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Protein

Arginine--tRNA ligase, cytoplasmic

Gene

RARS

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Forms part of a macromolecular complex that catalyzes the attachment of specific amino acids to cognate tRNAs during protein synthesis. Modulates the secretion of AIMP1 and may be involved in generation of the inflammatory cytokine EMAP2 from AIMP1.1 Publication

Catalytic activityi

ATP + L-arginine + tRNA(Arg) = AMP + diphosphate + L-arginyl-tRNA(Arg).

Kineticsi

  1. KM=3.9 µM for arginine (ATP-PPi exchange at 37 degrees Celsius)1 Publication
  2. KM=3.5 µM for arginine (arginylation at 37 degrees Celsius)1 Publication
  3. KM=1183 µM for ATP (ATP-PPi exchange at 37 Celsius)1 Publication
  4. KM=910 µM for ATP (arginylation at 37 Celsius)1 Publication
  5. KM=0.05 µM for calf liver tRNA-Arg (ATP-PPi exchange at 37 Celsius)1 Publication
  6. KM=0.41 µM for calf liver tRNA-Arg (arginylation at 37 Celsius)1 Publication

    GO - Molecular functioni

    GO - Biological processi

    • arginyl-tRNA aminoacylation Source: ProtInc
    • tRNA aminoacylation for protein translation Source: Reactome
    Complete GO annotation...

    Keywords - Molecular functioni

    Aminoacyl-tRNA synthetase, Ligase

    Keywords - Biological processi

    Protein biosynthesis

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    BioCyciZFISH:HS03704-MONOMER.
    ReactomeiR-HSA-2408517. SeMet incorporation into proteins.
    R-HSA-379716. Cytosolic tRNA aminoacylation.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Arginine--tRNA ligase, cytoplasmic (EC:6.1.1.19)
    Alternative name(s):
    Arginyl-tRNA synthetase
    Short name:
    ArgRS
    Gene namesi
    Name:RARS
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 5

    Organism-specific databases

    HGNCiHGNC:9870. RARS.

    Subcellular locationi

    GO - Cellular componenti

    • aminoacyl-tRNA synthetase multienzyme complex Source: Ensembl
    • cell-cell adherens junction Source: BHF-UCL
    • cytoplasm Source: HPA
    • cytosol Source: Reactome
    • extracellular exosome Source: UniProtKB
    • membrane Source: UniProtKB
    • mitochondrion Source: Ensembl
    • nucleoplasm Source: HPA
    Complete GO annotation...

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Involvement in diseasei

    Leukodystrophy, hypomyelinating, 9 (HLD9)1 Publication
    The disease is caused by mutations affecting the gene represented in this entry.
    Disease descriptionAn autosomal recessive neurodegenerative disorder characterized by delayed psychomotor development, severe spasticity, nystagmus, and ataxia associated with diffuse hypomyelination apparent on brain MRI.
    See also OMIM:616140
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_0726662D → G in HLD9. 1 PublicationCorresponds to variant rs672601372dbSNPEnsembl.1
    Natural variantiVAR_072667512R → Q in HLD9. 1 PublicationCorresponds to variant rs369398935dbSNPEnsembl.1

    Keywords - Diseasei

    Disease mutation, Leukodystrophy

    Organism-specific databases

    DisGeNETi5917.
    MalaCardsiRARS.
    MIMi616140. phenotype.
    OpenTargetsiENSG00000113643.
    PharmGKBiPA34231.

    Chemistry databases

    ChEMBLiCHEMBL2824.

    Polymorphism and mutation databases

    BioMutaiRARS.
    DMDMi20178331.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00000357971 – 660Arginine--tRNA ligase, cytoplasmicAdd BLAST660

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei1N-acetylmethionineCombined sources1

    Keywords - PTMi

    Acetylation

    Proteomic databases

    EPDiP54136.
    MaxQBiP54136.
    PaxDbiP54136.
    PeptideAtlasiP54136.
    PRIDEiP54136.

    PTM databases

    iPTMnetiP54136.
    PhosphoSitePlusiP54136.
    SwissPalmiP54136.

