ID   RELA_BACSU              Reviewed;         734 AA.
AC   O54408; O32043;
DT   30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT   07-JUL-2009, sequence version 3.
DT   03-AUG-2022, entry version 153.
DE   RecName: Full=GTP pyrophosphokinase;
DE            EC=2.7.6.5;
DE   AltName: Full=(p)ppGpp synthase;
DE   AltName: Full=ATP:GTP 3'-pyrophosphotransferase;
DE   AltName: Full=ppGpp synthase I;
GN   Name=relA; OrderedLocusNames=BSU27600;
OS   Bacillus subtilis (strain 168).
OC   Bacteria; Firmicutes; Bacilli; Bacillales; Bacillaceae; Bacillus.
OX   NCBI_TaxID=224308;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=168 / JH642;
RX   PubMed=9383190; DOI=10.1046/j.1365-2958.1997.5511919.x;
RA   Wendrich T.M., Marahiel M.A.;
RT   "Cloning and characterization of a relA/spoT homologue from Bacillus
RT   subtilis.";
RL   Mol. Microbiol. 26:65-79(1997).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=168;
RX   PubMed=9384377; DOI=10.1038/36786;
RA   Kunst F., Ogasawara N., Moszer I., Albertini A.M., Alloni G., Azevedo V.,
RA   Bertero M.G., Bessieres P., Bolotin A., Borchert S., Borriss R.,
RA   Boursier L., Brans A., Braun M., Brignell S.C., Bron S., Brouillet S.,
RA   Bruschi C.V., Caldwell B., Capuano V., Carter N.M., Choi S.-K.,
RA   Codani J.-J., Connerton I.F., Cummings N.J., Daniel R.A., Denizot F.,
RA   Devine K.M., Duesterhoeft A., Ehrlich S.D., Emmerson P.T., Entian K.-D.,
RA   Errington J., Fabret C., Ferrari E., Foulger D., Fritz C., Fujita M.,
RA   Fujita Y., Fuma S., Galizzi A., Galleron N., Ghim S.-Y., Glaser P.,
RA   Goffeau A., Golightly E.J., Grandi G., Guiseppi G., Guy B.J., Haga K.,
RA   Haiech J., Harwood C.R., Henaut A., Hilbert H., Holsappel S., Hosono S.,
RA   Hullo M.-F., Itaya M., Jones L.-M., Joris B., Karamata D., Kasahara Y.,
RA   Klaerr-Blanchard M., Klein C., Kobayashi Y., Koetter P., Koningstein G.,
RA   Krogh S., Kumano M., Kurita K., Lapidus A., Lardinois S., Lauber J.,
RA   Lazarevic V., Lee S.-M., Levine A., Liu H., Masuda S., Mauel C.,
RA   Medigue C., Medina N., Mellado R.P., Mizuno M., Moestl D., Nakai S.,
RA   Noback M., Noone D., O'Reilly M., Ogawa K., Ogiwara A., Oudega B.,
RA   Park S.-H., Parro V., Pohl T.M., Portetelle D., Porwollik S.,
RA   Prescott A.M., Presecan E., Pujic P., Purnelle B., Rapoport G., Rey M.,
RA   Reynolds S., Rieger M., Rivolta C., Rocha E., Roche B., Rose M., Sadaie Y.,
RA   Sato T., Scanlan E., Schleich S., Schroeter R., Scoffone F., Sekiguchi J.,
RA   Sekowska A., Seror S.J., Serror P., Shin B.-S., Soldo B., Sorokin A.,
RA   Tacconi E., Takagi T., Takahashi H., Takemaru K., Takeuchi M.,
RA   Tamakoshi A., Tanaka T., Terpstra P., Tognoni A., Tosato V., Uchiyama S.,
RA   Vandenbol M., Vannier F., Vassarotti A., Viari A., Wambutt R., Wedler E.,
RA   Wedler H., Weitzenegger T., Winters P., Wipat A., Yamamoto H., Yamane K.,
RA   Yasumoto K., Yata K., Yoshida K., Yoshikawa H.-F., Zumstein E.,
RA   Yoshikawa H., Danchin A.;
RT   "The complete genome sequence of the Gram-positive bacterium Bacillus
RT   subtilis.";
RL   Nature 390:249-256(1997).
RN   [3]
RP   SEQUENCE REVISION TO 320.
