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Q5JPH6 (SYEM_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 88. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | 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:
Probable glutamate--tRNA ligase, mitochondrial

EC=6.1.1.17
Alternative name(s):
Glutamyl-tRNA synthetase
Short name=GluRS
Gene names
Name:EARS2
Synonyms:KIAA1970
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length523 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Catalyzes the attachment of glutamate to tRNA(Glu) in a two-step reaction: glutamate is first activated by ATP to form Glu-AMP and then transferred to the acceptor end of tRNA(Glu) By similarity. HAMAP-Rule MF_00022_B

Catalytic activity

ATP + L-glutamate + tRNA(Glu) = AMP + diphosphate + L-glutamyl-tRNA(Glu). HAMAP-Rule MF_00022_B

Subcellular location

Mitochondrion matrix By similarity HAMAP-Rule MF_00022_B.

Involvement in disease

Combined oxidative phosphorylation deficiency 12 (COXPD12) [MIM:614924]: An autosomal recessive, mitochondrial, neurologic disorder characterized by onset in infancy of hypotonia and delayed psychomotor development, or early developmental regression, associated with T2-weighted hyperintensities in the deep cerebral white matter, brainstem, and cerebellar white matter. Serum lactate is increased due to a defect in mitochondrial respiration. There are 2 main phenotypic groups: those with a milder disease course and some recovery of skills after age 2 years, and those with a severe disease course resulting in marked disability.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8 Ref.9

Sequence similarities

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 4141Mitochondrion Potential
Chain42 – 523482Probable glutamate--tRNA ligase, mitochondrial HAMAP-Rule MF_00022_B
PRO_0000254560

Regions

Nucleotide binding284 – 2885ATP By similarity
Region40 – 423Glutamate binding By similarity
Region228 – 2325Glutamate binding By similarity
Motif45 – 539"HIGH" region HAMAP-Rule MF_00022_B
Motif284 – 2885"KMSKS" region HAMAP-Rule MF_00022_B

Sites

Binding site501ATP By similarity
Binding site761Glutamate By similarity
Binding site2461Glutamate By similarity
Binding site2491ATP By similarity

Amino acid modifications

Modified residue2561N6-succinyllysine By similarity
Modified residue4861N6-acetyllysine Ref.6

Natural variations

Natural variant551R → H in COXPD12. Ref.8
VAR_069235
Natural variant651K → E in COXPD12. Ref.9
VAR_069236
Natural variant961E → K in COXPD12. Ref.8
VAR_069237
Natural variant1071R → H in COXPD12. Ref.8
VAR_069238
Natural variant1081R → W in COXPD12. Ref.8
VAR_069239
Natural variant1101G → S in COXPD12. Ref.8
VAR_069240
Natural variant1671C → Y in COXPD12. Ref.8
VAR_069241
Natural variant1681R → G in COXPD12. Ref.8
VAR_069242
Natural variant2041G → S in COXPD12. Ref.8
VAR_069243
Natural variant2241G → S in COXPD12. Ref.8
VAR_069244
Natural variant3171G → C in COXPD12. Ref.8
VAR_069245
Natural variant426 – 4272TR → L in COXPD12.
VAR_069246
Natural variant4571S → G. Ref.1 Ref.2
Corresponds to variant rs6497671 [ dbSNP | Ensembl ].
VAR_028840
Natural variant5161R → Q in COXPD12. Ref.8
VAR_069247

Sequences

Sequence LengthMass (Da)Tools
Q5JPH6 [UniParc].

Last modified October 31, 2006. Version 2.
Checksum: FA9B19569AD9F5DB

FASTA52358,689
        10         20         30         40         50         60 
MAALLRRLLQ RERPSAASGR PVGRREANLG TDAGVAVRVR FAPSPTGFLH LGGLRTALYN 

        70         80         90        100        110        120 
YIFAKKYQGS FILRLEDTDQ TRVVPGAAEN IEDMLEWAGI PPDESPRRGG PAGPYQQSQR 

       130        140        150        160        170        180 
LELYAQATEA LLKTGAAYPC FCSPQRLELL KKEALRNHQT PRYDNRCRNM SQEQVAQKLA 

       190        200        210        220        230        240 
KDPKPAIRFR LEQVVPAFQD LVYGWNRHEV ASVEGDPVIM KSDGFPTYHL ACVVDDHHMG 

       250        260        270        280        290        300 
ISHVLRGSEW LVSTAKHLLL YQALGWQPPH FAHLPLLLNR DGSKLSKRQG DVFLEHFAAD 

       310        320        330        340        350        360 
GFLPDSLLDI ITNCGSGFAE NQMGRTLPEL ITQFNLTQVT CHSALLDLEK LPEFNRLHLQ 

       370        380        390        400        410        420 
RLVSNESQRR QLVGKLQVLV EEAFGCQLQN RDVLNPVYVE RILLLRQGHI CRLQDLVSPV 

       430        440        450        460        470        480 
YSYLWTRPAV GRAQLDAISE KVDVIAKRVL GLLERSSMSL TQDMLNGELK KLSEGLEGTK 

