ID   LCN1_HUMAN              Reviewed;         176 AA.
AC   P31025; Q5T8A1;
DT   01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT   01-JUL-1993, sequence version 1.
DT   27-MAR-2024, entry version 212.
DE   RecName: Full=Lipocalin-1;
DE   AltName: Full=Tear lipocalin;
DE            Short=Tlc;
DE   AltName: Full=Tear prealbumin;
DE            Short=TP;
DE   AltName: Full=von Ebner gland protein;
DE            Short=VEG protein;
DE   Flags: Precursor;
GN   Name=LCN1; Synonyms=VEGP;
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=Tongue;
RX   PubMed=7679926; DOI=10.1016/0167-4781(93)90279-m;
RA   Blaeker M., Kock K., Ahlers C., Buck F., Schmale H.;
RT   "Molecular cloning of human von Ebner's gland protein, a member of the
RT   lipocalin superfamily highly expressed in lingual salivary glands.";
RL   Biochim. Biophys. Acta 1172:131-137(1993).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Tear;
RX   PubMed=1400345; DOI=10.1016/s0021-9258(19)88698-2;
RA   Redl B., Holzfeind P., Lottspeich F.;
RT   "cDNA cloning and sequencing reveals human tear prealbumin to be a member
RT   of the lipophilic-ligand carrier protein superfamily.";
RL   J. Biol. Chem. 267:20282-20287(1992).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Tear;
RX   PubMed=8500570; DOI=10.1006/exer.1993.1075;
RA   Lassagne H., Gachon A.-M.;
RT   "Cloning of a human lacrimal lipocalin secreted in tears.";
RL   Exp. Eye Res. 56:605-609(1993).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=8112601; DOI=10.1016/0378-1119(94)90752-8;
RA   Holzfeind P., Redl B.;
RT   "Structural organization of the gene encoding the human lipocalin tear
RT   prealbumin and synthesis of the recombinant protein in Escherichia coli.";
RL   Gene 139:177-183(1994).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15164053; DOI=10.1038/nature02465;
RA   Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA   Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA   Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA   Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA   Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA   Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA   Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA   Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA   Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA   Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA   Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA   Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA   Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA   Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA   Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA   Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA   Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA   Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA   McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA   Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA   Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA   Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA   Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA   West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA   Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA   Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA   Dunham I.;
RT   "DNA sequence and analysis of human chromosome 9.";
RL   Nature 429:369-374(2004).
RN   [6]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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   [8]
RP   PROTEIN SEQUENCE OF 19-38.
RC   TISSUE=Nasal mucus;
RA   Scalfari F., Castagna M., Fattori B., Andreini I., Maremmani C., Pelosi P.;
RT   "Expression of a lipocalin in human nasal mucosa.";
RL   Comp. Biochem. Physiol. 118B:819-824(1997).
RN   [9]
RP   PROTEIN SEQUENCE OF 19-35 AND 138-176, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY.
RC   TISSUE=Tear;
RX   PubMed=25946035; DOI=10.1021/acs.jproteome.5b00179;
RA   Azkargorta M., Soria J., Ojeda C., Guzman F., Acera A., Iloro I.,
RA   Suarez T., Elortza F.;
RT   "Human basal tear peptidome characterization by CID, HCD, and ETD followed
RT   by in silico and in vitro analyses for antimicrobial peptide
RT   identification.";
RL   J. Proteome Res. 14:2649-2658(2015).
RN   [10]
RP   INTERACTION WITH LMBR1L.
RC   TISSUE=Pituitary;
RX   PubMed=11287427; DOI=10.1074/jbc.m101762200;
RA   Wojnar P., Lechner M., Merschak P., Redl B.;
RT   "Molecular cloning of a novel lipocalin-1 interacting human cell membrane
RT   receptor using phage display.";
RL   J. Biol. Chem. 276:20206-20212(2001).
RN   [11]
RP   INTERACTION WITH LMBR1L, AND ENDOCYTOSIS.
