BPIA1_HUMAN
ID BPIA1_HUMAN Reviewed; 256 AA.
AC Q9NP55; A6XMV5; A8K9R3; E1P5M9; Q9NZT0;
DT 18-OCT-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 169.
DE RecName: Full=BPI fold-containing family A member 1;
DE AltName: Full=Lung-specific protein X;
DE AltName: Full=Nasopharyngeal carcinoma-related protein;
DE AltName: Full=Palate lung and nasal epithelium clone protein;
DE AltName: Full=Secretory protein in upper respiratory tracts;
DE AltName: Full=Short PLUNC1;
DE Short=SPLUNC1;
DE AltName: Full=Tracheal epithelium-enriched protein;
DE AltName: Full=Von Ebner protein Hl;
DE Flags: Precursor;
GN Name=BPIFA1; Synonyms=LUNX, NASG, PLUNC, SPLUNC1, SPURT;
GN ORFNames=UNQ787/PRO1606;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), AND TISSUE
RP SPECIFICITY.
RX PubMed=11018263; DOI=10.1016/s0167-4781(00)00196-2;
RA Bingle C.D., Bingle L.;
RT "Characterization of the human plunc gene, a gene product with an upper
RT airways and nasopharyngeal restricted expression pattern.";
RL Biochim. Biophys. Acta 1493:363-367(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA He Z.W., Xie L., Xu L.G., Lan K., Liu W., Zhang L., Ren C., Shi J.,
RA Zhou W., Yao K.;
RT "Cloning of a novel gene associated with human nasopharyngeal carcinoma.";
RL Chin. Sci. Bull. 45:2267-2272(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RC TISSUE=Lung;
RX PubMed=11251963;
RX DOI=10.1002/1097-0215(200002)9999:9999<::aid-ijc1059>3.0.co;2-b;
RA Iwao K., Watanabe T., Fujiwara Y., Takami K., Kodama K., Higashiyama M.,
RA Yokouchi H., Ozaki K., Monden M., Tanigami A.;
RT "Isolation of a novel human lung-specific gene, LUNX, a potential molecular
RT marker for detection of micrometastasis in non-small-cell lung cancer.";
RL Int. J. Cancer 91:433-437(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Zhang B., Yu Y., Li G.;
RT "Isolation of nasopharynx-specific gene and nasopharyngeal carcinoma (NPC)
RT susceptibility gene by suppression subtractive hybridization and cDNA
RT microarray technique.";
RL Submitted (OCT-2001) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, AND INDUCTION BY ATRA.
RC TISSUE=Tracheobronchial epithelium;
RX PubMed=12409287; DOI=10.1074/jbc.m210523200;
RA Di Y.-P., Harper R., Zhao Y., Pahlavan N., Finkbeiner W., Wu R.;
RT "Molecular cloning and characterization of spurt, a human novel gene that
RT is retinoic acid-inducible and encodes a secretory protein specific in
RT upper respiratory tracts.";
RL J. Biol. Chem. 278:1165-1173(2003).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Trachea;
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., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., 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., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA 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 [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RA Yu Z., Zheng Z., Tang T., Fu Y.;
RT "A computer system platform used to predict novel genes.";
RL Submitted (JUL-2006) to the EMBL/GenBank/DDBJ databases.
RN [9]
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., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., 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., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Skeletal muscle;
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 [12]
RP PROTEIN SEQUENCE OF 95-152; 157-167 AND 214-232, FUNCTION, AND SUBCELLULAR
RP LOCATION.
RX PubMed=11425234;
RX DOI=10.1002/1522-2683(200105)22:9<1795::aid-elps1795>3.0.co;2-j;
RA Lindahl M., Stahlbom B., Tagesson C.;
RT "Identification of a new potential airway irritation marker, palate lung
RT nasal epithelial clone protein, in human nasal lavage fluid with two-
RT dimensional electrophoresis and matrix-assisted laser
RT desorption/ionization-time of flight.";
RL Electrophoresis 22:1795-1800(2001).
RN [13]
RP PROTEIN SEQUENCE OF 95-102; 115-152 AND 157-167, BINDING TO
RP LIPOPOLYSACCHARIDES, GLYCOSYLATION, AND SUBCELLULAR LOCATION.
