EPRS1
entrez
2058
canonical
uniprot
P07814
canonical
ensembl
ENSG00000136628
resolver
ensp
ENSP00000355890
resolver
enst
ENST00000366923
resolver
genesymbol
EPRS1
resolver
genesymbol_syn
EPRS
resolver
genesymbol_syn
GLNS
resolver
genesymbol_syn
PARS
resolver
genesymbol_syn
QARS
resolver
genesymbol_syn
QPRS
resolver
hgnc
HGNC:3418
resolver
uniprot
A0AVA9
resolver
uniprot
B9EGH3
resolver
uniprot
Q05BP6
resolver
uniprot
Q05DF8
resolver
uniprot
Q5DSM1
resolver
uniprot
Q5H9S5
resolver
uniprot
Q6PD57
resolver
uniprot
Q86X73
resolver
uniprot_entry
SYEP_HUMAN
resolver
uniprot_sec
A0AVA9
resolver
uniprot_sec
B9EGH3
resolver
uniprot_sec
Q05BP6
resolver
uniprot_sec
Q05DF8
resolver
uniprot_sec
Q5DSM1
resolver
uniprot_sec
Q5H9S5
resolver
uniprot_sec
Q6PD57
resolver
uniprot_sec
Q86X73
resolver
activity_regulation
ACTIVITY REGULATION: Inhibited by halofuginone (PubMed:23263184, PubMed:24100331). Can be activated by azetidine-2-carboxylic acid (Aze), a non-proteinogenic amino acids found in plants that mimics both proline and alanine, leading to misincorporation of Aze into proline positions of proteins (PubMed:29273753). {ECO:0000269|PubMed:23263184, ECO:0000269|PubMed:24100331, ECO:0000269|PubMed:29273753}.
uniprot
proteins
amino_acid_sequence
MATLSLTVNSGDPPLGALLAVEHVKDDVSISVEEGKENILHVSENVIFTDVNSILRYLARVATTAGLYGSNLMEHTEIDHWLEFSATKLSSCDSFTSTINELNHCLSLRTYLVGNSLSLADLCVWATLKGNAAWQEQLKQKKAPVHVKRWFGFLEAQQAFQSVGTKWDVSTTKARVAPEKKQDVGKFVELPGAEMGKVTVRFPPEASGYLHIGHAKAALLNQHYQVNFKGKLIMRFDDTNPEKEKEDFEKVILEDVAMLHIKPDQFTYTSDHFETIMKYAEKLIQEGKAYVDDTPAEQMKAEREQRIDSKHRKNPIEKNLQMWEEMKKGSQFGQSCCLRAKIDMSSNNGCMRDPTLYRCKIQPHPRTGNKYNVYPTYDFACPIVDSIEGVTHALRTTEYHDRDEQFYWIIEALGIRKPYIWEYSRLNLNNTVLSKRKLTWFVNEGLVDGWDDPRFPTVRGVLRRGMTVEGLKQFIAAQGSSRSVVNMEWDKIWAFNKKVIDPVAPRYVALLKKEVIPVNVPEAQEEMKEVAKHPKNPEVGLKPVWYSPKVFIEGADAETFSEGEMVTFINWGNLNITKIHKNADGKIISLDAKLNLENKDYKKTTKVTWLAETTHALPIPVICVTYEHLITKPVLGKDEDFKQYVNKNSKHEELMLGDPCLKDLKKGDIIQLQRRGFFICDQPYEPVSPYSCKEAPCVLIYIPDGHTKEMPTSGSKEKTKVEATKNETSAPFKERPTPSLNNNCTTSEDSLVLYNRVAVQGDVVRELKAKKAPKEDVDAAVKQLLSLKAEYKEKTGQEYKPGNPPAEIGQNISSNSSASILESKSLYDEVAAQGEVVRKLKAEKSPKAKINEAVECLLSLKAQYKEKTGKEYIPGQPPLSQSSDSSPTRNSEPAGLETPEAKVLFDKVASQGEVVRKLKTEKAPKDQVDIAVQELLQLKAQYKSLIGVEYKPVSATGAEDKDKKKKEKENKSEKQNKPQKQNDGQRKDPSKNQGGGLSSSGAGEGQGPKKQTRLGLEAKKEENLADWYSQVITKSEMIEYHDISGCYILRPWAYAIWEAIKDFFDAEIKKLGVENCYFPMFVSQSALEKEKTHVADFAPEVAWVTRSGKTELAEPIAIRPTSETVMYPAYAKWVQSHRDLPIKLNQWCNVVRWEFKHPQPFLRTREFLWQEGHSAFATMEEAAEEVLQILDLYAQVYEELLAIPVVKGRKTEKEKFAGGDYTTTIEAFISASGRAIQGGTSHHLGQNFSKMFEIVFEDPKIPGEKQFAYQNSWGLTTRTIGVMTMVHGDNMGLVLPPRVACVQVVIIPCGITNALSEEDKEALIAKCNDYRRRLLSVNIRVRADLRDNYSPGWKFNHWELKGVPIRLEVGPRDMKSCQFVAVRRDTGEKLTVAENEAETKLQAILEDIQVTLFTRASEDLKTHMVVANTMEDFQKILDSGKIVQIPFCGEIDCEDWIKKTTARDQDLEPGAPSMGAKSLCIPFKPLCELQPGAKCVCGKNPAKYYTLFGRSY
