P17213 (BPI_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Bactericidal permeability-increasing protein
Short name=BPI

Alternative name(s):
CAP 57

Gene names

Name:

BPI

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	487 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	The cytotoxic action of BPI is limited to many species of Gram-negative bacteria; this specificity may be explained by a strong affinity of the very basic N-terminal half for the negatively charged lipopolysaccharides that are unique to the Gram-negative bacterial outer envelope. Has antibacterial activity against the Gram-nagative bacterium P.aeruginosa, this activity is inhibited by LPS from P.aeruginosa. Ref.1 Ref.8
Subunit structure	Monomer. Homodimer; disulfide-linked. Ref.11
Subcellular location	Secreted. Cytoplasmic granule membrane. Note: Membrane-associated in polymorphonuclear Leukocytes (PMN) granules. Ref.1 Ref.11
Tissue specificity	Restricted to cells of the myeloid series.
Domain	The N-terminal region may be exposed to the interior of the granule, whereas the C-terminal portion may be embedded in the membrane. During phagocytosis and degranulation, proteases may be released and activated and cleave BPI at the junction of the N- and C-terminal portions of the molecule, providing controlled release of the N-terminal antibacterial fragment when bacteria are ingested. Ref.1
Sequence similarities	Belongs to the BPI/LBP/Plunc superfamily. BPI/LBP family.
Sequence caution	The sequence CAC10453.2 differs from that shown. Reason: Erroneous gene model prediction. The sequence CAC27350.2 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Cellular component	Membrane Secreted
Coding sequence diversity	Polymorphism
Domain	Signal
Molecular function	Antibiotic Antimicrobial
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	defense response to bacterium Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of interleukin-6 production Inferred from direct assay. Source: BHF-UCL negative regulation of interleukin-8 production Inferred from direct assay. Source: BHF-UCL negative regulation of macrophage activation Inferred from direct assay. Source: BHF-UCL negative regulation of tumor necrosis factor production Inferred from direct assay. Source: BHF-UCL
Cellular component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell integral to plasma membrane Traceable author statement. Source: ProtInc
Molecular function	lipid binding Inferred from electronic annotation. Source: InterPro lipopolysaccharide binding Inferred from direct assay. Source: BHF-UCL
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 31

31

Ref.1 Ref.8 Ref.9 Ref.10

Chain

32 – 487

456

Bactericidal permeability-increasing protein

PRO_0000017154

Regions

Region

240 – 245

6

Cleavage sites for elastase Potential

Amino acid modifications

Glycosylation

380

1

N-linked (GlcNAc...) Potential

Disulfide bond

166 ↔ 206

Natural variations

Natural variant

12

1

A → T.
Corresponds to variant rs5743497 [ dbSNP | Ensembl ].

VAR_049728

Natural variant

12

1

A → V.
Corresponds to variant rs5743498 [ dbSNP | Ensembl ].

VAR_049729

Natural variant

16

1

A → V. Ref.1 Ref.3
Corresponds to variant rs1341023 [ dbSNP | Ensembl ].

VAR_018401

Natural variant

90

1

R → C.
Corresponds to variant rs5743500 [ dbSNP | Ensembl ].

VAR_049730

Natural variant

140

1

E → Q.
Corresponds to variant rs5743506 [ dbSNP | Ensembl ].

VAR_049732

Natural variant

196

1

A → V.
Corresponds to variant rs5743509 [ dbSNP | Ensembl ].

VAR_018402

Natural variant

216

1

E → K. Ref.1 Ref.6 Ref.7
Corresponds to variant rs4358188 [ dbSNP | Ensembl ].

VAR_018403

Natural variant

280

1

A → V.
Corresponds to variant rs5741804 [ dbSNP | Ensembl ].

VAR_049733

Natural variant

377

1

V → I.
Corresponds to variant rs5743524 [ dbSNP | Ensembl ].

VAR_049734

Natural variant

404

1

N → D. Ref.4 Ref.7
Corresponds to variant rs5741809 [ dbSNP | Ensembl ].

VAR_049735

Natural variant

451

1

K → E.
Corresponds to variant rs5743542 [ dbSNP | Ensembl ].

VAR_049736

Experimental info

Mutagenesis

49

1

S → C: No impairment of secretion and increased propensity for dimer formation. Ref.11

Mutagenesis

163

1

C → A: No impairment of secretion and/or biological activity. Loss of dimer formation. Ref.11

Mutagenesis

166

1

C → S: Poorly secreted. Loss of LPS-binding and biological activity. Ref.11

Mutagenesis

206

1

C → A: Not secreted. Ref.11

Sequence conflict

5

1

M → L in AAH40955. Ref.6

Sequence conflict

53

1

T → R AA sequence Ref.8

Sequence conflict

355

1

P → S in AAG42844. Ref.7

Sequence conflict

375

1

F → L Ref.2

Sequence conflict

411

1

K → R in AAG42844. Ref.7

Sequence conflict

433

1

Q → L in BAG37729. Ref.4

Secondary structure

1

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487

Helix Strand Turn

Details...

