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Protein

Tryptophan--tRNA ligase, cytoplasmic

Gene

WARS

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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.4 Publications

Catalytic activityi

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

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • tryptophan-tRNA ligase activity Source: UniProtKB

GO - Biological processi

  • angiogenesis Source: UniProtKB-KW
  • negative regulation of cell proliferation Source: ProtInc
  • regulation of angiogenesis Source: UniProtKB
  • translation Source: ProtInc
  • tRNA aminoacylation for protein translation Source: Reactome
  • tryptophanyl-tRNA aminoacylation Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Aminoacyl-tRNA synthetase, Ligase

Keywords - Biological processi

Angiogenesis, Protein biosynthesis

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS06685-MONOMER.
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:6.1.1.2)
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

HGNCiHGNC:12729. WARS.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: Reactome
  • extracellular exosome Source: UniProtKB
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Organism-specific databases

DisGeNETi7453.
OpenTargetsiENSG00000140105.
PharmGKBiPA37340.

Chemistry databases

DrugBankiDB00150. L-Tryptophan.

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.

2D gel databases

OGPiP23381.

PTM databases

iPTMnetiP23381.
PhosphoSitePlusiP23381.
SwissPalmiP23381.

Expressioni

Inductioni

By IFNG/IFN-gamma.1 Publication

Gene expression databases

BgeeiENSG00000140105.
CleanExiHS_WARS.
ExpressionAtlasiP23381. baseline and differential.
GenevisibleiP23381. HS.

Organism-specific databases

HPAiHPA018944.

Interactioni

Subunit structurei

Homodimer. Isoform 1 and isoform 2 interact with an oxidized form of GAPDH. GAPDH stimulates the aminoacylation activity of isoform 2.

Binary interactionsi

WithEntry#Exp.IntActNotes
TERF1P542742EBI-721244,EBI-710997

Protein-protein interaction databases

BioGridi113292. 59 interactors.
DIPiDIP-29493N.
IntActiP23381. 7 interactors.
MINTiMINT-1408962.
STRINGi9606.ENSP00000347495.

Structurei

Secondary structure

1471
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi8 – 28Combined sources21
Helixi33 – 53Combined sources21
Beta strandi54 – 56Combined sources3
Beta strandi84 – 86Combined sources3
Beta strandi89 – 91Combined sources3
Turni100 – 102Combined sources3
Helixi103 – 106Combined sources4
Helixi114 – 124Combined sources11
Helixi130 – 133Combined sources4
Beta strandi136 – 142Combined sources7
Helixi143 – 150Combined sources8
Turni151 – 153Combined sources3
Beta strandi156 – 162Combined sources7
Helixi171 – 187Combined sources17
Beta strandi191 – 195Combined sources5
Helixi197 – 203Combined sources7
Helixi208 – 223Combined sources16
Turni224 – 226Combined sources3
Helixi229 – 231Combined sources3
Beta strandi232 – 236Combined sources5
Helixi237 – 240Combined sources4
Helixi241 – 243Combined sources3
Helixi247 – 256Combined sources10
Helixi260 – 267Combined sources8
Beta strandi271 – 274Combined sources4
Helixi275 – 285Combined sources11
Helixi286 – 288Combined sources3
Helixi290 – 292Combined sources3
Helixi294 – 297Combined sources4
Beta strandi304 – 310Combined sources7
Helixi311 – 313Combined sources3
Helixi314 – 323Combined sources10
Helixi324 – 327Combined sources4
Beta strandi333 – 337Combined sources5
Beta strandi345 – 349Combined sources5
Beta strandi354 – 357Combined sources4
Beta strandi360 – 362Combined sources3
Helixi365 – 374Combined sources10
Helixi384 – 390Combined sources7
Turni394 – 396Combined sources3
Helixi398 – 406Combined sources9
Helixi410 – 422Combined sources13
Beta strandi423 – 425Combined sources3
Helixi430 – 450Combined sources21
Helixi454 – 460Combined sources7

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[»]
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

Contains 1 WHEP-TRS domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG2145. Eukaryota.
COG0180. LUCA.
GeneTreeiENSGT00390000000666.
HOVERGENiHBG002325.
InParanoidiP23381.
KOiK01867.
OMAiFFFSHRD.
OrthoDBiEOG091G09U9.
PhylomeDBiP23381.
TreeFamiTF105669.

