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Protein

Arginine--tRNA ligase, cytoplasmic

Gene

RARS

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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 (PubMed:25288775). Modulates the secretion of AIMP1 and may be involved in generation of the inflammatory cytokine EMAP2 from AIMP1 (PubMed:17443684).2 Publications

Catalytic activityi

ATP + L-arginine + tRNA(Arg) = AMP + diphosphate + L-arginyl-tRNA(Arg).2 Publications

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

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Binding sitei211L-arginineCombined sources1 Publication1
    Binding sitei384L-arginineCombined sources1 Publication1
    Binding sitei388L-arginineCombined sources1 Publication1
    Binding sitei412L-arginineCombined sources1 Publication1

    GO - Molecular functioni

    • arginine binding Source: Ensembl
    • arginine-tRNA ligase activity Source: UniProtKB
    • ATP binding Source: UniProtKB-KW
    • cadherin binding Source: BHF-UCL
    • tRNA binding Source: Ensembl

    GO - Biological processi

    Keywordsi

    Molecular functionAminoacyl-tRNA synthetase, Ligase
    Biological processProtein biosynthesis
    LigandATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    ReactomeiR-HSA-2408517 SeMet incorporation into proteins
    R-HSA-379716 Cytosolic tRNA aminoacylation

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Arginine--tRNA ligase, cytoplasmic (EC:6.1.1.192 Publications)
    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

    EuPathDBiHostDB:ENSG00000113643.8
    HGNCiHGNC:9870 RARS
    MIMi107820 gene
    neXtProtiNX_P54136

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    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 dbSNP:rs672601372EnsemblClinVar.1
    Natural variantiVAR_072667512R → Q in HLD9. 1 PublicationCorresponds to variant dbSNP:rs369398935EnsemblClinVar.1

    Keywords - Diseasei

    Disease mutation, Leukodystrophy

    Organism-specific databases

    DisGeNETi5917
    MalaCardsiRARS
    MIMi616140 phenotype
    OpenTargetsiENSG00000113643
    Orphaneti438114 RARS-related autosomal recessive hypomyelinating leukodystrophy
    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
    ProteomicsDBi56650
    56651 [P54136-2]

    PTM databases

    iPTMnetiP54136
    PhosphoSitePlusiP54136
    SwissPalmiP54136

    Expressioni

    Gene expression databases

    BgeeiENSG00000113643 Expressed in 112 organ(s), highest expression level in kidney
    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 (PubMed:10358004, PubMed:25288775). Interacts (via N-terminus) with LARS2 (via C-terminus) (PubMed:16055448, PubMed:17443684). Monomer (PubMed:24859084). Part of a multisubunit complex that groups tRNA ligases for Arg (RARS), Asp (DARS), Gln (QARS), Ile (IARS), Leu (LARS), Lys (KARS), Met (MARS) the bifunctional ligase for Glu and Pro (EPRS) and the auxiliary subunits AIMP1/p43, AIMP2/p38 and EEF1E1/p18 (PubMed:19131329, PubMed:19289464). Interacts with QARS (PubMed:24656866). Part of a complex composed of RARS, QARS and AIMP1 (PubMed:25288775).8 Publications

    Binary interactionsi

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

    GO - Molecular functioni

    Protein-protein interaction databases

    BioGridi111852, 145 interactors
    CORUMiP54136
    IntActiP54136, 22 interactors
    MINTiP54136
    STRINGi9606.ENSP00000231572

    Chemistry databases

    BindingDBiP54136

    Structurei

    Secondary structure

    1660
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details

    3D structure databases

    ProteinModelPortaliP54136
    SMRiP54136
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni1 – 72Could be involved in the assembly of the multisynthetase complexAdd BLAST72
    Regioni200 – 202L-arginine bindingCombined sources1 Publication3
    Regioni529 – 543Interaction with tRNABy similarityAdd BLAST15

    Motif

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

    Domaini

    The alpha-helical N-terminus (residues 1-72) mediates interaction with AIMP1 and thereby contributes to the assembly of the multisynthetase complex.1 Publication

    Sequence similaritiesi

    Phylogenomic databases

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

    Family and domain databases

    CDDicd00671 ArgRS_core, 1 hit
    Gene3Di3.30.1360.70, 1 hit
    3.40.50.620, 1 hit
    HAMAPiMF_00123 Arg_tRNA_synth, 1 hit
    InterProiView protein in InterPro
    IPR001412 aa-tRNA-synth_I_CS
    IPR001278 Arg-tRNA-ligase
    IPR005148 Arg-tRNA-synth_N
    IPR036695 Arg-tRNA-synth_N_sf
    IPR035684 ArgRS_core
    IPR008909 DALR_anticod-bd
    IPR014729 Rossmann-like_a/b/a_fold
    IPR009080 tRNAsynth_Ia_anticodon-bd
    PANTHERiPTHR11956 PTHR11956, 1 hit
    PfamiView protein in Pfam
    PF03485 Arg_tRNA_synt_N, 1 hit
    PF05746 DALR_1, 1 hit
    PF00750 tRNA-synt_1d, 1 hit
    PRINTSiPR01038 TRNASYNTHARG
    SMARTiView protein in SMART
    SM01016 Arg_tRNA_synt_N, 1 hit
    SM00836 DALR_1, 1 hit
    SUPFAMiSSF47323 SSF47323, 1 hit
    SSF55190 SSF55190, 1 hit
    TIGRFAMsiTIGR00456 argS, 1 hit
    PROSITEiView protein in PROSITE
    PS00178 AA_TRNA_LIGASE_I, 1 hit

    Sequences (2+)i

    Sequence statusi: Complete.

