PKND_MYCTO
ID PKND_MYCTO Reviewed; 664 AA.
AC P9WI78; L0T6U6; O05871; P95308;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 42.
DE RecName: Full=Serine/threonine-protein kinase PknD;
DE EC=2.7.11.1 {ECO:0000250|UniProtKB:P9WI79};
GN Name=pknD; OrderedLocusNames=MT0958;
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).
RN [2]
RP FUNCTION IN VIRULENCE, INTERACTION WITH HOST LAMININ, AND DISRUPTION
RP PHENOTYPE.
RC STRAIN=CDC 1551 / Oshkosh;
RX PubMed=22243650; DOI=10.1186/1471-2180-12-7;
RA Be N.A., Bishai W.R., Jain S.K.;
RT "Role of Mycobacterium tuberculosis pknD in the pathogenesis of central
RT nervous system tuberculosis.";
RL BMC Microbiol. 12:7-7(2012).
CC -!- FUNCTION: Part of a signaling pathway that enables adaptation to
CC osmotic stress through cell wall remodeling and virulence factor
CC production. {ECO:0000250|UniProtKB:P9WI79}.
CC -!- FUNCTION: Key microbial factor required for central nervous system
CC tuberculosis. Required for invasion of host brain endothelia, but not
CC macrophages, lung epithelia or other endothelia.
CC {ECO:0000269|PubMed:22243650}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC Evidence={ECO:0000250|UniProtKB:P9WI79};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1; Evidence={ECO:0000250|UniProtKB:P9WI79};
CC -!- ACTIVITY REGULATION: Dimerization activates the kinase domain of
CC unphosphorylated PknD via an allosteric mechanism, triggering
CC autophosphorylation and phosphorylation of target proteins.
CC Phosphorylated PknD is fully active even in the absence of
CC dimerization. {ECO:0000250|UniProtKB:P9WI79}.
CC -!- SUBUNIT: Homodimer (By similarity). The extracellular domain interacts
CC with host laminin (PubMed:22243650). {ECO:0000250|UniProtKB:P9WI79,
CC ECO:0000269|PubMed:22243650}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Single-pass membrane
CC protein {ECO:0000305}.
CC -!- PTM: Autophosphorylated. Dephosphorylated by PstP.
CC {ECO:0000250|UniProtKB:P9WI79}.
CC -!- DISRUPTION PHENOTYPE: Mutants display defective invasion and reduced
CC survival in brain endothelia. {ECO:0000269|PubMed:22243650}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein
CC kinase family. {ECO:0000255|PROSITE-ProRule:PRU00159}.
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DR EMBL; AE000516; AAK45205.1; -; Genomic_DNA.
DR PIR; C70584; C70584.
DR RefSeq; WP_003404782.1; NZ_KK341227.1.
DR AlphaFoldDB; P9WI78; -.
DR SMR; P9WI78; -.
DR EnsemblBacteria; AAK45205; AAK45205; MT0958.
DR GeneID; 45424897; -.
DR KEGG; mtc:MT0958; -.
DR PATRIC; fig|83331.31.peg.1028; -.
DR HOGENOM; CLU_000288_63_44_11; -.
DR Proteomes; UP000001020; Chromosome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IEA:UniProtKB-KW.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
DR GO; GO:0031326; P:regulation of cellular biosynthetic process; IEA:UniProt.
DR CDD; cd14952; NHL_PKND_like; 1.
DR Gene3D; 2.120.10.30; -; 1.
DR InterPro; IPR011042; 6-blade_b-propeller_TolB-like.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR035016; NHL_PKND.
DR InterPro; IPR001258; NHL_repeat.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR InterPro; IPR013658; SGL.
DR Pfam; PF01436; NHL; 1.
DR Pfam; PF00069; Pkinase; 1.
DR Pfam; PF08450; SGL; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS51125; NHL; 6.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cell membrane; Kinase; Membrane; Nucleotide-binding;
KW Phosphoprotein; Repeat; Serine/threonine-protein kinase; Transferase;
KW Transmembrane; Transmembrane helix; Virulence.
FT CHAIN 1..664
FT /note="Serine/threonine-protein kinase PknD"
FT /id="PRO_0000428054"
FT TOPO_DOM 1..381
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 382..402
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 403..664
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT DOMAIN 15..276
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REPEAT 414..456
FT /note="NHL 1"
FT REPEAT 457..497
FT /note="NHL 2"
FT REPEAT 498..539
FT /note="NHL 3"
FT REPEAT 540..581
FT /note="NHL 4"
FT REPEAT 582..623
FT /note="NHL 5"
FT REPEAT 624..664
FT /note="NHL 6"
FT REGION 303..333
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 138
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 21..29
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 44
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 135
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P9WI79"
FT MOD_RES 169
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P9WI79"
FT MOD_RES 171
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P9WI79"
FT MOD_RES 173
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P9WI79"
FT MOD_RES 209
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P9WI79"
SQ SEQUENCE 664 AA; 69545 MW; FE39716825A41CC1 CRC64;
MSDAVPQVGS QFGPYQLLRL LGRGGMGEVY EAEDTRKHRV VALKLISPQY SDNAVFRARM
QREADTAGRL TEPHIVPIHD YGEINGQFFV EMRMIDGTSL RALLKQYGPL TPARAVAIVR
QIAAALDAAH ANGVTHRDVK PENILVTASD FAYLVDFGIA RAASDPGLTQ TGTAVGTYNY
MAPERFTGDE VTYRADIYAL ACVLGECLTG APPYRADSVE RLIAAHLMDP APQPSQLRPG
RVPPALDQVI AKGMAKNPAE RFMSAGDLAI AAHDALTTSE QHQATTILRR GDNATLLATP
ADTGLSQSES GIAGAGTGPP TPGAARWSPG DSATVAGPLA ADSRGGNWPS QTGHSPAVPN
ALQASLGHAV PPAGNKRKVW AVVGAAAIVL VAIVAAAGYL VLRPSWSPTQ ASGQTVLPFT
GIDFRLSPSG VAVDSAGNVY VTSEGMYGRV VKLATGSTGT TVLPFNGLYQ PQGLAVDGAG
TVYVTDFNNR VVTLAAGSNN QTVLPFDGLN YPEGLAVDTQ GAVYVADRGN NRVVKLAAGS
KTQTVLPFTG LNDPDGVAVD NSGNVYVTDT DNNRVVKLEA ESNNQVVLPF TDITAPWGIA
VDEAGTVYVT EHNTNQVVKL LAGSTTSTVL PFTGLNTPLA VAVDSDRTVY VADRGNDRVV
KLTS
