BPIA1_MOUSE
ID BPIA1_MOUSE Reviewed; 278 AA.
AC P97361; Q7TQJ2;
DT 18-OCT-2001, integrated into UniProtKB/Swiss-Prot.
DT 26-APR-2004, sequence version 3.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=BPI fold-containing family A member 1;
DE AltName: Full=Palate lung and nasal epithelium clone protein;
DE Flags: Precursor;
GN Name=Bpifa1; Synonyms=Plunc, Splunc1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND REPEAT.
RC STRAIN=ICR; TISSUE=Palate;
RX PubMed=10224143; DOI=10.1074/jbc.274.19.13698;
RA Weston W.M., LeClair E.E., Trzyna W., McHugh K.M., Nugent P.,
RA Lafferty C.M., Ma L., Tuan R.S., Greene R.M.;
RT "Differential display identification of plunc, a novel gene expressed in
RT embryonic palate, nasal epithelium, and adult lung.";
RL J. Biol. Chem. 274:13698-13703(1999).
RN [2]
RP ERRATUM OF PUBMED:10224143.
RA Weston W.M., LeClair E.E., Trzyna W., McHugh K.M., Nugent P.,
RA Lafferty C.M., Ma L., Tuan R.S., Greene R.M.;
RL J. Biol. Chem. 275:8262-8262(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], TISSUE SPECIFICITY, AND DEVELOPMENTAL
RP STAGE.
RC STRAIN=129/Sv;
RX PubMed=11396972; DOI=10.1006/bbrc.2001.5024;
RA LeClair E.E., Nguyen L., Bingle L., MacGowan A., Singleton V., Ward S.J.,
RA Bingle C.D.;
RT "Genomic organization of the mouse plunc gene and expression in the
RT developing airways and thymus.";
RL Biochem. Biophys. Res. Commun. 284:792-797(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Olfactory epithelium;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=23499554; DOI=10.1016/j.ajpath.2013.01.050;
RA Liu Y., Bartlett J.A., Di M.E., Bomberger J.M., Chan Y.R., Gakhar L.,
RA Mallampalli R.K., McCray P.B. Jr., Di Y.P.;
RT "SPLUNC1/BPIFA1 contributes to pulmonary host defense against Klebsiella
RT pneumoniae respiratory infection.";
RL Am. J. Pathol. 182:1519-1531(2013).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 38-278, AND DISULFIDE BOND.
RX PubMed=29717993; DOI=10.1107/s2053230x18004600;
RA Little M.S., Redinbo M.R.;
RT "Crystal structure of the mouse innate immunity factor bacterial
RT permeability-increasing family member A1.";
RL Acta Crystallogr. F Struct. Biol. Commun. 74:268-276(2018).
CC -!- FUNCTION: Lipid-binding protein which shows high specificity for the
CC surfactant phospholipid dipalmitoylphosphatidylcholine (DPPC) (By
CC similarity). Plays a role in the innate immune responses of the upper
CC airways (PubMed:23499554). Reduces the surface tension in secretions
CC from airway epithelia and inhibits the formation of biofilm by
CC pathogenic Gram-negative bacteria, such as P.aeruginosa and
CC K.pneumoniae (PubMed:23499554). Negatively regulates proteolytic
CC cleavage of SCNN1G, an event that is required for activation of the
CC epithelial sodium channel (ENaC), and thereby contributes to airway
CC surface liquid homeostasis and proper clearance of mucus (By
CC similarity). Plays a role in the airway inflammatory response after
CC exposure to irritants (By similarity). May attract macrophages and
CC neutrophils (By similarity). {ECO:0000250|UniProtKB:Q9NP55,
CC ECO:0000269|PubMed:23499554}.
CC -!- SUBUNIT: Monomer. Interacts (via N-terminus) with SCNN1B, a subunit of
CC the heterotrimeric epithelial sodium channel (ENaC); this inhibits
CC proteolytic activation of ENaC (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:23499554}.
CC Note=Apical side of airway epithelial cells. Detected in airway surface
CC liquid, nasal mucus and sputum.
