Q58635 (SYP_METJA) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Proline--tRNA ligase
EC=6.1.1.15

Alternative name(s):
Prolyl-tRNA synthetase
Short name=ProRS

Gene names

Name:	proS
Ordered Locus Names:	MJ1238

Organism

Methanocaldococcus jannaschii (strain ATCC 43067 / DSM 2661 / JAL-1 / JCM 10045 / NBRC 100440) (Methanococcus jannaschii)

Taxonomic identifier

243232 [NCBI]

Taxonomic lineage

Archaea › Euryarchaeota › Methanococci › Methanococcales › Methanocaldococcaceae › Methanocaldococcus

Protein attributes

Sequence length	455 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Catalyzes the attachment of proline to tRNA(Pro) in a two-step reaction: proline is first activated by ATP to form Pro-AMP and then transferred to the acceptor end of tRNA(Pro). Can inadvertently accommodate and process non-cognate amino acids such as cysteine and alanine. Ref.2 Ref.3 Ref.4 Ref.8
Catalytic activity	ATP + L-proline + tRNA(Pro) = AMP + diphosphate + L-prolyl-tRNA(Pro). HAMAP MF_01571
Enzyme regulation	Inhibited by high concentrations of prolinamide. HAMAP MF_01571
Subunit structure	Homodimer. The dimer is functionally asymmetric: only one of the two active sites at a time is able to form prolyl-adenylate, and only one tRNA molecule binds per dimer. Ref.10 Ref.11
Subcellular location	Cytoplasm HAMAP MF_01571.
Domain	Consists of three domains: the N-terminal catalytic domain, the anticodon-binding domain and the C-terminal extension. HAMAP MF_01571
Sequence similarities	Belongs to the class-II aminoacyl-tRNA synthetase family. ProS type 3 subfamily.
Caution	Was originally (Ref.2, Ref.3 and Ref.4) thought to have both prolyl- and cysteinyl-tRNA synthetase activities (ProCysRS). However, recent biochemical and structural studies show that ProRS misaminoacylates tRNA(Pro) with cysteine but is unable to aminoacylate tRNA(Cys). These conflicting results may be due to the fact that much of the previous work was done with unfractionated tRNA. According to Ref.7, ProRS is unable to edit the misacylated Cys-tRNA(Pro) and Ala-tRNA(Pro), whereas according to Ref.5, it hydrolyzes Ala-AMP and Ala-tRNA(Pro) by 'pretransfer' and 'posttransfer' editing activities, respectively.
Biophysicochemical properties	Kinetic parameters: KM=0.28 mM for proline (at 60 degrees Celsius) Ref.4 Ref.5 Ref.6 KM=0.09 mM for cysteine (at 60 degrees Celsius)

Ontologies

Keywords
Biological process	Protein biosynthesis
Cellular component	Cytoplasm
Ligand	ATP-binding Nucleotide-binding
Molecular function	Aminoacyl-tRNA synthetase Ligase
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	prolyl-tRNA aminoacylation Inferred from electronic annotation. Source: InterPro
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW proline-tRNA ligase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 455

455

Proline--tRNA ligase HAMAP MF_01571

PRO_0000139351

Regions

Region

329 – 359

31

Interaction with tRNA By similarity

Sites

Binding site

101

1

Proline By similarity

Binding site

103

1

Proline By similarity

Binding site

132

1

ATP By similarity

Binding site

132

1

Proline By similarity

Binding site

134

1

ATP By similarity

Binding site

216

1

ATP By similarity

Binding site

219

1

ATP By similarity

Binding site

221

1

Proline By similarity

Binding site

253

1

ATP By similarity

Binding site

255

1

ATP By similarity

Secondary structure

1

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455

Helix Strand Turn

Details...

