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Q54089 (RELA_STREQ) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 90. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
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Names and origin

Protein namesRecommended name:
Bifunctional (p)ppGpp synthase/hydrolase RelA

Including the following 2 domains:

  1. GTP pyrophosphokinase
    EC=2.7.6.5
    Alternative name(s):
    (p)ppGpp synthase
    ATP:GTP 3'-pyrophosphotransferase
    Stringent response-like protein
    ppGpp synthase I
  2. Guanosine-3',5'-bis(diphosphate) 3'-pyrophosphohydrolase
    EC=3.1.7.2
    Alternative name(s):
    Penta-phosphate guanosine-3'-pyrophosphohydrolase
    Short name=(ppGpp)ase
Gene names
Name:relA
Synonyms:rel
OrganismStreptococcus dysgalactiae subsp. equisimilis (Streptococcus equisimilis)
Taxonomic identifier119602 [NCBI]
Taxonomic lineageBacteriaFirmicutesBacilliLactobacillalesStreptococcaceaeStreptococcus

Protein attributes

Sequence length739 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

In eubacteria ppGpp (guanosine 3'-diphosphate 5-' diphosphate) is a mediator of the stringent response that coordinates a variety of cellular activities in response to changes in nutritional abundance. This enzyme catalyzes both the formation of pppGpp which is then hydrolyzed to form ppGpp, and the hydrolysis of ppGpp. The enzyme does not simultaneously display both synthase and hydrolase activities. In the structure of residues 1-385 there are 2 conformations seen, the hydrolase-OFF/synthase-ON and hydrolase-ON/synthase-OFF, suggesting there is ligand-induced signal transmission between the 2 active sites.

Catalytic activity

ATP + GTP = AMP + guanosine 3'-diphosphate 5'-triphosphate.

Guanosine 3',5'-bis(diphosphate) + H2O = guanosine 5'-diphosphate + diphosphate.

Cofactor

Binds 1 Mg2+ per subunit Potential. Ref.3

Binds 1 Mn2+ per subunit. Ref.3

Enzyme regulation

Alpha-beta methylenyl ATP, an ATP-analog inhibitor of the synthase activity also reduces the hydrolase activity about 4-fold. Ref.2 Ref.3

Pathway

Purine metabolism; ppGpp biosynthesis; ppGpp from GDP: step 1/1.

Purine metabolism; ppGpp biosynthesis; ppGpp from GTP: step 1/2.

Domain

Based on a random mutagenesis study of the catalytic fragment (residues 1-385), the (p)ppGpp phosphohydrolase domain seems to encompass approximately the first 225 residues, while the (p)ppGpp synthase domain seems to be found between residues 226 and 385.

Sequence similarities

Belongs to the RelA/SpoT family.

Contains 1 ACT domain.

Contains 1 HD domain.

Biophysicochemical properties

Kinetic parameters:

KM=2 mM for GTP Ref.2

KM=5 mM for ATP

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 739739Bifunctional (p)ppGpp synthase/hydrolase RelA
PRO_0000166565

Regions

Domain50 – 149100HD
Domain664 – 73976ACT

Sites

Active site811Nucleophile, for hydrolase activity Potential
Active site821Nucleophile, for hydrolase activity Potential
Metal binding531Manganese
Metal binding771Manganese
Metal binding1441Manganese
Metal binding2641Magnesium Potential

Experimental info

Mutagenesis441R → Q: No hydrolase activity. Ref.3
Mutagenesis781D → A: No hydrolase activity. Ref.3
Mutagenesis811E → G: No hydrolase activity. Ref.3
Mutagenesis821D → V: No hydrolase activity. Ref.3
Mutagenesis1511T → A or P: No hydrolase activity. Ref.3
Mutagenesis2641D → G: No synthase activity. Ref.3
Mutagenesis3231E → Q: No synthase activity. Ref.3

Secondary structure

.................................................. 739
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q54089 [UniParc].

