APA_MYCTU
ID APA_MYCTU Reviewed; 325 AA.
AC P9WIR7; L0T9G7; O08062; Q50906;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 25-MAY-2022, entry version 39.
DE RecName: Full=Alanine and proline-rich secreted protein Apa;
DE AltName: Full=45 kDa glycoprotein;
DE AltName: Full=45/47 kDa antigen {ECO:0000303|PubMed:7558311};
DE AltName: Full=Antigen MPT-32;
DE AltName: Full=FAP-B;
DE AltName: Full=Fibronectin attachment protein;
DE AltName: Full=Immunogenic protein MPT32;
DE Flags: Precursor;
GN Name=apa; Synonyms=modD; OrderedLocusNames=Rv1860; ORFNames=MTCY359.13;
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 25618 / H37Rv;
RX PubMed=7558311; DOI=10.1128/iai.63.10.4003-4010.1995;
RA Laqueyrerie A., Militzer P., Romain F., Eiglmeier K., Cole S., Marchel G.;
RT "Cloning, sequencing, and expression of the apa gene coding for the
RT Mycobacterium tuberculosis 45/47-kilodalton secreted antigen complex.";
RL Infect. Immun. 63:4003-4010(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RA Laqueyrerie A.;
RL Submitted (MAR-1997) 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 PARTIAL PROTEIN SEQUENCE, AND CHARACTERIZATION.
RX PubMed=1898899; DOI=10.1128/iai.59.1.372-382.1991;
RA Nagai S., Wiker H.G., Harboe M., Kinomoto M.;
RT "Isolation and partial characterization of major protein antigens in the
RT culture fluid of Mycobacterium tuberculosis.";
RL Infect. Immun. 59:372-382(1991).
RN [5]
RP PARTIAL PROTEIN SEQUENCE, AND GLYCOSYLATION.
RX PubMed=7622204; DOI=10.1128/iai.63.8.2846-2853.1995;
RA Dobos K.M., Swiderek K., Khoo K.-H., Brennan P.J., Belisle J.T.;
RT "Evidence for glycosylation sites on the 45-kilodalton glycoprotein of
RT Mycobacterium tuberculosis.";
RL Infect. Immun. 63:2846-2853(1995).
RN [6]
RP PARTIAL PROTEIN SEQUENCE, GLYCOSYLATION AT THR-49; THR-57; THR-66 AND
RP THR-316, AND STRUCTURE OF CARBOHYDRATE.
RX PubMed=8626314; DOI=10.1128/jb.178.9.2498-2506.1996;
RA Dobos K.M., Khoo K.-H., Swiderek K.M., Brennan P.J., Belisle J.T.;
RT "Definition of the full extent of glycosylation of the 45-kilodalton
RT glycoprotein of Mycobacterium tuberculosis.";
RL J. Bacteriol. 178:2498-2506(1996).
RN [7]
RP PROTEIN SEQUENCE OF 40-49, CHARACTERIZATION OF GLYCOSYLATION BY MASS
RP SPECTROMETRY, AND BIOTECHNOLOGY.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=10542234; DOI=10.1074/jbc.274.45.32023;
RA Horn C., Namane A., Pescher P., Riviere M., Romain F., Puzo G., Barzu O.,
RA Marchal G.;
RT "Decreased capacity of recombinant 45/47-kDa molecules (Apa) of
RT Mycobacterium tuberculosis to stimulate T lymphocyte responses related to
RT changes in their mannosylation pattern.";
RL J. Biol. Chem. 274:32023-32030(1999).
RN [8]
RP PROTEIN SEQUENCE OF 40-57, FUNCTION, CHARACTERIZATION OF GLYCOSYLATION BY
RP MASS SPECTROMETRY, AND BIOTECHNOLOGY.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=10531201; DOI=10.1128/iai.67.11.5567-5572.1999;
RA Romain F., Horn C., Pescher P., Namane A., Riviere M., Puzo G., Barzu O.,
RA Marchal G.;
RT "Deglycosylation of the 45/47-kilodalton antigen complex of Mycobacterium
RT tuberculosis decreases its capacity to elicit in vivo or in vitro cellular
RT immune responses.";
RL Infect. Immun. 67:5567-5572(1999).
RN [9]
RP FUNCTION, AND BIOTECHNOLOGY.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=12654810; DOI=10.1128/iai.71.4.1929-1937.2003;
RA Kumar P., Amara R.R., Challu V.K., Chadda V.K., Satchidanandam V.;
RT "The Apa protein of Mycobacterium tuberculosis stimulates gamma interferon-
RT secreting CD4+ and CD8+ T cells from purified protein derivative-positive
RT individuals and affords protection in a guinea pig model.";
RL Infect. Immun. 71:1929-1937(2003).
