RELA_MYCTO
ID RELA_MYCTO Reviewed; 738 AA.
AC P9WHG8; L0TBP7; P66014; Q50638;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 43.
DE RecName: Full=Bifunctional (p)ppGpp synthase/hydrolase RelA;
DE Includes:
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=Stringent response-like protein;
DE AltName: Full=ppGpp synthase II;
DE Includes:
DE RecName: Full=Guanosine-3',5'-bis(diphosphate) 3'-pyrophosphohydrolase;
DE EC=3.1.7.2;
DE AltName: Full=Penta-phosphate guanosine-3'-pyrophosphohydrolase;
DE Short=(ppGpp)ase;
GN Name=relA; OrderedLocusNames=MT2660;
OS Mycobacterium tuberculosis (strain CDC 1551 / Oshkosh).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83331;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=CDC 1551 / Oshkosh;
RX PubMed=12218036; DOI=10.1128/jb.184.19.5479-5490.2002;
RA Fleischmann R.D., Alland D., Eisen J.A., Carpenter L., White O.,
RA Peterson J.D., DeBoy R.T., Dodson R.J., Gwinn M.L., Haft D.H., Hickey E.K.,
RA Kolonay J.F., Nelson W.C., Umayam L.A., Ermolaeva M.D., Salzberg S.L.,
RA Delcher A., Utterback T.R., Weidman J.F., Khouri H.M., Gill J., Mikula A.,
RA Bishai W., Jacobs W.R. Jr., Venter J.C., Fraser C.M.;
RT "Whole-genome comparison of Mycobacterium tuberculosis clinical and
RT laboratory strains.";
RL J. Bacteriol. 184:5479-5490(2002).
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 both the formation of pppGpp, which is then
CC hydrolyzed to form ppGpp, as well as the hydrolysis of ppGpp. RelA is
CC probably a key factor in the pathogenesis of M.tuberculosis as it
CC regulates the intracellular concentrations of (p)ppGpp (By similarity).
CC {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=guanosine 3',5'-bis(diphosphate) + H2O = diphosphate + GDP +
CC H(+); Xref=Rhea:RHEA:14253, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:58189, ChEBI:CHEBI:77828; EC=3.1.7.2;
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 -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000305};
CC Note=Binds 1 Mg(2+) ion per subunit. {ECO:0000305};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000305};
CC Note=Binds 1 Mn(2+) ion per subunit. {ECO:0000305};
CC -!- PATHWAY: Purine metabolism; ppGpp biosynthesis; ppGpp from GDP: step
CC 1/1.
CC -!- PATHWAY: Purine metabolism; ppGpp biosynthesis; ppGpp from GTP: step
CC 1/2.
CC -!- SUBUNIT: Homotrimer. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the RelA/SpoT family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAK46973.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AE000516; AAK46973.1; ALT_INIT; Genomic_DNA.
DR PIR; F70725; F70725.
DR AlphaFoldDB; P9WHG8; -.
DR SMR; P9WHG8; -.
DR EnsemblBacteria; AAK46973; AAK46973; MT2660.
DR KEGG; mtc:MT2660; -.
DR HOGENOM; CLU_012300_3_0_11; -.
DR UniPathway; UPA00908; UER00884.
DR UniPathway; UPA00908; UER00886.
DR Proteomes; UP000001020; 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:0008893; F:guanosine-3',5'-bis(diphosphate) 3'-diphosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0016301; F:kinase activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; 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 3: Inferred from homology;
KW ATP-binding; GTP-binding; Hydrolase; Kinase; Magnesium; Manganese;
KW Metal-binding; Nucleotide-binding; Transferase.
FT CHAIN 1..738
FT /note="Bifunctional (p)ppGpp synthase/hydrolase RelA"
FT /id="PRO_0000428189"
FT DOMAIN 53..150
FT /note="HD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01175"
FT DOMAIN 398..459
FT /note="TGS"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01228"
FT DOMAIN 662..736
FT /note="ACT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01007"
FT REGION 568..592
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 84
FT /note="Nucleophile, for hydrolase activity"
FT /evidence="ECO:0000255"
FT ACT_SITE 85
FT /note="Nucleophile, for hydrolase activity"
FT /evidence="ECO:0000255"
FT BINDING 56
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000255"
FT BINDING 80
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000255"
FT BINDING 145
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000255"
FT BINDING 265
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
SQ SEQUENCE 738 AA; 81827 MW; BD74EBD5BDE4E15E CRC64;
MTAQRSTTNP VLEPLVAVHR EIYPKADLSI LQRAYEVADQ RHASQLRQSG DPYITHPLAV
ANILAELGMD TTTLVAALLH DTVEDTGYTL EALTEEFGEE VGHLVDGVTK LDRVVLGSAA
EGETIRKMIT AMARDPRVLV IKVADRLHNM RTMRFLPPEK QARKARETLE VIAPLAHRLG
MASVKWELED LSFAILHPKK YEEIVRLVAG RAPSRDTYLA KVRAEIVNTL TASKIKATVE
GRPKHYWSIY QKMIVKGRDF DDIHDLVGVR ILCDEIRDCY AAVGVVHSLW QPMAGRFKDY
IAQPRYGVYQ SLHTTVVGPE GKPLEVQIRT RDMHRTAEYG IAAHWRYKEA KGRNGVLHPH
AAAEIDDMAW MRQLLDWQRE AADPGEFLES LRYDLAVQEI FVFTPKGDVI TLPTGSTPVD
FAYAVHTEVG HRCIGARVNG RLVALERKLE NGEVVEVFTS KAPNAGPSRD WQQFVVSPRA
KTKIRQWFAK ERREEALETG KDAMAREVRR GGLPLQRLVN GESMAAVARE LHYADVSALY
TAIGEGHVSA KHVVQRLLAE LGGIDQAEEE LAERSTPATM PRRPRSTDDV GVSVPGAPGV
LTKLAKCCTP VPGDVIMGFV TRGGGVSVHR TDCTNAASLQ QQAERIIEVL WAPSPSSVFL
VAIQVEALDR HRLLSDVTRA LADEKVNILS ASVTTSGDRV AISRFTFEMG DPKHLGHLLN
AVRNVEGVYD VYRVTSAA
