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Protein

Aspartate--tRNA ligase, cytoplasmic

Gene

DARS

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

Functioni

Catalyzes the specific attachment of an amino acid to its cognate tRNA in a 2 step reaction: the amino acid (AA) is first activated by ATP to form AA-AMP and then transferred to the acceptor end of the tRNA.

Catalytic activityi

ATP + L-aspartate + tRNA(Asp) = AMP + diphosphate + L-aspartyl-tRNA(Asp).

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei229AspartateBy similarity1
Binding sitei273AspartateBy similarity1
Binding sitei424ATPBy similarity1
Binding sitei427AspartateBy similarity1
Binding sitei431AspartateBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi273 – 275ATPBy similarity3
Nucleotide bindingi281 – 283ATPBy similarity3
Nucleotide bindingi472 – 475ATPBy similarity4

GO - Molecular functioni

  • aminoacylase activity Source: ProtInc
  • aspartate-tRNA ligase activity Source: ProtInc
  • ATP binding Source: UniProtKB-KW
  • poly(A) RNA binding Source: UniProtKB

GO - Biological processi

  • aspartyl-tRNA aminoacylation Source: ProtInc
  • protein complex assembly Source: ProtInc
  • translation 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:HS03946-MONOMER.
BRENDAi6.1.1.12. 2681.
ReactomeiR-HSA-2408517. SeMet incorporation into proteins.
R-HSA-379716. Cytosolic tRNA aminoacylation.

Names & Taxonomyi

Protein namesi
Recommended name:
Aspartate--tRNA ligase, cytoplasmic (EC:6.1.1.12)
Alternative name(s):
Aspartyl-tRNA synthetase
Short name:
AspRS
Cell proliferation-inducing gene 40 protein
Gene namesi
Name:DARS
ORF Names:PIG40
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:2678. DARS.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: HPA
  • cytosol Source: Reactome
  • extracellular exosome Source: UniProtKB
  • membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Involvement in diseasei

Hypomyelination with brainstem and spinal cord involvement and leg spasticity (HBSL)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal recessive leukoencephalopathy characterized by onset in the first year of life of severe spasticity, mainly affecting the lower limbs and resulting in an inability to achieve independent ambulation. Affected individuals show delayed motor development and nystagmus; some may have mild mental retardation. Brain MRI shows hypomyelination and white matter lesions in the cerebrum, brainstem, cerebellum, and spinal cord.
See also OMIM:615281
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_070038256M → L in HBSL. 1 Publication1
Natural variantiVAR_070039274A → V in HBSL. 1 PublicationCorresponds to variant rs369152939dbSNPEnsembl.1
Natural variantiVAR_070040367D → Y in HBSL. 1 PublicationCorresponds to variant rs370064817dbSNPEnsembl.1
Natural variantiVAR_070041460R → H in HBSL. 1 PublicationCorresponds to variant rs587776985dbSNPEnsembl.1
Natural variantiVAR_070042464P → L in HBSL. 1 PublicationCorresponds to variant rs148806569dbSNPEnsembl.1
Natural variantiVAR_070043487R → C in HBSL. 1 PublicationCorresponds to variant rs587776984dbSNPEnsembl.1
Natural variantiVAR_070044494R → C in HBSL. 1 PublicationCorresponds to variant rs147077598dbSNPEnsembl.1
Natural variantiVAR_070045494R → G in HBSL. 1 PublicationCorresponds to variant rs147077598dbSNPEnsembl.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi1615.
MalaCardsiDARS.
MIMi615281. phenotype.
OpenTargetsiENSG00000115866.
Orphaneti363412. Hypomyelination with brain stem and spinal cord involvement and leg spasticity.
PharmGKBiPA27146.

Chemistry databases

DrugBankiDB00128. L-Aspartic Acid.

Polymorphism and mutation databases

BioMutaiDARS.
DMDMi20178330.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001110101 – 501Aspartate--tRNA ligase, cytoplasmicAdd BLAST501

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei52PhosphothreonineCombined sources1
Modified residuei74N6-acetyllysineCombined sources1
Modified residuei249PhosphoserineCombined sources1
Modified residuei374N6-acetyllysineCombined sources1
Modified residuei500Phosphothreonine; by PKASequence analysis1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP14868.
MaxQBiP14868.
PaxDbiP14868.
PeptideAtlasiP14868.
PRIDEiP14868.

2D gel databases

OGPiP14868.
REPRODUCTION-2DPAGEIPI00216951.

PTM databases

iPTMnetiP14868.
PhosphoSitePlusiP14868.
SwissPalmiP14868.

