Protein: Bifunctional glutamate/proline--tRNA ligase (Bifunctional aminoacyl-tRNA synthetase) (Cell proliferation-inducing gene 32 protein) (Glutamatyl-prolyl-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)] (P07814)
Organism: Homo sapiens (Human)
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. 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: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}.
Sequence: MATLSLTVNSGDPPLGALLAVEHVKDDVSISVEEGKENILHVSENVIFTDVNSILRYLARVATTAGLYGSNLMEHTEIDHWLEFSATKLSSCDSFTSTINELNHCLSLRTYLVGNSLSLADLCVWATLKGNAAWQEQLKQKKAPVHVKRWFGFLEAQQAFQSVGTKWDVSTTKARVAPEKKQDVGKFVELPGAEMGKVTVRFPPEASGYLHIGHAKAALLNQHYQVNFKGKLIMRFDDTNPEKEKEDFEKVILEDVAMLHIKPDQFTYTSDHFETIMKYAEKLIQEGKAYVDDTPAEQMKAEREQRIDSKHRKNPIEKNLQMWEEMKKGSQFGQSCCLRAKIDMSSNNGCMRDPTLYRCKIQPHPRTGNKYNVYPTYDFACPIVDSIEGVTHALRTTEYHDRDEQFYWIIEALGIRKPYIWEYSRLNLNNTVLSKRKLTWFVNEGLVDGWDDPRFPTVRGVLRRGMTVEGLKQFIAAQGSSRSVVNMEWDKIWAFNKKVIDPVAPRYVALLKKEVIPVNVPEAQEEMKEVAKHPKNPEVGLKPVWYSPKVFIEGADAETFSEGEMVTFINWGNLNITKIHKNADGKIISLDAKLNLENKDYKKTTKVTWLAETTHALPIPVICVTYEHLITKPVLGKDEDFKQYVNKNSKHEELMLGDPCLKDLKKGDIIQLQRRGFFICDQPYEPVSPYSCKEAPCVLIYIPDGHTKEMPTSGSKEKTKVEATKNETSAPFKERPTPSLNNNCTTSEDSLVLYNRVAVQGDVVRELKAKKAPKEDVDAAVKQLLSLKAEYKEKTGQEYKPGNPPAEIGQNISSNSSASILESKSLYDEVAAQGEVVRKLKAEKSPKAKINEAVECLLSLKAQYKEKTGKEYIPGQPPLSQSSDSSPTRNSEPAGLETPEAKVLFDKVASQGEVVRKLKTEKAPKDQVDIAVQELLQLKAQYKSLIGVEYKPVSATGAEDKDKKKKEKENKSEKQNKPQKQNDGQRKDPSKNQGGGLSSSGAGEGQGPKKQTRLGLEAKKEENLADWYSQVITKSEMIEYHDISGCYILRPWAYAIWEAIKDFFDAEIKKLGVENCYFPMFVSQSALEKEKTHVADFAPEVAWVTRSGKTELAEPIAIRPTSETVMYPAYAKWVQSHRDLPIKLNQWCNVVRWEFKHPQPFLRTREFLWQEGHSAFATMEEAAEEVLQILDLYAQVYEELLAIPVVKGRKTEKEKFAGGDYTTTIEAFISASGRAIQGGTSHHLGQNFSKMFEIVFEDPKIPGEKQFAYQNSWGLTTRTIGVMTMVHGDNMGLVLPPRVACVQVVIIPCGITNALSEEDKEALIAKCNDYRRRLLSVNIRVRADLRDNYSPGWKFNHWELKGVPIRLEVGPRDMKSCQFVAVRRDTGEKLTVAENEAETKLQAILEDIQVTLFTRASEDLKTHMVVANTMEDFQKILDSGKIVQIPFCGEIDCEDWIKKTTARDQDLEPGAPSMGAKSLCIPFKPLCELQPGAKCVCGKNPAKYYTLFGRSY
InterPro domains: - IPR036621: Anticodon-binding domain superfamily (homologous_superfamily) [1297-1421]
- IPR004526: Glutamyl-tRNA synthetase, archaeal/eukaryotic cytosolic (family) [77-691]
- IPR017449: Prolyl-tRNA synthetase, class II (homologous_superfamily) [1424-1512]
- IPR014729: Rossmann-like alpha/beta/alpha sandwich fold (homologous_superfamily) [172-507]
- IPR000738: WHEP-TRS domain (domain) [749-966]
- IPR001412: Aminoacyl-tRNA synthetase, class I, conserved site (conserved_site) [204-215]
- IPR045864: Class II Aminoacyl-tRNA synthetase/Biotinyl protein ligase (BPL) and lipoyl protein ligase (LPL) (homologous_superfamily) [1016-1296]
- IPR020059: Glutamyl/glutaminyl-tRNA synthetase, class Ib, anti-codon binding domain (domain) [504-594]
- IPR000924: Glutamyl/glutaminyl-tRNA synthetase (family) [201-399]
- IPR033721: Prolyl-tRNA synthetase, catalytic domain (domain) [1023-1286]
- IPR020056: Large ribosomal subunit protein bL25/Gln-tRNA synthetase, N-terminal (homologous_superfamily) [513-690]
- IPR006195: Aminoacyl-tRNA synthetase, class II (domain) [1056-1296]
- IPR011035: Large ribosomal subunit protein bL25/Gln-tRNA synthetase, anti-codon-binding domain superfamily (homologous_superfamily) [504-707]
- IPR004154: Anticodon-binding (domain) [1303-1403]
- IPR002314: Aminoacyl-tRNA synthetase, class II (G/ P/ S/T) (domain) [1113-1284]
- IPR020058: Glutamyl/glutaminyl-tRNA synthetase, class Ib, catalytic domain (domain) [197-501]
- IPR009068: uS15/NS1, RNA-binding domain superfamily (homologous_superfamily) [752-955]
- IPR004499: Proline-tRNA ligase, class IIa, archaeal-type (family) [585-1512]
- IPR036282: Glutathione S-transferase, C-terminal domain superfamily (homologous_superfamily) [51-162]
