MARS

Functionⁱ

Catalyzes the specific attachment of an amino acid to its cognate tRNA in a 2 step reaction: the amino acid (AA) is first activated by ATP to form AA-AMP and then transferred to the acceptor end of the tRNA.1 Publication

Catalytic activityⁱ

ATP + L-methionine + tRNA(Met) = AMP + diphosphate + L-methionyl-tRNA(Met).1 Publication

Activity regulationⁱ

Enzyme activity is increased by spermidine, EEF1A1, and when the Mg²⁺ concentration is increased from 5 mM to 13 mM (in vitro), possibly by promoting the dissociation of the complex between the enzyme and its product.1 Publication

Sites

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Binding siteⁱ	596	ATPBy similarity		1

GO - Molecular functionⁱ

ATP binding Source: UniProtKB-KW
methionine-tRNA ligase activity
Source: UniProtKB
Inferred from direct assayⁱ
- 11714285
tRNA binding Source: UniProtKB-KW

View the complete GO annotation on QuickGO ...

GO - Biological processⁱ

cellular response to epidermal growth factor stimulus
Source: CAFA
Inferred from direct assayⁱ
- 10791971
cellular response to insulin stimulus
Source: CAFA
Inferred from direct assayⁱ
- 10791971
cellular response to platelet-derived growth factor stimulus
Source: CAFA
Inferred from direct assayⁱ
- 10791971
cellular response to starvation
Source: CAFA
Inferred from direct assayⁱ
- 10791971
methionyl-tRNA aminoacylation
Source: UniProtKB
Inferred from direct assayⁱ
- 11714285
positive regulation of transcription of nucleolar large rRNA by RNA polymerase I
Source: CAFA
Inferred from mutant phenotypeⁱ
- 10791971
rRNA transcription
Source: CAFA
Inferred from mutant phenotypeⁱ
- 10791971
tRNA aminoacylation for protein translation Source: Reactome

View the complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	Aminoacyl-tRNA synthetase, Ligase, RNA-binding, tRNA-binding
Biological process	Protein biosynthesis
Ligand	ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAⁱ	6.1.1.10 2681
Reactomeⁱ	R-HSA-2408517 SeMet incorporation into proteins R-HSA-379716 Cytosolic tRNA aminoacylation
SignaLinkⁱ	P56192
SIGNORⁱ	P56192

Protein family/group databases

MoonProtⁱ	P56192

MoonProtⁱ

P56192

Names & Taxonomyⁱ

Protein namesⁱ	Recommended name: Methionine--tRNA ligase, cytoplasmic (EC:6.1.1.101 Publication) Alternative name(s): Methionyl-tRNA synthetase Short name: MetRS
Gene namesⁱ	Name:MARS
Organismⁱ	Homo sapiens (Human)
Taxonomic identifierⁱ	9606 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo
Proteomesⁱ	UP000005640 Componentⁱ: Chromosome 12

Organism-specific databases

EuPathDBⁱ	HostDB:ENSG00000166986.12
Human Gene Nomenclature Database More...HGNCⁱ	HGNC:6898 MARS
MIMⁱ	156560 gene
neXtProtⁱ	NX_P56192

Keywords - Cellular componentⁱ

Cytoplasm

Pathology & Biotechⁱ

Involvement in diseaseⁱ

Interstitial lung and liver disease (ILLD)2 Publications

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionAn autosomal recessive, life-threatening disorder characterized by respiratory insufficiency and progressive liver disease with onset in infancy or early childhood. Clinical features include failure to thrive, hypotonia, intermittent lactic acidosis, aminoaciduria, hypothyroidism, interstitial lung disease, pulmonary alveolar proteinosis, anemia, and liver canalicular cholestasis, steatosis, and iron deposition.

Feature key	Position(s)	DescriptionActions	Length
Natural variantⁱVAR_075361	344	Y → C in ILLD; when assayed in yeast, induces a slight growth retardation and reduction in methionine incorporation; may interfere with efficient substrate binding. 1 PublicationCorresponds to variant dbSNP:rs766466297EnsemblClinVar.	1
Natural variantⁱVAR_070872	370	F → L in ILLD. 1 PublicationCorresponds to variant dbSNP:rs140467171EnsemblClinVar.	1
Natural variantⁱVAR_075362	393	A → T in ILLD; may act as a disease modifier aggravating the phenotype; found in patients that carried additional mutations C-344 and/or L-567; when assayed in yeast, does not exhibit any phenotype; when assayed in yeast in association with L-567, increases L-567-induced growth retardation and reduction in methionine incorporation. 1 PublicationCorresponds to variant dbSNP:rs141340466EnsemblClinVar.	1
Natural variantⁱVAR_070873	523	I → T in ILLD. 1 PublicationCorresponds to variant dbSNP:rs201555303EnsemblClinVar.	1
Natural variantⁱVAR_075363	567	S → L in ILLD; when assayed in yeast, reduces methionine incorporation; when assayed in yeast in association with T-393, induces growth retardation and strong reduction in methionine incorporation; may interfere with efficient substrate binding. 1 PublicationCorresponds to variant dbSNP:rs143592405EnsemblClinVar.	1
Natural variantⁱVAR_075364	605	D → V in ILLD; when assayed in yeast, induces a slight growth retardation and reduction in methionine incorporation; may interfere with efficient substrate binding. 1 PublicationCorresponds to variant dbSNP:rs756021768EnsemblClinVar.	1

Charcot-Marie-Tooth disease 2U (CMT2U)2 Publications

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionAn axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. CMT2U is a slowly progressive, autosomal dominant form characterized by late-adult onset.

