ID   GLNE_MYCTU              Reviewed;         994 AA.
AC   P9WN27; L0T8Z5; P69942; Q10379;
DT   16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT   16-APR-2014, sequence version 1.
DT   03-AUG-2022, entry version 44.
DE   RecName: Full=Bifunctional glutamine synthetase adenylyltransferase/adenylyl-removing enzyme {ECO:0000255|HAMAP-Rule:MF_00802};
DE   AltName: Full=ATP:glutamine synthetase adenylyltransferase {ECO:0000255|HAMAP-Rule:MF_00802};
DE   AltName: Full=ATase {ECO:0000255|HAMAP-Rule:MF_00802};
DE   Includes:
DE     RecName: Full=Glutamine synthetase adenylyl-L-tyrosine phosphorylase {ECO:0000255|HAMAP-Rule:MF_00802};
DE              EC=2.7.7.89 {ECO:0000255|HAMAP-Rule:MF_00802};
DE     AltName: Full=Adenylyl removase {ECO:0000255|HAMAP-Rule:MF_00802};
DE              Short=AR {ECO:0000255|HAMAP-Rule:MF_00802};
DE              Short=AT-N {ECO:0000255|HAMAP-Rule:MF_00802};
DE   Includes:
DE     RecName: Full=Glutamine synthetase adenylyl transferase {ECO:0000255|HAMAP-Rule:MF_00802};
DE              EC=2.7.7.42 {ECO:0000255|HAMAP-Rule:MF_00802};
DE     AltName: Full=Adenylyl transferase {ECO:0000255|HAMAP-Rule:MF_00802};
DE              Short=AT {ECO:0000255|HAMAP-Rule:MF_00802};
DE              Short=AT-C {ECO:0000255|HAMAP-Rule:MF_00802};
GN   Name=glnE {ECO:0000255|HAMAP-Rule:MF_00802}; OrderedLocusNames=Rv2221c;
GN   ORFNames=MTCY190.32c, MTCY427.02c;
OS   Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC   Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC   Mycobacterium; Mycobacterium tuberculosis complex.
OX   NCBI_TaxID=83332;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 25618 / H37Rv;
RX   PubMed=9634230; DOI=10.1038/31159;
RA   Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E.,
RA   Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K.,
RA   Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K.,
RA   Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K.,
RA   Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J.,
RA   Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S.,
RA   Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S.,
RA   Barrell B.G.;
RT   "Deciphering the biology of Mycobacterium tuberculosis from the complete
RT   genome sequence.";
RL   Nature 393:537-544(1998).
RN   [2]
RP   IDENTIFICATION AS A DRUG TARGET [LARGE SCALE ANALYSIS].
RX   PubMed=19099550; DOI=10.1186/1752-0509-2-109;
RA   Raman K., Yeturu K., Chandra N.;
RT   "targetTB: a target identification pipeline for Mycobacterium tuberculosis
RT   through an interactome, reactome and genome-scale structural analysis.";
RL   BMC Syst. Biol. 2:109-109(2008).
RN   [3]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   STRAIN=ATCC 25618 / H37Rv;
RX   PubMed=21969609; DOI=10.1074/mcp.m111.011627;
RA   Kelkar D.S., Kumar D., Kumar P., Balakrishnan L., Muthusamy B., Yadav A.K.,
RA   Shrivastava P., Marimuthu A., Anand S., Sundaram H., Kingsbury R.,
RA   Harsha H.C., Nair B., Prasad T.S., Chauhan D.S., Katoch K., Katoch V.M.,
RA   Kumar P., Chaerkady R., Ramachandran S., Dash D., Pandey A.;
RT   "Proteogenomic analysis of Mycobacterium tuberculosis by high resolution
RT   mass spectrometry.";
RL   Mol. Cell. Proteomics 10:M111.011627-M111.011627(2011).
CC   -!- FUNCTION: Involved in the regulation of glutamine synthetase GlnA, a
CC       key enzyme in the process to assimilate ammonia. When cellular nitrogen
CC       levels are high, the C-terminal adenylyl transferase (AT) inactivates
CC       GlnA by covalent transfer of an adenylyl group from ATP to specific
CC       tyrosine residue of GlnA, thus reducing its activity. Conversely, when
CC       nitrogen levels are low, the N-terminal adenylyl removase (AR)
CC       activates GlnA by removing the adenylyl group by phosphorolysis,
CC       increasing its activity. The regulatory region of GlnE binds the signal
CC       transduction protein PII (GlnB) which indicates the nitrogen status of
CC       the cell. {ECO:0000255|HAMAP-Rule:MF_00802}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=[glutamine synthetase]-O(4)-(5'-adenylyl)-L-tyrosine +
CC         phosphate = [glutamine synthetase]-L-tyrosine + ADP;
CC         Xref=Rhea:RHEA:43716, Rhea:RHEA-COMP:10660, Rhea:RHEA-COMP:10661,
CC         ChEBI:CHEBI:43474, ChEBI:CHEBI:46858, ChEBI:CHEBI:83624,
CC         ChEBI:CHEBI:456216; EC=2.7.7.89; Evidence={ECO:0000255|HAMAP-
CC         Rule:MF_00802};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=[glutamine synthetase]-L-tyrosine + ATP = [glutamine
CC         synthetase]-O(4)-(5'-adenylyl)-L-tyrosine + diphosphate;
CC         Xref=Rhea:RHEA:18589, Rhea:RHEA-COMP:10660, Rhea:RHEA-COMP:10661,
CC         ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:46858,
CC         ChEBI:CHEBI:83624; EC=2.7.7.42; Evidence={ECO:0000255|HAMAP-
CC         Rule:MF_00802};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000255|HAMAP-Rule:MF_00802};
CC   -!- MISCELLANEOUS: Was identified as a high-confidence drug target.
