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Protein

Tryptophan--tRNA ligase, mitochondrial

Gene

WARS2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Mitochondrial aminoacyl-tRNA synthetase that activate and transfer the amino acids to their corresponding tRNAs during the translation of mitochondrial genes and protein synthesis.1 Publication

Catalytic activityi

ATP + L-tryptophan + tRNA(Trp) = AMP + diphosphate + L-tryptophyl-tRNA(Trp).

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei42ATPCombined sources1
Binding sitei167L-tryptophanCombined sources1
Binding sitei217ATP; via amide nitrogen and carbonyl oxygenCombined sources1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi48 – 51ATPCombined sources4
Nucleotide bindingi179 – 181ATPCombined sources3
Nucleotide bindingi226 – 230ATPCombined sources5

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionAminoacyl-tRNA synthetase, Ligase
Biological processProtein biosynthesis
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi6.1.1.2 2681
ReactomeiR-HSA-379726 Mitochondrial tRNA aminoacylation

Names & Taxonomyi

Protein namesi
Recommended name:
Tryptophan--tRNA ligase, mitochondrial (EC:6.1.1.2)
Alternative name(s):
(Mt)TrpRS
Tryptophanyl-tRNA synthetase
Short name:
TrpRS
Gene namesi
Name:WARS2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000116874.11
HGNCiHGNC:12730 WARS2
MIMi604733 gene
neXtProtiNX_Q9UGM6

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Involvement in diseasei

Neurodevelopmental disorder, mitochondrial, with abnormal movements and lactic acidosis, with or without seizures (NEMMLAS)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal recessive, mitochondrial disorder with a broad phenotypic spectrum ranging from severe neonatal lactic acidosis, encephalomyopathy and early death to an attenuated course with milder manifestations. Clinical features include delayed psychomotor development, intellectual disability, hypotonia, dystonia, ataxia, and spasticity. Severe combined respiratory chain deficiency may be found in severely affected individuals.
See also OMIM:617710
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07843513W → G in NEMMLAS; impaired mitochondrial localization. 1 PublicationCorresponds to variant dbSNP:rs139548132Ensembl.1
Natural variantiVAR_07973445G → V in NEMMLAS. 1 Publication1
Natural variantiVAR_07973577H → Q in NEMMLAS; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs766501807Ensembl.1
Natural variantiVAR_079736100Missing in NEMMLAS. 1 Publication1
Natural variantiVAR_079737178V → L in NEMMLAS. 1 Publication1
Natural variantiVAR_079738313K → M in NEMMLAS. 2 PublicationsCorresponds to variant dbSNP:rs145867327Ensembl.1
Natural variantiVAR_079739349V → L in NEMMLAS. 1 Publication1
Natural variantiVAR_079740352E → K in NEMMLAS; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs563341344Ensembl.1

Keywords - Diseasei

Disease mutation, Primary mitochondrial disease

Organism-specific databases

DisGeNETi10352
MIMi617710 phenotype
OpenTargetsiENSG00000116874
PharmGKBiPA37341

Chemistry databases

DrugBankiDB00150 L-Tryptophan

Polymorphism and mutation databases

BioMutaiWARS2
DMDMi21362967

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 18MitochondrionAdd BLAST18
ChainiPRO_000003582819 – 360Tryptophan--tRNA ligase, mitochondrialAdd BLAST342

Proteomic databases

EPDiQ9UGM6
PaxDbiQ9UGM6
PeptideAtlasiQ9UGM6
PRIDEiQ9UGM6

PTM databases

iPTMnetiQ9UGM6
PhosphoSitePlusiQ9UGM6

Expressioni

Tissue specificityi

Brain.1 Publication

Gene expression databases

BgeeiENSG00000116874
CleanExiHS_WARS2
GenevisibleiQ9UGM6 HS

Organism-specific databases

HPAiHPA069692

Interactioni

Protein-protein interaction databases

BioGridi115633, 3 interactors
IntActiQ9UGM6, 3 interactors
STRINGi9606.ENSP00000235521

Structurei

Secondary structure

1360
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi37 – 41Combined sources5
Beta strandi43 – 45Combined sources3
Helixi49 – 54Combined sources6
Helixi56 – 65Combined sources10
Beta strandi69 – 73Combined sources5
Helixi75 – 78Combined sources4
Helixi85 – 102Combined sources18
Turni106 – 108Combined sources3
Beta strandi109 – 113Combined sources5
Helixi114 – 116Combined sources3
Helixi119 – 128Combined sources10
Helixi133 – 137Combined sources5
Helixi140 – 143Combined sources4
Helixi147 – 152Combined sources6
Helixi155 – 169Combined sources15
Turni170 – 172Combined sources3
Beta strandi175 – 177Combined sources3
Helixi180 – 182Combined sources3
Helixi183 – 200Combined sources18
Beta strandi208 – 210Combined sources3
Turni213 – 216Combined sources4
Helixi234 – 236Combined sources3
Helixi244 – 253Combined sources10
Turni266 – 268Combined sources3
Helixi270 – 283Combined sources14
Helixi287 – 293Combined sources7
Turni294 – 296Combined sources3
Helixi299 – 324Combined sources26
Helixi328 – 357Combined sources30

