SYP_METJA
ID SYP_METJA Reviewed; 455 AA.
AC Q58635;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=Proline--tRNA ligase;
DE EC=6.1.1.15;
DE AltName: Full=Prolyl-tRNA synthetase;
DE Short=ProRS;
GN Name=proS; OrderedLocusNames=MJ1238;
OS Methanocaldococcus jannaschii (strain ATCC 43067 / DSM 2661 / JAL-1 / JCM
OS 10045 / NBRC 100440) (Methanococcus jannaschii).
OC Archaea; Euryarchaeota; Methanomada group; Methanococci; Methanococcales;
OC Methanocaldococcaceae; Methanocaldococcus.
OX NCBI_TaxID=243232;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 43067 / DSM 2661 / JAL-1 / JCM 10045 / NBRC 100440;
RX PubMed=8688087; DOI=10.1126/science.273.5278.1058;
RA Bult C.J., White O., Olsen G.J., Zhou L., Fleischmann R.D., Sutton G.G.,
RA Blake J.A., FitzGerald L.M., Clayton R.A., Gocayne J.D., Kerlavage A.R.,
RA Dougherty B.A., Tomb J.-F., Adams M.D., Reich C.I., Overbeek R.,
RA Kirkness E.F., Weinstock K.G., Merrick J.M., Glodek A., Scott J.L.,
RA Geoghagen N.S.M., Weidman J.F., Fuhrmann J.L., Nguyen D., Utterback T.R.,
RA Kelley J.M., Peterson J.D., Sadow P.W., Hanna M.C., Cotton M.D.,
RA Roberts K.M., Hurst M.A., Kaine B.P., Borodovsky M., Klenk H.-P.,
RA Fraser C.M., Smith H.O., Woese C.R., Venter J.C.;
RT "Complete genome sequence of the methanogenic archaeon, Methanococcus
RT jannaschii.";
RL Science 273:1058-1073(1996).
RN [2]
RP PROTEIN SEQUENCE OF 1-18, FUNCTION AS A PROLYL-TRNA SYNTHETASE, AND
RP PUTATIVE FUNCTION AS A CYSTEINYL-TRNA SYNTHETASE.
RX PubMed=10642548; DOI=10.1126/science.287.5452.479;
RA Stathopoulos C., Li T., Longman R., Vothknecht U.C., Becker H.D., Ibba M.,
RA Soell D.;
RT "One polypeptide with two aminoacyl-tRNA synthetase activities.";
RL Science 287:479-482(2000).
RN [3]
RP FUNCTION AS A PROLYL-TRNA SYNTHETASE, PUTATIVE FUNCTION AS A CYSTEINYL-TRNA
RP SYNTHETASE, AND INHIBITION BY PROLINAMIDE.
RC STRAIN=ATCC 43067 / DSM 2661 / JAL-1 / JCM 10045 / NBRC 100440;
RX PubMed=10869184; DOI=10.1021/bi0004955;
RA Lipman R.S.A., Sowers K.R., Hou Y.-M.;
RT "Synthesis of cysteinyl-tRNA(Cys) by a genome that lacks the normal
RT cysteine-tRNA synthetase.";
RL Biochemistry 39:7792-7798(2000).
RN [4]
RP FUNCTION AS A PROLYL-TRNA SYNTHETASE, PUTATIVE FUNCTION AS A CYSTEINYL-TRNA
RP SYNTHETASE, AND KINETIC PARAMETERS.
RX PubMed=11141055; DOI=10.1021/bi002108x;
RA Stathopoulos C., Jacquin-Becker C., Becker H.D., Li T., Ambrogelly A.,
RA Longman R., Soell D.;
RT "Methanococcus jannaschii prolyl-cysteinyl-tRNA synthetase possesses
RT overlapping amino acid binding sites.";
RL Biochemistry 40:46-52(2001).
RN [5]
RP MISAMINOACYLATION OF TRNA(PRO) WITH ALANINE OR CYSTEINE, EDITING ACTIVITY
RP AGAINST ALANINE, AND KINETIC PARAMETERS.
RX PubMed=11408489; DOI=10.1074/jbc.m104761200;
RA Beuning P.J., Musier-Forsyth K.;
RT "Species-specific differences in amino acid editing by class II prolyl-tRNA
RT synthetase.";
RL J. Biol. Chem. 276:30779-30785(2001).
RN [6]
RP MISAMINOACYLATION OF TRNA(PRO) WITH CYSTEINE, AND KINETIC PARAMETERS.
RX PubMed=12130657; DOI=10.1074/jbc.m206928200;
RA Ahel I., Stathopoulos C., Ambrogelly A., Sauerwald A., Toogood H.,
RA Hartsch T., Soell D.;
RT "Cysteine activation is an inherent in vitro property of prolyl-tRNA
RT synthetases.";
RL J. Biol. Chem. 277:34743-34748(2002).
