Q6PI48 (SYDM_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Aspartate--tRNA ligase, mitochondrial
EC=6.1.1.12

Alternative name(s):
Aspartyl-tRNA synthetase
Short name=AspRS

Gene names

Name:

DARS2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	645 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Catalytic activity	ATP + L-aspartate + tRNA(Asp) = AMP + diphosphate + L-aspartyl-tRNA(Asp).
Subunit structure	Homodimer. Ref.3
Subcellular location	Mitochondrion matrix Ref.3.
Involvement in disease	Defects in DARS2 are a cause of leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) [MIM:611105]. LBSL is an autosomal 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. Ref.6
Sequence similarities	Belongs to the class-II aminoacyl-tRNA synthetase family.

Ontologies

Keywords
Biological process	Protein biosynthesis
Cellular component	Mitochondrion
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Transit peptide
Ligand	ATP-binding Nucleotide-binding
Molecular function	Aminoacyl-tRNA synthetase Ligase
PTM	Acetylation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	mitochondrial asparaginyl-tRNA aminoacylation Inferred by curator Ref.3. Source: BHF-UCL
Cellular component	mitochondrial matrix Traceable author statement. Source: Reactome nucleus Inferred from direct assay. Source: HPA
Molecular function	ATP binding Traceable author statement Ref.3. Source: BHF-UCL aspartate-tRNA ligase activity Traceable author statement. Source: Reactome aspartate-tRNA(Asn) ligase activity Inferred from direct assay Ref.3Ref.6. Source: BHF-UCL protein homodimerization activity Inferred from physical interaction Ref.3. Source: BHF-UCL tRNA binding Traceable author statement Ref.3. Source: BHF-UCL
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Transit peptide	1 – 47	47	Mitochondrion Potential
	Chain	48 – 645	598	Aspartate--tRNA ligase, mitochondrial		PRO_0000250736
Amino acid modifications
	Modified residue	235	1	N6-acetyllysine Ref.4
	Modified residue	382	1	N6-acetyllysine Ref.4
	Modified residue	627	1	N6-acetyllysine Ref.4
Natural variations
	Natural variant	10	1	L → V. Corresponds to variant rs4427454 [ dbSNP | Ensembl ].		VAR_027612
	Natural variant	45	1	S → G in LBSL. Ref.6		VAR_037015
	Natural variant	152	1	C → F in LBSL. Ref.6		VAR_037016
	Natural variant	179	1	R → H in LBSL. Ref.6		VAR_037017
	Natural variant	184	1	Q → K in LBSL. Ref.6		VAR_037018
	Natural variant	196	1	K → R. Corresponds to variant rs35515638 [ dbSNP | Ensembl ].		VAR_034525
	Natural variant	248	1	Q → K in LBSL. Ref.6		VAR_037019
	Natural variant	263	1	R → Q in LBSL. Ref.6		VAR_037020
	Natural variant	560	1	D → V in LBSL. Ref.6		VAR_037021
	Natural variant	613	1	L → F in LBSL. Ref.6		VAR_037022
	Natural variant	626	1	L → Q in LBSL. Ref.6		VAR_037023
	Natural variant	626	1	L → V in LBSL. Ref.6		VAR_037024
	Natural variant	629	1	Y → C in LBSL. Ref.6		VAR_037025

Sequences

	Sequence		Length	Mass (Da)
	Q6PI48 [UniParc]. Last modified July 5, 2004. Version 1. Checksum: 8B668751542F01A1	FASTA	645	73,563
	10 20 30 40 50 60 MYFPSWLSQL YRGLSRPIRR TTQPIWGSLY RSLLQSSQRR IPEFSSFVVR TNTCGELRSS 70 80 90 100 110 120 HLGQEVTLCG WIQYRRQNTF LVLRDFDGLV QVIIPQDESA ASVKKILCEA PVESVVQVSG 130 140 150 160 170 180 TVISRPAGQE NPKMPTGEIE IKVKTAELLN ACKKLPFEIK NFVKKTEALR LQYRYLDLRS 190 200 210 220 230 240 FQMQYNLRLR SQMVMKMREY LCNLHGFVDI ETPTLFKRTP GGAKEFLVPS REPGKFYSLP 250 260 270 280 290 300 QSPQQFKQLL MVGGLDRYFQ VARCYRDEGS RPDRQPEFTQ IDIEMSFVDQ TGIQSLIEGL 310 320 330 340 350 360 LQYSWPNDKD PVVVPFPTMT FAEVLATYGT DKPDTRFGMK IIDISDVFRN TEIGFLQDAL 370 380 390 400 410 420 SKPHGTVKAI CIPEGAKYLK RKDIESIRNF AADHFNQEIL PVFLNANRNW NSPVANFIME 430 440 450 460 470 480 SQRLELIRLM ETQEEDVVLL TAGEHNKACS LLGKLRLECA DLLETRGVVL RDPTLFSFLW 490 500 510 520 530 540 VVDFPLFLPK EENPRELESA HHPFTAPHPS DIHLLYTEPK KARSQHYDLV LNGNEIGGGS 550 560 570 580 590 600 IRIHNAELQR YILATLLKED VKMLSHLLQA LDYGAPPHGG IALGLDRLIC LVTGSPSIRD 610 620 630 640 VIAFPKSFRG HDLMSNTPDS VPPEELKPYH IRVSKPTDSK AERAH

