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O95363 (SYFM_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 123. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Phenylalanine--tRNA ligase, mitochondrial

EC=6.1.1.20
Alternative name(s):
Phenylalanyl-tRNA synthetase
Short name=PheRS
Gene names
Name:FARS2
Synonyms:FARS1
ORF Names:HSPC320
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length451 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Is 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. Ref.10 Ref.11

Catalytic activity

ATP + L-phenylalanine + tRNA(Phe) = AMP + diphosphate + L-phenylalanyl-tRNA(Phe). Ref.10 Ref.11

Subunit structure

Monomer. Ref.1 Ref.9

Subcellular location

Mitochondrion matrix Potential.

Involvement in disease

Combined oxidative phosphorylation deficiency 14 (COXPD14) [MIM:614946]: 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.11 Ref.12

Sequence similarities

Belongs to the class-II aminoacyl-tRNA synthetase family.

Contains 1 FDX-ACB domain.

Biophysicochemical properties

Kinetic parameters:

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 (Ref.10).

KM=2.2 µM for L-phenylalanine (Ref.10) Ref.10 Ref.11

KM=1900 µM for L-tyrosine (Ref.10)

KM=11.7 µM for DL-m-tyrosine (Ref.10)

KM=7.3 µM for L-phenylalanine (Ref.11)

KM=2.9 mM for ATP (Ref.11)

KM=1.2 µM for tRNA(Phe) (Ref.11)

Sequence caution

The sequence AAF28998.1 differs from that shown. Reason: Frameshift at position 414.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – ?Mitochondrion Potential
Chain? – 451Phenylalanine--tRNA ligase, mitochondrialPRO_0000035813

Regions

Domain358 – 45093FDX-ACB
Region157 – 1604Substrate binding
Region186 – 1883Substrate binding
Region193 – 1953Substrate binding

Sites

Binding site1791Substrate
Binding site2871Substrate; via carbonyl oxygen
Binding site3121Substrate; via carbonyl oxygen

Amino acid modifications

Modified residue2021N6-acetyllysine Ref.8

Natural variations

Natural variant571S → C.
Corresponds to variant rs34382405 [ dbSNP | Ensembl ].
VAR_052642
Natural variant1441Y → C in COXPD14; results in decreased affinity for tRNA causing a decrease in the catalytic efficiency for tRNA charging; does not affect ATP or Phe binding. Ref.11 Ref.12
VAR_069487
Natural variant2801N → S. Ref.2 Ref.3 Ref.7
Corresponds to variant rs11243011 [ dbSNP | Ensembl ].
VAR_052643
Natural variant3291I → T in COXPD14; results in a 4-fold decrease in the catalytic efficiency of amino acid activation mainly due to a decreased affinity for ATP; does not affect Phe binding; affects the stability of the enzyme, leading to a significant decrease in overall charging capacity. Ref.11
VAR_069488
Natural variant3911D → V in COXPD14; results in a decrease in affinity for Phe causing a decrease in aminoacylation activity; affects the stability of the enzyme, leading to a significant decrease in overall charging capacity. Ref.11
VAR_069489

Experimental info

Sequence conflict1581A → T in BAD97143. Ref.4
Sequence conflict3611P → T in AAF28998. Ref.7

Secondary structure

.......................................................................... 451
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
O95363 [UniParc].

Last modified May 1, 1999. Version 1.
Checksum: 1E5CC647A4A7193B

FASTA45152,357
        10         20         30         40         50         60 
MVGSALRRGA HAYVYLVSKA SHISRGHQHQ AWGSRPPAAE CATQRAPGSV VELLGKSYPQ 

        70         80         90        100        110        120 
DDHSNLTRKV LTRVGRNLHN QQHHPLWLIK ERVKEHFYKQ YVGRFGTPLF SVYDNLSPVV 

       130        140        150        160        170        180 
TTWQNFDSLL IPADHPSRKK GDNYYLNRTH MLRAHTSAHQ WDLLHAGLDA FLVVGDVYRR 

       190        200        210        220        230        240 
DQIDSQHYPI FHQLEAVRLF SKHELFAGIK DGESLQLFEQ SSRSAHKQET HTMEAVKLVE 