RN [7]
RP MISAMINOACYLATION OF TRNA(PRO) WITH CYSTEINE, INABILITY TO SYNTHESIZE
RP CYSTEINYL-TRNA(CYS), AND LACK OF EDITING ACTIVITY.
RX PubMed=12130658; DOI=10.1074/jbc.m206929200;
RA Ambrogelly A., Ahel I., Polycarpo C., Bunjun-Srihari S., Krett B.,
RA Jacquin-Becker C., Ruan B., Koehrer C., Stathopoulos C., RajBhandary U.L.,
RA Soell D.;
RT "Methanocaldococcus jannaschii prolyl-tRNA synthetase charges tRNA(Pro)
RT with cysteine.";
RL J. Biol. Chem. 277:34749-34754(2002).
RN [8]
RP FUNCTION IN CYSTEINE ACTIVATION.
RX PubMed=11866507; DOI=10.1006/jmbi.2001.5373;
RA Lipman R.S.A., Beuning P.J., Musier-Forsyth K., Hou Y.-M.;
RT "Amino acid activation of a dual-specificity tRNA synthetase is independent
RT of tRNA.";
RL J. Mol. Biol. 316:421-427(2002).
RN [9]
RP INABILITY TO SYNTHESIZE CYSTEINYL-TRNA(CYS).
RX PubMed=14679218; DOI=10.1128/jb.186.1.8-14.2004;
RA Ruan B., Nakano H., Tanaka M., Mills J.A., DeVito J.A., Min B., Low K.B.,
RA Battista J.R., Soell D.;
RT "Cysteinyl-tRNA(Cys) formation in Methanocaldococcus jannaschii: the
RT mechanism is still unknown.";
RL J. Bacteriol. 186:8-14(2004).
RN [10]
RP SUBUNIT.
RX PubMed=16226256; DOI=10.1016/j.febslet.2005.09.025;
RA Ambrogelly A., Kamtekar S., Stathopoulos C., Kennedy D., Soell D.;
RT "Asymmetric behavior of archaeal prolyl-tRNA synthetase.";
RL FEBS Lett. 579:6017-6022(2005).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) OF APOENZYME, AND SUBUNIT.
RX PubMed=12578991; DOI=10.1073/pnas.0437911100;
RA Kamtekar S., Kennedy W.D., Wang J., Stathopoulos C., Soell D., Steitz T.A.;
RT "The structural basis of cysteine aminoacylation of tRNAPro by prolyl-tRNA
RT synthetases.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:1673-1678(2003).
CC -!- FUNCTION: Catalyzes the attachment of proline to tRNA(Pro) in a two-
CC step reaction: proline is first activated by ATP to form Pro-AMP and
CC then transferred to the acceptor end of tRNA(Pro). Can inadvertently
CC accommodate and process non-cognate amino acids such as cysteine and
CC alanine. {ECO:0000269|PubMed:10642548, ECO:0000269|PubMed:10869184,
CC ECO:0000269|PubMed:11141055, ECO:0000269|PubMed:11866507}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-proline + tRNA(Pro) = AMP + diphosphate + L-prolyl-
CC tRNA(Pro); Xref=Rhea:RHEA:14305, Rhea:RHEA-COMP:9700, Rhea:RHEA-
CC COMP:9702, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:60039,
CC ChEBI:CHEBI:78442, ChEBI:CHEBI:78532, ChEBI:CHEBI:456215;
CC EC=6.1.1.15;
CC -!- ACTIVITY REGULATION: Inhibited by high concentrations of prolinamide.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.28 mM for proline (at 60 degrees Celsius)
CC {ECO:0000269|PubMed:11141055, ECO:0000269|PubMed:11408489,
CC ECO:0000269|PubMed:12130657};
CC KM=0.09 mM for cysteine (at 60 degrees Celsius)
CC {ECO:0000269|PubMed:11141055, ECO:0000269|PubMed:11408489,
CC ECO:0000269|PubMed:12130657};
CC -!- SUBUNIT: Homodimer. The dimer is functionally asymmetric: only one of
CC the two active sites at a time is able to form prolyl-adenylate, and
CC only one tRNA molecule binds per dimer. {ECO:0000269|PubMed:12578991,
CC ECO:0000269|PubMed:16226256}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- DOMAIN: Consists of three domains: the N-terminal catalytic domain, the
CC anticodon-binding domain and the C-terminal extension.
CC -!- SIMILARITY: Belongs to the class-II aminoacyl-tRNA synthetase family.
CC ProS type 3 subfamily. {ECO:0000305}.
