PCKG_MYCTU
ID PCKG_MYCTU Reviewed; 606 AA.
AC P9WIH3; L0T2U6; P65686; P96393;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 48.
DE RecName: Full=Phosphoenolpyruvate carboxykinase [GTP] {ECO:0000255|HAMAP-Rule:MF_00452, ECO:0000303|PubMed:16691317};
DE Short=PEP carboxykinase {ECO:0000255|HAMAP-Rule:MF_00452, ECO:0000303|PubMed:16691317};
DE Short=PEPCK {ECO:0000255|HAMAP-Rule:MF_00452, ECO:0000303|PubMed:16691317};
DE EC=4.1.1.32 {ECO:0000255|HAMAP-Rule:MF_00452};
DE AltName: Full=GTP-dependent phosphoenolpyruvate carboxykinase {ECO:0000255|HAMAP-Rule:MF_00452};
DE Short=GTP-PEPCK {ECO:0000255|HAMAP-Rule:MF_00452};
GN Name=pckG {ECO:0000255|HAMAP-Rule:MF_00452}; Synonyms=pck1, pckA;
GN OrderedLocusNames=Rv0211; ORFNames=MTCY08D5.06;
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 FUNCTION.
RX PubMed=16691317; DOI=10.1007/s11010-006-9119-5;
RA Liu K., Ba X., Yu J., Li J., Wei Q., Han G., Li G., Cui Y.;
RT "The phosphoenolpyruvate carboxykinase of Mycobacterium tuberculosis
RT induces strong cell-mediated immune responses in mice.";
RL Mol. Cell. Biochem. 288:65-71(2006).
RN [3]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=20439709; DOI=10.1073/pnas.1000715107;
RA Marrero J., Rhee K.Y., Schnappinger D., Pethe K., Ehrt S.;
RT "Gluconeogenic carbon flow of tricarboxylic acid cycle intermediates is
RT critical for Mycobacterium tuberculosis to establish and maintain
RT infection.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:9819-9824(2010).
RN [4]
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).
CC -!- FUNCTION: Involved in the gluconeogenesis, in growth on fatty acids and
CC is important for initiation of infection in the macrophages. Catalyzes
CC the GTP-dependent conversion of oxaloacetate (OAA) to
CC phosphoenolpyruvate (PEP), the rate-limiting step in the metabolic
CC pathway that produces glucose from lactate and other precursors derived
CC from the citric acid cycle. {ECO:0000269|PubMed:16691317,
CC ECO:0000269|PubMed:20439709}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=GTP + oxaloacetate = CO2 + GDP + phosphoenolpyruvate;
CC Xref=Rhea:RHEA:10388, ChEBI:CHEBI:16452, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:37565, ChEBI:CHEBI:58189, ChEBI:CHEBI:58702; EC=4.1.1.32;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_00452};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_00452};
CC Note=Binds 1 Mn(2+) ion per subunit. {ECO:0000255|HAMAP-Rule:MF_00452};
CC -!- PATHWAY: Carbohydrate biosynthesis; gluconeogenesis.
CC {ECO:0000255|HAMAP-Rule:MF_00452}.
CC -!- SUBUNIT: Monomer. {ECO:0000255|HAMAP-Rule:MF_00452}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_00452}.
CC -!- DISRUPTION PHENOTYPE: Cells lacking this gene are unable to grow in the
CC absence of an external carbon source when grown with fatty acids
CC acetate, valerate, or butyrate as the sole carbon source. This mutant
CC also fails to replicate in mouse lungs. PEPCK depletion during the
CC chronic phase of infection results in mycobacterial clearance.
CC {ECO:0000269|PubMed:20439709}.
CC -!- MISCELLANEOUS: The number of CD4 T-cells is increased in the PEPCK
CC immunized mice although the change of the number of CD8 T-cells is not
CC significant. The cytokines IFN-gamma (IFNG), IL-12 (IL12A or IL12B) and
CC TNF-alpha (TNF) are increased significantly in the mice immunized with
CC PEPCK relative to those immunized with incomplete adjuvant.
