P54577 (SYYC_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Tyrosine--tRNA ligase, cytoplasmic
EC=6.1.1.1

Alternative name(s):
Tyrosyl-tRNA synthetase
Short name=TyrRS

Gene names

Name:

YARS

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	528 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Catalyzes the attachment of tyrosine to tRNA(Tyr) in a two-step reaction: tyrosine is first activated by ATP to form Tyr-AMP and then transferred to the acceptor end of tRNA(Tyr) By similarity.
Catalytic activity	ATP + L-tyrosine + tRNA(Tyr) = AMP + diphosphate + L-tyrosyl-tRNA(Tyr).
Subunit structure	Homodimer. Ref.11
Subcellular location	Cytoplasm Ref.13.
Involvement in disease	Charcot-Marie-Tooth disease, dominant, intermediate type, C (CMTDIC) [MIM:608323]: A 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. The dominant intermediate type C is characterized by clinical and pathologic features intermediate between demyelinating and axonal peripheral neuropathies, and motor median nerve conduction velocities ranging from 25 to 45 m/sec. 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 tRNA-binding domain.
Sequence caution	The sequence AAB39406.1 differs from that shown. Reason: Frameshift at position 354.

Ontologies

Keywords
Biological process	Protein biosynthesis
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Disease	Charcot-Marie-Tooth disease Disease mutation Neuropathy
Ligand	ATP-binding Nucleotide-binding RNA-binding tRNA-binding
Molecular function	Aminoacyl-tRNA synthetase Ligase
PTM	Acetylation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	apoptotic process Traceable author statement PubMed 10102815. Source: ProtInc tyrosyl-tRNA aminoacylation Traceable author statement Ref.2. Source: ProtInc
Cellular_component	cytosol Traceable author statement. Source: Reactome extracellular space Traceable author statement PubMed 10102815. Source: ProtInc nucleus Inferred from direct assay. Source: HPA
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW interleukin-8 receptor binding Traceable author statement PubMed 10102815. Source: ProtInc signal transducer activity Non-traceable author statement PubMed 10102815. Source: ProtInc tRNA binding Inferred from electronic annotation. Source: UniProtKB-KW tyrosine-tRNA ligase activity Traceable author statement. Source: Reactome
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.7 Ref.8

Chain

2 – 528

527

Tyrosine--tRNA ligase, cytoplasmic

PRO_0000055673

Regions

Domain

364 – 468

105

tRNA-binding

Motif

44 – 52

9

"HIGH" region

Motif

222 – 226

5

"KMSKS" region

Sites

Binding site

39

1

Tyrosine

Binding site

166

1

Tyrosine

Binding site

170

1

Tyrosine

Binding site

173

1

Tyrosine

Binding site

188

1

Tyrosine

Amino acid modifications

Modified residue

2

1

N-acetylglycine Ref.8

Modified residue

197

1

N6-acetyllysine Ref.9

Modified residue

206

1

N6-acetyllysine Ref.9

Modified residue

474

1

N6-acetyllysine Ref.9

Modified residue

482

1

N6-acetyllysine Ref.9

Modified residue

490

1

N6-acetyllysine Ref.9

Natural variations

Natural variant

41

1

G → R in CMTDIC; partial loss of activity. Ref.13

VAR_026681

Natural variant

153 – 156

4

Missing in CMTDIC.

VAR_026682

Natural variant

170

1

Q → H.
Corresponds to variant rs2128600 [ dbSNP | Ensembl ].

VAR_026683

Natural variant

196

1

E → K in CMTDIC; partial loss of activity. Ref.13

VAR_026684

Experimental info

Sequence conflict

143

1

H → R in BAD97328. Ref.4

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

528

Helix Strand Turn

Details...