       490        500        510        520 
YSNVMKLLRM ALSGQQQGPP VAEMMLALGP KEVRERIQKV VSS 

« Hide

References

« Hide 'large scale' references
[1]"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 GLY-457.
Tissue: Kidney.
[2]"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., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT GLY-457.
Tissue: Testis.
[3]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"Prediction of the coding sequences of unidentified human genes. XXII. The complete sequences of 50 new cDNA clones which code for large proteins."
Nagase T., Kikuno R., Ohara O.
DNA Res. 8:319-327(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 5-523.
Tissue: Brain.
[5]"Toward the full set of human mitochondrial aminoacyl-tRNA synthetases: characterization of AspRS and TyrRS."
Bonnefond L., Fender A., Rudinger-Thirion J., Giege R., Florentz C., Sissler M.
Biochemistry 44:4805-4816(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION.
[6]"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-486, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[7]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[8]"Leukoencephalopathy with thalamus and brainstem involvement and high lactate 'LTBL' caused by EARS2 mutations."
Steenweg M.E., Ghezzi D., Haack T., Abbink T.E., Martinelli D., van Berkel C.G., Bley A., Diogo L., Grillo E., Te Water Naude J., Strom T.M., Bertini E., Prokisch H., van der Knaap M.S., Zeviani M.
Brain 135:1387-1394(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS COXPD12 HIS-55; LYS-96; HIS-107; TRP-108; SER-110; TYR-167; GLY-168; SER-204; SER-224; CYS-317; 426-THR-ARG-427 DELINS LEU AND GLN-516.
[9]"Multisystem fatal infantile disease caused by a novel homozygous EARS2 mutation."
Talim B., Pyle A., Griffin H., Topaloglu H., Tokatli A., Keogh M.J., Santibanez-Koref M., Chinnery P.F., Horvath R.
Brain 136:E228-E228(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT COXPD12 GLU-65.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AK095998 mRNA. Translation: BAG53194.1.
AL832489 mRNA. Translation: CAI46121.1.
CH471145 Genomic DNA. Translation: EAW55822.1.
CH471145 Genomic DNA. Translation: EAW55824.1.
AB075850 mRNA. Translation: BAB85556.1.
CCDSCCDS42132.1.
RefSeqNP_001077083.1. NM_001083614.1.
UniGeneHs.620541.

3D structure databases

ProteinModelPortalQ5JPH6.
SMRQ5JPH6. Positions 36-518.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid125866. 2 interactions.
STRING9606.ENSP00000343488.

Chemistry

DrugBankDB00142. L-Glutamic Acid.

PTM databases

PhosphoSiteQ5JPH6.

Polymorphism databases

DMDM117949790.

Proteomic databases

MaxQBQ5JPH6.
PaxDbQ5JPH6.
PRIDEQ5JPH6.

Protocols and materials databases

DNASU124454.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000449606; ENSP00000395196; ENSG00000103356.
ENST00000563459; ENSP00000456467; ENSG00000103356.
GeneID124454.
KEGGhsa:124454.
UCSCuc002dlt.4. human.

Organism-specific databases

CTD124454.
GeneCardsGC16M023533.
HGNCHGNC:29419. EARS2.
HPAHPA043289.
HPA043633.
MIM612799. gene.
614924. phenotype.
neXtProtNX_Q5JPH6.
Orphanet314051. Leukoencephalopathy - thalamus and brainstem anomalies - high lactate.
PharmGKBPA144596439.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0008.
HOGENOMHOG000252720.
HOVERGENHBG056174.
InParanoidQ5JPH6.
KOK01885.
OrthoDBEOG73Z2SZ.
PhylomeDBQ5JPH6.
TreeFamTF313268.

Enzyme and pathway databases

ReactomeREACT_71. Gene Expression.

Gene expression databases

ArrayExpressQ5JPH6.
BgeeQ5JPH6.
CleanExHS_EARS2.
GenevestigatorQ5JPH6.

Family and domain databases

Gene3D1.10.10.350. 1 hit.
1.10.1160.10. 1 hit.
3.40.50.620. 2 hits.
HAMAPMF_00022_B. Glu_tRNA_synth_B.
InterProIPR008925. aa-tRNA-synth_I_codon-bd.
IPR020751. aa-tRNA-synth_I_codon-bd_sub2.
IPR001412. aa-tRNA-synth_I_CS.
IPR004527. Glu-tRNA-ligase_bac/mito.
IPR000924. Glu/Gln-tRNA-synth.
IPR020061. Glu/Gln-tRNA-synth_Ib_a-bdl.
IPR020058. Glu/Gln-tRNA-synth_Ib_cat-dom.
IPR014729. Rossmann-like_a/b/a_fold.
[Graphical view]
PANTHERPTHR10119. PTHR10119. 1 hit.
PfamPF00749. tRNA-synt_1c. 1 hit.
[Graphical view]
PRINTSPR00987. TRNASYNTHGLU.
SUPFAMSSF48163. SSF48163. 1 hit.
TIGRFAMsTIGR00464. gltX_bact. 1 hit.
PROSITEPS00178. AA_TRNA_LIGASE_I. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSEARS2. human.
GenomeRNAi124454.
NextBio81282.
PROQ5JPH6.
SOURCESearch...

Entry information

Entry nameSYEM_HUMAN
AccessionPrimary (citable) accession number: Q5JPH6
Secondary accession number(s): B3KTT2, D3DWF1, Q8TF31
Entry history
Integrated into UniProtKB/Swiss-Prot: October 31, 2006
Last sequence update: October 31, 2006
Last modified: July 9, 2014
This is version 88 of the entry and version 2 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

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 16

Human chromosome 16: entries, gene names and cross-references to MIM

Aminoacyl-tRNA synthetases

List of aminoacyl-tRNA synthetase entries