RX PubMed=15158712; DOI=10.1016/j.bbapap.2004.01.001;
RA Ghafouri B., Kihlstroem E., Tagesson C., Lindahl M.;
RT "PLUNC in human nasal lavage fluid: multiple isoforms that bind to
RT lipopolysaccharide.";
RL Biochim. Biophys. Acta 1699:57-63(2004).
RN [14]
RP PROTEIN SEQUENCE OF 110-121, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=12920053; DOI=10.1165/rcmb.2003-0142oc;
RA Campos M.A., Abreu A.R., Nlend M.C., Cobas M.A., Conner G.E., Whitney P.L.;
RT "Purification and characterization of PLUNC from human tracheobronchial
RT secretions.";
RL Am. J. Respir. Cell Mol. Biol. 30:184-192(2004).
RN [15]
RP FUNCTION, AND SUBCELLULAR LOCATION.
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 [16]
RP FUNCTION, INTERACTION WITH SCNN1B, SUBCELLULAR LOCATION, AND SUBUNIT.
RX PubMed=24124190; DOI=10.1152/ajplung.00103.2013;
RA Hobbs C.A., Blanchard M.G., Alijevic O., Tan C.D., Kellenberger S.,
RA Bencharit S., Cao R., Kesimer M., Walton W.G., Henderson A.G.,
RA Redinbo M.R., Stutts M.J., Tarran R.;
RT "Identification of the SPLUNC1 ENaC-inhibitory domain yields novel
RT strategies to treat sodium hyperabsorption in cystic fibrosis airway
RT epithelial cultures.";
RL Am. J. Physiol. 305:L990-L1001(2013).
RN [17]
RP FUNCTION.
RX PubMed=23132494; DOI=10.1128/iai.00500-12;
RA Sayeed S., Nistico L., St Croix C., Di Y.P.;
RT "Multifunctional role of human SPLUNC1 in Pseudomonas aeruginosa
RT infection.";
RL Infect. Immun. 81:285-291(2013).
RN [18]
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=26559477; DOI=10.1167/iovs.15-17560;
RA Schicht M., Rausch F., Beron M., Jacobi C., Garreis F., Hartjen N.,
RA Beileke S., Kruse F., Braeuer L., Paulsen F.;
RT "Palate Lung Nasal Clone (PLUNC), a Novel Protein of the Tear Film: Three-
RT Dimensional Structure, Immune Activation, and Involvement in Dry Eye
RT Disease (DED).";
RL Invest. Ophthalmol. Vis. Sci. 56:7312-7323(2015).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (2.81 ANGSTROMS) OF 19-256, FUNCTION, DISULFIDE BOND,
RP SUBCELLULAR LOCATION, SUBUNIT, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=24043776; DOI=10.1073/pnas.1311999110;
RA Garland A.L., Walton W.G., Coakley R.D., Tan C.D., Gilmore R.C.,
RA Hobbs C.A., Tripathy A., Clunes L.A., Bencharit S., Stutts M.J., Betts L.,
RA Redinbo M.R., Tarran R.;
RT "Molecular basis for pH-dependent mucosal dehydration in cystic fibrosis
RT airways.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:15973-15978(2013).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 43-256, FUNCTION, AND DISULFIDE
RP BOND.
RX PubMed=25223608; DOI=10.1096/fj.14-259291;
RA Ning F., Wang C., Berry K.Z., Kandasamy P., Liu H., Murphy R.C.,
RA Voelker D.R., Nho C.W., Pan C.H., Dai S., Niu L., Chu H.W., Zhang G.;
RT "Structural characterization of the pulmonary innate immune protein SPLUNC1
RT and identification of lipid ligands.";
RL FASEB J. 28:5349-5360(2014).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (2.54 ANGSTROMS) OF 19-256, FUNCTION, BINDING TO
RP LIPOPOLYSACCHARIDES, DISULFIDE BOND, AND MUTAGENESIS OF ALA-48; ILE-76;
RP 87-LEU--LEU-92; CYS-180; 191-LEU--LEU-195; 203-LEU-LEU-204; VAL-214;
RP CYS-224 AND VAL-253.
RX PubMed=27145151; DOI=10.1021/acs.biochem.6b00271;
RA Walton W.G., Ahmad S., Little M.S., Kim C.S., Tyrrell J., Lin Q., Di Y.P.,
RA Tarran R., Redinbo M.R.;
RT "Structural Features Essential to the Antimicrobial Functions of Human
RT SPLUNC1.";
RL Biochemistry 55:2979-2991(2016).
