Due to scheduled maintenance work, this service may not be available on Monday January 22nd between 08.00 am and 9.00 am CEST.
To improve security and privacy, we are moving our web pages and services from HTTP to HTTPS.
To give users of web services time to transition to HTTPS, we will support separate HTTP and HTTPS services until the end of 2017.
From January 2018 most HTTP traffic will be automatically redirected to HTTPS. [more...]
View this page in https
PROSITE documentation PDOC00187 [for PROSITE entry PS00213]

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 (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.


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)


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).

PROSITE is copyright. It is produced by the SIB Swiss Institute Bioinformatics. There are no restrictions on its use by non-profit institutions as long as its content is in no way modified. Usage by and for commercial entities requires a license agreement. For information about the licensing scheme send an email to
Prosite License or see: prosite_license.html.


View entry in original PROSITE document format
View entry in raw text format (no links)