ID   DNAK_MYCTU              Reviewed;         625 AA.
AC   P9WMJ9; I6QM76; O06301; P0A5B9; P32723;
DT   16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT   16-APR-2014, sequence version 1.
DT   03-AUG-2022, entry version 46.
DE   RecName: Full=Chaperone protein DnaK;
DE   AltName: Full=HSP70;
DE   AltName: Full=Heat shock 70 kDa protein;
DE   AltName: Full=Heat shock protein 70;
GN   Name=dnaK; OrderedLocusNames=Rv0350; ORFNames=MTCY13E10.10;
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=ATCC 35801 / TMC 107 / Erdman;
RA   Lathigra R., Alexander B., Stover C.K., Coadwell J., Young R.A.,
RA   Young D.B.;
RL   Submitted (FEB-1991) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=MTCC300;
RA   Dhakal J., Agrawal R.K., Brah G.S., Ramneek V., Pawar H.N., Kaur D.,
RA   Minhas P., Mothwal U., Saini N., Mahajan K.;
RL   Submitted (MAY-2012) to the EMBL/GenBank/DDBJ databases.
RN   [3]
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   [4]
RP   INDUCTION BY SIGH.
RC   STRAIN=ATCC 25618 / H37Rv;
RX   PubMed=11567012; DOI=10.1128/jb.183.20.6119-6125.2001;
RA   Raman S., Song T., Puyang X., Bardarov S., Jacobs W.R. Jr., Husson R.N.;
RT   "The alternative sigma factor SigH regulates major components of oxidative
RT   and heat stress responses in Mycobacterium tuberculosis.";
RL   J. Bacteriol. 183:6119-6125(2001).
RN   [5]
RP   FUNCTION IN INFECTION.
RX   PubMed=15809303; DOI=10.1074/jbc.m411379200;
RA   Bulut Y., Michelsen K.S., Hayrapetian L., Naiki Y., Spallek R., Singh M.,
RA   Arditi M.;
RT   "Mycobacterium tuberculosis heat shock proteins use diverse Toll-like
RT   receptor pathways to activate pro-inflammatory signals.";
RL   J. Biol. Chem. 280:20961-20967(2005).
RN   [6]
RP   SUBCELLULAR LOCATION.
RC   STRAIN=ATCC 35801 / TMC 107 / Erdman;
RX   PubMed=19470749; DOI=10.1128/iai.00143-09;
RA   Hickey T.B., Thorson L.M., Speert D.P., Daffe M., Stokes R.W.;
RT   "Mycobacterium tuberculosis Cpn60.2 and DnaK are located on the bacterial
RT   surface, where Cpn60.2 facilitates efficient bacterial association with
RT   macrophages.";
RL   Infect. Immun. 77:3389-3401(2009).
RN   [7]
RP   SUBCELLULAR LOCATION.
RC   STRAIN=H37Rv;
RX   PubMed=21364279; DOI=10.1172/jci44261;
RA   Prados-Rosales R., Baena A., Martinez L.R., Luque-Garcia J., Kalscheuer R.,
RA   Veeraraghavan U., Camara C., Nosanchuk J.D., Besra G.S., Chen B.,
RA   Jimenez J., Glatman-Freedman A., Jacobs W.R. Jr., Porcelli S.A.,
RA   Casadevall A.;
RT   "Mycobacteria release active membrane vesicles that modulate immune
RT   responses in a TLR2-dependent manner in mice.";
RL   J. Clin. Invest. 121:1471-1483(2011).
RN   [8]
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: Acts as a chaperone. {ECO:0000255|HAMAP-Rule:MF_00332}.
CC   -!- FUNCTION: Recombinant extracellular protein activates expression of NF-
CC       kappa-B in immortalized human dermal endothelial cells in a TLR2- and
CC       TLR4-dependent manner. Activation occurs via MYD88-dependent and
CC       -independent pathways and requires TIRAP, TRIF and TRAM (some
CC       experiments done in mouse cells, mice do not usually catch
CC       tuberculosis) (PubMed:15809303). {ECO:0000269|PubMed:15809303}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}. Secreted, capsule
CC       {ECO:0000269|PubMed:19470749}. Cell surface
CC       {ECO:0000269|PubMed:19470749}. Extracellular vesicle, bacterial
CC       extracellular vesicle {ECO:0000269|PubMed:21364279}. Note=Although
CC       thought of as a cytoplasmic chaperone this protein is routinely found
CC       extracellularly in the absence of cell lysis (PubMed:19470749). Present
CC       in extracytoplasmic vesicles (PubMed:21364279).
CC       {ECO:0000269|PubMed:19470749, ECO:0000269|PubMed:21364279}.
CC   -!- INDUCTION: By stress conditions e.g. heat shock and oxidative stress
CC       under control of SigH. There is another promoter.
CC       {ECO:0000269|PubMed:11567012}.
CC   -!- SIMILARITY: Belongs to the heat shock protein 70 family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=CAA41306.1; Type=Frameshift; Evidence={ECO:0000305};
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DR   EMBL; X58406; CAA41306.1; ALT_FRAME; Genomic_DNA.
DR   EMBL; JX026662; AFM37299.1; -; Genomic_DNA.
DR   EMBL; AL123456; CCP43080.1; -; Genomic_DNA.
DR   PIR; G70574; G70574.
DR   RefSeq; NP_214864.1; NC_000962.3.
DR   RefSeq; WP_003401814.1; NZ_NVQJ01000002.1.
DR   PDB; 6W6E; EM; 3.70 A; I=1-625.
DR   PDB; 7L6N; EM; 7.00 A; I/J/K=1-625.
DR   PDBsum; 6W6E; -.