CC -!- FUNCTION: Lipid-binding protein which shows high specificity for the
CC surfactant phospholipid dipalmitoylphosphatidylcholine (DPPC)
CC (PubMed:25223608). Plays a role in the innate immune responses of the
CC upper airways (PubMed:23499554, PubMed:23132494). Reduces the surface
CC tension in secretions from airway epithelia and inhibits the formation
CC of biofilm by pathogenic Gram-negative bacteria, such as P.aeruginosa
CC and K.pneumoniae (PubMed:23499554, PubMed:23132494, PubMed:27145151).
CC Negatively regulates proteolytic cleavage of SCNN1G, an event that is
CC required for activation of the epithelial sodium channel (ENaC), and
CC thereby contributes to airway surface liquid homeostasis and proper
CC clearance of mucus (PubMed:24124190, PubMed:24043776). Plays a role in
CC the airway inflammatory response after exposure to irritants
CC (PubMed:11425234). May attract macrophages and neutrophils
CC (PubMed:23132494). {ECO:0000269|PubMed:11425234,
CC ECO:0000269|PubMed:23132494, ECO:0000269|PubMed:23499554,
CC ECO:0000269|PubMed:24043776, ECO:0000269|PubMed:24124190,
CC ECO:0000269|PubMed:25223608, ECO:0000269|PubMed:27145151}.
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. {ECO:0000269|PubMed:24043776,
CC ECO:0000269|PubMed:24124190}.
CC -!- INTERACTION:
CC Q9NP55; Q9NXW9: ALKBH4; NbExp=3; IntAct=EBI-953896, EBI-8637516;
CC Q9NP55; P27658: COL8A1; NbExp=3; IntAct=EBI-953896, EBI-747133;
CC Q9NP55; P53672: CRYBA2; NbExp=3; IntAct=EBI-953896, EBI-750444;
CC Q9NP55; A8MUP2: CSKMT; NbExp=3; IntAct=EBI-953896, EBI-12842046;
CC Q9NP55; Q9H596: DUSP21; NbExp=3; IntAct=EBI-953896, EBI-7357329;
CC Q9NP55; P41970: ELK3; NbExp=3; IntAct=EBI-953896, EBI-1758534;
CC Q9NP55; A0A0C4DGQ7: EML2; NbExp=3; IntAct=EBI-953896, EBI-12112376;
CC Q9NP55; Q6NZ36-4: FAAP20; NbExp=3; IntAct=EBI-953896, EBI-12013806;
CC Q9NP55; Q8WU58: FAM222B; NbExp=3; IntAct=EBI-953896, EBI-2807642;
CC Q9NP55; Q8TAE8: GADD45GIP1; NbExp=3; IntAct=EBI-953896, EBI-372506;
CC Q9NP55; P28676: GCA; NbExp=3; IntAct=EBI-953896, EBI-947242;
CC Q9NP55; P08631-2: HCK; NbExp=3; IntAct=EBI-953896, EBI-9834454;
CC Q9NP55; P35680: HNF1B; NbExp=3; IntAct=EBI-953896, EBI-2798841;
CC Q9NP55; P17482: HOXB9; NbExp=3; IntAct=EBI-953896, EBI-745290;
CC Q9NP55; Q96LI6: HSFY2; NbExp=3; IntAct=EBI-953896, EBI-3957665;
CC Q9NP55; Q0VD86: INCA1; NbExp=3; IntAct=EBI-953896, EBI-6509505;
CC Q9NP55; Q9NRY2: INIP; NbExp=3; IntAct=EBI-953896, EBI-2881520;
CC Q9NP55; Q99706: KIR2DL4; NbExp=3; IntAct=EBI-953896, EBI-10294579;
CC Q9NP55; P12035: KRT3; NbExp=3; IntAct=EBI-953896, EBI-2430095;
CC Q9NP55; O14770-4: MEIS2; NbExp=3; IntAct=EBI-953896, EBI-8025850;
CC Q9NP55; Q13064: MKRN3; NbExp=3; IntAct=EBI-953896, EBI-2340269;
CC Q9NP55; Q9H2K0: MTIF3; NbExp=3; IntAct=EBI-953896, EBI-3923617;
CC Q9NP55; Q99743: NPAS2; NbExp=3; IntAct=EBI-953896, EBI-3932727;
CC Q9NP55; Q7Z3B4: NUP54; NbExp=3; IntAct=EBI-953896, EBI-741048;
CC Q9NP55; Q9HBE1-4: PATZ1; NbExp=3; IntAct=EBI-953896, EBI-11022007;
CC Q9NP55; Q9UBV8: PEF1; NbExp=3; IntAct=EBI-953896, EBI-724639;