    Expressioni

    Gene expression databases

    BgeeiENSG00000113643.
    CleanExiHS_RARS.
    ExpressionAtlasiP54136. baseline and differential.
    GenevisibleiP54136. HS.

    Organism-specific databases

    HPAiHPA003979.
    HPA004130.

    Interactioni

    Subunit structurei

    Interacts (via N-terminus) with AIMP1 (via N-terminus); this stimulates its catalytic activity. Interacts (via N-terminus) with LARS2 (via C-terminus). Monomer; also part of a multisubunit complex that groups tRNA ligases for Arg, Asp, Glu, Gln, Ile, Leu, Lys, Met and Pro. Interacts with QARS.4 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    LARSQ9P2J53EBI-355482,EBI-356077

    GO - Molecular functioni

    • cadherin binding involved in cell-cell adhesion Source: BHF-UCL

    Protein-protein interaction databases

    BioGridi111852. 59 interactors.
    IntActiP54136. 16 interactors.
    MINTiMINT-5006018.
    STRINGi9606.ENSP00000231572.

    Chemistry databases

    BindingDBiP54136.

    Structurei

    Secondary structure

    1660
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Helixi76 – 91Combined sources16
    Beta strandi102 – 104Combined sources3
    Beta strandi108 – 110Combined sources3
    Beta strandi112 – 115Combined sources4
    Helixi117 – 123Combined sources7
    Helixi134 – 143Combined sources10
    Beta strandi149 – 155Combined sources7
    Turni158 – 160Combined sources3
    Beta strandi162 – 166Combined sources5
    Helixi168 – 181Combined sources14
    Beta strandi193 – 197Combined sources5
    Helixi209 – 227Combined sources19
    Beta strandi231 – 236Combined sources6
    Beta strandi241 – 243Combined sources3
    Helixi244 – 255Combined sources12
    Helixi257 – 260Combined sources4
    Helixi269 – 282Combined sources14
    Helixi285 – 298Combined sources14
    Turni302 – 304Combined sources3
    Helixi305 – 325Combined sources21
    Helixi335 – 341Combined sources7
    Helixi342 – 351Combined sources10
    Beta strandi355 – 358Combined sources4
    Beta strandi361 – 364Combined sources4
    Beta strandi373 – 376Combined sources4
    Helixi384 – 397Combined sources14
    Beta strandi402 – 409Combined sources8
    Helixi410 – 412Combined sources3
    Helixi413 – 425Combined sources13
    Turni431 – 433Combined sources3
    Beta strandi434 – 441Combined sources8
    Beta strandi449 – 451Combined sources3
    Beta strandi455 – 458Combined sources4
    Helixi462 – 478Combined sources17
    Beta strandi482 – 485Combined sources4
    Helixi487 – 490Combined sources4
    Helixi493 – 508Combined sources16
    Beta strandi512 – 514Combined sources3
    Helixi520 – 523Combined sources4
    Beta strandi526 – 530Combined sources5
    Helixi531 – 546Combined sources16
    Turni547 – 549Combined sources3
    Helixi552 – 561Combined sources10
    Helixi569 – 578Combined sources10
    Helixi581 – 591Combined sources11
    Helixi595 – 614Combined sources20
    Beta strandi617 – 620Combined sources4
    Turni622 – 624Combined sources3
    Beta strandi627 – 630Combined sources4
    Helixi632 – 652Combined sources21

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    4Q2TX-ray2.40A/B73-660[»]
    4Q2XX-ray2.80A/B73-660[»]
    4Q2YX-ray2.80A/B73-660[»]
    4R3ZX-ray4.03B1-660[»]
    4ZAJX-ray2.22A73-660[»]
    ProteinModelPortaliP54136.
    SMRiP54136.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni1 – 72Could be involved in the assembly of the multisynthetase complexAdd BLAST72

    Motif

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Motifi201 – 212"HIGH" regionAdd BLAST12

    Domaini

    The N-terminus (AA 1-72) has two regions predicted to be alpha-helical that might be involved in the multisynthetase complex assembly.

