O95363 (SYFM_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	451 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Catalyzes direct attachment of p-Tyr (Tyr) to tRNAPhe. Permits also, with a lower efficiency, the attachment of m-Tyr to tRNAPhe, thereby opening the way for delivery of the misacylated tRNA to the ribosome and incorporation of ROS-damaged amino acid into proteins. Ref.10
Catalytic activity	ATP + L-phenylalanine + tRNA(Phe) = AMP + diphosphate + L-phenylalanyl-tRNA(Phe).
Subunit structure	Monomer. Ref.1 Ref.9
Subcellular location	Mitochondrion matrix Potential.
Sequence similarities	Belongs to the class-II aminoacyl-tRNA synthetase family. Contains 1 FDX-ACB domain.
Sequence caution	The sequence AAF28998.1 differs from that shown. Reason: Frameshift at position 414.

Ontologies

Keywords
Biological process	Protein biosynthesis
Cellular component	Mitochondrion
Coding sequence diversity	Polymorphism
Domain	Transit peptide
Ligand	ATP-binding Nucleotide-binding
Molecular function	Aminoacyl-tRNA synthetase Ligase
PTM	Acetylation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	phenylalanyl-tRNA aminoacylation Inferred from direct assay Ref.1. Source: UniProtKB tRNA processing Inferred from direct assay Ref.1. Source: UniProtKB
Cellular_component	mitochondrial matrix Traceable author statement. Source: Reactome
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW magnesium ion binding Inferred from electronic annotation. Source: InterPro phenylalanine-tRNA ligase activity Inferred from direct assay Ref.1. Source: UniProtKB tRNA binding Inferred from direct assay Ref.1. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Transit peptide

1 – ?

Mitochondrion Potential

Chain

? – 451

Phenylalanine--tRNA ligase, mitochondrial

PRO_0000035813

Regions

Domain

358 – 450

93

FDX-ACB

Region

157 – 160

4

Substrate binding

Region

186 – 188

3

Substrate binding

Region

193 – 195

3

Substrate binding

Sites

Binding site

179

1

Substrate

Binding site

287

1

Substrate; via carbonyl oxygen

Binding site

312

1

Substrate; via carbonyl oxygen

Amino acid modifications

Modified residue

202

1

N6-acetyllysine Ref.8

Natural variations

Natural variant

57

1

S → C.
Corresponds to variant rs34382405 [ dbSNP | Ensembl ].

VAR_052642

Natural variant

280

1

N → S. Ref.2 Ref.3 Ref.7
Corresponds to variant rs11243011 [ dbSNP | Ensembl ].

VAR_052643

Experimental info

Sequence conflict

158

1

A → T in BAD97143. Ref.4

Sequence conflict

361

1

P → T in AAF28998. Ref.7

Secondary structure

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451

Helix Strand Turn

Details...

