P49588 (SYAC_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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

Alternative name(s):
Alanyl-tRNA synthetase
Short name=AlaRS
Renal carcinoma antigen NY-REN-42

Gene names

Name:

AARS

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	968 AA.
Sequence status	Complete.
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. HAMAP-Rule MF_03133
Catalytic activity	ATP + L-alanine + tRNA(Ala) = AMP + diphosphate + L-alanyl-tRNA(Ala). HAMAP-Rule MF_03133
Cofactor	Binds 1 zinc ion per subunit Potential.
Subunit structure	Monomer.
Subcellular location	Cytoplasm By similarity.
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. Ref.10 The C-terminal C-Ala domain (residues 756 to 968), along with tRNA(Ala), serves as a bridge to cooperatively bring together the editing and aminoacylation centers thus stimulating deacylation of misacylated tRNAs. The human domain can be used in vitro to replace the corresponding domain in E.coli. Ref.10
Post-translational modification	ISGylated. Ref.8
Involvement in disease	Charcot-Marie-Tooth disease 2N (CMT2N) [MIM:613287]: An axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal regeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. Nerve conduction velocities are normal or slightly reduced. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.14 Ref.15 Ref.16
Sequence similarities	Belongs to the class-II aminoacyl-tRNA synthetase family.

Ontologies

Keywords
Biological process	Protein biosynthesis
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Disease	Charcot-Marie-Tooth disease Disease mutation Neuropathy
Ligand	ATP-binding Metal-binding Nucleotide-binding RNA-binding Zinc tRNA-binding
Molecular function	Aminoacyl-tRNA synthetase Ligase
PTM	Acetylation Phosphoprotein Ubl conjugation
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	alanyl-tRNA aminoacylation Traceable author statement PubMed 7761427. Source: ProtInc cerebellar Purkinje cell layer development Inferred from electronic annotation. Source: Compara endoplasmic reticulum unfolded protein response Inferred from electronic annotation. Source: Compara hair follicle development Inferred from electronic annotation. Source: Compara negative regulation of neuron apoptotic process Inferred from electronic annotation. Source: Compara neuromuscular process controlling balance Inferred from electronic annotation. Source: Compara protein folding Inferred from electronic annotation. Source: Compara response to amino acid stimulus Inferred from electronic annotation. Source: Compara skin development Inferred from electronic annotation. Source: Compara tRNA modification Inferred from electronic annotation. Source: Compara tRNA processing Traceable author statement Ref.1. Source: ProtInc
Cellular_component	cytosol Traceable author statement. Source: Reactome
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW alanine-tRNA ligase activity Inferred from electronic annotation. Source: EC amino acid binding Inferred from electronic annotation. Source: Compara aminoacyl-tRNA editing activity Inferred from electronic annotation. Source: Compara metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW tRNA binding Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 968	968	Alanine--tRNA ligase, cytoplasmic HAMAP-Rule MF_03133		PRO_0000075281
Sites
	Metal binding	605	1	Zinc Potential
	Metal binding	609	1	Zinc Potential
	Metal binding	723	1	Zinc Potential
	Metal binding	727	1	Zinc Potential
Amino acid modifications
	Modified residue	1	1	N-acetylmethionine Ref.6
	Modified residue	19	1	N6-acetyllysine Ref.11
	Modified residue	399	1	Phosphoserine Ref.12
	Modified residue	555	1	Phosphoserine Ref.9
	Modified residue	876	1	N6-acetyllysine Ref.11
Natural variations
	Natural variant	71	1	N → Y in CMT2N. Ref.15		VAR_067084
	Natural variant	275	1	G → D. Corresponds to variant rs11537667 [ dbSNP | Ensembl ].		VAR_028204