    Sequence similaritiesi

    Phylogenomic databases

    eggNOGiKOG1195. Eukaryota.
    COG0018. LUCA.
    GeneTreeiENSGT00530000063407.
    HOGENOMiHOG000247212.
    HOVERGENiHBG029238.
    InParanoidiP54136.
    KOiK01887.
    OMAiTAMFLLY.
    OrthoDBiEOG091G03A6.
    PhylomeDBiP54136.
    TreeFamiTF106111.

    Family and domain databases

    Gene3Di1.10.730.10. 1 hit.
    3.30.1360.70. 1 hit.
    3.40.50.620. 1 hit.
    HAMAPiMF_00123. Arg_tRNA_synth. 1 hit.
    InterProiIPR001412. aa-tRNA-synth_I_CS.
    IPR001278. Arg-tRNA-ligase.
    IPR005148. Arg-tRNA-synth_N.
    IPR008909. DALR_anticod-bd.
    IPR014729. Rossmann-like_a/b/a_fold.
    IPR009080. tRNAsynth_Ia_anticodon-bd.
    [Graphical view]
    PANTHERiPTHR11956. PTHR11956. 1 hit.
    PfamiPF03485. Arg_tRNA_synt_N. 1 hit.
    PF05746. DALR_1. 1 hit.
    PF00750. tRNA-synt_1d. 1 hit.
    [Graphical view]
    PRINTSiPR01038. TRNASYNTHARG.
    SMARTiSM01016. Arg_tRNA_synt_N. 1 hit.
    SM00836. DALR_1. 1 hit.
    [Graphical view]
    SUPFAMiSSF47323. SSF47323. 1 hit.
    SSF55190. SSF55190. 1 hit.
    TIGRFAMsiTIGR00456. argS. 1 hit.
    PROSITEiPS00178. AA_TRNA_LIGASE_I. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative initiation. AlignAdd to basket

    Isoform Complexed (identifier: P54136-1) [UniParc]FASTAAdd to basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

            10         20         30         40         50
    MDVLVSECSA RLLQQEEEIK SLTAEIDRLK NCGCLGASPN LEQLQEENLK
    60 70 80 90 100
    LKYRLNILRK SLQAERNKPT KNMINIISRL QEVFGHAIKA AYPDLENPPL
    110 120 130 140 150
    LVTPSQQAKF GDYQCNSAMG ISQMLKTKEQ KVNPREIAEN ITKHLPDNEC
    160 170 180 190 200
    IEKVEIAGPG FINVHLRKDF VSEQLTSLLV NGVQLPALGE NKKVIVDFSS
    210 220 230 240 250
    PNIAKEMHVG HLRSTIIGES ISRLFEFAGY DVLRLNHVGD WGTQFGMLIA
    260 270 280 290 300
    HLQDKFPDYL TVSPPIGDLQ VFYKESKKRF DTEEEFKKRA YQCVVLLQGK
    310 320 330 340 350
    NPDITKAWKL ICDVSRQELN KIYDALDVSL IERGESFYQD RMNDIVKEFE
    360 370 380 390 400
    DRGFVQVDDG RKIVFVPGCS IPLTIVKSDG GYTYDTSDLA AIKQRLFEEK
    410 420 430 440 450
    ADMIIYVVDN GQSVHFQTIF AAAQMIGWYD PKVTRVFHAG FGVVLGEDKK
    460 470 480 490 500
    KFKTRSGETV RLMDLLGEGL KRSMDKLKEK ERDKVLTAEE LNAAQTSVAY
    510 520 530 540 550
    GCIKYADLSH NRLNDYIFSF DKMLDDRGNT AAYLLYAFTR IRSIARLANI
    560 570 580 590 600
    DEEMLQKAAR ETKILLDHEK EWKLGRCILR FPEILQKILD DLFLHTLCDY
    610 620 630 640 650
    IYELATAFTE FYDSCYCVEK DRQTGKILKV NMWRMLLCEA VAAVMAKGFD
    660
    ILGIKPVQRM
    Length:660
    Mass (Da):75,379
    Last modified:April 16, 2002 - v2
    Checksum:iFE9FB5C910709956
    GO
    Isoform Monomeric (identifier: P54136-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-72: Missing.

