AARS1

Protein identityUniProt · HPA

UniProt accession

P49588

Gene

AARS1

Ensembl

ENSG00000090861

Chromosome

16

Canonical length

968 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Plasma proteins, Potential drug targets, Predicted intracellular proteins

Subcellular location

Cytosol

OverviewNCBI Gene

The human alanyl-tRNA synthetase (AARS) belongs to a family of tRNA synthases, of the class II enzymes. Class II tRNA synthases evolved early in evolution and are highly conserved. This is reflected by the fact that 498 of the 968-residue polypeptide human AARS shares 41% identity witht the E.coli protein. tRNA synthases are the enzymes that interpret the RNA code and attach specific aminoacids to the tRNAs that contain the cognate trinucleotide anticodons. They consist of a catalytic domain which interacts with the amino acid acceptor-T psi C helix of the tRNA, and a second domain which interacts with the rest of the tRNA structure. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

968 residues, UniProt reviewed canonical sequence.

>P49588|AARS1
     1  MDSTLTASEI RQRFIDFFKR NEHTYVHSSA TIPLDDPTLL FANAGMNQFK PIFLNTIDPS
    61  HPMAKLSRAA NTQKCIRAGG KHNDLDDVGK DVYHHTFFEM LGSWSFGDYF KELACKMALE
   121  LLTQEFGIPI ERLYVTYFGG DEAAGLEADL ECKQIWQNLG LDDTKILPGN MKDNFWEMGD
   181  TGPCGPCSEI HYDRIGGRDA AHLVNQDDPN VLEIWNLVFI QYNREADGIL KPLPKKSIDT
   241  GMGLERLVSV LQNKMSNYDT DLFVPYFEAI QKGTGARPYT GKVGAEDADG IDMAYRVLAD
   301  HARTITVALA DGGRPDNTGR GYVLRRILRR AVRYAHEKLN ASRGFFATLV DVVVQSLGDA
   361  FPELKKDPDM VKDIINEEEV QFLKTLSRGR RILDRKIQSL GDSKTIPGDT AWLLYDTYGF
   421  PVDLTGLIAE EKGLVVDMDG FEEERKLAQL KSQGKGAGGE DLIMLDIYAI EELRARGLEV
   481  TDDSPKYNYH LDSSGSYVFE NTVATVMALR REKMFVEEVS TGQECGVVLD KTCFYAEQGG
   541  QIYDEGYLVK VDDSSEDKTE FTVKNAQVRG GYVLHIGTIY GDLKVGDQVW LFIDEPRRRP
   601  IMSNHTATHI LNFALRSVLG EADQKGSLVA PDRLRFDFTA KGAMSTQQIK KAEEIANEMI
   661  EAAKAVYTQD CPLAAAKAIQ GLRAVFDETY PDPVRVVSIG VPVSELLDDP SGPAGSLTSV
   721  EFCGGTHLRN SSHAGAFVIV TEEAIAKGIR RIVAVTGAEA QKALRKAESL KKCLSVMEAK
   781  VKAQTAPNKD VQREIADLGE ALATAVIPQW QKDELRETLK SLKKVMDDLD RASKADVQKR
   841  VLEKTKQFID SNPNQPLVIL EMESGASAKA LNEALKLFKM HSPQTSAMLF TVDNEAGKIT
   901  CLCQVPQNAA NRGLKASEWV QQVSGLMDGK GGGKDVSAQA TGKNVGCLQE ALQLATSFAQ
   961  LRLGDVKN

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against AARS1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.24

Highest tissue expression

89 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about AARS1.

Disease | AllUniProt

Conditions AARS1 is implicated in, by any mechanism.

• Charcot-Marie-Tooth disease, axonal, type 2N (CMT2N) MIM:613287
• Developmental and epileptic encephalopathy 29 (DEE29) MIM:616339
• Leukoencephalopathy, hereditary diffuse, with spheroids 2 (HDLS2) MIM:619661
• Trichothiodystrophy 8, non-photosensitive (TTD8) MIM:619691

Disease | GeneticClinVar

85 pathogenic / likely-pathogenic of 1,682 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Charcot-Marie-Tooth disease type 2
• Developmental and epileptic encephalopathy, 29
• Charcot-Marie-Tooth disease axonal type 2N
• Inborn genetic diseases
• Trichothiodystrophy 8, nonphotosensitive

Disease | ImmuneIEDB

Conditions an epitope on AARS1 was assayed in.

• systemic scleroderma B cell

Disease | AutoantibodyPubMed

Conditions in which antibodies against AARS1 are reported. Each links to that disease's full target list.

• Myositis 3

ReferencesPubMed · IEDB

Publications for AARS1 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.62

gnomAD pLI

0

DepMap mean gene effect

-2.01

DepMap dependency class

pan

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• alanyl-tRNA aminoacylation
• cerebellar Purkinje cell layer development
• negative regulation of neuron apoptotic process
• negative regulation of signal transduction by p53 class mediator
• neuromuscular process controlling balance
• neuron apoptotic process
• positive regulation of hippo signaling
• tRNA aminoacylation for protein translation
• tRNA modification
• tRNA processing
• regulation of cytoplasmic translational fidelity

Molecular functions

• alanine-tRNA ligase activity
• amino acid binding
• aminoacyl-tRNA deacylase activity
• ATP binding
• peptide lactyltransferase (ATP-dependent) activity
• Ser-tRNA(Ala) deacylase activity
• tRNA binding
• zinc ion binding

Cellular components

• cytoplasm
• cytosol
• extracellular exosome
• membrane
• nucleus

Protein domainsUniProt · Pfam · InterPro

• Alanine-tRNA ligase, class IIc
• Translation protein, beta-barrel domain superfamily
• Threonyl/alanyl tRNA synthetase, SAD
• Alanine-tRNA ligase, class IIc, anti-codon-binding domain superfamily
• Threonyl/alanyl tRNA synthetase, class II-like, putative editing domain superfamily
• Alanyl-tRNA synthetase, class IIc, N-terminal
• Alanyl-tRNA synthetase, class IIc, core domain
• Alanine-tRNA ligase, eukaryota/bacteria
• Class II Aminoacyl-tRNA synthetase/Biotinyl protein ligase (BPL) and lipoyl protein ligase (LPL)
• Alanine--tRNA ligase
• tRNA synthetases class II (A)
• Threonyl and Alanyl tRNA synthetase second additional domain
• DHHA1 domain
• DHHA1 domain

KeywordsUniProt

• Acetylation
• Aminoacyl-tRNA synthetase
• ATP-binding
• Charcot-Marie-Tooth disease
• Cytoplasm
• Epilepsy
• Ligase
• Metal-binding
• Methylation
• Neurodegeneration
• Neuropathy
• Nucleotide-binding
• Nucleus
• Phosphoprotein
• Protein biosynthesis
• RNA-binding
• tRNA-binding
• Ubl conjugation
• Zinc

InteractionsUniProt · HPA

Protein binding partners of AARS1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• ANKRD16