Bifunctional (p)ppGpp synthase/hydrolase relA

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P66014 (RELA_MYCTU) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 68. History...

Clusters with 100%, 90%, 50% identity |

Documents (3) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

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 II
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 names

Name:	relA
Ordered Locus Names:	Rv2583c, MT2660
ORF Names:	MTCY227.18

Organism

Mycobacterium tuberculosis [Reference proteome] [HAMAP]

Taxonomic identifier

1773 [NCBI]

Taxonomic lineage

Bacteria › Actinobacteria › Actinobacteridae › Actinomycetales › Corynebacterineae › Mycobacteriaceae › Mycobacterium › Mycobacterium tuberculosis complex

Protein attributes

Sequence length	738 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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, as well as the hydrolysis of ppGpp. RelA is probably a key factor in the pathogenesis of M.tuberculosis as it regulates the intracellular concentrations of (p)ppGpp. Ref.3 Ref.5
Catalytic activity	Guanosine 3',5'-bis(diphosphate) + H₂O = guanosine 5'-diphosphate + diphosphate. Ref.3 ATP + GTP = AMP + guanosine 3'-diphosphate 5'-triphosphate. Ref.3
Cofactor	Binds 1 Mg²⁺ per subunit Potential. Ref.3 Binds 1 Mn²⁺ per subunit Potential. Ref.3
Enzyme regulation	Transferase activity occurs when RelA binds to a complex containing uncharged tRNA, ribosomes, and mRNA (RelA activating complex or RAC). The addition of charged tRNA to this complex has the opposite effect, inhibiting transferase activity and activating hydrolysis activity. Ref.4
Pathway	Purine metabolism; ppGpp biosynthesis; ppGpp from GDP: step 1/1. Purine metabolism; ppGpp biosynthesis; ppGpp from GTP: step 1/2.
Subunit structure	Homotrimer. Ref.6
Induction	By MazG. Ref.4 Ref.7
Domain	Based on a mutagenesis study of the catalytic fragment (residues 1-394), the (p)ppGpp phosphohydrolase domain seems to encompass approximately the first 203 residues, while the (p)ppGpp synthase domain seems to be found between residues 87 and 394.
Disruption phenotype	Cells lacking this gene fail to synthesize ppGpp in response to starvation. Ref.5
Sequence similarities	Belongs to the RelA/SpoT family. Contains 1 ACT domain. Contains 1 HD domain.
Biophysicochemical properties	Kinetic parameters: K_M=0.41 mM for ppGpp (at 30 degrees Celsius and pH 8) Ref.4 K_M=0.48 mM for pppGpp (at 30 degrees Celsius and pH 8)
Sequence caution	The sequence AAK46973.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened. The sequence CAB01260.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Ligand	ATP-binding GTP-binding Magnesium Manganese Metal-binding Nucleotide-binding
Molecular function	Hydrolase Kinase Transferase
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	guanosine tetraphosphate biosynthetic process Inferred from electronic annotation. Source: UniProtKB-UniPathway pathogenesis Inferred from mutant phenotype PubMed 12897239. Source: MTBBASE stringent response Inferred from mutant phenotype Ref.5. Source: MTBBASE
Cellular_component	cell wall Inferred from direct assay PubMed 15525680. Source: MTBBASE plasma membrane Inferred from direct assay PubMed 15525680. Source: MTBBASE
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW GTP binding Inferred from electronic annotation. Source: UniProtKB-KW GTP diphosphokinase activity Inferred from direct assay Ref.3. Source: MTBBASE guanosine-3',5'-bis(diphosphate) 3'-diphosphatase activity Inferred from direct assay Ref.3 Ref.4. Source: MTBBASE kinase activity Inferred from electronic annotation. Source: UniProtKB-KW manganese ion binding Inferred from direct assay Ref.3. Source: MTBBASE
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 738