CC -!- CAUTION: Was originally (PubMed:10642548, PubMed:10869184 and
CC PubMed:11141055) thought to have both prolyl- and cysteinyl-tRNA
CC synthetase activities (ProCysRS). However, recent biochemical and
CC structural studies show that ProRS misaminoacylates tRNA(Pro) with
CC cysteine but is unable to aminoacylate tRNA(Cys). These conflicting
CC results may be due to the fact that much of the previous work was done
CC with unfractionated tRNA. {ECO:0000305}.
CC -!- CAUTION: According to PubMed:12130658, ProRS is unable to edit the
CC misacylated Cys-tRNA(Pro) and Ala-tRNA(Pro), whereas according to
CC PubMed:11408489, it hydrolyzes Ala-AMP and Ala-tRNA(Pro) by
CC 'pretransfer' and 'posttransfer' editing activities, respectively.
CC {ECO:0000305}.
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DR EMBL; L77117; AAB99242.1; -; Genomic_DNA.
DR PIR; E64454; E64454.
DR RefSeq; WP_010870750.1; NC_000909.1.
DR PDB; 1NJ8; X-ray; 3.20 A; A/B/C/D=2-455.
DR PDBsum; 1NJ8; -.
DR AlphaFoldDB; Q58635; -.
DR SMR; Q58635; -.
DR STRING; 243232.MJ_1238; -.
DR EnsemblBacteria; AAB99242; AAB99242; MJ_1238.
DR GeneID; 1452134; -.
DR KEGG; mja:MJ_1238; -.
DR eggNOG; arCOG00402; Archaea.
DR HOGENOM; CLU_001882_4_2_2; -.
DR InParanoid; Q58635; -.
DR OMA; EVYWVTH; -.
DR OrthoDB; 14454at2157; -.
DR PhylomeDB; Q58635; -.
DR BRENDA; 6.1.1.15; 3260.
DR SABIO-RK; Q58635; -.
DR EvolutionaryTrace; Q58635; -.
DR Proteomes; UP000000805; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-UniRule.
DR GO; GO:0004827; F:proline-tRNA ligase activity; IBA:GO_Central.
DR GO; GO:0006433; P:prolyl-tRNA aminoacylation; IBA:GO_Central.
DR CDD; cd00778; ProRS_core_arch_euk; 1.
DR Gene3D; 3.30.110.30; -; 1.
DR Gene3D; 3.30.930.10; -; 1.
DR Gene3D; 3.40.50.800; -; 1.
DR HAMAP; MF_01571; Pro_tRNA_synth_type3; 1.
DR InterPro; IPR002314; aa-tRNA-synt_IIb.
DR InterPro; IPR006195; aa-tRNA-synth_II.
DR InterPro; IPR045864; aa-tRNA-synth_II/BPL/LPL.
DR InterPro; IPR004154; Anticodon-bd.
DR InterPro; IPR036621; Anticodon-bd_dom_sf.
DR InterPro; IPR002316; Pro-tRNA-ligase_IIa.
DR InterPro; IPR004499; Pro-tRNA-ligase_IIa_arc-type.
DR InterPro; IPR017449; Pro-tRNA_synth_II.
DR InterPro; IPR015264; Pro-tRNA_synth_II_arc.
DR InterPro; IPR033721; ProRS_core_arch_euk.
DR PANTHER; PTHR43382; PTHR43382; 1.
DR Pfam; PF03129; HGTP_anticodon; 1.
DR Pfam; PF09181; ProRS-C_2; 1.
DR Pfam; PF00587; tRNA-synt_2b; 1.
DR PRINTS; PR01046; TRNASYNTHPRO.
DR SUPFAM; SSF55681; SSF55681; 1.
DR SUPFAM; SSF64586; SSF64586; 1.
DR TIGRFAMs; TIGR00408; proS_fam_I; 1.
DR PROSITE; PS50862; AA_TRNA_LIGASE_II; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Aminoacyl-tRNA synthetase; ATP-binding; Cytoplasm;
KW Direct protein sequencing; Ligase; Nucleotide-binding;
KW Protein biosynthesis; Reference proteome.
