Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Valine--tRNA ligase

Gene

VARS

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

Functioni

Catalytic activityi

ATP + L-valine + tRNA(Val) = AMP + diphosphate + L-valyl-tRNA(Val).

Activity regulationi

Can be regulated by protein kinase C-dependent phosphorylation.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei865ATPBy similarity1

GO - Molecular functioni

  • aminoacyl-tRNA editing activity Source: InterPro
  • ATP binding Source: UniProtKB-KW
  • valine-tRNA ligase activity Source: UniProtKB

GO - Biological processi

  • tRNA aminoacylation for protein translation Source: Reactome
  • valyl-tRNA aminoacylation Source: GO_Central

Keywordsi

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

Enzyme and pathway databases

BRENDAi6.1.1.9 2681
ReactomeiR-HSA-379716 Cytosolic tRNA aminoacylation

Names & Taxonomyi

Protein namesi
Recommended name:
Valine--tRNA ligase (EC:6.1.1.9)
Alternative name(s):
Protein G7a
Valyl-tRNA synthetase
Short name:
ValRS
Gene namesi
Name:VARS
Synonyms:G7A, VARS2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

EuPathDBiHostDB:ENSG00000204394.12
HGNCiHGNC:12651 VARS
MIMi192150 gene
neXtProtiNX_P26640

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

Pathology & Biotechi

Involvement in diseasei

Neurodevelopmental disorder with microcephaly, seizures, and cortical atrophy (NDMSCA)1 Publication
The disease may be caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal recessive neurodevelopmental disorder characterized by severe developmental delay, intellectual disability, severe microcephaly, and cortical atrophy.
See also OMIM:617802
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_080602885L → F in NDMSCA; unknown pathological significance. 1 Publication1
Natural variantiVAR_0806031058R → Q in NDMSCA; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs769369302EnsemblClinVar.1

Keywords - Diseasei

Disease mutation, Epilepsy, Mental retardation

Organism-specific databases

DisGeNETi7407
MalaCardsiVARS
MIMi617802 phenotype
OpenTargetsiENSG00000204394
PharmGKBiPA37275

Chemistry databases

ChEMBLiCHEMBL2612
DrugBankiDB00161 L-Valine

Polymorphism and mutation databases

BioMutaiVARS
DMDMi12644177

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources1 Publication
ChainiPRO_00001062532 – 1264Valine--tRNA ligaseAdd BLAST1263

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserineCombined sources1 Publication1
Modified residuei437PhosphoserineCombined sources1
Modified residuei527PhosphoserineCombined sources1
Modified residuei645N6-acetyllysineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP26640
MaxQBiP26640
PaxDbiP26640
PeptideAtlasiP26640
PRIDEiP26640
ProteomicsDBi54358

PTM databases

iPTMnetiP26640
PhosphoSitePlusiP26640
SwissPalmiP26640

Expressioni

Gene expression databases

BgeeiENSG00000204394 Expressed in 201 organ(s), highest expression level in testis
CleanExiHS_VARS
HS_VARS2
ExpressionAtlasiP26640 baseline and differential
GenevisibleiP26640 HS

Organism-specific databases

HPAiHPA046710

Interactioni

Subunit structurei

Forms high-molecular-mass aggregates with elongation factor 1.

Binary interactionsi

WithEntry#Exp.IntActNotes
CALCOCO2Q131373EBI-355765,EBI-739580

Protein-protein interaction databases

BioGridi113250, 90 interactors
IntActiP26640, 43 interactors
MINTiP26640
STRINGi9606.ENSP00000364815

Chemistry databases

BindingDBiP26640

Structurei

3D structure databases

ProteinModelPortaliP26640
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini89 – 219GST C-terminalAdd BLAST131

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi344 – 354"HIGH" regionAdd BLAST11
Motifi862 – 866"KMSKS" region5

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0432 Eukaryota
KOG0867 Eukaryota
COG0525 LUCA
GeneTreeiENSGT00550000074727
HOGENOMiHOG000020094
HOVERGENiHBG017878
InParanoidiP26640
KOiK01873
OMAiFATKLWN
OrthoDBiEOG093719L8
PhylomeDBiP26640
TreeFamiTF300648

