Full text data of LBP
LBP
[Confidence: low (only semi-automatic identification from reviews)]
Lipopolysaccharide-binding protein; LBP; Flags: Precursor
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Lipopolysaccharide-binding protein; LBP; Flags: Precursor
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P18428
ID LBP_HUMAN Reviewed; 481 AA.
AC P18428; B2R938; O43438; Q92672; Q9H403; Q9UD66;
DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
read moreDT 17-OCT-2006, sequence version 3.
DT 22-JAN-2014, entry version 129.
DE RecName: Full=Lipopolysaccharide-binding protein;
DE Short=LBP;
DE Flags: Precursor;
GN Name=LBP;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT LEU-436.
RX PubMed=2402637; DOI=10.1126/science.2402637;
RA Schumann R.R., Leong S.R., Flaggs G.W., Gray P.W., Wright S.D.,
RA Mathison J.C., Tobias P.S., Ulevitch R.J.;
RT "Structure and function of lipopolysaccharide binding protein.";
RL Science 249:1429-1431(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=7517398;
RA Wilde C.G., Seilhamer J.J., McGrogan M., Ashton N., Snable J.L.,
RA Lane J.C., Leong S.R., Thornton M.B., Miller K.L., Scott R.W.;
RT "Bactericidal/permeability-increasing protein and lipopolysaccharide
RT (LPS)-binding protein. LPS binding properties and effects on LPS-
RT mediated cell activation.";
RL J. Biol. Chem. 269:17411-17416(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT LEU-436.
RX PubMed=9240454; DOI=10.1006/bbrc.1997.6970;
RA Hubacek J.A., Buchler C., Aslanidis C., Schmitz G.;
RT "The genomic organization of the genes for human lipopolysaccharide
RT binding protein (LBP) and bactericidal permeability increasing protein
RT (BPI) is highly conserved.";
RL Biochem. Biophys. Res. Commun. 236:427-430(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9441745; DOI=10.1006/geno.1997.5030;
RA Kirschning C.J., Au-Young J., Lamping N., Reuter D., Pfeil D.,
RA Seilhamer J.J., Schumann R.R.;
RT "Similar organization of the lipopolysaccharide-binding protein (LBP)
RT and phospholipid transfer protein (PLTP) genes suggests a common gene
RT family of lipid-binding proteins.";
RL Genomics 46:416-425(1997).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT LEU-436.
RC TISSUE=Liver;
RA Long J.Y., Liu J.Q., Xue Y.N., Wang H.X.;
RT "Cloning and sequencing of human lipopolysaccharide-binding protein
RT gene.";
RL Sheng Wu Hua Xue Yu Sheng Wu Wu Li Jin Zhan 25:469-471(1998).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Liver;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M.,
RA Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J.,
RA Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M.,
RA Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R.,
RA Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M.,
RA Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H.,
RA Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S.,
RA Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E.,
RA Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A.,
RA Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M.,
RA Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A.,
RA Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S.,
RA Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-41.
RA Sutton C.L., Smith R.I.F., Centola M.B., Theofan G.;
RT "Cloning and characterization of the human LBP upstream sequence.";
RL Submitted (MAY-1995) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP REVIEW ON FUNCTION AND SUBUNIT.
RX PubMed=17481951; DOI=10.1016/j.ijmm.2007.04.001;
RA Jerala R.;
RT "Structural biology of the LPS recognition.";
RL Int. J. Med. Microbiol. 297:353-363(2007).
RN [11]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-394, AND MASS
RP SPECTROMETRY.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of
RT multiple enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [12]
RP 3D-STRUCTURE MODELING.
RX PubMed=9568897;
RA Beamer L.J., Carroll S.F., Eisenberg D.;
RT "The BPI/LBP family of proteins: a structural analysis of conserved
RT regions.";
RL Protein Sci. 7:906-914(1998).
CC -!- FUNCTION: Binds to the lipid A moiety of bacterial
CC lipopolysaccharides (LPS), a glycolipid present in the outer
CC membrane of all Gram-negative bacteria, and acts as an affinity
CC enhancer for CD14, facilitating its association with LPS.
CC -!- SUBUNIT: When bound to LPS, interacts (via C-terminus) with
CC soluble CD14.
CC -!- INTERACTION:
CC Q13162:PRDX4; NbExp=4; IntAct=EBI-3927059, EBI-2211957;
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- SIMILARITY: Belongs to the BPI/LBP/Plunc superfamily. BPI/LBP
CC family.
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DR EMBL; M35533; AAA59493.1; -; mRNA.
DR EMBL; X98657; CAA67226.1; -; Genomic_DNA.
DR EMBL; X98658; CAA67226.1; JOINED; Genomic_DNA.
DR EMBL; X98659; CAA67226.1; JOINED; Genomic_DNA.
DR EMBL; X98660; CAA67226.1; JOINED; Genomic_DNA.
DR EMBL; X98661; CAA67226.1; JOINED; Genomic_DNA.
DR EMBL; X98662; CAA67226.1; JOINED; Genomic_DNA.
DR EMBL; X98663; CAA67226.1; JOINED; Genomic_DNA.
DR EMBL; X98664; CAA67226.1; JOINED; Genomic_DNA.
DR EMBL; X98665; CAA67226.1; JOINED; Genomic_DNA.
DR EMBL; X98666; CAA67226.1; JOINED; Genomic_DNA.
DR EMBL; X98667; CAA67226.1; JOINED; Genomic_DNA.
DR EMBL; X98668; CAA67226.1; JOINED; Genomic_DNA.
DR EMBL; AF013512; AAC39547.1; -; Genomic_DNA.
DR EMBL; AF013500; AAC39547.1; JOINED; Genomic_DNA.
DR EMBL; AF013501; AAC39547.1; JOINED; Genomic_DNA.
