RELA_ECOLI
ID RELA_ECOLI Reviewed; 744 AA.
AC P0AG20; P11585; Q2MA48;
DT 20-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 20-DEC-2005, sequence version 1.
DT 03-AUG-2022, entry version 126.
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=b2784, JW2755;
OS Escherichia coli (strain K12).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=83333;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=K12;
RX PubMed=2844820; DOI=10.1016/s0021-9258(19)37644-6;
RA Metzger S., Dror I.B., Aizenman E., Schreiber G., Toone M., Friesen J.D.,
RA Cashel M., Glaser G.;
RT "The nucleotide sequence and characterization of the relA gene of
RT Escherichia coli.";
RL J. Biol. Chem. 263:15699-15704(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=9278503; DOI=10.1126/science.277.5331.1453;
RA Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V.,
RA Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F.,
RA Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B.,
RA Shao Y.;
RT "The complete genome sequence of Escherichia coli K-12.";
RL Science 277:1453-1462(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=16738553; DOI=10.1038/msb4100049;
RA Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S.,
RA Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.;
RT "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655
RT and W3110.";
RL Mol. Syst. Biol. 2:E1-E5(2006).
RN [4]
RP FUNCTION IN PERSISTENCE, AND DISRUPTION PHENOTYPE.
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=14622409; DOI=10.1046/j.1365-2958.2003.03779.x;
RA Korch S.B., Henderson T.A., Hill T.M.;
RT "Characterization of the hipA7 allele of Escherichia coli and evidence that
RT high persistence is governed by (p)ppGpp synthesis.";
RL Mol. Microbiol. 50:1199-1213(2003).
RN [5]
RP FUNCTION IN BIOFILM FORMATION, AND DISRUPTION PHENOTYPE.
RC STRAIN=K12 / MG1655 / AB400;
RX PubMed=19460094; DOI=10.1111/j.1365-2958.2009.06739.x;
RA Boehm A., Steiner S., Zaehringer F., Casanova A., Hamburger F., Ritz D.,
RA Keck W., Ackermann M., Schirmer T., Jenal U.;
RT "Second messenger signalling governs Escherichia coli biofilm induction
RT upon ribosomal stress.";
RL Mol. Microbiol. 72:1500-1516(2009).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=K12 / CF7789, and K12 / MG1655 / ATCC 47076;
RX PubMed=21488981; DOI=10.1111/j.1365-2958.2011.07663.x;
RA Edwards A.N., Patterson-Fortin L.M., Vakulskas C.A., Mercante J.W.,
RA Potrykus K., Vinella D., Camacho M.I., Fields J.A., Thompson S.A.,
RA Georgellis D., Cashel M., Babitzke P., Romeo T.;
RT "Circuitry linking the Csr and stringent response global regulatory
RT systems.";
RL Mol. Microbiol. 80:1561-1580(2011).
RN [7]
RP FUNCTION IN PERSISTENCE, AND DISRUPTION PHENOTYPE.
RC STRAIN=K12 / BW25113;
RX PubMed=26051177; DOI=10.1016/j.molcel.2015.05.011;
RA Verstraeten N., Knapen W.J., Kint C.I., Liebens V., Van den Bergh B.,
RA Dewachter L., Michiels J.E., Fu Q., David C.C., Fierro A.C., Marchal K.,
RA Beirlant J., Versees W., Hofkens J., Jansen M., Fauvart M., Michiels J.;
RT "Obg and membrane depolarization are part of a microbial bet-hedging
RT strategy that leads to antibiotic tolerance.";
RL Mol. Cell 59:9-21(2015).
CC -!- FUNCTION: In eubacteria ppGpp (guanosine 3'-diphosphate 5'-diphosphate)
CC is a mediator of the stringent response which 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. The second messengers ppGpp and c-di-GMP together
CC control biofilm formation in response to translational stress; ppGpp
CC represses biofilm formation while c-di-GMP induces it. ppGpp activates
CC transcription of CsrA-antagonistic small RNAs CsrB and CsrC, which
CC down-regulate CsrA's action on translation during the stringent
CC response (PubMed:21488981). {ECO:0000269|PubMed:14622409,
CC ECO:0000269|PubMed:19460094, ECO:0000269|PubMed:21488981,
CC ECO:0000269|PubMed:26051177}.
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: A slight increase in biofilm formation in a csrA-
CC disrupted background; when combined with a spoT disruption (a ppGpp0
CC mutant) there is a very large increase in biofilm formation
CC (PubMed:19460094). The ppGpp0 mutant makes decreased levels of CsrA and
CC its inhibitory small RNAs (sRNA) CsrB and CsrC (PubMed:21488981).
CC Deletion of relA alone decreases persister cell formation in a hipA7
CC mutant; the double relA/spoT deletion obviates persister cell formation
CC (PubMed:14622409, PubMed:26051177). {ECO:0000269|PubMed:14622409,
CC ECO:0000269|PubMed:19460094, ECO:0000269|PubMed:21488981,
CC ECO:0000269|PubMed:26051177}.
CC -!- SIMILARITY: Belongs to the RelA/SpoT family. {ECO:0000305}.
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DR EMBL; J04039; AAA03237.1; -; Unassigned_DNA.
DR EMBL; U29580; AAA69294.1; -; Genomic_DNA.