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Natural variantⁱVAR_073377	618	R → C in CMT2U; loss of function mutation. 1 PublicationCorresponds to variant dbSNP:rs587777718EnsemblClinVar.		1
Natural variantⁱVAR_073378	800	P → T in CMT2U. 1 PublicationCorresponds to variant dbSNP:rs781249411EnsemblClinVar.		1

Mutagenesis

Feature key	Position(s)	DescriptionActions	Length
Mutagenesisⁱ	64	A → R: Loss of interaction with EEF1E1. 1 Publication	1
Mutagenesisⁱ	86	E → R: Loss of interaction with EEF1E1. 1 Publication	1
Mutagenesisⁱ	857	R → A: No effect on enzyme activity. 1 Publication	1
Mutagenesisⁱ	860	K → A: Strongly decreased affinity for tRNA. 1 Publication	1
Mutagenesisⁱ	863	K → A: Slightly decreased enzyme activity. 1 Publication	1
Mutagenesisⁱ	866	K → A: Slightly decreased enzyme activity. 1 Publication	1
Mutagenesisⁱ	880	K → A: Strongly decreased affinity for tRNA. 1 Publication	1

Keywords - Diseaseⁱ

Charcot-Marie-Tooth disease, Disease mutation, Neurodegeneration, Neuropathy

Organism-specific databases

DisGeNET More...DisGeNETⁱ	4141
MalaCards human disease database More...MalaCardsⁱ	MARS
MIMⁱ	615486 phenotype 616280 phenotype
Open Targets More...OpenTargetsⁱ	ENSG00000166986
Orphanetⁱ	397735 Autosomal dominant Charcot-Marie-Tooth disease type 2U 401835 Autosomal recessive spastic paraplegia type 70 440427 Severe early-onset pulmonary alveolar proteinosis due to MARS deficiency
PharmGKBⁱ	PA30642

Chemistry databases

ChEMBLⁱ	CHEMBL2870
Drug and drug target database More...DrugBankⁱ	DB00134 L-Methionine

Polymorphism and mutation databases

BioMutaⁱ	MARS
DMDMⁱ	20178332

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
ChainⁱPRO_0000139262	1 – 900	Methionine--tRNA ligase, cytoplasmicAdd BLAST		900

Amino acid modifications

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Modified residueⁱ	825	PhosphoserineBy similarity		1
Modified residueⁱ	835	PhosphothreonineBy similarity		1

Keywords - PTMⁱ

Phosphoprotein

Proteomic databases

EPDⁱ	P56192
MaxQB - The MaxQuant DataBase More...MaxQBⁱ	P56192
PaxDbⁱ	P56192
PeptideAtlas More...PeptideAtlasⁱ	P56192
PRIDEⁱ	P56192
ProteomicsDBⁱ	56902

PTM databases

CarbonylDBⁱ	P56192
iPTMnetⁱ	P56192
PhosphoSitePlusⁱ	P56192
SwissPalmⁱ	P56192

Expressionⁱ

Gene expression databases

Bgeeⁱ	ENSG00000166986 Expressed in 239 organ(s), highest expression level in cerebellar hemisphere
CleanExⁱ	HS_MARS
ExpressionAtlasⁱ	P56192 baseline and differential
Genevisibleⁱ	P56192 HS

Organism-specific databases

Human Protein Atlas More...HPAⁱ	CAB017097 HPA004125

HPAⁱ

CAB017097
HPA004125

Interactionⁱ

Subunit structureⁱ

Monomer (PubMed:11714285). Part of a multisubunit complex that groups tRNA ligases for Arg (RARS), Asp (DARS), Gln (QARS), Ile (IARS), Leu (LARS), Lys (KARS), Met (MARS) the bifunctional ligase for Glu and Pro (EPRS) and the auxiliary subunits AIMP1/p43, AIMP2/p38 and EEF1E1/p18 (PubMed:19131329, PubMed:19289464, Ref. 23, PubMed:26472928). Forms a linear complex that contains MARS, EEF1E1, EPRS and AIMP2 that is at the core of the multisubunit complex (PubMed:26472928).5 Publications

Protein-protein interaction databases

BioGridⁱ	110311, 157 interactors
CORUMⁱ	P56192
Database of interacting proteins More...DIPⁱ	DIP-38164N
IntActⁱ	P56192, 30 interactors
Molecular INTeraction database More...MINTⁱ	P56192
STRINGⁱ	9606.ENSP00000262027