CC Q9NP55; P78337: PITX1; NbExp=5; IntAct=EBI-953896, EBI-748265;
CC Q9NP55; O43447: PPIH; NbExp=3; IntAct=EBI-953896, EBI-1055615;
CC Q9NP55; P0CG20: PRR35; NbExp=3; IntAct=EBI-953896, EBI-11986293;
CC Q9NP55; P20618: PSMB1; NbExp=3; IntAct=EBI-953896, EBI-372273;
CC Q9NP55; Q9BTL3: RAMAC; NbExp=3; IntAct=EBI-953896, EBI-744023;
CC Q9NP55; Q9UHP6: RSPH14; NbExp=3; IntAct=EBI-953896, EBI-748350;
CC Q9NP55; Q14D33: RTP5; NbExp=3; IntAct=EBI-953896, EBI-10217913;
CC Q9NP55; Q9BVN2: RUSC1; NbExp=3; IntAct=EBI-953896, EBI-6257312;
CC Q9NP55; Q96NU1: SAMD11; NbExp=3; IntAct=EBI-953896, EBI-14067109;
CC Q9NP55; O00241-2: SIRPB1; NbExp=3; IntAct=EBI-953896, EBI-10179231;
CC Q9NP55; Q9BV90: SNRNP25; NbExp=3; IntAct=EBI-953896, EBI-9675976;
CC Q9NP55; Q9NQB0-10: TCF7L2; NbExp=3; IntAct=EBI-953896, EBI-11746252;
CC Q9NP55; Q96N21: TEPSIN; NbExp=3; IntAct=EBI-953896, EBI-11139477;
CC Q9NP55; Q92734: TFG; NbExp=3; IntAct=EBI-953896, EBI-357061;
CC Q9NP55; Q01085-2: TIAL1; NbExp=3; IntAct=EBI-953896, EBI-11064654;
CC Q9NP55; Q08117-2: TLE5; NbExp=5; IntAct=EBI-953896, EBI-11741437;
CC Q9NP55; O43711: TLX3; NbExp=3; IntAct=EBI-953896, EBI-3939165;
CC Q9NP55; Q9UMX0: UBQLN1; NbExp=3; IntAct=EBI-953896, EBI-741480;
CC Q9NP55; Q9UMX0-2: UBQLN1; NbExp=3; IntAct=EBI-953896, EBI-10173939;
CC Q9NP55; Q9UHD9: UBQLN2; NbExp=3; IntAct=EBI-953896, EBI-947187;
CC Q9NP55; Q9BRG1: VPS25; NbExp=3; IntAct=EBI-953896, EBI-741945;
CC Q9NP55; Q7L2R6-2: ZNF765; NbExp=3; IntAct=EBI-953896, EBI-12834294;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:11425234,
CC ECO:0000269|PubMed:12409287, ECO:0000269|PubMed:12920053,
CC ECO:0000269|PubMed:15158712, ECO:0000269|PubMed:23499554,
CC ECO:0000269|PubMed:24043776, ECO:0000269|PubMed:24124190,
CC ECO:0000269|PubMed:26559477}. Note=Apical side of airway epithelial
CC cells. Detected in airway surface liquid, nasal mucus and sputum.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9NP55-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9NP55-2; Sequence=VSP_057345;
CC -!- TISSUE SPECIFICITY: Highly expressed in lung, upper airways and
CC nasopharyngeal regions, including trachea and nasal epithelium (at
CC protein level) (PubMed:11018263, PubMed:11251963, PubMed:12409287,
CC PubMed:11425234, PubMed:26559477). Specifically expressed in the
CC secretory ducts and submucosal glands of tracheobronchial tissues (at
CC protein level) (PubMed:12409287, PubMed:11425234). Also expressed in
CC the eye where it is detected in lacrimal gland, eyelid, conjunctiva and
CC cornea (at protein level) (PubMed:26559477). Specifically localizes to
CC epithelial cell layers in cornea, eyelid (basal epithelium) and
CC conjunctiva (at protein level) (PubMed:26559477). Detected within
CC acinar cells and ducts in the lacrimal and Meibomian glands (at protein
CC level) (PubMed:26559477). In lung, shows highest expression in the
CC trachea and progressive decrease from proximal (bronchial) to distal
CC (bronchiolar) airways (PubMed:12409287). Also expressed in lung cancers
CC and some other types of cancer (PubMed:11251963).
