P56192 (SYMC_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Methionine--tRNA ligase, cytoplasmic
EC=6.1.1.10

Alternative name(s):
Methionyl-tRNA synthetase
Short name=MetRS

Gene names

Name:

MARS

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	900 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Catalytic activity	ATP + L-methionine + tRNA(Met) = AMP + diphosphate + L-methionyl-tRNA(Met).
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.
Sequence similarities	Belongs to the class-I aminoacyl-tRNA synthetase family. Contains 1 GST C-terminal domain. Contains 1 WHEP-TRS domain.

Ontologies

Keywords
Biological process	Protein biosynthesis
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Ligand	ATP-binding Nucleotide-binding RNA-binding tRNA-binding
Molecular function	Aminoacyl-tRNA synthetase Ligase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	methionyl-tRNA aminoacylation Inferred from electronic annotation. Source: InterPro tRNA aminoacylation for protein translation Traceable author statement. Source: Reactome
Cellular_component	cytosol Traceable author statement. Source: Reactome mitochondrion Inferred from electronic annotation. Source: Compara
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW methionine-tRNA ligase activity Traceable author statement. Source: Reactome tRNA binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
BRF2	Q9HAW0	1	EBI-355848,EBI-1055224
GIPC1	O14908	1	EBI-355848,EBI-373132
ILK	Q13418	1	EBI-355848,EBI-747644
MCC	P23508	1	EBI-355848,EBI-307531
PRKAB1	Q9Y478	1	EBI-355848,EBI-719769

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 900

900

Methionine--tRNA ligase, cytoplasmic

PRO_0000139262

Regions

Domain

74 – 198

125

GST C-terminal

Domain

841 – 897

57

WHEP-TRS

Motif

273 – 283

11

"HIGH" region

Motif

593 – 597

5

"KMSKS" region

Sites

Binding site

596

1

ATP By similarity

Natural variations

Natural variant

683

1

A → D.
Corresponds to variant rs1054403 [ dbSNP | Ensembl ].

VAR_020459

Experimental info

Sequence conflict

53

1

L → V in CAA64381. Ref.1

Sequence conflict

99

1

A → P in CAA64381. Ref.1

Sequence conflict

152

1

L → Q in CAA64381. Ref.1

Sequence conflict

172

1

W → S in AAH15011. Ref.5

Sequence conflict

250

1

L → P in BAD96487. Ref.4

Sequence conflict

683

1

A → G in CAA64381. Ref.1

Sequence conflict

683

1

A → G in CAA89153. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

900

Helix Strand Turn

Details...

Helix

838 – 861

24

Helix

866 – 887

22

Beta strand

893 – 895

3

Beta strand

897 – 899

3

Sequences

	Sequence		Length	Mass (Da)
	P56192 [UniParc]. Last modified April 16, 2002. Version 2. Checksum: 3D687C77E17C5C96	FASTA	900	101,116
	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

References

	« Hide 'large scale' referencesShow '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]	"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.
[9]	"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].
[10]	"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].
[11]	"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.
+	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.

IPI

IPI00008240.

PIR

JC5224.

RefSeq

NP_004981.2. NM_004990.3.

UniGene

Hs.632707.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2DJV	NMR	-	A	835-900	[»]

ProteinModelPortal

P56192.

ModBase

Search...

Protein-protein interaction databases

IntAct

P56192. 11 interactions.

MINT

MINT-5004366.

STRING

9606.ENSP00000262027.

PTM databases

PhosphoSite

P56192.

Polymorphism databases

DMDM

20178332.

Proteomic databases

PaxDb

P56192.

PeptideAtlas

P56192.

PRIDE

P56192.

Protocols and materials databases

DNASU

4141.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000262027; ENSP00000262027; ENSG00000166986.

GeneID

4141.

KEGG

hsa:4141.

UCSC

uc001sog.3. human.

Organism-specific databases

CTD

4141.

GeneCards

GC12P057881.

HGNC

HGNC:6898. MARS.

HPA

CAB017097.
HPA004125.

MIM

156560. gene.

neXtProt

NX_P56192.

PharmGKB

PA30642.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0143.

HOGENOM

HOG000200402.

HOVERGEN

HBG036191.

InParanoid

P56192.

KO

K01874.

OMA

HEIAPFK.

OrthoDB

EOG4Z0B50.

PhylomeDB

P56192.

Enzyme and pathway databases

Reactome

REACT_71. Gene Expression.

Gene expression databases

ArrayExpress

P56192.

Bgee

P56192.

CleanEx

HS_MARS.

Genevestigator

P56192.

GermOnline

ENSG00000166986. Homo sapiens.

Family and domain databases

Gene3D

1.10.287.10. 1 hit.
1.20.1050.10. 1 hit.
3.40.50.620. 2 hits.

InterPro

IPR001412. aa-tRNA-synth_I_CS.
IPR010987. Glutathione-S-Trfase_C-like.
IPR017933. Glutathione_S_Trfase/Cl_chnl_C.
IPR023458. Met-tRNA_ligase_1.
IPR014758. Met-tRNA_synth.
IPR015413. Methionyl/Leucyl_tRNA_Synth.
IPR014729. Rossmann-like_a/b/a_fold.
IPR009068. S15_NS1_RNA-bd.
IPR009080. tRNAsynth_1a_anticodon-bd.
IPR000738. WHEP-TRS.
[Graphical view]

Pfam

PF09334. tRNA-synt_1g. 1 hit.
PF00458. WHEP-TRS. 1 hit.
[Graphical view]

PRINTS

PR01041. TRNASYNTHMET.

SMART

SM00991. WHEP-TRS. 1 hit.
[Graphical view]

SUPFAM

SSF47616. GST_C_like. 1 hit.
SSF47060. S15/NS1_bind. 1 hit.
SSF47323. tRNAsyn_1a_bind. 1 hit.

TIGRFAMs

TIGR00398. metG. 1 hit.

PROSITE

PS00178. 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]

ProtoNet

Search...

Other

BindingDB

P56192.

ChEMBL

CHEMBL2870.

ChiTaRS

MARS. human.

DrugBank

DB00134. L-Methionine.

EvolutionaryTrace

P56192.

GenomeRNAi

4141.

NextBio

16264.

SOURCE

Search...

Entry information

Entry name

SYMC_HUMAN

Accession

Primary (citable) accession number: P56192
Secondary accession number(s): Q14895 , Q53H14, Q96A15, Q96BZ0, Q9NSE0

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	April 16, 2002
Last modified:	May 1, 2013
This is version 136 of the entry and version 2 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.