ID   BPIB2_HUMAN             Reviewed;         458 AA.
AC   Q8N4F0; Q6UWN3; Q6ZME0; Q8NFQ7;
DT   29-AUG-2003, integrated into UniProtKB/Swiss-Prot.
DT   29-MAR-2005, sequence version 2.
DT   24-JAN-2024, entry version 163.
DE   RecName: Full=BPI fold-containing family B member 2;
DE   AltName: Full=Bactericidal/permeability-increasing protein-like 1;
DE            Short=BPI-like 1;
DE   AltName: Full=Long palate, lung and nasal epithelium carcinoma-associated protein 2;
DE   AltName: Full=RYSR;
DE   Flags: Precursor;
GN   Name=BPIFB2; Synonyms=BPIL1, C20orf184, LPLUNC2;
GN   ORFNames=UNQ2489/PRO5776;
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 [MRNA].
RC   TISSUE=Trachea;
RX   PubMed=12185532; DOI=10.1007/s00251-002-0467-3;
RA   Mulero J.J., Boyle B.J., Bradley S., Bright J.M., Nelken S.T., Ho T.T.,
RA   Mize N.K., Childs J.D., Ballinger D.G., Ford J.E., Rupp F.;
RT   "Three new human members of the lipid transfer/lipopolysaccharide binding
RT   protein family (LT/LBP).";
RL   Immunogenetics 54:293-300(2002).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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   [4]
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   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton 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   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain, Lung, and Testis;
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   [7]
RP   PROTEIN SEQUENCE OF 21-35.
RX   PubMed=15340161; DOI=10.1110/ps.04682504;
RA   Zhang Z., Henzel W.J.;
RT   "Signal peptide prediction based on analysis of experimentally verified
RT   cleavage sites.";
RL   Protein Sci. 13:2819-2824(2004).
RN   [8]
RP   SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC   TISSUE=Fetal brain;
RX   PubMed=12837268; DOI=10.1016/s0888-7543(03)00102-2;
RA   Andrault J.-B., Gaillard I., Giorgi D., Rouquier S.;
RT   "Expansion of the BPI family by duplication on human chromosome 20:
RT   characterization of the RY gene cluster in 20q11.21 encoding olfactory
RT   transporters/antimicrobial-like peptides.";
RL   Genomics 82:172-184(2003).
RN   [9]
RP   PHOSPHORYLATION AT THR-52 AND SER-60.
RX   PubMed=26091039; DOI=10.1016/j.cell.2015.05.028;
RA   Tagliabracci V.S., Wiley S.E., Guo X., Kinch L.N., Durrant E., Wen J.,
RA   Xiao J., Cui J., Nguyen K.B., Engel J.L., Coon J.J., Grishin N.,
RA   Pinna L.A., Pagliarini D.J., Dixon J.E.;
RT   "A single kinase generates the majority of the secreted phosphoproteome.";
RL   Cell 161:1619-1632(2015).
RN   [10]
RP   GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-96; ASN-293 AND ASN-332.
RC   TISSUE=Saliva;
RX   PubMed=16740002; DOI=10.1021/pr050492k;
RA   Ramachandran P., Boontheung P., Xie Y., Sondej M., Wong D.T., Loo J.A.;
RT   "Identification of N-linked glycoproteins in human saliva by glycoprotein
RT   capture and mass spectrometry.";
RL   J. Proteome Res. 5:1493-1503(2006).
RN   [11]
RP   VARIANT [LARGE SCALE ANALYSIS] VAL-20.
RX   PubMed=16959974; DOI=10.1126/science.1133427;
RA   Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA   Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA   Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA   Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA   Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA   Velculescu V.E.;
RT   "The consensus coding sequences of human breast and colorectal cancers.";
RL   Science 314:268-274(2006).
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}.
CC   -!- TISSUE SPECIFICITY: Highly expressed in tonsils, especially in
CC       hypertrophic tonsils. Detected at very low levels in fetal liver.
CC       {ECO:0000269|PubMed:12837268}.