    Show »
    Length:588
    Mass (Da):67,140
    Checksum:i857EA1F69F3B6A3B
    GO

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti39P → S in AAB35627 (PubMed:7590355).Curated1
    Sequence conflicti130 – 131QK → PE in AAB35627 (PubMed:7590355).Curated2
    Sequence conflicti135 – 137REI → GEF in AAB35627 (PubMed:7590355).Curated3
    Sequence conflicti147 – 156DNECIEKVEI → AMDVLKRVEF in AAB35627 (PubMed:7590355).Curated10
    Sequence conflicti164V → G in AAB35627 (PubMed:7590355).Curated1
    Sequence conflicti278K → N in BAG37326 (PubMed:14702039).Curated1
    Sequence conflicti308 – 312WKLIC → YLLMS in AAB35627 (PubMed:7590355).Curated5
    Sequence conflicti341R → G in BAD96517 (Ref. 4) Curated1
    Sequence conflicti358D → G in BAG37326 (PubMed:14702039).Curated1
    Sequence conflicti487T → A in BAD96517 (Ref. 4) Curated1
    Sequence conflicti567D → V in AAB35627 (PubMed:7590355).Curated1
    Sequence conflicti635 – 640MLLCEA → ILCET in AAB35627 (PubMed:7590355).Curated6
    Sequence conflicti651I → T in AAB35627 (PubMed:7590355).Curated1
    Sequence conflicti657 – 660VQRM → GPRV in AAB35627 (PubMed:7590355).Curated4

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_0726662D → G in HLD9. 1 PublicationCorresponds to variant rs672601372dbSNPEnsembl.1
    Natural variantiVAR_0201063V → I.Corresponds to variant rs244903dbSNPEnsembl.1
    Natural variantiVAR_052635135R → G.Corresponds to variant rs1059443dbSNPEnsembl.1
    Natural variantiVAR_020107397F → Y.Corresponds to variant rs2305734dbSNPEnsembl.1
    Natural variantiVAR_072667512R → Q in HLD9. 1 PublicationCorresponds to variant rs369398935dbSNPEnsembl.1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_0189051 – 72Missing in isoform Monomeric. CuratedAdd BLAST72

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    S80343 mRNA. Translation: AAB35627.1.
    BT007394 mRNA. Translation: AAP36058.1.
    AK314795 mRNA. Translation: BAG37326.1.
    AK222797 mRNA. Translation: BAD96517.1.
    BC000528 mRNA. Translation: AAH00528.1.
    BC014619 mRNA. Translation: AAH14619.1.
    CCDSiCCDS4367.1. [P54136-1]
    PIRiJC4365.
    RefSeqiNP_002878.2. NM_002887.3. [P54136-1]
    UniGeneiHs.654907.

    Genome annotation databases

    EnsembliENST00000231572; ENSP00000231572; ENSG00000113643. [P54136-1]
    GeneIDi5917.
    KEGGihsa:5917.
    UCSCiuc003lzx.4. human. [P54136-1]

    Keywords - Coding sequence diversityi

    Alternative initiation, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    S80343 mRNA. Translation: AAB35627.1.
    BT007394 mRNA. Translation: AAP36058.1.
    AK314795 mRNA. Translation: BAG37326.1.
    AK222797 mRNA. Translation: BAD96517.1.
    BC000528 mRNA. Translation: AAH00528.1.
    BC014619 mRNA. Translation: AAH14619.1.
    CCDSiCCDS4367.1. [P54136-1]
    PIRiJC4365.
    RefSeqiNP_002878.2. NM_002887.3. [P54136-1]
    UniGeneiHs.654907.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    4Q2TX-ray2.40A/B73-660[»]
    4Q2XX-ray2.80A/B73-660[»]
    4Q2YX-ray2.80A/B73-660[»]
    4R3ZX-ray4.03B1-660[»]
    4ZAJX-ray2.22A73-660[»]
    ProteinModelPortaliP54136.
    SMRiP54136.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi111852. 59 interactors.
    IntActiP54136. 16 interactors.
    MINTiMINT-5006018.
    STRINGi9606.ENSP00000231572.

