TA47_TREPA
ID TA47_TREPA Reviewed; 434 AA.
AC P29723; O83584;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 15-DEC-1998, sequence version 2.
DT 03-AUG-2022, entry version 131.
DE RecName: Full=Putative DD-carboxypeptidase TP_0574 {ECO:0000303|PubMed:7972112};
DE EC=3.4.-.- {ECO:0000269|PubMed:7972112};
DE AltName: Full=47 kDa lipoprotein {ECO:0000303|PubMed:1372297};
DE Short=Tp47 {ECO:0000303|PubMed:12196546};
DE Short=Tpp47 {ECO:0000303|PubMed:7972112};
DE AltName: Full=47 kDa membrane antigen {ECO:0000303|PubMed:1372297};
DE AltName: Full=47-kilodalton major integral membrane immunogen {ECO:0000303|PubMed:9665876};
DE Flags: Precursor;
GN OrderedLocusNames=TP_0574;
OS Treponema pallidum (strain Nichols).
OC Bacteria; Spirochaetes; Spirochaetales; Treponemataceae; Treponema.
OX NCBI_TaxID=243276;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND PROTEIN SEQUENCE OF 84-96; 126-143;
RP 207-221; 266-298; 340-350; 366-390 AND 392-414.
RC STRAIN=Nichols;
RX PubMed=1372297; DOI=10.1128/iai.60.4.1568-1576.1992;
RA Weigel L.M., Brandt M.E., Norgard M.V.;
RT "Analysis of the N-terminal region of the 47-kilodalton integral membrane
RT lipoprotein of Treponema pallidum.";
RL Infect. Immun. 60:1568-1576(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Nichols;
RX PubMed=9665876; DOI=10.1126/science.281.5375.375;
RA Fraser C.M., Norris S.J., Weinstock G.M., White O., Sutton G.G.,
RA Dodson R.J., Gwinn M.L., Hickey E.K., Clayton R.A., Ketchum K.A.,
RA Sodergren E., Hardham J.M., McLeod M.P., Salzberg S.L., Peterson J.D.,
RA Khalak H.G., Richardson D.L., Howell J.K., Chidambaram M., Utterback T.R.,
RA McDonald L.A., Artiach P., Bowman C., Cotton M.D., Fujii C., Garland S.A.,
RA Hatch B., Horst K., Roberts K.M., Sandusky M., Weidman J.F., Smith H.O.,
RA Venter J.C.;
RT "Complete genome sequence of Treponema pallidum, the syphilis spirochete.";
RL Science 281:375-388(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 68-434, AND PROTEIN SEQUENCE OF 84-96;
RP 126-143; 207-221; 266-298; 340-350 AND 392-414.
RC STRAIN=Nichols;
RX PubMed=2642466; DOI=10.1128/iai.57.1.196-203.1989;
RA Hsu P.L., Chamberlain N.R., Orth K., Moomaw C.R., Zhang L.Q.,
RA Slaughter C.A., Radolf J.D., Sell S., Norgard M.V.;
RT "Sequence analysis of the 47-kilodalton major integral membrane immunogen
RT of Treponema pallidum.";
RL Infect. Immun. 57:196-203(1989).
RN [4]
RP PENICILLIN-BINDING, AND SUBCELLULAR LOCATION.
RC STRAIN=Nichols;
RX PubMed=2647634; DOI=10.1128/iai.57.4.1248-1254.1989;
RA Radolf J.D., Moomaw C., Slaughter C.A., Norgard M.V.;
RT "Penicillin-binding proteins and peptidoglycan of Treponema pallidum subsp.
RT pallidum.";
RL Infect. Immun. 57:1248-1254(1989).
RN [5]
RP PALMITOYLATION AT CYS-20, AND PROBABLE READTHROUGH.
RC STRAIN=Nichols;
RX PubMed=2668192; DOI=10.1128/iai.57.9.2878-2885.1989;
RA Chamberlain N.R., DeOgny L., Slaughter C., Radolf J.D., Norgard M.V.;
RT "Acylation of the 47-kilodalton major membrane immunogen of Treponema
RT pallidum determines its hydrophobicity.";
RL Infect. Immun. 57:2878-2885(1989).
RN [6]
RP POSSIBLE FUNCTION AS A ZINC-DEPENDENT CARBOXYPEPTIDASE, AND
RP PENICILLIN-BINDING.
RC STRAIN=Nichols;
RX PubMed=7972112; DOI=10.1073/pnas.91.24.11611;
RA Weigel L.M., Radolf J.D., Norgard M.V.;
RT "The 47-kDa major lipoprotein immunogen of Treponema pallidum is a
RT penicillin-binding protein with carboxypeptidase activity.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:11611-11615(1994).
