Reviewed, UniProtKB/Swiss-Prot P07814 (SYEP_HUMAN)

Names and origin

Protein names

Recommended name:
    Bifunctional aminoacyl-tRNA synthetase
Alternative name(s):
    Proliferation-inducing gene 32 protein
Including the following 2 domains:
    1- Recommended name:
            Glutamyl-tRNA synthetase
              EC=6.1.1.17
        Alternative name(s):
            Glutamate--tRNA ligase
    2- Recommended name:
            Prolyl-tRNA synthetase
              EC=6.1.1.15
        Alternative name(s):
            Proline--tRNA ligase

Gene names

Name:	EPRS
Synonyms:	GLNS, PARS, QARS, QPRS
ORF Names:	PIG32

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1512 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	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.
Catalytic activity	ATP + L-glutamate + tRNA(Glu) = AMP + diphosphate + L-glutamyl-tRNA(Glu). ATP + L-proline + tRNA(Pro) = AMP + diphosphate + L-prolyl-tRNA(Pro).
Subunit structure	Component of the multisynthetase complex which is comprised of a bifunctional glutamyl-prolyl-tRNA synthetase, the monospecific isoleucyl, leucyl, glutaminyl, methionyl, lysyl, arginyl, and aspartyl-tRNA synthetases as well as three auxiliary proteins, p18, p48 and p43. Interacts with DUS2L. Ref.9
Domain	The WHEP-TRS domain is involved in RNA binding.
Sequence similarities	In the N-terminal section; belongs to the class-I aminoacyl-tRNA synthetase family. In the C-terminal section; belongs to the class-II aminoacyl-tRNA synthetase family. Contains 3 WHEP-TRS domains.
Caution	Was originally thought to be a glutaminyl-tRNA synthetase.
Sequence caution	The sequence AAH15494.1 differs from that shown. Reason: Miscellaneous discrepancy. Contaminating sequence. Potential poly-A sequence. The sequence AAH34797.1 differs from that shown. Reason: Miscellaneous discrepancy. Contaminating sequence. Potential poly-A sequence. The sequence AAH46156.1 differs from that shown. Reason: Miscellaneous discrepancy. Contaminating sequence. Potential poly-A sequence. The sequence AAH58921.1 differs from that shown. Reason: Miscellaneous discrepancy. Contaminating sequence. Potential poly-A sequence. The sequence CAA30354.1 differs from that shown. Reason: Miscellaneous discrepancy. Sequencing errors.

Ontologies

Keywords
Biological process	Protein biosynthesis
Coding sequence diversity	Polymorphism
Domain	Repeat
Ligand	ATP-binding Nucleotide-binding RNA-binding
Molecular function	Aminoacyl-tRNA synthetase Ligase
PTM	Phosphoprotein
Technical term	3D-structure Multifunctional enzyme
Gene Ontology (GO)
Biological process	glutamyl-tRNA aminoacylation Inferred from electronic annotation. Source: InterPro prolyl-tRNA aminoacylation Inferred from electronic annotation. Source: InterPro protein complex assembly Traceable author statement. Source: ProtInc
Cellular component	cytoplasm Traceable author statement. Source: ProtInc soluble fraction Traceable author statement. Source: ProtInc
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW RNA binding Inferred from electronic annotation. Source: UniProtKB-KW glutamate-tRNA ligase activity Inferred from electronic annotation. Source: EC proline-tRNA ligase activity Inferred from electronic annotation. Source: EC protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
IKBKE	Q14164	1	EBI-355315,EBI-307369
MCC	P23508	1	EBI-355315,EBI-307531
TFE3	P19532	1	EBI-355315,EBI-1048957

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1512

1512

Bifunctional aminoacyl-tRNA synthetase

PRO_0000119743

Regions

Domain

749 – 805

57

WHEP-TRS 1

Domain

822 – 878

57

WHEP-TRS 2

Domain

900 – 956

57

WHEP-TRS 3

Nucleotide binding

432 – 436

5

ATP By similarity

Region

164 – 759

596

Glutamyl-tRNA synthetase

Region

760 – 956

197

3 X 57 AA approximate repeats

Region

959 – 991

33

Charged

Region

1007 – 1512

506

Prolyl-tRNA synthetase

Motif

204 – 214

11

"HIGH" region

Motif

432 – 436

5

"KMSKS" region

Sites

Binding site

211

1

ATP By similarity

Binding site

398

1

ATP By similarity

Amino acid modifications

Modified residue

872

1

Phosphotyrosine Ref.15

Modified residue

882

1

Phosphoserine Ref.15

Modified residue

883

1

Phosphoserine Ref.15

Modified residue

885

1

Phosphoserine Ref.15 Ref.12

Modified residue

886

1

Phosphoserine Ref.15 Ref.12 Ref.11 Ref.13 Ref.14

Modified residue

888

1

Phosphothreonine Ref.13

Modified residue

891

1

Phosphoserine Ref.15 Ref.12

Modified residue

898

1

Phosphothreonine Ref.15 Ref.8 Ref.10

Modified residue

1000

1

Phosphoserine Ref.8

Natural variations

Natural variant

296

1

A → P: dbSNP rs35999099.

