Q9P2J5 (SYLC_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Leucine--tRNA ligase, cytoplasmic
EC=6.1.1.4

Alternative name(s):
Leucyl-tRNA synthetase
Short name=LeuRS

Gene names

Name:	LARS
Synonyms:	KIAA1352

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	1176 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Catalyzes the specific attachment of an amino acid to its cognate tRNA in a two 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. Exhibits a post-transfer editing activity to hydrolyze mischarged tRNAs. Ref.6
Catalytic activity	ATP + L-leucine + tRNA(Leu) = AMP + diphosphate + L-leucyl-tRNA(Leu).
Enzyme regulation	(5-fluoro-1,3-dihydro-1-hydroxy-1,2-benzoxaborole) inhibits LARS by forming a covalent adduct with the 3' adenosine of tRNA(Leu) at the editing site, thus locking the enzyme in an inactive conformation.
Subcellular location	Cytoplasm By similarity.
Sequence similarities	Belongs to the class-I aminoacyl-tRNA synthetase family.
Sequence caution	The sequence BAA92590.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Protein biosynthesis
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Aminoacyl-tRNA synthetase Ligase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	leucyl-tRNA aminoacylation Inferred from electronic annotation. Source: InterPro regulation of translational fidelity Inferred from electronic annotation. Source: GOC tRNA aminoacylation for protein translation Traceable author statement. Source: Reactome
Cellular_component	cytosol Traceable author statement. Source: Reactome
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW aminoacyl-tRNA editing activity Inferred from electronic annotation. Source: InterPro leucine-tRNA ligase activity Traceable author statement. Source: Reactome
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
RARS	P54136	3	EBI-356077,EBI-355482
RPTOR	Q8N122	3	EBI-356077,EBI-1567928
RRAGD	Q9NQL2	13	EBI-356077,EBI-992949

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1176

1176

Leucine--tRNA ligase, cytoplasmic

PRO_0000152150

Regions

Region

260 – 509

250

Editing domain

Motif

53 – 63

11

"HIGH" region

Motif

716 – 720

5

"KMSKS" region

Sites

Binding site

719

1

ATP By similarity

Natural variations

Natural variant

1088

1

R → K. Ref.1
Corresponds to variant rs10988 [ dbSNP | Ensembl ].

VAR_052637

Experimental info

Sequence conflict

271

1

V → A in BAA95667. Ref.1

Sequence conflict

892

1

N → D in BAA95667. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

1176

Helix Strand Turn

Details...