Expressioni

Tissue specificityi

Expression in the developing and adult brain shows similar patterns. Highly expressed in the ventricular and subventricular zones, including hippocampal subfields, the midlateral temporaal cortex and the frontal polar cortex. The cerebellum, cereral cortex, hippocampus, and lateral ventricle show preferential neuronal expression. Expression in the peripheral neurons is evident in the colon.1 Publication

Gene expression databases

BgeeiENSG00000115866.
CleanExiHS_DARS.
ExpressionAtlasiP14868. baseline and differential.
GenevisibleiP14868. HS.

Organism-specific databases

HPAiHPA020451.
HPA029804.
HPA029805.

Interactioni

Subunit structurei

Homodimer; also part of a multisubunit complex that groups AIMP1, AIMP2, EEF1A1 and tRNA ligases for Arg, Asp, Glu, Gln, Ile, Leu, Lys, Met and Pro.

Binary interactionsi

WithEntry#Exp.IntActNotes
AIMP2Q1315511EBI-358730,EBI-745226
FOXM1Q080502EBI-358730,EBI-866480
GRB2P629932EBI-358730,EBI-401755

Protein-protein interaction databases

BioGridi107984. 82 interactors.
IntActiP14868. 24 interactors.
MINTiMINT-141082.
STRINGi9606.ENSP00000264161.

Structurei

Secondary structure

1501
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi26 – 28Combined sources3
Beta strandi29 – 31Combined sources3
Helixi48 – 50Combined sources3
Helixi53 – 55Combined sources3
Beta strandi59 – 72Combined sources14
Beta strandi75 – 82Combined sources8
Beta strandi85 – 93Combined sources9
Turni94 – 96Combined sources3
Helixi99 – 107Combined sources9
Beta strandi113 – 122Combined sources10
Beta strandi134 – 146Combined sources13
Helixi156 – 160Combined sources5
Helixi176 – 181Combined sources6
Helixi183 – 186Combined sources4
Helixi190 – 212Combined sources23
Helixi250 – 259Combined sources10
Beta strandi264 – 271Combined sources8
Beta strandi286 – 294Combined sources9
Helixi300 – 320Combined sources21
Helixi322 – 331Combined sources10
Beta strandi344 – 347Combined sources4
Helixi348 – 357Combined sources10
Helixi370 – 384Combined sources15
Beta strandi387 – 392Combined sources6
Helixi396 – 398Combined sources3
Beta strandi407 – 409Combined sources3
Beta strandi412 – 420Combined sources9
Beta strandi423 – 431Combined sources9
Helixi435 – 444Combined sources10
Helixi450 – 452Combined sources3
Helixi453 – 457Combined sources5
Turni458 – 461Combined sources4
Beta strandi466 – 472Combined sources7
Helixi473 – 481Combined sources9
Helixi486 – 489Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4J15X-ray2.24A/B1-501[»]
ProteinModelPortaliP14868.
SMRiP14868.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni251 – 254AspartateBy similarity4
Regioni411 – 415Binding site for the 3'-end of tRNASequence analysis5

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0556. Eukaryota.
COG0017. LUCA.
GeneTreeiENSGT00550000074880.
HOVERGENiHBG001028.
InParanoidiP14868.
KOiK01876.
OMAiWGDDLST.
OrthoDBiEOG091G0530.
PhylomeDBiP14868.
TreeFamiTF105676.

Family and domain databases

HAMAPiMF_02075. Asp_tRNA_synth_type2. 1 hit.
InterProiIPR004364. aa-tRNA-synt_II.
IPR018150. aa-tRNA-synt_II-like.
IPR006195. aa-tRNA-synth_II.
IPR004523. Asp-tRNA_synthase_arc.
IPR002312. Asp/Asn-tRNA-synth_IIb.
IPR012340. NA-bd_OB-fold.
IPR004365. NA-bd_OB_tRNA.
[Graphical view]
PANTHERiPTHR22594. PTHR22594. 1 hit.
PTHR22594:SF33. PTHR22594:SF33. 1 hit.
PfamiPF00152. tRNA-synt_2. 1 hit.
PF01336. tRNA_anti-codon. 1 hit.
[Graphical view]
PRINTSiPR01042. TRNASYNTHASP.
SUPFAMiSSF50249. SSF50249. 1 hit.
TIGRFAMsiTIGR00458. aspS_nondisc. 1 hit.
PROSITEiPS50862. AA_TRNA_LIGASE_II. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: P14868-1) [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
MPSASASRKS QEKPREIMDA AEDYAKERYG ISSMIQSQEK PDRVLVRVRD
60 70 80 90 100
LTIQKADEVV WVRARVHTSR AKGKQCFLVL RQQQFNVQAL VAVGDHASKQ
110 120 130 140 150
MVKFAANINK ESIVDVEGVV RKVNQKIGSC TQQDVELHVQ KIYVISLAEP
160 170 180 190 200
RLPLQLDDAV RPEAEGEEEG RATVNQDTRL DNRVIDLRTS TSQAVFRLQS
210 220 230 240 250
GICHLFRETL INKGFVEIQT PKIISAASEG GANVFTVSYF KNNAYLAQSP
260 270 280 290 300
QLYKQMCICA DFEKVFSIGP VFRAEDSNTH RHLTEFVGLD IEMAFNYHYH
310 320 330 340 350
EVMEEIADTM VQIFKGLQER FQTEIQTVNK QFPCEPFKFL EPTLRLEYCE
360 370 380 390 400
ALAMLREAGV EMGDEDDLST PNEKLLGHLV KEKYDTDFYI LDKYPLAVRP
410 420 430 440 450
FYTMPDPRNP KQSNSYDMFM RGEEILSGAQ RIHDPQLLTE RALHHGIDLE
460 470 480 490 500
KIKAYIDSFR FGAPPHAGGG IGLERVTMLF LGLHNVRQTS MFPRDPKRLT