738

Bifunctional (p)ppGpp synthase/hydrolase relA

PRO_0000166551

Regions

Domain

53 – 150

Domain

661 – 734

ACT

Sites

Active site

Nucleophile, for hydrolase activity Potential

Active site

Nucleophile, for hydrolase activity Potential

Metal binding

Manganese Potential

Metal binding

Manganese Potential

Metal binding

145

Manganese Potential

Metal binding

265

Magnesium By similarity

Experimental info

Mutagenesis

H → D: Loss of hydrolytic activity. Ref.6

Mutagenesis

D → A: Loss of hydrolytic activity. Ref.6

Mutagenesis

241

G → E: Loss of ppGpp synthase activity. Ref.6

Mutagenesis

344

H → Y: Loss of ppGpp synthase activity. Ref.6

Mutagenesis

632

D → A: Altered association with RAC components. Ref.6

Mutagenesis

633

C → A: Altered association with RAC components. Ref.6

Sequences

Sequence

Length

Mass (Da)

Tools

P66014 [UniParc].

Last modified November 30, 2010. Version 2.
Checksum: BD74EBD5BDE4E15E
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FASTA

738

81,827

        10         20         30         40         50         60 
MTAQRSTTNP VLEPLVAVHR EIYPKADLSI LQRAYEVADQ RHASQLRQSG DPYITHPLAV 

        70         80         90        100        110        120 
ANILAELGMD TTTLVAALLH DTVEDTGYTL EALTEEFGEE VGHLVDGVTK LDRVVLGSAA 

       130        140        150        160        170        180 
EGETIRKMIT AMARDPRVLV IKVADRLHNM RTMRFLPPEK QARKARETLE VIAPLAHRLG 

       190        200        210        220        230        240 
MASVKWELED LSFAILHPKK YEEIVRLVAG RAPSRDTYLA KVRAEIVNTL TASKIKATVE 

       250        260        270        280        290        300 
GRPKHYWSIY QKMIVKGRDF DDIHDLVGVR ILCDEIRDCY AAVGVVHSLW QPMAGRFKDY 

       310        320        330        340        350        360 
IAQPRYGVYQ SLHTTVVGPE GKPLEVQIRT RDMHRTAEYG IAAHWRYKEA KGRNGVLHPH 

       370        380        390        400        410        420 
AAAEIDDMAW MRQLLDWQRE AADPGEFLES LRYDLAVQEI FVFTPKGDVI TLPTGSTPVD 

       430        440        450        460        470        480 
FAYAVHTEVG HRCIGARVNG RLVALERKLE NGEVVEVFTS KAPNAGPSRD WQQFVVSPRA 

       490        500        510        520        530        540 
KTKIRQWFAK ERREEALETG KDAMAREVRR GGLPLQRLVN GESMAAVARE LHYADVSALY 

       550        560        570        580        590        600 
TAIGEGHVSA KHVVQRLLAE LGGIDQAEEE LAERSTPATM PRRPRSTDDV GVSVPGAPGV 

       610        620        630        640        650        660 
LTKLAKCCTP VPGDVIMGFV TRGGGVSVHR TDCTNAASLQ QQAERIIEVL WAPSPSSVFL 

       670        680        690        700        710        720 
VAIQVEALDR HRLLSDVTRA LADEKVNILS ASVTTSGDRV AISRFTFEMG DPKHLGHLLN 