VAR_037288

Natural variant

308

1

E → D: dbSNP rs2230301. Ref.2

VAR_037289

Natural variant

334

1

H → Q: dbSNP rs1063236. Ref.2 Ref.1

VAR_037290

Natural variant

893

1

P → H: dbSNP rs5030751.

VAR_037291

Natural variant

913

1

E → G: dbSNP rs2230302.

VAR_057358

Natural variant

1043

1

I → V: dbSNP rs5030752. Ref.1

VAR_037292

Natural variant

1107

1

S → F: dbSNP rs12144752.

VAR_037293

Natural variant

1399

1

T → N: dbSNP rs34559775.

VAR_037294

Experimental info

Sequence conflict

532

1

K → R in CAI45949. Ref.1

Sequence conflict

594

1

F → L in CAI45949. Ref.1

Sequence conflict

594

1

F → L in AAH58921. Ref.2

Sequence conflict

594

1

F → L in AAH34797. Ref.2

Sequence conflict

594

1

F → L in AAI26276. Ref.2

Sequence conflict

943

1

K → E in CAI45949. Ref.1

Sequence conflict

1177 – 1179

3

ATM → VTV in CAI45949. Ref.1

Sequence conflict

1441

1

K → R in CAI45949. Ref.1

Secondary structure

1

.

.

.

.

.

1512

Helix Strand Turn

Details...

Helix

750 – 769

20

Helix

774 – 795

22

Sequences

	Sequence		Length	Mass (Da)
	P07814-1 [UniParc]. Last modified December 4, 2007. Version 3. Checksum: 89402F1C51BECD31	FASTA	1,512	170,648
	10 20 30 40 50 60 MATLSLTVNS GDPPLGALLA VEHVKDDVSI SVEEGKENIL HVSENVIFTD VNSILRYLAR 70 80 90 100 110 120 VATTAGLYGS NLMEHTEIDH WLEFSATKLS SCDSFTSTIN ELNHCLSLRT YLVGNSLSLA 130 140 150 160 170 180 DLCVWATLKG NAAWQEQLKQ KKAPVHVKRW FGFLEAQQAF QSVGTKWDVS TTKARVAPEK 190 200 210 220 230 240 KQDVGKFVEL PGAEMGKVTV RFPPEASGYL HIGHAKAALL NQHYQVNFKG KLIMRFDDTN 250 260 270 280 290 300 PEKEKEDFEK VILEDVAMLH IKPDQFTYTS DHFETIMKYA EKLIQEGKAY VDDTPAEQMK 310 320 330 340 350 360 AEREQRIESK HRKNPIEKNL QMWEEMKKGS QFGHSCCLRA KIDMSSNNGC MRDPTLYRCK 370 380 390 400 410 420 IQPHPRTGNK YNVYPTYDFA CPIVDSIEGV THALRTTEYH DRDEQFYWII EALGIRKPYI 430 440 450 460 470 480 WEYSRLNLNN TVLSKRKLTW FVNEGLVDGW DDPRFPTVRG VLRRGMTVEG LKQFIAAQGS 490 500 510 520 530 540 SRSVVNMEWD KIWAFNKKVI DPVAPRYVAL LKKEVIPVNV PEAQEEMKEV AKHPKNPEVG 550 560 570 580 590 600 LKPVWYSPKV FIEGADAETF SEGEMVTFIN WGNLNITKIH KNADGKIISL DAKFNLENKD 610 620 630 640 650 660 YKKTTKVTWL AETTHALPIP VICVTYEHLI TKPVLGKDED FKQYVNKNSK HEELMLGDPC 670 680 690 700 710 720 LKDLKKGDII QLQRRGFFIC DQPYEPVSPY SCKEAPCVLI YIPDGHTKEM PTSGSKEKTK 730 740 750 760 770 780 VEATKNETSA PFKERPTPSL NNNCTTSEDS LVLYNRVAVQ GDVVRELKAK KAPKEDVDAA 790 800 810 820 830 840 VKQLLSLKAE YKEKTGQEYK PGNPPAEIGQ NISSNSSASI LESKSLYDEV AAQGEVVRKL 850 860 870 880 890 900 KAEKSPKAKI NEAVECLLSL KAQYKEKTGK EYIPGQPPLS QSSDSSPTRN SEPAGLETPE 910 920 930 940 950 960 AKVLFDKVAS QGEVVRKLKT EKAPKDQVDI AVQELLQLKA QYKSLIGVEY KPVSATGAED 970 980 990 1000 1010 1020 KDKKKKEKEN KSEKQNKPQK QNDGQRKDPS KNQGGGLSSS GAGEGQGPKK QTRLGLEAKK 1030 1040 1050 1060 1070 1080 EENLADWYSQ VITKSEMIEY HDISGCYILR PWAYAIWEAI KDFFDAEIKK LGVENCYFPM 1090 1100 1110 1120 1130 1140 FVSQSALEKE KTHVADFAPE VAWVTRSGKT ELAEPIAIRP TSETVMYPAY AKWVQSHRDL 1150 1160 1170 1180 1190 1200 PIKLNQWCNV VRWEFKHPQP FLRTREFLWQ EGHSAFATME EAAEEVLQIL DLYAQVYEEL 1210 1220 1230 1240 1250 1260 LAIPVVKGRK TEKEKFAGGD YTTTIEAFIS ASGRAIQGGT SHHLGQNFSK MFEIVFEDPK 1270 1280 1290 1300 1310 1320 IPGEKQFAYQ NSWGLTTRTI GVMTMVHGDN MGLVLPPRVA CVQVVIIPCG ITNALSEEDK 1330 1340 1350 1360 1370 1380 EALIAKCNDY RRRLLSVNIR VRADLRDNYS PGWKFNHWEL KGVPIRLEVG PRDMKSCQFV 1390 1400 1410 1420 1430 1440 AVRRDTGEKL TVAENEAETK LQAILEDIQV TLFTRASEDL KTHMVVANTM EDFQKILDSG 1450 1460 1470 1480 1490 1500 KIVQIPFCGE IDCEDWIKKT TARDQDLEPG APSMGAKSLC IPFKPLCELQ PGAKCVCGKN 1510 PAKYYTLFGR SY

