MetaCyc Enzyme: cellular retinol-binding protein 1

Gene: RBP1 Accession Number: HS03740 (MetaCyc)

Synonyms: CRBP1, cellular retinol-binding protein, cellular retinol-binding protein I, CRBP, CRBP-I, retinol-binding protein 1

Species: Homo sapiens

Plasma retinol-binding protein (RBPs) and cellular retinol-binding proteins (CRBPs) are specific carriers of the alcohol form of vitamin A (retinol) in body fluids and within the cell, respectively. The sequestration of retinol inside a high-affinity binding-protein draws retinol into the cell and protects it from unfettered metabolism, while still allowing the formation of retinyl esters [Newcomer98, Cowan93]. LRAT, the enzyme that forms retinyl-esters, can access retinol when it is bound to CRBP1 [Yost88, MacDonald88].

The CRBPs are monomeric proteins of approximately 15.5 kDa belonging to a superfamily of small cytoplasmic proteins that specifically interact with hydrophobic ligands. Two such proteins (CRBP I and CRBP II) with distinct tissue distributions and retinoid-binding properties have been recognized in mammals.

The human CRBP I is expressed at high levels in many tissues, including ovary, adrenal and pituitary glands, and testis [Ong86], while CRBP II is confined essentially to the small intestine. In addition, the Kd of the retinol-CRBP I complex is as low as 0.1 nM [Malpeli95], whereas the binding of retinol to CRBP II is ~100-fold weaker [Li91].

The very high-affinity retinol binding-protein, holo-CRBP1, represents the major physiological form of intracellular retinol. Apo-CRBP1 interacts with enzymes to signal that the intracellular concentration of retinol is low and stimulate the hydrolysis of retinyl-esters [Boerman91, Napoli11]. The total CRBP1 concentration remains steady even when vitamin A status varies.

The RBP1 gene has been assigned to human chromosome band 3q23 [Wei87, Nilsson88, De98].

Gene Citations: [Sherman87, Colantuoni85]

Map Position: [140,065,306 <- 140,087,521]

Molecular Weight of Polypeptide: 14.8 kD (experimental) [Ong82 ]

Unification Links: ArrayExpress:P09455 , Entrez-gene:5947 , PhylomeDB:P09455 , Pride:P09455 , Protein Model Portal:P09455 , SMR:P09455 , String:9606.ENSP00000232219 , UniProt:P09455

Relationship Links: InterPro:IN-FAMILY:IPR000463 , InterPro:IN-FAMILY:IPR000566 , InterPro:IN-FAMILY:IPR011038 , InterPro:IN-FAMILY:IPR012674 , Pfam:IN-FAMILY:PF00061 , Prints:IN-FAMILY:PR00178 , Prosite:IN-FAMILY:PS00214

Reactions known to consume the compound:

retinoate biosynthesis I , retinoate biosynthesis II , retinol biosynthesis , the visual cycle I (vertebrates) :
all-trans-retinol + a cellular-retinol-binding protein → an all-trans retinol-[cellular-retinol-binding-protein]

11-cis-3-hydroxyretinal biosynthesis :
a retinoid-binding protein + (3R)-11-cis-3-hydroxyretinal → a (3R)-11-cis-3-hydroxyretinal-[retinoid-binding protein]
a retinoid-binding protein + (3R)-all-trans-3-hydroxyretinal → a (3R)-all-trans-3-hydroxyretinal-[retinoid-binding protein]

the visual cycle (insects) :
a metarhodopsin Rh1 + a retinoid-binding protein + H2O + H+ → an all-trans-3-hydroxyretinal-[retinoid-binding protein] + an apo-rhodopsin Rh1

Reactions known to produce the compound:

retinoate biosynthesis I :
an all-trans retinal-[cellular-retinol-binding-protein] + NAD+ + H2O → all-trans-retinoate + a cellular-retinol-binding protein + NADH + 2 H+

retinol biosynthesis , the visual cycle I (vertebrates) :
an all-trans retinol-[cellular-retinol-binding-protein] + a phosphatidylcholine → a cellular-retinol-binding protein + an all-trans-retinyl ester + a 2-acyl 1-lyso-phosphatidylcholine

Not in pathways:
an 11-cis retinol-[cellular-retinol-binding-protein] + a phosphatidylcholine → a cellular-retinol-binding protein + an 11-cis-retinyl ester + a 2-acyl 1-lyso-phosphatidylcholine

the visual cycle (insects) :
an 11-cis-3-hydroxyretinal-[retinoid-binding protein] + an apo-rhodopsin Rh1 → a retinoid-binding protein + a rhodopsin Rh1 + H2O + H+

Gene-Reaction Schematic: ?

