Reviewed, UniProtKB/Swiss-Prot P54577 (SYYC_HUMAN)

Names and origin

Protein names

Recommended name:
    Tyrosyl-tRNA synthetase, cytoplasmic
    EC=6.1.1.1
Alternative name(s):
    Tyrosyl--tRNA ligase
      Short name=TyrRS

Gene names

Name:

YARS

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › 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.8
Subcellular location	Cytoplasm. Ref.10
Involvement in disease	Defects in YARS are the cause of Charcot-Marie-Tooth disease dominant intermediate type C (CMTDIC) [MIM:608323]. CMTDIC is a form of Charcot-Marie-Tooth disease 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. Ref.10
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 Direct protein sequencing
Gene Ontology (GO)
Biological process	apoptosis Traceable author statement. Source: ProtInc tyrosyl-tRNA aminoacylation Ref.2 Traceable author statement. Source: ProtInc
Cellular component	cytoplasm Ref.2 Traceable author statement. Source: ProtInc extracellular space Traceable author statement. Source: ProtInc soluble fraction Ref.2 Traceable author statement. Source: ProtInc
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW interleukin-8 receptor binding Traceable author statement. Source: ProtInc signal transducer activity Non-traceable author statement. Source: ProtInc tRNA binding Inferred from electronic annotation. Source: UniProtKB-KW tyrosine-tRNA ligase activity Ref.2 Traceable author statement. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ARF6	P62330	1	EBI-1048893,EBI-638181
EIF1B	O60739	1	EBI-1048893,EBI-1043343
EIF6	P56537	1	EBI-1048893,EBI-372243
SAP18	O00422	1	EBI-1048893,EBI-1044156

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.5 Ref.6

Chain

2 – 528

527

Tyrosyl-tRNA synthetase, 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.6

Natural variations

Natural variant

41

1

G → R in CMTDIC; partial loss of activity. Ref.10

VAR_026681

Natural variant

153 – 156

4

Missing in CMTDIC.

VAR_026682

Natural variant

170

1

Q → H: dbSNP rs2128600.

VAR_026683

Natural variant

196

1

E → K in CMTDIC; partial loss of activity. Ref.10

VAR_026684

Experimental info

Sequence conflict

143

1

H → R in BAD97328. Ref.3

Secondary structure

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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

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

Sequences

	Sequence		Length	Mass (Da)
	P54577-1 [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: 8552597] [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: 9162081] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	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].
[4]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Bone and Lung.
[5]	"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: 12665801] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-16. Tissue: Platelet.
[6]	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.
[7]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[8]	"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: 12427973] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.18 ANGSTROMS) OF 1-342, SUBUNIT.
[9]	"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: 14671330] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 1-364 IN COMPLEX WITH TYROSINE.
[10]	"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: 16429158] [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

EMBLGenBankDDBJ

U40714 mRNA. Translation: AAB39406.1. Frameshift.
U89436 mRNA. Translation: AAB88409.1.
AK223608 mRNA. Translation: BAD97328.1.
BC001933 mRNA. Translation: AAH01933.1.
BC004151 mRNA. Translation: AAH04151.1.
BC016689 mRNA. Translation: AAH16689.1.

IPI

IPI00007074.

RefSeq

NP_003671.1.

UniGene

Hs.706890

3D structure databases

PDBPDBe

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	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P54577. 8 interactions.

PTM databases

PhosphoSite

P54577.

2-D gel databases

REPRODUCTION-2DPAGE

IPI00007074.

Proteomic databases

PeptideAtlas

P54577.

PRIDE

P54577.

Genome annotation databases

Ensembl

ENSG00000134684. Homo sapiens. [Contig view]

GeneID

8565.

KEGG

hsa:8565.

NMPDR

fig|9606.3.peg.778.

Organism-specific databases

GeneCards

GC01M033013.

H-InvDB

HIX0000381.

HGNC

HGNC:12840. YARS.

HPA

HPA017936.
HPA018954.

MIM

603623. gene.
608323. phenotype.

Orphanet

90114. Autosomal dominant intermediate Charcot-Marie-Tooth disease.
100045. Autosomal dominant intermediate Charcot-Marie-Tooth disease, type C.

PharmGKB

PA37431.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P54577.

HOVERGEN

P54577.

OMA

P54577. LCASIEG.

Enzyme and pathway databases

BRENDA

6.1.1.1. 247.

Gene expression databases

ArrayExpress

P54577.

Bgee

P54577.

CleanEx

HS_YARS.

GermOnline

ENSG00000134684. Homo sapiens.

Family and domain databases

InterPro

IPR001412. aa-tRNA-synth_I_CS.
IPR002305. aa-tRNA-synth_Ib.
IPR012340. NA-bd_OB-fold.
IPR014729. Rossmann-like_a/b/a_fold.
IPR002547. tRNA_bd.
IPR015624. Tyr-tRNA-synth_Ib_arc/euk.
IPR002307. Tyr-tRNA-synth_Ib_bac/mito.
[Graphical view]

Gene3D

G3DSA:2.40.50.140. OB_NA_bd_sub. 1 hit.
G3DSA:3.40.50.620. Rossmann-like_a/b/a_fold. 1 hit.

PANTHER

PTHR11946:SF8. Tyr-tRNA_synth. 1 hit.

Pfam

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

PRINTS

PR01040. TRNASYNTHTYR.

TIGRFAMs

TIGR00234. tyrS. 1 hit.

PROSITE

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

ProtoNet

Search...

Other Resources

DrugBank

DB00135. L-Tyrosine.

NextBio

32113.

PMAP-CutDB

P54577.

SOURCE

Search...

Entry information

Entry name

SYYC_HUMAN

Accession

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

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	January 23, 2007
Last modified:	June 16, 2009
This is version 101 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)