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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(2006) [PubMed: 16710414] [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(2004) [PubMed: 15489334] [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(2005) [PubMed: 15779907] [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., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-235; LYS-382 AND LYS-627, MASS SPECTROMETRY.
[5]	"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: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[6]	"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(2007) [PubMed: 17384640] [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.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	AL109921 Genomic DNA. Translation: CAI20380.1. BC045173 mRNA. Translation: AAH45173.1.
IPI	IPI00100460.
RefSeq	NP_060592.2. NM_018122.4.
UniGene	Hs.647707.
3D structure databases
HSSP	HSSP built from PDB template 1BBW based on UniProtKB P0A8N3.
ProteinModelPortal	Q6PI48.
SMR	Q6PI48. Positions 48-639.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q6PI48. 2 interactions.
STRING	Q6PI48.
PTM databases
PhosphoSite	Q6PI48.
Polymorphism databases
DMDM	74758347.
Proteomic databases
PeptideAtlas	Q6PI48.
PRIDE	Q6PI48.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000361951; ENSP00000355086; ENSG00000117593.
GeneID	55157.
KEGG	hsa:55157.
UCSC	uc001gjh.1. human.
Organism-specific databases
CTD	55157.
GeneCards	GC01P173793.
H-InvDB	HIX0001343.
HGNC	HGNC:25538. DARS2.
HPA	HPA026506. HPA026528.
MIM	610956. gene. 611105. phenotype.
neXtProt	NX_Q6PI48.
Orphanet	137898. Leukoencephalopathy with brain stem and spinal cord involvement - lactate elevation.
PharmGKB	PA142672015.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG11013.
HOGENOM	HBG396032.
HOVERGEN	HBG055815.
InParanoid	Q6PI48.
OMA	AFPKTQQ.
OrthoDB	EOG4M91R5.
PhylomeDB	Q6PI48.
Enzyme and pathway databases
Reactome	REACT_71. Gene Expression.
Gene expression databases
ArrayExpress	Q6PI48.
Bgee	Q6PI48.
CleanEx	HS_DARS2.
Genevestigator	Q6PI48.
GermOnline	ENSG00000117593. Homo sapiens.
Family and domain databases
InterPro	IPR004364. aa-tRNA-synt_II. IPR018150. aa-tRNA-synt_II-like. IPR006195. aa-tRNA-synth_II. IPR004524. Asp-tRNA-synth_IIb_bac/mt. IPR002312. Asp/Asn-tRNA-synth_IIb. IPR004115. GAD_dom. IPR012340. NA-bd_OB-fold. IPR016027. NA-bd_OB-fold-like. IPR004365. NA-bd_OB_tRNA-helicase. [Graphical view]
Gene3D	G3DSA:3.30.1360.30. GAD_dom. 1 hit. G3DSA:2.40.50.140. OB_NA_bd_sub. 1 hit.
KO	K01876.
PANTHER	PTHR22594. aa-tRNA-synt_II. 1 hit. PTHR22594:SF5. AspS_bac. 1 hit.
Pfam	PF02938. GAD. 1 hit. PF00152. tRNA-synt_2. 1 hit. PF01336. tRNA_anti. 1 hit. [Graphical view]
PRINTS	PR01042. TRNASYNTHASP.
SUPFAM	SSF50249. Nucleic_acid_OB. 1 hit. SSF55261. SSF55261. 1 hit.
TIGRFAMs	TIGR00459. AspS_bact. 1 hit.
PROSITE	PS50862. AA_TRNA_LIGASE_II. 1 hit. [Graphical view]
ProtoNet	Search...
Other
DrugBank	DB00128. L-Aspartic Acid.
NextBio	58907.
SOURCE	Search...

Entry information

Entry name

SYDM_HUMAN

Accession

Primary (citable) accession number: Q6PI48

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 3, 2006
Last sequence update:	July 5, 2004
Last modified:	January 25, 2012
This is version 85 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.