DR EMBL; U00096; AAC75826.1; -; Genomic_DNA.
DR EMBL; AP009048; BAE76858.1; -; Genomic_DNA.
DR PIR; D65060; KIECG.
DR RefSeq; NP_417264.1; NC_000913.3.
DR RefSeq; WP_000226815.1; NZ_STEB01000030.1.
DR PDB; 5IQR; EM; 3.00 A; 8=1-744.
DR PDB; 5KPS; EM; 3.90 A; A=2-744.
DR PDB; 5KPV; EM; 4.10 A; 33=2-744.
DR PDB; 5KPW; EM; 3.90 A; 33=2-744.
DR PDB; 5KPX; EM; 3.90 A; 33=2-744.
DR PDB; 5L3P; EM; 3.70 A; z=1-744.
DR PDBsum; 5IQR; -.
DR PDBsum; 5KPS; -.
DR PDBsum; 5KPV; -.
DR PDBsum; 5KPW; -.
DR PDBsum; 5KPX; -.
DR PDBsum; 5L3P; -.
DR AlphaFoldDB; P0AG20; -.
DR SMR; P0AG20; -.
DR BioGRID; 4259226; 81.
DR DIP; DIP-10658N; -.
DR IntAct; P0AG20; 62.
DR STRING; 511145.b2784; -.
DR ChEMBL; CHEMBL1163114; -.
DR jPOST; P0AG20; -.
DR PaxDb; P0AG20; -.
DR PRIDE; P0AG20; -.
DR EnsemblBacteria; AAC75826; AAC75826; b2784.
DR EnsemblBacteria; BAE76858; BAE76858; BAE76858.
DR GeneID; 66673349; -.
DR GeneID; 947244; -.
DR KEGG; ecj:JW2755; -.
DR KEGG; eco:b2784; -.
DR PATRIC; fig|1411691.4.peg.3951; -.
DR EchoBASE; EB0828; -.
DR eggNOG; COG0317; Bacteria.
DR HOGENOM; CLU_012300_3_0_6; -.
DR InParanoid; P0AG20; -.
DR OMA; TEIGHNC; -.
DR PhylomeDB; P0AG20; -.
DR BioCyc; EcoCyc:RELA-MON; -.
DR BioCyc; MetaCyc:RELA-MON; -.
DR BRENDA; 2.7.6.5; 2026.
DR UniPathway; UPA00908; UER00884.
DR PRO; PR:P0AG20; -.
DR Proteomes; UP000000318; Chromosome.
DR Proteomes; UP000000625; 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; IDA:EcoCyc.
DR GO; GO:0008893; F:guanosine-3',5'-bis(diphosphate) 3'-diphosphatase activity; IBA:GO_Central.
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:0015969; P:guanosine tetraphosphate metabolic process; IMP:EcoCyc.
DR GO; GO:0015949; P:nucleobase-containing small molecule interconversion; IDA:EcoCyc.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0042594; P:response to starvation; IBA:GO_Central.
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; 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; 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..744
FT /note="GTP pyrophosphokinase"
FT /id="PRO_0000166546"
FT DOMAIN 55..160
FT /note="HD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01175"
FT DOMAIN 404..465
FT /note="TGS"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01228"
FT DOMAIN 668..743
FT /note="ACT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01007"
FT CONFLICT 307
FT /note="F -> K (in Ref. 1; AAA03237)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 744 AA; 83876 MW; FA269709F15E1F25 CRC64;
MVAVRSAHIN KAGEFDPEKW IASLGITSQK SCECLAETWA YCLQQTQGHP DASLLLWRGV
EMVEILSTLS MDIDTLRAAL LFPLADANVV SEDVLRESVG KSVVNLIHGV RDMAAIRQLK
ATHTDSVSSE QVDNVRRMLL AMVDDFRCVV IKLAERIAHL REVKDAPEDE RVLAAKECTN
IYAPLANRLG IGQLKWELED YCFRYLHPTE YKRIAKLLHE RRLDREHYIE EFVGHLRAEM
KAEGVKAEVY GRPKHIYSIW RKMQKKNLAF DELFDVRAVR IVAERLQDCY AALGIVHTHY
RHLPDEFDDY VANPKPNGYQ SIHTVVLGPG GKTVEIQIRT KQMHEDAELG VAAHWKYKEG
AAAGGARSGH EDRIAWLRKL IAWQEEMADS GEMLDEVRSQ VFDDRVYVFT PKGDVVDLPA
GSTPLDFAYH IHSDVGHRCI GAKIGGRIVP FTYQLQMGDQ IEIITQKQPN PSRDWLNPNL
GYVTTSRGRS KIHAWFRKQD RDKNILAGRQ ILDDELEHLG ISLKEAEKHL LPRYNFNDVD
ELLAAIGGGD IRLNQMVNFL QSQFNKPSAE EQDAAALKQL QQKSYTPQNR SKDNGRVVVE
GVGNLMHHIA RCCQPIPGDE IVGFITQGRG ISVHRADCEQ LAELRSHAPE RIVDAVWGES
YSAGYSLVVR VVANDRSGLL RDITTILANE KVNVLGVASR SDTKQQLATI DMTIEIYNLQ
VLGRVLGKLN QVPDVIDARR LHGS