       250        260        270        280        290        300 
FDLKQTLTRL MAHLFGDELE IRWVDCYFPF THPSFEMEIN FHGEWLEVLG CGVMEQQLVN 

       310        320        330        340        350        360 
SAGAQDRIGW AFGLGLERLA MILYDIPDIR LFWCEDERFL KQFCVSNINQ KVKFQPLSKY 

       370        380        390        400        410        420 
PAVINDISFW LPSENYAEND FYDLVRTIGG DLVEKVDLID KFVHPKTHKT SHCYRITYRH 

       430        440        450 
MERTLSQREV RHIHQALQEA AVQLLGVEGR F 

« Hide

References

« Hide 'large scale' references
[1]"Expression and characterization of a human mitochondrial phenylalanyl-tRNA synthetase."
Bullard J.M., Cai Y.-C., Demeler B., Spremulli L.L.
J. Mol. Biol. 288:567-577(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBUNIT.
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT SER-280.
Tissue: Caudate nucleus.
[3]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., LaBaer J.
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT SER-280.
[4]Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.
Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Kidney epithelium.
[5]"The DNA sequence and analysis of human chromosome 6."
Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. expand/collapse author list , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.
Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Pancreas.
[7]"Human partial CDS from CD34+ stem cells."
Ye M., Zhang Q.-H., Zhou J., Shen Y., Wu X.-Y., Guan Z.Q., Wang L., Fan H.-Y., Mao Y.-F., Dai M., Huang Q.-H., Chen S.-J., Chen Z.
Submitted (MAY-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 108-451, VARIANT SER-280.
Tissue: Umbilical cord blood.
[8]"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-202, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[9]"The tRNA-induced conformational activation of human mitochondrial phenylalanyl-tRNA synthetase."
Klipcan L., Levin I., Kessler N., Moor N., Finarov I., Safro M.
Structure 16:1095-1104(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 38-451 IN COMPLEX WITH SUBSTRATE, SUBUNIT.
[10]"Eukaryotic cytosolic and mitochondrial phenylalanyl-tRNA synthetases catalyze the charging of tRNA with the meta-tyrosine."
Klipcan L., Moor N., Kessler N., Safro M.G.
Proc. Natl. Acad. Sci. U.S.A. 106:11045-11048(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 38-451 IN COMPLEX WITH SUBSTRATE, FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, KINETIC PARAMETERS.
[11]"Mitochondrial phenylalanyl-tRNA synthetase mutations underlie fatal infantile Alpers encephalopathy."
Elo J.M., Yadavalli S.S., Euro L., Isohanni P., Gotz A., Carroll C.J., Valanne L., Alkuraya F.S., Uusimaa J., Paetau A., Caruso E.M., Pihko H., Ibba M., Tyynismaa H., Suomalainen A.
Hum. Mol. Genet. 21:4521-4529(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS COXPD14 THR-329 AND VAL-391, CHARACTERIZATION OF VARIANTS COXPD14 CYS-144; THR-329 AND VAL-391, FUNCTION, CATALYTIC ACTIVITY, KINETIC PARAMETERS.
[12]"Genomic analysis of mitochondrial diseases in a consanguineous population reveals novel candidate disease genes."
Shamseldin H.E., Alshammari M., Al-Sheddi T., Salih M.A., Alkhalidi H., Kentab A., Repetto G.M., Hashem M., Alkuraya F.S.
J. Med. Genet. 49:234-241(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT COXPD14 CYS-144.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF097441 mRNA. Translation: AAC83802.1.
AK312454 mRNA. Translation: BAG35361.1.
CR542279 mRNA. Translation: CAG47075.1.
AK223423 mRNA. Translation: BAD97143.1.
AL133473 expand/collapse EMBL AC list , AL022097, AL590868, AL121978, AL392184 Genomic DNA. Translation: CAI19901.1.
AL022097 expand/collapse EMBL AC list , AL121978, AL392184, AL590868, AL133473 Genomic DNA. Translation: CAI19950.1.
AL392184 expand/collapse EMBL AC list , AL121978, AL590868, AL133473, AL022097 Genomic DNA. Translation: CAI20375.1.
AL121978 expand/collapse EMBL AC list , AL133473, AL022097, AL392184, AL590868 Genomic DNA. Translation: CAI21657.1.
AL590868 expand/collapse EMBL AC list , AL392184, AL133473, AL121978, AL022097 Genomic DNA. Translation: CAI39442.1.
BC020239 mRNA. Translation: AAH20239.1.
BC021112 mRNA. Translation: AAH21112.1.
AF161438 mRNA. Translation: AAF28998.1. Frameshift.
RefSeqNP_006558.1. NM_006567.3.
XP_005248868.1. XM_005248811.1.
XP_005248869.1. XM_005248812.2.
UniGeneHs.484547.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3CMQX-ray2.20A38-451[»]
3HFVX-ray2.60A38-451[»]
3TEGX-ray2.20A38-451[»]
3TUPX-ray3.05A38-451[»]
ProteinModelPortalO95363.
SMRO95363. Positions 47-451.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid115909. 5 interactions.
IntActO95363. 4 interactions.
MINTMINT-3077661.
STRING9606.ENSP00000274680.