Helix

3 – 13

11

Helix

31 – 50

20

Beta strand

60 – 63

4

Helix

64 – 70

7

Beta strand

72 – 74

3

Helix

75 – 80

6

Beta strand

82 – 98

17

Beta strand

100 – 102

3

Helix

103 – 111

9

Beta strand

124 – 128

5

Turn

140 – 142

3

Beta strand

150 – 159

10

Helix

160 – 181

22

Beta strand

186 – 190

5

Beta strand

200 – 208

9

Beta strand

214 – 224

11

Helix

226 – 230

5

Beta strand

234 – 236

3

Beta strand

240 – 244

5

Beta strand

246 – 252

7

Helix

255 – 264

10

Beta strand

278 – 285

8

Helix

292 – 307

16

Beta strand

312 – 314

3

Helix

321 – 330

10

Beta strand

334 – 339

6

Helix

341 – 345

5

Beta strand

348 – 353

6

Turn

354 – 356

3

Beta strand

359 – 363

5

Helix

367 – 393

27

Beta strand

394 – 396

3

Helix

402 – 408

7

Turn

409 – 412

4

Beta strand

414 – 419

6

Helix

422 – 424

3

Helix

427 – 433

7

Beta strand

437 – 442

6

Beta strand

444 – 452

9

Sequences

	Sequence		Length	Mass (Da)
	Q58635 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 3D155A36AFE0CC3B	FASTA	455	53,309
	10 20 30 40 50 60 MEFSEWYSDI LEKAEIYDVR YPIKGCGVYL PYGFKIRRYT FEIIRNLLDE SGHDEALFPM 70 80 90 100 110 120 LIPEDLLAKE AEHIKGFEDE VYWVTHGGKT QLDVKLALRP TSETPIYYMM KLWVKVHTDL 130 140 150 160 170 180 PIKIYQIVNT FRYETKHTRP LIRLREIMTF KEAHTAHSTK EEAENQVKEA ISIYKKFFDT 190 200 210 220 230 240 LGIPYLISKR PEWDKFPGAE YTMAFDTIFP DGRTMQIATV HNLGQNFSKT FEIIFETPTG 250 260 270 280 290 300 DKDYAYQTCY GISDRVIASI IAIHGDEKGL ILPPIVAPIQ VVIVPLIFKG KEDIVMEKAK 310 320 330 340 350 360 EIYEKLKGKF RVHIDDRDIR PGRKFNDWEI KGVPLRIEVG PKDIENKKIT LFRRDTMEKF 370 380 390 400 410 420 QVDETQLMEV VEKTLNNIME NIKNRAWEKF ENFITILEDI NPDEIKNILS EKRGVILVPF 430 440 450 KEEIYNEELE EKVEATILGE TEYKGNKYIA IAKTY

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Complete genome sequence of the methanogenic archaeon, Methanococcus jannaschii." Bult C.J., White O., Olsen G.J., Zhou L., Fleischmann R.D., Sutton G.G., Blake J.A., FitzGerald L.M., Clayton R.A., Gocayne J.D., Kerlavage A.R., Dougherty B.A., Tomb J.-F., Adams M.D., Reich C.I., Overbeek R., Kirkness E.F., Weinstock K.G. , Merrick J.M., Glodek A., Scott J.L., Geoghagen N.S.M., Weidman J.F., Fuhrmann J.L., Nguyen D., Utterback T.R., Kelley J.M., Peterson J.D., Sadow P.W., Hanna M.C., Cotton M.D., Roberts K.M., Hurst M.A., Kaine B.P., Borodovsky M., Klenk H.-P., Fraser C.M., Smith H.O., Woese C.R., Venter J.C. Science 273:1058-1073(1996) [PubMed: 8688087] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 43067 / DSM 2661 / JAL-1 / JCM 10045 / NBRC 100440.
[2]	"One polypeptide with two aminoacyl-tRNA synthetase activities." Stathopoulos C., Li T., Longman R., Vothknecht U.C., Becker H.D., Ibba M., Soell D. Science 287:479-482(2000) [PubMed: 10642548] [Abstract] Cited for: PROTEIN SEQUENCE OF 1-18, FUNCTION AS A PROLYL-TRNA SYNTHETASE, PUTATIVE FUNCTION AS A CYSTEINYL-TRNA SYNTHETASE.
[3]	"Synthesis of cysteinyl-tRNA(Cys) by a genome that lacks the normal cysteine-tRNA synthetase." Lipman R.S.A., Sowers K.R., Hou Y.-M. Biochemistry 39:7792-7798(2000) [PubMed: 10869184] [Abstract] Cited for: FUNCTION AS A PROLYL-TRNA SYNTHETASE, PUTATIVE FUNCTION AS A CYSTEINYL-TRNA SYNTHETASE, INHIBITION BY PROLINAMIDE. Strain: ATCC 43067 / DSM 2661 / JAL-1 / JCM 10045 / NBRC 100440.
[4]	"Methanococcus jannaschii prolyl-cysteinyl-tRNA synthetase possesses overlapping amino acid binding sites." Stathopoulos C., Jacquin-Becker C., Becker H.D., Li T., Ambrogelly A., Longman R., Soell D. Biochemistry 40:46-52(2001) [PubMed: 11141055] [Abstract] Cited for: FUNCTION AS A PROLYL-TRNA SYNTHETASE, PUTATIVE FUNCTION AS A CYSTEINYL-TRNA SYNTHETASE, KINETIC PARAMETERS.
[5]	"Species-specific differences in amino acid editing by class II prolyl-tRNA synthetase." Beuning P.J., Musier-Forsyth K. J. Biol. Chem. 276:30779-30785(2001) [PubMed: 11408489] [Abstract] Cited for: MISAMINOACYLATION OF TRNA(PRO) WITH ALANINE OR CYSTEINE, EDITING ACTIVITY AGAINST ALANINE, KINETIC PARAMETERS.
[6]	"Cysteine activation is an inherent in vitro property of prolyl-tRNA synthetases." Ahel I., Stathopoulos C., Ambrogelly A., Sauerwald A., Toogood H., Hartsch T., Soell D. J. Biol. Chem. 277:34743-34748(2002) [PubMed: 12130657] [Abstract] Cited for: MISAMINOACYLATION OF TRNA(PRO) WITH CYSTEINE, KINETIC PARAMETERS.
[7]	"Methanocaldococcus jannaschii prolyl-tRNA synthetase charges tRNA(Pro) with cysteine." Ambrogelly A., Ahel I., Polycarpo C., Bunjun-Srihari S., Krett B., Jacquin-Becker C., Ruan B., Koehrer C., Stathopoulos C., RajBhandary U.L., Soell D. J. Biol. Chem. 277:34749-34754(2002) [PubMed: 12130658] [Abstract] Cited for: MISAMINOACYLATION OF TRNA(PRO) WITH CYSTEINE, INABILITY TO SYNTHESIZE CYSTEINYL-TRNA(CYS), LACK OF EDITING ACTIVITY.
[8]	"Amino acid activation of a dual-specificity tRNA synthetase is independent of tRNA." Lipman R.S.A., Beuning P.J., Musier-Forsyth K., Hou Y.-M. J. Mol. Biol. 316:421-427(2002) [PubMed: 11866507] [Abstract] Cited for: FUNCTION IN CYSTEINE ACTIVATION.
[9]	"Cysteinyl-tRNA(Cys) formation in Methanocaldococcus jannaschii: the mechanism is still unknown." Ruan B., Nakano H., Tanaka M., Mills J.A., DeVito J.A., Min B., Low K.B., Battista J.R., Soell D. J. Bacteriol. 186:8-14(2004) [PubMed: 14679218] [Abstract] Cited for: INABILITY TO SYNTHESIZE CYSTEINYL-TRNA(CYS).
[10]	"Asymmetric behavior of archaeal prolyl-tRNA synthetase." Ambrogelly A., Kamtekar S., Stathopoulos C., Kennedy D., Soell D. FEBS Lett. 579:6017-6022(2005) [PubMed: 16226256] [Abstract] Cited for: SUBUNIT.
[11]	"The structural basis of cysteine aminoacylation of tRNAPro by prolyl-tRNA synthetases." Kamtekar S., Kennedy W.D., Wang J., Stathopoulos C., Soell D., Steitz T.A. Proc. Natl. Acad. Sci. U.S.A. 100:1673-1678(2003) [PubMed: 12578991] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) OF APOENZYME, SUBUNIT.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

