AARS1 (alanyl-tRNA synthetase 1)

Gene

• Entrez ID: 16
• Gene name: Alanyl-tRNA synthetase 1
• Gene symbol: AARS1
• Synonyms: AARS, CMT2N, DEE29, EIEE29
• Chromosome: 16
• Chromosome location: 16q22.1
• Summary: 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]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs115882953	G>A,C,T	Conflicting-interpretations-of-pathogenicity	Synonymous variant, intron variant, coding sequence variant, missense variant
rs138081804	G>A	Conflicting-interpretations-of-pathogenicity, uncertain-significance	Non coding transcript variant, coding sequence variant, missense variant
rs143370729	T>C	Uncertain-significance, pathogenic	Coding sequence variant, non coding transcript variant, missense variant
rs147319762	T>C	Conflicting-interpretations-of-pathogenicity, likely-benign	Coding sequence variant, non coding transcript variant, missense variant
rs150080663	G>A	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, non coding transcript variant, synonymous variant
rs199976742	T>C	Uncertain-significance, conflicting-interpretations-of-pathogenicity	Non coding transcript variant, missense variant, coding sequence variant
rs267606621	C>T	Pathogenic	Non coding transcript variant, missense variant, coding sequence variant
rs387906792	T>A	Pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs576221121	C>T	Conflicting-interpretations-of-pathogenicity, likely-benign	Missense variant, non coding transcript variant, coding sequence variant
rs750552137	A>G	Conflicting-interpretations-of-pathogenicity, likely-benign	Synonymous variant, non coding transcript variant, coding sequence variant
rs758183257	G>A	Pathogenic	Coding sequence variant, stop gained, non coding transcript variant
rs763937206	AGTAA>-	Likely-pathogenic	Inframe indel, coding sequence variant, stop gained, non coding transcript variant
rs765398055	T>C	Uncertain-significance, conflicting-interpretations-of-pathogenicity	Missense variant, coding sequence variant, non coding transcript variant
rs771059047	C>A	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, non coding transcript variant, missense variant
rs777601008	G>A	Uncertain-significance, pathogenic	Coding sequence variant, non coding transcript variant, missense variant
rs786205157	T>G	Pathogenic, likely-pathogenic	Coding sequence variant, non coding transcript variant, missense variant
rs797044801	T>G	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, non coding transcript variant, missense variant
rs1064795664	G>A	Likely-pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs1480620711	G>A	Likely-pathogenic	Missense variant, intron variant, coding sequence variant
rs1555542415	A>G	Likely-pathogenic	Missense variant, non coding transcript variant, coding sequence variant
rs1597434047	->A	Likely-pathogenic	Non coding transcript variant, coding sequence variant, frameshift variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT022529	hsa-miR-124-3p	Microarray	18668037
MIRT037527	hsa-miR-744-5p	CLASH	23622248
MIRT038499	hsa-miR-296-3p	CLASH	23622248
MIRT039031	hsa-miR-766-3p	CLASH	23622248
MIRT039826	hsa-miR-615-3p	CLASH	23622248
MIRT041325	hsa-miR-193b-3p	CLASH	23622248
MIRT041952	hsa-miR-484	CLASH	23622248
MIRT043224	hsa-miR-324-5p	CLASH	23622248
MIRT043527	hsa-miR-331-3p	CLASH	23622248

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000049	Function	TRNA binding	IBA	21873635
GO:0002161	Function	Aminoacyl-tRNA editing activity	IBA	21873635
GO:0002161	Function	Aminoacyl-tRNA editing activity	IDA	28493438
GO:0002196	Function	Ser-tRNA(Ala) hydrolase activity	ISS
GO:0004813	Function	Alanine-tRNA ligase activity	IBA	21873635
GO:0004813	Function	Alanine-tRNA ligase activity	IDA	27622773, 28493438
GO:0004813	Function	Alanine-tRNA ligase activity	TAS
GO:0005524	Function	ATP binding	IBA	21873635
GO:0005737	Component	Cytoplasm	TAS	7654687
GO:0005739	Component	Mitochondrion	IBA	21873635
GO:0005829	Component	Cytosol	TAS
GO:0006400	Process	TRNA modification	IBA	21873635
GO:0006400	Process	TRNA modification	ISS
GO:0006418	Process	TRNA aminoacylation for protein translation	TAS
GO:0006419	Process	Alanyl-tRNA aminoacylation	IBA	21873635
GO:0006419	Process	Alanyl-tRNA aminoacylation	IDA	27622773, 28493438
GO:0008033	Process	TRNA processing	TAS	7654687
GO:0008270	Function	Zinc ion binding	IEA
GO:0016020	Component	Membrane	HDA	19946888
GO:0016597	Function	Amino acid binding	IBA	21873635
GO:0070062	Component	Extracellular exosome	HDA	20458337
GO:0106074	Process	Aminoacyl-tRNA metabolism involved in translational fidelity	IEA