Chemistry

BindingDBO95363.
ChEMBLCHEMBL2511.
DrugBankDB00120. L-Phenylalanine.

PTM databases

PhosphoSiteO95363.

Proteomic databases

PaxDbO95363.
PeptideAtlasO95363.
PRIDEO95363.

Protocols and materials databases

DNASU10667.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000274680; ENSP00000274680; ENSG00000145982.
ENST00000324331; ENSP00000316335; ENSG00000145982.
GeneID10667.
KEGGhsa:10667.
UCSCuc003mwr.2. human.

Organism-specific databases

CTD10667.
GeneCardsGC06P005207.
HGNCHGNC:21062. FARS2.
HPAHPA018148.
HPA028836.
MIM611592. gene.
614946. phenotype.
neXtProtNX_O95363.
Orphanet319519. Combined oxidative phosphorylation defect type 14.
PharmGKBPA134954893.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0016.
HOGENOMHOG000165163.
HOVERGENHBG082540.
InParanoidO95363.
KOK01889.
OMAEFTHPKT.
OrthoDBEOG7CG6ZS.
PhylomeDBO95363.
TreeFamTF105798.

Enzyme and pathway databases

ReactomeREACT_71. Gene Expression.

Gene expression databases

ArrayExpressO95363.
BgeeO95363.
CleanExHS_FARS2.
GenevestigatorO95363.

Family and domain databases

Gene3D3.30.70.380. 1 hit.
InterProIPR006195. aa-tRNA-synth_II.
IPR004530. Phe-tRNA-synth_IIc_mito.
IPR002319. Phenylalanyl-tRNA_Synthase.
IPR005121. PheS_beta_Fdx_antiC-bd.
[Graphical view]
PfamPF03147. FDX-ACB. 1 hit.
PF01409. tRNA-synt_2d. 2 hits.
[Graphical view]
SMARTSM00896. FDX-ACB. 1 hit.
[Graphical view]
SUPFAMSSF54991. SSF54991. 1 hit.
TIGRFAMsTIGR00469. pheS_mito. 1 hit.
PROSITEPS50862. AA_TRNA_LIGASE_II. 1 hit.
PS51447. FDX_ACB. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceO95363.
GeneWikiFARS2.
GenomeRNAi10667.
NextBio40563.
PROO95363.
SOURCESearch...

Entry information

Entry nameSYFM_HUMAN
AccessionPrimary (citable) accession number: O95363
Secondary accession number(s): B2R664 expand/collapse secondary AC list , Q53F66, Q5TCS3, Q6FG29, Q9NPY7, Q9P062
Entry history
Integrated into UniProtKB/Swiss-Prot: November 23, 2004
Last sequence update: May 1, 1999
Last modified: April 16, 2014
This is version 123 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 6

Human chromosome 6: entries, gene names and cross-references to MIM

Aminoacyl-tRNA synthetases

List of aminoacyl-tRNA synthetase entries