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Blocker H., Heubner D., Hoerlein A., Michel G., Wedler H., Kohrer K., Ottenwalder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed: 17974005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS GLN-334 AND VAL-1043. Tissue: Bone marrow.
[2]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS ASP-308 AND GLN-334. Tissue: Brain, Duodenum, Eye, Lung and Placenta.
[3]	"The primary structure of human glutaminyl-tRNA synthetase. A highly conserved core, amino acid repeat regions, and homologies with translation elongation factors." Fett R., Knippers R. J. Biol. Chem. 266:1448-1455(1991) [PubMed: 1988429] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 54-1512.
[4]	"Identification of a proliferation inducing gene." Kim J.W. Submitted (DEC-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 62-1512.
[5]	"The core region of human glutaminyl-tRNA synthetase homologies with the Escherichia coli and yeast enzymes." Thoemmes P., Fett R., Schray B., Kunze N., Knippers R. Nucleic Acids Res. 16:5391-5406(1988) [PubMed: 3290852] [Abstract] Cited for: PRELIMINARY NUCLEOTIDE SEQUENCE [MRNA] OF 168-959. Tissue: Cervix carcinoma.
[6]	"A component of the multisynthetase complex is a multifunctional aminoacyl-tRNA synthetase." Cerini C., Kerjan P., Astier M., Gratecos D., Mirande M., Semeriva M. EMBO J. 10:4267-4277(1991) [PubMed: 1756734] [Abstract] Cited for: FUNCTION.
[7]	"Exons encoding the highly conserved part of human glutaminyl-tRNA synthetase." Kaiser E., Eberhard D., Knippers R. J. Mol. Evol. 34:45-53(1992) [PubMed: 1556743] [Abstract] Cited for: GENE STRUCTURE.
[8]	"Large-scale characterization of HeLa cell nuclear phosphoproteins." Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004) [PubMed: 15302935] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-898 AND SER-1000, MASS SPECTROMETRY. Tissue: Epithelium.
[9]	"A novel human tRNA-dihydrouridine synthase involved in pulmonary carcinogenesis." Kato T., Daigo Y., Hayama S., Ishikawa N., Yamabuki T., Ito T., Miyamoto M., Kondo S., Nakamura Y. Cancer Res. 65:5638-5646(2005) [PubMed: 15994936] [Abstract] Cited for: INTERACTION WITH DUS2L.
[10]	"A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed: 16964243] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-898, MASS SPECTROMETRY. Tissue: Epithelium.
[11]	"Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra." Yu L.-R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D. J. Proteome Res. 6:4150-4162(2007) [PubMed: 17924679] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-886, MASS SPECTROMETRY. Tissue: Epithelium.
[12]	"Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry." Molina H., Horn D.M., Tang N., Mathivanan S., Pandey A. Proc. Natl. Acad. Sci. U.S.A. 104:2199-2204(2007) [PubMed: 17287340] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-885; SER-886 AND SER-891, MASS SPECTROMETRY.
[13]	"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed: 18220336] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-886 AND THR-888, MASS SPECTROMETRY.
[14]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-886, MASS SPECTROMETRY.
[15]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-872; SER-882; SER-883; SER-885; SER-886; SER-891 AND THR-898, MASS SPECTROMETRY.
[16]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[17]	"Structural analysis of multifunctional peptide motifs in human bifunctional tRNA synthetase: identification of RNA-binding residues and functional implications for tandem repeats." Jeong E.-J., Hwang G.-S., Kim K.H., Kim M.J., Kim S., Kim K.-S. Biochemistry 39:15775-15782(2000) [PubMed: 11123902] [Abstract] Cited for: STRUCTURE BY NMR OF 749-805, RNA-BINDING.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