DR EMBL; AF013502; AAC39547.1; JOINED; Genomic_DNA.
DR EMBL; AF013503; AAC39547.1; JOINED; Genomic_DNA.
DR EMBL; AF013504; AAC39547.1; JOINED; Genomic_DNA.
DR EMBL; AF013505; AAC39547.1; JOINED; Genomic_DNA.
DR EMBL; AF013506; AAC39547.1; JOINED; Genomic_DNA.
DR EMBL; AF013507; AAC39547.1; JOINED; Genomic_DNA.
DR EMBL; AF013508; AAC39547.1; JOINED; Genomic_DNA.
DR EMBL; AF013509; AAC39547.1; JOINED; Genomic_DNA.
DR EMBL; AF013510; AAC39547.1; JOINED; Genomic_DNA.
DR EMBL; AF013511; AAC39547.1; JOINED; Genomic_DNA.
DR EMBL; AF105067; AAD21962.1; -; mRNA.
DR EMBL; AK313625; BAG36385.1; -; mRNA.
DR EMBL; AL080249; CAC10462.1; -; Genomic_DNA.
DR EMBL; CH471077; EAW76034.1; -; Genomic_DNA.
DR EMBL; L42172; AAA66446.1; -; Genomic_DNA.
DR PIR; A35843; A35843.
DR PIR; A54136; A54136.
DR RefSeq; NP_004130.2; NM_004139.3.
DR UniGene; Hs.154078; -.
DR ProteinModelPortal; P18428; -.
DR SMR; P18428; 27-478.
DR DIP; DIP-90N; -.
DR IntAct; P18428; 13.
DR STRING; 9606.ENSP00000217407; -.
DR TCDB; 1.C.40.1.2; the bactericidal permeability increasing protein (bpip) family.
DR PhosphoSite; P18428; -.
DR DMDM; 116242615; -.
DR PaxDb; P18428; -.
DR PeptideAtlas; P18428; -.
DR PRIDE; P18428; -.
DR Ensembl; ENST00000217407; ENSP00000217407; ENSG00000129988.
DR GeneID; 3929; -.
DR KEGG; hsa:3929; -.
DR UCSC; uc002xic.2; human.
DR CTD; 3929; -.
DR GeneCards; GC20P036974; -.
DR HGNC; HGNC:6517; LBP.
DR HPA; CAB025905; -.
DR HPA; HPA001508; -.
DR MIM; 151990; gene.
DR neXtProt; NX_P18428; -.
DR PharmGKB; PA30303; -.
DR eggNOG; NOG262970; -.
DR HOGENOM; HOG000231250; -.
DR HOVERGEN; HBG002797; -.
DR InParanoid; P18428; -.
DR KO; K05399; -.
DR OMA; RNHRSPV; -.
DR OrthoDB; EOG76739B; -.
DR PhylomeDB; P18428; -.
DR Reactome; REACT_6900; Immune System.
DR SignaLink; P18428; -.
DR GeneWiki; Lipopolysaccharide-binding_protein; -.
DR GenomeRNAi; 3929; -.
DR NextBio; 15427; -.
DR PRO; PR:P18428; -.
DR Bgee; P18428; -.
DR CleanEx; HS_LBP; -.
DR Genevestigator; P18428; -.
DR GO; GO:0009986; C:cell surface; IDA:BHF-UCL.
DR GO; GO:0005615; C:extracellular space; IDA:BHF-UCL.
DR GO; GO:0001530; F:lipopolysaccharide binding; ISS:BHF-UCL.
DR GO; GO:0070891; F:lipoteichoic acid binding; IDA:MGI.
DR GO; GO:0005102; F:receptor binding; ISS:BHF-UCL.
DR GO; GO:0006953; P:acute-phase response; IEP:BHF-UCL.
DR GO; GO:0006968; P:cellular defense response; ISS:BHF-UCL.
DR GO; GO:0071223; P:cellular response to lipoteichoic acid; IDA:MGI.
DR GO; GO:0050829; P:defense response to Gram-negative bacterium; IDA:BHF-UCL.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IDA:BHF-UCL.
DR GO; GO:0032490; P:detection of molecule of bacterial origin; IDA:BHF-UCL.
DR GO; GO:0045087; P:innate immune response; ISS:BHF-UCL.
DR GO; GO:0002232; P:leukocyte chemotaxis involved in inflammatory response; IEA:Ensembl.
DR GO; GO:0015920; P:lipopolysaccharide transport; IDA:BHF-UCL.
DR GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; IDA:BHF-UCL.
DR GO; GO:0002281; P:macrophage activation involved in immune response; ISS:BHF-UCL.
DR GO; GO:0044130; P:negative regulation of growth of symbiont in host; IEA:Ensembl.
DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; IDA:BHF-UCL.
DR GO; GO:0008228; P:opsonization; ISS:BHF-UCL.
DR GO; GO:0032722; P:positive regulation of chemokine production; IEA:Ensembl.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; IDA:BHF-UCL.
DR GO; GO:0032757; P:positive regulation of interleukin-8 production; IDA:BHF-UCL.
DR GO; GO:0043032; P:positive regulation of macrophage activation; IDA:BHF-UCL.
DR GO; GO:0090023; P:positive regulation of neutrophil chemotaxis; IEA:Ensembl.
DR GO; GO:0060265; P:positive regulation of respiratory burst involved in inflammatory response; ISS:BHF-UCL.
DR GO; GO:0034145; P:positive regulation of toll-like receptor 4 signaling pathway; IDA:BHF-UCL.
DR GO; GO:0042535; P:positive regulation of tumor necrosis factor biosynthetic process; IEA:Ensembl.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IDA:BHF-UCL.
DR GO; GO:0034142; P:toll-like receptor 4 signaling pathway; TAS:Reactome.