Chemistry databases

BindingDBⁱ

P56192

Structureⁱ

Secondary structure

Legend: HelixTurnBeta strandPDB Structure known for this area

Feature key	Position(s)	DescriptionActions	Length
Beta strandⁱ	2 – 5	Combined sources	4
Helixⁱ	12 – 18	Combined sources	7
Helixⁱ	19 – 22	Combined sources	4
Turnⁱ	23 – 25	Combined sources	3
Beta strandⁱ	29 – 32	Combined sources	4
Beta strandⁱ	48 – 52	Combined sources	5
Helixⁱ	62 – 72	Combined sources	11
Helixⁱ	79 – 90	Combined sources	12
Helixⁱ	92 – 104	Combined sources	13
Helixⁱ	111 – 114	Combined sources	4
Helixⁱ	115 – 117	Combined sources	3
Helixⁱ	118 – 130	Combined sources	13
Beta strandⁱ	131 – 140	Combined sources	10
Helixⁱ	143 – 156	Combined sources	14
Helixⁱ	159 – 161	Combined sources	3
Helixⁱ	167 – 177	Combined sources	11
Helixⁱ	180 – 190	Combined sources	11
Helixⁱ	194 – 198	Combined sources	5
Helixⁱ	199 – 202	Combined sources	4
Helixⁱ	230 – 241	Combined sources	12
Helixⁱ	243 – 246	Combined sources	4
Beta strandⁱ	265 – 270	Combined sources	6
Helixⁱ	281 – 286	Combined sources	6
Helixⁱ	288 – 300	Combined sources	13
Beta strandⁱ	304 – 312	Combined sources	9
Helixⁱ	316 – 324	Combined sources	9
Helixⁱ	329 – 346	Combined sources	18
Beta strandⁱ	352 – 357	Combined sources	6
Helixⁱ	360 – 374	Combined sources	15
Turnⁱ	375 – 377	Combined sources	3
Beta strandⁱ	379 – 389	Combined sources	11
Turnⁱ	390 – 393	Combined sources	4
Helixⁱ	398 – 400	Combined sources	3
Beta strandⁱ	401 – 404	Combined sources	4
Turnⁱ	406 – 408	Combined sources	3
Beta strandⁱ	413 – 417	Combined sources	5
Turnⁱ	419 – 421	Combined sources	3
Helixⁱ	427 – 429	Combined sources	3
Beta strandⁱ	431 – 435	Combined sources	5
Turnⁱ	436 – 438	Combined sources	3
Beta strandⁱ	443 – 452	Combined sources	10
Helixⁱ	454 – 468	Combined sources	15
Helixⁱ	476 – 488	Combined sources	13
Beta strandⁱ	496 – 498	Combined sources	3
Beta strandⁱ	500 – 502	Combined sources	3
Helixⁱ	517 – 520	Combined sources	4
Turnⁱ	521 – 523	Combined sources	3
Helixⁱ	524 – 532	Combined sources	9
Turnⁱ	534 – 536	Combined sources	3
Helixⁱ	537 – 540	Combined sources	4
Turnⁱ	543 – 545	Combined sources	3
Beta strandⁱ	546 – 553	Combined sources	8
Helixⁱ	554 – 556	Combined sources	3
Helixⁱ	557 – 561	Combined sources	5
Helixⁱ	563 – 571	Combined sources	9
Beta strandⁱ	578 – 584	Combined sources	7
Beta strandⁱ	587 – 589	Combined sources	3
Turnⁱ	596 – 599	Combined sources	4
Turnⁱ	604 – 606	Combined sources	3
Helixⁱ	607 – 610	Combined sources	4
Helixⁱ	614 – 623	Combined sources	10
Beta strandⁱ	627 – 629	Combined sources	3
Beta strandⁱ	631 – 633	Combined sources	3
Helixⁱ	635 – 645	Combined sources	11
Turnⁱ	646 – 649	Combined sources	4
Helixⁱ	650 – 664	Combined sources	15
Helixⁱ	676 – 696	Combined sources	21
Turnⁱ	697 – 699	Combined sources	3
Helixⁱ	701 – 722	Combined sources	22
Helixⁱ	724 – 727	Combined sources	4
Helixⁱ	732 – 755	Combined sources	24
Turnⁱ	756 – 759	Combined sources	4
Helixⁱ	761 – 771	Combined sources	11
Helixⁱ	775 – 778	Combined sources	4
Helixⁱ	807 – 816	Combined sources	10
Beta strandⁱ	817 – 819	Combined sources	3
Helixⁱ	838 – 861	Combined sources	24
Helixⁱ	866 – 887	Combined sources	22
Beta strandⁱ	893 – 895	Combined sources	3
Beta strandⁱ	897 – 899	Combined sources	3

Show more details

3D structure databases

ProteinModelPortalⁱ	P56192
SMRⁱ	P56192
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Miscellaneous databases