RX   PubMed=12591932; DOI=10.1074/jbc.m210922200;
RA   Wojnar P., Lechner M., Redl B.;
RT   "Antisense down-regulation of lipocalin-interacting membrane receptor
RT   expression inhibits cellular internalization of lipocalin-1 in human NT2
RT   cells.";
RL   J. Biol. Chem. 278:16209-16215(2003).
RN   [12]
RP   SUBUNIT.
RX   PubMed=17869594; DOI=10.1016/j.bbapap.2007.07.014;
RA   Gasymov O.K., Abduragimov A.R., Merschak P., Redl B., Glasgow B.J.;
RT   "Oligomeric state of lipocalin-1 (LCN1) by multiangle laser light
RT   scattering and fluorescence anisotropy decay.";
RL   Biochim. Biophys. Acta 1774:1307-1315(2007).
RN   [13]
RP   X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 23-175.
RX   PubMed=15489503; DOI=10.1074/jbc.m410466200;
RA   Breustedt D.A., Korndorfer I.P., Redl B., Skerra A.;
RT   "The 1.8-A crystal structure of human tear lipocalin reveals an extended
RT   branched cavity with capacity for multiple ligands.";
RL   J. Biol. Chem. 280:484-493(2005).
CC   -!- FUNCTION: Could play a role in taste reception. Could be necessary for
CC       the concentration and delivery of sapid molecules in the gustatory
CC       system. Can bind various ligands, with chemical structures ranging from
CC       lipids and retinoids to the macrocyclic antibiotic rifampicin and even
CC       to microbial siderophores. Exhibits an extremely wide ligand pocket.
CC   -!- SUBUNIT: Predominantly monomer (PubMed:17869594). May form homodimer
CC       (PubMed:17869594). Interacts with LMBR1L; this interaction mediates the
CC       endocytosis of LCN1 (PubMed:11287427, PubMed:12591932).
CC       {ECO:0000269|PubMed:11287427, ECO:0000269|PubMed:12591932,
CC       ECO:0000269|PubMed:17869594}.
CC   -!- INTERACTION:
CC       P31025; P09917: ALOX5; NbExp=3; IntAct=EBI-1052433, EBI-79934;
CC       P31025; B3EWG5: FAM25C; NbExp=3; IntAct=EBI-1052433, EBI-14240149;
CC       P31025; Q6P9E2: RECK; NbExp=3; IntAct=EBI-1052433, EBI-10253121;
CC       P31025; Q9UHD9: UBQLN2; NbExp=3; IntAct=EBI-1052433, EBI-947187;
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- TISSUE SPECIFICITY: Mainly expressed in lachrymal and salivary glands.
CC       Also expressed in the prostate.
CC   -!- SIMILARITY: Belongs to the calycin superfamily. Lipocalin family.
CC       {ECO:0000305}.
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DR   EMBL; X62418; CAA44284.1; -; mRNA.
DR   EMBL; M90424; AAA61845.1; -; mRNA.
DR   EMBL; X67647; CAA47889.1; -; mRNA.
DR   EMBL; L14927; AAA18633.1; -; Genomic_DNA.
DR   EMBL; AL161452; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471090; EAW88156.1; -; Genomic_DNA.
DR   EMBL; BC065721; AAH65721.1; -; mRNA.
DR   EMBL; BC074925; AAH74925.1; -; mRNA.
DR   EMBL; BC074926; AAH74926.1; -; mRNA.
DR   CCDS; CCDS6991.1; -.
DR   PIR; A44029; LCHUL.
DR   RefSeq; NP_001239546.1; NM_001252617.1.
DR   RefSeq; NP_001239547.1; NM_001252618.1.
DR   RefSeq; NP_001239548.1; NM_001252619.1.
DR   RefSeq; NP_002288.1; NM_002297.3.
DR   PDB; 1XKI; X-ray; 1.80 A; A=23-176.
DR   PDB; 3EYC; X-ray; 2.60 A; A/B/C/D=23-176.