DR InterPro; IPR017943; Bactericidal_perm-incr_a/b_dom.
DR InterPro; IPR001124; Lipid-bd_serum_glycop_C.
DR InterPro; IPR017954; Lipid-bd_serum_glycop_CS.
DR InterPro; IPR017942; Lipid-bd_serum_glycop_N.
DR Pfam; PF01273; LBP_BPI_CETP; 1.
DR Pfam; PF02886; LBP_BPI_CETP_C; 1.
DR SMART; SM00328; BPI1; 1.
DR SMART; SM00329; BPI2; 1.
DR SUPFAM; SSF55394; SSF55394; 2.
DR PROSITE; PS00400; LBP_BPI_CETP; 1.
PE 1: Evidence at protein level;
KW Antibiotic; Antimicrobial; Complete proteome; Disulfide bond;
KW Glycoprotein; Lipid transport; Polymorphism; Reference proteome;
KW Secreted; Signal; Transport.
FT SIGNAL 1 25
FT CHAIN 26 481 Lipopolysaccharide-binding protein.
FT /FTId=PRO_0000017158.
FT CARBOHYD 300 300 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 355 355 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 386 386 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 394 394 N-linked (GlcNAc...).
FT DISULFID 159 198 By similarity.
FT VARIANT 9 9 P -> L (in dbSNP:rs2232580).
FT /FTId=VAR_028243.
FT VARIANT 111 111 R -> Q (in dbSNP:rs2232583).
FT /FTId=VAR_049737.
FT VARIANT 125 125 L -> I (in dbSNP:rs2232585).
FT /FTId=VAR_028244.
FT VARIANT 147 147 E -> K (in dbSNP:rs36015492).
FT /FTId=VAR_049738.
FT VARIANT 157 157 S -> C (in dbSNP:rs2232586).
FT /FTId=VAR_061293.
FT VARIANT 166 166 V -> M (in dbSNP:rs5744204).
FT /FTId=VAR_028245.
FT VARIANT 242 242 M -> I (in dbSNP:rs2232601).
FT /FTId=VAR_028246.
FT VARIANT 283 283 D -> G (in dbSNP:rs2232607).
FT /FTId=VAR_028247.
FT VARIANT 294 294 H -> R (in dbSNP:rs2232608).
FT /FTId=VAR_028248.
FT VARIANT 333 333 P -> L (in dbSNP:rs2232613).
FT /FTId=VAR_028249.
FT VARIANT 339 339 L -> F (in dbSNP:rs5744212).
FT /FTId=VAR_028250.
FT VARIANT 364 364 I -> T (in dbSNP:rs2232615).
FT /FTId=VAR_049739.
FT VARIANT 436 436 F -> L (in dbSNP:rs2232618).
FT /FTId=VAR_028251.
FT VARIANT 445 445 A -> T (in dbSNP:rs2232619).
FT /FTId=VAR_028252.
FT CONFLICT 6 6 R -> H (in Ref. 2).
FT CONFLICT 22 22 E -> C (in Ref. 2).
FT CONFLICT 82 82 N -> K (in Ref. 4; AAC39547).
FT CONFLICT 128 128 S -> F (in Ref. 4; AAC39547).
FT CONFLICT 154 157 VTAS -> GYCL (in Ref. 1; AAA59493).
FT CONFLICT 174 174 L -> S (in Ref. 1; AAA59493).
FT CONFLICT 257 257 R -> S (in Ref. 4; AAC39547).
FT CONFLICT 266 270 VMSLP -> A (in Ref. 1; AAA59493).
FT CONFLICT 369 369 L -> H (in Ref. 4; AAC39547).
SQ SEQUENCE 481 AA; 53384 MW; 5A0E4B9E5E604C72 CRC64;
MGALARALPS ILLALLLTST PEALGANPGL VARITDKGLQ YAAQEGLLAL QSELLRITLP
DFTGDLRIPH VGRGRYEFHS LNIHSCELLH SALRPVPGQG LSLSISDSSI RVQGRWKVRK
SFFKLQGSFD VSVKGISISV NLLLGSESSG RPTVTASSCS SDIADVEVDM SGDLGWLLNL
FHNQIESKFQ KVLESRICEM IQKSVSSDLQ PYLQTLPVTT EIDSFADIDY SLVEAPRATA
QMLEVMFKGE IFHRNHRSPV TLLAAVMSLP EEHNKMVYFA ISDYVFNTAS LVYHEEGYLN
FSITDDMIPP DSNIRLTTKS FRPFVPRLAR LYPNMNLELQ GSVPSAPLLN FSPGNLSVDP
YMEIDAFVLL PSSSKEPVFR LSVATNVSAT LTFNTSKITG FLKPGKVKVE LKESKVGLFN
AELLEALLNY YILNTFYPKF NDKLAEGFPL PLLKRVQLYD LGLQIHKDFL FLGANVQYMR
V
//
ID LBP_HUMAN Reviewed; 481 AA.
AC P18428; B2R938; O43438; Q92672; Q9H403; Q9UD66;
DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
read moreDT 17-OCT-2006, sequence version 3.
DT 22-JAN-2014, entry version 129.
DE RecName: Full=Lipopolysaccharide-binding protein;
DE Short=LBP;
DE Flags: Precursor;
GN Name=LBP;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT LEU-436.
RX PubMed=2402637; DOI=10.1126/science.2402637;
RA Schumann R.R., Leong S.R., Flaggs G.W., Gray P.W., Wright S.D.,
RA Mathison J.C., Tobias P.S., Ulevitch R.J.;
RT "Structure and function of lipopolysaccharide binding protein.";
RL Science 249:1429-1431(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=7517398;
RA Wilde C.G., Seilhamer J.J., McGrogan M., Ashton N., Snable J.L.,
RA Lane J.C., Leong S.R., Thornton M.B., Miller K.L., Scott R.W.;
RT "Bactericidal/permeability-increasing protein and lipopolysaccharide
RT (LPS)-binding protein. LPS binding properties and effects on LPS-
RT mediated cell activation.";
RL J. Biol. Chem. 269:17411-17416(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT LEU-436.