EvolutionaryTraceⁱ	P56192

EvolutionaryTraceⁱ

P56192

Family & Domainsⁱ

Domains and Repeats

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Domainⁱ	74 – 198	GST C-terminalAdd BLAST		125
Domainⁱ	841 – 897	WHEP-TRSAdd BLAST		57

Motif

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Motifⁱ	273 – 283	"HIGH" regionAdd BLAST		11
Motifⁱ	593 – 597	"KMSKS" region		5

Sequence similaritiesⁱ

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

Phylogenomic databases

eggNOGⁱ	KOG0867 Eukaryota KOG1247 Eukaryota COG0143 LUCA
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00550000075017
HOGENOMⁱ	HOG000200402
HOVERGENⁱ	HBG036191
InParanoidⁱ	P56192
KEGG Orthology (KO) More...KOⁱ	K01874
OMAⁱ	HAVHSEV
Database of Orthologous Groups More...OrthoDBⁱ	EOG091G020Y
PhylomeDBⁱ	P56192
TreeFamⁱ	TF300526

Family and domain databases

Conserved Domains Database More...CDDⁱ	cd00814 MetRS_core, 1 hit
Gene3Dⁱ	2.20.28.20, 1 hit 3.40.50.620, 1 hit
HAMAPⁱ	MF_00098 Met_tRNA_synth_type1, 1 hit
InterProⁱ	View protein in InterPro IPR001412 aa-tRNA-synth_I_CS IPR010987 Glutathione-S-Trfase_C-like IPR036282 Glutathione-S-Trfase_C_sf IPR004046 GST_C IPR023458 Met-tRNA_ligase_1 IPR014758 Met-tRNA_synth IPR015413 Methionyl/Leucyl_tRNA_Synth IPR033911 MetRS_core IPR029038 MetRS_Zn IPR014729 Rossmann-like_a/b/a_fold IPR009068 S15_NS1_RNA-bd IPR009080 tRNAsynth_Ia_anticodon-bd IPR000738 WHEP-TRS_dom
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF00043 GST_C, 1 hit PF09334 tRNA-synt_1g, 1 hit PF00458 WHEP-TRS, 1 hit
PRINTSⁱ	PR01041 TRNASYNTHMET
SMARTⁱ	View protein in SMART SM00991 WHEP-TRS, 1 hit
SUPFAMⁱ	SSF47060 SSF47060, 1 hit SSF47323 SSF47323, 1 hit SSF47616 SSF47616, 1 hit SSF57770 SSF57770, 1 hit
TIGRFAMsⁱ	TIGR00398 metG, 1 hit
PROSITEⁱ	View protein in 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

Sequences (2+)ⁱ

Sequence statusⁱ: Complete.

This entry describes 2 isoformsⁱ produced by alternative splicing. Align Add to basket

This entry has 2 described isoforms and 12 potential isoforms that are computationally mapped.Show all Align All

Isoform 1 (identifier: P56192-1) [UniParc]FASTA Add to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MRLFVSDGVP GCLPVLAAAG RARGRAEVLI STVGPEDCVV PFLTRPKVPV 
        60         70         80         90        100
LQLDSGNYLF STSAICRYFF LLSGWEQDDL TNQWLEWEAT ELQPALSAAL 
       110        120        130        140        150
YYLVVQGKKG EDVLGSVRRA LTHIDHSLSR QNCPFLAGET ESLADIVLWG 
       160        170        180        190        200
ALYPLLQDPA YLPEELSALH SWFQTLSTQE PCQRAAETVL KQQGVLALRP 
       210        220        230        240        250
YLQKQPQPSP AEGRAVTNEP EEEELATLSE EEIAMAVTAW EKGLESLPPL 
       260        270        280        290        300
RPQQNPVLPV AGERNVLITS ALPYVNNVPH LGNIIGCVLS ADVFARYSRL 
       310        320        330        340        350
RQWNTLYLCG TDEYGTATET KALEEGLTPQ EICDKYHIIH ADIYRWFNIS 
       360        370        380        390        400
FDIFGRTTTP QQTKITQDIF QQLLKRGFVL QDTVEQLRCE HCARFLADRF 
       410        420        430        440        450
VEGVCPFCGY EEARGDQCDK CGKLINAVEL KKPQCKVCRS CPVVQSSQHL 
       460        470        480        490        500
FLDLPKLEKR LEEWLGRTLP GSDWTPNAQF ITRSWLRDGL KPRCITRDLK 
       510        520        530        540        550
WGTPVPLEGF EDKVFYVWFD ATIGYLSITA NYTDQWERWW KNPEQVDLYQ 
       560        570        580        590        600
FMAKDNVPFH SLVFPCSALG AEDNYTLVSH LIATEYLNYE DGKFSKSRGV 
       610        620        630        640        650
GVFGDMAQDT GIPADIWRFY LLYIRPEGQD SAFSWTDLLL KNNSELLNNL 
       660        670        680        690        700
GNFINRAGMF VSKFFGGYVP EMVLTPDDQR LLAHVTLELQ HYHQLLEKVR 
       710        720        730        740        750
IRDALRSILT ISRHGNQYIQ VNEPWKRIKG SEADRQRAGT VTGLAVNIAA 
       760        770        780        790        800
LLSVMLQPYM PTVSATIQAQ LQLPPPACSI LLTNFLCTLP AGHQIGTVSP 
       810        820        830        840        850
LFQKLENDQI ESLRQRFGGG QAKTSPKPAV VETVTTAKPQ QIQALMDEVT 
       860        870        880        890        900
KQGNIVRELK AQKADKNEVA AEVAKLLDLK KQLAVAEGKP PEAPKGKKKK

