GARA_MYCTU
ID GARA_MYCTU Reviewed; 162 AA.
AC P9WJA9; I3V6A5; P64897; Q50606;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 47.
DE RecName: Full=Glycogen accumulation regulator GarA;
GN Name=garA; OrderedLocusNames=Rv1827; ORFNames=MTCY1A11.16c;
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 [GENOMIC DNA].
RC STRAIN=AIIMS/LM/SS/TB-2016 I/05 SP;
RA Singh A., Singh S.;
RT "Complete Rv1827 gene sequence of Mycobactarium tuberculosis strain
RT AIIMS/LM/SS/TB-2016 I/05 SP.";
RL Submitted (APR-2012) to the EMBL/GenBank/DDBJ databases.
RN [2]
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 [3]
RP PROTEIN SEQUENCE OF 20-28, INTERACTION WITH PKNB, PHOSPHORYLATION AT
RP THR-22, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=15978616; DOI=10.1016/j.jmb.2005.05.049;
RA Villarino A., Duran R., Wehenkel A., Fernandez P., England P., Brodin P.,
RA Cole S.T., Zimny-Arndt U., Jungblut P.R., Cervenansky C., Alzari P.M.;
RT "Proteomic identification of M. tuberculosis protein kinase substrates:
RT PknB recruits GarA, a FHA domain-containing protein, through activation
RT loop-mediated interactions.";
RL J. Mol. Biol. 350:953-963(2005).
RN [4]
RP FUNCTION, INTERACTION WITH KGD; GDH AND PKNG, PHOSPHORYLATION AT THR-21,
RP AND MUTAGENESIS OF THR-21 AND THR-22.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=19019160; DOI=10.1111/j.1365-2958.2008.06489.x;
RA O'Hare H.M., Duran R., Cervenansky C., Bellinzoni M., Wehenkel A.M.,
RA Pritsch O., Obal G., Baumgartner J., Vialaret J., Johnsson K., Alzari P.M.;
RT "Regulation of glutamate metabolism by protein kinases in mycobacteria.";
RL Mol. Microbiol. 70:1408-1423(2008).
RN [5]
RP FUNCTION, ACTIVITY REGULATION, AND SUBUNIT.
RX PubMed=19114043; DOI=10.1016/j.febslet.2008.12.036;
RA England P., Wehenkel A., Martins S., Hoos S., Andre-Leroux G.,
RA Villarino A., Alzari P.M.;
RT "The FHA-containing protein GarA acts as a phosphorylation-dependent
RT molecular switch in mycobacterial signaling.";
RL FEBS Lett. 583:301-307(2009).
RN [6]
RP PHOSPHORYLATION BY PKNG.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=19638631; DOI=10.1074/jbc.m109.036095;
RA Tiwari D., Singh R.K., Goswami K., Verma S.K., Prakash B., Nandicoori V.K.;
RT "Key residues in Mycobacterium tuberculosis protein kinase G play a role in
RT regulating kinase activity and survival in the host.";
RL J. Biol. Chem. 284:27467-27479(2009).
RN [7]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT THR-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [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).
RN [8]
RP STRUCTURE BY NMR OF 2-162, FUNCTION, ACTIVITY REGULATION, INTERACTION WITH
RP KGD; GDH AND GLTB, AND MUTAGENESIS OF SER-95.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=19318624; DOI=10.1126/scisignal.2000212;
RA Nott T.J., Kelly G., Stach L., Li J., Westcott S., Patel D., Hunt D.M.,
RA Howell S., Buxton R.S., O'Hare H.M., Smerdon S.J.;
RT "An intramolecular switch regulates phosphoindependent FHA domain
RT interactions in Mycobacterium tuberculosis.";
RL Sci. Signal. 2:RA12-RA12(2009).
CC -!- FUNCTION: Involved in regulation of glutamate metabolism. Acts as a
CC phosphorylation-dependent molecular switch that modulates the
CC activities of Kgd, Gdh and GltB. {ECO:0000269|PubMed:19019160,
CC ECO:0000269|PubMed:19114043, ECO:0000269|PubMed:19318624}.
CC -!- ACTIVITY REGULATION: Phosphorylation triggers an intra-molecular
CC protein closure, which blocks the FHA binding site and interaction with
CC target enzymes, and switches off the regulatory function of GarA.
CC {ECO:0000269|PubMed:19114043, ECO:0000269|PubMed:19318624}.
CC -!- SUBUNIT: Monomer. Binds via its FHA domain to Kgd, Gdh, GltB, PknB, and
CC the N-terminal region of PknG. {ECO:0000269|PubMed:19114043}.
CC -!- INTERACTION:
CC P9WJA9; P9WJA9: garA; NbExp=3; IntAct=EBI-6405522, EBI-6405522;
CC P9WJA9; O53203: gdh; NbExp=5; IntAct=EBI-6405522, EBI-6405569;
CC P9WJA9; P9WIS5: kgd; NbExp=4; IntAct=EBI-6405522, EBI-6405560;
CC P9WJA9; P9WI81: pknB; NbExp=2; IntAct=EBI-6405522, EBI-2946037;
CC P9WJA9; P9WI73: pknG; NbExp=6; IntAct=EBI-6405522, EBI-6405537;
CC -!- PTM: Phosphorylated on Thr-22 by PknB. Phosphorylated on Thr-21 by
CC PknG. Phosphorylation at either Thr-21 or Thr-22 prevents binding to
CC target enzymes. Phosphorylation at these two threonines is mutually
CC exclusive in vitro. Could also be phosphorylated by PknD, PknE and
CC PknF. {ECO:0000269|PubMed:15978616, ECO:0000269|PubMed:19019160,
CC ECO:0000269|PubMed:19638631}.
