Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Aspartate--tRNA ligase, cytoplasmic

Gene

DARS

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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.By similarity

Catalytic activityi

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

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: GO_Central
  • ATP binding Source: UniProtKB-KW
  • RNA binding Source: UniProtKB

GO - Biological processi

Keywordsi

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

Enzyme and pathway databases

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:6.1.1.12By similarity)
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

EuPathDBiHostDB:ENSG00000115866.10
HGNCiHGNC:2678 DARS
MIMi603084 gene
neXtProtiNX_P14868

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

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 PublicationCorresponds to variant dbSNP:rs886037635EnsemblClinVar.1
Natural variantiVAR_070039274A → V in HBSL. 1 PublicationCorresponds to variant dbSNP:rs369152939EnsemblClinVar.1
Natural variantiVAR_070040367D → Y in HBSL. 1 PublicationCorresponds to variant dbSNP:rs370064817EnsemblClinVar.1
Natural variantiVAR_070041460R → H in HBSL. 1 PublicationCorresponds to variant dbSNP:rs587776985EnsemblClinVar.1
Natural variantiVAR_070042464P → L in HBSL. 1 PublicationCorresponds to variant dbSNP:rs148806569Ensembl.1
Natural variantiVAR_070043487R → C in HBSL. 1 PublicationCorresponds to variant dbSNP:rs587776984EnsemblClinVar.1
Natural variantiVAR_070044494R → C in HBSL. 1 PublicationCorresponds to variant dbSNP:rs147077598EnsemblClinVar.1
Natural variantiVAR_070045494R → G in HBSL. 1 PublicationCorresponds to variant dbSNP:rs147077598EnsemblClinVar.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
ProteomicsDBi53092

2D gel databases

OGPiP14868
REPRODUCTION-2DPAGEiIPI00216951

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 Expressed in 242 organ(s), highest expression level in oocyte
CleanExiHS_DARS
ExpressionAtlasiP14868 baseline and differential
GenevisibleiP14868 HS

Organism-specific databases

HPAiHPA020451
HPA029804
HPA029805

Interactioni

Subunit structurei

Homodimer (PubMed:23609930). 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).3 Publications

Binary interactionsi

Protein-protein interaction databases

BioGridi107984, 180 interactors
CORUMiP14868
IntActiP14868, 35 interactors
MINTiP14868
STRINGi9606.ENSP00000264161

Structurei

Secondary structure

1501
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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
KOiK22503
OMAiWVHEIRD
OrthoDBiEOG091G0530
PhylomeDBiP14868
TreeFamiTF105676

Family and domain databases

HAMAPiMF_02075 Asp_tRNA_synth_type2, 1 hit
InterProiView protein in InterPro
IPR004364 aa-tRNA-synt_II
IPR006195 aa-tRNA-synth_II
IPR004523 Asp-tRNA_synthase_2
IPR002312 Asp/Asn-tRNA-synth_IIb
IPR012340 NA-bd_OB-fold
IPR004365 NA-bd_OB_tRNA
PANTHERiPTHR43450 PTHR43450, 1 hit
PfamiView protein in Pfam
PF00152 tRNA-synt_2, 1 hit
PF01336 tRNA_anti-codon, 1 hit
PRINTSiPR01042 TRNASYNTHASP
SUPFAMiSSF50249 SSF50249, 1 hit
TIGRFAMsiTIGR00458 aspS_nondisc, 1 hit
PROSITEiView protein in PROSITE
PS50862 AA_TRNA_LIGASE_II, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

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

This entry has 2 described isoforms and 5 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
C9JLC1C9JLC1_HUMAN
Aspartate--tRNA ligase, cytoplasmic
DARS
182Annotation score:
H7C278H7C278_HUMAN
Aspartate--tRNA ligase, cytoplasmic
DARS
179Annotation score:
C9JQM9C9JQM9_HUMAN
Aspartate--tRNA ligase, cytoplasmic
DARS
135Annotation score:
C9J7S3C9J7S3_HUMAN
Aspartate--tRNA ligase, cytoplasmic
DARS
175Annotation score:
H7BZ35H7BZ35_HUMAN
Aspartate--tRNA ligase, cytoplasmic
DARS
188Annotation score:

