{PDOC00187} {PS00213; LIPOCALIN} {BEGIN} *********************** * Lipocalin signature * *********************** Proteins which transport small hydrophobic molecules such as steroids, bilins, retinoids, and lipids share limited regions of sequence homology and a common tertiary structure architecture [1 to 5]. This is an eight stranded antiparallel beta-barrel with a repeated + 1 topology enclosing a internal ligand binding site [1,3]. The name 'lipocalin' has been proposed [5] for this protein family. Proteins known to belong to this family are listed below (references are only provided for recently determined sequences). - Alpha-1-microglobulin (protein HC), which seems to bind porphyrin. - Alpha-1-acid glycoprotein (orosomucoid), which can bind a remarkable array of natural and synthetic compounds [6]. - Aphrodisin which, in hamsters, functions as an aphrodisiac pheromone. - Apolipoprotein D, which probably binds heme-related compounds. - Beta-lactoglobulin, a milk protein whose physiological function appears to bind retinol. - Complement component C8 gamma chain, which seems to bind retinol [7]. - Crustacyanin [8], a protein from lobster carapace, which binds astaxanthin, a carotenoid. - Epididymal-retinoic acid binding protein (E-RABP) [9] involved in sperm maturation. - Insectacyanin, a moth bilin-binding protein, and a related butterfly bilin- binding protein (BBP). - Late Lactation protein (LALP), a milk protein from tammar wallaby [10]. - Neutrophil gelatinase-associated lipocalin (NGAL) (p25) (SV-40 induced 24p3 protein) [11]. - Odorant-binding protein (OBP), which binds odorants. - Plasma retinol-binding proteins (PRBP). - Human pregnancy-associated endometrial alpha-2 globulin. - Probasin (PB), a rat prostatic protein. - Prostaglandin D synthase (EC 5.3.99.2) (GSH-independent PGD synthase), a lipocalin with enzymatic activity [12]. - Purpurin, a retinal protein which binds retinol and heparin. - Quiescence specific protein p20K from chicken (embryo CH21 protein). - Rodent urinary proteins (alpha-2-microglobulin), which may bind pheromones. - VNSP 1 and 2, putative pheromone transport proteins from mouse vomeronasal organ [13]. - Von Ebner's gland protein (VEGP) [14] (also called tear lipocalin), a mammalian protein which may be involved in taste recognition. - A frog olfactory protein, which may transport odorants. - A protein found in the cerebrospinal fluid of the toad Bufo Marinus with a supposed function similar to transthyretin in transport across the blood brain barrier [15]. - Lizard's epididymal secretory protein IV (LESP IV), which could transport small hydrophobic molecules into the epididymal fluid during sperm maturation [16]. - Prokaryotic outer-membrane protein blc [17]. The sequences of most members of the family, the core or kernal lipocalins, are characterized by three short conserved stretches of residues [3,18]. Others, the outlier lipocalin group, share only one or two of these [3,18]. A signature pattern was built around the first, common to all outlier and kernal lipocalins, which occurs near the start of the first beta-strand. -Consensus pattern: [DENG]-{A}-[DENQGSTARK]-x(0,2)-[DENQARK]-[LIVFY]-{CP}-G- {C}-W-[FYWLRH]-{D}-[LIVMTA] -Sequences known to belong to this class detected by the pattern: ALL, except for rodent alpha-1-acid glycoproteins, kangaroo beta-lactoglobulin, VEGP and LESP IV. -Other sequence(s) detected in Swiss-Prot: 82. -Note: It is suggested, on the basis of similarities of structure, function, and sequence, that this family forms an overall superfamily, called the calycins, with the avidin/streptavidin and the cytosolic fatty- acid binding proteins families [3,19]. -Expert(s) to contact by email: Flower D.R.; darren.flower@jenner.ac.uk -Last update: December 2004 / Pattern and text revised. [ 1] Cowan S.W., Newcomer M.E., Jones T.A. "Crystallographic refinement of human serum retinol binding protein at 2A resolution." Proteins 8:44-61(1990). PubMed=2217163 [ 2] Igaraishi M., Nagata A., Toh H., Urade H., Hayaishi N. Proc. Natl. Acad. Sci. U.S.A. 89:5376-5380(1992). [ 3] Flower D.R., North A.C.T., Attwood T.K. "Structure and sequence relationships in the lipocalins and related proteins." Protein Sci. 2:753-761(1993). PubMed=7684291 [ 4] Godovac-Zimmermann J. Trends Biochem. Sci. 13:64-66(1988). [ 5] Pervaiz S., Brew K. "Homology and structure-function correlations between alpha 1-acid glycoprotein and serum retinol-binding protein and its relatives." FASEB J. 1:209-214(1987). PubMed=3622999 [ 6] Kremer J.M.H., Wilting J., Janssen L.H. "Drug binding to human alpha-1-acid glycoprotein in health and disease." Pharmacol. Rev. 40:1-47(1988). PubMed=3064105 [ 7] Haefliger J.-A., Peitsch M.C., Jenne D.E., Tschopp J. "Structural and functional characterization of complement C8 gamma, a member of the lipocalin protein family." Mol. Immunol. 28:123-131(1991). PubMed=1707134 [ 8] Keen J.N., Caceres I., Eliopoulos E.E., Zagalsky P.F., Findlay J.B.C. "Complete sequence and model for the A2 subunit of the carotenoid pigment complex, crustacyanin." Eur. J. Biochem. 197:407-417(1991). PubMed=2026162 [ 9] Newcomer M.E. "Structure of the epididymal retinoic acid binding protein at 2.1 A resolution." Structure 1:7-18(1993). PubMed=8069623 [10] Collet C., Joseph R. Biochim. Biophys. Acta 1167:219-222(1993). [11] Kjeldsen L., Johnsen A.H., Sengelov H., Borregaard N. J. Biol. Chem. 268:10425-10432(1993). [12] Peitsch M.C., Boguski M.S. Trends Biochem. Sci. 16:363-363(1991). [13] Miyawaki A., Matsushita Y.R., Ryo Y., Mikoshiba T. EMBO J. 13:5835-5842(1994). [14] Kock K., Ahlers C., Schmale H. Eur. J. Biochem. 221:905-916(1994). [15] Achen M.G., Harms P.J., Thomas T., Richardson S.J., Wettenhall R.E.H., Schreiber G. J. Biol. Chem. 267:23170-23174(1992). [16] Morel L., Dufarre J.-P., Depeiges A. J. Biol. Chem. 268:10274-10281(1993). [17] Bishop R.E., Penfold S.S., Frost L.S., Holtje J.V., Weiner J.H. J. Biol. Chem. 270:23097-23103(1995). [18] Flower D.R., North A.C.T., Attwood T.K. Biochem. Biophys. Res. Commun. 180:69-74(1991). [19] Flower D.R. FEBS Lett. 333:99-102(1993). -------------------------------------------------------------------------------- PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html -------------------------------------------------------------------------------- {END}