ID   PPE02_MYCTO             Reviewed;         556 AA.
AC   P9WI46; L0T342; Q79FZ4; Q7DA58;
DT   16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT   16-APR-2014, sequence version 1.
DT   25-MAY-2022, entry version 29.
DE   RecName: Full=PPE family protein PPE2 {ECO:0000250|UniProtKB:P9WI47};
GN   Name=PPE2; OrderedLocusNames=MT0269;
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).
CC   -!- FUNCTION: Inhibits nitric oxide (NO) production in activated
CC       macrophages. Acts by inhibiting expression of the host inducible nitric
CC       oxide synthase (iNOS). PPE2 is translocated into the host macrophage
CC       nucleus, where it interacts with a GATA-binding site overlapping with
CC       the TATA box of NOS2 (iNOS) promoter, and strongly inhibits NOS2 gene
CC       transcription. Reduction in NO production in turn facilitates
CC       intracellular survival of the bacilli inside the macrophage. In
CC       addition, disrupts the assembly of NADPH oxidase complex, which
CC       inhibits NADPH oxidase-mediated reactive oxygen species (ROS)
CC       generation in macrophages and favors M.tuberculosis survival. Acts by
CC       interacting with NCF2, the cytosolic subunit of NADPH oxidase, and
CC       preventing translocation of NCF2 and NCF1 to the membrane, which causes
CC       a reduction of the functional assembly of NADPH oxidase complex and a
CC       decrease in NADPH oxidase activity. {ECO:0000250|UniProtKB:P9WI47}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P9WI47}. Host
CC       cytoplasm {ECO:0000250|UniProtKB:P9WI47}. Host nucleus
CC       {ECO:0000250|UniProtKB:P9WI47}.
CC   -!- DOMAIN: Contains a conserved PPE N-terminal domain and a variable C-
CC       terminal domain. The C-terminal region includes a SH3-like region, a
CC       leucine zipper DNA-binding motif and a functional nuclear localization
CC       signal (NLS). {ECO:0000250|UniProtKB:P9WI47}.
CC   -!- SIMILARITY: Belongs to the mycobacterial PPE family. {ECO:0000305}.
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DR   EMBL; AE000516; AAK44487.1; -; Genomic_DNA.
DR   PIR; D70940; D70940.
DR   RefSeq; WP_010924211.1; NC_002755.2.
DR   AlphaFoldDB; P9WI46; -.
DR   SMR; P9WI46; -.
DR   EnsemblBacteria; AAK44487; AAK44487; MT0269.
DR   KEGG; mtc:MT0269; -.
DR   HOGENOM; CLU_000243_5_2_11; -.
DR   Proteomes; UP000001020; Chromosome.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
DR   Gene3D; 1.20.1260.20; -; 1.
DR   InterPro; IPR043641; PPE-PPW_C.
DR   InterPro; IPR000030; PPE_family.
DR   InterPro; IPR038332; PPE_sf.
DR   Pfam; PF00823; PPE; 1.
DR   Pfam; PF18878; PPE-PPW; 1.
PE   3: Inferred from homology;
KW   Host cytoplasm; Host nucleus; Secreted; Virulence.
FT   CHAIN           1..556
FT                   /note="PPE family protein PPE2"
FT                   /id="PRO_0000428070"
FT   REGION          8..164
FT                   /note="PPE"
FT                   /evidence="ECO:0000250|UniProtKB:P9WI47"
FT   REGION          201..256
FT                   /note="SH3-like"
FT                   /evidence="ECO:0000250|UniProtKB:P9WI47"
FT   REGION          319..340
FT                   /note="Leucine zipper motif"
FT                   /evidence="ECO:0000250|UniProtKB:P9WI47"
FT   REGION          385..418
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          443..556
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           473..481
FT                   /note="Nuclear localization signal"
FT                   /evidence="ECO:0000250|UniProtKB:P9WI47"
FT   COMPBIAS        385..416
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ   SEQUENCE   556 AA;  56984 MW;  9E4EE08AED075DBF CRC64;
     MTAPIWMASP PEVHSALLSS GPGPGPLLVS AEGWHSLSIA YAETADELAA LLAAVQAGTW
     DGPTAAVYVA AHTPYLAWLV QASANSAAMA TRQETAATAY GTALAAMPTL AELGANHALH
     GVLMATNFFG INTIPIALNE SDYARMWIQA ATTMASYQAV STAAVAAAPQ TTPAPQIVKA
     NAPTAASDEP NQVQEWLQWL QKIGYTDFYN NVIQPFINWL TNLPFLQAMF SGFDPWLPSL
     GNPLTFLSPA NIAFALGYPM DIGSYVAFLS QTFAFIGADL AAAFASGNPA TIAFTLMFTT
     VEAIGTIITD TIALVKTLLE QTLALLPAAL PLLAAPLAPL TLAPASAAGG FAGLSGLAGL
     VGIPPSAPPV IPPVAAIAPS IPTPTPTPAP APAPTAVTAP TPPLGPPPPP VTAPPPVTGA
     GIQSFGYLVG DLNSAAQARK AVGTGVRKKT PEPDSAEAPA SAAAPEEQVQ PQRRRRPKIK
     QLGRGYEYLD LDPETGHDPT GSPQGAGTLG FAGTTHKASP GQVAGLITLP NDAFGGSPRT
     PMMPGTWDTD SATRVE