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P14868 (SYDC_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 150. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:DARS
ORF Names:PIG40
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length501 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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 activity

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

Subunit structure

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.

Subcellular location

Cytoplasm.

Tissue specificity

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. Ref.14

Involvement in disease

Hypomyelination with brainstem and spinal cord involvement and leg spasticity (HBSL) [MIM:615281]: An 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.14

Sequence similarities

Belongs to the class-II aminoacyl-tRNA synthetase family.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

GRB2P629932EBI-358730,EBI-401755

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 501501Aspartate--tRNA ligase, cytoplasmic
PRO_0000111010

Regions

Nucleotide binding273 – 2753ATP By similarity
Nucleotide binding281 – 2833ATP By similarity
Nucleotide binding472 – 4754ATP By similarity
Region251 – 2544Aspartate By similarity
Region411 – 4155Binding site for the 3'-end of tRNA Potential

Sites

Binding site2291Aspartate By similarity
Binding site2731Aspartate By similarity
Binding site4241ATP By similarity
Binding site4271Aspartate By similarity
Binding site4311Aspartate By similarity

Amino acid modifications

Modified residue741N6-acetyllysine Ref.10
Modified residue2491Phosphoserine Ref.12
Modified residue3741N6-acetyllysine Ref.10
Modified residue5001Phosphothreonine; by PKA Potential

Natural variations

Natural variant2561M → L in HBSL. Ref.14
VAR_070038
Natural variant2741A → V in HBSL. Ref.14
VAR_070039
Natural variant3671D → Y in HBSL. Ref.14
VAR_070040
Natural variant4261L → F.
Corresponds to variant rs1803165 [ dbSNP | Ensembl ].
VAR_027611
Natural variant4601R → H in HBSL. Ref.14
VAR_070041
Natural variant4641P → L in HBSL. Ref.14
VAR_070042
Natural variant4871R → C in HBSL. Ref.14
VAR_070043
Natural variant4941R → C in HBSL. Ref.14
VAR_070044
Natural variant4941R → G in HBSL. Ref.14
VAR_070045

Experimental info

Sequence conflict5 – 73SAS → TQ in AAA35567. Ref.1
Sequence conflict311I → T in AAI07750. Ref.7
Sequence conflict381Q → H in BAD96196. Ref.5
Sequence conflict1641A → Q in AAA35567. Ref.1
Sequence conflict3121Q → H in AAX07827. Ref.2
Sequence conflict4141N → K in AAA35567. Ref.1
Sequence conflict4471I → N in AAA35567. Ref.1

Secondary structure

................................................................. 501
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P14868 [UniParc].

Last modified April 16, 2002. Version 2.
Checksum: B181572DF0AF5F94

FASTA50157,136
        10         20         30         40         50         60 
MPSASASRKS QEKPREIMDA AEDYAKERYG ISSMIQSQEK PDRVLVRVRD LTIQKADEVV 

        70         80         90        100        110        120 
WVRARVHTSR AKGKQCFLVL RQQQFNVQAL VAVGDHASKQ MVKFAANINK ESIVDVEGVV 

       130        140        150        160        170        180 
RKVNQKIGSC TQQDVELHVQ KIYVISLAEP RLPLQLDDAV RPEAEGEEEG RATVNQDTRL 

       190        200        210        220        230        240 
DNRVIDLRTS TSQAVFRLQS GICHLFRETL INKGFVEIQT PKIISAASEG GANVFTVSYF 

       250        260        270        280        290        300 
KNNAYLAQSP QLYKQMCICA DFEKVFSIGP VFRAEDSNTH RHLTEFVGLD IEMAFNYHYH 

       310        320        330        340        350        360 
EVMEEIADTM VQIFKGLQER FQTEIQTVNK QFPCEPFKFL EPTLRLEYCE ALAMLREAGV 

       370        380        390        400        410        420 
EMGDEDDLST PNEKLLGHLV KEKYDTDFYI LDKYPLAVRP FYTMPDPRNP KQSNSYDMFM 

       430        440        450        460        470        480 
RGEEILSGAQ RIHDPQLLTE RALHHGIDLE KIKAYIDSFR FGAPPHAGGG IGLERVTMLF 