DR   PDB; 4QAF; X-ray; 1.80 A; A/B=23-174.
DR   PDB; 5T43; NMR; -; A=19-176.
DR   PDBsum; 1XKI; -.
DR   PDBsum; 3EYC; -.
DR   PDBsum; 4QAF; -.
DR   PDBsum; 5T43; -.
DR   AlphaFoldDB; P31025; -.
DR   SMR; P31025; -.
DR   BioGRID; 110125; 131.
DR   IntAct; P31025; 17.
DR   MINT; P31025; -.
DR   STRING; 9606.ENSP00000263598; -.
DR   DrugBank; DB00755; Tretinoin.
DR   SwissLipids; SLP:000001525; -.
DR   Allergome; 3990; Hom s TL.
DR   iPTMnet; P31025; -.
DR   PhosphoSitePlus; P31025; -.
DR   BioMuta; LCN1; -.
DR   DMDM; 401346; -.
DR   EPD; P31025; -.
DR   jPOST; P31025; -.
DR   MassIVE; P31025; -.
DR   MaxQB; P31025; -.
DR   PaxDb; 9606-ENSP00000263598; -.
DR   PeptideAtlas; P31025; -.
DR   PRIDE; P31025; -.
DR   ProteomicsDB; 54757; -.
DR   TopDownProteomics; P31025; -.
DR   Antibodypedia; 32051; 280 antibodies from 33 providers.
DR   DNASU; 3933; -.
DR   Ensembl; ENST00000263598.6; ENSP00000263598.2; ENSG00000160349.10.
DR   Ensembl; ENST00000371781.4; ENSP00000360846.3; ENSG00000160349.10.
DR   GeneID; 3933; -.
DR   KEGG; hsa:3933; -.
DR   MANE-Select; ENST00000371781.4; ENSP00000360846.3; NM_002297.4; NP_002288.1.
DR   UCSC; uc004cfz.3; human.
DR   AGR; HGNC:6525; -.
DR   CTD; 3933; -.
DR   DisGeNET; 3933; -.
DR   GeneCards; LCN1; -.
DR   HGNC; HGNC:6525; LCN1.
DR   HPA; ENSG00000160349; Group enriched (esophagus, seminal vesicle).
DR   MIM; 151675; gene.
DR   neXtProt; NX_P31025; -.
DR   OpenTargets; ENSG00000160349; -.
DR   PharmGKB; PA30308; -.
DR   VEuPathDB; HostDB:ENSG00000160349; -.
DR   eggNOG; ENOG502S22P; Eukaryota.
DR   GeneTree; ENSGT01050000244868; -.
DR   HOGENOM; CLU_125034_0_0_1; -.
DR   InParanoid; P31025; -.
DR   OMA; SGQCQEM; -.
DR   OrthoDB; 4840370at2759; -.
DR   PhylomeDB; P31025; -.
DR   TreeFam; TF338197; -.
DR   PathwayCommons; P31025; -.
DR   Reactome; R-HSA-804914; Transport of fatty acids.
DR   SignaLink; P31025; -.
DR   BioGRID-ORCS; 3933; 31 hits in 1112 CRISPR screens.
DR   ChiTaRS; LCN1; human.
DR   EvolutionaryTrace; P31025; -.
DR   GeneWiki; LCN1; -.
DR   GenomeRNAi; 3933; -.
DR   Pharos; P31025; Tbio.
DR   PRO; PR:P31025; -.
DR   Proteomes; UP000005640; Chromosome 9.
DR   RNAct; P31025; Protein.
DR   Bgee; ENSG00000160349; Expressed in lacrimal gland and 77 other cell types or tissues.
DR   ExpressionAtlas; P31025; baseline and differential.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR   GO; GO:0031404; F:chloride ion binding; IDA:CAFA.
DR   GO; GO:0004869; F:cysteine-type endopeptidase inhibitor activity; TAS:ProtInc.
DR   GO; GO:0005102; F:signaling receptor binding; IPI:UniProtKB.
DR   GO; GO:0036094; F:small molecule binding; IEA:InterPro.
DR   GO; GO:0008270; F:zinc ion binding; IDA:CAFA.
DR   GO; GO:0006508; P:proteolysis; TAS:ProtInc.
DR   GO; GO:0050896; P:response to stimulus; IEA:UniProtKB-KW.
DR   GO; GO:0050909; P:sensory perception of taste; IEA:UniProtKB-KW.
DR   CDD; cd19414; lipocalin_1_3_4_13-like; 1.
DR   Gene3D; 2.40.128.20; -; 1.
DR   InterPro; IPR012674; Calycin.
DR   InterPro; IPR002345; Lipocalin.
DR   InterPro; IPR000566; Lipocln_cytosolic_FA-bd_dom.
DR   InterPro; IPR002450; von_Ebner_gland.
DR   PANTHER; PTHR11430; LIPOCALIN; 1.
DR   PANTHER; PTHR11430:SF136; LIPOCALIN-1; 1.
DR   Pfam; PF00061; Lipocalin; 1.
DR   PRINTS; PR01175; VNEBNERGLAND.
DR   SUPFAM; SSF50814; Lipocalins; 1.
DR   UCD-2DPAGE; P31025; -.
DR   Genevisible; P31025; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Direct protein sequencing; Disulfide bond;
KW   Reference proteome; Secreted; Sensory transduction; Signal; Taste;
KW   Transport.
FT   SIGNAL          1..18
FT                   /evidence="ECO:0000269|PubMed:25946035, ECO:0000269|Ref.8"
FT   CHAIN           19..176
FT                   /note="Lipocalin-1"
FT                   /id="PRO_0000017974"
FT   DISULFID        79..171
FT   STRAND          25..27
FT                   /evidence="ECO:0007829|PDB:5T43"
FT   STRAND          33..42
FT                   /evidence="ECO:0007829|PDB:1XKI"
FT   STRAND          44..46
FT                   /evidence="ECO:0007829|PDB:5T43"
FT   STRAND          49..54
FT                   /evidence="ECO:0007829|PDB:4QAF"
FT   STRAND          57..61
FT                   /evidence="ECO:0007829|PDB:1XKI"
FT   TURN            63..65
FT                   /evidence="ECO:0007829|PDB:5T43"
FT   STRAND          67..73
FT                   /evidence="ECO:0007829|PDB:1XKI"
FT   STRAND          75..78
FT                   /evidence="ECO:0007829|PDB:4QAF"
FT   STRAND          80..88
FT                   /evidence="ECO:0007829|PDB:1XKI"
FT   STRAND          94..97
FT                   /evidence="ECO:0007829|PDB:1XKI"
FT   HELIX           98..100
FT                   /evidence="ECO:0007829|PDB:1XKI"
FT   STRAND          102..108
FT                   /evidence="ECO:0007829|PDB:1XKI"
FT   STRAND          111..113
FT                   /evidence="ECO:0007829|PDB:4QAF"
FT   STRAND          114..121
FT                   /evidence="ECO:0007829|PDB:1XKI"
FT   STRAND          128..139
FT                   /evidence="ECO:0007829|PDB:1XKI"
FT   HELIX           145..154
FT                   /evidence="ECO:0007829|PDB:1XKI"
FT   STRAND          160..163
FT                   /evidence="ECO:0007829|PDB:1XKI"
SQ   SEQUENCE   176 AA;  19250 MW;  0DDBF124C8C78CB8 CRC64;
     MKPLLLAVSL GLIAALQAHH LLASDEEIQD VSGTWYLKAM TVDREFPEMN LESVTPMTLT
     TLEGGNLEAK VTMLISGRCQ EVKAVLEKTD EPGKYTADGG KHVAYIIRSH VKDHYIFYCE
     GELHGKPVRG VKLVGRDPKN NLEALEDFEK AAGARGLSTE SILIPRQSET CSPGSD
//