Last modified November 1, 1997. Version 1.
Checksum: E65CBEF99103D171

FASTA73983,913
        10         20         30         40         50         60 
MAKEINLTGE EVVALAAKYM NETDAAFVKK ALDYATAAHF YQVRKSGEPY IVHPIQVAGI 

        70         80         90        100        110        120 
LADLHLDAVT VACGFLHDVV EDTDITLDNI EFDFGKDVRD IVDGVTKLGK VEYKSHEEQL 

       130        140        150        160        170        180 
AENHRKMLMA MSKDIRVILV KLADRLHNMR TLKHLRKDKQ ERISRETMEI YAPLAHRLGI 

       190        200        210        220        230        240 
SRIKWELEDL AFRYLNETEF YKISHMMNEK RREREALVDD IVTKIKSYTT EQGLFGDVYG 

       250        260        270        280        290        300 
RPKHIYSIYR KMRDKKKRFD QIFDLIAIRC VMETQSDVYA MVGYIHELWR PMPGRFKDYI 

       310        320        330        340        350        360 
AAPKANGYQS IHTTVYGPKG PIEIQIRTKE MHQVAEYGVA AHWAYKKGVR GKVNQAEQKV 

       370        380        390        400        410        420 
GMNWIKELVE LQDASNGDAV DFVDSVKEDI FSERIYVFTP TGAVQELPKD SGPIDFAYAI 

       430        440        450        460        470        480 
HTQVGEKAIG AKVNGRMVPL TAKLKTGDVV EIVTNPNSFG PSRDWIKLVK TNKARNKIRQ 

       490        500        510        520        530        540 
FFKNQDKELS VNKGRDMLVS YFQEQGYVAN KYLDKKRIEA ILPKVSVKSE ESLYAAVGFG 

       550        560        570        580        590        600 
DISPVSVFNK LTEKERREEE RAKAKAEAEE LVNGGEIKHE NKDVLKVRSE NGVIIQGASG 

       610        620        630        640        650        660 
LLMRIAKCCN PVPGDPIEGY ITKGRGIAIH RADCNNIKSQ DGYQERLIEV EWDLDNSSKD 

       670        680        690        700        710        720 
YQAEIDIYGL NRRGLLNDVL QILSNSTKSI STVNAQPTKD MKFANIHVSF GIPNLTHLTT 

       730 
VVEKIKAVPD VYSVKRTNG 

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References

[1]"Genetic organization of the streptokinase region of the Streptococcus equisimilis H46A chromosome."
Mechold U., Steiner K., Vettermann S., Malke H.
Mol. Gen. Genet. 241:129-140(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Strain: H46A.
[2]"Intramolecular regulation of the opposing (p)ppGpp catalytic activities of Rel(Seq), the Rel/Spo enzyme from Streptococcus equisimilis."
Mechold U., Murphy H., Brown L., Cashel M.
J. Bacteriol. 184:2878-2888(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION.
[3]"Conformational antagonism between opposing active sites in a bifunctional RelA/SpoT homolog modulates (p)ppGpp metabolism during the stringent response."
Hogg T., Mechold U., Malke H., Cashel M., Hilgenfeld R.
Cell 117:57-68(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 1-385 BOUND TO GUANOSINE-NUCLEOTIDE DERIVATIVES, HYDROLASE AND SYNTHASE ACTIVITIES, COFACTOR, ENZYME REGULATION, MUTAGENESIS OF ARG-44; ASP-78; GLU-81; ASP-82; THR-151; ASP-264 AND GLU-323.
Strain: H46A.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X72832 Genomic DNA. Translation: CAA51353.1.
PIRS39975.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1VJ7X-ray2.10A/B1-385[»]
ProteinModelPortalQ54089.
SMRQ54089. Positions 5-371.
ModBaseSearch...
MobiDBSearch...

Chemistry

ChEMBLCHEMBL1163118.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Enzyme and pathway databases

SABIO-RKQ54089.
UniPathwayUPA00908; UER00884.
UPA00908; UER00886.

Family and domain databases

Gene3D3.10.20.30. 1 hit.
InterProIPR002912. ACT_dom.
IPR012675. Beta-grasp_dom.
IPR003607. HD/PDEase_dom.
IPR006674. HD_domain.
IPR004811. RelA/Spo_fam.
IPR007685. RelA_SpoT.
IPR004095. TGS.
IPR012676. TGS-like.
[Graphical view]
PfamPF01842. ACT. 1 hit.
PF01966. HD. 1 hit.
PF04607. RelA_SpoT. 1 hit.
PF02824. TGS. 1 hit.
[Graphical view]
SMARTSM00471. HDc. 1 hit.
SM00954. RelA_SpoT. 1 hit.
[Graphical view]
SUPFAMSSF81271. SSF81271. 1 hit.
TIGRFAMsTIGR00691. spoT_relA. 1 hit.
PROSITEPS51671. ACT. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ54089.

Entry information

Entry nameRELA_STREQ
AccessionPrimary (citable) accession number: Q54089
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1997
Last modified: June 11, 2014
This is version 90 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways