Retinol binding protein 4

RBP4
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1BRP, 1BRQ, 1JYD, 1JYJ, 1QAB, 1RBP, 1RLB, 2WQ9, 2WQA, 2WR6, 3BSZ, 3FMZ, 4O9S, 4PSQ
Identifiers
Aliases	RBP4, MCOPCB10, RDCCAS, retinol binding protein 4
External IDs	OMIM: 180250 MGI: 97879 HomoloGene: 4908 GeneCards: RBP4
Gene ontology Molecular function • retinol transporter activity • transporter activity • protein binding • retinoid binding • protein heterodimerization activity • retinol binding • retinal binding • small molecule binding Cellular component • cytosol • protein complex • extracellular space • extracellular region • extracellular exosome Biological process • eye development • gluconeogenesis • heart trabecula formation • response to retinoic acid • glucose homeostasis • response to stimulus • cardiac muscle tissue development • lung development • vagina development • urinary bladder development • retinol metabolic process • embryonic organ morphogenesis • embryonic skeletal system development • retinoid metabolic process • female genitalia morphogenesis • uterus development • heart development • maintenance of gastrointestinal epithelium • retinol transport • transport • embryonic retina morphogenesis in camera-type eye • response to ethanol • negative regulation of cardiac muscle cell proliferation • positive regulation of immunoglobulin secretion • visual perception • positive regulation of insulin secretion Sources:Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	5950	19662
Ensembl	ENSG00000138207	ENSMUSG00000024990
UniProt	P02753	Q00724
RefSeq (mRNA)	NM_006744 NM_001323517 NM_001323518	NM_001159487 NM_011255
RefSeq (protein)	NP_006735.2 NP_001310446.1 NP_001310447.1	NP_001152959.1 NP_035385.1
Location (UCSC)	Chr 10: 93.59 – 93.6 Mb	Chr 19: 38.12 – 38.13 Mb
PubMed search	[1]	[2]
Wikidata

Retinol binding protein 4, plasma, also known as RBP4, is a protein^[3] that in humans is encoded by the RBP4 gene.^[4][5]

Function

This protein belongs to the lipocalin family and is the specific carrier for retinol (vitamin A alcohol) in the blood. It delivers retinol from the liver stores to the peripheral tissues. In plasma, the RBP-retinol complex interacts with transthyretin, which prevents its loss by filtration through the kidney glomeruli. A deficiency of vitamin A blocks secretion of the binding protein posttranslationally and results in defective delivery and supply to the epidermal cells.^[5]

Clinical significance

Retinol-binding protein 4 has recently been described as an adipokine that contributes to insulin resistance in the AG4KO mouse model.^[6] It is secreted by adipocytes, and can act as a signal to other cells, when there is a decrease in plasma glucose concentration.^[7]

Mutations in the RBP4 gene have recently been linked to a form of autosomal dominant microphthalmia, anophthalmia, and coloboma (MAC) disease.^[8] A unique feature of this disease is the maternal inheritance effect, meaning the disease occurs when a fetus inherits a mutated copy of the RBP4 gene from its mother, but not its father. The physiologic basis lies in pregnancy whereby the mutated gene product, retinol binding protein (RBP), has negative effects in transferring vitamin A from maternal liver storage sites to the placenta, and then again on the fetal circulation side when delivering vitamin A from the placenta to developing fetal tissues, most notably the developing eye. This 'double whammy' effect does not exist when the mutant RBP4 gene is inherited from the father. The above mechanism is separate from previously known types of maternal inheritance effects such as genomic imprinting, mitochondrial inheritance, or maternal oocyte mRNA transfer. The authors of the above study cite the potential of vitamin A supplementation in pregnant females who are known to carry an RBP4 mutation with retinyl ester which utilizes an RBP-independent pathway to deliver retinoids from the maternal intestines directly to the placenta and ultimately is uptaken by the fetus. The key would be to supplement during the first several months of life when the eye begins to develop, as supplementing later in pregnancy would be too late to avoid any potential MAC disease.

See also

• Retinol binding protein

References

Further reading

External links

• RBP4 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)

PDB gallery
1aqb: RETINOL-BINDING PROTEIN (RBP) FROM PIG PLASMA  1brp: CRYSTAL STRUCTURE OF THE TRIGONAL FORM OF HUMAN PLASMA RETINOL-BINDING PROTEIN AT 2.5 ANGSTROMS RESOLUTION  1brq: CRYSTAL STRUCTURE OF THE TRIGONAL FORM OF HUMAN PLASMA RETINOL-BINDING PROTEIN AT 2.5 ANGSTROMS RESOLUTION  1erb: THE INTERACTION OF N-ETHYL RETINAMIDE WITH PLASMA RETINOL-BINDING PROTEIN (RBP) AND THE CRYSTAL STRUCTURE OF THE RETINOID-RBP COMPLEX AT 1.9 ANGSTROMS RESOLUTION  1fel: CRYSTALLOGRAPHIC STUDIES ON COMPLEXES BETWEEN RETINOIDS AND PLASMA RETINOL-BINDING PROTEIN  1fem: CRYSTALLOGRAPHIC STUDIES ON COMPLEXES BETWEEN RETINOIDS AND PLASMA RETINOL-BINDING PROTEIN  1fen: CRYSTALLOGRAPHIC STUDIES ON COMPLEXES BETWEEN RETINOIDS AND PLASMA RETINOL-BINDING PROTEIN  1hbp: CRYSTAL STRUCTURE OF LIGANDED AND UNLIGANDED FORMS OF BOVINE PLASMA RETINOL-BINDING PROTEIN  1hbq: CRYSTAL STRUCTURE OF LIGANDED AND UNLIGANDED FORMS OF BOVINE PLASMA RETINOL-BINDING PROTEIN  1jyd: Crystal Structure of Recombinant Human Serum Retinol-Binding Protein at 1.7 A Resolution  1jyj: Crystal Structure of a Double Variant (W67L/W91H) of Recombinant Human Serum Retinol-binding Protein at 2.0 A Resolution  1kt3: Crystal structure of bovine holo-RBP at pH 2.0  1kt4: Crystal structure of bovine holo-RBP at pH 3.0  1kt5: Crystal structure of bovine holo-RBP at pH 4.0  1kt6: Crystal structure of bovine holo-RBP at pH 9.0  1kt7: Crystal structure of bovine holo-RBP at pH 7.0  1qab: The structure of human retinol binding protein with its carrier protein transthyretin reveals interaction with the carboxy terminus of RBP  1rbp: CRYSTALLOGRAPHIC REFINEMENT OF HUMAN SERUM RETINOL BINDING PROTEIN AT 2 ANGSTROMS RESOLUTION  1rlb: RETINOL BINDING PROTEIN COMPLEXED WITH TRANSTHYRETIN