Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Bifunctional (p)ppGpp synthase/hydrolase RelA

Gene

relA

Organism
Streptococcus dysgalactiae subsp. equisimilis (Streptococcus equisimilis)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 activityi

ATP + GTP = AMP + guanosine 3'-diphosphate 5'-triphosphate.
Guanosine 3',5'-bis(diphosphate) + H2O = guanosine 5'-diphosphate + diphosphate.

Cofactori

Protein has several cofactor binding sites:
  • Mg2+CuratedNote: Binds 1 Mg2+ ion per subunit.Curated
  • Mn2+1 PublicationNote: Binds 1 Mn2+ ion per subunit.1 Publication

Enzyme regulationi

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

Kineticsi

  1. KM=2 mM for GTP1 Publication
  2. KM=5 mM for ATP1 Publication

    Pathwayi: ppGpp biosynthesis

    This protein is involved in step 1 of the subpathway that synthesizes ppGpp from GDP.
    Proteins known to be involved in this subpathway in this organism are:
    1. Bifunctional (p)ppGpp synthase/hydrolase RelA (relA)
    This subpathway is part of the pathway ppGpp biosynthesis, which is itself part of Purine metabolism.
    View all proteins of this organism that are known to be involved in the subpathway that synthesizes ppGpp from GDP, the pathway ppGpp biosynthesis and in Purine metabolism.

    Pathwayi: ppGpp biosynthesis

    This protein is involved in step 1 of the subpathway that synthesizes ppGpp from GTP.
    Proteins known to be involved in the 2 steps of the subpathway in this organism are:
    1. Bifunctional (p)ppGpp synthase/hydrolase RelA (relA)
    2. no protein annotated in this organism
    This subpathway is part of the pathway ppGpp biosynthesis, which is itself part of Purine metabolism.
    View all proteins of this organism that are known to be involved in the subpathway that synthesizes ppGpp from GTP, the pathway ppGpp biosynthesis and in Purine metabolism.

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Metal bindingi53Manganese1
    Metal bindingi77Manganese1
    Active sitei81Nucleophile, for hydrolase activitySequence analysis1
    Active sitei82Nucleophile, for hydrolase activitySequence analysis1
    Metal bindingi144Manganese1
    Metal bindingi264MagnesiumSequence analysis1

    GO - Molecular functioni

    GO - Biological processi

    Complete GO annotation...

    Keywords - Molecular functioni

    Hydrolase, Kinase, Transferase

    Keywords - Ligandi

    ATP-binding, GTP-binding, Magnesium, Manganese, Metal-binding, Nucleotide-binding

    Enzyme and pathway databases

    SABIO-RKQ54089.
    UniPathwayiUPA00908; UER00884.
    UPA00908; UER00886.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Bifunctional (p)ppGpp synthase/hydrolase RelA
    Including the following 2 domains:
    GTP pyrophosphokinase (EC:2.7.6.5)
    Alternative name(s):
    (p)ppGpp synthase
    ATP:GTP 3'-pyrophosphotransferase
    Stringent response-like protein
    ppGpp synthase I
    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 namesi
    Name:relA
    Synonyms:rel
    OrganismiStreptococcus dysgalactiae subsp. equisimilis (Streptococcus equisimilis)
    Taxonomic identifieri119602 [NCBI]
    Taxonomic lineageiBacteriaFirmicutesBacilliLactobacillalesStreptococcaceaeStreptococcus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi44R → Q: No hydrolase activity. 1 Publication1
    Mutagenesisi78D → A: No hydrolase activity. 1 Publication1
    Mutagenesisi81E → G: No hydrolase activity. 1 Publication1
    Mutagenesisi82D → V: No hydrolase activity. 1 Publication1
    Mutagenesisi151T → A or P: No hydrolase activity. 1 Publication1
    Mutagenesisi264D → G: No synthase activity. 1 Publication1
    Mutagenesisi323E → Q: No synthase activity. 1 Publication1

    Chemistry databases

    ChEMBLiCHEMBL1163118.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00001665651 – 739Bifunctional (p)ppGpp synthase/hydrolase RelAAdd BLAST739

    Proteomic databases

    PRIDEiQ54089.

    Structurei

    Secondary structure

    1739
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Helixi9 – 19Combined sources11
    Helixi22 – 38Combined sources17
    Turni39 – 41Combined sources3
    Helixi52 – 63Combined sources12
    Helixi68 – 76Combined sources9
    Helixi79 – 82Combined sources4
    Helixi87 – 94Combined sources8
    Helixi96 – 108Combined sources13
    Turni128 – 130Combined sources3
    Helixi135 – 150Combined sources16
    Helixi160 – 169Combined sources10
    Helixi171 – 177Combined sources7
    Helixi181 – 195Combined sources15
    Helixi197 – 209Combined sources13
    Helixi211 – 230Combined sources20
    Turni231 – 233Combined sources3
    Beta strandi237 – 240Combined sources4
    Helixi245 – 255Combined sources11
    Helixi256 – 258Combined sources3
    Helixi263 – 265Combined sources3
    Beta strandi267 – 274Combined sources8
    Helixi275 – 288Combined sources14
    Turni299 – 301Combined sources3
    Beta strandi311 – 316Combined sources6
    Beta strandi318 – 328Combined sources11
    Helixi329 – 337Combined sources9
    Helixi364 – 370Combined sources7

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    1VJ7X-ray2.10A/B1-385[»]
    ProteinModelPortaliQ54089.
    SMRiQ54089.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ54089.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Domaini50 – 149HDAdd BLAST100
    Domaini664 – 739ACTPROSITE-ProRule annotationAdd BLAST76

    Domaini

    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 similaritiesi

    Belongs to the RelA/SpoT family.Curated
    Contains 1 ACT domain.PROSITE-ProRule annotation
    Contains 1 HD domain.Curated