uniprot
proteins
disease_involvement
DISEASE: Leukodystrophy, hypomyelinating, 15 (HLD15) [MIM:617951]: An autosomal recessive disorder characterized by hypomyelinating leukodystrophy with thinning of the corpus callosum. Clinical features include motor and cognitive impairment appearing in the first or second decade of life, dystonia, ataxia, spasticity, and dysphagia. Most patients develop severe optic atrophy, and some have hearing loss. {ECO:0000269|PubMed:29576217}. Note=The disease may be caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
6.1.1.15
uniprot
proteins
ec_number
6.1.1.17
uniprot
proteins
function
FUNCTION: Multifunctional protein which primarily functions within the aminoacyl-tRNA synthetase multienzyme complex, also known as multisynthetase complex. Within the complex it catalyzes the attachment of both L-glutamate and L-proline to their cognate tRNAs in a two-step reaction where the amino acid is first activated by ATP to form a covalent intermediate with AMP. Subsequently, the activated amino acid is transferred to the acceptor end of the cognate tRNA to form L-glutamyl-tRNA(Glu) and L-prolyl-tRNA(Pro) (PubMed:23263184, PubMed:24100331, PubMed:29576217, PubMed:3290852, PubMed:37212275). Upon interferon-gamma stimulation, EPRS1 undergoes phosphorylation, causing its dissociation from the aminoacyl-tRNA synthetase multienzyme complex. It is recruited to form the GAIT complex, which binds to stem loop-containing GAIT elements found in the 3'-UTR of various inflammatory mRNAs, such as ceruloplasmin. The GAIT complex inhibits the translation of these mRNAs, allowing interferon-gamma to redirect the function of EPRS1 from protein synthesis to translation inhibition in specific cell contexts (PubMed:15479637, PubMed:23071094). Furthermore, it can function as a downstream effector in the mTORC1 signaling pathway, by promoting the translocation of SLC27A1 from the cytoplasm to the plasma membrane where it mediates the uptake of long-chain fatty acid by adipocytes. Thereby, EPRS1 also plays a role in fat metabolism and more indirectly influences lifespan (PubMed:28178239). {ECO:0000269|PubMed:15479637, ECO:0000269|PubMed:23071094, ECO:0000269|PubMed:23263184, ECO:0000269|PubMed:24100331, ECO:0000269|PubMed:28178239, ECO:0000269|PubMed:29576217, ECO:0000269|PubMed:3290852, ECO:0000269|PubMed:37212275}.