RN [10]
RP FUNCTION.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=16092920; DOI=10.1042/bj20050709;
RA Pitarque S., Herrmann J.L., Duteyrat J.L., Jackson M., Stewart G.R.,
RA Lecointe F., Payre B., Schwartz O., Young D.B., Marchal G., Lagrange P.H.,
RA Puzo G., Gicquel B., Nigou J., Neyrolles O.;
RT "Deciphering the molecular bases of Mycobacterium tuberculosis binding to
RT the lectin DC-SIGN reveals an underestimated complexity.";
RL Biochem. J. 392:615-624(2005).
RN [11]
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 [12]
RP FUNCTION, SUBCELLULAR LOCATION, AND GLYCOSYLATION.
RC STRAIN=H37Rv;
RX PubMed=25359607; DOI=10.1111/sji.12249;
RA Esparza M., Palomares B., Garcia T., Espinosa P., Zenteno E., Mancilla R.;
RT "PstS-1, the 38-kDa Mycobacterium tuberculosis glycoprotein, is an adhesin,
RT which binds the macrophage mannose receptor and promotes phagocytosis.";
RL Scand. J. Immunol. 81:46-55(2015).
CC -!- FUNCTION: A potent antigen in animals immunized with live bacteria, it
CC induces a strong delayed-type hypersensitivity (DTH) in immunized
CC animals (PubMed:10531201). Elicits a mostly Th1 type of T-cell response
CC in healthy humans; induces IFN-gamma production from CD4(+) and CD8(+)
CC cells (PubMed:12654810). Functions as an adhesin, binds to mouse
CC macrophages via mannose residues (PubMed:10531201, PubMed:25359607).
CC Might interact via host CD209 (PubMed:16092920).
CC {ECO:0000269|PubMed:10531201, ECO:0000269|PubMed:12654810,
CC ECO:0000269|PubMed:16092920, ECO:0000269|PubMed:25359607}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:10531201}. Cell
CC surface {ECO:0000269|PubMed:25359607}.
CC -!- PTM: Glycosylated, with mannose residues (PubMed:8626314,
CC PubMed:10542234, PubMed:10531201, PubMed:25359607). The secreted
CC protein has from 0 to 9 mannose residues, the majority have 6, 7, or 8
CC mannose residues (22, 24 and 17% respectively) (PubMed:10531201).
CC Deglycosylated molecules had a significantly lower capacity to elicit a
CC DTH reaction in guinea pigs in vivo or to activate specific T
CC lymphocytes in vitro (PubMed:10531201). Pretreating mouse macrophages
CC with mannan decreases binding of M.tuberculosis (PubMed:25359607). The
CC non-glycosylated form stimulates IFN-gamma production however, so
CC glycosylation is not essential (PubMed:12654810).
CC {ECO:0000269|PubMed:10531201, ECO:0000269|PubMed:10542234,
CC ECO:0000269|PubMed:25359607, ECO:0000269|PubMed:8626314,
CC ECO:0000305|PubMed:12654810}.
CC -!- PTM: Runs as 45 and 47 kDa protein, the nature of the difference
CC between the 2 forms is not known but is still seen after alpha-
CC mannosidase treatment (PubMed:10531201). {ECO:0000269|PubMed:10531201}.
CC -!- MASS SPECTROMETRY: Mass=28782; Mass_error=1.6; Method=Electrospray;
CC Note=Chemically or enzymatically deglycosylated protein.;
CC Evidence={ECO:0000269|PubMed:10531201};
CC -!- BIOTECHNOLOGY: Major immunodominant antigen that has potential as a
CC vaccine against tuberculosis (PubMed:10542234, PubMed:10531201,
CC PubMed:12654810). Can be used as a DNA vaccine in guinea pigs
CC (PubMed:12654810). Apa-ELISA could be used in diagnosis.
CC {ECO:0000269|PubMed:10531201, ECO:0000269|PubMed:10542234,
CC ECO:0000269|PubMed:12654810}.
CC -!- SIMILARITY: Belongs to the Apa family. {ECO:0000305}.
CC -!- CAUTION: Was originally thought to be involved in molybdenum transport.
CC {ECO:0000305}.
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DR EMBL; X80268; CAA56555.1; -; Genomic_DNA.
DR EMBL; X99258; CAA67645.1; -; Genomic_DNA.
DR EMBL; AL123456; CCP44626.1; -; Genomic_DNA.
DR PIR; D70666; D70666.
DR RefSeq; WP_003911690.1; NZ_NVQJ01000013.1.