DR   PDBsum; 7L6N; -.
DR   AlphaFoldDB; P9WMJ9; -.
DR   SMR; P9WMJ9; -.
DR   IntAct; P9WMJ9; 1.
DR   STRING; 83332.Rv0350; -.
DR   PaxDb; P9WMJ9; -.
DR   PRIDE; P9WMJ9; -.
DR   DNASU; 885946; -.
DR   GeneID; 45424316; -.
DR   GeneID; 885946; -.
DR   KEGG; mtu:Rv0350; -.
DR   TubercuList; Rv0350; -.
DR   eggNOG; COG0443; Bacteria.
DR   OMA; ISIKRHM; -.
DR   PhylomeDB; P9WMJ9; -.
DR   Proteomes; UP000001584; Chromosome.
DR   GO; GO:0097691; C:bacterial extracellular vesicle; IDA:UniProtKB.
DR   GO; GO:0042603; C:capsule; IDA:CAFA.
DR   GO; GO:0009986; C:cell surface; IEA:UniProtKB-SubCell.
DR   GO; GO:0005829; C:cytosol; HDA:MTBBASE.
DR   GO; GO:0005576; C:extracellular region; IDA:CAFA.
DR   GO; GO:0009274; C:peptidoglycan-based cell wall; IDA:MTBBASE.
DR   GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-UniRule.
DR   GO; GO:0140662; F:ATP-dependent protein folding chaperone; IEA:InterPro.
DR   GO; GO:0001968; F:fibronectin binding; IPI:CAFA.
DR   GO; GO:0051082; F:unfolded protein binding; IEA:InterPro.
DR   GO; GO:0035375; F:zymogen binding; IPI:CAFA.
DR   GO; GO:0071451; P:cellular response to superoxide; IEP:MTBBASE.
DR   GO; GO:0010756; P:positive regulation of plasminogen activation; IDA:CAFA.
DR   GO; GO:2000679; P:positive regulation of transcription regulatory region DNA binding; IDA:CAFA.
DR   GO; GO:0046777; P:protein autophosphorylation; IDA:MTBBASE.
DR   GO; GO:0046677; P:response to antibiotic; IEP:MTBBASE.
DR   GO; GO:0046688; P:response to copper ion; IEP:MTBBASE.
DR   GO; GO:0009408; P:response to heat; IEP:MTBBASE.
DR   Gene3D; 1.20.1270.10; -; 1.
DR   Gene3D; 2.60.34.10; -; 1.
DR   HAMAP; MF_00332; DnaK; 1.
DR   InterPro; IPR043129; ATPase_NBD.
DR   InterPro; IPR012725; Chaperone_DnaK.
DR   InterPro; IPR018181; Heat_shock_70_CS.
DR   InterPro; IPR029048; HSP70_C_sf.
DR   InterPro; IPR029047; HSP70_peptide-bd_sf.
DR   InterPro; IPR013126; Hsp_70_fam.
DR   PANTHER; PTHR19375; PTHR19375; 2.
DR   Pfam; PF00012; HSP70; 2.
DR   SUPFAM; SSF100920; SSF100920; 1.
DR   SUPFAM; SSF100934; SSF100934; 1.
DR   SUPFAM; SSF53067; SSF53067; 2.
DR   TIGRFAMs; TIGR02350; prok_dnaK; 1.
DR   PROSITE; PS00297; HSP70_1; 1.
DR   PROSITE; PS00329; HSP70_2; 1.
DR   PROSITE; PS01036; HSP70_3; 1.
PE   1: Evidence at protein level;
KW   3D-structure; ATP-binding; Chaperone; Cytoplasm; Nucleotide-binding;
KW   Phosphoprotein; Reference proteome; Secreted; Stress response.
FT   CHAIN           1..625
FT                   /note="Chaperone protein DnaK"
FT                   /id="PRO_0000078499"
FT   REGION          586..625
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         175
FT                   /note="Phosphothreonine; by autocatalysis"
FT                   /evidence="ECO:0000250"
FT   CONFLICT        153..154
FT                   /note="LA -> PG (in Ref. 1; CAA41306)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   625 AA;  66831 MW;  23935906094D1A91 CRC64;
     MARAVGIDLG TTNSVVSVLE GGDPVVVANS EGSRTTPSIV AFARNGEVLV GQPAKNQAVT
     NVDRTVRSVK RHMGSDWSIE IDGKKYTAPE ISARILMKLK RDAEAYLGED ITDAVITTPA
     YFNDAQRQAT KDAGQIAGLN VLRIVNEPTA AALAYGLDKG EKEQRILVFD LGGGTFDVSL
     LEIGEGVVEV RATSGDNHLG GDDWDQRVVD WLVDKFKGTS GIDLTKDKMA MQRLREAAEK
     AKIELSSSQS TSINLPYITV DADKNPLFLD EQLTRAEFQR ITQDLLDRTR KPFQSVIADT
     GISVSEIDHV VLVGGSTRMP AVTDLVKELT GGKEPNKGVN PDEVVAVGAA LQAGVLKGEV
     KDVLLLDVTP LSLGIETKGG VMTRLIERNT TIPTKRSETF TTADDNQPSV QIQVYQGERE
     IAAHNKLLGS FELTGIPPAP RGIPQIEVTF DIDANGIVHV TAKDKGTGKE NTIRIQEGSG
     LSKEDIDRMI KDAEAHAEED RKRREEADVR NQAETLVYQT EKFVKEQREA EGGSKVPEDT
     LNKVDAAVAE AKAALGGSDI SAIKSAMEKL GQESQALGQA IYEAAQAASQ ATGAAHPGGE
     PGGAHPGSAD DVVDAEVVDD GREAK