uniprot
proteins
mass_dalton
170591
uniprot
proteins
mutagenesis
MUTAGEN 886; /note="S->A: Abolishes release from the aminoacyl-tRNA synthetase multienzyme complex and association with the GAIT complex upon interferon-gamma treatment. Abolishes interaction with SYNCRIP."; /evidence="ECO:0000269|PubMed:23071094"; MUTAGEN 886; /note="S->D: Not active in translation inhibition (phosphomimetic) and abolishes GAIT complex association with eiF4G. No effect on interaction with SYNCRIP."; /evidence="ECO:0000269|PubMed:23071094"; MUTAGEN 999; /note="S->A: Not active in translation inhibition, abolishes release from the aminoacyl-tRNA synthetase multienzyme complex and association with the GAIT complex upon interferon-gamma treatment."; /evidence="ECO:0000269|PubMed:23071094"; MUTAGEN 999; /note="S->D: Active in translation inhibition (phosphomimetic). No effect on GAIT complex association with eiF4G."; /evidence="ECO:0000269|PubMed:23071094"; MUTAGEN 1097; /note="F->A: Almost complete loss of prolyl-tRNA ligase activity."; /evidence="ECO:0000269|PubMed:24100331"; MUTAGEN 1097; /note="F->W: No effect on prolyl-tRNA ligase activity. Decreases inhibition by halofuginone."; /evidence="ECO:0000269|PubMed:24100331"; MUTAGEN 1152; /note="R->K: No effect on prolyl-tRNA ligase activity. Decreases inhibition by halofuginone."; /evidence="ECO:0000269|PubMed:24100331"; MUTAGEN 1152; /note="R->L: Almost complete loss of prolyl-tRNA ligase activity."; /evidence="ECO:0000269|PubMed:24100331
uniprot
proteins
post_translational_modification
PTM: Phosphorylated at Ser-886 by CDK5 (PubMed:19647514, PubMed:21220307). Phosphorylated at Ser-999 by RPS6KB1; triggers EPRS1 release from the aminoacyl-tRNA synthetase multienzyme complex (PubMed:19647514, PubMed:21220307, PubMed:28178239). In monocytes, the IFN-gamma-induced sequential phosphorylation at Ser-886 and Ser-999 releases EPRS1 from the aminoacyl-tRNA synthetase multienzyme complex, allowing its association with the GAIT complex. Phosphorylation at Ser-999 is specifically required for the RPL13A-mediated interaction of the GAIT complex with eIF4G (PubMed:19647514, PubMed:21220307). Phosphorylation at Ser-999 by RPS6KB1, is also induced by insulin through activation of the mTORC1 signaling pathway and promotes the interaction of EPRS1 with SLC27A1 (PubMed:28178239). {ECO:0000269|PubMed:19647514, ECO:0000269|PubMed:21220307, ECO:0000269|PubMed:28178239}.
uniprot
proteins
protein_family
Class-I aminoacyl-tRNA synthetase family
uniprot
proteins
protein_family
Glutamate--tRNA ligase type 2 subfamily; Class-II aminoacyl-tRNA synthetase family
uniprot
proteins
pubmed
10791971
uniprot
proteins
pubmed
11123902
uniprot
proteins
pubmed
14654843
uniprot
proteins
pubmed
15479637
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
1556743
uniprot
proteins
pubmed
15994936
uniprot
proteins
pubmed
16710414
uniprot
proteins
pubmed
16964243
uniprot
proteins
pubmed
17081983
uniprot
proteins
pubmed
17974005
uniprot
proteins
pubmed
18220336
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18691976
uniprot
proteins
pubmed
19131329
uniprot
proteins
pubmed
19289464
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
19608861
uniprot
proteins
pubmed
19647514
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
1988429
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
21220307
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
21908771
uniprot
proteins
pubmed
23071094
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23263184
uniprot
proteins
pubmed
24100331
uniprot
proteins
pubmed
24129315
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
24312579
uniprot
proteins
pubmed
25944712
uniprot
proteins
pubmed
26472928
uniprot
proteins
pubmed
28178239
uniprot
proteins
pubmed
29273753
uniprot
proteins
pubmed
29576217
uniprot
proteins
pubmed
3290852
uniprot
proteins
pubmed
37212275
uniprot
proteins
sequence_length
1512
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:10791971, ECO:0000269|PubMed:19289464, ECO:0000269|PubMed:3290852}. Membrane {ECO:0000269|PubMed:28178239}; Peripheral membrane protein {ECO:0000305|PubMed:19289464, ECO:0000305|PubMed:28178239}. Note=Translocates from cytosol to membranes upon phosphorylation at Ser-999. {ECO:0000269|PubMed:19289464, ECO:0000269|PubMed:28178239}.
uniprot
proteins