RX   PubMed=19383706; DOI=10.1099/mic.0.027839-0;
RA   Barbe V., Cruveiller S., Kunst F., Lenoble P., Meurice G., Sekowska A.,
RA   Vallenet D., Wang T., Moszer I., Medigue C., Danchin A.;
RT   "From a consortium sequence to a unified sequence: the Bacillus subtilis
RT   168 reference genome a decade later.";
RL   Microbiology 155:1758-1775(2009).
RN   [4]
RP   FUNCTION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF ASP-264.
RC   STRAIN=168;
RX   PubMed=18067544; DOI=10.1111/j.1365-2958.2007.06018.x;
RA   Nanamiya H., Kasai K., Nozawa A., Yun C.S., Narisawa T., Murakami K.,
RA   Natori Y., Kawamura F., Tozawa Y.;
RT   "Identification and functional analysis of novel (p)ppGpp synthetase genes
RT   in Bacillus subtilis.";
RL   Mol. Microbiol. 67:291-304(2008).
CC   -!- FUNCTION: In eubacteria ppGpp (guanosine 3'-diphosphate 5'-diphosphate)
CC       is a mediator of the stringent response that coordinates a variety of
CC       cellular activities in response to changes in nutritional abundance.
CC       This enzyme catalyzes the formation of pppGpp which is then hydrolyzed
CC       to form ppGpp, it is probably the hydrolysis activity that is required
CC       for optimal growth (Probable). {ECO:0000250,
CC       ECO:0000305|PubMed:18067544}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + GTP = AMP + guanosine 3'-diphosphate 5'-triphosphate;
CC         Xref=Rhea:RHEA:22088, ChEBI:CHEBI:30616, ChEBI:CHEBI:37565,
CC         ChEBI:CHEBI:142410, ChEBI:CHEBI:456215; EC=2.7.6.5;
CC   -!- PATHWAY: Purine metabolism; ppGpp biosynthesis; ppGpp from GTP: step
CC       1/2.
CC   -!- DISRUPTION PHENOTYPE: Decreased growth rate; growth is almost
CC       completely restored in a triple relA-yjbM-ywaC mutant
CC       (PubMed:18067544). {ECO:0000269|PubMed:18067544}.
CC   -!- SIMILARITY: Belongs to the RelA/SpoT family. {ECO:0000305}.
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DR   EMBL; U86377; AAC46041.1; -; Genomic_DNA.
DR   EMBL; AL009126; CAB14719.2; -; Genomic_DNA.
DR   PIR; C69691; C69691.
DR   RefSeq; NP_390638.2; NC_000964.3.
DR   RefSeq; WP_003229747.1; NZ_JNCM01000036.1.
DR   PDB; 6HTQ; EM; 4.50 A; x=391-731.
DR   PDB; 6YXA; X-ray; 3.95 A; A=1-556.
DR   PDBsum; 6HTQ; -.
DR   PDBsum; 6YXA; -.
DR   AlphaFoldDB; O54408; -.
DR   SMR; O54408; -.
DR   IntAct; O54408; 1.
DR   STRING; 224308.BSU27600; -.
DR   jPOST; O54408; -.
DR   PaxDb; O54408; -.
DR   EnsemblBacteria; CAB14719; CAB14719; BSU_27600.
DR   GeneID; 936753; -.
DR   KEGG; bsu:BSU27600; -.
DR   PATRIC; fig|224308.179.peg.2999; -.
DR   eggNOG; COG0317; Bacteria.
DR   InParanoid; O54408; -.
DR   OMA; DWISSPK; -.
DR   PhylomeDB; O54408; -.
DR   BioCyc; BSUB:BSU27600-MON; -.
DR   BRENDA; 2.7.6.5; 658.
DR   UniPathway; UPA00908; UER00884.
DR   Proteomes; UP000001570; Chromosome.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR   GO; GO:0008728; F:GTP diphosphokinase activity; IEA:UniProtKB-EC.
DR   GO; GO:0016301; F:kinase activity; IEA:UniProtKB-KW.
DR   GO; GO:0015970; P:guanosine tetraphosphate biosynthetic process; IEA:UniProtKB-UniPathway.
DR   GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR   CDD; cd00077; HDc; 1.
DR   CDD; cd05399; NT_Rel-Spo_like; 1.
DR   CDD; cd01668; TGS_RSH; 1.
DR   Gene3D; 3.10.20.30; -; 1.