Gene-Reaction Schematic

GO Terms:

Biological Process: GO:0006776 - vitamin A metabolic process
GO:0006810 - transport
Molecular Function: GO:0005215 - transporter activity
GO:0005501 - retinoid binding
GO:0008289 - lipid binding
GO:0019841 - retinol binding

Created 10-Aug-2011 by Caspi R , SRI International

Enzymatic reaction of: cellular retinol-binding protein

all-trans-retinol + a cellular-retinol-binding protein <=> an all-trans retinol-[cellular-retinol-binding-protein]

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.

The reaction is favored in the direction shown.

In Pathways: the visual cycle I (vertebrates) , retinol biosynthesis , retinoate biosynthesis I , retinoate biosynthesis II


Schematic showing introns, exons and/or isoforms of RBP1


Boerman91: Boerman MH, Napoli JL (1991). "Cholate-independent retinyl ester hydrolysis. Stimulation by Apo-cellular retinol-binding protein." J Biol Chem 266(33);22273-8. PMID: 1939249

Colantuoni85: Colantuoni V, Cortese R, Nilsson M, Lundvall J, Bavik CO, Eriksson U, Peterson PA, Sundelin J (1985). "Cloning and sequencing of a full length cDNA corresponding to human cellular retinol-binding protein." Biochem Biophys Res Commun 130(1);431-9. PMID: 2992469

Cowan93: Cowan SW, Newcomer ME, Jones TA (1993). "Crystallographic studies on a family of cellular lipophilic transport proteins. Refinement of P2 myelin protein and the structure determination and refinement of cellular retinol-binding protein in complex with all-trans-retinol." J Mol Biol 230(4);1225-46. PMID: 7683727

De98: De Baere E, Speleman F, Van Roy N, De Paepe A, Messiaen L (1998). "Assignment of the cellular retinol-binding protein 1 gene (RBP1) and of the coatomer beta subunit gene (COPB2) to human chromosome band 3q23 by in situ hybridization." Cytogenet Cell Genet 82(3-4);226-7. PMID: 9858824

Li91: Li E, Qian SJ, Winter NS, d'Avignon A, Levin MS, Gordon JI (1991). "Fluorine nuclear magnetic resonance analysis of the ligand binding properties of two homologous rat cellular retinol-binding proteins expressed in Escherichia coli." J Biol Chem 266(6);3622-9. PMID: 1995621

MacDonald88: MacDonald PN, Ong DE (1988). "A lecithin:retinol acyltransferase activity in human and rat liver." Biochem Biophys Res Commun 156(1);157-63. PMID: 3178828

Malpeli95: Malpeli G, Stoppini M, Zapponi MC, Folli C, Berni R (1995). "Interactions with retinol and retinoids of bovine cellular retinol-binding protein." Eur J Biochem 229(2);486-93. PMID: 7744071

Napoli11: Napoli JL (2011). "Physiological insights into all-trans-retinoic acid biosynthesis." Biochim Biophys Acta. PMID: 21621639

Newcomer98: Newcomer ME, Jamison RS, Ong DE (1998). "Structure and function of retinoid-binding proteins." Subcell Biochem 30;53-80. PMID: 9932510

Nilsson88: Nilsson MH, Spurr NK, Lundvall J, Rask L, Peterson PA (1988). "Human cellular retinol-binding protein gene organization and chromosomal location." Eur J Biochem 173(1);35-44. PMID: 3356192

Ong82: Ong DE (1982). "Purification and partial characterization of cellular retinol-binding protein from human liver." Cancer Res 42(3);1033-7. PMID: 7199377

Ong86: Ong DE, Page DL (1986). "Quantitation of cellular retinol-binding protein in human organs." Am J Clin Nutr 44(3);425-30. PMID: 3751963

Sherman87: Sherman DR, Lloyd RS, Chytil F (1987). "Rat cellular retinol-binding protein: cDNA sequence and rapid retinol-dependent accumulation of mRNA." Proc Natl Acad Sci U S A 84(10);3209-13. PMID: 3472205

Wei87: Wei LN, Mertz JR, Goodman DS, Nguyen-Huu MC (1987). "Cellular retinoic acid- and cellular retinol-binding proteins: complementary deoxyribonucleic acid cloning, chromosomal assignment, and tissue specific expression." Mol Endocrinol 1(8);526-34. PMID: 2856408

Yost88: Yost RW, Harrison EH, Ross AC (1988). "Esterification by rat liver microsomes of retinol bound to cellular retinol-binding protein." J Biol Chem 263(35);18693-701. PMID: 3198596

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Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 19.0 on Mon Jul 6, 2015, BIOCYC14B.