CR933648 mRNA. Translation: CAI45949.1.
BC015494 mRNA. Translation: AAH15494.1. Sequence problems.
BC034797 mRNA. Translation: AAH34797.1. Sequence problems.
BC046156 mRNA. Translation: AAH46156.1. Sequence problems.
BC058921 mRNA. Translation: AAH58921.1. Sequence problems.
BC126275 mRNA. Translation: AAI26276.1.
X54326 mRNA. Translation: CAA38224.1. Different initiation.
AY493416 mRNA. Translation: AAS72877.1. Different initiation.
X07466 mRNA. Translation: CAA30354.1. Sequence problems.

IPI

IPI00013452.

PIR

SYHUQT. A38663.

RefSeq

NP_004437.2.

UniGene

Hs.497788

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1FYJ	NMR	-	A	749-805	[»]

SMR

P07814. Positions 677-733.

ModBase

Search...

Protein-protein interaction databases

IntAct

P07814. 16 interactions.

PTM databases

PhosphoSite

P07814.

Proteomic databases

PRIDE

P07814.

Genome annotation databases

Ensembl

ENSG00000136628. Homo sapiens. [Contig view]

GeneID

2058.

KEGG

hsa:2058.

Organism-specific databases

GeneCards

GC01M218208.

HGNC

HGNC:3418. EPRS.

MIM

138295. gene.

PharmGKB

PA27837.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

P07814.

Enzyme and pathway databases

BRENDA

6.1.1.15. 247.
6.1.1.17. 247.

Gene expression databases

ArrayExpress

P07814.

Bgee

P07814.

CleanEx

HS_EPRS.
HS_QARS.

GermOnline

ENSG00000136628. Homo sapiens.

Family and domain databases

InterPro

IPR002314. aa-tRNA-synt_IIb_cons-reg.
IPR001412. aa-tRNA-synth_I_CS.
IPR006195. aa-tRNA-synth_II_cons-reg.
IPR004154. Anticodon_bd.
IPR004526. Glu-tRNA-synth_Ic_arc/euk.
IPR000924. Glu/Gln-tRNA-synth_Ic.
IPR010987. Glutathione-S-Trfase_C-like.
IPR004499. Pro-tRNA-synth_IIa_pro-type.
IPR016061. Pro-tRNA_synth_II_C.
IPR009068. S15_NS1_RNA_bd.
IPR000738. WHEP-TRS.
[Graphical view]

Gene3D

G3DSA:3.40.50.800. Anticodon_bd. 2 hits.
G3DSA:1.20.1050.10. GST_C_like. 2 hits.
G3DSA:3.30.110.30. Pro-tRNA-synth_II_C_arc/euk. 2 hits.
G3DSA:1.10.287.10. S15_NS1_RNA_bd. 6 hits.

PANTHER

PTHR10119. Glu_tRNA-synt_1c. 2 hits.

Pfam

PF03129. HGTP_anticodon. 1 hit.
PF09180. ProRS-C_1. 1 hit.
PF00587. tRNA-synt_2b. 1 hit.
PF00458. WHEP-TRS. 3 hits.
[Graphical view]

TIGRFAMs

TIGR00463. gltX_arch. 1 hit.
TIGR00408. proS_fam_I. 1 hit.

PROSITE

PS00178. AA_TRNA_LIGASE_I. 1 hit.
PS50862. AA_TRNA_LIGASE_II. 1 hit.
PS00762. WHEP_TRS_1. 3 hits.
PS51185. WHEP_TRS_2. 3 hits.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB00142. L-Glutamic Acid.
DB00172. L-Proline.

NextBio

8369.

SOURCE

Search...

Entry information

Entry name

SYEP_HUMAN

Accession

Primary (citable) accession number: P07814
Secondary accession number(s): A0AVA9 , Q05BP6, Q05DF8, Q5DSM1, Q5H9S5, Q6PD57, Q86X73

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1988
Last sequence update:	December 4, 2007
Last modified:	June 16, 2009
This is version 122 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)