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 PublicationCorresponds to variant dbSNP:rs886037635EnsemblClinVar.1
Natural variantiVAR_070039274A → V in HBSL. 1 PublicationCorresponds to variant dbSNP:rs369152939EnsemblClinVar.1
Natural variantiVAR_070040367D → Y in HBSL. 1 PublicationCorresponds to variant dbSNP:rs370064817EnsemblClinVar.1
Natural variantiVAR_027611426L → F. Corresponds to variant dbSNP:rs1803165Ensembl.1
Natural variantiVAR_070041460R → H in HBSL. 1 PublicationCorresponds to variant dbSNP:rs587776985EnsemblClinVar.1
Natural variantiVAR_070042464P → L in HBSL. 1 PublicationCorresponds to variant dbSNP:rs148806569Ensembl.1
Natural variantiVAR_070043487R → C in HBSL. 1 PublicationCorresponds to variant dbSNP:rs587776984EnsemblClinVar.1
Natural variantiVAR_070044494R → C in HBSL. 1 PublicationCorresponds to variant dbSNP:rs147077598EnsemblClinVar.1
Natural variantiVAR_070045494R → G in HBSL. 1 PublicationCorresponds to variant dbSNP:rs147077598EnsemblClinVar.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

Similar proteinsi

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[»]
5Y6LX-ray2.90E1-501[»]
ProteinModelPortaliP14868
SMRiP14868
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107984, 180 interactors
CORUMiP14868
IntActiP14868, 35 interactors
MINTiP14868
STRINGi9606.ENSP00000264161

Chemistry databases

DrugBankiDB00128 L-Aspartic Acid

PTM databases

iPTMnetiP14868
PhosphoSitePlusiP14868
SwissPalmiP14868

Polymorphism and mutation databases

BioMutaiDARS
DMDMi20178330

2D gel databases

OGPiP14868
REPRODUCTION-2DPAGEiIPI00216951

Proteomic databases

EPDiP14868
MaxQBiP14868
PaxDbiP14868
PeptideAtlasiP14868
PRIDEiP14868
ProteomicsDBi53092

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
EuPathDBiHostDB:ENSG00000115866.10
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
KOiK22503
OMAiWVHEIRD
OrthoDBiEOG091G0530
PhylomeDBiP14868
TreeFamiTF105676

Enzyme and pathway databases

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
PROiPR:P14868
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000115866 Expressed in 242 organ(s), highest expression level in oocyte
CleanExiHS_DARS
ExpressionAtlasiP14868 baseline and differential
GenevisibleiP14868 HS

Family and domain databases

HAMAPiMF_02075 Asp_tRNA_synth_type2, 1 hit
InterProiView protein in InterPro
IPR004364 aa-tRNA-synt_II
IPR006195 aa-tRNA-synth_II
IPR004523 Asp-tRNA_synthase_2
IPR002312 Asp/Asn-tRNA-synth_IIb
IPR012340 NA-bd_OB-fold
IPR004365 NA-bd_OB_tRNA
PANTHERiPTHR43450 PTHR43450, 1 hit
PfamiView protein in Pfam
PF00152 tRNA-synt_2, 1 hit
PF01336 tRNA_anti-codon, 1 hit
PRINTSiPR01042 TRNASYNTHASP
SUPFAMiSSF50249 SSF50249, 1 hit
TIGRFAMsiTIGR00458 aspS_nondisc, 1 hit
PROSITEiView protein in PROSITE
PS50862 AA_TRNA_LIGASE_II, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiSYDC_HUMAN
AccessioniPrimary (citable) accession number: P14868
Secondary accession number(s): A8K3J2
, D3DP77, Q2TNI3, Q32Q69, Q53HV4, Q53YC5, Q68CR9, Q9BW52
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: April 16, 2002
Last modified: November 7, 2018
This is version 196 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, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  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. Aminoacyl-tRNA synthetases
    List of aminoacyl-tRNA synthetase entries
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again