PROSITE documentation PDOC00187

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 [1,2,3,4,5]. This is an eight stranded antiparallel β-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).

• α-1-microglobulin (protein HC), which seems to bind porphyrin.
• α-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.
• β-lactoglobulin, a milk protein whose physiological function appears to bind retinol.
• Complement component C8 γ 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 α-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 (α-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 β-strand.