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Protein

Tryptophan--tRNA ligase, cytoplasmic

Gene

WARS

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

Functioni

Isoform 1, isoform 2 and T1-TrpRS have aminoacylation activity while T2-TrpRS lacks it. Isoform 2, T1-TrpRS and T2-TrpRS possess angiostatic activity whereas isoform 1 lacks it. T2-TrpRS inhibits fluid shear stress-activated responses of endothelial cells. Regulates ERK, Akt, and eNOS activation pathways that are associated with angiogenesis, cytoskeletal reorganization and shear stress-responsive gene expression.5 Publications

Catalytic activityi

ATP + L-tryptophan + tRNA(Trp) = AMP + diphosphate + L-tryptophyl-tRNA(Trp).2 Publications

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • kinase inhibitor activity Source: CAFA
  • protein domain specific binding Source: CAFA
  • protein homodimerization activity Source: UniProtKB
  • protein kinase binding Source: CAFA
  • tryptophan-tRNA ligase activity Source: UniProtKB

GO - Biological processi

Keywordsi

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

Enzyme and pathway databases

BRENDAi6.1.1.2 2681
ReactomeiR-HSA-379716 Cytosolic tRNA aminoacylation

Protein family/group databases

MoonProtiP23381

Names & Taxonomyi

Protein namesi
Recommended name:
Tryptophan--tRNA ligase, cytoplasmic (EC:6.1.1.22 Publications)
Alternative name(s):
Interferon-induced protein 53
Short name:
IFP53
Tryptophanyl-tRNA synthetase
Short name:
TrpRS
Short name:
hWRS
Cleaved into the following 2 chains:
Gene namesi
Name:WARS
Synonyms:IFI53, WRS
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 14

Organism-specific databases

EuPathDBiHostDB:ENSG00000140105.17
HGNCiHGNC:12729 WARS
MIMi191050 gene
neXtProtiNX_P23381

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

Cytoplasm

Pathology & Biotechi

Involvement in diseasei

Neuronopathy, distal hereditary motor, 9 (HMN9)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal dominant neurologic disorder characterized by juvenile onset of slowly progressive distal muscle weakness and atrophy affecting both the lower and upper limbs.
See also OMIM:617721
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_080407257H → R in HMN9; decreased tryptophan-tRNA ligase activity; dominant negative effect; decreased general protein synthesis; decreased cell viability; no effect on homodimerization. 1 Publication1

Keywords - Diseasei

Disease mutation, Neurodegeneration, Neuropathy

Organism-specific databases

DisGeNETi7453
MalaCardsiWARS
MIMi617721 phenotype
OpenTargetsiENSG00000140105
PharmGKBiPA37340

Chemistry databases

DrugBankiDB00150 L-Tryptophan
DB04537 L-Tryptophanamide
DB01831 Tryptophanyl-5'amp

Polymorphism and mutation databases

BioMutaiWARS
DMDMi135191

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources2 Publications
ChainiPRO_00001367382 – 471Tryptophan--tRNA ligase, cytoplasmicAdd BLAST470
ChainiPRO_000038646171 – 471T1-TrpRSAdd BLAST401
ChainiPRO_000038646294 – 471T2-TrpRSAdd BLAST378

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei154N6-succinyllysineBy similarity1
Modified residuei351PhosphoserineCombined sources1

Post-translational modificationi

Proteolytic cleavage generates 2 forms; T1-TrpRS and T2-TrpRS.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiP23381
MaxQBiP23381
PaxDbiP23381
PeptideAtlasiP23381
PRIDEiP23381
ProteomicsDBi54085
54086 [P23381-2]

2D gel databases

OGPiP23381

PTM databases

iPTMnetiP23381
PhosphoSitePlusiP23381
SwissPalmiP23381

Expressioni

Inductioni

By IFNG/IFN-gamma.1 Publication

Gene expression databases

BgeeiENSG00000140105 Expressed in 234 organ(s), highest expression level in epithelium of bronchus
CleanExiHS_WARS
ExpressionAtlasiP23381 baseline and differential
GenevisibleiP23381 HS