RN [7]
RP FUNCTION IN INFECTION, SUBCELLULAR LOCATION, DIACYLGLYCEROL AT CYS-20, AND
RP PALMITOYLATION AT CYS-20.
RX PubMed=10426995; DOI=10.1126/science.285.5428.732;
RA Brightbill H.D., Libraty D.H., Krutzik S.R., Yang R.B., Belisle J.T.,
RA Bleharski J.R., Maitland M., Norgard M.V., Plevy S.E., Smale S.T.,
RA Brennan P.J., Bloom B.R., Godowski P.J., Modlin R.L.;
RT "Host defense mechanisms triggered by microbial lipoproteins through Toll-
RT like receptors.";
RL Science 285:732-736(1999).
RN [8]
RP FUNCTION IN HOST DENDRITIC CELL MATURATION.
RX PubMed=11160304; DOI=10.4049/jimmunol.166.4.2444;
RA Hertz C.J., Kiertscher S.M., Godowski P.J., Bouis D.A., Norgard M.V.,
RA Roth M.D., Modlin R.L.;
RT "Microbial lipopeptides stimulate dendritic cell maturation via Toll-like
RT receptor 2.";
RL J. Immunol. 166:2444-2450(2001).
RN [9] {ECO:0007744|PDB:1O75}
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 26-434, FUNCTION, SUBUNIT,
RP MUTAGENESIS OF 24-HIS--HIS-28; SER-119; LYS-306 AND CYS-315, AND
RP PENICILLIN-BINDING.
RX PubMed=12196546; DOI=10.1074/jbc.m207402200;
RA Deka R.K., Machius M., Norgard M.V., Tomchick D.R.;
RT "Crystal structure of the 47-kDa lipoprotein of Treponema pallidum reveals
RT a novel penicillin-binding protein.";
RL J. Biol. Chem. 277:41857-41864(2002).
CC -!- FUNCTION: A possible D,D-carboxypeptidase, that releases amino acids
CC sequentially from a proteins C-terminus (PubMed:7972112,
CC PubMed:12196546). Has zinc-dependent carboxypeptidase activity on
CC synthetic depsipeptide substrates (PubMed:7972112). May serve to
CC decrease cross-linking of peptidoglycan, promoting the highly sinusous
CC motility of this spirochaete (Probable). Overexpression of the whole
CC protein in E.coli leads to aberrant cell morphology and extrusion of
CC the cytoplasm, while overexpression of a construct with the first 62
CC resides of the protein fused to PhoA does have this effect, suggesting
CC the whole protein, not the lipoprotein moiety, is toxic
CC (PubMed:7972112). Binds penicillin (PubMed:2647634, PubMed:7972112).
CC Penicillin binding is covalent, does not require lipidation, and is
CC zinc-dependent (PubMed:7972112, PubMed:12196546). While this protein
CC has beta-lactamase activity in vitro, that is probably not its role in
CC vivo, as T.pallidum is very sensitive to penicillin antibiotics
CC (PubMed:12196546). {ECO:0000269|PubMed:12196546,
CC ECO:0000269|PubMed:2647634, ECO:0000269|PubMed:7972112,
CC ECO:0000305|PubMed:7972112}.
CC -!- FUNCTION: A pathogen-specific membrane antigen (PubMed:2642466,
CC PubMed:1372297). Most abundant of the membrane lipoproteins, only found
CC in pathogenic treponemes, suggesting that it is an important structural
CC moiety in the cell envelope of virulent treponemal subspecies. A
CC lipopeptide corresponding to the first 6 mature residues induces host
CC (human and mouse) cytokine release by monocyte cell lines via TLR2 and
CC CD14; nonlipidated protein does not stimulate host cells
CC (PubMed:10426995). Stimulates host (human) dendritic cell maturation to
CC become MHC class II-positive antigen presenting cells via TLR2, which
CC depends on lipidation; nonlipidated protein does not stimulate
CC maturation (PubMed:11160304). {ECO:0000269|PubMed:10426995,
CC ECO:0000269|PubMed:11160304, ECO:0000269|PubMed:1372297,
CC ECO:0000269|PubMed:2642466}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:7972112};
CC Note=Carboxypeptidase activity is stimulated by zinc (PubMed:7972112).
CC Penicillin-binding is stimulated by zinc (PubMed:12196546).
CC {ECO:0000269|PubMed:12196546, ECO:0000269|PubMed:7972112};
CC -!- SUBUNIT: Probably a monomer; a non-lipidated construct (residues 22-
CC 434) is monomeric in solution but crystallizes as a homodimer.
CC {ECO:0000269|PubMed:12196546}.