       490        500 
LGLHNVRQTS MFPRDPKRLT P 

« Hide

References

« Hide 'large scale' references
[1]"cDNA sequence, predicted primary structure, and evolving amphiphilic helix of human aspartyl-tRNA synthetase."
Jacobo-Molina A., Peterson R., Yang D.C.H.
J. Biol. Chem. 264:16608-16612(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Identification of a cell proliferation-inducing gene."
Kim J.W.
Submitted (SEP-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Heart.
[5]Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.
Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Adipose tissue.
[6]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"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(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Eye.
[8]"Lysyl-tRNA synthetase interacts with EF1alpha, aspartyl-tRNA synthetase and p38 in vitro."
Guzzo C.M., Yang D.C.H.
Biochem. Biophys. Res. Commun. 365:718-723(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH KARS.
[9]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]"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(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-74 AND LYS-374, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-249, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[14]"Mutations in DARS cause hypomyelination with brain stem and spinal cord involvement and leg spasticity."
Taft R.J., Vanderver A., Leventer R.J., Damiani S.A., Simons C., Grimmond S.M., Miller D., Schmidt J., Lockhart P.J., Pope K., Ru K., Crawford J., Rosser T., de Coo I.F., Juneja M., Verma I.C., Prabhakar P., Blaser S. expand/collapse author list , Raiman J., Pouwels P.J., Bevova M.R., Abbink T.E., van der Knaap M.S., Wolf N.I.
Am. J. Hum. Genet. 92:774-780(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, VARIANTS HBSL LEU-256; VAL-274; TYR-367; HIS-460; LEU-464; CYS-487; CYS-494 AND GLY-494.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
J05032 mRNA. Translation: AAA35567.1.
AY762100 mRNA. Translation: AAX07827.1.
BT006710 mRNA. Translation: AAP35356.1.
AK222476 mRNA. Translation: BAD96196.1.
AK290607 mRNA. Translation: BAF83296.1.
CH471058 Genomic DNA. Translation: EAX11617.1.
CH471058 Genomic DNA. Translation: EAX11620.1.
BC000629 mRNA. Translation: AAH00629.1.
BC107749 mRNA. Translation: AAI07750.1.
CCDSCCDS2180.1.
PIRSYHUDT. A34393.
RefSeqNP_001340.2. NM_001349.2.
UniGeneHs.503787.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4J15X-ray2.24A/B1-501[»]
ProteinModelPortalP14868.
SMRP14868. Positions 21-495.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107984. 54 interactions.
IntActP14868. 12 interactions.
MINTMINT-141082.
STRING9606.ENSP00000264161.

Chemistry

DrugBankDB00128. L-Aspartic Acid.

PTM databases

PhosphoSiteP14868.

Polymorphism databases

DMDM20178330.

2D gel databases

OGPP14868.
REPRODUCTION-2DPAGEIPI00216951.

Proteomic databases

MaxQBP14868.
PaxDbP14868.
PeptideAtlasP14868.
PRIDEP14868.

Protocols and materials databases

DNASU1615.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000264161; ENSP00000264161; ENSG00000115866.
GeneID1615.
KEGGhsa:1615.
UCSCuc002tux.1. human.

Organism-specific databases

CTD1615.
GeneCardsGC02M136686.
HGNCHGNC:2678. DARS.
HPAHPA020451.
HPA029804.
HPA029805.
MIM603084. gene.
615281. phenotype.
neXtProtNX_P14868.
Orphanet363412. Hypomyelination with brain stem and spinal cord involvement and leg spasticity.
PharmGKBPA27146.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0017.
HOVERGENHBG001028.
InParanoidP14868.
KOK01876.
OMAFCVGPVF.
OrthoDBEOG7P5T0X.
PhylomeDBP14868.
TreeFamTF105676.

Enzyme and pathway databases

ReactomeREACT_71. Gene Expression.

Gene expression databases

ArrayExpressP14868.
BgeeP14868.
CleanExHS_DARS.
GenevestigatorP14868.

Family and domain databases

Gene3D2.40.50.140. 1 hit.
InterProIPR004364. aa-tRNA-synt_II.
IPR018150. aa-tRNA-synt_II-like.
IPR006195. aa-tRNA-synth_II.
IPR004523. Asp-tRNA_synthase.
IPR002312. Asp/Asn-tRNA-synth_IIb.
IPR012340. NA-bd_OB-fold.
IPR004365. NA-bd_OB_tRNA.
[Graphical view]
PANTHERPTHR22594. PTHR22594. 1 hit.
PTHR22594:SF10. PTHR22594:SF10. 1 hit.
PfamPF00152. tRNA-synt_2. 1 hit.
PF01336. tRNA_anti-codon. 1 hit.
[Graphical view]
PRINTSPR01042. TRNASYNTHASP.
SUPFAMSSF50249. SSF50249. 1 hit.
TIGRFAMsTIGR00458. aspS_nondisc. 1 hit.
PROSITEPS50862. AA_TRNA_LIGASE_II. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSDARS. human.
GeneWikiDARS_(gene).
GenomeRNAi1615.
NextBio6634.
PROP14868.
SOURCESearch...

Entry information

Entry nameSYDC_HUMAN
AccessionPrimary (citable) accession number: P14868
Secondary accession number(s): A8K3J2 expand/collapse secondary AC list , D3DP77, Q2TNI3, Q32Q69, Q53HV4, Q53YC5, Q9BW52
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: April 16, 2002
Last modified: July 9, 2014
This is version 150 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM

Aminoacyl-tRNA synthetases

List of aminoacyl-tRNA synthetase entries