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DR EMBL; JQ885576; AFK73561.1; -; Genomic_DNA.
DR EMBL; AL123456; CCP44593.1; -; Genomic_DNA.
DR PIR; D70721; D70721.
DR RefSeq; NP_216343.1; NC_000962.3.
DR RefSeq; WP_003899041.1; NZ_NVQJ01000013.1.
DR PDB; 2KFU; NMR; -; A=2-162.
DR PDB; 6I2P; X-ray; 2.37 A; D/E=1-162.
DR PDBsum; 2KFU; -.
DR PDBsum; 6I2P; -.
DR AlphaFoldDB; P9WJA9; -.
DR BMRB; P9WJA9; -.
DR SMR; P9WJA9; -.
DR ELM; P9WJA9; -.
DR IntAct; P9WJA9; 6.
DR MINT; P9WJA9; -.
DR STRING; 83332.Rv1827; -.
DR TCDB; 9.B.321.1.1; the actinobacterial nutrient-sensing signal transduction pathway controlling glutamate metabolism (sigt) family.
DR iPTMnet; P9WJA9; -.
DR PaxDb; P9WJA9; -.
DR DNASU; 885735; -.
DR GeneID; 45425801; -.
DR GeneID; 885735; -.
DR KEGG; mtu:Rv1827; -.
DR TubercuList; Rv1827; -.
DR eggNOG; COG1716; Bacteria.
DR OMA; IGKFRLT; -.
DR PhylomeDB; P9WJA9; -.
DR SABIO-RK; P9WJA9; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005576; C:extracellular region; HDA:MTBBASE.
DR GO; GO:0009274; C:peptidoglycan-based cell wall; HDA:MTBBASE.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0003729; F:mRNA binding; IBA:GO_Central.
DR GO; GO:0045820; P:negative regulation of glycolytic process; IDA:MTBBASE.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:MTBBASE.
DR GO; GO:0043457; P:regulation of cellular respiration; IDA:MTBBASE.
DR CDD; cd00060; FHA; 1.
DR DisProt; DP01589; -.
DR InterPro; IPR000253; FHA_dom.
DR InterPro; IPR008984; SMAD_FHA_dom_sf.
DR Pfam; PF00498; FHA; 1.
DR SMART; SM00240; FHA; 1.
DR SUPFAM; SSF49879; SSF49879; 1.
DR PROSITE; PS50006; FHA_DOMAIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Direct protein sequencing; Phosphoprotein;
KW Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:21969609"
FT CHAIN 2..162
FT /note="Glycogen accumulation regulator GarA"
FT /id="PRO_0000103902"
FT DOMAIN 77..126
FT /note="FHA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00086"
FT MOD_RES 2
FT /note="N-acetylthreonine"
FT /evidence="ECO:0007744|PubMed:21969609"
FT MOD_RES 21
FT /note="Phosphothreonine; by PknG"
FT /evidence="ECO:0000269|PubMed:19019160"
FT MOD_RES 22
FT /note="Phosphothreonine; by PknB"
FT /evidence="ECO:0000269|PubMed:15978616"
FT MUTAGEN 21
FT /note="T->A: Lack of phosphorylation by PknG."
FT /evidence="ECO:0000269|PubMed:19019160"
FT MUTAGEN 22
FT /note="T->A: Does not affect phosphorylation by PknG."
FT /evidence="ECO:0000269|PubMed:19019160"
FT MUTAGEN 95
FT /note="S->A: Decreases ability to bind to and regulate the
FT activities of Gdh and GltB, but does not affect ability to
FT inhibit Kgd."
FT /evidence="ECO:0000269|PubMed:19318624"
FT STRAND 12..14
FT /evidence="ECO:0007829|PDB:2KFU"
FT TURN 27..30
FT /evidence="ECO:0007829|PDB:2KFU"
FT HELIX 31..33
FT /evidence="ECO:0007829|PDB:6I2P"
FT STRAND 47..50
FT /evidence="ECO:0007829|PDB:2KFU"
FT STRAND 56..60
FT /evidence="ECO:0007829|PDB:6I2P"
FT TURN 64..67
FT /evidence="ECO:0007829|PDB:6I2P"
FT STRAND 69..72
FT /evidence="ECO:0007829|PDB:6I2P"
FT STRAND 74..82
FT /evidence="ECO:0007829|PDB:6I2P"
FT STRAND 86..88
FT /evidence="ECO:0007829|PDB:6I2P"
FT TURN 90..92
FT /evidence="ECO:0007829|PDB:2KFU"
FT STRAND 93..96
FT /evidence="ECO:0007829|PDB:2KFU"
FT STRAND 99..104
FT /evidence="ECO:0007829|PDB:6I2P"
FT STRAND 107..112
FT /evidence="ECO:0007829|PDB:6I2P"
FT STRAND 119..121
FT /evidence="ECO:0007829|PDB:6I2P"
FT STRAND 124..131
FT /evidence="ECO:0007829|PDB:6I2P"
FT STRAND 136..139
FT /evidence="ECO:0007829|PDB:6I2P"
FT STRAND 142..148
FT /evidence="ECO:0007829|PDB:6I2P"
SQ SEQUENCE 162 AA; 17251 MW; 18B1C42151ED0CCA CRC64;
MTDMNPDIEK DQTSDEVTVE TTSVFRADFL SELDAPAQAG TESAVSGVEG LPPGSALLVV
KRGPNAGSRF LLDQAITSAG RHPDSDIFLD DVTVSRRHAE FRLENNEFNV VDVGSLNGTY
VNREPVDSAV LANGDEVQIG KFRLVFLTGP KQGEDDGSTG GP