RX PubMed=9240454; DOI=10.1006/bbrc.1997.6970;
RA Hubacek J.A., Buchler C., Aslanidis C., Schmitz G.;
RT "The genomic organization of the genes for human lipopolysaccharide
RT binding protein (LBP) and bactericidal permeability increasing protein
RT (BPI) is highly conserved.";
RL Biochem. Biophys. Res. Commun. 236:427-430(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9441745; DOI=10.1006/geno.1997.5030;
RA Kirschning C.J., Au-Young J., Lamping N., Reuter D., Pfeil D.,
RA Seilhamer J.J., Schumann R.R.;
RT "Similar organization of the lipopolysaccharide-binding protein (LBP)
RT and phospholipid transfer protein (PLTP) genes suggests a common gene
RT family of lipid-binding proteins.";
RL Genomics 46:416-425(1997).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT LEU-436.
RC TISSUE=Liver;
RA Long J.Y., Liu J.Q., Xue Y.N., Wang H.X.;
RT "Cloning and sequencing of human lipopolysaccharide-binding protein
RT gene.";
RL Sheng Wu Hua Xue Yu Sheng Wu Wu Li Jin Zhan 25:469-471(1998).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Liver;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M.,
RA Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J.,
RA Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M.,
RA Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R.,
RA Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M.,
RA Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H.,
RA Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S.,
RA Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E.,
RA Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A.,
RA Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M.,
RA Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A.,
RA Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S.,
RA Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-41.
RA Sutton C.L., Smith R.I.F., Centola M.B., Theofan G.;
RT "Cloning and characterization of the human LBP upstream sequence.";
RL Submitted (MAY-1995) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP REVIEW ON FUNCTION AND SUBUNIT.
RX PubMed=17481951; DOI=10.1016/j.ijmm.2007.04.001;
RA Jerala R.;
RT "Structural biology of the LPS recognition.";
RL Int. J. Med. Microbiol. 297:353-363(2007).
RN [11]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-394, AND MASS
RP SPECTROMETRY.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of
RT multiple enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [12]
RP 3D-STRUCTURE MODELING.
RX PubMed=9568897;
RA Beamer L.J., Carroll S.F., Eisenberg D.;
RT "The BPI/LBP family of proteins: a structural analysis of conserved
RT regions.";
RL Protein Sci. 7:906-914(1998).
CC -!- FUNCTION: Binds to the lipid A moiety of bacterial
CC lipopolysaccharides (LPS), a glycolipid present in the outer
CC membrane of all Gram-negative bacteria, and acts as an affinity
CC enhancer for CD14, facilitating its association with LPS.
CC -!- SUBUNIT: When bound to LPS, interacts (via C-terminus) with
CC soluble CD14.
CC -!- INTERACTION:
CC Q13162:PRDX4; NbExp=4; IntAct=EBI-3927059, EBI-2211957;
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- SIMILARITY: Belongs to the BPI/LBP/Plunc superfamily. BPI/LBP
CC family.
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DR EMBL; M35533; AAA59493.1; -; mRNA.
DR EMBL; X98657; CAA67226.1; -; Genomic_DNA.
DR EMBL; X98658; CAA67226.1; JOINED; Genomic_DNA.
DR EMBL; X98659; CAA67226.1; JOINED; Genomic_DNA.
DR EMBL; X98660; CAA67226.1; JOINED; Genomic_DNA.
DR EMBL; X98661; CAA67226.1; JOINED; Genomic_DNA.
DR EMBL; X98662; CAA67226.1; JOINED; Genomic_DNA.
DR EMBL; X98663; CAA67226.1; JOINED; Genomic_DNA.
DR EMBL; X98664; CAA67226.1; JOINED; Genomic_DNA.
DR EMBL; X98665; CAA67226.1; JOINED; Genomic_DNA.
DR EMBL; X98666; CAA67226.1; JOINED; Genomic_DNA.
DR EMBL; X98667; CAA67226.1; JOINED; Genomic_DNA.
DR EMBL; X98668; CAA67226.1; JOINED; Genomic_DNA.
DR EMBL; AF013512; AAC39547.1; -; Genomic_DNA.
DR EMBL; AF013500; AAC39547.1; JOINED; Genomic_DNA.
DR EMBL; AF013501; AAC39547.1; JOINED; Genomic_DNA.
DR EMBL; AF013502; AAC39547.1; JOINED; Genomic_DNA.
DR EMBL; AF013503; AAC39547.1; JOINED; Genomic_DNA.
DR EMBL; AF013504; AAC39547.1; JOINED; Genomic_DNA.
DR EMBL; AF013505; AAC39547.1; JOINED; Genomic_DNA.
DR EMBL; AF013506; AAC39547.1; JOINED; Genomic_DNA.
DR EMBL; AF013507; AAC39547.1; JOINED; Genomic_DNA.
DR EMBL; AF013508; AAC39547.1; JOINED; Genomic_DNA.
DR EMBL; AF013509; AAC39547.1; JOINED; Genomic_DNA.
DR EMBL; AF013510; AAC39547.1; JOINED; Genomic_DNA.
DR EMBL; AF013511; AAC39547.1; JOINED; Genomic_DNA.
DR EMBL; AF105067; AAD21962.1; -; mRNA.
DR EMBL; AK313625; BAG36385.1; -; mRNA.
DR EMBL; AL080249; CAC10462.1; -; Genomic_DNA.
DR EMBL; CH471077; EAW76034.1; -; Genomic_DNA.
DR EMBL; L42172; AAA66446.1; -; Genomic_DNA.