    Chemistry databases

    BindingDBiP54136.
    ChEMBLiCHEMBL2824.

    PTM databases

    iPTMnetiP54136.
    PhosphoSitePlusiP54136.
    SwissPalmiP54136.

    Polymorphism and mutation databases

    BioMutaiRARS.
    DMDMi20178331.

    Proteomic databases

    EPDiP54136.
    MaxQBiP54136.
    PaxDbiP54136.
    PeptideAtlasiP54136.
    PRIDEiP54136.

    Protocols and materials databases

    DNASUi5917.
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000231572; ENSP00000231572; ENSG00000113643. [P54136-1]
    GeneIDi5917.
    KEGGihsa:5917.
    UCSCiuc003lzx.4. human. [P54136-1]

    Organism-specific databases

    CTDi5917.
    DisGeNETi5917.
    GeneCardsiRARS.
    HGNCiHGNC:9870. RARS.
    HPAiHPA003979.
    HPA004130.
    MalaCardsiRARS.
    MIMi107820. gene.
    616140. phenotype.
    neXtProtiNX_P54136.
    OpenTargetsiENSG00000113643.
    PharmGKBiPA34231.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG1195. Eukaryota.
    COG0018. LUCA.
    GeneTreeiENSGT00530000063407.
    HOGENOMiHOG000247212.
    HOVERGENiHBG029238.
    InParanoidiP54136.
    KOiK01887.
    OMAiTAMFLLY.
    OrthoDBiEOG091G03A6.
    PhylomeDBiP54136.
    TreeFamiTF106111.

    Enzyme and pathway databases

    BioCyciZFISH:HS03704-MONOMER.
    ReactomeiR-HSA-2408517. SeMet incorporation into proteins.
    R-HSA-379716. Cytosolic tRNA aminoacylation.

    Miscellaneous databases

    ChiTaRSiRARS. human.
    GeneWikiiRARS_(gene).
    GenomeRNAii5917.
    PROiP54136.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000113643.
    CleanExiHS_RARS.
    ExpressionAtlasiP54136. baseline and differential.
    GenevisibleiP54136. HS.

    Family and domain databases

    Gene3Di1.10.730.10. 1 hit.
    3.30.1360.70. 1 hit.
    3.40.50.620. 1 hit.
    HAMAPiMF_00123. Arg_tRNA_synth. 1 hit.
    InterProiIPR001412. aa-tRNA-synth_I_CS.
    IPR001278. Arg-tRNA-ligase.
    IPR005148. Arg-tRNA-synth_N.
    IPR008909. DALR_anticod-bd.
    IPR014729. Rossmann-like_a/b/a_fold.
    IPR009080. tRNAsynth_Ia_anticodon-bd.
    [Graphical view]
    PANTHERiPTHR11956. PTHR11956. 1 hit.
    PfamiPF03485. Arg_tRNA_synt_N. 1 hit.
    PF05746. DALR_1. 1 hit.
    PF00750. tRNA-synt_1d. 1 hit.
    [Graphical view]
    PRINTSiPR01038. TRNASYNTHARG.
    SMARTiSM01016. Arg_tRNA_synt_N. 1 hit.
    SM00836. DALR_1. 1 hit.
    [Graphical view]
    SUPFAMiSSF47323. SSF47323. 1 hit.
    SSF55190. SSF55190. 1 hit.
    TIGRFAMsiTIGR00456. argS. 1 hit.
    PROSITEiPS00178. AA_TRNA_LIGASE_I. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Entry informationi

    Entry nameiSYRC_HUMAN
    AccessioniPrimary (citable) accession number: P54136
    Secondary accession number(s): B2RBS9, Q53GY4, Q9BWA1
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 1, 1996
    Last sequence update: April 16, 2002
    Last modified: November 30, 2016
    This is version 170 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Aminoacyl-tRNA synthetases
      List of aminoacyl-tRNA synthetase entries
    2. Human chromosome 5
      Human chromosome 5: entries, gene names and cross-references to MIM
    3. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    4. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    5. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    6. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    7. SIMILARITY comments
      Index of protein domains and families

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.