CC -!- SUBCELLULAR LOCATION: Cell inner membrane {ECO:0000305|PubMed:7972112};
CC Lipid-anchor {ECO:0000305|PubMed:10426995}.
CC -!- PTM: The N-terminus is blocked (PubMed:2642466). Present as a doublet
CC of low abundance 48 kDa and high abundance 47 kDa proteins
CC (PubMed:2647634, PubMed:2668192, PubMed:1372297). The longer form is
CC probably due to readthrough of the stop codon; the extra amino acids at
CC the C-terminus would be X-Lys-Arg-Gly-Val-Leu-Ser-Arg-Val-Ser, a
CC peptide antibody against this sequence detects only the 48 kDa form
CC (PubMed:2668192). {ECO:0000269|PubMed:1372297,
CC ECO:0000269|PubMed:2642466, ECO:0000269|PubMed:2647634,
CC ECO:0000269|PubMed:2668192}.
CC -!- MISCELLANEOUS: A recombinant non-lipidated form (residues 20-434) is
CC recognized by human antisera, indicating the lipidation site is not
CC essential for antigenicity, although the acylated lipopeptide clearly
CC is antigenic (PubMed:1372297, PubMed:10426995). The non-lipidated form
CC binds also penicillin (PubMed:7972112). {ECO:0000269|PubMed:10426995,
CC ECO:0000269|PubMed:1372297, ECO:0000269|PubMed:7972112}.
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DR EMBL; M88769; AAA75016.1; -; Genomic_DNA.
DR EMBL; M88769; AAA75017.1; ALT_TERM; Genomic_DNA.
DR EMBL; AE000520; AAC65545.1; -; Genomic_DNA.
DR PIR; D71309; D71309.
DR RefSeq; WP_010882021.1; NC_021490.2.
DR PDB; 1O75; X-ray; 1.95 A; A/B=20-434.
DR PDBsum; 1O75; -.
DR AlphaFoldDB; P29723; -.
DR SMR; P29723; -.
DR STRING; 243276.TPANIC_0574; -.
DR DrugBank; DB02879; 2,3-Di-O-Sulfo-Alpha-D-Glucopyranose.
DR PRIDE; P29723; -.
DR EnsemblBacteria; AAC65545; AAC65545; TP_0574.
DR KEGG; tpa:TP_0574; -.
DR HOGENOM; CLU_562301_0_0_12; -.
DR OMA; TRATTNH; -.
DR OrthoDB; 751593at2; -.
DR SABIO-RK; P29723; -.
DR EvolutionaryTrace; P29723; -.
DR Proteomes; UP000000811; Chromosome.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0008233; F:peptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR Gene3D; 2.60.40.1270; -; 1.
DR Gene3D; 2.60.40.1300; -; 1.
DR InterPro; IPR029220; BP-Tp47_dom_D.
DR InterPro; IPR029221; PBP-Tp47_A.
DR InterPro; IPR029218; PBP-Tp47_dom_C.
DR InterPro; IPR038698; PBP_Tp47_domC_sf.
DR InterPro; IPR038031; Tp47_mid_C_dom.
DR InterPro; IPR036154; Tp47_N_sf.
DR Pfam; PF14889; PBP-Tp47_a; 1.
DR Pfam; PF14888; PBP-Tp47_c; 1.
DR SUPFAM; SSF81986; SSF81986; 2.
DR SUPFAM; SSF82220; SSF82220; 1.
DR PROSITE; PS51257; PROKAR_LIPOPROTEIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell inner membrane; Cell membrane;
KW Direct protein sequencing; Hydrolase; Lipoprotein; Membrane; Palmitate;
KW Protease; Reference proteome; Signal.
FT SIGNAL 1..19
FT CHAIN 20..434
FT /note="Putative DD-carboxypeptidase TP_0574"
FT /id="PRO_0000018202"
FT LIPID 20
FT /note="N-palmitoyl cysteine"
FT /evidence="ECO:0000305|PubMed:10426995,
FT ECO:0000305|PubMed:2668192"
FT LIPID 20
FT /note="S-diacylglycerol cysteine"
FT /evidence="ECO:0000305|PubMed:10426995"
FT MUTAGEN 24..28
FT /note="HHETH->SHETS: Protein still binds ampicillin, in
FT nonlipidated fragment (residues 21-43), crystallized."
FT /evidence="ECO:0000303|PubMed:12196546"
FT MUTAGEN 119
FT /note="S->C,G: Protein still binds ampicillin and
FT penicillin, in nonlipidated fragment (residues 21-43)."
FT /evidence="ECO:0000303|PubMed:12196546"
FT MUTAGEN 306
FT /note="K->Q: Protein still binds ampicillin, in
FT nonlipidated fragment (residues 21-43)."
