Protein: Bifunctional glutamate/proline--tRNA ligase (Bifunctional aminoacyl-tRNA synthetase) [Includes: Glutamate--tRNA ligase (EC 6.1.1.17) (Glutamyl-tRNA synthetase) (GluRS); Proline--tRNA ligase (EC 6.1.1.15) (Prolyl-tRNA synthetase) (ProRS)] (Q8CGC7)
Organism: Mus musculus (Mouse)
Function: Multifunctional protein which is primarily part of the aminoacyl-tRNA synthetase multienzyme complex, also know as multisynthetase complex, that catalyzes the attachment of the cognate amino acid to the corresponding tRNA in a two-step reaction: the amino acid is first activated by ATP to form a covalent intermediate with AMP and is then transferred to the acceptor end of the cognate tRNA (By similarity). The phosphorylation of EPRS1, induced by interferon-gamma, dissociates the protein from the aminoacyl-tRNA synthetase multienzyme complex and recruits it to the GAIT complex that binds to stem loop-containing GAIT elements in the 3'-UTR of diverse inflammatory mRNAs (such as ceruplasmin), suppressing their translation. Interferon-gamma can therefore redirect, in specific cells, the EPRS1 function from protein synthesis to translation inhibition. Also functions as an effector of the mTORC1 signaling pathway by promoting, through SLC27A1, the uptake of long-chain fatty acid by adipocytes. Thereby, it also plays a role in fat metabolism and more indirectly influences lifespan.
Subcellular location: Cytoplasm, cytosol {ECO:0000250|UniProtKB:P07814}. Membrane {ECO:0000269|PubMed:28178239}; Peripheral membrane protein {ECO:0000305|PubMed:28178239}. Note=Translocates from cytosol to membranes upon phosphorylation at Ser-999. {ECO:0000305|PubMed:28178239}.
Interaction partners:
- Methionine--tRNA ligase, cytoplasmic
- Isoleucine--tRNA ligase, mitochondrial
- Leucine--tRNA ligase, cytoplasmic
- Tyrosine--tRNA ligase, cytoplasmic
- Lysine--tRNA ligase
- Aspartate--tRNA ligase, cytoplasmic
- Glyceraldehyde-3-phosphate dehydrogenase
- Asparagine--tRNA ligase, cytoplasmic
- Aminoacyl tRNA synthase complex-interacting multifunctional protein 1
- Heterogeneous nuclear ribonucleoprotein Q
Sequence:
MAALCLTVNAGNPPLEALLAVEHVKGDVSISVEEGKENLLRVSETVAFTDVNSILRYLARIATTSGLYGTNLMEHTEIDHWLEFSATKLSSCDRLTSAINELNHCLSLRTYLVGNSLTLADLCVWATLKGSAAWQEHLKQNKTLVHVKRWFGFLEAQQAFRSVGTKWDVSGNRATVAPDKKQDVGKFVELPGAEMGKVTVRFPPEASGYLHIGHAKAALLNQHYQVNFKGKLIMRFDDTNPEKEKEDFEKVILEDVAMLHIKPDQFTYTSDHFETIMKYAEKLIQEGKAYVDDTPAEQMKAEREQRTESKHRKNSVEKNLQMWEEMKKGSQFGQSCCLRAKIDMSSNNGCMRDPTLYRCKIQPHPRTGNKYNVYPTYDFACPIVDSIEGVTHALRTTEYHDRDEQFYWIIEALGIRKPYIWEYSRLNLNNTVLSKRKLTWFVNEGLVDGWDDPRFPTVRGVLRRGMTVEGLKQFIAAQGSSRSVVNMEWDKIWAFNKKVIDPVAPRYVALLKKEVVPVNVLDAQEEMKEVARHPKNPDVGLKPVWYSPKVFIEGADAETFSEGEMVTFINWGNINITKIHKNADGKITSLDAKLNLENKDYKKTTKITWLAESTHALSIPAVCVTYEHLITKPVLGKDEDFKQYINKDSKHEELMLGDPCLKDLKKGDIIQLQRRGFFICDQPYEPVSPYSCREAPCILIYIPDGHTKEMPTSGSKEKTKVEISKKETSSAPKERPAPAVSSTCATAEDSSVLYSRVAVQGDVVRELKAKKAPKEDIDAAVKQLLTLKAEYKEKTGQEYKPGNPSAAAVQTVSTKSSSNTVESTSLYNKVAAQGEVVRKLKAEKAPKAKVTEAVECLLSLKAEYKEKTGKDYVPGQPPASQNSHSNPVSNAQPAGAEKPEAKVLFDRVACQGEVVRKLKAEKASKDQVDSAVQELLQLKAQYKSLTGIEYKPVSATGAEDKDKKKKEKENKSEKQNKPQKQNDGQGKDSSKSQGSGLSSGGAGEGQGPKKQTRLGLEAKKEENLAEWYSQVITKSEMIEYYDVSGCYILRPWSYSIWESIKDFFDAEIKKLGVENCYFPIFVSQAALEKEKNHIEDFAPEVAWVTRSGKTELAEPIAIRPTSETVMYPAYAKWVQSHRDLPVRLNQWCNVVRWEFKHPQPFLRTREFLWQEGHSAFATFEEAADEVLQILELYARVYEELLAIPVVRGRKTEKEKFAGGDYTTTIEAFISASGRAIQGATSHHLGQNFSKMCEIVFEDPKTPGEKQFAYQCSWGLTTRTIGVMVMVHGDNMGLVLPPRVASVQVVVIPCGITNALSEEDREALMAKCNEYRRRLLGANIRVRVDLRDNYSPGWKFNHWELKGVPVRLEVGPRDMKSCQFVAVRRDTGEKLTIAEKEAEAKLEKVLEDIQLNLFTRASEDLKTHMVVSNTLEDFQKVLDAGKVAQIPFCGEIDCEDWIKKMTARDQDVEPGAPSMGAKSLCIPFNPLCELQPGAMCVCGKNPAKFYTLFGRSY