PROSITE documentation PDOC00187

Lipocalin signature




Description

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.

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 <PDOC00499> and the cytosolic fatty- acid binding proteins <PDOC00188> families [3,19].

Expert(s) to contact by email:

Flower D.R.

Last update:

December 2004 / Pattern and text revised.

Technical section

PROSITE method (with tools and information) covered by this documentation:

LIPOCALIN, PS00213; Lipocalin signature  (PATTERN)


References

1AuthorsCowan S.W., Newcomer M.E., Jones T.A.
TitleCrystallographic refinement of human serum retinol binding protein at 2A resolution.
SourceProteins 8:44-61(1990).
PubMed ID2217163

2AuthorsIgaraishi M., Nagata A., Toh H., Urade H., Hayaishi N.
SourceProc. Natl. Acad. Sci. U.S.A. 89:5376-5380(1992).

3AuthorsFlower D.R., North A.C.T., Attwood T.K.
TitleStructure and sequence relationships in the lipocalins and related proteins.
SourceProtein Sci. 2:753-761(1993).
PubMed ID7684291

4AuthorsGodovac-Zimmermann J.
SourceTrends Biochem. Sci. 13:64-66(1988).

5AuthorsPervaiz S., Brew K.
TitleHomology and structure-function correlations between alpha 1-acid glycoprotein and serum retinol-binding protein and its relatives.
SourceFASEB J. 1:209-214(1987).
PubMed ID3622999

6AuthorsKremer J.M.H., Wilting J., Janssen L.H.
TitleDrug binding to human alpha-1-acid glycoprotein in health and disease.
SourcePharmacol. Rev. 40:1-47(1988).
PubMed ID3064105

7AuthorsHaefliger J.-A., Peitsch M.C., Jenne D.E., Tschopp J.
TitleStructural and functional characterization of complement C8 gamma, a member of the lipocalin protein family.
SourceMol. Immunol. 28:123-131(1991).
PubMed ID1707134

8AuthorsKeen J.N., Caceres I., Eliopoulos E.E., Zagalsky P.F., Findlay J.B.C.
TitleComplete sequence and model for the A2 subunit of the carotenoid pigment complex, crustacyanin.
SourceEur. J. Biochem. 197:407-417(1991).
PubMed ID2026162

9AuthorsNewcomer M.E.
TitleStructure of the epididymal retinoic acid binding protein at 2.1 A resolution.
SourceStructure 1:7-18(1993).
PubMed ID8069623

10AuthorsCollet C., Joseph R.
SourceBiochim. Biophys. Acta 1167:219-222(1993).

11AuthorsKjeldsen L., Johnsen A.H., Sengelov H., Borregaard N.
SourceJ. Biol. Chem. 268:10425-10432(1993).

12AuthorsPeitsch M.C., Boguski M.S.
SourceTrends Biochem. Sci. 16:363-363(1991).

13AuthorsMiyawaki A., Matsushita Y.R., Ryo Y., Mikoshiba T.
SourceEMBO J. 13:5835-5842(1994).

14AuthorsKock K., Ahlers C., Schmale H.
SourceEur. J. Biochem. 221:905-916(1994).

15AuthorsAchen M.G., Harms P.J., Thomas T., Richardson S.J., Wettenhall R.E.H., Schreiber G.
SourceJ. Biol. Chem. 267:23170-23174(1992).

16AuthorsMorel L., Dufarre J.-P., Depeiges A.
SourceJ. Biol. Chem. 268:10274-10281(1993).

17AuthorsBishop R.E., Penfold S.S., Frost L.S., Holtje J.V., Weiner J.H.
SourceJ. Biol. Chem. 270:23097-23103(1995).

18AuthorsFlower D.R., North A.C.T., Attwood T.K.
SourceBiochem. Biophys. Res. Commun. 180:69-74(1991).

19AuthorsFlower D.R.
SourceFEBS Lett. 333:99-102(1993).



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