CC   -!- SIMILARITY: Belongs to the GlnE family. {ECO:0000255|HAMAP-
CC       Rule:MF_00802}.
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DR   EMBL; AL123456; CCP44999.1; -; Genomic_DNA.
DR   PIR; A70776; A70776.
DR   RefSeq; NP_216737.1; NC_000962.3.
DR   RefSeq; WP_003411478.1; NZ_NVQJ01000008.1.
DR   AlphaFoldDB; P9WN27; -.
DR   SMR; P9WN27; -.
DR   STRING; 83332.Rv2221c; -.
DR   PaxDb; P9WN27; -.
DR   DNASU; 887995; -.
DR   GeneID; 45426198; -.
DR   GeneID; 887995; -.
DR   KEGG; mtu:Rv2221c; -.
DR   TubercuList; Rv2221c; -.
DR   eggNOG; COG1391; Bacteria.
DR   OMA; EFMVQYA; -.
DR   PhylomeDB; P9WN27; -.
DR   BRENDA; 2.7.7.42; 3445.
DR   Proteomes; UP000001584; Chromosome.
DR   GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR   GO; GO:0009274; C:peptidoglycan-based cell wall; HDA:MTBBASE.
DR   GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR   GO; GO:0008882; F:[glutamate-ammonia-ligase] adenylyltransferase activity; IMP:MTBBASE.
DR   GO; GO:0047388; F:[glutamine synthetase]-adenylyl-L-tyrosine phosphorylase; IEA:UniProtKB-EC.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-UniRule.
DR   GO; GO:0000287; F:magnesium ion binding; IEA:UniProtKB-UniRule.
DR   GO; GO:0008152; P:metabolic process; IEA:UniProtKB-KW.
DR   GO; GO:0000820; P:regulation of glutamine family amino acid metabolic process; IMP:MTBBASE.
DR   GO; GO:0060359; P:response to ammonium ion; IEP:MTBBASE.
DR   Gene3D; 3.30.460.10; -; 2.
DR   HAMAP; MF_00802; GlnE; 1.
DR   InterPro; IPR023057; GlnE.
DR   InterPro; IPR005190; GlnE_rpt_dom.
DR   InterPro; IPR043519; NT_sf.
DR   InterPro; IPR013546; PII_UdlTrfase/GS_AdlTrfase.
DR   PANTHER; PTHR30621; PTHR30621; 1.
DR   Pfam; PF08335; GlnD_UR_UTase; 2.
DR   Pfam; PF03710; GlnE; 2.
DR   SUPFAM; SSF81301; SSF81301; 2.
PE   1: Evidence at protein level;
KW   ATP-binding; Magnesium; Multifunctional enzyme; Nucleotide-binding;
KW   Nucleotidyltransferase; Reference proteome; Transferase.
FT   CHAIN           1..994
FT                   /note="Bifunctional glutamine synthetase
FT                   adenylyltransferase/adenylyl-removing enzyme"
FT                   /id="PRO_0000209257"
FT   REGION          1..487
FT                   /note="Adenylyl removase"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00802"
FT   REGION          492..994
FT                   /note="Adenylyl transferase"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00802"
SQ   SEQUENCE   994 AA;  109138 MW;  8E5EA5D63CCE25E0 CRC64;
     MVVTKLATQR PKLPSVGRLG LVDPPAGERL AQLGWDRHED QAHVDLLWSL SRAPDADAAL
     RALIRLSENP DTGWDELNAA LLRERSLRGR LFSVLGSSLA LGDHLVAHPQ SWKLLRGKVT
     LPSHDQLQRS FVECVEESEG MPGSLVHRLR TQYRDYVLML AALDLAATVE DEPVLPFTVV
     AARLADAADA ALAAALRVAE ASVCGEHPPP RLAVIAMGKC GARELNYVSD VDVIFVAERS
     DPRNARVASE MMRVASAAFF EVDAALRPEG RNGELVRTLE SHIAYYQRWA KTWEFQALLK
     ARPVVGDAEL GERYLTALMP MVWRACERED FVVEVQAMRR RVEQLVPADV RGRELKLGSG
     GLRDVEFAVQ LLQLVHARSD ESLRVASTVD ALAALGEGGY IGREDAANMT ASYEFLRLLE
     HRLQLQRLKR THLLPDPEDE EAVRWLARAA HIRPDGRNDA AGVLREELKK QNVRVSKLHT
     KLFYQPLLES IGPTGLEIAH GMTLEAAGRR LAALGYEGPQ TALKHMSALV NQSGRRGRVQ
     SVLLPRLLDW MSYAPDPDGG LLAYRRLSEA LATESWYLAT LRDKPAVAKR LMHVLGTSAY
     VPDLLMRAPR VIQQYEDGPA GPKLLETEPA AVARALIASA SRYPDPERAI AGARTLRRRE
     LARIGSADLL GLLEVTEVCR ALTSVWVAVL QAALDVMIRA SLPDDDRAPA AIAVIGMGRL
     GGAELGYGSD ADVMFVCEPA TGVDDARAVK WSTSIAERVR ALLGTPSVDP PLELDANLRP
     EGRNGPLVRT LGSYAAYYEQ WAQPWEIQAL LRAHAVAGDA ELGQRFLRMV DKTRYPPDGV
     SADSVREIRR IKARIESERL PRGADPNTHT KLGRGGLADI EWTVQLLQLQ HAHQVPALHN
     TSTLQSLDVI AAADLVPAAD VELLRQAWLT ATRARNALVL VRGKPTDQLP GPGRQLNAVA
     VAAGWRNDDG GEFLDNYLRV TRRAKAVVRK VFGS