Length:900

Mass (Da):101,116

Last modified:April 16, 2002 - v2

Checksum:ⁱ3D687C77E17C5C96

GO

Isoform 2 (identifier: P56192-2) [UniParc]FASTA Add to basket

The sequence of this isoform differs from the canonical sequence as follows:
546-546: V → P
547-900: Missing.

« Hide

        10         20         30         40         50
MRLFVSDGVP GCLPVLAAAG RARGRAEVLI STVGPEDCVV PFLTRPKVPV 
        60         70         80         90        100
LQLDSGNYLF STSAICRYFF LLSGWEQDDL TNQWLEWEAT ELQPALSAAL 
       110        120        130        140        150
YYLVVQGKKG EDVLGSVRRA LTHIDHSLSR QNCPFLAGET ESLADIVLWG 
       160        170        180        190        200
ALYPLLQDPA YLPEELSALH SWFQTLSTQE PCQRAAETVL KQQGVLALRP 
       210        220        230        240        250
YLQKQPQPSP AEGRAVTNEP EEEELATLSE EEIAMAVTAW EKGLESLPPL 
       260        270        280        290        300
RPQQNPVLPV AGERNVLITS ALPYVNNVPH LGNIIGCVLS ADVFARYSRL 
       310        320        330        340        350
RQWNTLYLCG TDEYGTATET KALEEGLTPQ EICDKYHIIH ADIYRWFNIS 
       360        370        380        390        400
FDIFGRTTTP QQTKITQDIF QQLLKRGFVL QDTVEQLRCE HCARFLADRF 
       410        420        430        440        450
VEGVCPFCGY EEARGDQCDK CGKLINAVEL KKPQCKVCRS CPVVQSSQHL 
       460        470        480        490        500
FLDLPKLEKR LEEWLGRTLP GSDWTPNAQF ITRSWLRDGL KPRCITRDLK 
       510        520        530        540 
WGTPVPLEGF EDKVFYVWFD ATIGYLSITA NYTDQWERWW KNPEQP

Note: No experimental confirmation available.

Show »

Length:546

Mass (Da):61,816

Checksum:ⁱED19F00468D3C6AB

GO

Computationally mapped potential isoform sequencesⁱ

There are 12 potential isoforms mapped to this entry.BLAST Align Show all Add to basket

	Entry	Entry name	Protein names	Gene names	Length	Annotation

	H0YHV5	H0YHV5_HUMAN	Methionine--tRNA ligase, cytoplasmi... Methionine--tRNA ligase, cytoplasmic	MARS	233	Annotation score:
	H0YIP0	H0YIP0_HUMAN	Methionine--tRNA ligase, cytoplasmi... Methionine--tRNA ligase, cytoplasmic	MARS	219	Annotation score:
	H0YI27	H0YI27_HUMAN	Methionine--tRNA ligase, cytoplasmi... Methionine--tRNA ligase, cytoplasmic	MARS	124	Annotation score:
	H0YI94	H0YI94_HUMAN	Methionine--tRNA ligase, cytoplasmi... Methionine--tRNA ligase, cytoplasmic	MARS	119	Annotation score:
	H0YIC2	H0YIC2_HUMAN	Methionine--tRNA ligase, cytoplasmi... Methionine--tRNA ligase, cytoplasmic	MARS	58	Annotation score:
	H0YHL6	H0YHL6_HUMAN	Methionine--tRNA ligase, cytoplasmi... Methionine--tRNA ligase, cytoplasmic	MARS	81	Annotation score:
	F5H2V6	F5H2V6_HUMAN	Methionine--tRNA ligase, cytoplasmi... Methionine--tRNA ligase, cytoplasmic	MARS	140	Annotation score:
	F8W0M7	F8W0M7_HUMAN	Methionine--tRNA ligase, cytoplasmi... Methionine--tRNA ligase, cytoplasmic	MARS	95	Annotation score:
	F8VZZ9	F8VZZ9_HUMAN	Methionine--tRNA ligase, cytoplasmi... Methionine--tRNA ligase, cytoplasmic	MARS	114	Annotation score:
	F8W0S4	F8W0S4_HUMAN	Methionine--tRNA ligase, cytoplasmi... Methionine--tRNA ligase, cytoplasmic	MARS	110	Annotation score:
There are more potential isoformsShow all