- IPR016061: Proline-tRNA ligase, class II, C-terminal (domain) [1430-1512]
Interaction partners: - Eukaryotic translation elongation factor 1 epsilon-1
- Probable arginine--tRNA ligase, mitochondrial
- Isoleucine--tRNA ligase, cytoplasmic
- Aminoacyl tRNA synthase complex-interacting multifunctional protein 2
- Large ribosomal subunit protein uL13
- Tyrosine--tRNA ligase, cytoplasmic
- Arginine--tRNA ligase, cytoplasmic
- Aminoacyl tRNA synthase complex-interacting multifunctional protein 1
- Probable proline--tRNA ligase, mitochondrial
- Heterogeneous nuclear ribonucleoprotein Q
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0003824 (catalytic activity), GO:0016874 (ligase activity), GO:0140640 (catalytic activity, acting on a nucleic acid), GO:0005515 (protein binding), GO:0140098 (catalytic activity, acting on RNA), GO:0016875 (ligase activity, forming carbon-oxygen bonds), GO:0004812 (aminoacyl-tRNA ligase activity), GO:0140101 (catalytic activity, acting on a tRNA)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0050789 (regulation of biological process), GO:0044419 (biological process involved in interspecies interaction between organisms), GO:0002376 (immune system process), GO:0065007 (biological regulation), GO:0050896 (response to stimulus), GO:0009987 (cellular process), GO:0048519 (negative regulation of biological process), GO:0009605 (response to external stimulus), GO:0009058 (biosynthetic process), GO:0042221 (response to chemical), GO:0019222 (regulation of metabolic process), GO:0006955 (immune response), GO:0032879 (regulation of localization), GO:0006807 (nitrogen compound metabolic process), GO:0071704 (organic substance metabolic process), GO:0009892 (negative regulation of metabolic process), GO:0044237 (cellular metabolic process), GO:0044281 (small molecule metabolic process), GO:0009607 (response to biotic stimulus), GO:0009719 (response to endogenous stimulus), GO:0050794 (regulation of cellular process), GO:0051716 (cellular response to stimulus), GO:0006950 (response to stress), GO:0048523 (negative regulation of cellular process), GO:0051707 (response to other organism), GO:0044238 (primary metabolic process), GO:0051172 (negative regulation of nitrogen compound metabolic process), GO:0051049 (regulation of transport), GO:1901564 (organonitrogen compound metabolic process), GO:1901576 (organic substance biosynthetic process), GO:0043207 (response to external biotic stimulus), GO:0046483 (heterocycle metabolic process), GO:1905952 (regulation of lipid localization), GO:0019538 (protein metabolic process), GO:0006952 (defense response), GO:0071495 (cellular response to endogenous stimulus), GO:0060255 (regulation of macromolecule metabolic process), GO:0044249 (cellular biosynthetic process), GO:1901700 (response to oxygen-containing compound), GO:0006520 (amino acid metabolic process), GO:0006725 (cellular aromatic compound metabolic process), GO:0034641 (cellular nitrogen compound metabolic process), GO:0031324 (negative regulation of cellular metabolic process), GO:0043170 (macromolecule metabolic process), GO:0010033 (response to organic substance), GO:0009725 (response to hormone), GO:0045087 (innate immune response), GO:0098542 (defense response to other organism), GO:1901360 (organic cyclic compound metabolic process), GO:0006139 (nucleobase-containing compound metabolic process), GO:1901698 (response to nitrogen compound), GO:0070887 (cellular response to chemical stimulus), GO:0010605 (negative regulation of macromolecule metabolic process), GO:0006082 (organic acid metabolic process), GO:0009889 (regulation of biosynthetic process), GO:0051171 (regulation of nitrogen compound metabolic process), GO:0031323 (regulation of cellular metabolic process), GO:0009890 (negative regulation of biosynthetic process), GO:0043603 (amide metabolic process), GO:0080090 (regulation of primary metabolic process), GO:0044260 (cellular macromolecule metabolic process), GO:1901652 (response to peptide), GO:0071417 (cellular response to organonitrogen compound), GO:0009059 (macromolecule biosynthetic process), GO:0034097 (response to cytokine), GO:0006518 (peptide metabolic process), GO:0010556 (regulation of macromolecule biosynthetic process), GO:0051246 (regulation of protein metabolic process), GO:0071310 (cellular response to organic substance), GO:0043436 (oxoacid metabolic process), GO:0051248 (negative regulation of protein metabolic process), GO:1901699 (cellular response to nitrogen compound), GO:0043604 (amide biosynthetic process), GO:0043038 (amino acid activation), GO:0032368 (regulation of lipid transport), GO:0010468 (regulation of gene expression), GO:1901566 (organonitrogen compound biosynthetic process), GO:0043434 (response to peptide hormone), GO:0006412 (translation), GO:0032870 (cellular response to hormone stimulus), GO:0034248 (regulation of amide metabolic process), GO:0010243 (response to organonitrogen compound), GO:0090304 (nucleic acid metabolic process), GO:0032890 (regulation of organic acid transport), GO:0031326 (regulation of cellular biosynthetic process), GO:0010558 (negative regulation of macromolecule biosynthetic process), GO:0044271 (cellular nitrogen compound biosynthetic process), GO:0034645 (cellular macromolecule biosynthetic process), GO:0031327 (negative regulation of cellular biosynthetic process), GO:0034341 (response to type II interferon), GO:1901701 (cellular response to oxygen-containing compound), GO:0010467 (gene expression), GO:0010629 (negative regulation of gene expression), GO:0034249 (negative regulation of amide metabolic process), GO:0017148 (negative regulation of translation), GO:0016070 (RNA metabolic process), GO:0043043 (peptide biosynthetic process), GO:0071375 (cellular response to peptide hormone stimulus), GO:0032868 (response to insulin), GO:0043039 (tRNA aminoacylation), GO:0071345 (cellular response to cytokine stimulus), GO:2000191 (regulation of fatty acid transport), GO:0019752 (carboxylic acid metabolic process), GO:1901653 (cellular response to peptide), GO:0006418 (tRNA aminoacylation for protein translation), GO:2000112 (regulation of cellular macromolecule biosynthetic process), GO:0006417 (regulation of translation), GO:0071346 (cellular response to type II interferon), GO:2000113 (negative regulation of cellular macromolecule biosynthetic process), GO:0010608 (post-transcriptional regulation of gene expression), GO:0032869 (cellular response to insulin stimulus), GO:0034660 (ncRNA metabolic process), GO:0006399 (tRNA metabolic process)
Cellular Component (CC): GO:0005575 (cellular component), GO:0032991 (protein-containing complex), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0016020 (membrane), GO:0005829 (cytosol), GO:0005615 (extracellular space), GO:1902494 (catalytic complex), GO:0005737 (cytoplasm), GO:0031974 (membrane-enclosed lumen), GO:0005576 (extracellular region), GO:0005739 (mitochondrion), GO:0043233 (organelle lumen), GO:0043229 (intracellular organelle), GO:0043227 (membrane-bounded organelle), GO:0017101 (aminoacyl-tRNA synthetase multienzyme complex), GO:0043231 (intracellular membrane-bounded organelle), GO:0005759 (mitochondrial matrix), GO:0070013 (intracellular organelle lumen)