; Ligase; Metal-binding; Neuropathy; Nucleotide-binding; Phosphoprotein; Polymorphism; Protein biosynthesis; Reference proteome; RNA-binding; tRNA-binding; Ubl conjugation; Zinc. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 968 AA 
Protein Sequence
MDSTLTASEI RQRFIDFFKR NEHTYVHSSA TIPLDDPTLL FANAGMNQFK PIFLNTIDPS 60
HPMAKLSRAA NTQKCIRAGG KHNDLDDVGK DVYHHTFFEM LGSWSFGDYF KELACKMALE 120
LLTQEFGIPI ERLYVTYFGG DEAAGLEADL ECKQIWQNLG LDDTKILPGN MKDNFWEMGD 180
TGPCGPCSEI HYDRIGGRDA AHLVNQDDPN VLEIWNLVFI QYNREADGIL KPLPKKSIDT 240
GMGLERLVSV LQNKMSNYDT DLFVPYFEAI QKGTGARPYT GKVGAEDADG IDMAYRVLAD 300
HARTITVALA DGGRPDNTGR GYVLRRILRR AVRYAHEKLN ASRGFFATLV DVVVQSLGDA 360
FPELKKDPDM VKDIINEEEV QFLKTLSRGR RILDRKIQSL GDSKTIPGDT AWLLYDTYGF 420
PVDLTGLIAE EKGLVVDMDG FEEERKLAQL KSQGKGAGGE DLIMLDIYAI EELRARGLEV 480
TDDSPKYNYH LDSSGSYVFE NTVATVMALR REKMFVEEVS TGQECGVVLD KTCFYAEQGG 540
QIYDEGYLVK VDDSSEDKTE FTVKNAQVRG GYVLHIGTIY GDLKVGDQVW LFIDEPRRRP 600
IMSNHTATHI LNFALRSVLG EADQKGSLVA PDRLRFDFTA KGAMSTQQIK KAEEIANEMI 660
EAAKAVYTQD CPLAAAKAIQ GLRAVFDETY PDPVRVVSIG VPVSELLDDP SGPAGSLTSV 720
EFCGGTHLRN SSHAGAFVIV TEEAIAKGIR RIVAVTGAEA QKALRKAESL KKCLSVMEAK 780
VKAQTAPNKD VQREIADLGE ALATAVIPQW QKDELRETLK SLKKVMDDLD RASKADVQKR 840
VLEKTKQFID SNPNQPLVIL EMESGASAKA LNEALKLFKM HSPQTSAMLF TVDNEAGKIT 900
CLCQVPQNAA NRGLKASEWV QQVSGLMDGK GGGKDVSAQA TGKNVGCLQE ALQLATSFAQ 960
LRLGDVKN 968 
Gene Ontology
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0004813; F:alanine-tRNA ligase activity; IEA:EC.
 GO:0016597; F:amino acid binding; IEA:Compara.
 GO:0002161; F:aminoacyl-tRNA editing activity; IEA:Compara.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
 GO:0000049; F:tRNA binding; TAS:ProtInc.
 GO:0006419; P:alanyl-tRNA aminoacylation; TAS:ProtInc.
 GO:0021680; P:cerebellar Purkinje cell layer development; IEA:Compara.
 GO:0030968; P:endoplasmic reticulum unfolded protein response; IEA:Compara.
 GO:0001942; P:hair follicle development; IEA:Compara.
 GO:0043524; P:negative regulation of neuron apoptotic process; IEA:Compara.
 GO:0050885; P:neuromuscular process controlling balance; IEA:Compara.
 GO:0006457; P:protein folding; IEA:Compara.
 GO:0043200; P:response to amino acid stimulus; IEA:Compara.
 GO:0043588; P:skin development; IEA:Compara.
 GO:0006400; P:tRNA modification; IEA:Compara.
 GO:0008033; P:tRNA processing; TAS:ProtInc. 
Interpro
 IPR002318; Ala-tRNA-lgiase_IIc.
 IPR018162; Ala-tRNA-ligase_IIc_anticod-bd.
 IPR018165; Ala-tRNA-synth_IIc_core.
 IPR018164; Ala-tRNA-synth_IIc_N.
 IPR023033; Ala_tRNA_ligase_euk/bac.
 IPR003156; Pesterase_DHHA1.
 IPR018163; Thr/Ala-tRNA-synth_IIc_edit.
 IPR012947; tRNA_SAD. 
Pfam
 PF02272; DHHA1
 PF01411; tRNA-synt_2c
 PF07973; tRNA_SAD 
SMART
 SM00863; tRNA_SAD 
PROSITE
 PS50860; AA_TRNA_LIGASE_II_ALA 
PRINTS
 PR00980; TRNASYNTHALA.