CC   -!- SIMILARITY: Belongs to the BPI/LBP/Plunc superfamily. BPI/LBP family.
CC       {ECO:0000305}.
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DR   EMBL; AF465765; AAM73983.1; -; mRNA.
DR   EMBL; AY358723; AAQ89085.1; -; mRNA.
DR   EMBL; AK172819; BAD18788.1; -; mRNA.
DR   EMBL; AL121756; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471077; EAW76341.1; -; Genomic_DNA.
DR   EMBL; BC034415; AAH34415.1; -; mRNA.
DR   CCDS; CCDS13210.1; -.
DR   RefSeq; NP_079503.1; NM_025227.2.
DR   AlphaFoldDB; Q8N4F0; -.
DR   SMR; Q8N4F0; -.
DR   BioGRID; 123248; 13.
DR   IntAct; Q8N4F0; 3.
DR   STRING; 9606.ENSP00000170150; -.
DR   TCDB; 1.C.40.1.6; the bactericidal permeability increasing protein (bpip) family.
DR   CarbonylDB; Q8N4F0; -.
DR   GlyCosmos; Q8N4F0; 4 sites, No reported glycans.
DR   GlyGen; Q8N4F0; 4 sites.
DR   iPTMnet; Q8N4F0; -.
DR   PhosphoSitePlus; Q8N4F0; -.
DR   BioMuta; BPIFB2; -.
DR   DMDM; 62298542; -.
DR   jPOST; Q8N4F0; -.
DR   MassIVE; Q8N4F0; -.
DR   PaxDb; 9606-ENSP00000170150; -.
DR   PeptideAtlas; Q8N4F0; -.
DR   PRIDE; Q8N4F0; -.
DR   ProteomicsDB; 71926; -.
DR   Antibodypedia; 25479; 128 antibodies from 25 providers.
DR   DNASU; 80341; -.
DR   Ensembl; ENST00000170150.4; ENSP00000170150.3; ENSG00000078898.7.
DR   GeneID; 80341; -.
DR   KEGG; hsa:80341; -.
DR   MANE-Select; ENST00000170150.4; ENSP00000170150.3; NM_025227.3; NP_079503.1.
DR   UCSC; uc002wyj.5; human.
DR   AGR; HGNC:16177; -.
DR   CTD; 80341; -.
DR   DisGeNET; 80341; -.
DR   GeneCards; BPIFB2; -.
DR   HGNC; HGNC:16177; BPIFB2.
DR   HPA; ENSG00000078898; Tissue enriched (salivary).
DR   MIM; 614108; gene.
DR   neXtProt; NX_Q8N4F0; -.
DR   OpenTargets; ENSG00000078898; -.
DR   PharmGKB; PA25404; -.
DR   VEuPathDB; HostDB:ENSG00000078898; -.
DR   eggNOG; KOG4160; Eukaryota.
DR   GeneTree; ENSGT01100000263546; -.
DR   HOGENOM; CLU_597102_0_0_1; -.
DR   InParanoid; Q8N4F0; -.
DR   OMA; QVTVPYF; -.
DR   OrthoDB; 5324050at2759; -.
DR   PhylomeDB; Q8N4F0; -.
DR   TreeFam; TF315617; -.
DR   PathwayCommons; Q8N4F0; -.
DR   Reactome; R-HSA-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR   Reactome; R-HSA-6803157; Antimicrobial peptides.
DR   Reactome; R-HSA-8957275; Post-translational protein phosphorylation.
DR   SignaLink; Q8N4F0; -.
DR   BioGRID-ORCS; 80341; 13 hits in 1147 CRISPR screens.
DR   GeneWiki; BPIL1; -.
DR   GenomeRNAi; 80341; -.
DR   Pharos; Q8N4F0; Tbio.
DR   PRO; PR:Q8N4F0; -.
DR   Proteomes; UP000005640; Chromosome 20.
DR   RNAct; Q8N4F0; Protein.
DR   Bgee; ENSG00000078898; Expressed in trachea and 99 other cell types or tissues.
