HBP2_LISMO
ID HBP2_LISMO Reviewed; 569 AA.
AC Q7AP54;
DT 05-DEC-2018, integrated into UniProtKB/Swiss-Prot.
DT 16-MAY-2012, sequence version 1.
DT 03-AUG-2022, entry version 57.
DE RecName: Full=Hemin/hemoglobin-binding protein 2 {ECO:0000303|PubMed:21545655};
DE Short=Hn/Hb-binding protein 2 {ECO:0000303|PubMed:21545655};
DE AltName: Full=P64;
DE AltName: Full=Surface virulence-associated protein A {ECO:0000303|PubMed:11700342};
DE Flags: Precursor;
GN Name=hbp2 {ECO:0000303|PubMed:21545655};
GN Synonyms=svpA {ECO:0000303|PubMed:11700342}; OrderedLocusNames=lmo2185;
OS Listeria monocytogenes serovar 1/2a (strain ATCC BAA-679 / EGD-e).
OC Bacteria; Firmicutes; Bacilli; Bacillales; Listeriaceae; Listeria.
OX NCBI_TaxID=169963;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC BAA-679 / EGD-e;
RX PubMed=11679669; DOI=10.1126/science.1063447;
RA Glaser P., Frangeul L., Buchrieser C., Rusniok C., Amend A., Baquero F.,
RA Berche P., Bloecker H., Brandt P., Chakraborty T., Charbit A.,
RA Chetouani F., Couve E., de Daruvar A., Dehoux P., Domann E.,
RA Dominguez-Bernal G., Duchaud E., Durant L., Dussurget O., Entian K.-D.,
RA Fsihi H., Garcia-del Portillo F., Garrido P., Gautier L., Goebel W.,
RA Gomez-Lopez N., Hain T., Hauf J., Jackson D., Jones L.-M., Kaerst U.,
RA Kreft J., Kuhn M., Kunst F., Kurapkat G., Madueno E., Maitournam A.,
RA Mata Vicente J., Ng E., Nedjari H., Nordsiek G., Novella S., de Pablos B.,
RA Perez-Diaz J.-C., Purcell R., Remmel B., Rose M., Schlueter T., Simoes N.,
RA Tierrez A., Vazquez-Boland J.-A., Voss H., Wehland J., Cossart P.;
RT "Comparative genomics of Listeria species.";
RL Science 294:849-852(2001).
RN [2]
RP ACTIVITY REGULATION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RC STRAIN=LO28;
RX PubMed=11700342; DOI=10.1099/00221287-147-11-2913;
RA Borezee E., Pellegrini E., Beretti J.L., Berche P.;
RT "SvpA, a novel surface virulence-associated protein required for
RT intracellular survival of Listeria monocytogenes.";
RL Microbiology 147:2913-2923(2001).
RN [3]
RP SUBCELLULAR LOCATION, INDUCTION, AND OPERON.
RC STRAIN=ATCC BAA-679 / EGD-e;
RX PubMed=15028680; DOI=10.1128/jb.186.7.1972-1982.2004;
RA Bierne H., Garandeau C., Pucciarelli M.G., Sabet C., Newton S.,
RA Garcia-del Portillo F., Cossart P., Charbit A.;
RT "Sortase B, a new class of sortase in Listeria monocytogenes.";
RL J. Bacteriol. 186:1972-1982(2004).
RN [4]
RP FUNCTION, HEMIN-BINDING, SUBCELLULAR LOCATION, INDUCTION BY IRON-DEPLETION,
RP AND DISRUPTION PHENOTYPE.
RC STRAIN=ATCC BAA-679 / EGD-e;
RX PubMed=15661014; DOI=10.1111/j.1365-2958.2004.04436.x;
RA Newton S.M., Klebba P.E., Raynaud C., Shao Y., Jiang X., Dubail I.,
RA Archer C., Frehel C., Charbit A.;
RT "The svpA-srtB locus of Listeria monocytogenes: fur-mediated iron
RT regulation and effect on virulence.";
RL Mol. Microbiol. 55:927-940(2005).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY, INDUCTION, AND PROCESSING BY SRTB.