Organism-specific databases

HPAiHPA005573
HPA018944

Interactioni

Subunit structurei

Homodimer (PubMed:28369220). Isoform 1 and isoform 2 interact with an oxidized form of GAPDH. GAPDH stimulates the aminoacylation activity of isoform 2 (PubMed:15628863).2 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi113292, 65 interactors
DIPiDIP-29493N
IntActiP23381, 11 interactors
MINTiP23381
STRINGi9606.ENSP00000347495

Structurei

Secondary structure

1471
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP23381
SMRiP23381
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP23381

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini8 – 64WHEP-TRSPROSITE-ProRule annotationAdd BLAST57

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi164 – 173"HIGH" region10
Motifi349 – 353"KMSKS" region5

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG2145 Eukaryota
COG0180 LUCA
GeneTreeiENSGT00390000000666
HOVERGENiHBG002325
InParanoidiP23381
KOiK01867
OMAiADILHPQ
OrthoDBiEOG091G09U9
PhylomeDBiP23381
TreeFamiTF105669

Family and domain databases

CDDicd00806 TrpRS_core, 1 hit
Gene3Di3.40.50.620, 1 hit
InterProiView protein in InterPro
IPR001412 aa-tRNA-synth_I_CS
IPR002305 aa-tRNA-synth_Ic
IPR014729 Rossmann-like_a/b/a_fold
IPR009068 S15_NS1_RNA-bd
IPR002306 Trp-tRNA-ligase
IPR000738 WHEP-TRS_dom
PfamiView protein in Pfam
PF00579 tRNA-synt_1b, 1 hit
PF00458 WHEP-TRS, 1 hit
PRINTSiPR01039 TRNASYNTHTRP
SMARTiView protein in SMART
SM00991 WHEP-TRS, 1 hit
SUPFAMiSSF47060 SSF47060, 1 hit
TIGRFAMsiTIGR00233 trpS, 1 hit
PROSITEiView protein in PROSITE
PS00178 AA_TRNA_LIGASE_I, 1 hit
PS00762 WHEP_TRS_1, 1 hit
PS51185 WHEP_TRS_2, 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

This entry has 2 described isoforms and 26 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: P23381-1) [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
MPNSEPASLL ELFNSIATQG ELVRSLKAGN ASKDEIDSAV KMLVSLKMSY
60 70 80 90 100
KAAAGEDYKA DCPPGNPAPT SNHGPDATEA EEDFVDPWTV QTSSAKGIDY
110 120 130 140 150
DKLIVRFGSS KIDKELINRI ERATGQRPHH FLRRGIFFSH RDMNQVLDAY
160 170 180 190 200
ENKKPFYLYT GRGPSSEAMH VGHLIPFIFT KWLQDVFNVP LVIQMTDDEK
210 220 230 240 250
YLWKDLTLDQ AYSYAVENAK DIIACGFDIN KTFIFSDLDY MGMSSGFYKN
260 270 280 290 300
VVKIQKHVTF NQVKGIFGFT DSDCIGKISF PAIQAAPSFS NSFPQIFRDR
310 320 330 340 350
TDIQCLIPCA IDQDPYFRMT RDVAPRIGYP KPALLHSTFF PALQGAQTKM
360 370 380 390 400
SASDPNSSIF LTDTAKQIKT KVNKHAFSGG RDTIEEHRQF GGNCDVDVSF
410 420 430 440 450
MYLTFFLEDD DKLEQIRKDY TSGAMLTGEL KKALIEVLQP LIAEHQARRK
460 470
EVTDEIVKEF MTPRKLSFDF Q
Length:471
Mass (Da):53,165
Last modified:December 1, 1992 - v2
Checksum:iE96344449053A0D0
GO
Isoform 2 (identifier: P23381-2) [UniParc]FASTAAdd to basket
Also known as: mini TrpRS

The sequence of this isoform differs from the canonical sequence as follows:
     1-41: Missing.