CC {ECO:0000269|PubMed:11018263, ECO:0000269|PubMed:11251963,
CC ECO:0000269|PubMed:11425234, ECO:0000269|PubMed:12409287,
CC ECO:0000269|PubMed:26559477}.
CC -!- INDUCTION: Up-regulated in response to all-trans retinoic acid (ATRA)
CC (PubMed:12409287). Up-regulated in tear fluid of patients suffering
CC from dry eye disease (PubMed:26559477). Up-regulated in response to the
CC pro-inflammatory cytokines IL1B and TNF, and the bacteria E.coli and
CC P.aeruginosa (PubMed:26559477). {ECO:0000269|PubMed:12409287,
CC ECO:0000269|PubMed:26559477}.
CC -!- PTM: May be N-glycosylated. {ECO:0000269|PubMed:15158712}.
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 (PubMed:15158712, PubMed:27145151). However, the in vivo
CC significance of this is uncertain since other studies indicate little
CC or no specificity for LPS (PubMed:12920053, PubMed:25223608).
CC {ECO:0000269|PubMed:12920053, ECO:0000269|PubMed:15158712,
CC ECO:0000269|PubMed:25223608, ECO:0000269|PubMed:27145151}.
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DR EMBL; AF214562; AAG13653.1; -; Genomic_DNA.
DR EMBL; AF172993; AAF70860.1; -; mRNA.
DR EMBL; AF158745; AAF82622.1; -; mRNA.
DR EMBL; AB024937; BAA93633.1; -; mRNA.
DR EMBL; AF439448; AAL87636.1; -; mRNA.
DR EMBL; AF417256; AAO12198.1; -; mRNA.
DR EMBL; AF417257; AAO12199.1; -; mRNA.
DR EMBL; AF421369; AAO12200.1; -; Genomic_DNA.
DR EMBL; AY359020; AAQ89379.1; -; mRNA.
DR EMBL; AK292778; BAF85467.1; -; mRNA.
DR EMBL; DQ846869; ABI63356.1; -; mRNA.
DR EMBL; AL121901; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471077; EAW76327.1; -; Genomic_DNA.
DR EMBL; CH471077; EAW76328.1; -; Genomic_DNA.
DR EMBL; CH471077; EAW76329.1; -; Genomic_DNA.
DR EMBL; BC012549; AAH12549.1; -; mRNA.
DR CCDS; CCDS13217.1; -. [Q9NP55-1]
DR RefSeq; NP_001230122.1; NM_001243193.1. [Q9NP55-1]
DR RefSeq; NP_057667.1; NM_016583.3. [Q9NP55-1]
DR RefSeq; NP_570913.1; NM_130852.2. [Q9NP55-1]
DR PDB; 4KEG; X-ray; 2.50 A; A=43-256.
DR PDB; 4KGH; X-ray; 2.81 A; A/B=19-256.
DR PDB; 4KGO; X-ray; 3.19 A; A/B=19-256.
DR PDB; 4N4X; X-ray; 2.50 A; A=43-256.
DR PDB; 5I7J; X-ray; 2.54 A; A/B=19-256.
DR PDB; 5I7K; X-ray; 2.55 A; A/B=19-256.
DR PDB; 5I7L; X-ray; 2.60 A; A/B=19-256.
DR PDBsum; 4KEG; -.
DR PDBsum; 4KGH; -.
DR PDBsum; 4KGO; -.
DR PDBsum; 4N4X; -.
DR PDBsum; 5I7J; -.
DR PDBsum; 5I7K; -.
DR PDBsum; 5I7L; -.
DR AlphaFoldDB; Q9NP55; -.
DR SMR; Q9NP55; -.
DR BioGRID; 119448; 107.
DR IntAct; Q9NP55; 58.
DR MINT; Q9NP55; -.
DR STRING; 9606.ENSP00000346251; -.
DR iPTMnet; Q9NP55; -.
DR PhosphoSitePlus; Q9NP55; -.
DR BioMuta; BPIFA1; -.
DR DMDM; 17380173; -.
DR MassIVE; Q9NP55; -.
DR PaxDb; Q9NP55; -.
DR PeptideAtlas; Q9NP55; -.
DR PRIDE; Q9NP55; -.
