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P56192 (SYMC_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 150. 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:
Methionine--tRNA ligase, cytoplasmic

EC=6.1.1.10
Alternative name(s):
Methionyl-tRNA synthetase
Short name=MetRS
Gene names
Name:MARS
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length900 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Catalytic activity

ATP + L-methionine + tRNA(Met) = AMP + diphosphate + L-methionyl-tRNA(Met). HAMAP-Rule MF_00098

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.

Subcellular location

Cytoplasm Probable HAMAP-Rule MF_00098.

Involvement in disease

Infantile liver failure syndrome 2 (ILFS2) [MIM:615486]: A life-threatening disorder of hepatic function that manifests with liver failure in the first months of life. Clinical features include failure to thrive, hypotonia, intermittent lactic acidosis, aminoaciduria, hypothyroidism, interstitial lung disease, anemia, liver canalicular cholestasis, steatosis, and iron deposition.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.13

Sequence similarities

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

Contains 1 GST C-terminal domain.

Contains 1 WHEP-TRS domain.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 900900Methionine--tRNA ligase, cytoplasmic HAMAP-Rule MF_00098
PRO_0000139262

Regions

Domain74 – 198125GST C-terminal
Domain841 – 89757WHEP-TRS
Motif273 – 28311"HIGH" region HAMAP-Rule MF_00098
Motif593 – 5975"KMSKS" region HAMAP-Rule MF_00098

Sites

Binding site5961ATP By similarity

Natural variations

Natural variant3701F → L in ILFS2. Ref.13
VAR_070872
Natural variant5231I → T in ILFS2. Ref.13
VAR_070873
Natural variant6831A → D.
Corresponds to variant rs1054403 [ dbSNP | Ensembl ].
VAR_020459

Experimental info

Sequence conflict531L → V in CAA64381. Ref.1
Sequence conflict991A → P in CAA64381. Ref.1
Sequence conflict1521L → Q in CAA64381. Ref.1
Sequence conflict1721W → S in AAH15011. Ref.5
Sequence conflict2501L → P in BAD96487. Ref.4
Sequence conflict6831A → G in CAA64381. Ref.1
Sequence conflict6831A → G in CAA89153. Ref.1

Secondary structure

......... 900
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P56192 [UniParc].

Last modified April 16, 2002. Version 2.
Checksum: 3D687C77E17C5C96

FASTA900101,116
        10         20         30         40         50         60 
MRLFVSDGVP GCLPVLAAAG RARGRAEVLI STVGPEDCVV PFLTRPKVPV LQLDSGNYLF 

        70         80         90        100        110        120 
STSAICRYFF LLSGWEQDDL TNQWLEWEAT ELQPALSAAL YYLVVQGKKG EDVLGSVRRA 

       130        140        150        160        170        180 
LTHIDHSLSR QNCPFLAGET ESLADIVLWG ALYPLLQDPA YLPEELSALH SWFQTLSTQE 

       190        200        210        220        230        240 
PCQRAAETVL KQQGVLALRP YLQKQPQPSP AEGRAVTNEP EEEELATLSE EEIAMAVTAW 

       250        260        270        280        290        300 
EKGLESLPPL RPQQNPVLPV AGERNVLITS ALPYVNNVPH LGNIIGCVLS ADVFARYSRL 

       310        320        330        340        350        360 
RQWNTLYLCG TDEYGTATET KALEEGLTPQ EICDKYHIIH ADIYRWFNIS FDIFGRTTTP 

       370        380        390        400        410        420 
QQTKITQDIF QQLLKRGFVL QDTVEQLRCE HCARFLADRF VEGVCPFCGY EEARGDQCDK 

       430        440        450        460        470        480 
CGKLINAVEL KKPQCKVCRS CPVVQSSQHL FLDLPKLEKR LEEWLGRTLP GSDWTPNAQF 

       490        500        510        520        530        540 
ITRSWLRDGL KPRCITRDLK WGTPVPLEGF EDKVFYVWFD ATIGYLSITA NYTDQWERWW 

       550        560        570        580        590        600 
KNPEQVDLYQ FMAKDNVPFH SLVFPCSALG AEDNYTLVSH LIATEYLNYE DGKFSKSRGV 

       610        620        630        640        650        660 
GVFGDMAQDT GIPADIWRFY LLYIRPEGQD SAFSWTDLLL KNNSELLNNL GNFINRAGMF 

       670        680        690        700        710        720 
VSKFFGGYVP EMVLTPDDQR LLAHVTLELQ HYHQLLEKVR IRDALRSILT ISRHGNQYIQ 

       730        740        750        760        770        780 
VNEPWKRIKG SEADRQRAGT VTGLAVNIAA LLSVMLQPYM PTVSATIQAQ LQLPPPACSI 

       790        800        810        820        830        840 
LLTNFLCTLP AGHQIGTVSP LFQKLENDQI ESLRQRFGGG QAKTSPKPAV VETVTTAKPQ 

       850        860        870        880        890        900 
QIQALMDEVT KQGNIVRELK AQKADKNEVA AEVAKLLDLK KQLAVAEGKP PEAPKGKKKK 