CC {ECO:0000269|PubMed:16691317}.
CC -!- SIMILARITY: Belongs to the phosphoenolpyruvate carboxykinase [GTP]
CC family. {ECO:0000255|HAMAP-Rule:MF_00452}.
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DR EMBL; AL123456; CCP42939.1; -; Genomic_DNA.
DR PIR; A70960; A70960.
DR RefSeq; NP_214725.1; NC_000962.3.
DR RefSeq; WP_003401212.1; NZ_NVQJ01000001.1.
DR PDB; 4R43; X-ray; 1.80 A; A=1-606.
DR PDB; 4RCG; X-ray; 2.60 A; A=1-606.
DR PDBsum; 4R43; -.
DR PDBsum; 4RCG; -.
DR AlphaFoldDB; P9WIH3; -.
DR SMR; P9WIH3; -.
DR STRING; 83332.Rv0211; -.
DR iPTMnet; P9WIH3; -.
DR PaxDb; P9WIH3; -.
DR DNASU; 886744; -.
DR GeneID; 886744; -.
DR KEGG; mtu:Rv0211; -.
DR TubercuList; Rv0211; -.
DR eggNOG; COG1274; Bacteria.
DR OMA; GPTNNWV; -.
DR PhylomeDB; P9WIH3; -.
DR UniPathway; UPA00138; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005829; C:cytosol; HDA:MTBBASE.
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:0005525; F:GTP binding; IEA:UniProtKB-UniRule.
DR GO; GO:0030145; F:manganese ion binding; IBA:GO_Central.
DR GO; GO:0004613; F:phosphoenolpyruvate carboxykinase (GTP) activity; IBA:GO_Central.
DR GO; GO:0071333; P:cellular response to glucose stimulus; IBA:GO_Central.
DR GO; GO:0010106; P:cellular response to iron ion starvation; IEP:MTBBASE.
DR GO; GO:0006094; P:gluconeogenesis; IBA:GO_Central.
DR GO; GO:0046327; P:glycerol biosynthetic process from pyruvate; IBA:GO_Central.
DR GO; GO:0019543; P:propionate catabolic process; IBA:GO_Central.
DR GO; GO:0052572; P:response to host immune response; IEP:MTBBASE.
DR GO; GO:0033993; P:response to lipid; IBA:GO_Central.
DR GO; GO:0042594; P:response to starvation; IBA:GO_Central.
DR CDD; cd00819; PEPCK_GTP; 1.
DR Gene3D; 3.40.449.10; -; 1.
DR Gene3D; 3.90.228.20; -; 1.
DR HAMAP; MF_00452; PEPCK_GTP; 1.
DR InterPro; IPR018091; PEP_carboxykin_GTP_CS.
DR InterPro; IPR013035; PEP_carboxykinase_C.
DR InterPro; IPR008209; PEP_carboxykinase_GTP.
DR InterPro; IPR035077; PEP_carboxykinase_GTP_C.
DR InterPro; IPR035078; PEP_carboxykinase_GTP_N.
DR InterPro; IPR008210; PEP_carboxykinase_N.
DR PANTHER; PTHR11561; PTHR11561; 1.
DR Pfam; PF00821; PEPCK_GTP; 1.
DR Pfam; PF17297; PEPCK_N; 1.
DR PIRSF; PIRSF001348; PEP_carboxykinase_GTP; 1.
DR SUPFAM; SSF68923; SSF68923; 1.