Beta strand

35 – 41

7

Helix

42 – 60

19

Beta strand

68 – 74

7

Turn

75 – 77

3

Beta strand

78 – 93

16

Beta strand

97 – 102

6

Turn

103 – 105

3

Beta strand

106 – 126

21

Beta strand

129 – 152

24

Turn

154 – 156

3

Beta strand

159 – 167

9

Beta strand

172 – 176

5

Helix

183 – 192

10

Helix

194 – 221

28

Beta strand

226 – 229

4

Beta strand

231 – 237

7

Beta strand

248 – 255

8

Beta strand

258 – 264

7

Beta strand

282 – 290

9

Helix

291 – 303

13

Beta strand

307 – 311

5

Helix

313 – 315

3

Helix

326 – 329

4

Turn

330 – 332

3

Helix

336 – 339

4

Beta strand

344 – 353

10

Beta strand

356 – 360

5

Beta strand

363 – 367

5

Beta strand

369 – 377

9

Beta strand

383 – 392

10

Beta strand

395 – 402

8

Beta strand

405 – 412

8

Beta strand

419 – 422

4

Helix

429 – 432

4

Helix

433 – 454

22

Beta strand

464 – 474

11

Beta strand

477 – 486

10

Sequences

	Sequence		Length	Mass (Da)
	P17213 [UniParc]. Last modified November 25, 2008. Version 4. Checksum: 30BC73B1B465B62D	FASTA	487	53,900
	10 20 30 40 50 60 MRENMARGPC NAPRWASLMV LVAIGTAVTA AVNPGVVVRI SQKGLDYASQ QGTAALQKEL 70 80 90 100 110 120 KRIKIPDYSD SFKIKHLGKG HYSFYSMDIR EFQLPSSQIS MVPNVGLKFS ISNANIKISG 130 140 150 160 170 180 KWKAQKRFLK MSGNFDLSIE GMSISADLKL GSNPTSGKPT ITCSSCSSHI NSVHVHISKS 190 200 210 220 230 240 KVGWLIQLFH KKIESALRNK MNSQVCEKVT NSVSSELQPY FQTLPVMTKI DSVAGINYGL 250 260 270 280 290 300 VAPPATTAET LDVQMKGEFY SENHHNPPPF APPVMEFPAA HDRMVYLGLS DYFFNTAGLV 310 320 330 340 350 360 YQEAGVLKMT LRDDMIPKES KFRLTTKFFG TFLPEVAKKF PNMKIQIHVS ASTPPHLSVQ 370 380 390 400 410 420 PTGLTFYPAV DVQAFAVLPN SSLASLFLIG MHTTGSMEVS AESNRLVGEL KLDRLLLELK 430 440 450 460 470 480 HSNIGPFPVE LLQDIMNYIV PILVLPRVNE KLQKGFPLPT PARVQLYNVV LQPHQNFLLF GADVVYK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of the cDNA of a human neutrophil bactericidal protein. Structural and functional correlations." Gray P.W., Flaggs G., Leong S.R., Gumina R.J., Weiss J., Ooi C.E., Elsbach P. J. Biol. Chem. 264:9505-9509(1989) [PubMed: 2722846] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 32-68, FUNCTION, SUBCELLULAR LOCATION, DOMAIN, VARIANTS VAL-16 AND LYS-216.
[2]	"Bactericidal/permeability-increasing protein and lipopolysaccharide (LPS)-binding protein. LPS binding properties and effects on LPS-mediated cell activation." Wilde C.G., Seilhamer J.J., McGrogan M., Ashton N., Snable J.L., Lane J.C., Leong S.R., Thornton M.B., Miller K.L., Scott R.W. J. Biol. Chem. 269:17411-17416(1994) [PubMed: 7517398] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"cDNA cloning and sequence analysis of human bactericidal/permeability protein." Ma H., Cao X., Sun Y., Lei W. Submitted (FEB-2006) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT VAL-16.
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ASP-404. Tissue: Fetal heart.
[5]	"The DNA sequence and comparative analysis of human chromosome 20." Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E. , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J. Nature 414:865-871(2001) [PubMed: 11780052] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT LYS-216. Tissue: Leukocyte.
[7]	"Cloning of cDNA of human bactericidal/permeability-increasing protein." Xu J., Wang H. Submitted (NOV-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 5-487, VARIANTS LYS-216 AND ASP-404.
[8]	"Comparison of granule proteins from human polymorphonuclear leukocytes which are bactericidal toward Pseudomonas aeruginosa." Wasiluk K.R., Skubitz K.M., Gray B.H. Infect. Immun. 59:4193-4200(1991) [PubMed: 1937776] [Abstract] Cited for: PROTEIN SEQUENCE OF 32-53, FUNCTION. Tissue: Leukocyte.
[9]	"Antibiotic proteins of human polymorphonuclear leukocytes." Gabay J.E., Scott R.W., Campanelli D., Griffith J., Wilde C., Marra M.N., Seeger M., Nathan C.F. Proc. Natl. Acad. Sci. U.S.A. 86:5610-5614(1989) [PubMed: 2501794] [Abstract] Cited for: PROTEIN SEQUENCE OF 32-51.
[10]	"A 25-kDa NH2-terminal fragment carries all the antibacterial activities of the human neutrophil 60-kDa bactericidal/permeability-increasing protein." Ooi C.E., Weiss J., Elsbach P., Frangione B., Mannion B. J. Biol. Chem. 262:14891-14894(1987) [PubMed: 3667613] [Abstract] Cited for: PROTEIN SEQUENCE OF 32-48.
[11]	"Expression and characterization of cysteine-modified variants of an amino-terminal fragment of bactericidal/permeability-increasing protein." Horwitz A.H., Leigh S.D., Abrahamson S., Gazzano-Santoro H., Liu P.-S., Williams R.E., Carroll S.F., Theofan G. Protein Expr. Purif. 8:28-40(1996) [PubMed: 8812832] [Abstract] Cited for: SUBUNIT, SUBCELLULAR LOCATION, MUTAGENESIS OF SER-49; CYS-163; CYS-166 AND CYS-206.
[12]	"Crystal structure of human BPI and two bound phospholipids at 2.4-A resolution." Beamer L.J., Carroll S.F., Eisenberg D. Science 276:1861-1864(1997) [PubMed: 9188532] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 32-487.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