FT /evidence="ECO:0000303|PubMed:12196546"
FT MUTAGEN 315
FT /note="C->A: Protein still binds ampicillin, in
FT nonlipidated fragment (residues 21-43)."
FT /evidence="ECO:0000303|PubMed:12196546"
FT CONFLICT 239
FT /note="G -> V (in Ref. 1; AAA75016/AAA75017)"
FT /evidence="ECO:0000305"
FT STRAND 27..35
FT /evidence="ECO:0007829|PDB:1O75"
FT HELIX 36..44
FT /evidence="ECO:0007829|PDB:1O75"
FT HELIX 49..51
FT /evidence="ECO:0007829|PDB:1O75"
FT STRAND 67..70
FT /evidence="ECO:0007829|PDB:1O75"
FT STRAND 72..75
FT /evidence="ECO:0007829|PDB:1O75"
FT HELIX 79..84
FT /evidence="ECO:0007829|PDB:1O75"
FT TURN 85..87
FT /evidence="ECO:0007829|PDB:1O75"
FT STRAND 88..104
FT /evidence="ECO:0007829|PDB:1O75"
FT STRAND 110..126
FT /evidence="ECO:0007829|PDB:1O75"
FT STRAND 128..133
FT /evidence="ECO:0007829|PDB:1O75"
FT STRAND 139..143
FT /evidence="ECO:0007829|PDB:1O75"
FT STRAND 155..159
FT /evidence="ECO:0007829|PDB:1O75"
FT STRAND 162..182
FT /evidence="ECO:0007829|PDB:1O75"
FT HELIX 183..185
FT /evidence="ECO:0007829|PDB:1O75"
FT HELIX 186..193
FT /evidence="ECO:0007829|PDB:1O75"
FT STRAND 208..213
FT /evidence="ECO:0007829|PDB:1O75"
FT STRAND 231..239
FT /evidence="ECO:0007829|PDB:1O75"
FT STRAND 247..256
FT /evidence="ECO:0007829|PDB:1O75"
FT HELIX 264..271
FT /evidence="ECO:0007829|PDB:1O75"
FT STRAND 274..281
FT /evidence="ECO:0007829|PDB:1O75"
FT STRAND 293..295
FT /evidence="ECO:0007829|PDB:1O75"
FT TURN 300..302
FT /evidence="ECO:0007829|PDB:1O75"
FT STRAND 307..310
FT /evidence="ECO:0007829|PDB:1O75"
FT STRAND 312..317
FT /evidence="ECO:0007829|PDB:1O75"
FT HELIX 322..324
FT /evidence="ECO:0007829|PDB:1O75"
FT STRAND 329..338
FT /evidence="ECO:0007829|PDB:1O75"
FT STRAND 344..350
FT /evidence="ECO:0007829|PDB:1O75"
FT STRAND 359..372
FT /evidence="ECO:0007829|PDB:1O75"
FT TURN 374..379
FT /evidence="ECO:0007829|PDB:1O75"
FT STRAND 380..386
FT /evidence="ECO:0007829|PDB:1O75"
FT STRAND 392..398
FT /evidence="ECO:0007829|PDB:1O75"
FT STRAND 400..409
FT /evidence="ECO:0007829|PDB:1O75"
FT STRAND 414..420
FT /evidence="ECO:0007829|PDB:1O75"
FT STRAND 422..424
FT /evidence="ECO:0007829|PDB:1O75"
FT STRAND 427..432
FT /evidence="ECO:0007829|PDB:1O75"
SQ SEQUENCE 434 AA; 47665 MW; B5C2A75D4A8849E0 CRC64;
MKVKYALLSA GALQLLVVGC GSSHHETHYG YATLSYADYW AGELGQSRDV LLAGNAEADR
AGDLDAGMFD AVSRATHGHG AFRQQFQYAV EVLGEKVLSK QETEDSRGRK KWEYETDPSV
TKMVRASASF QDLGEDGEIK FEAVEGAVAL ADRASSFMVD SEEYKITNVK VHGMKFVPVA
VPHELKGIAK EKFHFVEDSR VTENTNGLKT MLTEDSFSAR KVSSMESPHD LVVDTVGTGY
HSRFGSDAEA SVMLKRADGS ELSHREFIDY VMNFNTVRYD YYGDDASYTN LMASYGTKHS
ADSWWKTGRV PRISCGINYG FDRFKGSGPG YYRLTLIANG YRDVVADVRF LPKYEGNIDI
GLKGKVLTIG GADAETLMDA AVDVFADGQP KLVSDQAVSL GQNVLSADFT PGTEYTVEVR
FKEFGSVRAK VVAQ