CC -!- TISSUE SPECIFICITY: Detected in airway epithelia (trachea and lung) and
CC in bronchoalveolar fluid (at protein level). Upper airways,
CC nasopharyngeal epithelium and thymus. Highest expression in the trachea
CC and progressive decrease from proximal (bronchial) to distal
CC (bronchiolar) airways. No expression is detected in the terminal
CC bronchioles, respiratory bronchioles or lung alveoli.
CC {ECO:0000269|PubMed:10224143, ECO:0000269|PubMed:11396972,
CC ECO:0000269|PubMed:23499554}.
CC -!- DEVELOPMENTAL STAGE: First detected at 14.5 dpc in the nasopharyngeal
CC epithelium and persists there into adulthood. In the thymus, weak
CC expression is detected at 16.5 dpc and appears to be restricted to
CC epithelial cells lining the medullary venules. This pattern of thymic
CC expression persists until birth and into early postnatal life but is
CC greatly decreased in the adult thymus. No expression is detected in the
CC lung until 2 days after birth, after which expression is detected in
CC cells lining the trachea. {ECO:0000269|PubMed:11396972}.
CC -!- SIMILARITY: Belongs to the BPI/LBP/Plunc superfamily. Plunc family.
CC {ECO:0000305}.
CC -!- CAUTION: Reported to bind to bacterial lipopolysaccharide (LPS) in
CC vitro. However, the in vivo significance of this is uncertain since
CC other studies indicate little or no specificity for LPS.
CC {ECO:0000250|UniProtKB:Q9NP55}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; U69172; AAB63256.1; -; mRNA.
DR EMBL; AF356785; AAK63069.1; -; Genomic_DNA.
DR EMBL; BC054375; AAH54375.1; -; mRNA.
DR CCDS; CCDS16925.1; -.
DR RefSeq; NP_035256.2; NM_011126.3.
DR PDB; 6BAQ; X-ray; 2.50 A; A/B/C/D/E/F/G/H=38-278.
DR PDBsum; 6BAQ; -.
DR AlphaFoldDB; P97361; -.
DR SMR; P97361; -.
DR STRING; 10090.ENSMUSP00000028985; -.
DR GlyGen; P97361; 2 sites.
DR PhosphoSitePlus; P97361; -.
DR MaxQB; P97361; -.
DR PaxDb; P97361; -.
DR PeptideAtlas; P97361; -.
DR PRIDE; P97361; -.
DR ProteomicsDB; 265452; -.
DR DNASU; 18843; -.
DR Ensembl; ENSMUST00000028985; ENSMUSP00000028985; ENSMUSG00000027483.
DR GeneID; 18843; -.
DR KEGG; mmu:18843; -.
DR UCSC; uc008niu.2; mouse.
DR CTD; 51297; -.
DR MGI; MGI:1338036; Bpifa1.
DR VEuPathDB; HostDB:ENSMUSG00000027483; -.
DR eggNOG; ENOG502SR58; Eukaryota.
DR GeneTree; ENSGT01020000230460; -.
DR HOGENOM; CLU_095915_0_0_1; -.
DR InParanoid; P97361; -.
DR OMA; ANMLIHG; -.
DR OrthoDB; 1275829at2759; -.
DR PhylomeDB; P97361; -.
DR TreeFam; TF337052; -.
DR Reactome; R-MMU-6803157; Antimicrobial peptides.
DR BioGRID-ORCS; 18843; 0 hits in 71 CRISPR screens.
DR ChiTaRS; Bpifa1; mouse.
DR PRO; PR:P97361; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; P97361; protein.
DR Bgee; ENSMUSG00000027483; Expressed in trachea and 45 other tissues.
DR Genevisible; P97361; MM.
DR GO; GO:0005576; C:extracellular region; ISS:UniProtKB.
DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR GO; GO:0005902; C:microvillus; ISO:MGI.
DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR GO; GO:0019731; P:antibacterial humoral response; IMP:UniProtKB.
DR GO; GO:0061844; P:antimicrobial humoral immune response mediated by antimicrobial peptide; IBA:GO_Central.
DR GO; GO:0002395; P:immune response in nasopharyngeal-associated lymphoid tissue; IBA:GO_Central.
DR GO; GO:0045087; P:innate immune response; IMP:UniProtKB.
DR GO; GO:0050891; P:multicellular organismal water homeostasis; ISS:UniProtKB.
DR GO; GO:1900229; P:negative regulation of single-species biofilm formation in or on host organism; IMP:UniProtKB.