DR PROSITE; PS00505; PEPCK_GTP; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Cytoplasm; Decarboxylase; Gluconeogenesis;
KW GTP-binding; Lyase; Manganese; Metal-binding; Nucleotide-binding;
KW Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:21969609"
FT CHAIN 2..606
FT /note="Phosphoenolpyruvate carboxykinase [GTP]"
FT /id="PRO_0000103611"
FT ACT_SITE 273
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00452"
FT BINDING 81
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00452"
FT BINDING 220..222
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00452"
FT BINDING 229
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00452"
FT BINDING 249
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00452"
FT BINDING 271
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00452"
FT BINDING 272..277
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00452"
FT BINDING 296
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00452"
FT BINDING 387..389
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00452"
FT BINDING 389
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00452"
FT BINDING 420
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00452"
FT BINDING 515..518
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00452"
FT MOD_RES 2
FT /note="N-acetylthreonine"
FT /evidence="ECO:0007744|PubMed:21969609"
FT TURN 7..11
FT /evidence="ECO:0007829|PDB:4R43"
FT HELIX 17..30
FT /evidence="ECO:0007829|PDB:4R43"
FT STRAND 33..37
FT /evidence="ECO:0007829|PDB:4R43"
FT HELIX 42..54
FT /evidence="ECO:0007829|PDB:4R43"
FT STRAND 57..60
FT /evidence="ECO:0007829|PDB:4R43"
FT TURN 63..65
FT /evidence="ECO:0007829|PDB:4R43"
FT STRAND 66..68
FT /evidence="ECO:0007829|PDB:4R43"
FT STRAND 70..72
FT /evidence="ECO:0007829|PDB:4R43"
FT HELIX 83..85
FT /evidence="ECO:0007829|PDB:4R43"
FT STRAND 86..88
FT /evidence="ECO:0007829|PDB:4R43"
FT HELIX 93..95
FT /evidence="ECO:0007829|PDB:4R43"
FT HELIX 105..116
FT /evidence="ECO:0007829|PDB:4R43"
FT TURN 117..122
FT /evidence="ECO:0007829|PDB:4R43"
FT STRAND 123..133
FT /evidence="ECO:0007829|PDB:4R43"
FT STRAND 137..139
FT /evidence="ECO:0007829|PDB:4R43"
FT STRAND 141..148
FT /evidence="ECO:0007829|PDB:4R43"
FT HELIX 150..159
FT /evidence="ECO:0007829|PDB:4R43"
FT STRAND 160..163
FT /evidence="ECO:0007829|PDB:4R43"
FT HELIX 164..170
FT /evidence="ECO:0007829|PDB:4R43"
FT TURN 171..173
FT /evidence="ECO:0007829|PDB:4R43"
FT STRAND 177..182
FT /evidence="ECO:0007829|PDB:4R43"
FT STRAND 203..207
FT /evidence="ECO:0007829|PDB:4R43"
FT TURN 208..211
FT /evidence="ECO:0007829|PDB:4R43"
FT STRAND 212..217
FT /evidence="ECO:0007829|PDB:4R43"
FT HELIX 221..223
FT /evidence="ECO:0007829|PDB:4R43"
FT HELIX 227..233
FT /evidence="ECO:0007829|PDB:4R43"
FT HELIX 234..243
FT /evidence="ECO:0007829|PDB:4R43"
FT STRAND 246..249
FT /evidence="ECO:0007829|PDB:4R43"
FT STRAND 251..256