DR   GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR   GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0008289; F:lipid binding; IEA:InterPro.
DR   CDD; cd00026; BPI2; 1.
DR   InterPro; IPR017943; Bactericidal_perm-incr_a/b_dom.
DR   InterPro; IPR030675; BPI/LBP.
DR   InterPro; IPR001124; Lipid-bd_serum_glycop_C.
DR   InterPro; IPR017942; Lipid-bd_serum_glycop_N.
DR   PANTHER; PTHR46019:SF1; BPI FOLD-CONTAINING FAMILY B MEMBER 2; 1.
DR   PANTHER; PTHR46019; BPI FOLD-CONTAINING FAMILY B MEMBER 4-RELATED; 1.
DR   Pfam; PF01273; LBP_BPI_CETP; 1.
DR   Pfam; PF02886; LBP_BPI_CETP_C; 1.
DR   PIRSF; PIRSF002417; Lipid_binding_protein; 1.
DR   SMART; SM00329; BPI2; 1.
DR   SUPFAM; SSF55394; Bactericidal permeability-increasing protein, BPI; 2.
DR   Genevisible; Q8N4F0; HS.
PE   1: Evidence at protein level;
KW   Direct protein sequencing; Disulfide bond; Glycoprotein; Phosphoprotein;
KW   Reference proteome; Secreted; Signal.
FT   SIGNAL          1..20
FT                   /evidence="ECO:0000269|PubMed:15340161"
FT   CHAIN           21..458
FT                   /note="BPI fold-containing family B member 2"
FT                   /id="PRO_0000017164"
FT   MOD_RES         52
FT                   /note="Phosphothreonine; by FAM20C"
FT                   /evidence="ECO:0000269|PubMed:26091039"
FT   MOD_RES         60
FT                   /note="Phosphoserine; by FAM20C"
FT                   /evidence="ECO:0000269|PubMed:26091039"
FT   CARBOHYD        96
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:16740002"
FT   CARBOHYD        151
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        293
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:16740002"
FT   CARBOHYD        332
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:16740002"
FT   DISULFID        137..174
FT                   /evidence="ECO:0000250"
FT   VARIANT         20
FT                   /note="A -> V (in a colorectal cancer sample; somatic
FT                   mutation)"
FT                   /evidence="ECO:0000269|PubMed:16959974"
FT                   /id="VAR_036550"
FT   VARIANT         31
FT                   /note="K -> M (in dbSNP:rs6088066)"
FT                   /id="VAR_024515"
FT   VARIANT         63
FT                   /note="A -> V (in dbSNP:rs34128772)"
FT                   /id="VAR_049740"
FT   CONFLICT        231
FT                   /note="K -> N (in Ref. 2; AAQ89085)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        257
FT                   /note="V -> G (in Ref. 6; AAH34415)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   458 AA;  49172 MW;  E2016619A93ABECD CRC64;
     MAWASRLGLL LALLLPVVGA STPGTVVRLN KAALSYVSEI GKAPLQRALQ VTVPHFLDWS
     GEALQPTRIR ILNVHVPRLH LKFIAGFGVR LLAAANFTFK VFRAPEPLEL TLPVELLADT
     RVTQSSIRTP VVSISACSLF SGHANEFDGS NSTSHALLVL VQKHIKAVLS NKLCLSISNL
     VQGVNVHLGT LIGLNPVGPE SQIRYSMVSV PTVTSDYISL EVNAVLFLLG KPIILPTDAT
     PFVLPRHVGT EGSMATVGLS QQLFDSALLL LQKAGALNLD ITGQLRSDDN LLNTSALGRL
     IPEVARQFPE PMPVVLKVRL GATPVAMLHT NNATLRLQPF VEVLATASNS AFQSLFSLDV
     VVNLRLQLSV SKVKLQGTTS VLGDVQLTVA SSNVGFIDTD QVRTLMGTVF EKPLLDHLNA
     LLAMGIALPG VVNLHYVAPE IFVYEGYVVI SSGLFYQS
//