Family and domain databases

CDDicd07962 Anticodon_Ia_Val, 1 hit
Gene3Di1.10.287.380, 1 hit
3.40.50.620, 2 hits
3.90.740.10, 1 hit
HAMAPiMF_02004 Val_tRNA_synth_type1, 1 hit
InterProiView protein in InterPro
IPR001412 aa-tRNA-synth_I_CS
IPR002300 aa-tRNA-synth_Ia
IPR033705 Anticodon_Ia_Val
IPR010987 Glutathione-S-Trfase_C-like
IPR036282 Glutathione-S-Trfase_C_sf
IPR004046 GST_C
IPR013155 M/V/L/I-tRNA-synth_anticd-bd
IPR014729 Rossmann-like_a/b/a_fold
IPR009080 tRNAsynth_Ia_anticodon-bd
IPR037118 Val-tRNA_synth_C_sf
IPR009008 Val/Leu/Ile-tRNA-synth_edit
IPR002303 Valyl-tRNA_ligase
PfamiView protein in Pfam
PF08264 Anticodon_1, 1 hit
PF00043 GST_C, 1 hit
PF00133 tRNA-synt_1, 1 hit
PRINTSiPR00986 TRNASYNTHVAL
SUPFAMiSSF47323 SSF47323, 1 hit
SSF47616 SSF47616, 1 hit
SSF50677 SSF50677, 1 hit
TIGRFAMsiTIGR00422 valS, 1 hit
PROSITEiView protein in PROSITE
PS00178 AA_TRNA_LIGASE_I, 1 hit
PS50405 GST_CTER, 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 6 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: P26640-1) [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
MSTLYVSPHP DAFPSLRALI AARYGEAGEG PGWGGAHPRI CLQPPPTSRT
60 70 80 90 100
PFPPPRLPAL EQGPGGLWVW GATAVAQLLW PAGLGGPGGS RAAVLVQQWV
110 120 130 140 150
SYADTELIPA ACGATLPALG LRSSAQDPQA VLGALGRALS PLEEWLRLHT
160 170 180 190 200
YLAGEAPTLA DLAAVTALLL PFRYVLDPPA RRIWNNVTRW FVTCVRQPEF
210 220 230 240 250
RAVLGEVVLY SGARPLSHQP GPEAPALPKT AAQLKKEAKK REKLEKFQQK
260 270 280 290 300
QKIQQQQPPP GEKKPKPEKR EKRDPGVITY DLPTPPGEKK DVSGPMPDSY
310 320 330 340 350
SPRYVEAAWY PWWEQQGFFK PEYGRPNVSA ANPRGVFMMC IPPPNVTGSL
360 370 380 390 400
HLGHALTNAI QDSLTRWHRM RGETTLWNPG CDHAGIATQV VVEKKLWREQ
410 420 430 440 450
GLSRHQLGRE AFLQEVWKWK EEKGDRIYHQ LKKLGSSLDW DRACFTMDPK
460 470 480 490 500
LSAAVTEAFV RLHEEGIIYR STRLVNWSCT LNSAISDIEV DKKELTGRTL
510 520 530 540 550
LSVPGYKEKV EFGVLVSFAY KVQGSDSDEE VVVATTRIET MLGDVAVAVH
560 570 580 590 600
PKDTRYQHLK GKNVIHPFLS RSLPIVFDEF VDMDFGTGAV KITPAHDQND
610 620 630 640 650
YEVGQRHGLE AISIMDSRGA LINVPPPFLG LPRFEARKAV LVALKERGLF
660 670 680 690 700
RGIEDNPMVV PLCNRSKDVV EPLLRPQWYV RCGEMAQAAS AAVTRGDLRI
710 720 730 740 750
LPEAHQRTWH AWMDNIREWC ISRQLWWGHR IPAYFVTVSD PAVPPGEDPD
760 770 780 790 800
GRYWVSGRNE AEAREKAAKE FGVSPDKISL QQDEDVLDTW FSSGLFPLSI
810 820 830 840 850
LGWPNQSEDL SVFYPGTLLE TGHDILFFWV ARMVMLGLKL TGRLPFREVY
860 870 880 890 900
LHAIVRDAHG RKMSKSLGNV IDPLDVIYGI SLQGLHNQLL NSNLDPSEVE
910 920 930 940 950
KAKEGQKADF PAGIPECGTD ALRFGLCAYM SQGRDINLDV NRILGYRHFC
960 970 980 990 1000
NKLWNATKFA LRGLGKGFVP SPTSQPGGHE SLVDRWIRSR LTEAVRLSNQ
1010 1020 1030 1040 1050
GFQAYDFPAV TTAQYSFWLY ELCDVYLECL KPVLNGVDQV AAECARQTLY
1060 1070 1080 1090 1100
TCLDVGLRLL SPFMPFVTEE LFQRLPRRMP QAPPSLCVTP YPEPSECSWK
1110 1120 1130 1140 1150
DPEAEAALEL ALSITRAVRS LRADYNLTRI RPDCFLEVAD EATGALASAV
1160 1170 1180 1190 1200
SGYVQALASA GVVAVLALGA PAPQGCAVAL ASDRCSIHLQ LQGLVDPARE
1210 1220 1230 1240 1250
LGKLQAKRVE AQRQAQRLRE RRAASGYPVK VPLEVQEADE AKLQQTEAEL
1260
RKVDEAIALF QKML
Length:1,264
Mass (Da):140,476
Last modified:December 1, 2000 - v4
Checksum:i95CCDDBB3AB148AD
GO
Isoform 2 (identifier: P26640-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-295: Missing.
     589-592: AVKI → PAQV
     593-1264: Missing.