DR PIR; A35843; A35843.
DR PIR; A54136; A54136.
DR RefSeq; NP_004130.2; NM_004139.3.
DR UniGene; Hs.154078; -.
DR ProteinModelPortal; P18428; -.
DR SMR; P18428; 27-478.
DR DIP; DIP-90N; -.
DR IntAct; P18428; 13.
DR STRING; 9606.ENSP00000217407; -.
DR TCDB; 1.C.40.1.2; the bactericidal permeability increasing protein (bpip) family.
DR PhosphoSite; P18428; -.
DR DMDM; 116242615; -.
DR PaxDb; P18428; -.
DR PeptideAtlas; P18428; -.
DR PRIDE; P18428; -.
DR Ensembl; ENST00000217407; ENSP00000217407; ENSG00000129988.
DR GeneID; 3929; -.
DR KEGG; hsa:3929; -.
DR UCSC; uc002xic.2; human.
DR CTD; 3929; -.
DR GeneCards; GC20P036974; -.
DR HGNC; HGNC:6517; LBP.
DR HPA; CAB025905; -.
DR HPA; HPA001508; -.
DR MIM; 151990; gene.
DR neXtProt; NX_P18428; -.
DR PharmGKB; PA30303; -.
DR eggNOG; NOG262970; -.
DR HOGENOM; HOG000231250; -.
DR HOVERGEN; HBG002797; -.
DR InParanoid; P18428; -.
DR KO; K05399; -.
DR OMA; RNHRSPV; -.
DR OrthoDB; EOG76739B; -.
DR PhylomeDB; P18428; -.
DR Reactome; REACT_6900; Immune System.
DR SignaLink; P18428; -.
DR GeneWiki; Lipopolysaccharide-binding_protein; -.
DR GenomeRNAi; 3929; -.
DR NextBio; 15427; -.
DR PRO; PR:P18428; -.
DR Bgee; P18428; -.
DR CleanEx; HS_LBP; -.
DR Genevestigator; P18428; -.
DR GO; GO:0009986; C:cell surface; IDA:BHF-UCL.
DR GO; GO:0005615; C:extracellular space; IDA:BHF-UCL.
DR GO; GO:0001530; F:lipopolysaccharide binding; ISS:BHF-UCL.
DR GO; GO:0070891; F:lipoteichoic acid binding; IDA:MGI.
DR GO; GO:0005102; F:receptor binding; ISS:BHF-UCL.
DR GO; GO:0006953; P:acute-phase response; IEP:BHF-UCL.
DR GO; GO:0006968; P:cellular defense response; ISS:BHF-UCL.
DR GO; GO:0071223; P:cellular response to lipoteichoic acid; IDA:MGI.
DR GO; GO:0050829; P:defense response to Gram-negative bacterium; IDA:BHF-UCL.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IDA:BHF-UCL.
DR GO; GO:0032490; P:detection of molecule of bacterial origin; IDA:BHF-UCL.
DR GO; GO:0045087; P:innate immune response; ISS:BHF-UCL.
DR GO; GO:0002232; P:leukocyte chemotaxis involved in inflammatory response; IEA:Ensembl.
DR GO; GO:0015920; P:lipopolysaccharide transport; IDA:BHF-UCL.
DR GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; IDA:BHF-UCL.
DR GO; GO:0002281; P:macrophage activation involved in immune response; ISS:BHF-UCL.
DR GO; GO:0044130; P:negative regulation of growth of symbiont in host; IEA:Ensembl.
DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; IDA:BHF-UCL.
DR GO; GO:0008228; P:opsonization; ISS:BHF-UCL.
DR GO; GO:0032722; P:positive regulation of chemokine production; IEA:Ensembl.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; IDA:BHF-UCL.
DR GO; GO:0032757; P:positive regulation of interleukin-8 production; IDA:BHF-UCL.
DR GO; GO:0043032; P:positive regulation of macrophage activation; IDA:BHF-UCL.
DR GO; GO:0090023; P:positive regulation of neutrophil chemotaxis; IEA:Ensembl.
DR GO; GO:0060265; P:positive regulation of respiratory burst involved in inflammatory response; ISS:BHF-UCL.
DR GO; GO:0034145; P:positive regulation of toll-like receptor 4 signaling pathway; IDA:BHF-UCL.
DR GO; GO:0042535; P:positive regulation of tumor necrosis factor biosynthetic process; IEA:Ensembl.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IDA:BHF-UCL.
DR GO; GO:0034142; P:toll-like receptor 4 signaling pathway; TAS:Reactome.
DR InterPro; IPR017943; Bactericidal_perm-incr_a/b_dom.
DR InterPro; IPR001124; Lipid-bd_serum_glycop_C.
DR InterPro; IPR017954; Lipid-bd_serum_glycop_CS.
DR InterPro; IPR017942; Lipid-bd_serum_glycop_N.
DR Pfam; PF01273; LBP_BPI_CETP; 1.
DR Pfam; PF02886; LBP_BPI_CETP_C; 1.
DR SMART; SM00328; BPI1; 1.
DR SMART; SM00329; BPI2; 1.
DR SUPFAM; SSF55394; SSF55394; 2.
DR PROSITE; PS00400; LBP_BPI_CETP; 1.
PE 1: Evidence at protein level;
KW Antibiotic; Antimicrobial; Complete proteome; Disulfide bond;
KW Glycoprotein; Lipid transport; Polymorphism; Reference proteome;
KW Secreted; Signal; Transport.
FT SIGNAL 1 25
FT CHAIN 26 481 Lipopolysaccharide-binding protein.
FT /FTId=PRO_0000017158.
FT CARBOHYD 300 300 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 355 355 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 386 386 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 394 394 N-linked (GlcNAc...).
FT DISULFID 159 198 By similarity.
