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Protein

Aspartate--tRNA ligase, mitochondrial

Gene

DARS2

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

Functioni

Catalytic activityi

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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei266 – 2661AspartateBy similarity
Binding sitei535 – 5351ATPBy similarity
Binding sitei542 – 5421AspartateBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi266 – 2683ATPBy similarity
Nucleotide bindingi584 – 5874ATPBy similarity

GO - Molecular functioni

  1. aspartate-tRNA(Asn) ligase activity Source: BHF-UCL
  2. aspartate-tRNA ligase activity Source: Reactome
  3. ATP binding Source: BHF-UCL
  4. protein homodimerization activity Source: BHF-UCL
  5. tRNA binding Source: BHF-UCL

GO - Biological processi

  1. gene expression Source: Reactome
  2. mitochondrial asparaginyl-tRNA aminoacylation Source: BHF-UCL
  3. tRNA aminoacylation Source: BHF-UCL
  4. 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

BRENDAi6.1.1.12. 2681.
ReactomeiREACT_15302. Mitochondrial tRNA aminoacylation.

Names & Taxonomyi

Protein namesi
Recommended name:
Aspartate--tRNA ligase, mitochondrial (EC:6.1.1.12)
Alternative name(s):
Aspartyl-tRNA synthetase
Short name:
AspRS
Gene namesi
Name:DARS2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:25538. DARS2.

Subcellular locationi

Mitochondrion matrix 1 Publication

GO - Cellular componenti

  1. mitochondrial matrix Source: Reactome
  2. mitochondrion Source: BHF-UCL
  3. nucleoplasm Source: HPA
  4. nucleus Source: HPA
Complete GO annotation...

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Involvement in diseasei

Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL)1 Publication

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionAutosomal recessive disease and is defined on the basis of a highly characteristic constellation of abnormalities observed by magnetic resonance imaging and spectroscopy. Affected individuals develop slowly progressive cerebellar ataxia, spasticity, and dorsal column dysfunction, sometimes with a mild cognitive deficit or decline.

See also OMIM:611105
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti45 – 451S → G in LBSL. 1 Publication
VAR_037015
Natural varianti152 – 1521C → F in LBSL. 1 Publication
VAR_037016
Natural varianti179 – 1791R → H in LBSL. 1 Publication
VAR_037017
Natural varianti184 – 1841Q → K in LBSL. 1 Publication
VAR_037018
Natural varianti248 – 2481Q → K in LBSL. 1 Publication
VAR_037019
Natural varianti263 – 2631R → Q in LBSL. 1 Publication
VAR_037020
Natural varianti560 – 5601D → V in LBSL. 1 Publication
VAR_037021
Natural varianti613 – 6131L → F in LBSL. 1 Publication
VAR_037022
Natural varianti626 – 6261L → Q in LBSL. 1 Publication
VAR_037023
Natural varianti626 – 6261L → V in LBSL. 1 Publication
VAR_037024
Natural varianti629 – 6291Y → C in LBSL. 1 Publication
VAR_037025

Keywords - Diseasei

Disease mutation

Organism-specific databases

MIMi611105. phenotype.
Orphaneti137898. Leukoencephalopathy with brain stem and spinal cord involvement - high lactate.
PharmGKBiPA142672015.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transit peptidei1 – 4747MitochondrionSequence AnalysisAdd
BLAST
Chaini48 – 645598Aspartate--tRNA ligase, mitochondrialPRO_0000250736Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei219 – 2191PhosphothreonineBy similarity
Modified residuei382 – 3821N6-acetyllysine1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiQ6PI48.
PaxDbiQ6PI48.
PeptideAtlasiQ6PI48.
PRIDEiQ6PI48.

PTM databases

PhosphoSiteiQ6PI48.

Expressioni

Gene expression databases

BgeeiQ6PI48.
CleanExiHS_DARS2.
ExpressionAtlasiQ6PI48. baseline and differential.
GenevestigatoriQ6PI48.

Organism-specific databases

HPAiHPA026506.
HPA026528.

Interactioni

Subunit structurei

Homodimer.1 Publication

Protein-protein interaction databases

BioGridi120459. 13 interactions.
IntActiQ6PI48. 3 interactions.
STRINGi9606.ENSP00000355086.

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4AH6X-ray3.70A/B/C/D41-645[»]
ProteinModelPortaliQ6PI48.
SMRiQ6PI48. Positions 42-630.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni244 – 2474AspartateBy similarity

Sequence similaritiesi

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiCOG0173.
GeneTreeiENSGT00550000074971.
HOGENOMiHOG000275159.
HOVERGENiHBG055815.
InParanoidiQ6PI48.
KOiK01876.
OMAiYQLDVEM.
OrthoDBiEOG773XFN.
PhylomeDBiQ6PI48.
TreeFamiTF314827.

