Q5JTZ9 (SYAM_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Alanine--tRNA ligase, mitochondrial
EC=6.1.1.7

Alternative name(s):
Alanyl-tRNA synthetase
Short name=AlaRS

Gene names

Name:	AARS2
Synonyms:	AARSL, KIAA1270

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	985 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)

Function	Catalyzes the attachment of alanine to tRNA(Ala) in a two-step reaction: alanine is first activated by ATP to form Ala-AMP and then transferred to the acceptor end of tRNA(Ala). Also edits incorrectly charged tRNA(Ala) via its editing domain By similarity.
Catalytic activity	ATP + L-alanine + tRNA(Ala) = AMP + diphosphate + L-alanyl-tRNA(Ala).
Cofactor	Binds 1 zinc ion per subunit Potential.
Subunit structure	Monomer By similarity.
Subcellular location	Mitochondrion Ref.5.
Domain	Consists of three domains; the N-terminal catalytic domain, the editing domain and the C-terminal C-Ala domain. The editing domain removes incorrectly charged amino acids, while the C-Ala domain, along with tRNA(Ala), serves as a bridge to cooperatively bring together the editing and aminoacylation centers thus stimulating deacylation of misacylated tRNAs By similarity.
Involvement in disease	Defects in AARS2 are the cause of combined oxidative phosphorylation deficiency type 8 (COXPD8) [MIM:614096]. A mitochondrial disease characterized by a lethal infantile hypertrophic cardiomyopathy, generalized muscle dysfunction and some neurologic involvement. The liver is not affected. Ref.5
Sequence similarities	Belongs to the class-II aminoacyl-tRNA synthetase family.
Sequence caution	The sequence BAA86584.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Protein biosynthesis
Cellular component	Mitochondrion
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Transit peptide
Ligand	ATP-binding Metal-binding Nucleotide-binding RNA-binding Zinc tRNA-binding
Molecular function	Aminoacyl-tRNA synthetase Ligase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	alanyl-tRNA aminoacylation Inferred from electronic annotation. Source: InterPro
Cellular component	mitochondrion Inferred from direct assay Ref.5. Source: UniProtKB
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW alanine-tRNA ligase activity Inferred from electronic annotation. Source: EC metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW tRNA binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Transit peptide	1 – 23	23	Mitochondrion Potential
	Chain	24 – 985	962	Alanine--tRNA ligase, mitochondrial		PRO_0000250725
Sites
	Metal binding	632	1	Zinc Potential
	Metal binding	636	1	Zinc Potential
	Metal binding	749	1	Zinc Potential
	Metal binding	753	1	Zinc Potential
Natural variations
	Natural variant	155	1	L → R in COXPD8. Ref.5		VAR_065956
	Natural variant	339	1	I → V. Ref.1 Ref.3 Corresponds to variant rs324136 [ dbSNP | Ensembl ].		VAR_027609
	Natural variant	484	1	A → D. Corresponds to variant rs495294 [ dbSNP | Ensembl ].		VAR_027610
	Natural variant	592	1	R → W in COXPD8. Ref.5		VAR_065957
	Natural variant	850	1	M → V. Corresponds to variant rs35783144 [ dbSNP | Ensembl ].		VAR_057357