FT VARIANT 9 9 P -> L (in dbSNP:rs2232580).
FT /FTId=VAR_028243.
FT VARIANT 111 111 R -> Q (in dbSNP:rs2232583).
FT /FTId=VAR_049737.
FT VARIANT 125 125 L -> I (in dbSNP:rs2232585).
FT /FTId=VAR_028244.
FT VARIANT 147 147 E -> K (in dbSNP:rs36015492).
FT /FTId=VAR_049738.
FT VARIANT 157 157 S -> C (in dbSNP:rs2232586).
FT /FTId=VAR_061293.
FT VARIANT 166 166 V -> M (in dbSNP:rs5744204).
FT /FTId=VAR_028245.
FT VARIANT 242 242 M -> I (in dbSNP:rs2232601).
FT /FTId=VAR_028246.
FT VARIANT 283 283 D -> G (in dbSNP:rs2232607).
FT /FTId=VAR_028247.
FT VARIANT 294 294 H -> R (in dbSNP:rs2232608).
FT /FTId=VAR_028248.
FT VARIANT 333 333 P -> L (in dbSNP:rs2232613).
FT /FTId=VAR_028249.
FT VARIANT 339 339 L -> F (in dbSNP:rs5744212).
FT /FTId=VAR_028250.
FT VARIANT 364 364 I -> T (in dbSNP:rs2232615).
FT /FTId=VAR_049739.
FT VARIANT 436 436 F -> L (in dbSNP:rs2232618).
FT /FTId=VAR_028251.
FT VARIANT 445 445 A -> T (in dbSNP:rs2232619).
FT /FTId=VAR_028252.
FT CONFLICT 6 6 R -> H (in Ref. 2).
FT CONFLICT 22 22 E -> C (in Ref. 2).
FT CONFLICT 82 82 N -> K (in Ref. 4; AAC39547).
FT CONFLICT 128 128 S -> F (in Ref. 4; AAC39547).
FT CONFLICT 154 157 VTAS -> GYCL (in Ref. 1; AAA59493).
FT CONFLICT 174 174 L -> S (in Ref. 1; AAA59493).
FT CONFLICT 257 257 R -> S (in Ref. 4; AAC39547).
FT CONFLICT 266 270 VMSLP -> A (in Ref. 1; AAA59493).
FT CONFLICT 369 369 L -> H (in Ref. 4; AAC39547).
SQ SEQUENCE 481 AA; 53384 MW; 5A0E4B9E5E604C72 CRC64;
MGALARALPS ILLALLLTST PEALGANPGL VARITDKGLQ YAAQEGLLAL QSELLRITLP
DFTGDLRIPH VGRGRYEFHS LNIHSCELLH SALRPVPGQG LSLSISDSSI RVQGRWKVRK
SFFKLQGSFD VSVKGISISV NLLLGSESSG RPTVTASSCS SDIADVEVDM SGDLGWLLNL
FHNQIESKFQ KVLESRICEM IQKSVSSDLQ PYLQTLPVTT EIDSFADIDY SLVEAPRATA
QMLEVMFKGE IFHRNHRSPV TLLAAVMSLP EEHNKMVYFA ISDYVFNTAS LVYHEEGYLN
FSITDDMIPP DSNIRLTTKS FRPFVPRLAR LYPNMNLELQ GSVPSAPLLN FSPGNLSVDP
YMEIDAFVLL PSSSKEPVFR LSVATNVSAT LTFNTSKITG FLKPGKVKVE LKESKVGLFN
AELLEALLNY YILNTFYPKF NDKLAEGFPL PLLKRVQLYD LGLQIHKDFL FLGANVQYMR
V
//
MIM
151990
*RECORD*
*FIELD* NO
151990
*FIELD* TI
*151990 LIPOPOLYSACCHARIDE-BINDING PROTEIN; LBP
;;LPS-BINDING PROTEIN
*FIELD* TX
DESCRIPTION
read more
Lipopolysaccharide-binding protein is an acute-phase reactant produced
during gram-negative bacterial infections. Higher eukaryotes have
evolved several mechanisms for protecting against such infections.
Gram-negative bacteria express lipopolysaccharide (LPS; endotoxin) on
their outer cell wall, and mammals respond rapidly to the presence of
LPS in serum. LBP and another acute-phase reactant, bactericidal
permeability-increasing protein (BPI; 109195), bind LPS with high
affinity. LBP is made in the liver during the acute phase of infections
and is thought to function as a carrier for LPS and to help control
LPS-dependent monocyte responses. See CD14 (158120) for information on
the receptor for the lipopolysaccharide binding
protein/lipopolysaccharide complex.
CLONING
By screening a human liver cDNA library with an oligonucleotide derived
from the rabbit LBP protein sequence, Schumann et al. (1990) isolated
cDNAs encoding LBP. The predicted human LBP protein consists of a
25-amino acid signal sequence followed by a 452-amino acid mature
protein containing 4 cysteine residues and 5 potential glycosylation
sites. Human LBP shares 69% amino acid identity with rabbit LBP, 44%
identity with human BPI, and 23% identity with human CETP (118470). In
rabbits, Schumann et al. (1990) found that LBP functions as a carrier
protein for LPS in plasma and controls LPS-dependent monocytic
responses.
GENE STRUCTURE
Hubacek et al. (1997) found that the LBP gene spans approximately 28.5
kb of DNA and contains 14 exons. Comparison of the genomic structures of
LBP, BPI, PLTP (172425), and CETP, which constitute a family of
functionally related proteins, revealed a remarkable conservation of
exon/intron junctions and exon size.