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5EKDX-ray1.82A/B18-360[»]
ProteinModelPortaliQ9UGM6
SMRiQ9UGM6
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG2713 Eukaryota
COG0180 LUCA
GeneTreeiENSGT00510000047425
HOGENOMiHOG000059940
HOVERGENiHBG027444
InParanoidiQ9UGM6
KOiK01867
OMAiQRMTQFK
OrthoDBiEOG091G04TZ
PhylomeDBiQ9UGM6
TreeFamiTF314321

Family and domain databases

CDDicd00806 TrpRS_core, 1 hit
Gene3Di3.40.50.620, 2 hits
HAMAPiMF_00140_B Trp_tRNA_synth_B, 1 hit
InterProiView protein in InterPro
IPR001412 aa-tRNA-synth_I_CS
IPR002305 aa-tRNA-synth_Ic
IPR014729 Rossmann-like_a/b/a_fold
IPR002306 Trp-tRNA-ligase
IPR024109 Trp-tRNA-ligase_bac-type
PfamiView protein in Pfam
PF00579 tRNA-synt_1b, 1 hit
PRINTSiPR01039 TRNASYNTHTRP
TIGRFAMsiTIGR00233 trpS, 1 hit
PROSITEiView protein in PROSITE
PS00178 AA_TRNA_LIGASE_I, 1 hit

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9UGM6-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MALHSMRKAR ERWSFIRALH KGSAAAPALQ KDSKKRVFSG IQPTGILHLG
60 70 80 90 100
NYLGAIESWV RLQDEYDSVL YSIVDLHSIT VPQDPAVLRQ SILDMTAVLL
110 120 130 140 150
ACGINPEKSI LFQQSQVSEH TQLSWILSCM VRLPRLQHLH QWKAKTTKQK
160 170 180 190 200
HDGTVGLLTY PVLQAADILL YKSTHVPVGE DQVQHMELVQ DLAQGFNKKY
210 220 230 240 250
GEFFPVPESI LTSMKKVKSL RDPSAKMSKS DPDKLATVRI TDSPEEIVQK
260 270 280 290 300
FRKAVTDFTS EVTYDPAGRA GVSNIVAVHA AVTGLSVEEV VRRSAGMNTA
310 320 330 340 350
RYKLAVADAV IEKFAPIKRE IEKLKLDKDH LEKVLQIGSA KAKELAYTVC
360
QEVKKLVGFL
Length:360
Mass (Da):40,147
Last modified:May 1, 2000 - v1
Checksum:i8C80DF6FCA214A91
GO
Isoform 2 (identifier: Q9UGM6-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     212-220: TSMKKVKSL → SMCVLVFLT
     221-360: Missing.

Show »
Length:220
Mass (Da):24,813
Checksum:i2535F75EDCD833F5
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti151H → R in BAD96917 (Ref. 3) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07843513W → G in NEMMLAS; impaired mitochondrial localization. 1 PublicationCorresponds to variant dbSNP:rs139548132Ensembl.1
Natural variantiVAR_07973445G → V in NEMMLAS. 1 Publication1
Natural variantiVAR_02884850G → S1 PublicationCorresponds to variant dbSNP:rs11552864Ensembl.1
Natural variantiVAR_07973577H → Q in NEMMLAS; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs766501807Ensembl.1
Natural variantiVAR_079736100Missing in NEMMLAS. 1 Publication1
Natural variantiVAR_079737178V → L in NEMMLAS. 1 Publication1
Natural variantiVAR_020217267A → P. Corresponds to variant dbSNP:rs3790549Ensembl.1
Natural variantiVAR_079738313K → M in NEMMLAS. 2 PublicationsCorresponds to variant dbSNP:rs145867327Ensembl.1
Natural variantiVAR_079739349V → L in NEMMLAS. 1 Publication1
Natural variantiVAR_079740352E → K in NEMMLAS; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs563341344Ensembl.1
Natural variantiVAR_052407360L → P. Corresponds to variant dbSNP:rs17023101Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_041414212 – 220TSMKKVKSL → SMCVLVFLT in isoform 2. 1 Publication9
Alternative sequenceiVSP_041415221 – 360Missing in isoform 2. 1 PublicationAdd BLAST140

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ242739 mRNA Translation: CAB63107.1
AK223197 mRNA Translation: BAD96917.1
AK313740 mRNA Translation: BAG36481.1
AL359823 Genomic DNA No translation available.
AL139420 Genomic DNA No translation available.
AL590288 Genomic DNA No translation available.
CH471122 Genomic DNA Translation: EAW56693.1
BC044575 mRNA Translation: AAH44575.1
BC039889 mRNA No translation available.
CCDSiCCDS30817.1 [Q9UGM6-2]
CCDS900.1 [Q9UGM6-1]
RefSeqiNP_056651.1, NM_015836.3 [Q9UGM6-1]
NP_957715.1, NM_201263.2 [Q9UGM6-2]
UniGeneiHs.523506

Genome annotation databases

EnsembliENST00000235521; ENSP00000235521; ENSG00000116874 [Q9UGM6-1]
ENST00000369426; ENSP00000358434; ENSG00000116874 [Q9UGM6-2]
GeneIDi10352
KEGGihsa:10352
UCSCiuc001ehm.4 human [Q9UGM6-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiSYWM_HUMAN
AccessioniPrimary (citable) accession number: Q9UGM6
Secondary accession number(s): B1ALR1
, B2R9D4, Q53FT4, Q5VUD2, Q86TQ0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 6, 2002
Last sequence update: May 1, 2000
Last modified: April 25, 2018
This is version 150 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome
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Main funding by: National Institutes of Health