Search Results

Overview

Uniprot IDP49588
Protein NameAlanine--tRNA ligase, cytoplasmic
Gene NameAARS1
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
172 KILPGNMKDNFWEMG
338 AVRYAHEKLNASRGF
396 GRRILDRKIQSLGDS
74 SRAANTQKCIRAGGK
747 VTEEAIAKGIRRIVA
762 VTGAEAQKALRKAES
789 KAQTAPNKDVQREIA
934 MDGKGGGKDVSAQAT

Function

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) (PubMed:27622773, PubMed:27911835, PubMed:28493438, PubMed:33909043). Also edits incorrectly charged tRNA(Ala) via its editing domain (PubMed:27622773, PubMed:27911835, PubMed:28493438, PubMed:29273753). In presence of high levels of lactate, also acts as a protein lactyltransferase that mediates lactylation of lysine residues in target proteins, such as TEAD1, TP53/p53 and YAP1 (PubMed:38512451, PubMed:38653238). Protein lactylation takes place in a two-step reaction: lactate is first activated by ATP to form lactate-AMP and then transferred to lysine residues of target proteins (PubMed:38512451, PubMed:38653238, PubMed:39322678). Acts as an inhibitor of TP53/p53 activity by catalyzing lactylation of TP53/p53 (PubMed:38653238). Acts as a positive regulator of the Hippo pathway by mediating lactylation of TEAD1 and YAP1 (PubMed:38512451)

Protein Sequence

10 MDSTLTASEI 20 RQRFIDFFKR 30 NEHTYVHSSA 40 TIPLDDPTLL 50 FANAGMNQFK 60 PIFLNTIDPS 70 HPMAKLSRAA 80 NTQKCIRAGG 90 KHNDLDDVGK 100 DVYHHTFFEM 110 LGSWSFGDYF 120 KELACKMALE 130 LLTQEFGIPI 140 ERLYVTYFGG 150 DEAAGLEADL 160 ECKQIWQNLG 170 LDDTKILPGN 180 MKDNFWEMGD 190 TGPCGPCSEI 200 HYDRIGGRDA 210 AHLVNQDDPN 220 VLEIWNLVFI 230 QYNREADGIL 240 KPLPKKSIDT 250 GMGLERLVSV 260 LQNKMSNYDT 270 DLFVPYFEAI 280 QKGTGARPYT 290 GKVGAEDADG 300 IDMAYRVLAD 310 HARTITVALA 320 DGGRPDNTGR 330 GYVLRRILRR 340 AVRYAHEKLN 350 ASRGFFATLV 360 DVVVQSLGDA 370 FPELKKDPDM 380 VKDIINEEEV 390 QFLKTLSRGR 400 RILDRKIQSL 410 GDSKTIPGDT 420 AWLLYDTYGF 430 PVDLTGLIAE 440 EKGLVVDMDG 450 FEEERKLAQL 460 KSQGKGAGGE 470 DLIMLDIYAI 480 EELRARGLEV 490 TDDSPKYNYH 500 LDSSGSYVFE 510 NTVATVMALR 520 REKMFVEEVS 530 TGQECGVVLD 540 KTCFYAEQGG 550 QIYDEGYLVK 560 VDDSSEDKTE 570 FTVKNAQVRG 580 GYVLHIGTIY 590 GDLKVGDQVW 600 LFIDEPRRRP 610 IMSNHTATHI 620 LNFALRSVLG 630 EADQKGSLVA 640 PDRLRFDFTA 650 KGAMSTQQIK 660 KAEEIANEMI 670 EAAKAVYTQD 680 CPLAAAKAIQ 690 GLRAVFDETY 700 PDPVRVVSIG 710 VPVSELLDDP 720 SGPAGSLTSV 730 EFCGGTHLRN 740 SSHAGAFVIV 750 TEEAIAKGIR 760 RIVAVTGAEA 770 QKALRKAESL 780 KKCLSVMEAK 790 VKAQTAPNKD 800 VQREIADLGE 810 ALATAVIPQW 820 QKDELRETLK 830 SLKKVMDDLD 840 RASKADVQKR 850 VLEKTKQFID 860 SNPNQPLVIL 870 EMESGASAKA 880 LNEALKLFKM 890 HSPQTSAMLF 900 TVDNEAGKIT 910 CLCQVPQNAA 920 NRGLKASEWV 930 QQVSGLMDGK 940 GGGKDVSAQA 950 TGKNVGCLQE 960 ALQLATSFAQ LRLGDVKN

Gene Ontology

Classification GO ID Description
Cellular Component GO:0005737 cytoplasm
Cellular Component GO:0005829 cytosol
Cellular Component GO:0070062 extracellular exosome
Cellular Component GO:0016020 membrane
Cellular Component GO:0005634 nucleus
Molecular Function GO:0004813 alanine-tRNA ligase activity
Molecular Function GO:0016597 amino acid binding
Molecular Function GO:0002161 aminoacyl-tRNA deacylase activity
Molecular Function GO:0005524 ATP binding
Molecular Function GO:0141207 peptide lactyltransferase (ATP-dependent) activity
Molecular Function GO:0002196 Ser-tRNA(Ala) deacylase activity
Molecular Function GO:0000049 tRNA binding
Molecular Function GO:0008270 zinc ion binding
Biological Process GO:0006419 alanyl-tRNA aminoacylation
Biological Process GO:1901797 negative regulation of signal transduction by p53 class mediator
Biological Process GO:0035332 positive regulation of hippo signaling
Biological Process GO:0140018 regulation of cytoplasmic translational fidelity
Biological Process GO:0006418 tRNA aminoacylation for protein translation
Biological Process GO:0006400 tRNA modification
Biological Process GO:0008033 tRNA processing

Reference

[1] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.

[2] Hong H, Chen X, Wang H, Gu X, Yuan Y et al.. Global profiling of protein lysine lactylation and potential target modified protein analysis in hepatocellular carcinoma.. Proteomics 23(9):e2200432. 2023 May. PMID: 36625413.

[3] Guo X, Ren X, Yan C, Huang H. Quantitative Proteomics Reveals the Role of Lysine Lactylation in Lenalidomide-Resistance in Multiple Myeloma Cells.. ACS Chem Biol 20(7):1728-1738. 2025 Jul 18. PMID: 40590393.

[4] Wu Q, Li Z, Gong T, Zheng X, Zhou X et al.. Porphyromonas gingivalis infection induces lysine lactylation reprogramming in human umbilical vein endothelial cells.. Front Cell Infect Microbiol 16:1706727. 2026. PMID: 41696360.