	Natural variant	329	1	R → H in CMT2N; severely reduces enzyme activity. Ref.14 Ref.16		VAR_063527
Experimental info
	Sequence conflict	82	1	H → Q in BAA06808. Ref.1
	Sequence conflict	867	1	S → T in BAD96544. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P49588 [UniParc]. Last modified October 3, 2006. Version 2. Checksum: 8683F111CEE42506	FASTA	968	106,810
	10 20 30 40 50 60 MDSTLTASEI RQRFIDFFKR NEHTYVHSSA TIPLDDPTLL FANAGMNQFK PIFLNTIDPS 70 80 90 100 110 120 HPMAKLSRAA NTQKCIRAGG KHNDLDDVGK DVYHHTFFEM LGSWSFGDYF KELACKMALE 130 140 150 160 170 180 LLTQEFGIPI ERLYVTYFGG DEAAGLEADL ECKQIWQNLG LDDTKILPGN MKDNFWEMGD 190 200 210 220 230 240 TGPCGPCSEI HYDRIGGRDA AHLVNQDDPN VLEIWNLVFI QYNREADGIL KPLPKKSIDT 250 260 270 280 290 300 GMGLERLVSV LQNKMSNYDT DLFVPYFEAI QKGTGARPYT GKVGAEDADG IDMAYRVLAD 310 320 330 340 350 360 HARTITVALA DGGRPDNTGR GYVLRRILRR AVRYAHEKLN ASRGFFATLV DVVVQSLGDA 370 380 390 400 410 420 FPELKKDPDM VKDIINEEEV QFLKTLSRGR RILDRKIQSL GDSKTIPGDT AWLLYDTYGF 430 440 450 460 470 480 PVDLTGLIAE EKGLVVDMDG FEEERKLAQL KSQGKGAGGE DLIMLDIYAI EELRARGLEV 490 500 510 520 530 540 TDDSPKYNYH LDSSGSYVFE NTVATVMALR REKMFVEEVS TGQECGVVLD KTCFYAEQGG 550 560 570 580 590 600 QIYDEGYLVK VDDSSEDKTE FTVKNAQVRG GYVLHIGTIY GDLKVGDQVW LFIDEPRRRP 610 620 630 640 650 660 IMSNHTATHI LNFALRSVLG EADQKGSLVA PDRLRFDFTA KGAMSTQQIK KAEEIANEMI 670 680 690 700 710 720 EAAKAVYTQD CPLAAAKAIQ GLRAVFDETY PDPVRVVSIG VPVSELLDDP SGPAGSLTSV 730 740 750 760 770 780 EFCGGTHLRN SSHAGAFVIV TEEAIAKGIR RIVAVTGAEA QKALRKAESL KKCLSVMEAK 790 800 810 820 830 840 VKAQTAPNKD VQREIADLGE ALATAVIPQW QKDELRETLK SLKKVMDDLD RASKADVQKR 850 860 870 880 890 900 VLEKTKQFID SNPNQPLVIL EMESGASAKA LNEALKLFKM HSPQTSAMLF TVDNEAGKIT 910 920 930 940 950 960 CLCQVPQNAA NRGLKASEWV QQVSGLMDGK GGGKDVSAQA TGKNVGCLQE ALQLATSFAQ LRLGDVKN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human alanyl-tRNA synthetase: conservation in evolution of catalytic core and microhelix recognition." Shiba K., Ripmaster T.L., Suzuki N., Nichols R., Plotz P., Noda T., Schimmel P. Biochemistry 34:10340-10349(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	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: Liver.
[3]	"The sequence and analysis of duplication-rich human chromosome 16." Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J. , Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., Rubin E.M., Pennacchio L.A. Nature 432:988-994(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	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. , 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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: Placenta.
[6]	Bienvenut W.V., Glen H., Brunton V.G., Frame M.C. Submitted (JUL-2007) to UniProtKB Cited for: PROTEIN SEQUENCE OF 1-11; 304-320 AND 684-695, ACETYLATION AT MET-1, MASS SPECTROMETRY. Tissue: Osteosarcoma.
[7]	"Antigens recognized by autologous antibody in patients with renal-cell carcinoma." Scanlan M.J., Gordan J.D., Williamson B., Stockert E., Bander N.H., Jongeneel C.V., Gure A.O., Jaeger D., Jaeger E., Knuth A., Chen Y.-T., Old L.J. Int. J. Cancer 83:456-464(1999) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION AS A RENAL CANCER ANTIGEN. Tissue: Renal cell carcinoma.
[8]	"Proteomic identification of proteins conjugated to ISG15 in mouse and human cells." Giannakopoulos N.V., Luo J.K., Papov V., Zou W., Lenschow D.J., Jacobs B.S., Borden E.C., Li J., Virgin H.W., Zhang D.E. Biochem. Biophys. Res. Commun. 336:496-506(2005) [PubMed] [Europe PMC] [Abstract] Cited for: ISGYLATION.
[9]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-555, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[10]	"The C-Ala domain brings together editing and aminoacylation functions on one tRNA." Guo M., Chong Y.E., Beebe K., Shapiro R., Yang X.-L., Schimmel P. Science 325:744-747(2009) [PubMed] [Europe PMC] [Abstract] Cited for: DOMAIN EXCHANGE EXPERIMENTS.
