ID   PPE04_MYCTU             Reviewed;         513 AA.
AC   P9WI43; L0T372; Q6MX52; Q7DA35;
DT   16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT   16-APR-2014, sequence version 1.
DT   03-AUG-2022, entry version 34.
DE   RecName: Full=PPE family protein PPE4 {ECO:0000305};
GN   Name=PPE4; OrderedLocusNames=Rv0286;
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   IDENTIFICATION AS A DRUG TARGET [LARGE SCALE ANALYSIS].
RX   PubMed=19099550; DOI=10.1186/1752-0509-2-109;
RA   Raman K., Yeturu K., Chandra N.;
RT   "targetTB: a target identification pipeline for Mycobacterium tuberculosis
RT   through an interactome, reactome and genome-scale structural analysis.";
RL   BMC Syst. Biol. 2:109-109(2008).
RN   [3]
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).
RN   [4]
RP   FUNCTION IN IRON ACQUISITION, AND DISRUPTION PHENOTYPE.
RX   PubMed=26729876; DOI=10.1073/pnas.1523321113;
RA   Tufariello J.M., Chapman J.R., Kerantzas C.A., Wong K.W., Vilcheze C.,
RA   Jones C.M., Cole L.E., Tinaztepe E., Thompson V., Fenyoe D., Niederweis M.,
RA   Ueberheide B., Philips J.A., Jacobs W.R. Jr.;
RT   "Separable roles for Mycobacterium tuberculosis ESX-3 effectors in iron
RT   acquisition and virulence.";
RL   Proc. Natl. Acad. Sci. U.S.A. 113:E348-E357(2016).
CC   -!- FUNCTION: Important for the siderophore-mediated iron-acquisition
CC       function of ESX-3. {ECO:0000269|PubMed:26729876}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Multi-pass membrane
CC       protein {ECO:0000255}.
CC   -!- DISRUPTION PHENOTYPE: PE5-PPE4 double mutant exhibits a severe iron
CC       phenotype but secretes EsxG and EsxH normally. Mildly attenuated in
CC       vivo. {ECO:0000269|PubMed:26729876}.
CC   -!- MISCELLANEOUS: Was identified as a high-confidence drug target.
CC       {ECO:0000269|PubMed:19099550}.
CC   -!- SIMILARITY: Belongs to the mycobacterial PPE family. {ECO:0000305}.
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DR   EMBL; AL123456; CCP43016.1; -; Genomic_DNA.
DR   PIR; D70836; D70836.
DR   RefSeq; WP_003401488.1; NZ_NVQJ01000026.1.
DR   RefSeq; YP_177711.1; NC_000962.3.
DR   PDB; 6UUJ; X-ray; 3.00 A; B/E/H/K=1-178.
DR   PDB; 6VHR; X-ray; 3.30 A; B=1-178.
DR   PDBsum; 6UUJ; -.
DR   PDBsum; 6VHR; -.
DR   AlphaFoldDB; P9WI43; -.
DR   SASBDB; P9WI43; -.
DR   SMR; P9WI43; -.
DR   STRING; 83332.Rv0286; -.
DR   PaxDb; P9WI43; -.
DR   GeneID; 886607; -.
DR   KEGG; mtu:Rv0286; -.
DR   TubercuList; Rv0286; -.
DR   eggNOG; COG5651; Bacteria.
DR   OMA; PMGFAGT; -.
DR   PhylomeDB; P9WI43; -.
DR   Proteomes; UP000001584; 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:0052572; P:response to host immune response; IBA:GO_Central.
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   1: Evidence at protein level;
KW   3D-structure; Cell membrane; Membrane; Reference proteome; Transmembrane;
KW   Transmembrane helix.
FT   CHAIN           1..513
FT                   /note="PPE family protein PPE4"
FT                   /id="PRO_0000378475"
FT   TRANSMEM        233..253
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        277..297
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        309..329
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   REGION          395..446
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          469..513
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   HELIX           6..8
FT                   /evidence="ECO:0007829|PDB:6UUJ"
FT   HELIX           11..19
FT                   /evidence="ECO:0007829|PDB:6UUJ"
FT   STRAND          20..22
FT                   /evidence="ECO:0007829|PDB:6UUJ"
FT   HELIX           25..49
FT                   /evidence="ECO:0007829|PDB:6UUJ"
FT   HELIX           67..72
FT                   /evidence="ECO:0007829|PDB:6UUJ"
FT   HELIX           75..106
FT                   /evidence="ECO:0007829|PDB:6UUJ"
FT   HELIX           110..123
FT                   /evidence="ECO:0007829|PDB:6UUJ"
FT   HELIX           129..131
FT                   /evidence="ECO:0007829|PDB:6VHR"
FT   HELIX           135..163
FT                   /evidence="ECO:0007829|PDB:6UUJ"
SQ   SEQUENCE   513 AA;  51788 MW;  E8FBEB74E2F578E1 CRC64;
     MAAPIWMASP PEVHSALLSN GPGPGSLVAA ATAWSQLSAE YASTAAELSG LLGAVPGWAW
     QGPSAEWYVA AHLPYVAWLT QASADAAGAA AQHEAAAAAY TTALAAMPTL AELAANHVIH
     TVLVATNFFG INTIPITLNE ADYVRMWLQA AAVMGLYQAA SGAALASAPR TVPAPTVMNP
     GGGAASTVGA VNPWQWLLAL LQQLWNAYTG FYGWMLQLIW QFLQDPIGNS IKIIIAFLTN
     PIQALITYGP LLFALGYQIF FNLVGWPTWG MILSSPFLLP AGLGLGLAAI AFLPIVLAPA
     VIPPASTPLA AAAVAAGSVW PAVSMAVTGA GTAGAATPAA GAAPSAGAAP APAAPATASF
     AYAVGGSGDW GPSLGPTVGG RGGIKAPAAT VPAAAAAAAT RGQSRARRRR RSELRDYGDE
     FLDMDSDSGF GPSTGDHGAQ ASERGAGTLG FAGTATKERR VRAVGLTALA GDEFGNGPRM
     PMVPGTWEQG SNEPEAPDGS GRGGGDGLPH DSK