    Family and domain databases

    CDDicd05399. NT_Rel-Spo_like. 1 hit.
    cd01668. TGS_RelA_SpoT. 1 hit.
    Gene3Di3.10.20.30. 1 hit.
    InterProiIPR002912. ACT_dom.
    IPR012675. Beta-grasp_dom.
    IPR003607. HD/PDEase_dom.
    IPR004811. RelA/Spo_fam.
    IPR007685. RelA_SpoT.
    IPR004095. TGS.
    IPR012676. TGS-like.
    IPR033655. TGS_RelA.
    [Graphical view]
    PfamiPF13291. ACT_4. 1 hit.
    PF13328. HD_4. 1 hit.
    PF04607. RelA_SpoT. 1 hit.
    PF02824. TGS. 1 hit.
    [Graphical view]
    SMARTiSM00471. HDc. 1 hit.
    SM00954. RelA_SpoT. 1 hit.
    [Graphical view]
    SUPFAMiSSF81271. SSF81271. 1 hit.
    TIGRFAMsiTIGR00691. spoT_relA. 1 hit.
    PROSITEiPS51671. ACT. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q54089-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MAKEINLTGE EVVALAAKYM NETDAAFVKK ALDYATAAHF YQVRKSGEPY
    60 70 80 90 100
    IVHPIQVAGI LADLHLDAVT VACGFLHDVV EDTDITLDNI EFDFGKDVRD
    110 120 130 140 150
    IVDGVTKLGK VEYKSHEEQL AENHRKMLMA MSKDIRVILV KLADRLHNMR
    160 170 180 190 200
    TLKHLRKDKQ ERISRETMEI YAPLAHRLGI SRIKWELEDL AFRYLNETEF
    210 220 230 240 250
    YKISHMMNEK RREREALVDD IVTKIKSYTT EQGLFGDVYG RPKHIYSIYR
    260 270 280 290 300
    KMRDKKKRFD QIFDLIAIRC VMETQSDVYA MVGYIHELWR PMPGRFKDYI
    310 320 330 340 350
    AAPKANGYQS IHTTVYGPKG PIEIQIRTKE MHQVAEYGVA AHWAYKKGVR
    360 370 380 390 400
    GKVNQAEQKV GMNWIKELVE LQDASNGDAV DFVDSVKEDI FSERIYVFTP
    410 420 430 440 450
    TGAVQELPKD SGPIDFAYAI HTQVGEKAIG AKVNGRMVPL TAKLKTGDVV
    460 470 480 490 500
    EIVTNPNSFG PSRDWIKLVK TNKARNKIRQ FFKNQDKELS VNKGRDMLVS
    510 520 530 540 550
    YFQEQGYVAN KYLDKKRIEA ILPKVSVKSE ESLYAAVGFG DISPVSVFNK
    560 570 580 590 600
    LTEKERREEE RAKAKAEAEE LVNGGEIKHE NKDVLKVRSE NGVIIQGASG
    610 620 630 640 650
    LLMRIAKCCN PVPGDPIEGY ITKGRGIAIH RADCNNIKSQ DGYQERLIEV
    660 670 680 690 700
    EWDLDNSSKD YQAEIDIYGL NRRGLLNDVL QILSNSTKSI STVNAQPTKD
    710 720 730
    MKFANIHVSF GIPNLTHLTT VVEKIKAVPD VYSVKRTNG
    Length:739
    Mass (Da):83,913
    Last modified:November 1, 1997 - v1
    Checksum:iE65CBEF99103D171
    GO

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    X72832 Genomic DNA. Translation: CAA51353.1.
    PIRiS39975.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    X72832 Genomic DNA. Translation: CAA51353.1.
    PIRiS39975.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    1VJ7X-ray2.10A/B1-385[»]
    ProteinModelPortaliQ54089.
    SMRiQ54089.
    ModBaseiSearch...
    MobiDBiSearch...

    Chemistry databases

    ChEMBLiCHEMBL1163118.

    Proteomic databases

    PRIDEiQ54089.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Enzyme and pathway databases

    UniPathwayiUPA00908; UER00884.
    UPA00908; UER00886.
    SABIO-RKQ54089.

    Miscellaneous databases

    EvolutionaryTraceiQ54089.

    Family and domain databases

    CDDicd05399. NT_Rel-Spo_like. 1 hit.
    cd01668. TGS_RelA_SpoT. 1 hit.
    Gene3Di3.10.20.30. 1 hit.
    InterProiIPR002912. ACT_dom.
    IPR012675. Beta-grasp_dom.
    IPR003607. HD/PDEase_dom.
    IPR004811. RelA/Spo_fam.
    IPR007685. RelA_SpoT.
    IPR004095. TGS.
    IPR012676. TGS-like.
    IPR033655. TGS_RelA.
    [Graphical view]
    PfamiPF13291. ACT_4. 1 hit.
    PF13328. HD_4. 1 hit.
    PF04607. RelA_SpoT. 1 hit.
    PF02824. TGS. 1 hit.
    [Graphical view]
    SMARTiSM00471. HDc. 1 hit.
    SM00954. RelA_SpoT. 1 hit.
    [Graphical view]
    SUPFAMiSSF81271. SSF81271. 1 hit.
    TIGRFAMsiTIGR00691. spoT_relA. 1 hit.
    PROSITEiPS51671. ACT. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Entry informationi

    Entry nameiRELA_STREQ
    AccessioniPrimary (citable) accession number: Q54089
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 1, 1997
    Last sequence update: November 1, 1997
    Last modified: November 2, 2016
    This is version 99 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programProkaryotic Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure

    Documents

    1. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    2. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    3. SIMILARITY comments
      Index of protein domains and families

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.