GENE FUNCTION
LPS interacts with LBP and CD14 to present LPS to TLR4 (603030), which
activates inflammatory gene expression through NF-kappa-B (see 164011)
and MAPK signaling. Bochkov et al. (2002) demonstrated that oxidized
phospholipids inhibit LPS-induced but not TNF-alpha (191160)-induced or
interleukin-1-beta (147720)-induced NF-kappa-B-mediated upregulation of
inflammatory genes by blocking the interaction of LPS with LBP and CD14.
Moreover, in LPS-injected mice, oxidized phospholipids inhibited
inflammation and protected mice from lethal endotoxin shock. Thus, in
severe gram-negative bacterial infection, endogenously formed oxidized
phospholipids may function as a negative feedback to blunt innate immune
responses. Furthermore, Bochkov et al. (2002) identified chemical
structures capable of inhibiting the effects of endotoxins such as LPS
that could be used for the development of new drugs for treatment of
sepsis.
Weber et al. (2003) found that LBP was present in the cerebrospinal
fluid of patients with pneumococcal meningitis. Injection of living
pneumococci or pneumococcal cell wall (PCW) into spinal canals of Lbp
+/- mice resulted in leukocyte influx and severe meningitis. In
contrast, injection into Lbp -/- mice produced no meningeal
inflammation. Lbp enhanced PCW-induced signaling and Tnf release in
rodent cell lines, and Lbp bound to PCW multimers independently of the
phosphorylcholine and teichoic acid components of PCW. Experiments using
human LBP suggested that the binding site for PCW may overlap with that
for LPS. Weber et al. (2003) concluded that LBP is also involved in
gram-positive infections.
MAPPING
In addition to the functional relationship and extensive structural
similarity between the LBP and BPI proteins, the LBP and BPI genes were
found by Southern blot analysis of human/mouse somatic cell hybrids and
by in situ hybridization to map to the same region of the genome:
20q11.23-q.12 (Gray et al., 1993).
ANIMAL MODEL
By using mice deficient in LBP through gene knockout experiments, Jack
et al. (1997) investigated how LBP functions in vivo. To their surprise,
they found that LBP is not required in vivo for the clearance of LPS
from the circulation, but is essential for the rapid induction of an
inflammatory response by small amounts of LPS or gram-negative bacteria
and for survival of an intraperitoneal Salmonella infection.
*FIELD* RF
1. Bochkov, V. N.; Kadl, A.; Huber, J.; Gruber, F.; Binder, B. R.;
Leitinger, N.: Protective role of phospholipid oxidation products
in endotoxin-induced tissue damage. Nature 419: 77-81, 2002.
2. Gray, P. W.; Corcorran, A. E.; Eddy, R. L., Jr.; Byers, M. G.;
Shows, T. B.: The genes for the lipopolysaccharide binding protein
(LBP) and the bactericidal permeability increasing protein (BPI) are
encoded in the same region of human chromosome 20. Genomics 15:
188-190, 1993.
3. Hubacek, J. A.; Buchler, C.; Aslanidis, C.; Schmitz, G.: The genomic
organization of the genes for human lipopolysaccharide binding protein
(LBP) and bactericidal permeability increasing protein (BPI) is highly
conserved. Biochem. Biophys. Res. Commun. 236: 427-430, 1997.
4. Jack, R. S.; Fan, X.; Bernheiden, M.; Rune, G.; Ehlers, M.; Webert,
A.; Kirsch, G.; Mentel, R.; Furll, B.; Freudenberg, M.; Schmitz, G.;
Stelter, F.; Schutt, C.: Lipopolysaccharide-binding protein is required
to combat a murine gram-negative bacterial infection. Nature 389:
742-744, 1997.
5. Schumann, R. R.; Leong, S. R.; Flaggs, G. W.; Gray, P. W.; Wright,
S. D.; Mathison, J. C.; Tobias, P. S.; Ulevitch, R. J.: Structure
and function of lipopolysaccharide binding protein. Science 249:
1429-1431, 1990.
6. Weber, J. R.; Freyer, D.; Alexander, C.; Schroder, N. W. J.; Reiss,
A.; Kuster, C.; Pfeil, D.; Tuomanen, E. I.; Schumann, R. R.: Recognition
of pneumococcal peptidoglycan: an expanded, pivotal role for LPS binding
protein. Immunity 19: 269-279, 2003.
*FIELD* CN
Paul J. Converse - updated: 5/2/2006
Ada Hamosh - updated: 9/12/2002
Sheryl A. Jankowski - updated: 8/5/1999
Victor A. McKusick - updated: 10/15/1997
*FIELD* CD
Victor A. McKusick: 2/17/1993
*FIELD* ED
mgross: 05/10/2006
terry: 5/2/2006
tkritzer: 3/24/2003
alopez: 9/12/2002
psherman: 8/5/1999
psherman: 11/19/1998
mark: 10/15/1997
terry: 10/14/1997
carol: 2/17/1993
*RECORD*
*FIELD* NO
151990
*FIELD* TI
*151990 LIPOPOLYSACCHARIDE-BINDING PROTEIN; LBP
;;LPS-BINDING PROTEIN
*FIELD* TX
DESCRIPTION
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Lipopolysaccharide-binding protein is an acute-phase reactant produced
during gram-negative bacterial infections. Higher eukaryotes have
evolved several mechanisms for protecting against such infections.
Gram-negative bacteria express lipopolysaccharide (LPS; endotoxin) on
their outer cell wall, and mammals respond rapidly to the presence of
LPS in serum. LBP and another acute-phase reactant, bactericidal
permeability-increasing protein (BPI; 109195), bind LPS with high
affinity. LBP is made in the liver during the acute phase of infections
and is thought to function as a carrier for LPS and to help control
LPS-dependent monocyte responses. See CD14 (158120) for information on
the receptor for the lipopolysaccharide binding
protein/lipopolysaccharide complex.