DR GO; GO:0050828; P:regulation of liquid surface tension; ISS:UniProtKB.
DR GO; GO:1902305; P:regulation of sodium ion transmembrane transport; ISS:UniProtKB.
DR InterPro; IPR017943; Bactericidal_perm-incr_a/b_dom.
DR InterPro; IPR034307; BPIFA1.
DR InterPro; IPR017942; Lipid-bd_serum_glycop_N.
DR PANTHER; PTHR47015:SF1; PTHR47015:SF1; 1.
DR Pfam; PF01273; LBP_BPI_CETP; 1.
DR SUPFAM; SSF55394; SSF55394; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antibiotic; Antimicrobial; Disulfide bond; Glycoprotein;
KW Immunity; Innate immunity; Lipid-binding; Reference proteome; Repeat;
KW Secreted; Signal.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..278
FT /note="BPI fold-containing family A member 1"
FT /id="PRO_0000017176"
FT REPEAT 23..28
FT /note="Repeat 1"
FT /evidence="ECO:0000305|PubMed:10224143"
FT REPEAT 30..36
FT /note="Repeat 2"
FT /evidence="ECO:0000305|PubMed:10224143"
FT REPEAT 39..44
FT /note="Repeat 3"
FT /evidence="ECO:0000305|PubMed:10224143"
FT REPEAT 47..52
FT /note="Repeat 4"
FT /evidence="ECO:0000305|PubMed:10224143"
FT REGION 23..52
FT /note="4 X 6 AA repeats of G-[LPQ]-[PL]-L-P-L"
FT /evidence="ECO:0000305|PubMed:10224143"
FT REGION 112..117
FT /note="Important for surfactant activity and antibacterial
FT properties"
FT /evidence="ECO:0000250|UniProtKB:Q9NP55"
FT CARBOHYD 182
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 228
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 204..246
FT /evidence="ECO:0000269|PubMed:29717993,
FT ECO:0007744|PDB:6BAQ"
FT HELIX 68..71
FT /evidence="ECO:0007829|PDB:6BAQ"
FT HELIX 72..86
FT /evidence="ECO:0007829|PDB:6BAQ"
FT HELIX 89..94
FT /evidence="ECO:0007829|PDB:6BAQ"
FT HELIX 98..103
FT /evidence="ECO:0007829|PDB:6BAQ"
FT HELIX 112..120
FT /evidence="ECO:0007829|PDB:6BAQ"
FT HELIX 124..128
FT /evidence="ECO:0007829|PDB:6BAQ"
FT STRAND 132..140
FT /evidence="ECO:0007829|PDB:6BAQ"
FT STRAND 144..147
FT /evidence="ECO:0007829|PDB:6BAQ"
FT STRAND 151..167
FT /evidence="ECO:0007829|PDB:6BAQ"
FT HELIX 169..171
FT /evidence="ECO:0007829|PDB:6BAQ"
FT STRAND 175..191
FT /evidence="ECO:0007829|PDB:6BAQ"
FT STRAND 197..206
FT /evidence="ECO:0007829|PDB:6BAQ"
FT STRAND 212..215
FT /evidence="ECO:0007829|PDB:6BAQ"
FT STRAND 223..226
FT /evidence="ECO:0007829|PDB:6BAQ"
FT HELIX 227..254
FT /evidence="ECO:0007829|PDB:6BAQ"
FT HELIX 258..269
FT /evidence="ECO:0007829|PDB:6BAQ"
SQ SEQUENCE 278 AA; 28625 MW; 2540BED994475387 CRC64;
MFLVGSLVVL CGLLAHSTAQ LAGLPLPLGQ GPPLPLNQGP PLPLNQGQLL PLAQGLPLAV
SPALPSNPTD LLAGKFTDAL SGGLLSGGLL GILENIPLLD VIKSGGGNSN GLVGGLLGKL
TSSVPLLNNI LDIKITDPQL LELGLVQSPD GHRLYVTIPL GLTLNVNMPV VGSLLQLAVK
LNITAEVLAV KDNQGRIHLV LGDCTHSPGS LKISLLNGVT PVQSFLDNLT GILTKVLPEL
IQGKVCPLVN GILSGLDVTL VHNIAELLIH GLQFVIKV
