AARS1
entrez
16
canonical
uniprot
P49588
canonical
ensembl
ENSG00000090861
resolver
ensp
ENSP00000261772
resolver
ensp
ENSP00000502479
resolver
ensp
ENSP00000502645
resolver
enst
ENST00000675371
resolver
enst
ENST00000676168
resolver
genesymbol
AARS1
resolver
genesymbol_syn
AARS
resolver
hgnc
HGNC:20
resolver
uniprot
A0A6Q8PH44
resolver
uniprot
A6NF14
resolver
uniprot
B4DR45
resolver
uniprot
Q53GV7
resolver
uniprot
Q96FA0
resolver
uniprot_entry
A0A6Q8PH44_HUMAN
resolver
uniprot_entry
SYAC_HUMAN
resolver
uniprot_sec
A6NF14
resolver
uniprot_sec
B4DR45
resolver
uniprot_sec
Q53GV7
resolver
uniprot_sec
Q96FA0
resolver
activity_regulation
ACTIVITY REGULATION: The protein lactyltransferase activity is inhibited by beta-alanine. {ECO:0000269|PubMed:38653238}.
uniprot
proteins
amino_acid_sequence
MDSTLTASEIRQRFIDFFKRNEHTYVHSSATIPLDDPTLLFANAGMNQFKPIFLNTIDPSHPMAKLSRAANTQKCIRAGGKHNDLDDVGKDVYHHTFFEMLGSWSFGDYFKELACKMALELLTQEFGIPIERLYVTYFGGDEAAGLEADLECKQIWQNLGLDDTKILPGNMKDNFWEMGDTGPCGPCSEIHYDRIGGRDAAHLVNQDDPNVLEIWNLVFIQYNREADGILKPLPKKSIDTGMGLERLVSVLQNKMSNYDTDLFVPYFEAIQKGTGARPYTGKVGAEDADGIDMAYRVLADHARTITVALADGGRPDNTGRGYVLRRILRRAVRYAHEKLNASRGFFATLVDVVVQSLGDAFPELKKDPDMVKDIINEEEVQFLKTLSRGRRILDRKIQSLGDSKTIPGDTAWLLYDTYGFPVDLTGLIAEEKGLVVDMDGFEEERKLAQLKSQGKGAGGEDLIMLDIYAIEELRARGLEVTDDSPKYNYHLDSSGSYVFENTVATVMALRREKMFVEEVSTGQECGVVLDKTCFYAEQGGQIYDEGYLVKVDDSSEDKTEFTVKNAQVRGGYVLHIGTIYGDLKVGDQVWLFIDEPRRRPIMSNHTATHILNFALRSVLGEADQKGSLVAPDRLRFDFTAKGAMSTQQIKKAEEIANEMIEAAKAVYTQDCPLAAAKAIQGLRAVFDETYPDPVRVVSIGVPVSELLDDPSGPAGSLTSVEFCGGTHLRNSSHAGAFVIVTEEAIAKGIRRIVAVTGAEAQKALRKAESLKKCLSVMEAKVKAQTAPNKDVQREIADLGEALATAVIPQWQKDELRETLKSLKKVMDDLDRASKADVQKRVLEKTKQFIDSNPNQPLVILEMESGASAKALNEALKLFKMHSPQTSAMLFTVDNEAGKITCLCQVPQNAANRGLKASEWVQQVSGLMDGKGGGKDVSAQATGKNVGCLQEALQLATSFAQLRLGDVKN
uniprot
proteins
disease_involvement
DISEASE: Charcot-Marie-Tooth disease, axonal, type 2N (CMT2N) [MIM:613287]: An axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. {ECO:0000269|PubMed:20045102, ECO:0000269|PubMed:22009580, ECO:0000269|PubMed:22206013, ECO:0000269|PubMed:35911843, ECO:0000269|PubMed:35971119}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Developmental and epileptic encephalopathy 29 (DEE29) [MIM:616339]: A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE29 patients manifest severe infantile epileptic encephalopathy, clubfoot, absent deep tendon reflexes, extrapyramidal symptoms, and persistently deficient myelination. {ECO:0000269|PubMed:25817015, ECO:0000269|PubMed:28493438}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Leukoencephalopathy, hereditary diffuse, with spheroids 2 (HDLS2) [MIM:619661]: An autosomal dominant neurodegenerative disorder characterized by progressive cognitive and executive dysfunction, psychiatric disturbances, and neurologic symptoms, such as gait abnormalities, paresis, seizures, and rigidity. Symptom onset is usually in adulthood, although earlier onset has been reported. Some patients have an acute encephalopathic course with severe neurologic decline resulting in early death, whereas other patients have a more protracted and chronic disease course. Neuropathologic examination shows a leukoencephalopathy with axonal spheroids and myelination defects. {ECO:0000269|PubMed:31775912, ECO:0000269|PubMed:37106376}. Note=The disease may be caused by variants affecting the gene represented in this entry.; DISEASE: Trichothiodystrophy 8, non-photosensitive (TTD8) [MIM:619691]: A form of trichothiodystrophy, a disease characterized by sulfur-deficient brittle hair and multisystem variable abnormalities. The spectrum of clinical features varies from mild disease with only hair involvement to severe disease with cutaneous, neurologic and profound developmental defects. Ichthyosis, intellectual and developmental disabilities, decreased fertility, abnormal characteristics at birth, ocular abnormalities, short stature, and infections are common manifestations. There are both photosensitive and non-photosensitive forms of the disorder. TTD8 is an autosomal recessive, non-photosensitive form characterized by brittle hair and nails, scaly skin, accompanied by failure to thrive, microcephaly, and neuromotor developmental delay. {ECO:0000269|PubMed:33909043}. Note=The disease may be caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
6.-.-.-
uniprot
proteins
ec_number
6.1.1.7
uniprot
proteins
function
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). {ECO:0000269|PubMed:27622773, ECO:0000269|PubMed:27911835, ECO:0000269|PubMed:28493438, ECO:0000269|PubMed:29273753, ECO:0000269|PubMed:33909043, ECO:0000269|PubMed:38512451, ECO:0000269|PubMed:38653238, ECO:0000269|PubMed:39322678}.
