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Protein

Glycine--tRNA ligase

Gene

Gars

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Catalyzes the ligation of glycine to the 3'-end of its cognate tRNA. Is also able produce diadenosine tetraphosphate (Ap4A), a universal pleiotropic signaling molecule needed for cell regulation pathways, by direct condensation of 2 ATPs (By similarity).By similarity

Catalytic activityi

ATP + glycine + tRNA(Gly) = AMP + diphosphate + glycyl-tRNA(Gly).By similarity
P1,P4-bis(5'-guanosyl) tetraphosphate + H2O = GTP + GMP.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei203SubstrateBy similarity1
Binding sitei289SubstrateBy similarity1
Binding sitei425SubstrateBy similarity1
Binding sitei425Substrate; via carbonyl oxygenBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi321 – 323ATPBy similarity3
Nucleotide bindingi331 – 336ATPBy similarity6
Nucleotide bindingi447 – 448ATPBy similarity2
Nucleotide bindingi570 – 573ATPBy similarity4

GO - Molecular functioni

GO - Biological processi

Keywordsi

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

Protein family/group databases

MoonProtiQ9CZD3

Names & Taxonomyi

Protein namesi
Recommended name:
Glycine--tRNA ligase (EC:3.6.1.17, EC:6.1.1.14)
Alternative name(s):
Diadenosine tetraphosphate synthetase
Short name:
AP-4-A synthetase
Glycyl-tRNA synthetase
Short name:
GlyRS
Gene namesi
Name:Gars
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 6

Organism-specific databases

MGIiMGI:2449057 Gars

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

Cell projection, Cytoplasm, Secreted

Pathology & Biotechi

Involvement in diseasei

Mice (Nmf249) heterozygous for the P278YK variant are used a model for human Charcot-Marie-Tooth 2D (CMT2D), which is caused by dominant GARS mutations. They exhibit reduced amplitudes of muscle compound action potentials and a large reduction in sciatic nerve conduction velocity in the absence of demyelination or remyelination, resulting from an age-related decrease in the number of large myelinated motor and sensory axons. The loss of myelinated axons is length-dependent, and there is a length- and time-dependent decrease in motor innervation of distal versus proximal muscles. Most of the axonal loss occurs by 1 month of age and mice that survive this period can be long-lived. At the molecular level, the P278YK mutation creates a neomorphic binding activity leading to the interaction of the variant with NRP1. This interaction competes out VEGFA binding and inhibits VEGFA-NRP1 signling which is essential for motor neuron survival. VEGFA, but not GDNF treatment significantly ameliorates the loss of motor function in mutant mice.1 Publication

Keywords - Diseasei

Disease mutation

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000729991 – 729Glycine--tRNA ligaseAdd BLAST729

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei194N6-acetyllysineBy similarity1
Modified residuei443PhosphotyrosineCombined sources1
Modified residuei491N6-acetyllysineBy similarity1
Modified residuei690PhosphoserineCombined sources1
Modified residuei726PhosphothreonineBy similarity1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ9CZD3
MaxQBiQ9CZD3
PaxDbiQ9CZD3
PeptideAtlasiQ9CZD3
PRIDEiQ9CZD3

2D gel databases

REPRODUCTION-2DPAGEQ9CZD3

PTM databases

iPTMnetiQ9CZD3
PhosphoSitePlusiQ9CZD3
SwissPalmiQ9CZD3

Expressioni

Gene expression databases

BgeeiENSMUSG00000029777
CleanExiMM_GARS
GenevisibleiQ9CZD3 MM

Interactioni

Subunit structurei

Homodimer.By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
GARSP412502EBI-8321941,EBI-724143From Homo sapiens.

GO - Molecular functioni

Protein-protein interaction databases

BioGridi237263, 3 interactors
DIPiDIP-60956N
IntActiQ9CZD3, 3 interactors
MINTiQ9CZD3
STRINGi10090.ENSMUSP00000003572

Structurei

3D structure databases

ProteinModelPortaliQ9CZD3
SMRiQ9CZD3
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini53 – 109WHEP-TRSPROSITE-ProRule annotationAdd BLAST57

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni336 – 340Substrate bindingBy similarity5
Regioni566 – 570Substrate bindingBy similarity5

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG2298 Eukaryota
COG0423 LUCA
GeneTreeiENSGT00390000016949
HOGENOMiHOG000242015
HOVERGENiHBG036190
InParanoidiQ9CZD3
KOiK01880
OMAiEPSYGID
OrthoDBiEOG091G02U0
PhylomeDBiQ9CZD3
TreeFamiTF343504