DR   Gene3D; 3.30.460.10; -; 1.
DR   InterPro; IPR045865; ACT-like_dom_sf.
DR   InterPro; IPR002912; ACT_dom.
DR   InterPro; IPR012675; Beta-grasp_dom_sf.
DR   InterPro; IPR003607; HD/PDEase_dom.
DR   InterPro; IPR006674; HD_domain.
DR   InterPro; IPR043519; NT_sf.
DR   InterPro; IPR004811; RelA/Spo_fam.
DR   InterPro; IPR045600; RelA/SpoT_AH_RIS.
DR   InterPro; IPR007685; RelA_SpoT.
DR   InterPro; IPR004095; TGS.
DR   InterPro; IPR012676; TGS-like.
DR   InterPro; IPR033655; TGS_RelA/SpoT.
DR   Pfam; PF13291; ACT_4; 1.
DR   Pfam; PF19296; DUF5913; 1.
DR   Pfam; PF04607; RelA_SpoT; 1.
DR   Pfam; PF02824; TGS; 1.
DR   SMART; SM00471; HDc; 1.
DR   SMART; SM00954; RelA_SpoT; 1.
DR   SUPFAM; SSF55021; SSF55021; 1.
DR   SUPFAM; SSF81271; SSF81271; 1.
DR   SUPFAM; SSF81301; SSF81301; 1.
DR   TIGRFAMs; TIGR00691; spoT_relA; 1.
DR   PROSITE; PS51671; ACT; 1.
DR   PROSITE; PS51831; HD; 1.
DR   PROSITE; PS51880; TGS; 1.
PE   1: Evidence at protein level;
KW   3D-structure; ATP-binding; GTP-binding; Kinase; Nucleotide-binding;
KW   Reference proteome; Transferase.
FT   CHAIN           1..734
FT                   /note="GTP pyrophosphokinase"
FT                   /id="PRO_0000166544"
FT   DOMAIN          50..149
FT                   /note="HD"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01175"
FT   DOMAIN          392..453
FT                   /note="TGS"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01228"
FT   DOMAIN          660..734
FT                   /note="ACT"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01007"
FT   REGION          552..584
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        552..569
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MUTAGEN         264
FT                   /note="D->G: Wild-type growth rate, this enzyme probably
FT                   has no synthase activity but can still degrade pppGpp to
FT                   ppGpp."
FT                   /evidence="ECO:0000269|PubMed:18067544"
SQ   SEQUENCE   734 AA;  84824 MW;  6F06A3E0B9FFAB36 CRC64;
     MANEQVLTAE QVIDKARSYL SDEHIAFVEK AYLYAEDAHR EQYRKSGEPY IIHPIQVAGI
     LVDLEMDPST IAGGFLHDVV EDTDVTLDDL KEAFSEEVAM LVDGVTKLGK IKYKSQEEQQ
     AENHRKMFVA MAQDIRVILI KLADRLHNMR TLKHLPQEKQ RRISNETLEI FAPLAHRLGI
     SKIKWELEDT ALRYLNPQQY YRIVNLMKKK RAERELYVDE VVNEVKKRVE EVNIKADFSG
     RPKHIYSIYR KMVLQNKQFN EIYDLLAVRI LVNSIKDCYA VLGIIHTCWK PMPGRFKDYI
     AMPKPNMYQS LHTTVIGPKG DPLEVQIRTF EMHEIAEYGV AAHWAYKEGK AANEGATFEK
     KLSWFREILE FQNESTDAEE FMESLKIDLF SDMVYVFTPK GDVIELPSGS VPIDFSYRIH
     SEIGNKTIGA KVNGKMVTLD HKLRTGDIVE ILTSKHSYGP SQDWVKLAQT SQAKHKIRQF
     FKKQRREENV EKGRELVEKE IKNLDFELKD VLTPENIQKV ADKFNFSNEE DMYAAVGYNG
     ITALQVANRL TEKERKQRDQ EEQEKIVQEV TGEPKPYPQG RKREAGVRVK GIDNLLVRLS
     KCCNPVPGDD IVGFITKGRG VSVHREDCPN VKTNEAQERL IPVEWEHESQ VQKRKEYNVE
     IEILGYDRRG LLNEVLQAVN ETKTNISSVS GKSDRNKVAT IHMAIFIQNI NHLHKVVERI
     KQIRDIYSVR RVMN