O95363B2R664Q53F66Q5TCS3Q6FG29Q9NPY7Q9P062SYFM_HUMANPhenylalanine--tRNA ligase, mitochondrial6.1.1.20Phenylalanyl-tRNA synthetasePheRSFARS2FARS1HSPC320Homo sapiensHumanEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomoExpression and characterization of a human mitochondrial phenylalanyl-tRNA synthetase.NUCLEOTIDE SEQUENCE [MRNA]SUBUNITComplete sequencing and characterization of 21,243 full-length human cDNAs.NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]VARIANT SER-280Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201).NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]VARIANT SER-280NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]The DNA sequence and analysis of human chromosome 6.NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]Human partial CDS from CD34+ stem cells.NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 108-451VARIANT SER-280Lysine acetylation targets protein complexes and co-regulates major cellular functions.ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-202IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]N-terminome analysis of the human mitochondrial proteome.IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]The tRNA-induced conformational activation of human mitochondrial phenylalanyl-tRNA synthetase.X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 38-451 IN COMPLEX WITH SUBSTRATESUBUNITEukaryotic cytosolic and mitochondrial phenylalanyl-tRNA synthetases catalyze the charging of tRNA with the meta-tyrosine.X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 38-451 IN COMPLEX WITH SUBSTRATEFUNCTIONCATALYTIC ACTIVITYSUBSTRATE SPECIFICITYKINETIC PARAMETERSMitochondrial phenylalanyl-tRNA synthetase mutations underlie fatal infantile Alpers encephalopathy.VARIANTS COXPD14 THR-329 AND VAL-391CHARACTERIZATION OF VARIANTS COXPD14 CYS-144; THR-329 AND VAL-391FUNCTIONCATALYTIC ACTIVITYKINETIC PARAMETERSGenomic analysis of mitochondrial diseases in a consanguineous population reveals novel candidate disease genes.VARIANT COXPD14 CYS-144A newly identified missense mutation in FARS2 causes autosomal-recessive spastic paraplegia.VARIANT SPG77 TYR-142CHARACTERIZATION OF VARIANT SPG77 TYR-142Is responsible for the charging of tRNA(Phe) with phenylalanine in mitochondrial translation. To a lesser extent, also catalyzes direct attachment of m-Tyr (an oxidized version of Phe) to tRNA(Phe), thereby opening the way for delivery of the misacylated tRNA to the ribosome and incorporation of ROS-damaged amino acid into proteins.ATP + L-phenylalanine + tRNA(Phe) = AMP + diphosphate + H(+) + L-phenylalanyl-tRNA(Phe)2.2 uM for L-phenylalanine1900 uM for L-tyrosine11.7 uM for DL-m-tyrosine7.3 uM for L-phenylalanine2.9 mM for ATP1.2 uM for tRNA(Phe)kcat is 2.8 min(-1), 2.0 min(-1) and 3.1 min(-1) with L-phenylalanine, L-tyrosine and m-tyrosine as substrate, respectively. Thus, the catalytic efficiency of the m-Tyr attachment is only 5-fold lower than that of the correct amino acid, while that of Tyr attachment is 1000-fold lower (PubMed:19549855).Monomer.O95363Q6UY14-3false3O95363Q6RW13false3O95363Q6RW13-2false3O95363Q96IF1false3O95363Q10567-3false3O95363Q9UKG1false9O95363Q9BYV9false3O95363O95429false3O95363Q8N9N5-2false4O95363Q5H9J7false3O95363Q13137false7O95363Q8NA61-2false3O95363Q4G0S7false3O95363Q9BXL8false3O95363Q96DZ9false3O95363Q96DZ9-2false3O95363A8MQ03false3O95363Q6ZPD8false3O95363Q9BQC3false3O95363Q92997false3O95363Q5TD97false3O95363Q9Y680false3O95363A1L4K1false3O95363Q13322-4false3O95363A8MV81false3O95363Q6NT76false3O95363Q9UKT9false6O95363Q9ULR0-1false3O95363Q9H3M0false3O95363Q8N5Z5false3O95363A1A4E9false3O95363Q15323false3O95363O76011false3O95363Q6A162false6O95363Q07627false3O95363P60370false3O95363P60409false6O95363P60410false3O95363P60411false6O95363Q9BYR6false3O95363Q9NR34false3O95363Q99750false3O95363Q14696false3O95363Q9UJV3-2false6O95363Q13064false3O95363Q6PF18false3O95363Q8NI38false3O95363Q7Z3S9false3O95363Q92824-2false3O95363Q96T49false3O95363O95199false6O95363Q9UFD9false3O95363O43609false3O95363O75558false3O95363P08247false3O95363O75478false3O95363Q96N21false3O95363Q12800false3O95363P07951-2false3O95363Q12933false3O95363P14373false3O95363Q9BYV2false3O95363Q15654false3O95363O95070false3O95363Q7Z4V0false3O95363O60304false3O95363Q8TF50false3O95363Q8N720false3O95363Q9UGI0false3Mitochondrion matrixMitochondrionCombined oxidative phosphorylation deficiency 14
COXPD14
A severe multisystemic autosomal recessive disorder characterized by neonatal onset of global developmental delay, refractory seizures, and lactic acidosis. Biochemical studies show deficiencies of multiple mitochondrial respiratory enzymes.The disease is caused by variants affecting the gene represented in this entry.Spastic paraplegia 77, autosomal recessive
SPG77
A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body.The disease is caused by variants affecting the gene represented in this entry.Belongs to the class-II aminoacyl-tRNA synthetase family.3D-structureAcetylationAminoacyl-tRNA synthetaseATP-bindingDisease variantHereditary spastic paraplegiaLigaseMitochondrionNeurodegenerationNucleotide-bindingPrimary mitochondrial diseaseProtein biosynthesisReference proteomeTransit peptidesubstratesubstratesubstratesubstratesubstratesubstrateSCDYYCNSITDVATPTMVGSALRRGAHAYVYLVSKASHISRGHQHQAWGSRPPAAECATQRAPGSVVELLGKSYPQDDHSNLTRKVLTRVGRNLHNQQHHPLWLIKERVKEHFYKQYVGRFGTPLFSVYDNLSPVVTTWQNFDSLLIPADHPSRKKGDNYYLNRTHMLRAHTSAHQWDLLHAGLDAFLVVGDVYRRDQIDSQHYPIFHQLEAVRLFSKHELFAGIKDGESLQLFEQSSRSAHKQETHTMEAVKLVEFDLKQTLTRLMAHLFGDELEIRWVDCYFPFTHPSFEMEINFHGEWLEVLGCGVMEQQLVNSAGAQDRIGWAFGLGLERLAMILYDIPDIRLFWCEDERFLKQFCVSNINQKVKFQPLSKYPAVINDISFWLPSENYAENDFYDLVRTIGGDLVEKVDLIDKFVHPKTHKTSHCYRITYRHMERTLSQREVRHIHQALQEAAVQLLGVEGRF
Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms Distributed under the Creative Commons Attribution (CC BY 4.0) License