RGD Reference Report - Identification by photoaffinity labeling of fatty acid-binding protein as a potential warfarin receptor in rat liver. - Rat Genome Database

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Identification by photoaffinity labeling of fatty acid-binding protein as a potential warfarin receptor in rat liver.

Authors: Myszka, DG  Swenson, RP 
Citation: Myszka DG and Swenson RP, J Biol Chem. 1991 Nov 5;266(31):20725-31.
RGD ID: 1626448
Pubmed: PMID:1939124   (View Abstract at PubMed)

Two different photoaffinity analogs of 4-hydroxy coumarin, 3-(p-azidobenzyl)-4-hydroxycoumarin (AzBHC) and 3-(4-azido-5-iodosalicylamido)-4-hydroxycoumarin (AzISAHC), are being used in the identification of warfarin-binding proteins present in mammalian tissue (Myszka, D. G., and Swenson, R. P. (1990) Biochem. Biophys. Res. Commun. 172, 415-422; Myszka, D. G., and Swenson, R. P. (1991) J. Biol. Chem. 266, 4789-4797). In this study, [14C]AzBHC, but not [125I]AzISAHC, was observed to specifically label a 15,000-dalton protein present in both the microsomal and cytosolic fractions of rat liver. Pretreatment of the crude protein samples with warfarin or dicoumarol completely protected the 15-kDa protein from modification by [14C]AzBHC, indicating that this photoaffinity reagent is specifically labeling a coumarin-binding protein. 4-Hydroxycoumarin itself and AzISAHC were unable to block the incorporation of this photoaffinity probe. The 15-kDa protein was isolated by two-dimensional electrophoresis and subjected to amino-terminal sequence analysis. The first 20 amino acid residues analyzed were found to be identical with the amino-terminal sequence of rat liver fatty acid-binding protein (L-FABP) (Gordon J. I., Alpers, D. H., Ockner, R. K., and Strauss, A. W. (1983) J. Biol. Chem. 258, 3356-3363). Photoaffinity labeling and protection experiments carried out on purified preparations of L-FABP paralleled the labeling results obtained in the microsomes and cytosol, confirming that L-FABP is capable of specifically binding AzBHC, warfarin, and dicoumarol. Oleic acid, an established ligand for L-FABP, can compete with the binding of the photoaffinity probe; however, it was less effective in protecting the protein than warfarin. The specificity of labeling of crude liver fractions by warfarin photoaffinity analogs reported here as well as the high concentration of FABP in liver tissue together suggest that this protein may represent a major hepatic receptor responsible for the uptake and/or transport of various oral 4-hydroxycoumarin-based anticoagulant drugs.



Gene-Chemical Interaction Annotations    Click to see Annotation Detail View
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
FABP1Humandicoumarol multiple interactionsISOFabp1 (Rattus norvegicus)Dicoumarol inhibits the reaction [3-(p-azidobenzyl)-4-hydroxycoumarin binds to Fabp1 protein]RGD 
Fabp1Ratdicoumarol multiple interactionsEXP Dicoumarol inhibits the reaction [3-(p-azidobenzyl)-4-hydroxycoumarin binds to Fabp1 protein]RGD 
Fabp1Mousedicoumarol multiple interactionsISOFabp1 (Rattus norvegicus)Dicoumarol inhibits the reaction [3-(p-azidobenzyl)-4-hydroxycoumarin binds to Fabp1 protein]RGD 
FABP1Humanoleic acid affects bindingISOFabp1 (Rattus norvegicus)Oleic acid binds to Fabp1 proteinRGD 
Fabp1Ratoleic acid affects bindingEXP Oleic acid binds to Fabp1 proteinRGD 
Fabp1Mouseoleic acid affects bindingISOFabp1 (Rattus norvegicus)Oleic acid binds to Fabp1 proteinRGD 
FABP1Humanwarfarin multiple interactionsISOFabp1 (Rattus norvegicus)Warfarin inhibits the reaction [3-(p-azidobenzyl)-4-hydroxycoumarin binds to Fabp1 protein]RGD 
Fabp1Ratwarfarin multiple interactionsEXP Warfarin inhibits the reaction [3-(p-azidobenzyl)-4-hydroxycoumarin binds to Fabp1 protein]RGD 
Fabp1Mousewarfarin multiple interactionsISOFabp1 (Rattus norvegicus)Warfarin inhibits the reaction [3-(p-azidobenzyl)-4-hydroxycoumarin binds to Fabp1 protein]RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Fabp1Ratheterocyclic compound binding  IPIdicoumarol and warfarin RGD 
Fabp1Ratheterocyclic compound binding  IDA 3-p-azidobenzyl-4-hydroxycoumarinRGD 
Fabp1Ratoleic acid binding  IPIoleic acid RGD 

Objects Annotated

Genes (Rattus norvegicus)
Fabp1  (fatty acid binding protein 1)

Genes (Mus musculus)
Fabp1  (fatty acid binding protein 1, liver)

Genes (Homo sapiens)
FABP1  (fatty acid binding protein 1)


Additional Information