Beta strand

263 – 274

12

Helix

277 – 282

6

Beta strand

287 – 294

8

Helix

296 – 301

6

Beta strand

304 – 307

4

Beta strand

309 – 311

3

Beta strand

314 – 317

4

Beta strand

323 – 326

4

Helix

328 – 335

8

Turn

336 – 338

3

Beta strand

339 – 342

4

Beta strand

348 – 351

4

Helix

354 – 357

4

Beta strand

361 – 363

3

Beta strand

368 – 370

3

Beta strand

372 – 376

5

Beta strand

382 – 385

4

Beta strand

387 – 391

5

Turn

393 – 395

3

Helix

397 – 408

12

Helix

411 – 414

4

Turn

415 – 417

3

Helix

420 – 422

3

Turn

423 – 425

3

Beta strand

432 – 434

3

Turn

435 – 437

3

Beta strand

438 – 440

3

Helix

441 – 448

8

Helix

457 – 474

18

Helix

487 – 500

14

Beta strand

503 – 508

6

Sequences

	Sequence		Length	Mass (Da)
	Q9P2J5 [UniParc]. Last modified June 7, 2004. Version 2. Checksum: 44A4D1A1EF31634A	FASTA	1,176	134,466
	10 20 30 40 50 60 MAERKGTAKV DFLKKIEKEI QQKWDTERVF EVNASNLEKQ TSKGKYFVTF PYPYMNGRLH 70 80 90 100 110 120 LGHTFSLSKC EFAVGYQRLK GKCCLFPFGL HCTGMPIKAC ADKLKREIEL YGCPPDFPDE 130 140 150 160 170 180 EEEEEETSVK TEDIIIKDKA KGKKSKAAAK AGSSKYQWGI MKSLGLSDEE IVKFSEAEHW 190 200 210 220 230 240 LDYFPPLAIQ DLKRMGLKVD WRRSFITTDV NPYYDSFVRW QFLTLRERNK IKFGKRYTIY 250 260 270 280 290 300 SPKDGQPCMD HDRQTGEGVG PQEYTLLKLK VLEPYPSKLS GLKGKNIFLV AATLRPETMF 310 320 330 340 350 360 GQTNCWVRPD MKYIGFETVN GDIFICTQKA ARNMSYQGFT KDNGVVPVVK ELMGEEILGA 370 380 390 400 410 420 SLSAPLTSYK VIYVLPMLTI KEDKGTGVVT SVPSDSPDDI AALRDLKKKQ ALRAKYGIRD 430 440 450 460 470 480 DMVLPFEPVP VIEIPGFGNL SAVTICDELK IQSQNDREKL AEAKEKIYLK GFYEGIMLVD 490 500 510 520 530 540 GFKGQKVQDV KKTIQKKMID AGDALIYMEP EKQVMSRSSD ECVVALCDQW YLDYGEENWK 550 560 570 580 590 600 KQTSQCLKNL ETFCEETRRN FEATLGWLQE HACSRTYGLG THLPWDEQWL IESLSDSTIY 610 620 630 640 650 660 MAFYTVAHLL QGGNLHGQAE SPLGIRPQQM TKEVWDYVFF KEAPFPKTQI AKEKLDQLKQ 670 680 690 700 710 720 EFEFWYPVDL RVSGKDLVPN HLSYYLYNHV AMWPEQSDKW PTAVRANGHL LLNSEKMSKS 730 740 750 760 770 780 TGNFLTLTQA IDKFSADGMR LALADAGDTV EDANFVEAMA DAGILRLYTW VEWVKEMVAN 790 800 810 820 830 840 WDSLRSGPAS TFNDRVFASE LNAGIIKTDQ NYEKMMFKEA LKTGFFEFQA AKDKYRELAV 850 860 870 880 890 900 EGMHRELVFR FIEVQTLLLA PFCPHLCEHI WTLLGKPDSI MNASWPVAGP VNEVLIHSSQ 910 920 930 940 950 960 YLMEVTHDLR LRLKNYMMPA KGKKTDKQPL QKPSHCTIYV AKNYPPWQHT TLSVLRKHFE 970 980 990 1000 1010 1020 ANNGKLPDNK VIASELGSMP ELKKYMKKVM PFVAMIKENL EKMGPRILDL QLEFDEKAVL 1030 1040 1050 1060 1070 1080 MENIVYLTNS LELEHIEVKF ASEAEDKIRE DCCPGKPLNV FRIEPGVSVS LVNPQPSNGH 1090 1100 1110 1120 1130 1140 FSTKIEIRQG DNCDSIIRRL MKMNRGIKDL SKVKLMRFDD PLLGPRRVPV LGKEYTEKTP 1150 1160 1170 ISEHAVFNVD LMSKKIHLTE NGIRVDIGDT IIYLVH

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and sequence determination of a human cytoplasmic leucyl-tRNA synthetase gene." Motegi H., Noda T., Shiba K. Submitted (MAR-1996) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT LYS-1088. Tissue: Brain.
[2]	"Prediction of the coding sequences of unidentified human genes. XVI. The complete sequences of 150 new cDNA clones from brain which code for large proteins in vitro." Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O. DNA Res. 7:65-73(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[3]	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 (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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].
[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] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[6]	"Crystal structures of the human and fungal cytosolic Leucyl-tRNA synthetase editing domains: A structural basis for the rational design of antifungal benzoxaboroles." Seiradake E., Mao W., Hernandez V., Baker S.J., Plattner J.J., Alley M.R.K., Cusack S. J. Mol. Biol. 390:196-207(2009) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.25 ANGSTROMS) OF 260-509 IN COMPLEX WITH (6-(ETHYLAMINO)-5-FLUOROBENZO[C][1,2]OXABOROL-1(3H)-OL) AND AMP, FUNCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