Beta strand

49 – 53

5

Beta strand

56 – 59

4

Helix

68 – 71

4

Turn

72 – 75

4

Helix

78 – 80

3

Beta strand

81 – 84

4

Helix

85 – 103

19

Beta strand

105 – 107

3

Beta strand

111 – 113

3

Beta strand

118 – 121

4

Helix

122 – 125

4

Helix

127 – 129

3

Helix

136 – 138

3

Helix

140 – 142

3

Beta strand

145 – 152

8

Helix

156 – 159

4

Helix

160 – 165

6

Beta strand

169 – 178

10

Beta strand

184 – 186

3

Beta strand

189 – 201

13

Helix

202 – 205

4

Turn

206 – 208

3

Helix

212 – 214

3

Helix

233 – 255

23

Helix

256 – 258

3

Beta strand

261 – 268

8

Beta strand

271 – 281

11

Beta strand

284 – 294

11

Helix

296 – 301

6

Beta strand

307 – 315

9

Helix

316 – 323

8

Helix

329 – 333

5

Helix

337 – 340

4

Helix

341 – 343

3

Beta strand

363 – 370

8

Helix

378 – 389

12

Helix

390 – 392

3

Beta strand

393 – 403

11

Turn

405 – 407

3

Beta strand

410 – 418

9

Beta strand

421 – 423

3

Helix

427 – 444

18

Beta strand

448 – 451

4

Sequences

	Sequence		Length	Mass (Da)
	O95363 [UniParc]. Last modified May 1, 1999. Version 1. Checksum: 1E5CC647A4A7193B	FASTA	451	52,357
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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, MASS SPECTROMETRY.
[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.
+	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 , AL022097, AL590868, AL121978, AL392184 Genomic DNA. Translation: CAI19901.1.
AL022097 , AL121978, AL392184, AL590868, AL133473 Genomic DNA. Translation: CAI19950.1.
AL392184 , AL121978, AL590868, AL133473, AL022097 Genomic DNA. Translation: CAI20375.1.
AL121978 , AL133473, AL022097, AL392184, AL590868 Genomic DNA. Translation: CAI21657.1.
AL590868 , 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.

IPI

IPI00008579.

RefSeq

NP_006558.1. NM_006567.3.

UniGene

Hs.484547.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3CMQ	X-ray	2.20	A	38-451	[»]
3HFV	X-ray	2.60	A	38-451	[»]
3TEG	X-ray	2.20	A	38-451	[»]
3TUP	X-ray	3.05	A	38-451	[»]

ProteinModelPortal

O95363.

ModBase

Search...

Protein-protein interaction databases

IntAct

O95363. 2 interactions.

STRING

9606.ENSP00000274680.

PTM databases

PhosphoSite

O95363.

Proteomic databases

PaxDb

O95363.

PeptideAtlas

O95363.

PRIDE

O95363.

Protocols and materials databases

DNASU

10667.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000274680; ENSP00000274680; ENSG00000145982.
ENST00000324331; ENSP00000316335; ENSG00000145982.

GeneID

10667.

KEGG

hsa:10667.

UCSC

uc003mwr.2. human.

Organism-specific databases

CTD

10667.

GeneCards

GC06P005207.

HGNC

HGNC:21062. FARS2.

HPA

HPA018148.
HPA028836.

MIM

611592. gene.

neXtProt

NX_O95363.

PharmGKB

PA134954893.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0016.

HOGENOM

HOG000165163.

HOVERGEN

HBG082540.

InParanoid

O95363.

KO

K01889.

OMA

SWELEIY.

OrthoDB

EOG46WZ8R.

Enzyme and pathway databases

Reactome

REACT_71. Gene Expression.

Gene expression databases

ArrayExpress

O95363.

Bgee

O95363.

CleanEx

HS_FARS2.

Genevestigator

O95363.

GermOnline

ENSG00000145982. Homo sapiens.

Family and domain databases

Gene3D

3.30.70.380. 1 hit.

InterPro

IPR006195. aa-tRNA-synth_II.
IPR004530. Phe-tRNA-synth_IIc_mito.
IPR002319. Phenylalanyl-tRNA_Synthase.
IPR005121. PheS_beta_Fdx_antiC-bd.
[Graphical view]

Pfam

PF03147. FDX-ACB. 1 hit.
PF01409. tRNA-synt_2d. 2 hits.
[Graphical view]

SMART

SM00896. FDX-ACB. 1 hit.
[Graphical view]

SUPFAM

SSF54991. Fdx_AntiC_bd. 1 hit.

TIGRFAMs

TIGR00469. pheS_mito. 1 hit.

PROSITE

PS50862. AA_TRNA_LIGASE_II. 1 hit.
PS51447. FDX_ACB. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

O95363.

ChEMBL

CHEMBL2511.

DrugBank

DB00120. L-Phenylalanine.

EvolutionaryTrace

O95363.

GenomeRNAi

10667.

NextBio

40563.

SOURCE

Search...

Entry information

Entry name

SYFM_HUMAN

Accession

Primary (citable) accession number: O95363
Secondary accession number(s): B2R664 , Q53F66, Q5TCS3, Q6FG29, Q9NPY7, Q9P062

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 23, 2004
Last sequence update:	May 1, 1999
Last modified:	May 1, 2013
This is version 113 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.