DR ProteomicsDB; 1772; -.
DR ProteomicsDB; 81886; -. [Q9NP55-1]
DR Antibodypedia; 10611; 152 antibodies from 33 providers.
DR DNASU; 51297; -.
DR Ensembl; ENST00000354297.9; ENSP00000346251.4; ENSG00000198183.12. [Q9NP55-1]
DR Ensembl; ENST00000375413.8; ENSP00000364562.4; ENSG00000198183.12. [Q9NP55-1]
DR Ensembl; ENST00000375422.6; ENSP00000364571.2; ENSG00000198183.12. [Q9NP55-1]
DR Ensembl; ENST00000618484.1; ENSP00000482297.1; ENSG00000198183.12. [Q9NP55-2]
DR GeneID; 51297; -.
DR KEGG; hsa:51297; -.
DR MANE-Select; ENST00000354297.9; ENSP00000346251.4; NM_130852.3; NP_570913.1.
DR UCSC; uc002wyt.5; human. [Q9NP55-1]
DR CTD; 51297; -.
DR DisGeNET; 51297; -.
DR GeneCards; BPIFA1; -.
DR HGNC; HGNC:15749; BPIFA1.
DR HPA; ENSG00000198183; Tissue enhanced (cervix, lung, pituitary gland).
DR MIM; 607412; gene.
DR neXtProt; NX_Q9NP55; -.
DR OpenTargets; ENSG00000198183; -.
DR PharmGKB; PA33423; -.
DR VEuPathDB; HostDB:ENSG00000198183; -.
DR eggNOG; ENOG502SR58; Eukaryota.
DR GeneTree; ENSGT01020000230460; -.
DR HOGENOM; CLU_095915_0_0_1; -.
DR InParanoid; Q9NP55; -.
DR OMA; ANMLIHG; -.
DR OrthoDB; 1275829at2759; -.
DR PhylomeDB; Q9NP55; -.
DR TreeFam; TF337052; -.
DR PathwayCommons; Q9NP55; -.
DR Reactome; R-HSA-6803157; Antimicrobial peptides.
DR SignaLink; Q9NP55; -.
DR BioGRID-ORCS; 51297; 8 hits in 1064 CRISPR screens.
DR ChiTaRS; BPIFA1; human.
DR GeneWiki; Plunc; -.
DR GenomeRNAi; 51297; -.
DR Pharos; Q9NP55; Tbio.
DR PRO; PR:Q9NP55; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; Q9NP55; protein.
DR Bgee; ENSG00000198183; Expressed in olfactory segment of nasal mucosa and 58 other tissues.
DR Genevisible; Q9NP55; HS.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR GO; GO:0019731; P:antibacterial humoral response; IDA:UniProtKB.
DR GO; GO:0061844; P:antimicrobial humoral immune response mediated by antimicrobial peptide; IEP:UniProtKB.
DR GO; GO:0051607; P:defense response to virus; IEP:UniProtKB.
DR GO; GO:0002395; P:immune response in nasopharyngeal-associated lymphoid tissue; IEP:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IDA:UniProtKB.
DR GO; GO:0050891; P:multicellular organismal water homeostasis; IDA: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; IDA:UniProtKB.
DR GO; GO:1902305; P:regulation of sodium ion transmembrane transport; IDA: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; Alternative splicing; Antibiotic; Antimicrobial;
KW Direct protein sequencing; Disulfide bond; Glycoprotein; Immunity;
KW Innate immunity; Lipid-binding; Reference proteome; Secreted; Signal.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..256
FT /note="BPI fold-containing family A member 1"
FT /id="PRO_0000017175"
FT REGION 87..92
FT /note="Important for surfactant activity and antibacterial
FT properties"
FT /evidence="ECO:0000269|PubMed:27145151"
FT DISULFID 180..224
FT /evidence="ECO:0000269|PubMed:24043776,
FT ECO:0000269|PubMed:25223608, ECO:0000269|PubMed:27145151,
FT ECO:0007744|PDB:4KEG, ECO:0007744|PDB:4KGH,
FT ECO:0007744|PDB:4KGO, ECO:0007744|PDB:4N4X,
FT ECO:0007744|PDB:5I7J, ECO:0007744|PDB:5I7K,
FT ECO:0007744|PDB:5I7L"
FT VAR_SEQ 16..29
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.8"
FT /id="VSP_057345"
FT MUTAGEN 48
FT /note="A->C: Forms an artificial disulfide bond. Negligible
FT effect on surfactant activity; when associated with C-253."