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

    This entry has 2 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All

    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

    Computationally mapped potential isoform sequencesi

    There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
    EntryEntry nameProtein names
    Gene namesLengthAnnotation
    E5RJM9E5RJM9_HUMAN
    Arginine--tRNA ligase, cytoplasmic
    RARS
    129Annotation score:
    E5RH09E5RH09_HUMAN
    Arginine--tRNA ligase, cytoplasmic
    RARS
    113Annotation score:
    E5RI24E5RI24_HUMAN
    Arginine--tRNA ligase, cytoplasmic
    RARS
    58Annotation score:

    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 dbSNP:rs672601372EnsemblClinVar.1
    Natural variantiVAR_0201063V → I. Corresponds to variant dbSNP:rs244903EnsemblClinVar.1
    Natural variantiVAR_052635135R → G. Corresponds to variant dbSNP:rs1059443Ensembl.1
    Natural variantiVAR_020107397F → Y. Corresponds to variant dbSNP:rs2305734EnsemblClinVar.1
    Natural variantiVAR_072667512R → Q in HLD9. 1 PublicationCorresponds to variant dbSNP:rs369398935EnsemblClinVar.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

    Similar proteinsi

    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, 145 interactors
    CORUMiP54136
    IntActiP54136, 22 interactors
    MINTiP54136
    STRINGi9606.ENSP00000231572

    Chemistry databases

    BindingDBiP54136
    ChEMBLiCHEMBL2824

    PTM databases

    iPTMnetiP54136
    PhosphoSitePlusiP54136
    SwissPalmiP54136

    Polymorphism and mutation databases

    BioMutaiRARS
    DMDMi20178331

    Proteomic databases

    EPDiP54136
    MaxQBiP54136
    PaxDbiP54136
    PeptideAtlasiP54136
    PRIDEiP54136
    ProteomicsDBi56650
    56651 [P54136-2]

    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
    EuPathDBiHostDB:ENSG00000113643.8
    GeneCardsiRARS
    HGNCiHGNC:9870 RARS
    HPAiHPA003979
    HPA004130
    MalaCardsiRARS
    MIMi107820 gene
    616140 phenotype
    neXtProtiNX_P54136
    OpenTargetsiENSG00000113643
    Orphaneti438114 RARS-related autosomal recessive hypomyelinating leukodystrophy
    PharmGKBiPA34231
    GenAtlasiSearch...

    Phylogenomic databases

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

    Enzyme and pathway databases

    ReactomeiR-HSA-2408517 SeMet incorporation into proteins
    R-HSA-379716 Cytosolic tRNA aminoacylation

    Miscellaneous databases

    ChiTaRSiRARS human
    GeneWikiiRARS_(gene)
    GenomeRNAii5917
    PROiPR:P54136
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000113643 Expressed in 112 organ(s), highest expression level in kidney
    CleanExiHS_RARS
    ExpressionAtlasiP54136 baseline and differential
    GenevisibleiP54136 HS

    Family and domain databases

    CDDicd00671 ArgRS_core, 1 hit
    Gene3Di3.30.1360.70, 1 hit
    3.40.50.620, 1 hit
    HAMAPiMF_00123 Arg_tRNA_synth, 1 hit
    InterProiView protein in InterPro
    IPR001412 aa-tRNA-synth_I_CS
    IPR001278 Arg-tRNA-ligase
    IPR005148 Arg-tRNA-synth_N
    IPR036695 Arg-tRNA-synth_N_sf
    IPR035684 ArgRS_core
    IPR008909 DALR_anticod-bd
    IPR014729 Rossmann-like_a/b/a_fold
    IPR009080 tRNAsynth_Ia_anticodon-bd
    PANTHERiPTHR11956 PTHR11956, 1 hit
    PfamiView protein in Pfam
    PF03485 Arg_tRNA_synt_N, 1 hit
    PF05746 DALR_1, 1 hit
    PF00750 tRNA-synt_1d, 1 hit
    PRINTSiPR01038 TRNASYNTHARG
    SMARTiView protein in SMART
    SM01016 Arg_tRNA_synt_N, 1 hit
    SM00836 DALR_1, 1 hit
    SUPFAMiSSF47323 SSF47323, 1 hit
    SSF55190 SSF55190, 1 hit
    TIGRFAMsiTIGR00456 argS, 1 hit
    PROSITEiView protein in PROSITE
    PS00178 AA_TRNA_LIGASE_I, 1 hit
    ProtoNetiSearch...

    Entry informationi

    Entry nameiSYRC_HUMAN
    AccessioniPrimary (citable) accession number: P54136
    Secondary accession number(s): B2RBS9, Q53GY4, Q9BWA1
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
    Last sequence update: April 16, 2002
    Last modified: November 7, 2018
    This is version 190 of the entry and version 2 of the sequence. See 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. SIMILARITY comments
      Index of protein domains and families
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. Human chromosome 5
      Human chromosome 5: entries, gene names and cross-references to MIM
    7. Aminoacyl-tRNA synthetases
      List of aminoacyl-tRNA synthetase entries
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