P
Length:501
Mass (Da):57,136
Last modified:April 16, 2002 - v2
Checksum:iB181572DF0AF5F94
GO
Isoform 2 (identifier: P14868-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-100: Missing.

Note: No experimental confirmation available.
Show »
Length:401
Mass (Da):45,771
Checksum:i0383EB6177DD0739
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti5 – 7SAS → TQ in AAA35567 (PubMed:2674137).Curated3
Sequence conflicti31I → T in AAI07750 (PubMed:15489334).Curated1
Sequence conflicti38Q → H in BAD96196 (Ref. 5) Curated1
Sequence conflicti164A → Q in AAA35567 (PubMed:2674137).Curated1
Sequence conflicti312Q → H in AAX07827 (Ref. 2) Curated1
Sequence conflicti414N → K in AAA35567 (PubMed:2674137).Curated1
Sequence conflicti447I → N in AAA35567 (PubMed:2674137).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_070038256M → L in HBSL. 1 Publication1
Natural variantiVAR_070039274A → V in HBSL. 1 PublicationCorresponds to variant rs369152939dbSNPEnsembl.1
Natural variantiVAR_070040367D → Y in HBSL. 1 PublicationCorresponds to variant rs370064817dbSNPEnsembl.1
Natural variantiVAR_027611426L → F.Corresponds to variant rs1803165dbSNPEnsembl.1
Natural variantiVAR_070041460R → H in HBSL. 1 PublicationCorresponds to variant rs587776985dbSNPEnsembl.1
Natural variantiVAR_070042464P → L in HBSL. 1 PublicationCorresponds to variant rs148806569dbSNPEnsembl.1
Natural variantiVAR_070043487R → C in HBSL. 1 PublicationCorresponds to variant rs587776984dbSNPEnsembl.1
Natural variantiVAR_070044494R → C in HBSL. 1 PublicationCorresponds to variant rs147077598dbSNPEnsembl.1
Natural variantiVAR_070045494R → G in HBSL. 1 PublicationCorresponds to variant rs147077598dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0561921 – 100Missing in isoform 2. 1 PublicationAdd BLAST100

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J05032 mRNA. Translation: AAA35567.1.
AY762100 mRNA. Translation: AAX07827.1.
BT006710 mRNA. Translation: AAP35356.1.
AK290607 mRNA. Translation: BAF83296.1.
AK222476 mRNA. Translation: BAD96196.1.
CR749809 mRNA. Translation: CAH18669.1.
AC011999 Genomic DNA. No translation available.
AC093391 Genomic DNA. No translation available.
CH471058 Genomic DNA. Translation: EAX11617.1.
CH471058 Genomic DNA. Translation: EAX11620.1.
BC000629 mRNA. Translation: AAH00629.1.
BC107749 mRNA. Translation: AAI07750.1.
CCDSiCCDS2180.1. [P14868-1]
PIRiA34393. SYHUDT.
RefSeqiNP_001280241.1. NM_001293312.1. [P14868-2]
NP_001340.2. NM_001349.3. [P14868-1]
UniGeneiHs.503787.
Hs.595819.