FT /evidence="ECO:0000269|PubMed:27145151"
FT MUTAGEN 76
FT /note="I->C: Forms an artificial disulfide bond. Reduced
FT surfactant activity; when associated with C-214."
FT /evidence="ECO:0000269|PubMed:27145151"
FT MUTAGEN 87..92
FT /note="LLGGLL->AAGGAA,SSGGSS: Impaired surfactant activity
FT and lipopolysaccharide (LPS) binding. Reduced
FT bacteriostatic activity."
FT /evidence="ECO:0000269|PubMed:27145151"
FT MUTAGEN 180
FT /note="C->A: No effect on surfactant activity; when
FT associated with A-224."
FT /evidence="ECO:0000269|PubMed:27145151"
FT MUTAGEN 191..195
FT /note="LLDGL->AADGA: No effect on surfactant activity; when
FT associated with 203-A-A-204."
FT /evidence="ECO:0000269|PubMed:27145151"
FT MUTAGEN 203..204
FT /note="LL->AA: No effect on surfactant activity; when
FT associated with 191-A--A-195."
FT /evidence="ECO:0000269|PubMed:27145151"
FT MUTAGEN 214
FT /note="V->C: Forms an artificial disulfide bond. Reduced
FT surfactant activity; when associated with C-76."
FT /evidence="ECO:0000269|PubMed:27145151"
FT MUTAGEN 224
FT /note="C->A: No effect on surfactant activity; when
FT associated with A-180."
FT /evidence="ECO:0000269|PubMed:27145151"
FT MUTAGEN 253
FT /note="V->C: Forms an artificial disulfide bond. Negligible
FT effect on surfactant activity; when associated with C-48."
FT /evidence="ECO:0000269|PubMed:27145151"
FT CONFLICT 220
FT /note="Q -> K (in Ref. 1; AAF70860)"
FT /evidence="ECO:0000305"
FT HELIX 47..61
FT /evidence="ECO:0007829|PDB:4KEG"
FT HELIX 64..69
FT /evidence="ECO:0007829|PDB:4KEG"
FT HELIX 73..75
FT /evidence="ECO:0007829|PDB:5I7J"
FT HELIX 92..96
FT /evidence="ECO:0007829|PDB:5I7J"
FT STRAND 99..101
FT /evidence="ECO:0007829|PDB:5I7L"
FT STRAND 109..115
FT /evidence="ECO:0007829|PDB:4KEG"
FT STRAND 119..122
FT /evidence="ECO:0007829|PDB:4KEG"
FT STRAND 124..127
FT /evidence="ECO:0007829|PDB:4KGO"
FT STRAND 129..140
FT /evidence="ECO:0007829|PDB:4KEG"
FT TURN 144..146
FT /evidence="ECO:0007829|PDB:5I7J"
FT STRAND 152..167
FT /evidence="ECO:0007829|PDB:4KEG"
FT STRAND 169..171
FT /evidence="ECO:0007829|PDB:4KEG"
FT STRAND 173..177
FT /evidence="ECO:0007829|PDB:4KEG"
FT TURN 184..186
FT /evidence="ECO:0007829|PDB:4N4X"
FT STRAND 188..191
FT /evidence="ECO:0007829|PDB:4KEG"
FT STRAND 193..196
FT /evidence="ECO:0007829|PDB:5I7J"
FT HELIX 200..202
FT /evidence="ECO:0007829|PDB:5I7L"
FT HELIX 206..232
FT /evidence="ECO:0007829|PDB:4KEG"
FT HELIX 236..247
FT /evidence="ECO:0007829|PDB:4KEG"
SQ SEQUENCE 256 AA; 26713 MW; EDF152FBC35315BC CRC64;
MFQTGGLIVF YGLLAQTMAQ FGGLPVPLDQ TLPLNVNPAL PLSPTGLAGS LTNALSNGLL
SGGLLGILEN LPLLDILKPG GGTSGGLLGG LLGKVTSVIP GLNNIIDIKV TDPQLLELGL
VQSPDGHRLY VTIPLGIKLQ VNTPLVGASL LRLAVKLDIT AEILAVRDKQ ERIHLVLGDC
THSPGSLQIS LLDGLGPLPI QGLLDSLTGI LNKVLPELVQ GNVCPLVNEV LRGLDITLVH
DIVNMLIHGL QFVIKV