RC STRAIN=ATCC BAA-679 / EGD-e;
RX PubMed=16247833; DOI=10.1002/pmic.200402075;
RA Pucciarelli M.G., Calvo E., Sabet C., Bierne H., Cossart P.,
RA Garcia-del Portillo F.;
RT "Identification of substrates of the Listeria monocytogenes sortases A and
RT B by a non-gel proteomic analysis.";
RL Proteomics 5:4808-4817(2005).
RN [6]
RP DISRUPTION PHENOTYPE.
RC STRAIN=ATCC BAA-679 / EGD-e;
RX PubMed=16430693; DOI=10.1111/j.1365-2958.2005.05015.x;
RA Jin B., Newton S.M., Shao Y., Jiang X., Charbit A., Klebba P.E.;
RT "Iron acquisition systems for ferric hydroxamates, haemin and haemoglobin
RT in Listeria monocytogenes.";
RL Mol. Microbiol. 59:1185-1198(2006).
RN [7]
RP SUBCELLULAR LOCATION, PROCESSING BY SRTB, SORTING SIGNAL, AND MUTAGENESIS
RP OF 536-ASN--ASN-540.
RC STRAIN=ATCC BAA-679 / EGD-e;
RX PubMed=19129190; DOI=10.1074/jbc.m807989200;
RA Mariscotti J.F., Garcia-del Portillo F., Pucciarelli M.G.;
RT "The Listeria monocytogenes sortase-B recognizes varied amino acids at
RT position 2 of the sorting motif.";
RL J. Biol. Chem. 284:6140-6146(2009).
RN [8]
RP SUBCELLULAR LOCATION, AND INDUCTION.
RC STRAIN=ATCC BAA-679 / EGD-e;
RX PubMed=21725001; DOI=10.1128/jb.01154-10;
RA Bruck S., Personnic N., Prevost M.C., Cossart P., Bierne H.;
RT "Regulated shift from helical to polar localization of Listeria
RT monocytogenes cell wall-anchored proteins.";
RL J. Bacteriol. 193:4425-4437(2011).
RN [9]
RP FUNCTION, HEMIN-BINDING, AND DISRUPTION PHENOTYPE.
RC STRAIN=ATCC BAA-679 / EGD-e;
RX PubMed=21545655; DOI=10.1111/j.1365-2958.2011.07667.x;
RA Xiao Q., Jiang X., Moore K.J., Shao Y., Pi H., Dubail I., Charbit A.,
RA Newton S.M., Klebba P.E.;
RT "Sortase independent and dependent systems for acquisition of haem and
RT haemoglobin in Listeria monocytogenes.";
RL Mol. Microbiol. 80:1581-1597(2011).
RN [10] {ECO:0007744|PDB:4MYP, ECO:0007744|PDB:4NLA}
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 183-303 IN COMPLEX WITH AND
RP WITHOUT HEME, FUNCTION IN HEMIN AND HEMOGLOBIN-BINDING, DOMAIN, AND
RP MUTAGENESIS OF TYR-280 AND TYR-289.
RC STRAIN=ATCC BAA-679 / EGD-e;
RX PubMed=25315777; DOI=10.1074/jbc.m114.583013;
RA Malmirchegini G.R., Sjodt M., Shnitkind S., Sawaya M.R., Rosinski J.,
RA Newton S.M., Klebba P.E., Clubb R.T.;
RT "Novel mechanism of hemin capture by Hbp2, the hemoglobin-binding hemophore
RT from Listeria monocytogenes.";
RL J. Biol. Chem. 289:34886-34899(2014).
