Expasy logo

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P41250: Variant p.Glu125Gly

Glycine--tRNA ligase
Gene: GARS1
Feedback?
Variant information Variant position: help 125 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help LP/P [Disclaimer] The variants are classified into three categories: LP/P, LB/B and US.
  • LP/P: likely pathogenic or pathogenic.
  • LB/B: likely benign or benign.
  • US: uncertain significance

Residue change: help From Glutamate (E) to Glycine (G) at position 125 (E125G, p.Glu125Gly). Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.
Physico-chemical properties: help Change from medium size and acidic (E) to glycine (G) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -2 The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:
  • Lowest score: -4 (low probability of substitution).
  • Highest score: 11 (high probability of substitution).
More information can be found on the following page

Variant description: help In CMT2D; phenotype overlapping with HMND5; complements the defect of the wild-type gene in yeast; contrary to the wild-type protein, strongly binds to NRP1 and competes with VEGFA for NRP1-binding; displays slightly elevated aminoacylation activity over wild-type. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 125 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 739 The length of the canonical sequence.
Location on the sequence: help LEAKELALQPKDDIVDRAKM E DTLKRRFFYDQAFAIYGGVS The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.
Residue conservation: help The multiple alignment of the region surrounding the variant against various orthologous sequences.
Human                         LEAKELALQPKDDIVDRAKMEDTLKRRFFYDQAFAIYGGVS

Mouse                         LEAKELALQPKDDIVDRAKMEDTLKRRFFYDQAFAIYGGVS

Rat                           LEAKELALQPKDDIVDRAKMEDTLKRRFFYDQAFAIYGGVS

Caenorhabditis elegans        LEDTEIALAPKEASFDRLKLEDLLKRRFFYDQSFAIYGGVT

Drosophila                    LEDKELALTPSVVSFDRAKMEDLLKRRFFYDQSFAIYGGIT

Sequence annotation in neighborhood: help The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:
  • Type: the type of sequence feature.
  • Positions: endpoints of the sequence feature.
  • Description: contains additional information about the feature.
TypePositionsDescription
Chain 37 – 739 Glycine--tRNA ligase
Mutagenesis 121 – 121 R -> A. Decrease in catalytic activity by about 10-fold.
Helix 121 – 130



Literature citations
Glycyl tRNA synthetase mutations in Charcot-Marie-Tooth disease type 2D and distal spinal muscular atrophy type V.
Antonellis A.; Ellsworth R.E.; Sambuughin N.; Puls I.; Abel A.; Lee-Lin S.Q.; Jordanova A.; Kremensky I.; Christodoulou K.; Middleton L.T.; Sivakumar K.; Ionasescu V.; Funalot B.; Vance J.M.; Goldfarb L.G.; Fischbeck K.H.; Green E.D.;
Am. J. Hum. Genet. 72:1293-1299(2003)
Cited for: INVOLVEMENT IN CMT2D; VARIANTS CMT2D GLY-125 AND ARG-294; VARIANTS HMND5 PRO-183 AND ARG-580; TISSUE SPECIFICITY; Functional analyses of glycyl-tRNA synthetase mutations suggest a key role for tRNA-charging enzymes in peripheral axons.
Antonellis A.; Lee-Lin S.Q.; Wasterlain A.; Leo P.; Quezado M.; Goldfarb L.G.; Myung K.; Burgess S.; Fischbeck K.H.; Green E.D.;
J. Neurosci. 26:10397-10406(2006)
Cited for: SUBCELLULAR LOCATION; VARIANTS CMT2D GLY-125 AND ARG-294; CHARACTERIZATION OF VARIANTS CMT2D GLY-125 AND ARG-294; VARIANTS HMND5 PRO-183; ARG-472 AND ARG-580; CHARACTERIZATION OF VARIANTS HMND5 PRO-183; ARG-472 AND ARG-580; Impaired function is a common feature of neuropathy-associated glycyl-tRNA synthetase mutations.
Griffin L.B.; Sakaguchi R.; McGuigan D.; Gonzalez M.A.; Searby C.; Zuchner S.; Hou Y.M.; Antonellis A.;
Hum. Mutat. 35:1363-1371(2014)
Cited for: SUBCELLULAR LOCATION (ISOFORM 2); VARIANTS CMT2D VAL-111; ASN-200; PHE-265; ARG-294; LEU-298; PHE-334; ARG-472; ASN-554; ARG-580 AND ALA-652; VARIANT LEU-635; CHARACTERIZATION OF VARIANTS CMT2D VAL-111; GLY-125; PRO-183; ASN-200; PHE-265; ARG-294; LEU-298; PHE-334; ARG-472; ASN-554; ARG-580 AND ALA-652; CHARACTERIZATION OF VARIANT LEU-635; Cocrystal structures of glycyl-tRNA synthetase in complex with tRNA suggest multiple conformational states in glycylation.
Qin X.; Hao Z.; Tian Q.; Zhang Z.; Zhou C.; Xie W.;
J. Biol. Chem. 289:20359-20369(2014)
Cited for: X-RAY CRYSTALLOGRAPHY (3.23 ANGSTROMS) OF 114-739 OF WILD-TYPE AND VARIANT GLY-125 IN COMPLEXES WITH TRNA(GLY); AMP; ATP ANALOG AND GLYCINE; FUNCTION; CATALYTIC ACTIVITY; SUBUNIT; MUTAGENESIS OF ARG-121; ARG-337; ARG-602; TYR-658 AND GLN-729; CHARACTERIZATION OF VARIANT GLY-125; Large Conformational Changes of Insertion 3 in Human Glycyl-tRNA Synthetase (hGlyRS) during Catalysis.
Deng X.; Qin X.; Chen L.; Jia Q.; Zhang Y.; Zhang Z.; Lei D.; Ren G.; Zhou Z.; Wang Z.; Li Q.; Xie W.;
J. Biol. Chem. 291:5740-5752(2016)
Cited for: X-RAY CRYSTALLOGRAPHY (2.74 ANGSTROMS) OF ISOFORM 2 WITH VARIANT GLY-125 AND DOUBLE MUTANT GLY-125/ARG-211 IN COMPLEX WITH TRNA(GLY) AND AMP; MUTAGENESIS OF CYS-211 AND 486-LEU--LYS-490; CMT2D neuropathy is linked to the neomorphic binding activity of glycyl-tRNA synthetase.
He W.; Bai G.; Zhou H.; Wei N.; White N.M.; Lauer J.; Liu H.; Shi Y.; Dumitru C.D.; Lettieri K.; Shubayev V.; Jordanova A.; Guergueltcheva V.; Griffin P.R.; Burgess R.W.; Pfaff S.L.; Yang X.L.;
Nature 526:710-714(2015)
Cited for: CHARACTERIZATION OF VARIANTS CMT2D GLY-125 AND ARG-294; CHARACTERIZATION OF VARIANT HMND5 PRO-183;
Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.