D84223 mRNA. Translation: BAA95667.1.
AB037773 mRNA. Translation: BAA92590.1. Different initiation.
CH471062 Genomic DNA. Translation: EAW61848.1.
BC150213 mRNA. Translation: AAI50214.1.
BC151214 mRNA. Translation: AAI51215.1.
BC152422 mRNA. Translation: AAI52423.1.

IPI

IPI00103994.

RefSeq

NP_064502.9. NM_020117.9.

UniGene

Hs.432674.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2WFD	X-ray	3.25	A/B	260-509	[»]

ProteinModelPortal

Q9P2J5.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9P2J5. 12 interactions.

MINT

MINT-1158952.

STRING

9606.ENSP00000377954.

PTM databases

PhosphoSite

Q9P2J5.

Polymorphism databases

DMDM

48428689.

Proteomic databases

PaxDb

Q9P2J5.

PeptideAtlas

Q9P2J5.

PRIDE

Q9P2J5.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000394434; ENSP00000377954; ENSG00000133706.

GeneID

51520.

KEGG

hsa:51520.

UCSC

uc003lnx.1. human.

Organism-specific databases

CTD

51520.

GeneCards

GC05M145473.

HGNC

HGNC:6512. LARS.

HPA

HPA036424.

MIM

151350. gene.

neXtProt

NX_Q9P2J5.

PharmGKB

PA30297.

HUGE

Search...

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0495.

HOGENOM

HOG000216621.

HOVERGEN

HBG055325.

InParanoid

Q9P2J5.

KO

K01869.

OMA

LRTFTIP.

OrthoDB

EOG4G1MFK.

PhylomeDB

Q9P2J5.

Enzyme and pathway databases

Reactome

REACT_71. Gene Expression.

Gene expression databases

ArrayExpress

Q9P2J5.

Bgee

Q9P2J5.

CleanEx

HS_LARS.

Genevestigator

Q9P2J5.

GermOnline

ENSG00000133706. Homo sapiens.

Family and domain databases

Gene3D

3.40.50.620. 3 hits.
3.90.740.10. 1 hit.

InterPro

IPR001412. aa-tRNA-synth_I_CS.
IPR002300. aa-tRNA-synth_Ia.
IPR004493. Leu-tRNA-synth_Ia_arc/euk.
IPR014729. Rossmann-like_a/b/a_fold.
IPR009080. tRNAsynth_1a_anticodon-bd.
IPR013155. V/L/I-tRNA-synth_anticodon-bd.
IPR009008. Val/Leu/Ile-tRNA-synth_edit.
[Graphical view]

Pfam

PF08264. Anticodon_1. 1 hit.
PF00133. tRNA-synt_1. 2 hits.
[Graphical view]

SUPFAM

SSF47323. tRNAsyn_1a_bind. 1 hit.
SSF50677. ValRS_IleRS_edit. 1 hit.

TIGRFAMs

TIGR00395. leuS_arch. 1 hit.

PROSITE

PS00178. AA_TRNA_LIGASE_I. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

Q9P2J5.

ChEMBL

CHEMBL3258.

ChiTaRS

LARS. human.

DrugBank

DB00149. L-Leucine.

EvolutionaryTrace

Q9P2J5.

GenomeRNAi

51520.

NextBio

55220.

SOURCE

Search...

Entry information

Entry name

SYLC_HUMAN

Accession

Primary (citable) accession number: Q9P2J5
Secondary accession number(s): A7E266, Q9NSE1

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 7, 2004
Last sequence update:	June 7, 2004
Last modified:	May 1, 2013
This is version 106 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.