CC -!- FUNCTION: Acts as an extracellular and cell wall-bound hemophore;
CC scavenges host heme and hemoglobin from the environment and also serves
CC as a cell wall receptor for both (Probable). At low hemin (Hn) and
CC hemoglobin (Hb) concentrations adsorbs Hn/Hb and presumably directs it
CC to membrane transporters (Probable). Soluble Hbp2 can probably pass
CC Hn/Hb to cell wall-anchored Hbp2, and both forms can accept Hn/Hb from
CC Hbp1 (PubMed:25315777). May be involved in crossing the digestive
CC barrier in infected animals (PubMed:15661014). Binds host hemin
CC (Probable) (PubMed:21545655, PubMed:25315777). Binds host hemoglobin
CC with affinity in the nanomolar range (PubMed:25315777).
CC {ECO:0000269|PubMed:15661014, ECO:0000269|PubMed:21545655,
CC ECO:0000269|PubMed:25315777, ECO:0000305|PubMed:15661014,
CC ECO:0000305|PubMed:21545655, ECO:0000305|PubMed:25315777}.
CC -!- ACTIVITY REGULATION: Is overexpressed in mecA, clpC and clpP mutants,
CC suggesting the protein level is controlled by MecA, ClpC and ClpP (at
CC protein level). {ECO:0000269|PubMed:11700342}.
CC -!- SUBCELLULAR LOCATION: Cell surface {ECO:0000269|PubMed:11700342}.
CC Secreted, cell wall {ECO:0000269|PubMed:15028680,
CC ECO:0000269|PubMed:16247833, ECO:0000269|PubMed:19129190,
CC ECO:0000269|PubMed:21725001}; Peptidoglycan-anchor
CC {ECO:0000269|PubMed:16247833, ECO:0000269|PubMed:19129190,
CC ECO:0000305|PubMed:15028680}. Secreted {ECO:0000269|PubMed:15028680,
CC ECO:0000269|PubMed:15661014, ECO:0000305|PubMed:11700342}. Note=Most
CC protein is secreted (PubMed:15028680, PubMed:15661014). Cell wall
CC attachment is iron-regulated, only occurring when iron levels are low
CC or fur is deleted (PubMed:15661014). Cell wall-anchored protein
CC localizes to one cell pole or laterally (PubMed:15028680). Protein does
CC not have to be cell wall-anchored for virulence (PubMed:15028680).
CC During exponential growth detected on the cell surface as a series of
CC dots in a helical pattern, it is excluded from the septum
CC (PubMed:21725001). The helical pattern of InlA does not overlap with
CC that of InlH, InlJ or Hbp2 (PubMed:21725001). Under iron-limiting
CC conditions accumulates at the old cell pole (PubMed:21725001).
CC {ECO:0000269|PubMed:15028680, ECO:0000269|PubMed:15661014,
CC ECO:0000269|PubMed:21725001}.
CC -!- INDUCTION: Expressed in mid-log phase, cotranscribed with lmo2184, the
CC second gene in a possible lmo2186-lmo2180 operon (PubMed:15028680).
CC Present in both exponential and stationary phase; more protein is
CC expressed in log phase (at protein level) (PubMed:15028680,
CC PubMed:16247833, PubMed:21725001). Induced under iron-deficient
CC conditions and when fur (lmo1956, AC Q8Y5U9) is deleted (at protein
CC level) (PubMed:15661014). Induced when bacteria are grown in human cell
CC lines (PubMed:15661014). {ECO:0000269|PubMed:15028680,
CC ECO:0000269|PubMed:15661014, ECO:0000269|PubMed:16247833,
CC ECO:0000269|PubMed:21725001}.
CC -!- DOMAIN: Each NEAT domain binds hemin, whereas only NEAT1 and NEAT3 bind
CC hemoglobin. {ECO:0000269|PubMed:25315777}.
CC -!- DISRUPTION PHENOTYPE: Moderate reduction in growth rate at 37 degrees
CC Celsius, reduced bacterial density in stationary phase (in strain
CC LO28); no change in bacterial adherence to Caco-2 cells
CC (PubMed:11700342). 2-fold reduction virulence in mice
CC (PubMed:15661014). Does not impair iron transport (PubMed:15661014,
CC PubMed:16430693). More sensitive measurements show that disruption
CC decreases hemin uptake at low concentrations (0.5 uM and 5 uM; at 50 uM
CC no effect is seen) (PubMed:21545655). Decreased hemin-binding and hemin
CC uptake by whole bacteria at low concentrations of iron
CC (PubMed:21545655). {ECO:0000269|PubMed:11700342,
CC ECO:0000269|PubMed:15661014, ECO:0000269|PubMed:16430693,
CC ECO:0000269|PubMed:21545655}.