Family and domain databases

Gene3Di2.40.50.140. 1 hit.
3.30.1360.30. 1 hit.
HAMAPiMF_00044. Asp_tRNA_synth.
InterProiIPR004364. aa-tRNA-synt_II.
IPR018150. aa-tRNA-synt_II-like.
IPR006195. aa-tRNA-synth_II.
IPR004524. Asp-tRNA-ligase_IIb_bac/mt.
IPR002312. Asp/Asn-tRNA-synth_IIb.
IPR004115. GAD-like.
IPR029351. GAD_dom.
IPR012340. NA-bd_OB-fold.
IPR004365. NA-bd_OB_tRNA.
[Graphical view]
PANTHERiPTHR22594. PTHR22594. 1 hit.
PTHR22594:SF5. PTHR22594:SF5. 1 hit.
PfamiPF02938. GAD. 1 hit.
PF00152. tRNA-synt_2. 1 hit.
PF01336. tRNA_anti-codon. 1 hit.
[Graphical view]
PRINTSiPR01042. TRNASYNTHASP.
SUPFAMiSSF50249. SSF50249. 1 hit.
SSF55261. SSF55261. 1 hit.
TIGRFAMsiTIGR00459. aspS_bact. 1 hit.
PROSITEiPS50862. AA_TRNA_LIGASE_II. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q6PI48-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MYFPSWLSQL YRGLSRPIRR TTQPIWGSLY RSLLQSSQRR IPEFSSFVVR
60 70 80 90 100
TNTCGELRSS HLGQEVTLCG WIQYRRQNTF LVLRDFDGLV QVIIPQDESA
110 120 130 140 150
ASVKKILCEA PVESVVQVSG TVISRPAGQE NPKMPTGEIE IKVKTAELLN
160 170 180 190 200
ACKKLPFEIK NFVKKTEALR LQYRYLDLRS FQMQYNLRLR SQMVMKMREY
210 220 230 240 250
LCNLHGFVDI ETPTLFKRTP GGAKEFLVPS REPGKFYSLP QSPQQFKQLL
260 270 280 290 300
MVGGLDRYFQ VARCYRDEGS RPDRQPEFTQ IDIEMSFVDQ TGIQSLIEGL
310 320 330 340 350
LQYSWPNDKD PVVVPFPTMT FAEVLATYGT DKPDTRFGMK IIDISDVFRN
360 370 380 390 400
TEIGFLQDAL SKPHGTVKAI CIPEGAKYLK RKDIESIRNF AADHFNQEIL
410 420 430 440 450
PVFLNANRNW NSPVANFIME SQRLELIRLM ETQEEDVVLL TAGEHNKACS
460 470 480 490 500
LLGKLRLECA DLLETRGVVL RDPTLFSFLW VVDFPLFLPK EENPRELESA
510 520 530 540 550
HHPFTAPHPS DIHLLYTEPK KARSQHYDLV LNGNEIGGGS IRIHNAELQR
560 570 580 590 600
YILATLLKED VKMLSHLLQA LDYGAPPHGG IALGLDRLIC LVTGSPSIRD
610 620 630 640
VIAFPKSFRG HDLMSNTPDS VPPEELKPYH IRVSKPTDSK AERAH
Length:645
Mass (Da):73,563
Last modified:July 4, 2004 - v1
Checksum:i8B668751542F01A1
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti10 – 101L → V.
Corresponds to variant rs4427454 [ dbSNP | Ensembl ].
VAR_027612
Natural varianti45 – 451S → G in LBSL. 1 Publication
VAR_037015
Natural varianti152 – 1521C → F in LBSL. 1 Publication
VAR_037016
Natural varianti179 – 1791R → H in LBSL. 1 Publication
VAR_037017
Natural varianti184 – 1841Q → K in LBSL. 1 Publication
VAR_037018
Natural varianti196 – 1961K → R.
Corresponds to variant rs35515638 [ dbSNP | Ensembl ].
VAR_034525
Natural varianti248 – 2481Q → K in LBSL. 1 Publication
VAR_037019
Natural varianti263 – 2631R → Q in LBSL. 1 Publication
VAR_037020
Natural varianti560 – 5601D → V in LBSL. 1 Publication
VAR_037021
Natural varianti613 – 6131L → F in LBSL. 1 Publication
VAR_037022
Natural varianti626 – 6261L → Q in LBSL. 1 Publication
VAR_037023
Natural varianti626 – 6261L → V in LBSL. 1 Publication
VAR_037024
Natural varianti629 – 6291Y → C in LBSL. 1 Publication
VAR_037025

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL109921 Genomic DNA. Translation: CAI20380.1.
BC045173 mRNA. Translation: AAH45173.1.
CCDSiCCDS1311.1.
RefSeqiNP_060592.2. NM_018122.4.
UniGeneiHs.647707.

Genome annotation databases

EnsembliENST00000361951; ENSP00000355086; ENSG00000117593.
GeneIDi55157.
KEGGihsa:55157.
UCSCiuc001gjh.2. human.