FT /evidence="ECO:0007829|PDB:4R43"
FT STRAND 258..260
FT /evidence="ECO:0007829|PDB:4R43"
FT STRAND 262..268
FT /evidence="ECO:0007829|PDB:4R43"
FT HELIX 275..279
FT /evidence="ECO:0007829|PDB:4R43"
FT STRAND 289..296
FT /evidence="ECO:0007829|PDB:4R43"
FT STRAND 298..302
FT /evidence="ECO:0007829|PDB:4R43"
FT STRAND 304..306
FT /evidence="ECO:0007829|PDB:4RCG"
FT STRAND 308..311
FT /evidence="ECO:0007829|PDB:4R43"
FT STRAND 315..320
FT /evidence="ECO:0007829|PDB:4R43"
FT TURN 326..328
FT /evidence="ECO:0007829|PDB:4R43"
FT HELIX 330..337
FT /evidence="ECO:0007829|PDB:4R43"
FT STRAND 342..345
FT /evidence="ECO:0007829|PDB:4R43"
FT STRAND 347..349
FT /evidence="ECO:0007829|PDB:4RCG"
FT STRAND 359..361
FT /evidence="ECO:0007829|PDB:4R43"
FT STRAND 364..367
FT /evidence="ECO:0007829|PDB:4R43"
FT STRAND 373..375
FT /evidence="ECO:0007829|PDB:4R43"
FT TURN 376..378
FT /evidence="ECO:0007829|PDB:4R43"
FT STRAND 389..393
FT /evidence="ECO:0007829|PDB:4R43"
FT HELIX 394..396
FT /evidence="ECO:0007829|PDB:4R43"
FT HELIX 402..405
FT /evidence="ECO:0007829|PDB:4R43"
FT STRAND 410..418
FT /evidence="ECO:0007829|PDB:4R43"
FT STRAND 422..425
FT /evidence="ECO:0007829|PDB:4R43"
FT STRAND 427..430
FT /evidence="ECO:0007829|PDB:4R43"
FT HELIX 434..442
FT /evidence="ECO:0007829|PDB:4R43"
FT TURN 451..453
FT /evidence="ECO:0007829|PDB:4R43"
FT HELIX 463..465
FT /evidence="ECO:0007829|PDB:4R43"
FT TURN 467..469
FT /evidence="ECO:0007829|PDB:4R43"
FT HELIX 474..486
FT /evidence="ECO:0007829|PDB:4R43"
FT HELIX 490..492
FT /evidence="ECO:0007829|PDB:4R43"
FT STRAND 495..499
FT /evidence="ECO:0007829|PDB:4R43"
FT STRAND 510..512
FT /evidence="ECO:0007829|PDB:4R43"
FT HELIX 515..518
FT /evidence="ECO:0007829|PDB:4R43"
FT HELIX 519..529
FT /evidence="ECO:0007829|PDB:4R43"
FT STRAND 536..538
FT /evidence="ECO:0007829|PDB:4R43"
FT STRAND 541..543
FT /evidence="ECO:0007829|PDB:4R43"
FT HELIX 546..548
FT /evidence="ECO:0007829|PDB:4R43"
FT HELIX 558..565
FT /evidence="ECO:0007829|PDB:4R43"
FT HELIX 569..586
FT /evidence="ECO:0007829|PDB:4R43"
FT HELIX 587..589
FT /evidence="ECO:0007829|PDB:4R43"
FT HELIX 592..605
FT /evidence="ECO:0007829|PDB:4R43"
SQ SEQUENCE 606 AA; 67253 MW; AEE29412E6BCCAE3 CRC64;
MTSATIPGLD TAPTNHQGLL SWVEEVAELT QPDRVVFTDG SEEEFQRLCD QLVEAGTFIR
LNPEKHKNSY LALSDPSDVA RVESRTYICS AKEIDAGPTN NWMDPGEMRS IMKDLYRGCM
RGRTMYVVPF CMGPLGAEDP KLGVEITDSE YVVVSMRTMT RMGKAALEKM GDDGFFVKAL
HSVGAPLEPG QKDVAWPCSE TKYITHFPET REIWSYGSGY GGNALLGKKC YSLRIASAMA
HDEGWLAEHM LILKLISPEN KAYYFAAAFP SACGKTNLAM LQPTIPGWRA ETLGDDIAWM
RFGKDGRLYA VNPEFGFFGV APGTNWKSNP NAMRTIAAGN TVFTNVALTD DGDVWWEGLE
GDPQHLIDWK GNDWYFRETE TNAAHPNSRY CTPMSQCPIL APEWDDPQGV PISGILFGGR
RKTTVPLVTE ARDWQHGVFI GATLGSEQTA AAEGKVGNVR RDPMAMLPFL GYNVGDYFQH
WINLGKHADE SKLPKVFFVN WFRRGDDGRF LWPGFGENSR VLKWIVDRIE HKAGGATTPI
GTVPAVEDLD LDGLDVDAAD VAAALAVDAD EWRQELPLIE EWLQFVGEKL PTGVKDEFDA
LKERLG