Experimental Info

Feature key	Position(s)	DescriptionActions	Length
Sequence conflictⁱ	53	L → V in CAA64381 (PubMed:8921912).Curated	1
Sequence conflictⁱ	99	A → P in CAA64381 (PubMed:8921912).Curated	1
Sequence conflictⁱ	152	L → Q in CAA64381 (PubMed:8921912).Curated	1
Sequence conflictⁱ	172	W → S in AAH15011 (PubMed:15489334).Curated	1
Sequence conflictⁱ	250	L → P in BAD96487 (Ref. 5) Curated	1
Sequence conflictⁱ	683	A → G in CAA64381 (PubMed:8921912).Curated	1
Sequence conflictⁱ	683	A → G in CAA89153 (PubMed:8921912).Curated	1

Natural variant

Feature key	Position(s)	DescriptionActions	Length
Natural variantⁱVAR_077848	5	V → M Found in a patient with spastic paraplegia; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs587777227EnsemblClinVar.	1
Natural variantⁱVAR_075360	206	P → L1 PublicationCorresponds to variant dbSNP:rs138776588EnsemblClinVar.	1
Natural variantⁱVAR_075361	344	Y → C in ILLD; when assayed in yeast, induces a slight growth retardation and reduction in methionine incorporation; may interfere with efficient substrate binding. 1 PublicationCorresponds to variant dbSNP:rs766466297EnsemblClinVar.	1
Natural variantⁱVAR_070872	370	F → L in ILLD. 1 PublicationCorresponds to variant dbSNP:rs140467171EnsemblClinVar.	1
Natural variantⁱVAR_075362	393	A → T in ILLD; may act as a disease modifier aggravating the phenotype; found in patients that carried additional mutations C-344 and/or L-567; when assayed in yeast, does not exhibit any phenotype; when assayed in yeast in association with L-567, increases L-567-induced growth retardation and reduction in methionine incorporation. 1 PublicationCorresponds to variant dbSNP:rs141340466EnsemblClinVar.	1
Natural variantⁱVAR_070873	523	I → T in ILLD. 1 PublicationCorresponds to variant dbSNP:rs201555303EnsemblClinVar.	1
Natural variantⁱVAR_075363	567	S → L in ILLD; when assayed in yeast, reduces methionine incorporation; when assayed in yeast in association with T-393, induces growth retardation and strong reduction in methionine incorporation; may interfere with efficient substrate binding. 1 PublicationCorresponds to variant dbSNP:rs143592405EnsemblClinVar.	1
Natural variantⁱVAR_075364	605	D → V in ILLD; when assayed in yeast, induces a slight growth retardation and reduction in methionine incorporation; may interfere with efficient substrate binding. 1 PublicationCorresponds to variant dbSNP:rs756021768EnsemblClinVar.	1
Natural variantⁱVAR_073377	618	R → C in CMT2U; loss of function mutation. 1 PublicationCorresponds to variant dbSNP:rs587777718EnsemblClinVar.	1
Natural variantⁱVAR_020459	683	A → D. Corresponds to variant dbSNP:rs1054403Ensembl.	1
Natural variantⁱVAR_077849	702	R → W Found in a patient with spastic paraplegia; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs587777228EnsemblClinVar.	1
Natural variantⁱVAR_075365	727	R → Q1 PublicationCorresponds to variant dbSNP:rs113808165EnsemblClinVar.	1
Natural variantⁱVAR_073378	800	P → T in CMT2U. 1 PublicationCorresponds to variant dbSNP:rs781249411EnsemblClinVar.	1

Alternative sequence

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Alternative sequenceⁱVSP_056563	546	V → P in isoform 2. 1 Publication		1
Alternative sequenceⁱVSP_056564	547 – 900	Missing in isoform 2. 1 PublicationAdd BLAST		354

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	X94754 mRNA Translation: CAA64381.1 Z49216 mRNA Translation: CAA89153.1 D84224 mRNA Translation: BAA95668.1 BT007338 mRNA Translation: AAP36002.1 AK122956 mRNA Translation: BAG53819.1 AK222767 mRNA Translation: BAD96487.1 AC022506 Genomic DNA No translation available. 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
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS8942.1 [P56192-1]
PIRⁱ	JC5224
NCBI Reference Sequences More...RefSeqⁱ	NP_004981.2, NM_004990.3 [P56192-1]
UniGeneⁱ	Hs.632707

Genome annotation databases

Ensemblⁱ	ENST00000262027; ENSP00000262027; ENSG00000166986 [P56192-1] ENST00000537638; ENSP00000446168; ENSG00000166986 [P56192-2]
GeneIDⁱ	4141
KEGGⁱ	hsa:4141
UCSC genome browser More...UCSCⁱ	uc001sof.2 human [P56192-1]

Keywords - Coding sequence diversityⁱ

Alternative splicing, Polymorphism

Similar proteinsⁱ

90% Identity
50% Identity

Protein	Similar proteins		Species	Score	Length	Source
P56192	Uncharacterized protein		PIG		961	UniRef90_P56192
methionine--tRNA ligase, cytoplasmic isoform X1		BALAS		958
Uncharacterized protein		PAPAN		908
Uncharacterized protein		CERAT		905
Uncharacterized protein		COLAP		903
+29
P56192-2	MARS isoform 1		PONAB		546	UniRef90_P56192-2
MARS isoform 1		PANTR		546
UPI00045DEE5F		CHLSB		463