« Hide

References

« Hide 'large scale' references
[1]"Cloning of a human cDNA encoding a protein with high homology to yeast methionyl-tRNA synthetase."
Lage H., Dietel M.
Gene 178:187-189(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Gastric carcinoma.
[2]"Cloning and sequence determination of a human cytoplasmic methionyl-tRNA synthetase gene."
Motegi H., Noda T., Shiba K.
Submitted (FEB-1996) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Brain.
[3]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]Suzuki Y., Sugano S., 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: Liver.
[5]"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: Brain, Colon and Muscle.
[6]"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] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[7]"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] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[8]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[9]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[10]"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].
[11]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]"Solution structures of the WHEP-TRS domain of human methionyl-tRNA synthetase."
RIKEN structural genomics initiative (RSGI)
Submitted (OCT-2006) to the PDB data bank
Cited for: STRUCTURE BY NMR OF 835-900.
[13]"Rare recessive loss-of-function methionyl-tRNA synthetase mutations presenting as a multi-organ phenotype."
van Meel E., Wegner D.J., Cliften P., Willing M.C., White F.V., Kornfeld S., Cole F.S.
BMC Med. Genet. 14:106-106(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ILFS2 LEU-370 AND THR-523.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X94754 mRNA. Translation: CAA64381.1.
Z49216 mRNA. Translation: CAA89153.1.
D84224 mRNA. Translation: BAA95668.1.
BT007338 mRNA. Translation: AAP36002.1.
AK222767 mRNA. Translation: BAD96487.1.
BC002384 mRNA. Translation: AAH02384.1.
BC006328 mRNA. Translation: AAH06328.1.
BC011639 mRNA. Translation: AAH11639.1.
BC011849 mRNA. Translation: AAH11849.1.
BC015011 mRNA. Translation: AAH15011.1.
CCDSCCDS8942.1.
PIRJC5224.
RefSeqNP_004981.2. NM_004990.3.
UniGeneHs.632707.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2DJVNMR-A835-900[»]
4BL7X-ray1.89A1-224[»]
ProteinModelPortalP56192.
SMRP56192. Positions 267-893.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110311. 42 interactions.
DIPDIP-38164N.
IntActP56192. 14 interactions.
MINTMINT-5004366.
STRING9606.ENSP00000262027.

Chemistry

BindingDBP56192.
ChEMBLCHEMBL2870.
DrugBankDB00134. L-Methionine.

PTM databases

PhosphoSiteP56192.

Polymorphism databases

DMDM20178332.

Proteomic databases

MaxQBP56192.
PaxDbP56192.
PeptideAtlasP56192.
PRIDEP56192.

Protocols and materials databases

DNASU4141.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000262027; ENSP00000262027; ENSG00000166986.
GeneID4141.
KEGGhsa:4141.
UCSCuc001sog.3. human.

Organism-specific databases

CTD4141.
GeneCardsGC12P057881.
HGNCHGNC:6898. MARS.
HPACAB017097.
HPA004125.
MIM156560. gene.
615486. phenotype.
neXtProtNX_P56192.
Orphanet370088. Acute infantile liver failure-multisystemic involvement syndrome.
PharmGKBPA30642.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0143.
HOGENOMHOG000200402.
HOVERGENHBG036191.
InParanoidP56192.
KOK01874.
OMAFIKADTY.
PhylomeDBP56192.
TreeFamTF300526.

Enzyme and pathway databases

ReactomeREACT_71. Gene Expression.
SignaLinkP56192.

Gene expression databases

ArrayExpressP56192.
BgeeP56192.
CleanExHS_MARS.
GenevestigatorP56192.

Family and domain databases

Gene3D1.10.287.10. 1 hit.
1.10.730.10. 1 hit.
1.20.1050.10. 1 hit.
3.40.50.620. 2 hits.
HAMAPMF_00098. Met_tRNA_synth_type1.
InterProIPR001412. aa-tRNA-synth_I_CS.
IPR010987. Glutathione-S-Trfase_C-like.
IPR023458. Met-tRNA_ligase_1.
IPR014758. Met-tRNA_synth.
IPR015413. Methionyl/Leucyl_tRNA_Synth.
IPR029038. MetRS_Zn.
IPR014729. Rossmann-like_a/b/a_fold.
IPR009068. S15_NS1_RNA-bd.
IPR009080. tRNAsynth_1a_anticodon-bd.
IPR000738. WHEP-TRS.
[Graphical view]
PfamPF09334. tRNA-synt_1g. 1 hit.
PF00458. WHEP-TRS. 1 hit.
[Graphical view]
PRINTSPR01041. TRNASYNTHMET.
SMARTSM00991. WHEP-TRS. 1 hit.
[Graphical view]
SUPFAMSSF47060. SSF47060. 1 hit.
SSF47323. SSF47323. 1 hit.
SSF47616. SSF47616. 1 hit.
SSF57770. SSF57770. 1 hit.
TIGRFAMsTIGR00398. metG. 1 hit.
PROSITEPS00178. AA_TRNA_LIGASE_I. 1 hit.
PS50405. GST_CTER. 1 hit.
PS00762. WHEP_TRS_1. 1 hit.
PS51185. WHEP_TRS_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSMARS. human.
EvolutionaryTraceP56192.
GeneWikiMARS_(gene).
GenomeRNAi4141.
NextBio16264.
PROP56192.
SOURCESearch...

Entry information

Entry nameSYMC_HUMAN
AccessionPrimary (citable) accession number: P56192
Secondary accession number(s): Q14895 expand/collapse secondary AC list , Q53H14, Q96A15, Q96BZ0, Q9NSE0
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: April 16, 2002
Last modified: July 9, 2014
This is version 150 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

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 12

Human chromosome 12: entries, gene names and cross-references to MIM

Aminoacyl-tRNA synthetases

List of aminoacyl-tRNA synthetase entries