L77117 Genomic DNA. Translation: AAB99242.1.

PIR

E64454.

RefSeq

NP_248233.1. NC_000909.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1NJ8	X-ray	3.20	A/B/C/D	2-455	[»]

ProteinModelPortal

Q58635.

SMR

Q58635. Positions 1-455.

ModBase

Search...

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

GeneID

1452134.

GenomeReviews

Gene locus MJ1238 in contig L77117_GR.

KEGG

mja:MJ_1238.

NMPDR

fig|243232.1.peg.1270.

TIGR

MJ1238.

Phylogenomic databases

HOGENOM

HBG334108.

OMA

KFAEYEL.

ProtClustDB

PRK08661.

Enzyme and pathway databases

BioCyc

MJAN243232:MJ_1238-MONOMER.

Family and domain databases

HAMAP

MF_01571. Pro_tRNA_synth_type3.
[Tree]

InterPro

IPR002314. aa-tRNA-synt_IIb_cons-dom.
IPR006195. aa-tRNA-synth_II.
IPR004154. Anticodon-bd.
IPR002316. Pro-tRNA-synth_IIa.
IPR004499. Pro-tRNA-synth_IIa_arc-type.
IPR017449. Pro-tRNA_synth_II.
IPR015264. Pro-tRNA_synth_II_arc.
IPR016061. Pro-tRNA_synth_II_C.
[Graphical view]

Gene3D

G3DSA:3.40.50.800. Anticodon_bd. 1 hit.
G3DSA:3.30.110.30. Pro-tRNA-synth_II_C_arc/euk. 1 hit.

KO

K01881.

PANTHER

PTHR11451:SF6. ProS_fam_I. 1 hit.

Pfam

PF03129. HGTP_anticodon. 1 hit.
PF09181. ProRS-C_2. 1 hit.
PF00587. tRNA-synt_2b. 1 hit.
[Graphical view]

PRINTS

PR01046. TRNASYNTHPRO.

SUPFAM

SSF52954. Anticodon_bd. 1 hit.
SSF64586. Pro-tRNA_synth_II_C. 1 hit.

TIGRFAMs

TIGR00408. ProS_fam_I. 1 hit.

PROSITE

PS50862. AA_TRNA_LIGASE_II. 1 hit.
[Graphical view]

ProtoNet

Search...

Entry information

Entry name

SYP_METJA

Accession

Primary (citable) accession number: Q58635

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1996
Last modified:	January 25, 2012
This is version 88 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program