Genome annotation databases

EnsembliENST00000264161; ENSP00000264161; ENSG00000115866. [P14868-1]
GeneIDi1615.
KEGGihsa:1615.
UCSCiuc002tux.2. human. [P14868-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J05032 mRNA. Translation: AAA35567.1.
AY762100 mRNA. Translation: AAX07827.1.
BT006710 mRNA. Translation: AAP35356.1.
AK290607 mRNA. Translation: BAF83296.1.
AK222476 mRNA. Translation: BAD96196.1.
CR749809 mRNA. Translation: CAH18669.1.
AC011999 Genomic DNA. No translation available.
AC093391 Genomic DNA. No translation available.
CH471058 Genomic DNA. Translation: EAX11617.1.
CH471058 Genomic DNA. Translation: EAX11620.1.
BC000629 mRNA. Translation: AAH00629.1.
BC107749 mRNA. Translation: AAI07750.1.
CCDSiCCDS2180.1. [P14868-1]
PIRiA34393. SYHUDT.
RefSeqiNP_001280241.1. NM_001293312.1. [P14868-2]
NP_001340.2. NM_001349.3. [P14868-1]
UniGeneiHs.503787.
Hs.595819.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4J15X-ray2.24A/B1-501[»]
ProteinModelPortaliP14868.
SMRiP14868.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107984. 82 interactors.
IntActiP14868. 24 interactors.
MINTiMINT-141082.
STRINGi9606.ENSP00000264161.

Chemistry databases

DrugBankiDB00128. L-Aspartic Acid.

PTM databases

iPTMnetiP14868.
PhosphoSitePlusiP14868.
SwissPalmiP14868.

Polymorphism and mutation databases

BioMutaiDARS.
DMDMi20178330.

2D gel databases

OGPiP14868.
REPRODUCTION-2DPAGEIPI00216951.

Proteomic databases

EPDiP14868.
MaxQBiP14868.
PaxDbiP14868.
PeptideAtlasiP14868.
PRIDEiP14868.

Protocols and materials databases

DNASUi1615.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000264161; ENSP00000264161; ENSG00000115866. [P14868-1]
GeneIDi1615.
KEGGihsa:1615.
UCSCiuc002tux.2. human. [P14868-1]

Organism-specific databases

CTDi1615.
DisGeNETi1615.
GeneCardsiDARS.
HGNCiHGNC:2678. DARS.
HPAiHPA020451.
HPA029804.
HPA029805.
MalaCardsiDARS.
MIMi603084. gene.
615281. phenotype.
neXtProtiNX_P14868.
OpenTargetsiENSG00000115866.
Orphaneti363412. Hypomyelination with brain stem and spinal cord involvement and leg spasticity.
PharmGKBiPA27146.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0556. Eukaryota.
COG0017. LUCA.
GeneTreeiENSGT00550000074880.
HOVERGENiHBG001028.
InParanoidiP14868.
KOiK01876.
OMAiWGDDLST.
OrthoDBiEOG091G0530.
PhylomeDBiP14868.
TreeFamiTF105676.

Enzyme and pathway databases

BioCyciZFISH:HS03946-MONOMER.
BRENDAi6.1.1.12. 2681.
ReactomeiR-HSA-2408517. SeMet incorporation into proteins.
R-HSA-379716. Cytosolic tRNA aminoacylation.

Miscellaneous databases

ChiTaRSiDARS. human.
GeneWikiiDARS_(gene).
GenomeRNAii1615.
PROiP14868.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000115866.
CleanExiHS_DARS.
ExpressionAtlasiP14868. baseline and differential.
GenevisibleiP14868. HS.

Family and domain databases

HAMAPiMF_02075. Asp_tRNA_synth_type2. 1 hit.
InterProiIPR004364. aa-tRNA-synt_II.
IPR018150. aa-tRNA-synt_II-like.
IPR006195. aa-tRNA-synth_II.
IPR004523. Asp-tRNA_synthase_arc.
IPR002312. Asp/Asn-tRNA-synth_IIb.
IPR012340. NA-bd_OB-fold.
IPR004365. NA-bd_OB_tRNA.
[Graphical view]
PANTHERiPTHR22594. PTHR22594. 1 hit.
PTHR22594:SF33. PTHR22594:SF33. 1 hit.
PfamiPF00152. tRNA-synt_2. 1 hit.
PF01336. tRNA_anti-codon. 1 hit.
[Graphical view]
PRINTSiPR01042. TRNASYNTHASP.
SUPFAMiSSF50249. SSF50249. 1 hit.
TIGRFAMsiTIGR00458. aspS_nondisc. 1 hit.
PROSITEiPS50862. AA_TRNA_LIGASE_II. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiSYDC_HUMAN
AccessioniPrimary (citable) accession number: P14868
Secondary accession number(s): A8K3J2
, D3DP77, Q2TNI3, Q32Q69, Q53HV4, Q53YC5, Q68CR9, Q9BW52
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: April 16, 2002
Last modified: November 30, 2016
This is version 176 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, Reference proteome

Documents

  1. Aminoacyl-tRNA synthetases
    List of aminoacyl-tRNA synthetase entries
  2. Human chromosome 2
    Human chromosome 2: 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.