Note: No experimental confirmation available.
Show »
Length:297
Mass (Da):33,795
Checksum:i67A51E4BB45D4A57
GO

Computationally mapped potential isoform sequencesi

There are 6 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A140T936A0A140T936_HUMAN
Valine--tRNA ligase
VARS
1,183Annotation score:
H0Y426H0Y426_HUMAN
Valine--tRNA ligase
VARS
288Annotation score:
A0A140T954A0A140T954_HUMAN
Valine--tRNA ligase
VARS
366Annotation score:
A2ABF4A2ABF4_HUMAN
Valine--tRNA ligase
VARS
174Annotation score:
A0A140T904A0A140T904_HUMAN
Valine--tRNA ligase
VARS
95Annotation score:
A0A0G2JJT9A0A0G2JJT9_HUMAN
Valine--tRNA ligase
VARS
174Annotation score:

Sequence cautioni

The sequence CAA41990 differs from that shown. Reason: Frameshift at positions 620 and 640.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti51P → S in CAA41990 (PubMed:1898367).Curated1
Sequence conflicti51P → S in AAH12808 (Ref. 6) Curated1
Sequence conflicti331A → G in AAA81332 (PubMed:8428657).Curated1
Sequence conflicti590V → G in CAA41990 (PubMed:1898367).Curated1
Sequence conflicti792S → F in CAA41990 (PubMed:1898367).Curated1
Sequence conflicti1064M → I in AAA81332 (PubMed:8428657).Curated1
Sequence conflicti1169Missing in AAA81332 (PubMed:8428657).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05264751P → R. Corresponds to variant dbSNP:rs2607015Ensembl.1
Natural variantiVAR_06190951P → T. Corresponds to variant dbSNP:rs2753960Ensembl.1
Natural variantiVAR_052648181R → C. Corresponds to variant dbSNP:rs35196751Ensembl.1
Natural variantiVAR_052649626P → S. Corresponds to variant dbSNP:rs11531Ensembl.1
Natural variantiVAR_080602885L → F in NDMSCA; unknown pathological significance. 1 Publication1
Natural variantiVAR_0526501008P → L. Corresponds to variant dbSNP:rs1076827Ensembl.1
Natural variantiVAR_0806031058R → Q in NDMSCA; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs769369302EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0564801 – 295Missing in isoform 2. 1 PublicationAdd BLAST295
Alternative sequenceiVSP_056481589 – 592AVKI → PAQV in isoform 2. 1 Publication4
Alternative sequenceiVSP_056482593 – 1264Missing in isoform 2. 1 PublicationAdd BLAST672

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X59303 mRNA Translation: CAA41990.1 Frameshift.
AF134726 Genomic DNA Translation: AAD21819.1
BA000025 Genomic DNA Translation: BAB63303.1
AK302762 mRNA Translation: BAG63973.1
AL662834 Genomic DNA No translation available.
AL662899 Genomic DNA No translation available.
AL671762 Genomic DNA No translation available.
CR925765 Genomic DNA No translation available.
CH471081 Genomic DNA Translation: EAX03523.1
BC012808 mRNA Translation: AAH12808.1
M98326 mRNA Translation: AAA81332.1
CCDSiCCDS34412.1 [P26640-1]
PIRiS17675
RefSeqiNP_006286.1, NM_006295.2 [P26640-1]
UniGeneiHs.520026

Genome annotation databases

EnsembliENST00000211402; ENSP00000211402; ENSG00000096171 [P26640-1]
ENST00000375663; ENSP00000364815; ENSG00000204394 [P26640-1]
ENST00000422694; ENSP00000401121; ENSG00000224264
ENST00000435657; ENSP00000415316; ENSG00000231116
ENST00000457796; ENSP00000403359; ENSG00000226589 [P26640-1]
GeneIDi7407
KEGGihsa:7407
UCSCiuc003nxe.4 human [P26640-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X59303 mRNA Translation: CAA41990.1 Frameshift.
AF134726 Genomic DNA Translation: AAD21819.1
BA000025 Genomic DNA Translation: BAB63303.1
AK302762 mRNA Translation: BAG63973.1
AL662834 Genomic DNA No translation available.
AL662899 Genomic DNA No translation available.
AL671762 Genomic DNA No translation available.
CR925765 Genomic DNA No translation available.
CH471081 Genomic DNA Translation: EAX03523.1
BC012808 mRNA Translation: AAH12808.1
M98326 mRNA Translation: AAA81332.1
CCDSiCCDS34412.1 [P26640-1]
PIRiS17675
RefSeqiNP_006286.1, NM_006295.2 [P26640-1]
UniGeneiHs.520026