Show »
Length:430
Mass (Da):48,852
Checksum:i5FE1254E781221DD
GO

Computationally mapped potential isoform sequencesi

There are 26 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
G3V3H8G3V3H8_HUMAN
Tryptophan--tRNA ligase, cytoplasmi...
WARS
223Annotation score:
G3V3Y5G3V3Y5_HUMAN
Tryptophan--tRNA ligase, cytoplasmi...
WARS
226Annotation score:
G3V277G3V277_HUMAN
Tryptophan--tRNA ligase, cytoplasmi...
WARS
212Annotation score:
H0YJP3H0YJP3_HUMAN
Tryptophan--tRNA ligase, cytoplasmi...
WARS
185Annotation score:
G3V5U1G3V5U1_HUMAN
Tryptophan--tRNA ligase, cytoplasmi...
WARS
153Annotation score:
G3V456G3V456_HUMAN
Tryptophan--tRNA ligase, cytoplasmi...
WARS
154Annotation score:
G3V227G3V227_HUMAN
Tryptophan--tRNA ligase, cytoplasmi...
WARS
152Annotation score:
G3V3X0G3V3X0_HUMAN
Tryptophan--tRNA ligase, cytoplasmi...
WARS
124Annotation score:
G3V3P2G3V3P2_HUMAN
Tryptophan--tRNA ligase, cytoplasmi...
WARS
150Annotation score:
G3V3S7G3V3S7_HUMAN
Tryptophan--tRNA ligase, cytoplasmi...
WARS
114Annotation score:
There are more potential isoformsShow all

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti213 – 214SY → GD in AAA61298 (PubMed:1765274).Curated2
Sequence conflicti310A → V in AAH95453 (PubMed:15489334).Curated1
Sequence conflicti424A → R in CAA44450 (PubMed:1537332).Curated1
Sequence conflicti439Q → L in AAH95453 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05240654A → S. Corresponds to variant dbSNP:rs2234521Ensembl.1
Natural variantiVAR_080407257H → R in HMN9; decreased tryptophan-tRNA ligase activity; dominant negative effect; decreased general protein synthesis; decreased cell viability; no effect on homodimerization. 1 Publication1
Natural variantiVAR_080408443A → S1 PublicationCorresponds to variant dbSNP:rs139914390Ensembl.1
Natural variantiVAR_036466455E → D in a breast cancer sample; somatic mutation. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0382211 – 41Missing in isoform 2. 1 PublicationAdd BLAST41

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M77804 mRNA Translation: AAA67324.1
X59892 mRNA Translation: CAA42545.1
M61715 mRNA Translation: AAA61298.1
X62570 mRNA Translation: CAA44450.1
BX248006 mRNA Translation: CAD62335.1
AK056100 mRNA Translation: BAG51626.1
AK291141 mRNA Translation: BAF83830.1
AL157871 Genomic DNA No translation available.
CH471061 Genomic DNA Translation: EAW81700.1
BC017489 mRNA Translation: AAH17489.1
BC095453 mRNA Translation: AAH95453.1
S82905 Genomic DNA Translation: AAB39381.1
X67920, X67921, X67922 Genomic DNA Translation: CAB94198.1
X67923
, X67924, X67925, X67926, X67927, X67928 Genomic DNA Translation: CAB94199.1
CCDSiCCDS9960.1 [P23381-1]
CCDS9961.1 [P23381-2]
PIRiA41633 A41706
RefSeqiNP_004175.2, NM_004184.3 [P23381-1]
NP_776049.1, NM_173701.1 [P23381-1]
NP_998810.1, NM_213645.1 [P23381-2]
NP_998811.1, NM_213646.1 [P23381-2]
XP_005268101.1, XM_005268044.3 [P23381-1]
XP_006720312.1, XM_006720249.3 [P23381-1]
XP_011535435.1, XM_011537133.2 [P23381-1]
XP_011535437.1, XM_011537135.2
XP_011535438.1, XM_011537136.2 [P23381-2]
XP_016877116.1, XM_017021627.1 [P23381-1]
XP_016877117.1, XM_017021628.1
XP_016877118.1, XM_017021629.1 [P23381-1]
UniGeneiHs.497599