Polymorphism databases

DMDMi74758347.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL109921 Genomic DNA. Translation: CAI20380.1.
BC045173 mRNA. Translation: AAH45173.1.
CCDSiCCDS1311.1.
RefSeqiNP_060592.2. NM_018122.4.
UniGeneiHs.647707.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4AH6X-ray3.70A/B/C/D41-645[»]
ProteinModelPortaliQ6PI48.
SMRiQ6PI48. Positions 42-630.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi120459. 13 interactions.
IntActiQ6PI48. 3 interactions.
STRINGi9606.ENSP00000355086.

Chemistry

DrugBankiDB00128. L-Aspartic Acid.

PTM databases

PhosphoSiteiQ6PI48.

Polymorphism databases

DMDMi74758347.

Proteomic databases

MaxQBiQ6PI48.
PaxDbiQ6PI48.
PeptideAtlasiQ6PI48.
PRIDEiQ6PI48.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000361951; ENSP00000355086; ENSG00000117593.
GeneIDi55157.
KEGGihsa:55157.
UCSCiuc001gjh.2. human.

Organism-specific databases

CTDi55157.
GeneCardsiGC01P173793.
GeneReviewsiDARS2.
HGNCiHGNC:25538. DARS2.
HPAiHPA026506.
HPA026528.
MIMi610956. gene.
611105. phenotype.
neXtProtiNX_Q6PI48.
Orphaneti137898. Leukoencephalopathy with brain stem and spinal cord involvement - high lactate.
PharmGKBiPA142672015.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG0173.
GeneTreeiENSGT00550000074971.
HOGENOMiHOG000275159.
HOVERGENiHBG055815.
InParanoidiQ6PI48.
KOiK01876.
OMAiYQLDVEM.
OrthoDBiEOG773XFN.
PhylomeDBiQ6PI48.
TreeFamiTF314827.

Enzyme and pathway databases

BRENDAi6.1.1.12. 2681.
ReactomeiREACT_15302. Mitochondrial tRNA aminoacylation.

Miscellaneous databases

ChiTaRSiDARS2. human.
GenomeRNAii55157.
NextBioi58907.
PROiQ6PI48.
SOURCEiSearch...

Gene expression databases

BgeeiQ6PI48.
CleanExiHS_DARS2.
ExpressionAtlasiQ6PI48. baseline and differential.
GenevestigatoriQ6PI48.

Family and domain databases

Gene3Di2.40.50.140. 1 hit.
3.30.1360.30. 1 hit.
HAMAPiMF_00044. Asp_tRNA_synth.
InterProiIPR004364. aa-tRNA-synt_II.
IPR018150. aa-tRNA-synt_II-like.
IPR006195. aa-tRNA-synth_II.
IPR004524. Asp-tRNA-ligase_IIb_bac/mt.
IPR002312. Asp/Asn-tRNA-synth_IIb.
IPR004115. GAD-like.
IPR029351. GAD_dom.
IPR012340. NA-bd_OB-fold.
IPR004365. NA-bd_OB_tRNA.
[Graphical view]
PANTHERiPTHR22594. PTHR22594. 1 hit.
PTHR22594:SF5. PTHR22594:SF5. 1 hit.
PfamiPF02938. GAD. 1 hit.
PF00152. tRNA-synt_2. 1 hit.
PF01336. tRNA_anti-codon. 1 hit.
[Graphical view]
PRINTSiPR01042. TRNASYNTHASP.
SUPFAMiSSF50249. SSF50249. 1 hit.
SSF55261. SSF55261. 1 hit.
TIGRFAMsiTIGR00459. aspS_bact. 1 hit.
PROSITEiPS50862. AA_TRNA_LIGASE_II. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "The DNA sequence and biological annotation of human chromosome 1."
    Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.
    , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
    Nature 441:315-321(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Testis.
  3. "Toward the full set of human mitochondrial aminoacyl-tRNA synthetases: characterization of AspRS and TyrRS."
    Bonnefond L., Fender A., Rudinger-Thirion J., Giege R., Florentz C., Sissler M.
    Biochemistry 44:4805-4816(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, SUBUNIT.
  4. "Lysine acetylation targets protein complexes and co-regulates major cellular functions."
    Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
    Science 325:834-840(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-382, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  5. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  6. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
    Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
    J. Proteomics 96:253-262(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  7. "Mitochondrial aspartyl-tRNA synthetase deficiency causes leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation."
    Scheper G.C., van der Klok T., van Andel R.J., van Berkel C.G.M., Sissler M., Smet J., Muravina T.I., Serkov S.V., Uziel G., Bugiani M., Schiffmann R., Kraegeloh-Mann I., Smeitink J.A.M., Florentz C., Van Coster R., Pronk J.C., van der Knaap M.S.
    Nat. Genet. 39:534-539(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS LBSL GLY-45; PHE-152; HIS-179; LYS-184; LYS-248; GLN-263; VAL-560; PHE-613; VAL-626; GLN-626 AND CYS-629.

Entry informationi

Entry nameiSYDM_HUMAN
AccessioniPrimary (citable) accession number: Q6PI48
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 2, 2006
Last sequence update: July 4, 2004
Last modified: March 31, 2015
This is version 116 of the entry and version 1 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 1
    Human chromosome 1: 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

External Data

Dasty 3

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 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.