Protein	Similar proteins		Species	Score	Length	Source
P56192	Methionine--tRNA ligase, cytoplasmic		MOUSE		902	UniRef50_P56192
Methionine--tRNA ligase, cytoplasmic		BOVIN		898
Uncharacterized protein		PIG		961
methionine--tRNA ligase, cytoplasmic isoform X1		BALAS		958
Uncharacterized protein		PAPAN		908
+465
P56192-2	MARS isoform 1		PONAB		546	UniRef50_P56192-2
MARS isoform 1		PANTR		546
Methionine-tRNA synthetase (Fragment)		Nothobranchius korthausae		521
Uncharacterized protein (Fragment)		Cuerna arida		544
Methionine--tRNA ligase, cytoplasmic (Fragment)		ESCRO		524
+7

Cross-referencesⁱ

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	X94754 mRNA Translation: CAA64381.1 Z49216 mRNA Translation: CAA89153.1 D84224 mRNA Translation: BAA95668.1 BT007338 mRNA Translation: AAP36002.1 AK122956 mRNA Translation: BAG53819.1 AK222767 mRNA Translation: BAD96487.1 AC022506 Genomic DNA No translation available. 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
CCDSⁱ	CCDS8942.1 [P56192-1]
PIRⁱ	JC5224
RefSeqⁱ	NP_004981.2, NM_004990.3 [P56192-1]
UniGeneⁱ	Hs.632707

3D structure databases

Select the link destinations: Protein Data Bank Europe More...PDBeⁱ Protein Data Bank RCSB More...RCSB PDBⁱ Protein Data Bank Japan More...PDBjⁱ Links Updated	PDB entry	Method	Resolution (Å)	Chain	Positions	PDBsum
	2DJV	NMR	-	A	835-900	[»]
	4BL7	X-ray	1.89	A	1-224	[»]
	4BVX	X-ray	1.60	A	1-207	[»]
	4BVY	X-ray	1.99	A	1-225	[»]
	5GL7	X-ray	2.01	A	221-834	[»]
	5GOY	X-ray	2.28	A	221-834	[»]
	5Y6L	X-ray	2.90	A	1-224	[»]
ProteinModelPortalⁱ	P56192
SMRⁱ	P56192
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Protein-protein interaction databases

BioGridⁱ	110311, 157 interactors
CORUMⁱ	P56192
DIPⁱ	DIP-38164N
IntActⁱ	P56192, 30 interactors
MINTⁱ	P56192
STRINGⁱ	9606.ENSP00000262027

Chemistry databases

BindingDBⁱ	P56192
ChEMBLⁱ	CHEMBL2870
DrugBankⁱ	DB00134 L-Methionine

Protein family/group databases

MoonProtⁱ	P56192

MoonProtⁱ

P56192

PTM databases

CarbonylDBⁱ	P56192
iPTMnetⁱ	P56192
PhosphoSitePlusⁱ	P56192
SwissPalmⁱ	P56192

Polymorphism and mutation databases

BioMutaⁱ	MARS
DMDMⁱ	20178332

Proteomic databases

EPDⁱ	P56192
MaxQBⁱ	P56192
PaxDbⁱ	P56192
PeptideAtlasⁱ	P56192
PRIDEⁱ	P56192
ProteomicsDBⁱ	56902

Protocols and materials databases

The DNASU plasmid repository More...DNASUⁱ	4141
Structural Biology Knowledgebase	Search...

Genome annotation databases

Ensemblⁱ	ENST00000262027; ENSP00000262027; ENSG00000166986 [P56192-1] ENST00000537638; ENSP00000446168; ENSG00000166986 [P56192-2]
GeneIDⁱ	4141
KEGGⁱ	hsa:4141
UCSCⁱ	uc001sof.2 human [P56192-1]

Organism-specific databases

CTDⁱ	4141
DisGeNETⁱ	4141
EuPathDBⁱ	HostDB:ENSG00000166986.12
GeneCardsⁱ	MARS
HGNCⁱ	HGNC:6898 MARS
HPAⁱ	CAB017097 HPA004125
MalaCardsⁱ	MARS
MIMⁱ	156560 gene 615486 phenotype 616280 phenotype
neXtProtⁱ	NX_P56192
OpenTargetsⁱ	ENSG00000166986
Orphanetⁱ	397735 Autosomal dominant Charcot-Marie-Tooth disease type 2U 401835 Autosomal recessive spastic paraplegia type 70 440427 Severe early-onset pulmonary alveolar proteinosis due to MARS deficiency
PharmGKBⁱ	PA30642
GenAtlas: human gene database More...GenAtlasⁱ	Search...