Genome annotation databases

EnsembliENST00000344102; ENSP00000339485; ENSG00000140105 [P23381-2]
ENST00000355338; ENSP00000347495; ENSG00000140105 [P23381-1]
ENST00000358655; ENSP00000351481; ENSG00000140105 [P23381-2]
ENST00000392882; ENSP00000376620; ENSG00000140105 [P23381-1]
ENST00000556645; ENSP00000451887; ENSG00000140105 [P23381-2]
ENST00000557135; ENSP00000451460; ENSG00000140105 [P23381-1]
GeneIDi7453
KEGGihsa:7453
UCSCiuc001yhg.3 human [P23381-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M77804 mRNA Translation: AAA67324.1
X59892 mRNA Translation: CAA42545.1
M61715 mRNA Translation: AAA61298.1
X62570 mRNA Translation: CAA44450.1
BX248006 mRNA Translation: CAD62335.1
AK056100 mRNA Translation: BAG51626.1
AK291141 mRNA Translation: BAF83830.1
AL157871 Genomic DNA No translation available.
CH471061 Genomic DNA Translation: EAW81700.1
BC017489 mRNA Translation: AAH17489.1
BC095453 mRNA Translation: AAH95453.1
S82905 Genomic DNA Translation: AAB39381.1
X67920, X67921, X67922 Genomic DNA Translation: CAB94198.1
X67923
, X67924, X67925, X67926, X67927, X67928 Genomic DNA Translation: CAB94199.1
CCDSiCCDS9960.1 [P23381-1]
CCDS9961.1 [P23381-2]
PIRiA41633 A41706
RefSeqiNP_004175.2, NM_004184.3 [P23381-1]
NP_776049.1, NM_173701.1 [P23381-1]
NP_998810.1, NM_213645.1 [P23381-2]
NP_998811.1, NM_213646.1 [P23381-2]
XP_005268101.1, XM_005268044.3 [P23381-1]
XP_006720312.1, XM_006720249.3 [P23381-1]
XP_011535435.1, XM_011537133.2 [P23381-1]
XP_011535437.1, XM_011537135.2
XP_011535438.1, XM_011537136.2 [P23381-2]
XP_016877116.1, XM_017021627.1 [P23381-1]
XP_016877117.1, XM_017021628.1
XP_016877118.1, XM_017021629.1 [P23381-1]
UniGeneiHs.497599

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1O5TX-ray2.50A94-471[»]
1R6TX-ray2.10A/B1-466[»]
1R6UX-ray2.00A/B48-471[»]
1ULHX-ray2.31A/B82-471[»]
2AKEX-ray3.10A94-471[»]
2AZXX-ray2.80A/B1-471[»]
2DR2X-ray3.00A94-471[»]
2QUHX-ray2.40A/B1-471[»]
2QUIX-ray2.40A/B1-471[»]
2QUJX-ray2.42A/B1-471[»]
2QUKX-ray2.80A1-471[»]
5UJIX-ray2.79A/B97-471[»]
5UJJX-ray2.10A/B1-471[»]
ProteinModelPortaliP23381
SMRiP23381
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113292, 65 interactors
DIPiDIP-29493N
IntActiP23381, 11 interactors
MINTiP23381
STRINGi9606.ENSP00000347495

Chemistry databases

DrugBankiDB00150 L-Tryptophan
DB04537 L-Tryptophanamide
DB01831 Tryptophanyl-5'amp