       730 
AVRNVEGVYD VYRVTSAA

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References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence." Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E., Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K., Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K. Barrell B.G. Nature 393:537-544(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 25618 / H37Rv.
[2]	"Whole-genome comparison of Mycobacterium tuberculosis clinical and laboratory strains." Fleischmann R.D., Alland D., Eisen J.A., Carpenter L., White O., Peterson J.D., DeBoy R.T., Dodson R.J., Gwinn M.L., Haft D.H., Hickey E.K., Kolonay J.F., Nelson W.C., Umayam L.A., Ermolaeva M.D., Salzberg S.L., Delcher A., Utterback T.R. Fraser C.M. J. Bacteriol. 184:5479-5490(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: CDC 1551 / Oshkosh.
[3]	"Cloning and characterization of a bifunctional RelA/SpoT homologue from Mycobacterium tuberculosis." Avarbock D., Salem J., Li L.S., Wang Z.M., Rubin H. Gene 233:261-269(1999) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 306-329, FUNCTION AS A PYROPHOSPHORYLTRANSFERASE AND PYROPHOSPHOHYDROLASE, CATALYTIC ACTIVITY, COFACTOR.
[4]	"Differential regulation of opposing RelMtb activities by the aminoacylation state of a tRNA.ribosome.mRNA.RelMtb complex." Avarbock D., Avarbock A., Rubin H. Biochemistry 39:11640-11648(2000) [PubMed] [Europe PMC] [Abstract] Cited for: ENZYME REGULATION, BIOPHYSICOCHEMICAL PROPERTIES.
[5]	"The stringent response of Mycobacterium tuberculosis is required for long-term survival." Primm T.P., Andersen S.J., Mizrahi V., Avarbock D., Rubin H., Barry C.E. III J. Bacteriol. 182:4889-4898(2000) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN REGULATION OF STRINGENT RESPONSE, DISRUPTION PHENOTYPE.
[6]	"Functional regulation of the opposing (p)ppGpp synthetase/hydrolase activities of RelMtb from Mycobacterium tuberculosis." Avarbock A., Avarbock D., Teh J.S., Buckstein M., Wang Z.M., Rubin H. Biochemistry 44:9913-9923(2005) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF HIS-80; ASP-81; GLY-241; HIS-344; ASP-632 AND CYS-633, SUBUNIT.
[7]	"Mycobacterial MazG is a novel NTP pyrophosphohydrolase involved in oxidative stress response." Lu L.D., Sun Q., Fan X.Y., Zhong Y., Yao Y.F., Zhao G.P. J. Biol. Chem. 285:28076-28085(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION. Strain: ATCC 25618 / H37Rv.

Cross-references

Sequence databases
EMBL GenBank DDBJ	BX842580 Genomic DNA. Translation: CAB01260.1. Different initiation. AE000516 Genomic DNA. Translation: AAK46973.1. Different initiation.
PIR	F70725.
RefSeq	NP_217099.1. NC_000962.3. NP_337159.1. NC_002755.2. YP_006516024.1. NC_018143.1.
3D structure databases
ProteinModelPortal	P66014.
SMR	P66014. Positions 13-345, 398-461.
ModBase	Search...
Protein-protein interaction databases
STRING	83332.Rv2583c.
Protocols and materials databases
DNASU	925657.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
EnsemblBacteria	AAK46973; AAK46973; MT2660.
GeneID	13319303. 887888. 925657.
KEGG	mtc:MT2660. mtu:Rv2583c. mtv:RVBD_2583c.
PATRIC	18127594. VBIMycTub22151_2900.
Organism-specific databases
TubercuList	Rv2583c.
Phylogenomic databases
eggNOG	COG0317.
HOGENOM	HOG000018301.
KO	K00951.
ProtClustDB	CLSK791939.
Enzyme and pathway databases
UniPathway	UPA00908; UER00884. UPA00908; UER00886.
Family and domain databases
Gene3D	3.10.20.30. 1 hit.
InterPro	IPR026020. (p)ppGpp_Synthase. IPR012675. Beta-grasp_dom. IPR003607. HD/PDEase_dom. IPR004811. RelA/Spo_fam. IPR007685. RelA_SpoT. IPR004095. TGS. IPR012676. TGS-like. [Graphical view]
PANTHER	PTHR21262. PTHR21262. 1 hit.
Pfam	PF04607. RelA_SpoT. 1 hit. PF02824. TGS. 1 hit. [Graphical view]
SMART	SM00471. HDc. 1 hit. SM00954. RelA_SpoT. 1 hit. [Graphical view]
SUPFAM	SSF81271. TGS-like. 1 hit.
TIGRFAMs	TIGR00691. spoT_relA. 1 hit.
ProtoNet	Search...

Entry information

Entry name

RELA_MYCTU

Accession

Primary (citable) accession number: P66014
Secondary accession number(s): Q50638

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 11, 2004
Last sequence update:	November 30, 2010
Last modified:	May 1, 2013
This is version 68 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program

Relevant documents

Mycobacterium tuberculosis strains ATCC 25618 / H37Rv and CDC 1551 / Oshkosh

Mycobacterium tuberculosis strains ATCC 25618 / H37Rv and CDC 1551 / Oshkosh: entries and gene names

PATHWAY comments

Index of metabolic and biosynthesis pathways

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Including the following 2 domains:

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Sites

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Family and domain databases

Entry information

Relevant documents