Phylogenomic databases

eggNOGⁱ	KOG0867 Eukaryota KOG1247 Eukaryota COG0143 LUCA
GeneTreeⁱ	ENSGT00550000075017
HOGENOMⁱ	HOG000200402
HOVERGENⁱ	HBG036191
InParanoidⁱ	P56192
KOⁱ	K01874
OMAⁱ	HAVHSEV
OrthoDBⁱ	EOG091G020Y
PhylomeDBⁱ	P56192
TreeFamⁱ	TF300526

Enzyme and pathway databases

BRENDAⁱ	6.1.1.10 2681
Reactomeⁱ	R-HSA-2408517 SeMet incorporation into proteins R-HSA-379716 Cytosolic tRNA aminoacylation
SignaLinkⁱ	P56192
SIGNORⁱ	P56192

Miscellaneous databases

ChiTaRSⁱ	MARS human
EvolutionaryTraceⁱ	P56192
GeneWikiⁱ	MARS_(gene)
GenomeRNAiⁱ	4141
Protein Ontology More...PROⁱ	PR:P56192
SOURCEⁱ	Search...

Gene expression databases

Bgeeⁱ	ENSG00000166986 Expressed in 239 organ(s), highest expression level in cerebellar hemisphere
CleanExⁱ	HS_MARS
ExpressionAtlasⁱ	P56192 baseline and differential
Genevisibleⁱ	P56192 HS

Family and domain databases

CDDⁱ	cd00814 MetRS_core, 1 hit
Gene3Dⁱ	2.20.28.20, 1 hit 3.40.50.620, 1 hit
HAMAPⁱ	MF_00098 Met_tRNA_synth_type1, 1 hit
InterProⁱ	View protein in InterPro IPR001412 aa-tRNA-synth_I_CS IPR010987 Glutathione-S-Trfase_C-like IPR036282 Glutathione-S-Trfase_C_sf IPR004046 GST_C IPR023458 Met-tRNA_ligase_1 IPR014758 Met-tRNA_synth IPR015413 Methionyl/Leucyl_tRNA_Synth IPR033911 MetRS_core IPR029038 MetRS_Zn IPR014729 Rossmann-like_a/b/a_fold IPR009068 S15_NS1_RNA-bd IPR009080 tRNAsynth_Ia_anticodon-bd IPR000738 WHEP-TRS_dom
Pfamⁱ	View protein in Pfam PF00043 GST_C, 1 hit PF09334 tRNA-synt_1g, 1 hit PF00458 WHEP-TRS, 1 hit
PRINTSⁱ	PR01041 TRNASYNTHMET
SMARTⁱ	View protein in SMART SM00991 WHEP-TRS, 1 hit
SUPFAMⁱ	SSF47060 SSF47060, 1 hit SSF47323 SSF47323, 1 hit SSF47616 SSF47616, 1 hit SSF57770 SSF57770, 1 hit
TIGRFAMsⁱ	TIGR00398 metG, 1 hit
PROSITEⁱ	View protein in 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
ProtoNetⁱ	Search...

Entry informationⁱ

Entry nameⁱ	SYMC_HUMAN
Accessionⁱ	P56192Primary (citable) accession number: P56192 Secondary accession number(s): B3KVK7 , Q14895, Q53H14, Q96A15, Q96BZ0, Q9NSE0
Entry historyⁱ	Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
	Last sequence update:	April 16, 2002
	Last modified:	November 7, 2018
	This is version 197 of the entry and version 2 of the sequence. See complete history.
Entry statusⁱ	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.

Miscellaneousⁱ

Keywords - Technical termⁱ

3D-structure, Complete proteome, Reference proteome

Documents

SIMILARITY comments
Index of protein domains and families
Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations
Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations
MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
PDB cross-references
Index of Protein Data Bank (PDB) cross-references
Human chromosome 12
Human chromosome 12: entries, gene names and cross-references to MIM
Aminoacyl-tRNA synthetases
List of aminoacyl-tRNA synthetase entries

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UniProtKB - P56192 (SYMC_HUMAN)

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Methionine--tRNA ligase, cytoplasmic

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<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Sites

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GO - Biological processi

Enzyme and pathway databases

Protein family/group databases

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

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Cytosol

Cytosol

Extracellular region or secreted

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Keywords - Cellular componenti

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

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Keywords - Diseasei

Organism-specific databases

Chemistry databases

Polymorphism and mutation databases

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Amino acid modifications

Keywords - PTMi

Proteomic databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

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<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

Protein-protein interaction databases

Chemistry databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

3D structure databases

Miscellaneous databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

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<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

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Experimental Info

Natural variant

Alternative sequence

Sequence databases

Genome annotation databases

Keywords - Coding sequence diversityi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

3D structure databases

Protein-protein interaction databases

Chemistry databases

Protein family/group databases

PTM databases

Polymorphism and mutation databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Miscellaneous databases

Gene expression databases

Family and domain databases

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

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Functionⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Keywords - Cellular componentⁱ

Pathology & Biotechⁱ

Keywords - Diseaseⁱ

PTM / Processingⁱ

Keywords - PTMⁱ

Expressionⁱ

Interactionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Keywords - Coding sequence diversityⁱ

Cross-referencesⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