J04739 mRNA. Translation: AAA51841.1.
DQ414688 mRNA. Translation: ABD66755.1.
AK315328 mRNA. Translation: BAG37729.1.
AL391692, AL499625, AL583962 Genomic DNA. Translation: CAC10453.2. Sequence problems.
AL359555, AL391692, AL499625 Genomic DNA. Translation: CAC13043.3.
AL499625, AL391692, AL583962 Genomic DNA. Translation: CAC27350.2. Sequence problems.
AL391692, AL359555, AL499625 Genomic DNA. Translation: CAI41452.2.
AL499625, AL359555, AL391692 Genomic DNA. Translation: CAI43242.2.
BC040955 mRNA. Translation: AAH40955.1.
AF322588 mRNA. Translation: AAG42844.1.

IPI

IPI00827847.

PIR

A30909. A33850.

RefSeq

NP_001716.2. NM_001725.2.

UniGene

Hs.529019.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1BP1	X-ray	2.40	A	32-487	[»]
1EWF	X-ray	1.70	A	32-483	[»]

ProteinModelPortal

P17213.

SMR

P17213. Positions 32-487.

ModBase

Search...

Protein-protein interaction databases

STRING

P17213.

Protein family/group databases

TCDB

1.C.40.1.1. bactericidal permeability increasing protein (BPIP) family.

Polymorphism databases

DMDM

215274242.

Proteomic databases

PRIDE

P17213.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000262865; ENSP00000262865; ENSG00000101425.

GeneID

671.

KEGG

hsa:671.

Organism-specific databases

CTD

671.

GeneCards

GC20P036888.

H-InvDB

HIX0027669.

HGNC

HGNC:1095. BPI.

MIM

109195. gene.

neXtProt

NX_P17213.

PharmGKB

PA25403.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG15354.

GeneTree

ENSGT00600000084091.

HOVERGEN

HBG002797.

InParanoid

P17213.

OMA

HQNFLLF.

PhylomeDB

P17213.

Gene expression databases

ArrayExpress

P17213.

Bgee

P17213.

Genevestigator

P17213.

GermOnline

ENSG00000101425. Homo sapiens.

Family and domain databases

InterPro

IPR017943. Bactericidal_perm-incr_a/b_dom.
IPR001124. Lipid-bd_serum_glycop_C.
IPR017954. Lipid-bd_serum_glycop_CS.
IPR017942. Lipid-bd_serum_glycop_N.
[Graphical view]

Pfam

PF01273. LBP_BPI_CETP. 1 hit.
PF02886. LBP_BPI_CETP_C. 1 hit.
[Graphical view]

SMART

SM00328. BPI1. 1 hit.
SM00329. BPI2. 1 hit.
[Graphical view]

SUPFAM

SSF55394. Bactericidal_perm-incr_a/b_dom. 2 hits.

PROSITE

PS00400. LBP_BPI_CETP. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

2748.

SOURCE

Search...

Entry information

Entry name

BPI_HUMAN

Accession

Primary (citable) accession number: P17213
Secondary accession number(s): B2RCY2 , Q1ZZU8, Q5JRW0, Q8IW58, Q9BYZ9, Q9H1L2, Q9H1M8, Q9H203, Q9UCT4, Q9UD65

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1990
Last sequence update:	November 25, 2008
Last modified:	December 14, 2011
This is version 124 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.