3D structure databases

ProteinModelPortaliP26640
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113250, 90 interactors
IntActiP26640, 43 interactors
MINTiP26640
STRINGi9606.ENSP00000364815

Chemistry databases

BindingDBiP26640
ChEMBLiCHEMBL2612
DrugBankiDB00161 L-Valine

PTM databases

iPTMnetiP26640
PhosphoSitePlusiP26640
SwissPalmiP26640

Polymorphism and mutation databases

BioMutaiVARS
DMDMi12644177

Proteomic databases

EPDiP26640
MaxQBiP26640
PaxDbiP26640
PeptideAtlasiP26640
PRIDEiP26640
ProteomicsDBi54358

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000211402; ENSP00000211402; ENSG00000096171 [P26640-1]
ENST00000375663; ENSP00000364815; ENSG00000204394 [P26640-1]
ENST00000422694; ENSP00000401121; ENSG00000224264
ENST00000435657; ENSP00000415316; ENSG00000231116
ENST00000457796; ENSP00000403359; ENSG00000226589 [P26640-1]
GeneIDi7407
KEGGihsa:7407
UCSCiuc003nxe.4 human [P26640-1]

Organism-specific databases

CTDi7407
DisGeNETi7407
EuPathDBiHostDB:ENSG00000204394.12
GeneCardsiVARS
H-InvDBiHIX0005731
HIX0165932
HIX0166155
HIX0166435
HIX0166904
HIX0167447
HGNCiHGNC:12651 VARS
HPAiHPA046710
MalaCardsiVARS
MIMi192150 gene
617802 phenotype
neXtProtiNX_P26640
OpenTargetsiENSG00000204394
PharmGKBiPA37275
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0432 Eukaryota
KOG0867 Eukaryota
COG0525 LUCA
GeneTreeiENSGT00550000074727
HOGENOMiHOG000020094
HOVERGENiHBG017878
InParanoidiP26640
KOiK01873
OMAiFATKLWN
OrthoDBiEOG093719L8
PhylomeDBiP26640
TreeFamiTF300648

Enzyme and pathway databases

BRENDAi6.1.1.9 2681
ReactomeiR-HSA-379716 Cytosolic tRNA aminoacylation

Miscellaneous databases

ChiTaRSiVARS human
GeneWikiiVARS
GenomeRNAii7407
PROiPR:P26640
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000204394 Expressed in 201 organ(s), highest expression level in testis
CleanExiHS_VARS
HS_VARS2
ExpressionAtlasiP26640 baseline and differential
GenevisibleiP26640 HS

Family and domain databases

CDDicd07962 Anticodon_Ia_Val, 1 hit
Gene3Di1.10.287.380, 1 hit
3.40.50.620, 2 hits
3.90.740.10, 1 hit
HAMAPiMF_02004 Val_tRNA_synth_type1, 1 hit
InterProiView protein in InterPro
IPR001412 aa-tRNA-synth_I_CS
IPR002300 aa-tRNA-synth_Ia
IPR033705 Anticodon_Ia_Val
IPR010987 Glutathione-S-Trfase_C-like
IPR036282 Glutathione-S-Trfase_C_sf
IPR004046 GST_C
IPR013155 M/V/L/I-tRNA-synth_anticd-bd
IPR014729 Rossmann-like_a/b/a_fold
IPR009080 tRNAsynth_Ia_anticodon-bd
IPR037118 Val-tRNA_synth_C_sf
IPR009008 Val/Leu/Ile-tRNA-synth_edit
IPR002303 Valyl-tRNA_ligase
PfamiView protein in Pfam
PF08264 Anticodon_1, 1 hit
PF00043 GST_C, 1 hit
PF00133 tRNA-synt_1, 1 hit
PRINTSiPR00986 TRNASYNTHVAL
SUPFAMiSSF47323 SSF47323, 1 hit
SSF47616 SSF47616, 1 hit
SSF50677 SSF50677, 1 hit
TIGRFAMsiTIGR00422 valS, 1 hit
PROSITEiView protein in PROSITE
PS00178 AA_TRNA_LIGASE_I, 1 hit
PS50405 GST_CTER, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiSYVC_HUMAN
AccessioniPrimary (citable) accession number: P26640
Secondary accession number(s): B0V1N1
, B4DZ61, Q5JQ90, Q96E77, Q9UQM2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: December 1, 2000
Last modified: November 7, 2018
This is version 202 of the entry and version 4 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

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  6. Aminoacyl-tRNA synthetases
    List of aminoacyl-tRNA synthetase entries
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again