Sequences

	Sequence		Length	Mass (Da)
	Q5JTZ9 [UniParc]. Last modified February 15, 2005. Version 1. Checksum: 721368BD05474F86	FASTA	985	107,340
	10 20 30 40 50 60 MAASVAAAAR RLRRAIRRSP AWRGLSHRPL SSEPPAAKAS AVRAAFLNFF RDRHGHRLVP 70 80 90 100 110 120 SASVRPRGDP SLLFVNAGMN QFKPIFLGTV DPRSEMAGFR RVANSQKCVR AGGHHNDLED 130 140 150 160 170 180 VGRDLSHHTF FEMLGNWAFG GEYFKEEACN MAWELLTQVY GIPEERLWIS YFDGDPKAGL 190 200 210 220 230 240 DPDLETRDIW LSLGVPASRV LSFGPQENFW EMGDTGPCGP CTEIHYDLAG GVGAPQLVEL 250 260 270 280 290 300 WNLVFMQHNR EADGSLQPLP QRHVDTGMGL ERLVAVLQGK HSTYDTDLFS PLLNAIQQGC 310 320 330 340 350 360 RAPPYLGRVG VADEGRTDTA YRVVADHIRT LSVCISDGIF PGMSGPPLVL RRILRRAVRF 370 380 390 400 410 420 SMEILKAPPG FLGSLVPVVV ETLGDAYPEL QRNSAQIANL VSEDEAAFLA SLERGRRIID 430 440 450 460 470 480 RTLRTLGPSD MFPAEVAWSL SLCGDLGLPL DMVELMLEEK GVQLDSAGLE RLAQEEAQHR 490 500 510 520 530 540 ARQAEPVQKQ GLWLDVHALG ELQRQGVPPT DDSPKYNYSL RPSGSYEFGT CEAQVLQLYT 550 560 570 580 590 600 EDGTAVASVG KGQRCGLLLD RTNFYAEQGG QASDRGYLVR AGQEDVLFPV ARAQVCGGFI 610 620 630 640 650 660 LHEAVAPECL RLGDQVQLHV DEAWRLGCMA KHTATHLLNW ALRQTLGPGT EQQGSHLNPE 670 680 690 700 710 720 QLRLDVTTQT PLTPEQLRAV ENTVQEAVGQ DEAVYMEEVP LALTAQVPGL RSLDEVYPDP 730 740 750 760 770 780 VRVVSVGVPV AHALDPASQA ALQTSVELCC GTHLLRTGAV GDLVIIGDRQ LSKGTTRLLA 790 800 810 820 830 840 VTGEQAQQAR ELGQSLAQEV KAATERLSLG SRDVAEALRL SKDIGRLIEA VETAVMPQWQ 850 860 870 880 890 900 RRELLATVKM LQRRANTAIR KLQMGQAAKK TQELLERHSK GPLIVDTVSA ESLSVLVKVV 910 920 930 940 950 960 RQLCEQAPST SVLLLSPQPM GKVLCACQVA QGAMPTFTAE AWALAVCSHM GGKAWGSRVV 970 980 AQGTGSTTDL EAALSIAQTY ALSQL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Prediction of the coding sequences of unidentified human genes. XV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro." Nagase T., Ishikawa K., Kikuno R., Hirosawa M., Nomura N., Ohara O. DNA Res. 6:337-345(1999) [PubMed: 10574462] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT VAL-339. Tissue: Brain.
[2]	"The DNA sequence and analysis of human chromosome 6." Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S. Nature 425:805-811(2003) [PubMed: 14574404] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"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], VARIANT VAL-339. Tissue: Lung.
[4]	"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: IDENTIFICATION.
[5]	"Exome sequencing identifies mitochondrial alanyl-tRNA synthetase mutations in infantile mitochondrial cardiomyopathy." Gotz A., Tyynismaa H., Euro L., Ellonen P., Hyotylainen T., Ojala T., Hamalainen R.H., Tommiska J., Raivio T., Oresic M., Karikoski R., Tammela O., Simola K.O., Paetau A., Tyni T., Suomalainen A. Am. J. Hum. Genet. 88:635-642(2011) [PubMed: 21549344] [Abstract] Cited for: SUBCELLULAR LOCATION, VARIANTS COXPD8 ARG-155 AND TRP-592.
[6]	"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].
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB033096 mRNA. Translation: BAA86584.1. Different initiation. AL353588 Genomic DNA. Translation: CAI40747.1. BC013593 mRNA. Translation: AAH13593.1. BC033169 mRNA. Translation: AAH33169.1. BC131728 mRNA. Translation: AAI31729.1.
IPI	IPI00394788.
RefSeq	NP_065796.1. NM_020745.2.
UniGene	Hs.158381.
3D structure databases
HSSP	HSSP built from PDB template 1YFS based on UniProtKB O67323.
ProteinModelPortal	Q5JTZ9.
SMR	Q5JTZ9. Positions 13-784.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q5JTZ9. 1 interaction.
STRING	Q5JTZ9.
PTM databases
PhosphoSite	Q5JTZ9.
Polymorphism databases
DMDM	74742244.
Proteomic databases
PeptideAtlas	Q5JTZ9.
PRIDE	Q5JTZ9.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000244571; ENSP00000244571; ENSG00000124608.
GeneID	57505.
KEGG	hsa:57505.
NMPDR	fig|9606.3.peg.27241.
UCSC	uc010jza.1. human.
Organism-specific databases
CTD	57505.
GeneCards	GC06M044266.
HGNC	HGNC:21022. AARS2.
HPA	HPA035636.
MIM	612035. gene. 614096. phenotype.
neXtProt	NX_Q5JTZ9.
Orphanet	1561. Fatal infantile cytochrome C oxidase deficiency.
PharmGKB	PA162375129.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG17101.
GeneTree	ENSGT00390000016019.
HOGENOM	HBG354397.
HOVERGEN	HBG017874.
InParanoid	Q5JTZ9.
OMA	MFTNSGM.
OrthoDB	EOG4320XD.
PhylomeDB	Q5JTZ9.
Enzyme and pathway databases
Reactome	REACT_71. Gene Expression.
Gene expression databases
ArrayExpress	Q5JTZ9.
Bgee	Q5JTZ9.
CleanEx	HS_AARS2.
Genevestigator	Q5JTZ9.
GermOnline	ENSG00000124608. Homo sapiens.
Family and domain databases
InterPro	IPR002318. Ala-tRNA-synth_IIc. IPR018162. Ala-tRNA-synth_IIc_anticod-bd. IPR018165. Ala-tRNA-synth_IIc_core. IPR018164. Ala-tRNA-synth_IIc_N. IPR023033. Ala_tRNA_synth_euk/bac. IPR018163. Thr/Ala-tRNA-synth_IIc_edit. IPR012947. tRNA_SAD. [Graphical view]
KO	K01872.
Pfam	PF01411. tRNA-synt_2c. 1 hit. PF07973. tRNA_SAD. 1 hit. [Graphical view]
PRINTS	PR00980. TRNASYNTHALA.
SMART	SM00863. tRNA_SAD. 1 hit. [Graphical view]
SUPFAM	SSF101353. Ala-tRNA-synth_IIc_anticod-bd. 1 hit. SSF55186. Thr/Ala-tRNA-synth_IIc_edit. 1 hit.
TIGRFAMs	TIGR00344. AlaS. 1 hit.
PROSITE	PS50860. AA_TRNA_LIGASE_II_ALA. 1 hit. [Graphical view]
ProtoNet	Search...
Other
DrugBank	DB00160. L-Alanine.
SOURCE	Search...

Entry information

Entry name

SYAM_HUMAN

Accession

Primary (citable) accession number: Q5JTZ9
Secondary accession number(s): A2RRN5 , Q8N198, Q96D02, Q9ULF0

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 3, 2006
Last sequence update:	February 15, 2005
Last modified:	January 25, 2012
This is version 66 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.