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Protein

Bifunctional (p)ppGpp synthase/hydrolase RelA

Gene

relA

Organism
Streptococcus dysgalactiae subsp. equisimilis (Streptococcus equisimilis)
Status
Reviewed-Annotation score: -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

    Keywordsi

    Molecular functionHydrolase, Kinase, Transferase
    LigandATP-binding, GTP-binding, Magnesium, Manganese, Metal-binding, Nucleotide-binding

    Enzyme and pathway databases

    SABIO-RKiQ54089
    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
    DrugBankiDB02836 Guanosine 5'-Diphosphate 2':3'-Cyclic Monophosphate
    DB04315 Guanosine-5'-Diphosphate

    PTM / Processingi

    Molecule processing

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

    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 – 149HDPROSITE-ProRule annotationAdd 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

    Family and domain databases

    CDDicd00077 HDc, 1 hit
    cd05399 NT_Rel-Spo_like, 1 hit
    cd01668 TGS_RelA_SpoT, 1 hit
    Gene3Di3.10.20.30, 1 hit
    InterProiView protein in InterPro
    IPR002912 ACT_dom
    IPR012675 Beta-grasp_dom_sf
    IPR003607 HD/PDEase_dom
    IPR004811 RelA/Spo_fam
    IPR007685 RelA_SpoT
    IPR004095 TGS
    IPR012676 TGS-like
    IPR033655 TGS_RelA
    PfamiView protein in Pfam
    PF13291 ACT_4, 1 hit
    PF13328 HD_4, 1 hit
    PF04607 RelA_SpoT, 1 hit
    PF02824 TGS, 1 hit
    SMARTiView protein in SMART
    SM00471 HDc, 1 hit
    SM00954 RelA_SpoT, 1 hit
    SUPFAMiSSF81271 SSF81271, 1 hit
    TIGRFAMsiTIGR00691 spoT_relA, 1 hit
    PROSITEiView protein in PROSITE
    PS51671 ACT, 1 hit
    PS51831 HD, 1 hit

    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

    Similar proteinsi

    Entry informationi

    Entry nameiRELA_STREQ
    AccessioniPrimary (citable) accession number: Q54089
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
    Last sequence update: November 1, 1997
    Last modified: May 23, 2018
    This is version 106 of the entry and version 1 of the sequence. See 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

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