uniprot
proteins
mass_dalton
106810
uniprot
proteins
mutagenesis
MUTAGEN 46; /note="M->A: In mutant 5A; abolished binding to lactate and protein lactylation; when associated with A-77, A-216 and 239-A--A-241."; /evidence="ECO:0000269|PubMed:38653238, ECO:0000269|PubMed:39322678"; MUTAGEN 77; /note="R->A: In mutant 5A; abolished binding to lactate and protein lactylation; when associated with A-46, A-216 and 239-A--A-241. In mutant 5M; abolished binding to lactate and protein lactylation; when associated with A-100, E-176, D-218 and A-239. In ATP-binding mutant; abolished ability to mediate protein lactylation; when associated with A-176 and A-243."; /evidence="ECO:0000269|PubMed:38512451, ECO:0000269|PubMed:38653238, ECO:0000269|PubMed:39322678"; MUTAGEN 100; /note="M->A: In mutant 5M; abolished binding to lactate and protein lactylation; when associated with A-77, E-176, D-218 and A-239."; /evidence="ECO:0000269|PubMed:38512451"; MUTAGEN 176; /note="W->A: In ATP-binding mutant; abolished ability to mediate protein lactylation; when associated with A-77 and A-243."; /evidence="ECO:0000269|PubMed:39322678"; MUTAGEN 176; /note="W->E: In mutant 5M; abolished binding to lactate and protein lactylation; when associated with A-77, A-100, D-218 and A-239."; /evidence="ECO:0000269|PubMed:38512451"; MUTAGEN 216; /note="N->A: In mutant 5A; abolished binding to lactate and protein lactylation; when associated with A-46, A-77 and 239-A--A-241."; /evidence="ECO:0000269|PubMed:38653238, ECO:0000269|PubMed:39322678"; MUTAGEN 218; /note="V->D: In mutant 5M; abolished binding to lactate and protein lactylation; when associated with A-77, A-100, E-176 and A-239."; /evidence="ECO:0000269|PubMed:38512451"; MUTAGEN 239..241; /note="DTG->ATA: In mutant 5A; abolished binding to lactate and protein lactylation; when associated with A-46, A-77 and A-216."; /evidence="ECO:0000269|PubMed:38653238, ECO:0000269|PubMed:39322678"; MUTAGEN 239; /note="D->A: In mutant 5M; abolished binding to lactate and protein lactylation; when associated with A-77, A-100, E-176 and D-218."; /evidence="ECO:0000269|PubMed:38512451"; MUTAGEN 243; /note="G->A: In ATP-binding mutant; abolished ability to mediate protein lactylation; when associated with A-77 and A-176."; /evidence="ECO:0000269|PubMed:39322678"; MUTAGEN 448; /note="A->Q: Decreases misincorporation of Cys instead of Ala."; /evidence="ECO:0000269|PubMed:27622773"; MUTAGEN 723; /note="C->A: Decreases editing activity."; /evidence="ECO:0000269|PubMed:28493438"; MUTAGEN 750..763; /note="Missing: Abolished nuclear translocation in presence of lactate."; /evidence="ECO:0000269|PubMed:38512451"; MUTAGEN 943; /note="K->A: Abrogates METTL21C methylation of AARS1."; /evidence="ECO:0000269|PubMed:32611769
uniprot
proteins
post_translational_modification
PTM: ISGylated. {ECO:0000255|HAMAP-Rule:MF_03133, ECO:0000269|PubMed:16139798}.; PTM: Methylation at 'Lys-943' by METTL21C. {ECO:0000269|PubMed:32611769}.
uniprot
proteins
protein_family
Class-II aminoacyl-tRNA synthetase family
uniprot
proteins
pubmed
10508479
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15616553
uniprot
proteins
pubmed
16139798
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
19608861
uniprot
proteins
pubmed
19661429
uniprot
proteins
pubmed
20045102
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
22009580
uniprot
proteins
pubmed
22206013
uniprot
proteins
pubmed
22223895
uniprot
proteins
pubmed
22814378
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
24627108
uniprot
proteins
pubmed
25817015
uniprot
proteins
pubmed
25944712
uniprot
proteins
pubmed
27622773
uniprot
proteins
pubmed
27911835
uniprot
proteins
pubmed
28493438
uniprot
proteins
pubmed
29273753
uniprot
proteins
pubmed
31775912
uniprot
proteins
pubmed
32611769
uniprot
proteins
pubmed
33909043
uniprot
proteins
pubmed
35911843
uniprot
proteins
pubmed
35971119
uniprot
proteins
pubmed
37106376
uniprot
proteins
pubmed
38512451
uniprot
proteins
pubmed
38653238
uniprot
proteins
pubmed
39322678
uniprot
proteins
pubmed
7654687
uniprot
proteins
sequence_length
968
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_03133, ECO:0000269|PubMed:27911835, ECO:0000269|PubMed:38512451}. Nucleus {ECO:0000269|PubMed:38512451}. Note=Translocates to the nucleus in response to increased levels of lactate; nuclear translocation is dependent on KPNA4. {ECO:0000269|PubMed:38512451}.
uniprot
proteins