Protein family/group databases

MoonProtiP23381

PTM databases

iPTMnetiP23381
PhosphoSitePlusiP23381
SwissPalmiP23381

Polymorphism and mutation databases

BioMutaiWARS
DMDMi135191

2D gel databases

OGPiP23381

Proteomic databases

EPDiP23381
MaxQBiP23381
PaxDbiP23381
PeptideAtlasiP23381
PRIDEiP23381
ProteomicsDBi54085
54086 [P23381-2]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000344102; ENSP00000339485; ENSG00000140105 [P23381-2]
ENST00000355338; ENSP00000347495; ENSG00000140105 [P23381-1]
ENST00000358655; ENSP00000351481; ENSG00000140105 [P23381-2]
ENST00000392882; ENSP00000376620; ENSG00000140105 [P23381-1]
ENST00000556645; ENSP00000451887; ENSG00000140105 [P23381-2]
ENST00000557135; ENSP00000451460; ENSG00000140105 [P23381-1]
GeneIDi7453
KEGGihsa:7453
UCSCiuc001yhg.3 human [P23381-1]

Organism-specific databases

CTDi7453
DisGeNETi7453
EuPathDBiHostDB:ENSG00000140105.17
GeneCardsiWARS
HGNCiHGNC:12729 WARS
HPAiHPA005573
HPA018944
MalaCardsiWARS
MIMi191050 gene
617721 phenotype
neXtProtiNX_P23381
OpenTargetsiENSG00000140105
PharmGKBiPA37340
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2145 Eukaryota
COG0180 LUCA
GeneTreeiENSGT00390000000666
HOVERGENiHBG002325
InParanoidiP23381
KOiK01867
OMAiADILHPQ
OrthoDBiEOG091G09U9
PhylomeDBiP23381
TreeFamiTF105669

Enzyme and pathway databases

BRENDAi6.1.1.2 2681
ReactomeiR-HSA-379716 Cytosolic tRNA aminoacylation

Miscellaneous databases

ChiTaRSiWARS human
EvolutionaryTraceiP23381
GeneWikiiWARS_(gene)
GenomeRNAii7453
PROiPR:P23381
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000140105 Expressed in 234 organ(s), highest expression level in epithelium of bronchus
CleanExiHS_WARS
ExpressionAtlasiP23381 baseline and differential
GenevisibleiP23381 HS

Family and domain databases

CDDicd00806 TrpRS_core, 1 hit
Gene3Di3.40.50.620, 1 hit
InterProiView protein in InterPro
IPR001412 aa-tRNA-synth_I_CS
IPR002305 aa-tRNA-synth_Ic
IPR014729 Rossmann-like_a/b/a_fold
IPR009068 S15_NS1_RNA-bd
IPR002306 Trp-tRNA-ligase
IPR000738 WHEP-TRS_dom
PfamiView protein in Pfam
PF00579 tRNA-synt_1b, 1 hit
PF00458 WHEP-TRS, 1 hit
PRINTSiPR01039 TRNASYNTHTRP
SMARTiView protein in SMART
SM00991 WHEP-TRS, 1 hit
SUPFAMiSSF47060 SSF47060, 1 hit
TIGRFAMsiTIGR00233 trpS, 1 hit
PROSITEiView protein in PROSITE
PS00178 AA_TRNA_LIGASE_I, 1 hit
PS00762 WHEP_TRS_1, 1 hit
PS51185 WHEP_TRS_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiSYWC_HUMAN
AccessioniPrimary (citable) accession number: P23381
Secondary accession number(s): A6NGN1
, A6NID3, P78535, Q502Y0, Q53XB6, Q9UDI5, Q9UDL3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1991
Last sequence update: December 1, 1992
Last modified: October 10, 2018
This is version 190 of the entry and version 2 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, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 14
    Human chromosome 14: entries, gene names and cross-references to MIM
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families
  4. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  5. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  6. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  7. Aminoacyl-tRNA synthetases
    List of aminoacyl-tRNA synthetase entries
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