CC -!- CAUTION: Was originally thought to have a more extreme phenotype upon
CC deletion; however the 100-fold reduction in virulence of the first
CC deletion experiment, and impairment of phagosome escape seen in
CC infected mice, is probably due to the kanamycin-cassette derivative
CC used in that experiment. {ECO:0000269|PubMed:11700342,
CC ECO:0000305|PubMed:15661014}.
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DR EMBL; AL591982; CAD00263.1; -; Genomic_DNA.
DR PIR; AI1347; AI1347.
DR RefSeq; NP_465709.1; NC_003210.1.
DR RefSeq; WP_003722309.1; NZ_CP023861.1.
DR PDB; 4MYP; X-ray; 1.80 A; A/B=183-303.
DR PDB; 4NLA; X-ray; 2.70 A; A=183-303.
DR PDBsum; 4MYP; -.
DR PDBsum; 4NLA; -.
DR AlphaFoldDB; Q7AP54; -.
DR SMR; Q7AP54; -.
DR STRING; 169963.lmo2185; -.
DR PaxDb; Q7AP54; -.
DR EnsemblBacteria; CAD00263; CAD00263; CAD00263.
DR GeneID; 984803; -.
DR KEGG; lmo:lmo2185; -.
DR PATRIC; fig|169963.11.peg.2237; -.
DR eggNOG; COG5386; Bacteria.
DR HOGENOM; CLU_008730_0_0_9; -.
DR OMA; MAWYITL; -.
DR BioCyc; LMON169963:LMO2185-MON; -.
DR Proteomes; UP000000817; Chromosome.
DR GO; GO:0009986; C:cell surface; IEA:UniProtKB-SubCell.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0071281; P:cellular response to iron ion; IEP:CollecTF.
DR GO; GO:0006811; P:ion transport; IEA:UniProtKB-KW.
DR GO; GO:0055072; P:iron ion homeostasis; IEA:UniProtKB-KW.
DR CDD; cd06920; NEAT; 3.
DR Gene3D; 2.60.40.1850; -; 3.
DR InterPro; IPR006635; NEAT_dom.
DR InterPro; IPR037250; NEAT_dom_sf.
DR InterPro; IPR017502; Sortase_SrtB_target.
DR Pfam; PF05031; NEAT; 3.
DR SMART; SM00725; NEAT; 3.
DR SUPFAM; SSF158911; SSF158911; 3.
DR TIGRFAMs; TIGR03063; srtB_target; 1.
DR PROSITE; PS50978; NEAT; 3.
PE 1: Evidence at protein level;
KW 3D-structure; Cell wall; Heme; Ion transport; Iron; Iron transport;
KW Metal-binding; Peptidoglycan-anchor; Reference proteome; Repeat; Secreted;
KW Signal; Transport; Virulence.
FT SIGNAL 1..28
FT /evidence="ECO:0000255"
FT CHAIN 29..569
FT /note="Hemin/hemoglobin-binding protein 2"
FT /evidence="ECO:0000255"
FT /id="PRO_5004287703"
FT PROPEP 540..569
FT /note="Removed by sortase B"
FT /evidence="ECO:0000305|PubMed:16247833,
FT ECO:0000305|PubMed:19129190"
FT /id="PRO_0000445906"
FT DOMAIN 34..173
FT /note="NEAT 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00337"
FT DOMAIN 184..307
FT /note="NEAT 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00337,
FT ECO:0000305|PubMed:25315777"
FT DOMAIN 360..484
FT /note="NEAT 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00337"
FT REGION 307..357
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 502..537
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 536..540
FT /note="NXZTN sorting signal"
FT /evidence="ECO:0000269|PubMed:19129190,
FT ECO:0000305|PubMed:16247833"
FT COMPBIAS 321..351
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 522..537
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 204..205
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /evidence="ECO:0000269|PubMed:25315777"
FT BINDING 280
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000269|PubMed:25315777,
FT ECO:0007744|PDB:4MYP"
FT BINDING 289
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /evidence="ECO:0000269|PubMed:25315777"
FT MOD_RES 539
FT /note="Pentaglycyl murein peptidoglycan amidated threonine"
FT /evidence="ECO:0000305|PubMed:16247833"
FT MUTAGEN 280
FT /note="Y->A: NEAT domain 2 no longer binds hemin."