CLONING
By screening a human liver cDNA library with an oligonucleotide derived
from the rabbit LBP protein sequence, Schumann et al. (1990) isolated
cDNAs encoding LBP. The predicted human LBP protein consists of a
25-amino acid signal sequence followed by a 452-amino acid mature
protein containing 4 cysteine residues and 5 potential glycosylation
sites. Human LBP shares 69% amino acid identity with rabbit LBP, 44%
identity with human BPI, and 23% identity with human CETP (118470). In
rabbits, Schumann et al. (1990) found that LBP functions as a carrier
protein for LPS in plasma and controls LPS-dependent monocytic
responses.
GENE STRUCTURE
Hubacek et al. (1997) found that the LBP gene spans approximately 28.5
kb of DNA and contains 14 exons. Comparison of the genomic structures of
LBP, BPI, PLTP (172425), and CETP, which constitute a family of
functionally related proteins, revealed a remarkable conservation of
exon/intron junctions and exon size.
GENE FUNCTION
LPS interacts with LBP and CD14 to present LPS to TLR4 (603030), which
activates inflammatory gene expression through NF-kappa-B (see 164011)
and MAPK signaling. Bochkov et al. (2002) demonstrated that oxidized
phospholipids inhibit LPS-induced but not TNF-alpha (191160)-induced or
interleukin-1-beta (147720)-induced NF-kappa-B-mediated upregulation of
inflammatory genes by blocking the interaction of LPS with LBP and CD14.
Moreover, in LPS-injected mice, oxidized phospholipids inhibited
inflammation and protected mice from lethal endotoxin shock. Thus, in
severe gram-negative bacterial infection, endogenously formed oxidized
phospholipids may function as a negative feedback to blunt innate immune
responses. Furthermore, Bochkov et al. (2002) identified chemical
structures capable of inhibiting the effects of endotoxins such as LPS
that could be used for the development of new drugs for treatment of
sepsis.
Weber et al. (2003) found that LBP was present in the cerebrospinal
fluid of patients with pneumococcal meningitis. Injection of living
pneumococci or pneumococcal cell wall (PCW) into spinal canals of Lbp
+/- mice resulted in leukocyte influx and severe meningitis. In
contrast, injection into Lbp -/- mice produced no meningeal
inflammation. Lbp enhanced PCW-induced signaling and Tnf release in
rodent cell lines, and Lbp bound to PCW multimers independently of the
phosphorylcholine and teichoic acid components of PCW. Experiments using
human LBP suggested that the binding site for PCW may overlap with that
for LPS. Weber et al. (2003) concluded that LBP is also involved in
gram-positive infections.
MAPPING
In addition to the functional relationship and extensive structural
similarity between the LBP and BPI proteins, the LBP and BPI genes were
found by Southern blot analysis of human/mouse somatic cell hybrids and
by in situ hybridization to map to the same region of the genome:
20q11.23-q.12 (Gray et al., 1993).
ANIMAL MODEL
By using mice deficient in LBP through gene knockout experiments, Jack
et al. (1997) investigated how LBP functions in vivo. To their surprise,
they found that LBP is not required in vivo for the clearance of LPS
from the circulation, but is essential for the rapid induction of an
inflammatory response by small amounts of LPS or gram-negative bacteria
and for survival of an intraperitoneal Salmonella infection.
*FIELD* RF
1. Bochkov, V. N.; Kadl, A.; Huber, J.; Gruber, F.; Binder, B. R.;
Leitinger, N.: Protective role of phospholipid oxidation products
in endotoxin-induced tissue damage. Nature 419: 77-81, 2002.
2. Gray, P. W.; Corcorran, A. E.; Eddy, R. L., Jr.; Byers, M. G.;
Shows, T. B.: The genes for the lipopolysaccharide binding protein
(LBP) and the bactericidal permeability increasing protein (BPI) are
encoded in the same region of human chromosome 20. Genomics 15:
188-190, 1993.
3. Hubacek, J. A.; Buchler, C.; Aslanidis, C.; Schmitz, G.: The genomic
organization of the genes for human lipopolysaccharide binding protein
(LBP) and bactericidal permeability increasing protein (BPI) is highly
conserved. Biochem. Biophys. Res. Commun. 236: 427-430, 1997.
4. Jack, R. S.; Fan, X.; Bernheiden, M.; Rune, G.; Ehlers, M.; Webert,
A.; Kirsch, G.; Mentel, R.; Furll, B.; Freudenberg, M.; Schmitz, G.;
Stelter, F.; Schutt, C.: Lipopolysaccharide-binding protein is required
to combat a murine gram-negative bacterial infection. Nature 389:
742-744, 1997.
5. Schumann, R. R.; Leong, S. R.; Flaggs, G. W.; Gray, P. W.; Wright,
S. D.; Mathison, J. C.; Tobias, P. S.; Ulevitch, R. J.: Structure
and function of lipopolysaccharide binding protein. Science 249:
1429-1431, 1990.
6. Weber, J. R.; Freyer, D.; Alexander, C.; Schroder, N. W. J.; Reiss,
A.; Kuster, C.; Pfeil, D.; Tuomanen, E. I.; Schumann, R. R.: Recognition
of pneumococcal peptidoglycan: an expanded, pivotal role for LPS binding
protein. Immunity 19: 269-279, 2003.
*FIELD* CN
Paul J. Converse - updated: 5/2/2006
Ada Hamosh - updated: 9/12/2002
Sheryl A. Jankowski - updated: 8/5/1999
Victor A. McKusick - updated: 10/15/1997
*FIELD* CD
Victor A. McKusick: 2/17/1993
*FIELD* ED
mgross: 05/10/2006
terry: 5/2/2006
tkritzer: 3/24/2003
alopez: 9/12/2002
psherman: 8/5/1999
psherman: 11/19/1998
mark: 10/15/1997
terry: 10/14/1997
carol: 2/17/1993