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HPE_HAEI3
ID   HPE_HAEI3               Reviewed;         160 AA.
AC   A4NBN9;
DT   13-NOV-2013, integrated into UniProtKB/Swiss-Prot.
DT   15-MAY-2007, sequence version 1.
DT   25-MAY-2022, entry version 28.
DE   RecName: Full=Surface-adhesin protein E;
DE   Flags: Precursor;
GN   Name=pe; ORFNames=CGSHi3655_04936;
OS   Haemophilus influenzae (strain NTHi 3655).
OC   Bacteria; Proteobacteria; Gammaproteobacteria; Pasteurellales;
OC   Pasteurellaceae; Haemophilus.
OX   NCBI_TaxID=375177;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=NTHi 3655;
RX   PubMed=17550610; DOI=10.1186/gb-2007-8-6-r103;
RA   Hogg J.S., Hu F.Z., Janto B., Boissy R., Hayes J., Keefe R., Post J.C.,
RA   Ehrlich G.D.;
RT   "Characterization and modeling of the Haemophilus influenzae core and
RT   supragenomes based on the complete genomic sequences of Rd and 12 clinical
RT   nontypeable strains.";
RL   Genome Biol. 8:R103.1-R103.18(2007).
RN   [2]
RP   FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RC   STRAIN=NTHi 3655, and NTHi 772;
RX   PubMed=18069033; DOI=10.1016/j.micinf.2007.10.006;
RA   Ronander E., Brant M., Janson H., Sheldon J., Forsgren A., Riesbeck K.;
RT   "Identification of a novel Haemophilus influenzae protein important for
RT   adhesion to epithelial cells.";
RL   Microbes Infect. 10:87-96(2008).
RN   [3]
RP   FUNCTION, INTERACTION WITH VITRONECTIN, AND DISRUPTION PHENOTYPE.
RC   STRAIN=NTHi 3655;
RX   PubMed=19635912; DOI=10.4049/jimmunol.0803226;
RA   Hallstrom T., Blom A.M., Zipfel P.F., Riesbeck K.;
RT   "Nontypeable Haemophilus influenzae protein E binds vitronectin and is
RT   important for serum resistance.";
RL   J. Immunol. 183:2593-2601(2009).
RN   [4]
RP   FUNCTION.
RC   STRAIN=NTHi 3655;
RX   PubMed=19125675; DOI=10.1086/596211;
RA   Ronander E., Brant M., Eriksson E., Morgelin M., Hallgren O.,
RA   Westergren-Thorsson G., Forsgren A., Riesbeck K.;
RT   "Nontypeable Haemophilus influenzae adhesin protein E: characterization and
RT   biological activity.";
RL   J. Infect. Dis. 199:522-531(2009).
RN   [5]
RP   FUNCTION, INTERACTION WITH LAMININ AND VITRONECTIN, AND DISRUPTION
RP   PHENOTYPE.
RC   STRAIN=NTHi 3655;
RX   PubMed=21881122; DOI=10.1093/infdis/jir459;
RA   Hallstrom T., Singh B., Resman F., Blom A.M., Morgelin M., Riesbeck K.;
RT   "Haemophilus influenzae protein E binds to the extracellular matrix by
RT   concurrently interacting with laminin and vitronectin.";
RL   J. Infect. Dis. 204:1065-1074(2011).
RN   [6]
RP   FUNCTION, INTERACTION WITH VITRONECTIN, AND MUTAGENESIS OF LYS-85 AND
RP   ARG-86.
RC   STRAIN=NTHi 3655;
RX   PubMed=21542857; DOI=10.1111/j.1365-2958.2011.07678.x;
RA   Singh B., Jalalvand F., Morgelin M., Zipfel P., Blom A.M., Riesbeck K.;
RT   "Haemophilus influenzae protein E recognizes the C-terminal domain of
RT   vitronectin and modulates the membrane attack complex.";
RL   Mol. Microbiol. 81:80-98(2011).
RN   [7]
RP   FUNCTION, INTERACTION WITH PLASMINOGEN, AND DISRUPTION PHENOTYPE.
RC   STRAIN=NTHi 3655;
RX   PubMed=22124123; DOI=10.4049/jimmunol.1101927;
RA   Barthel D., Singh B., Riesbeck K., Zipfel P.F.;
RT   "Haemophilus influenzae uses the surface protein E to acquire human
RT   plasminogen and to evade innate immunity.";
RL   J. Immunol. 188:379-385(2012).
RN   [8]
RP   CRYSTALLIZATION, AND SUBUNIT.
RX   PubMed=22298005; DOI=10.1107/s1744309111055503;
RA   Singh B., Al Jubair T., Fornvik K., Thunnissen M.M., Riesbeck K.;
RT   "Crystallization and X-ray diffraction analysis of a novel surface-adhesin
RT   protein: protein E from Haemophilus influenzae.";
RL   Acta Crystallogr. F 68:222-226(2012).
RN   [9]
RP   X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 26-157, AND SUBUNIT.
RX   PubMed=23275089; DOI=10.1128/iai.01111-12;
RA   Singh B., Al-Jubair T., Morgelin M., Thunnissen M.M., Riesbeck K.;
RT   "The unique structure of Haemophilus influenzae protein E reveals multiple
RT   binding sites for host factors.";
RL   Infect. Immun. 81:801-814(2013).