FT CHAIN 1..455
FT /note="Proline--tRNA ligase"
FT /id="PRO_0000139351"
FT REGION 329..359
FT /note="Interaction with tRNA"
FT /evidence="ECO:0000250"
FT BINDING 101
FT /ligand="L-proline"
FT /ligand_id="ChEBI:CHEBI:60039"
FT /evidence="ECO:0000250"
FT BINDING 103
FT /ligand="L-proline"
FT /ligand_id="ChEBI:CHEBI:60039"
FT /evidence="ECO:0000250"
FT BINDING 132
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 132
FT /ligand="L-proline"
FT /ligand_id="ChEBI:CHEBI:60039"
FT /evidence="ECO:0000250"
FT BINDING 134
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 216
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 219
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 221
FT /ligand="L-proline"
FT /ligand_id="ChEBI:CHEBI:60039"
FT /evidence="ECO:0000250"
FT BINDING 253
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 255
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT HELIX 3..13
FT /evidence="ECO:0007829|PDB:1NJ8"
FT HELIX 31..50
FT /evidence="ECO:0007829|PDB:1NJ8"
FT STRAND 60..63
FT /evidence="ECO:0007829|PDB:1NJ8"
FT HELIX 64..70
FT /evidence="ECO:0007829|PDB:1NJ8"
FT STRAND 72..74
FT /evidence="ECO:0007829|PDB:1NJ8"
FT HELIX 75..80
FT /evidence="ECO:0007829|PDB:1NJ8"
FT STRAND 82..98
FT /evidence="ECO:0007829|PDB:1NJ8"
FT STRAND 100..102
FT /evidence="ECO:0007829|PDB:1NJ8"
FT HELIX 103..111
FT /evidence="ECO:0007829|PDB:1NJ8"
FT STRAND 124..128
FT /evidence="ECO:0007829|PDB:1NJ8"
FT TURN 140..142
FT /evidence="ECO:0007829|PDB:1NJ8"
FT STRAND 150..159
FT /evidence="ECO:0007829|PDB:1NJ8"
FT HELIX 160..181
FT /evidence="ECO:0007829|PDB:1NJ8"
FT STRAND 186..190
FT /evidence="ECO:0007829|PDB:1NJ8"
FT STRAND 200..208
FT /evidence="ECO:0007829|PDB:1NJ8"
FT STRAND 214..224
FT /evidence="ECO:0007829|PDB:1NJ8"
FT HELIX 226..230
FT /evidence="ECO:0007829|PDB:1NJ8"
FT STRAND 234..236
FT /evidence="ECO:0007829|PDB:1NJ8"
FT STRAND 240..244
FT /evidence="ECO:0007829|PDB:1NJ8"
FT STRAND 246..252
FT /evidence="ECO:0007829|PDB:1NJ8"
FT HELIX 255..264
FT /evidence="ECO:0007829|PDB:1NJ8"
FT STRAND 278..285
FT /evidence="ECO:0007829|PDB:1NJ8"
FT HELIX 292..307
FT /evidence="ECO:0007829|PDB:1NJ8"
FT STRAND 312..314
FT /evidence="ECO:0007829|PDB:1NJ8"
FT HELIX 321..330
FT /evidence="ECO:0007829|PDB:1NJ8"
FT STRAND 334..339
FT /evidence="ECO:0007829|PDB:1NJ8"
FT HELIX 341..345
FT /evidence="ECO:0007829|PDB:1NJ8"
FT STRAND 348..353
FT /evidence="ECO:0007829|PDB:1NJ8"
FT TURN 354..356
FT /evidence="ECO:0007829|PDB:1NJ8"
FT STRAND 359..363
FT /evidence="ECO:0007829|PDB:1NJ8"
FT HELIX 367..393
FT /evidence="ECO:0007829|PDB:1NJ8"
FT STRAND 394..396
FT /evidence="ECO:0007829|PDB:1NJ8"
FT HELIX 402..408
FT /evidence="ECO:0007829|PDB:1NJ8"
FT TURN 409..412
FT /evidence="ECO:0007829|PDB:1NJ8"
FT STRAND 414..419
FT /evidence="ECO:0007829|PDB:1NJ8"
FT HELIX 422..424
FT /evidence="ECO:0007829|PDB:1NJ8"
FT HELIX 427..433
FT /evidence="ECO:0007829|PDB:1NJ8"
FT STRAND 437..442
FT /evidence="ECO:0007829|PDB:1NJ8"
FT STRAND 444..452
FT /evidence="ECO:0007829|PDB:1NJ8"
SQ SEQUENCE 455 AA; 53309 MW; 3D155A36AFE0CC3B CRC64;
MEFSEWYSDI LEKAEIYDVR YPIKGCGVYL PYGFKIRRYT FEIIRNLLDE SGHDEALFPM
LIPEDLLAKE AEHIKGFEDE VYWVTHGGKT QLDVKLALRP TSETPIYYMM KLWVKVHTDL
PIKIYQIVNT FRYETKHTRP LIRLREIMTF KEAHTAHSTK EEAENQVKEA ISIYKKFFDT
LGIPYLISKR PEWDKFPGAE YTMAFDTIFP DGRTMQIATV HNLGQNFSKT FEIIFETPTG
DKDYAYQTCY GISDRVIASI IAIHGDEKGL ILPPIVAPIQ VVIVPLIFKG KEDIVMEKAK
EIYEKLKGKF RVHIDDRDIR PGRKFNDWEI KGVPLRIEVG PKDIENKKIT LFRRDTMEKF
QVDETQLMEV VEKTLNNIME NIKNRAWEKF ENFITILEDI NPDEIKNILS EKRGVILVPF
KEEIYNEELE EKVEATILGE TEYKGNKYIA IAKTY