Family and domain databases

CDDicd00774 GlyRS-like_core, 1 hit
Gene3Di3.40.50.800, 1 hit
InterProiView protein in InterPro
IPR002314 aa-tRNA-synt_IIb
IPR006195 aa-tRNA-synth_II
IPR004154 Anticodon-bd
IPR036621 Anticodon-bd_dom_sf
IPR027031 Gly-tRNA_synthase/POLG2
IPR033731 GlyRS-like_core
IPR009068 S15_NS1_RNA-bd
IPR002315 tRNA-synt_gly
IPR000738 WHEP-TRS_dom
PANTHERiPTHR10745 PTHR10745, 1 hit
PfamiView protein in Pfam
PF03129 HGTP_anticodon, 1 hit
PF00587 tRNA-synt_2b, 1 hit
PF00458 WHEP-TRS, 1 hit
PRINTSiPR01043 TRNASYNTHGLY
SMARTiView protein in SMART
SM00991 WHEP-TRS, 1 hit
SUPFAMiSSF47060 SSF47060, 1 hit
TIGRFAMsiTIGR00389 glyS_dimeric, 1 hit
PROSITEiView protein in PROSITE
PS50862 AA_TRNA_LIGASE_II, 1 hit
PS00762 WHEP_TRS_1, 1 hit
PS51185 WHEP_TRS_2, 1 hit

Sequencei

Sequence statusi: Complete.

Q9CZD3-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPCLLPSLLR ATRAALPLLS PPRVVAASAS QRLLSAPAQP AASRSSMDSA
60 70 80 90 100
EELLAPLRLA VRQQGDFVRK LKEDKAPQVD VDRAVAELKA RKRVLEAKEL
110 120 130 140 150
ALQPKDDIVD RAKMEDTLKR RFFYDQAFAI YGGVSGLYDF GPVGCALKNN
160 170 180 190 200
IIQAWRQHFI QEEQILEIDC TMLTPEPVLK TSGHVDKFAD FMVKDVKNGE
210 220 230 240 250
CFRADHLLKA HLQKLMSDKK CSAEKKSEME SVLAQLDNYG QQELADLFVN
260 270 280 290 300
YNVKSPTTGN DLSPPVPFNL MFQTFIGPGG NMPGYLRPET AQGIFLNFKR
310 320 330 340 350
LLEFNQGKLP FAAAQIGNSF RNEISPRSGL IRVREFTMAE IEHFVDPTEK
360 370 380 390 400
DHPKFQSVAD LCLYLYSAKA QVTGQSARKM RLGDAVEQGV INNSVLGYFI
410 420 430 440 450
GRIYLYLTKV GISPDKLRFR QHMENEMAHY ACDCWDAESK TSYGWIEIVG
460 470 480 490 500
CADRSCYDLS CHARATKVPL VAEKPLKEPK TVNVVQFEPN KGAVGKAYKK
510 520 530 540 550
DAKLVLEYLS ACDECYISEM ELLLSEKGEF TIETEGKTFQ LTKDMVSVKR
560 570 580 590 600
FQKTLHVEEV VPSVIEPSFG LGRIMYTILE HTFHVREGDE QRTFFSFPAV
610 620 630 640 650
VAPFKCSVLP LSQNQEFMPF VKELSEALTR NGVSHKVDDS SGSIGRRYAR
660 670 680 690 700
TDEIGVAFGI TIDFDTVNKT PHTATLRDRD SMRQIRAEVS ELPNVVRDLA
710 720
NGNITWADVE ARYPLFEGQE TGKKETVEE
Length:729
Mass (Da):81,878
Last modified:June 1, 2001 - v1
Checksum:i596613F746B9C7D0
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti5L → V in BAE38417 (PubMed:16141072).Curated1
Sequence conflicti584H → N in BAE27003 (PubMed:16141072).Curated1
Sequence conflicti597F → L in BAE27003 (PubMed:16141072).Curated1
Sequence conflicti694N → S in AAH21747 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti278P → YK Disease-associated mutation found in Nmf249 mice, a Charcot-Marie-Tooth 2D model; contrary to the wild-type protein, strongly interacts with NRP1 and competes with VEGFA for NRP1-binding; no effect on subcellular location. 2 Publications1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK146238 mRNA Translation: BAE27003.1
AK165857 mRNA Translation: BAE38417.1
BC021747 mRNA Translation: AAH21747.1
CCDSiCCDS39492.1
RefSeqiNP_851009.2, NM_180678.3
UniGeneiMm.250004

Genome annotation databases

EnsembliENSMUST00000003572; ENSMUSP00000003572; ENSMUSG00000029777
GeneIDi353172
KEGGimmu:353172
UCSCiuc009cai.1 mouse

Similar proteinsi

Entry informationi

Entry nameiGARS_MOUSE
AccessioniPrimary (citable) accession number: Q9CZD3
Secondary accession number(s): Q3TMM4, Q3UK01, Q8VC67
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 27, 2002
Last sequence update: June 1, 2001
Last modified: May 23, 2018
This is version 146 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

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