Helix

7 – 15

9

Beta strand

19 – 22

4

Helix

24 – 31

8

Beta strand

37 – 42

6

Helix

50 – 52

3

Helix

53 – 64

12

Beta strand

68 – 73

6

Helix

75 – 80

6

Turn

81 – 84

4

Helix

87 – 108

22

Beta strand

115 – 119

5

Helix

120 – 122

3

Turn

123 – 125

3

Helix

127 – 137

11

Helix

142 – 148

7

Turn

149 – 152

4

Helix

161 – 176

16

Beta strand

180 – 185

6

Helix

186 – 188

3

Helix

189 – 198

10

Helix

199 – 202

4

Beta strand

208 – 212

5

Helix

238 – 246

9

Beta strand

247 – 249

3

Helix

259 – 266

8

Turn

267 – 273

7

Beta strand

275 – 277

3

Helix

281 – 283

3

Beta strand

287 – 291

5

Helix

292 – 300

9

Helix

306 – 327

22

Helix

331 – 340

10

Helix

365 – 367

3

Beta strand

370 – 380

11

Beta strand

388 – 393

6

Beta strand

395 – 398

4

Beta strand

400 – 405

6

Turn

407 – 409

3

Helix

412 – 414

3

Turn

415 – 417

3

Beta strand

419 – 423

5

Beta strand

429 – 431

3

Beta strand

434 – 436

3

Beta strand

442 – 454

13

Beta strand

466 – 469

4

Beta strand

479 – 481

3

Helix

483 – 485

3

Helix

487 – 492

6

Beta strand

495 – 497

3

Beta strand

501 – 505

5

Beta strand

508 – 512

5

Beta strand

526 – 528

3

Sequences

	Sequence		Length	Mass (Da)
	P54577 [UniParc]. Last modified January 23, 2007. Version 4. Checksum: 00C7E88843905780	FASTA	528	59,143
	10 20 30 40 50 60 MGDAPSPEEK LHLITRNLQE VLGEEKLKEI LKERELKIYW GTATTGKPHV AYFVPMSKIA 70 80 90 100 110 120 DFLKAGCEVT ILFADLHAYL DNMKAPWELL ELRVSYYENV IKAMLESIGV PLEKLKFIKG 130 140 150 160 170 180 TDYQLSKEYT LDVYRLSSVV TQHDSKKAGA EVVKQVEHPL LSGLLYPGLQ ALDEEYLKVD 190 200 210 220 230 240 AQFGGIDQRK IFTFAEKYLP ALGYSKRVHL MNPMVPGLTG SKMSSSEEES KIDLLDRKED 250 260 270 280 290 300 VKKKLKKAFC EPGNVENNGV LSFIKHVLFP LKSEFVILRD EKWGGNKTYT AYVDLEKDFA 310 320 330 340 350 360 AEVVHPGDLK NSVEVALNKL LDPIREKFNT PALKKLASAA YPDPSKQKPM AKGPAKNSEP 370 380 390 400 410 420 EEVIPSRLDI RVGKIITVEK HPDADSLYVE KIDVGEAEPR TVVSGLVQFV PKEELQDRLV 430 440 450 460 470 480 VVLCNLKPQK MRGVESQGML LCASIEGINR QVEPLDPPAG SAPGEHVFVK GYEKGQPDEE 490 500 510 520 LKPKKKVFEK LQADFKISEE CIAQWKQTNF MTKLGSISCK SLKGGNIS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Evidence that two present-day components needed for the genetic code appeared after nucleated cells separated from eubacteria." Ribas de Pouplana L., Frugier M., Quinn C.L., Schimmel P. Proc. Natl. Acad. Sci. U.S.A. 93:166-170(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Human tyrosyl-tRNA synthetase shares amino acid sequence homology with a putative cytokine." Kleeman T.A., Wei D., Simpson K.L., First E.A. J. Biol. Chem. 272:14420-14425(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"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. , 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]. Tissue: Brain.
[4]	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].
[5]	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. , 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].
[6]	"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: Bone and Lung.
[7]	"Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides." Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R., Vandekerckhove J. Nat. Biotechnol. 21:566-569(2003) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-16. Tissue: Platelet.
[8]	Bienvenut W.V. Submitted (OCT-2004) to UniProtKB Cited for: PROTEIN SEQUENCE OF 2-16, ACETYLATION AT GLY-2, MASS SPECTROMETRY. Tissue: B-cell lymphoma.
[9]	"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-197; LYS-206; LYS-474; LYS-482 AND LYS-490, MASS SPECTROMETRY.
[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]	"Crystal structure of a human aminoacyl-tRNA synthetase cytokine." Yang X.-L., Skene R.J., McRee D.E., Schimmel P. Proc. Natl. Acad. Sci. U.S.A. 99:15369-15374(2002) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.18 ANGSTROMS) OF 1-342, SUBUNIT.
[12]	"Crystal structures that suggest late development of genetic code components for differentiating aromatic side chains." Yang X.-L., Otero F.J., Skene R.J., McRee D.E., Schimmel P., Ribas de Pouplana L. Proc. Natl. Acad. Sci. U.S.A. 100:15376-15380(2003) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 1-364 IN COMPLEX WITH TYROSINE.
[13]	"Disrupted function and axonal distribution of mutant tyrosyl-tRNA synthetase in dominant intermediate Charcot-Marie-Tooth neuropathy." Jordanova A., Irobi J., Thomas F.P., Van Dijck P., Meerschaert K., Dewil M., Dierick I., Jacobs A., De Vriendt E., Guergueltcheva V., Rao C.V., Tournev I., Gondim F.A.A., D'Hooghe M., Van Gerwen V., Callaerts P., Van Den Bosch L., Timmermans J.-P. , Robberecht W., Gettemans J., Thevelein J.M., De Jonghe P., Kremensky I., Timmerman V. Nat. Genet. 38:197-202(2006) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, VARIANTS CMTDIC 153-VAL--VAL-156 DEL; ARG-41 AND LYS-196, CHARACTERIZATION OF VARIANTS CMTDIC ARG-41 AND LYS-196.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U40714 mRNA. Translation: AAB39406.1. Frameshift.
U89436 mRNA. Translation: AAB88409.1.
AK125213 mRNA. Translation: BAG54166.1.
AK223608 mRNA. Translation: BAD97328.1.
CH471059 Genomic DNA. Translation: EAX07506.1.
CH471059 Genomic DNA. Translation: EAX07507.1.
BC001933 mRNA. Translation: AAH01933.1.
BC004151 mRNA. Translation: AAH04151.1.
BC016689 mRNA. Translation: AAH16689.1.