Other IDs

• MIM: 601065
• HGNC: 20
• e!Ensembl: ENSG00000090861

Protein

• UniProt ID: P49588
• Protein name: Alanine--tRNA ligase, cytoplasmic (EC 6.1.1.7) (Alanyl-tRNA synthetase) (AlaRS) (Renal carcinoma antigen NY-REN-42)
• Protein 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). Also edits incorrectly charged tRNA(Ala) via its editing domain (PubMed:27622773, PubMed:27911835, PubMed:28493438).
• PDB: 4XEM, 4XEO, 5KNN, 5T5S, 5T76, 5V59
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF01411	tRNA-synt_2c	9 → 597	tRNA synthetases class II (A)	Family
  PF07973	tRNA_SAD	694 → 753	Threonyl and Alanyl tRNA synthetase second additional domain	Domain
  PF02272	DHHA1	812 → 959	DHHA1 domain	Family

• Sequence:

  MDSTLTASEIRQRFIDFFKRNEHTYVHSSATIPLDDPTLLFANAGMNQFKPIFLNTIDPS
  HPMAKLSRAANTQKCIRAGGKHNDLDDVGKDVYHHTFFEMLGSWSFGDYFKELACKMALE
  LLTQEFGIPIERLYVTYFGGDEAAGLEADLECKQIWQNLGLDDTKILPGNMKDNFWEMGD
  TGPCGPCSEIHYDRIGGRDAAHLVNQDDPNVLEIWNLVFIQYNREADGILKPLPKKSIDT
  GMGLERLVSVLQNKMSNYDTDLFVPYFEAIQKGTGARPYTGKVGAEDADGIDMAYRVLAD
  HARTITVALADGGRPDNTGRGYVLRRILRRAVRYAHEKLNASRGFFATLVDVVVQSLGDA
  FPELKKDPDMVKDIINEEEVQFLKTLSRGRRILDRKIQSLGDSKTIPGDTAWLLYDTYGF
  PVDLTGLIAEEKGLVVDMDGFEEERKLAQLKSQGKGAGGEDLIMLDIYAIEELRARGLEV
  TDDSPKYNYHLDSSGSYVFENTVATVMALRREKMFVEEVSTGQECGVVLDKTCFYAEQGG
  QIYDEGYLVKVDDSSEDKTEFTVKNAQVRGGYVLHIGTIYGDLKVGDQVWLFIDEPRRRP
  IMSNHTATHILNFALRSVLGEADQKGSLVAPDRLRFDFTAKGAMSTQQIKKAEEIANEMI
  EAAKAVYTQDCPLAAAKAIQGLRAVFDETYPDPVRVVSIGVPVSELLDDPSGPAGSLTSV
  EFCGGTHLRNSSHAGAFVIVTEEAIAKGIRRIVAVTGAEAQKALRKAESLKKCLSVMEAK
  VKAQTAPNKDVQREIADLGEALATAVIPQWQKDELRETLKSLKKVMDDLDRASKADVQKR
  VLEKTKQFIDSNPNQPLVILEMESGASAKALNEALKLFKMHSPQTSAMLFTVDNEAGKIT
  CLCQVPQNAANRGLKASEWVQQVSGLMDGKGGGKDVSAQATGKNVGCLQEALQLATSFAQ
  LRLGDVKN

• Sequence length: 968

Pathways

KEGG:

Aminoacyl-tRNA biosynthesis

Reactome:

Cytosolic tRNA aminoacylation

Associated diseases

Disease name	Disease term	References
	Attention deficit hyperactivity disorder
	Autistic Disorder
	Blepharospasm
	Cerebral atrophy
	Charcot-Marie-Tooth Disease
	Charcot-Marie-Tooth Disease, Axonal, Type 2n	20045102, 22009580, 26032230, 22206013, 24357685, 26257172
	Autosomal dominant Charcot-Marie-Tooth disease type 2N
	Global developmental delay
	Developmental regression
	Dwarfism
	Hereditary Motor and Sensory-Neuropathy Type II	20045102, 30124830, 22009580
	Dyskinetic syndrome
	Encephalopathies
	Epileptic encephalopathy
	EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 29	28493438, 25817015
	Gastroesophageal reflux disease
	Sensorineural Hearing Loss (disorder)
	Hypodontia
	Intellectual Disability
	Microcephaly
	Peripheral Nervous System Diseases
	Non-specific early-onset epileptic encephalopathy
	Nystagmus
	Optic Atrophy
	Peripheral axonal neuropathy
	Blepharoptosis
	Ptosis
	Status Epilepticus