FT /evidence="ECO:0000269|PubMed:25315777"
FT MUTAGEN 289
FT /note="Y->A: NEAT domain 2 binds hemin with considerably
FT less affinity."
FT /evidence="ECO:0000269|PubMed:25315777"
FT MUTAGEN 536..540
FT /note="Missing: No longer attached to the cell wall."
FT /evidence="ECO:0000269|PubMed:19129190"
FT MUTAGEN 537..540
FT /note="AKTN->PKSS: No change in cell wall attachment."
FT /evidence="ECO:0000269|PubMed:19129190"
FT MUTAGEN 537..538
FT /note="AK->KV: No longer attached to the cell wall."
FT /evidence="ECO:0000269|PubMed:19129190"
FT STRAND 186..191
FT /evidence="ECO:0007829|PDB:4MYP"
FT STRAND 193..203
FT /evidence="ECO:0007829|PDB:4MYP"
FT HELIX 205..209
FT /evidence="ECO:0007829|PDB:4MYP"
FT STRAND 212..219
FT /evidence="ECO:0007829|PDB:4MYP"
FT STRAND 222..230
FT /evidence="ECO:0007829|PDB:4MYP"
FT TURN 232..234
FT /evidence="ECO:0007829|PDB:4MYP"
FT STRAND 235..242
FT /evidence="ECO:0007829|PDB:4MYP"
FT STRAND 245..248
FT /evidence="ECO:0007829|PDB:4MYP"
FT STRAND 250..255
FT /evidence="ECO:0007829|PDB:4MYP"
FT TURN 256..259
FT /evidence="ECO:0007829|PDB:4MYP"
FT STRAND 260..266
FT /evidence="ECO:0007829|PDB:4MYP"
FT STRAND 274..284
FT /evidence="ECO:0007829|PDB:4MYP"
FT STRAND 287..299
FT /evidence="ECO:0007829|PDB:4MYP"
SQ SEQUENCE 569 AA; 63380 MW; 702B6382193D2784 CRC64;
MKKLWKKGLV AFLALTLIFQ LIPGFASAAD SRLKDGGEYQ VQVNFYKDNT GKTTKESSEA
DKYIDHTATI KVENGQPYMY LTITNSTWWQ TMAVSKNGTR PEKPAQADVY QDRYEDVQTV
STDAAKDTRV EKFKLSSLDD VIFSYMHIKV DAISYDHWYQ VDLTIDPSTF KVISEPAVTT
PVTLSDGIYT IPFVAKKAND DSNSSMQNYF NNPAWLKVKN GKKMVAMTVN DNKTVTALKT
TLAGTLQDVK VVSEDKDANT RIVEFEVEDL NQPLAAHVNY EAPFNGSVYK GQADFRYVFD
TAKATAASSY PGSDETPPVV NPGETNPPVT KPDPGTTNPP VTTPPTTPSK PAVVDPKNLL
NNHTYSIDFD VFKDGTTETS MMESYVMKPA LIKVENNQPY VYLTLTNSSW IKTFQYKVNG
VWKDMEVVSG DINKNTRTVK YPVKDGTANT DVKTHVLIED MPGFSYDHEY TVQVKLNAAT
IKDITGKDVT LKEPVKKDIL NTGNVASNNN AGPKLAKPDF DDTNSVQKTA SKTEKNAKTN
DSSSMVWYIT LFGASFLYLA YRLKRKRLS