DR RefSeq; YP_177849.1; NC_000962.3.
DR PDB; 5ZX9; X-ray; 1.55 A; A=1-325.
DR PDB; 5ZXA; X-ray; 1.77 A; A=1-325.
DR PDBsum; 5ZX9; -.
DR PDBsum; 5ZXA; -.
DR AlphaFoldDB; P9WIR7; -.
DR SMR; P9WIR7; -.
DR STRING; 83332.Rv1860; -.
DR iPTMnet; P9WIR7; -.
DR PaxDb; P9WIR7; -.
DR GeneID; 885896; -.
DR KEGG; mtu:Rv1860; -.
DR TubercuList; Rv1860; -.
DR eggNOG; ENOG50346X3; Bacteria.
DR OMA; WVESDAS; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0009986; C:cell surface; IEA:UniProtKB-SubCell.
DR GO; GO:0005576; C:extracellular region; IDA:MTBBASE.
DR GO; GO:0050840; F:extracellular matrix binding; IEA:InterPro.
DR GO; GO:0009267; P:cellular response to starvation; IEP:MTBBASE.
DR GO; GO:0052559; P:induction by symbiont of host immune response; IDA:MTBBASE.
DR InterPro; IPR010801; FAP.
DR Pfam; PF07174; FAP; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Glycoprotein; Reference proteome;
KW Repeat; Secreted; Signal.
FT SIGNAL 1..39
FT /evidence="ECO:0000269|PubMed:10531201,
FT ECO:0000269|PubMed:10542234"
FT CHAIN 40..325
FT /note="Alanine and proline-rich secreted protein Apa"
FT /id="PRO_0000020745"
FT REPEAT 85..88
FT /note="1"
FT REPEAT 94..97
FT /note="2"
FT REPEAT 104..107
FT /note="3"
FT REGION 38..110
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 85..107
FT /note="3 X 4 AA approximate repeats of [DA]-P-N-A"
FT REGION 286..325
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 39..107
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 49
FT /note="O-linked (Man...) threonine"
FT /evidence="ECO:0000269|PubMed:8626314"
FT CARBOHYD 57
FT /note="O-linked (Man...) threonine"
FT /evidence="ECO:0000269|PubMed:8626314"
FT CARBOHYD 66
FT /note="O-linked (Man) threonine"
FT /evidence="ECO:0000269|PubMed:8626314"
FT CARBOHYD 316
FT /note="O-linked (Man...) threonine"
FT /evidence="ECO:0000269|PubMed:8626314"
FT STRAND 112..115
FT /evidence="ECO:0007829|PDB:5ZX9"
FT TURN 116..119
FT /evidence="ECO:0007829|PDB:5ZX9"
FT STRAND 120..123
FT /evidence="ECO:0007829|PDB:5ZX9"
FT STRAND 128..131
FT /evidence="ECO:0007829|PDB:5ZX9"
FT HELIX 133..138
FT /evidence="ECO:0007829|PDB:5ZX9"
FT STRAND 140..146
FT /evidence="ECO:0007829|PDB:5ZX9"
FT STRAND 164..169
FT /evidence="ECO:0007829|PDB:5ZX9"
FT HELIX 182..197
FT /evidence="ECO:0007829|PDB:5ZX9"
FT STRAND 202..214
FT /evidence="ECO:0007829|PDB:5ZX9"
FT STRAND 217..230
FT /evidence="ECO:0007829|PDB:5ZX9"
FT STRAND 236..244
FT /evidence="ECO:0007829|PDB:5ZX9"
FT STRAND 258..269
FT /evidence="ECO:0007829|PDB:5ZX9"
FT HELIX 273..281
FT /evidence="ECO:0007829|PDB:5ZX9"
SQ SEQUENCE 325 AA; 32721 MW; 59E5D0455A997BED CRC64;
MHQVDPNLTR RKGRLAALAI AAMASASLVT VAVPATANAD PEPAPPVPTT AASPPSTAAA
PPAPATPVAP PPPAAANTPN AQPGDPNAAP PPADPNAPPP PVIAPNAPQP VRIDNPVGGF
SFALPAGWVE SDAAHFDYGS ALLSKTTGDP PFPGQPPPVA NDTRIVLGRL DQKLYASAEA
TDSKAAARLG SDMGEFYMPY PGTRINQETV SLDANGVSGS ASYYEVKFSD PSKPNGQIWT
GVIGSPAANA PDAGPPQRWF VVWLGTANNP VDKGAAKALA ESIRPLVAPP PAPAPAPAEP
APAPAPAGEV APTPTTPTPQ RTLPA