IPI

IPI00007074.

RefSeq

NP_003671.1. NM_003680.3.

UniGene

Hs.213264.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1N3L	X-ray	1.18	A	1-364	[»]
1NTG	X-ray	2.21	A/B/C/D	359-528	[»]
1Q11	X-ray	1.60	A	1-364	[»]

ProteinModelPortal

P54577.

ModBase

Search...

Protein-protein interaction databases

IntAct

P54577. 1 interaction.

STRING

9606.ENSP00000362576.

PTM databases

PhosphoSite

P54577.

Polymorphism databases

DMDM

13638438.

2D gel databases

REPRODUCTION-2DPAGE

IPI00007074.

Proteomic databases

PaxDb

P54577.

PeptideAtlas

P54577.

PRIDE

P54577.

Protocols and materials databases

DNASU

8565.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000373477; ENSP00000362576; ENSG00000134684.

GeneID

8565.

KEGG

hsa:8565.

UCSC

uc001bvy.1. human.

Organism-specific databases

CTD

8565.

GeneCards

GC01M033240.

HGNC

HGNC:12840. YARS.

HPA

HPA017936.
HPA018950.
HPA018954.

MIM

603623. gene.
608323. phenotype.

neXtProt

NX_P54577.

Orphanet

100045. Autosomal dominant intermediate Charcot-Marie-Tooth disease type C.

PharmGKB

PA37431.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0162.

HOGENOM

HOG000228237.

HOVERGEN

HBG080113.

InParanoid

P54577.

KO

K01866.

OMA

QKMRGVE.

OrthoDB

EOG4RV2R7.

PhylomeDB

P54577.

Enzyme and pathway databases

Reactome

REACT_71. Gene Expression.

Gene expression databases

Bgee

P54577.

CleanEx

HS_YARS.

Genevestigator

P54577.

GermOnline

ENSG00000134684. Homo sapiens.

Family and domain databases

Gene3D

2.40.50.140. 1 hit.
3.40.50.620. 1 hit.

InterPro

IPR002305. aa-tRNA-synth_Ic.
IPR012340. NA-bd_OB-fold.
IPR014729. Rossmann-like_a/b/a_fold.
IPR002547. tRNA-bd_dom.
IPR002307. Tyr-tRNA-ligase.
IPR023617. Tyr-tRNA-ligase_arc/euk-type.
[Graphical view]

PANTHER

PTHR11946:SF8. PTHR11946:SF8. 1 hit.

Pfam

PF00579. tRNA-synt_1b. 1 hit.
PF01588. tRNA_bind. 1 hit.
[Graphical view]

PRINTS

PR01040. TRNASYNTHTYR.

SUPFAM

SSF50249. Nucleic_acid_OB. 1 hit.

TIGRFAMs

TIGR00234. tyrS. 1 hit.

PROSITE

PS00178. AA_TRNA_LIGASE_I. False negative.
PS50886. TRBD. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P54577.

ChEMBL

CHEMBL3179.

ChiTaRS

YARS. human.

DrugBank

DB00135. L-Tyrosine.

EvolutionaryTrace

P54577.

GenomeRNAi

8565.

NextBio

32113.

PMAP-CutDB

P54577.

SOURCE

Search...

Entry information

Entry name

SYYC_HUMAN

Accession

Primary (citable) accession number: P54577
Secondary accession number(s): B3KWK4 , D3DPQ4, O43276, Q53EN1

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	January 23, 2007
Last modified:	May 1, 2013
This is version 144 of the entry and version 4 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.