Family and domain databases

CDDicd00806. TrpRS_core. 1 hit.
Gene3Di1.10.287.10. 1 hit.
3.40.50.620. 1 hit.
InterProiIPR001412. 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.
[Graphical view]
PANTHERiPTHR10055. PTHR10055. 1 hit.
PfamiPF00579. tRNA-synt_1b. 1 hit.
PF00458. WHEP-TRS. 1 hit.
[Graphical view]
PRINTSiPR01039. TRNASYNTHTRP.
SMARTiSM00991. WHEP-TRS. 1 hit.
[Graphical view]
SUPFAMiSSF47060. SSF47060. 1 hit.
TIGRFAMsiTIGR00233. trpS. 1 hit.
PROSITEiPS00178. AA_TRNA_LIGASE_I. 1 hit.
PS00762. WHEP_TRS_1. 1 hit.
PS51185. WHEP_TRS_2. 1 hit.
[Graphical view]

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: 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

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 rs2234521dbSNPEnsembl.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. [P23381-1]
XP_011535438.1. XM_011537136.2. [P23381-2]
XP_016877116.1. XM_017021627.1. [P23381-1]
XP_016877117.1. XM_017021628.1. [P23381-1]
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

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. [P23381-1]
XP_011535438.1. XM_011537136.2. [P23381-2]
XP_016877116.1. XM_017021627.1. [P23381-1]
XP_016877117.1. XM_017021628.1. [P23381-1]
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[»]
ProteinModelPortaliP23381.
SMRiP23381.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113292. 59 interactors.
DIPiDIP-29493N.
IntActiP23381. 7 interactors.
MINTiMINT-1408962.
STRINGi9606.ENSP00000347495.

Chemistry databases

DrugBankiDB00150. L-Tryptophan.

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.

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.
GeneCardsiWARS.
HGNCiHGNC:12729. WARS.
HPAiHPA018944.
MIMi191050. gene.
neXtProtiNX_P23381.
OpenTargetsiENSG00000140105.
PharmGKBiPA37340.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2145. Eukaryota.
COG0180. LUCA.
GeneTreeiENSGT00390000000666.
HOVERGENiHBG002325.
InParanoidiP23381.
KOiK01867.
OMAiFFFSHRD.
OrthoDBiEOG091G09U9.
PhylomeDBiP23381.
TreeFamiTF105669.

Enzyme and pathway databases

BioCyciZFISH:HS06685-MONOMER.
BRENDAi6.1.1.2. 2681.
ReactomeiR-HSA-379716. Cytosolic tRNA aminoacylation.

Miscellaneous databases

ChiTaRSiWARS. human.
EvolutionaryTraceiP23381.
GeneWikiiWARS_(gene).
GenomeRNAii7453.
PROiP23381.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000140105.
CleanExiHS_WARS.
ExpressionAtlasiP23381. baseline and differential.
GenevisibleiP23381. HS.

Family and domain databases

CDDicd00806. TrpRS_core. 1 hit.
Gene3Di1.10.287.10. 1 hit.
3.40.50.620. 1 hit.
InterProiIPR001412. 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.
[Graphical view]
PANTHERiPTHR10055. PTHR10055. 1 hit.
PfamiPF00579. tRNA-synt_1b. 1 hit.
PF00458. WHEP-TRS. 1 hit.
[Graphical view]
PRINTSiPR01039. TRNASYNTHTRP.
SMARTiSM00991. WHEP-TRS. 1 hit.
[Graphical view]
SUPFAMiSSF47060. SSF47060. 1 hit.
TIGRFAMsiTIGR00233. trpS. 1 hit.
PROSITEiPS00178. AA_TRNA_LIGASE_I. 1 hit.
PS00762. WHEP_TRS_1. 1 hit.
PS51185. WHEP_TRS_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiSYWC_HUMAN
AccessioniPrimary (citable) accession number: P23381
Secondary accession number(s): A6NGN1
, A6NID3, P78535, Q502Y0, Q53XB6, Q9UDI5, Q9UDL3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1991
Last sequence update: December 1, 1992
Last modified: November 30, 2016
This is version 173 of the entry and version 2 of the sequence. [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. Aminoacyl-tRNA synthetases
    List of aminoacyl-tRNA synthetase entries
  2. Human chromosome 14
    Human chromosome 14: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.