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PROSITE documentation PDOC00187

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{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 <PDOC00499> and the cytosolic fatty-
 acid binding proteins <PDOC00188> 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}