[11]	"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-19 AND LYS-876, MASS SPECTROMETRY.
[12]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-399, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[13]	"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].
[14]	"A major determinant for binding and aminoacylation of tRNA(Ala) in cytoplasmic Alanyl-tRNA synthetase is mutated in dominant axonal Charcot-Marie-Tooth disease." Latour P., Thauvin-Robinet C., Baudelet-Mery C., Soichot P., Cusin V., Faivre L., Locatelli M.C., Mayencon M., Sarcey A., Broussolle E., Camu W., David A., Rousson R. Am. J. Hum. Genet. 86:77-82(2010) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT CMT2N HIS-329.
[15]	"The mutational spectrum in a cohort of Charcot-Marie-Tooth disease type 2 among the Han Chinese in Taiwan." Lin K.P., Soong B.W., Yang C.C., Huang L.W., Chang M.H., Lee I.H., Antonellis A., Lee Y.C. PLoS ONE 6:E29393-E29393(2011) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT CMT2N TYR-71.
[16]	"A recurrent loss-of-function alanyl-tRNA synthetase (AARS) mutation in patients with Charcot-Marie-Tooth disease type 2N (CMT2N)." McLaughlin H.M., Sakaguchi R., Giblin W., Wilson T.E., Biesecker L., Lupski J.R., Talbot K., Vance J.M., Zuchner S., Lee Y.C., Kennerson M., Hou Y.M., Nicholson G., Antonellis A. Hum. Mutat. 33:244-253(2012) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT CMT2N HIS-329, CHARACTERIZATION OF VARIANT CMT2N HIS-329.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	D32050 mRNA. Translation: BAA06808.1. AK222824 mRNA. Translation: BAD96544.1. AC012184 Genomic DNA. No translation available. CH471241 Genomic DNA. Translation: EAW51839.1. BC011451 mRNA. Translation: AAH11451.1.
IPI	IPI00027442.
PIR	I60107.
RefSeq	NP_001596.2. NM_001605.2.
UniGene	Hs.315137.
3D structure databases
ProteinModelPortal	P49588.
ModBase	Search...
Protein-protein interaction databases
IntAct	P49588. 4 interactions.
MINT	MINT-1490092.
STRING	9606.ENSP00000261772.
PTM databases
PhosphoSite	P49588.
Polymorphism databases
DMDM	115502460.
Proteomic databases
PaxDb	P49588.
PRIDE	P49588.
Protocols and materials databases
DNASU	16.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000261772; ENSP00000261772; ENSG00000090861.
GeneID	16.
KEGG	hsa:16.
UCSC	uc002eyn.1. human.
Organism-specific databases
CTD	16.
GeneCards	GC16M070286.
HGNC	HGNC:20. AARS.
HPA	CAB034261. HPA040870.
MIM	601065. gene. 613287. phenotype.
neXtProt	NX_P49588.
Orphanet	228174. Autosomal dominant Charcot-Marie-Tooth disease type 2N.
PharmGKB	PA24367.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0013.
HOGENOM	HOG000156964.
HOVERGEN	HBG017874.
InParanoid	P49588.
KO	K01872.
OMA	EWFDFPK.
OrthoDB	EOG45X7VC.
Enzyme and pathway databases
Reactome	REACT_71. Gene Expression.
Gene expression databases
ArrayExpress	P49588.
Bgee	P49588.
CleanEx	HS_AARS.
Genevestigator	P49588.
GermOnline	ENSG00000090861. Homo sapiens.
Family and domain databases
HAMAP	MF_00036_B. Ala_tRNA_synth_B.
InterPro	IPR002318. Ala-tRNA-lgiase_IIc. IPR018162. Ala-tRNA-ligase_IIc_anticod-bd. IPR018165. Ala-tRNA-synth_IIc_core. IPR018164. Ala-tRNA-synth_IIc_N. IPR023033. Ala_tRNA_ligase_euk/bac. IPR003156. Pesterase_DHHA1. IPR018163. Thr/Ala-tRNA-synth_IIc_edit. IPR012947. tRNA_SAD. [Graphical view]
PANTHER	PTHR11777:SF6. PTHR11777:SF6. 1 hit.
Pfam	PF02272. DHHA1. 1 hit. 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
BindingDB	P49588.
ChEMBL	CHEMBL3574.
ChiTaRS	AARS. human.
DrugBank	DB00160. L-Alanine.
GenomeRNAi	16.
NextBio	39.
SOURCE	Search...

Entry information

Entry name

SYAC_HUMAN

Accession

Primary (citable) accession number: P49588
Secondary accession number(s): A6NF14, Q53GV7, Q96FA0

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1996
Last sequence update:	October 3, 2006
Last modified:	May 1, 2013
This is version 122 of the entry and version 2 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.