CC   -!- FUNCTION: Acts as a multifunctional adhesin involved in direct
CC       interactions with host epithelial cells and host proteins, including
CC       vitronectin, laminin and plasminogen. In addition, interaction with
CC       serum vitronectin plays an important role in bacterial serum
CC       resistance, and conversion of plasminogen to plasmin at the cell
CC       surface aids in immune evasion and contributes to bacterial virulence.
CC       Induces a pro-inflammatory epithelial cell response, leading to
CC       interleukin-8 (IL-8) secretion and up-regulation of ICAM1.
CC       {ECO:0000269|PubMed:18069033, ECO:0000269|PubMed:19125675,
CC       ECO:0000269|PubMed:19635912, ECO:0000269|PubMed:21542857,
CC       ECO:0000269|PubMed:21881122, ECO:0000269|PubMed:22124123}.
CC   -!- SUBUNIT: Homodimer. Interacts with host vitronectin, laminin and
CC       plasminogen. Can interact with both immobilized and soluble
CC       vitronectin. {ECO:0000269|PubMed:19635912, ECO:0000269|PubMed:21542857,
CC       ECO:0000269|PubMed:21881122, ECO:0000269|PubMed:22124123,
CC       ECO:0000269|PubMed:22298005, ECO:0000269|PubMed:23275089}.
CC   -!- SUBCELLULAR LOCATION: Cell outer membrane
CC       {ECO:0000269|PubMed:18069033}; Lipid-anchor {ECO:0000255|PROSITE-
CC       ProRule:PRU00303, ECO:0000269|PubMed:18069033}. Cell surface
CC       {ECO:0000269|PubMed:18069033}.
CC   -!- DISRUPTION PHENOTYPE: Mutant displays a reduced binding to vitronectin,
CC       laminin, plasminogen and epithelial cells, and is more sensitive to
CC       killing by human serum compared with the wild type.
CC       {ECO:0000269|PubMed:18069033, ECO:0000269|PubMed:19635912,
CC       ECO:0000269|PubMed:21881122, ECO:0000269|PubMed:22124123}.
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DR   EMBL; AAZF01000008; EDJ92417.1; -; Genomic_DNA.
DR   RefSeq; WP_005658162.1; NZ_AAZF01000008.1.
DR   PDB; 3ZH5; X-ray; 1.80 A; A/B=26-157.
DR   PDB; 3ZH6; X-ray; 2.29 A; A/B=26-157.
DR   PDB; 3ZH7; X-ray; 2.10 A; A/B=29-153.
DR   PDBsum; 3ZH5; -.
DR   PDBsum; 3ZH6; -.
DR   PDBsum; 3ZH7; -.
DR   AlphaFoldDB; A4NBN9; -.
DR   SMR; A4NBN9; -.
DR   IntAct; A4NBN9; 1.
DR   EnsemblBacteria; EDJ92417; EDJ92417; CGSHi3655_04936.
DR   Proteomes; UP000003185; Unassembled WGS sequence.
DR   GO; GO:0009279; C:cell outer membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0009986; C:cell surface; IEA:UniProtKB-SubCell.
DR   Gene3D; 2.40.128.710; -; 1.
DR   InterPro; IPR043088; Adhesin_E.
DR   InterPro; IPR031939; Adhesin_E-like.
DR   InterPro; IPR016595; Adhesin_E_Pasteurellaceae.
DR   Pfam; PF16747; Adhesin_E; 1.
DR   PIRSF; PIRSF012320; Prplsmic_HI0178_prd; 1.
DR   PROSITE; PS51257; PROKAR_LIPOPROTEIN; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Cell outer membrane; Lipoprotein; Membrane; Palmitate;
KW   Signal; Virulence.
FT   SIGNAL          1..15
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00303"
FT   CHAIN           16..160
FT                   /note="Surface-adhesin protein E"
FT                   /id="PRO_0000424421"
FT   REGION          41..68
FT                   /note="Interaction with laminin and plasminogen"
FT   REGION          84..108
FT                   /note="Interaction with vitronectin and epithelial cells"
FT   LIPID           16
FT                   /note="N-palmitoyl cysteine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00303"
FT   LIPID           16
FT                   /note="S-diacylglycerol cysteine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00303"
FT   MUTAGEN         85
FT                   /note="K->E: 50% reduction in binding to vitronectin. Does
FT                   not bind vitronectin; when associated with D-86."
FT                   /evidence="ECO:0000269|PubMed:21542857"
FT   MUTAGEN         86
FT                   /note="R->D: 48% reduction in binding to vitronectin. Does
FT                   not bind vitronectin; when associated with E-85."
FT                   /evidence="ECO:0000269|PubMed:21542857"
SQ   SEQUENCE   160 AA;  18350 MW;  D6F1115CD7C5DD00 CRC64;
     MKKIILTLSL GLLTACSAQI QKAEQNDMKL APPTDVRSGY IRLVKNVNYY IDSESIWVDN
     QEPQIVHFDA VVNLDKGLYV YPEPKRYARS VRQYKILNCA NYHLTQVRTD FYDEFWGQGL
     RAAPKKQKKH TLSLTPDTTL YNAAQIICAN YGKAFSVDKK
 
 
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