RBP2

Summary

RBP2 (retinol binding protein 2, HGNC:9920) is a protein-coding gene on chromosome 3q23, encoding Retinol-binding protein 2 (P50120). Intracellular transport of retinol.

This gene encodes an abundant protein present in the small intestinal epithelium. It is thought to participate in the uptake and/or intracellular metabolism of vitamin A. Vitamin A is a fat-soluble vitamin necessary for growth, reproduction, differentiation of epithelial tissues, and vision. This protein may also modulate the supply of retinoic acid to the nuclei of endometrial cells during the menstrual cycle.

Source: NCBI Gene 5948 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 1 total
• MANE Select transcript: NM_004164

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9920
Approved symbol	RBP2
Name	retinol binding protein 2
Location	3q23
Locus type	gene with protein product
Status	Approved
Aliases	CRBP2, RBPC2, CRBPII, CRABP-II
Ensembl gene	ENSG00000114113
Ensembl biotype	protein_coding
OMIM	180280
Entrez	5948

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000232217, ENST00000506825, ENST00000511956, ENST00000950403

RefSeq mRNA: 1 — MANE Select: NM_004164 NM_004164

CCDS: CCDS3109

Canonical transcript exons

ENST00000232217 — 4 exons

Exon	Start	End
ENSE00000778975	139454729	139454830
ENSE00000778977	139462112	139462290
ENSE00000794927	139452884	139453166
ENSE00002067741	139476387	139476516

Expression profiles

Bgee: expression breadth ubiquitous, 158 present calls, max score 99.98.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 5.4946 / max 3548.0526, expressed in 86 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
44789	5.4217	81
44792	0.0389	4
44793	0.0201	1
44791	0.0095	3
44790	0.0044	2

Top tissues by expression

253 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	99.98	gold quality
ileal mucosa	UBERON:0000331	99.76	gold quality
duodenum	UBERON:0002114	97.48	gold quality
small intestine	UBERON:0002108	93.32	gold quality
small intestine Peyer’s patch	UBERON:0003454	92.65	gold quality
jejunum	UBERON:0002115	86.24	gold quality
buccal mucosa cell	CL:0002336	83.09	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.33	gold quality
tendon of biceps brachii	UBERON:0008188	76.83	gold quality
right lung	UBERON:0002167	75.35	gold quality
amniotic fluid	UBERON:0000173	73.69	gold quality
right uterine tube	UBERON:0001302	72.99	gold quality
mucosa of transverse colon	UBERON:0004991	72.31	gold quality
upper arm skin	UBERON:0004263	72.19	gold quality
nasal cavity epithelium	UBERON:0005384	70.70	gold quality
upper lobe of left lung	UBERON:0008952	69.43	gold quality
rectum	UBERON:0001052	69.39	gold quality
upper lobe of lung	UBERON:0008948	67.66	gold quality
intestine	UBERON:0000160	67.47	gold quality
kidney epithelium	UBERON:0004819	67.20	gold quality
corpus callosum	UBERON:0002336	67.02	gold quality
islet of Langerhans	UBERON:0000006	66.77	gold quality
oviduct epithelium	UBERON:0004804	66.35	silver quality
pancreatic ductal cell	CL:0002079	65.17	silver quality
metanephros cortex	UBERON:0010533	64.99	gold quality
lung	UBERON:0002048	64.90	gold quality
vastus lateralis	UBERON:0001379	64.48	gold quality
gall bladder	UBERON:0002110	64.38	gold quality
quadriceps femoris	UBERON:0001377	64.33	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	64.10	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-9906	yes	10060.77
E-GEOD-125970	yes	5295.73
E-CURD-122	yes	2099.42
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): BMAL1, CLOCK, FOXC1, HNF4A, KDM5A, NR2F2, PITX2, PPARA, RARA, RARB, RARG, RXRA, RXRB, RXRG, TBP

miRNA regulators (miRDB)

21 targeting RBP2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-221-3P	99.86	71.56	1329
HSA-MIR-222-3P	99.86	71.35	1337
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-155-5P	99.35	70.16	1509
HSA-MIR-329-5P	99.27	68.11	1597
HSA-MIR-548AS-3P	99.12	69.12	2294
HSA-MIR-4748	98.95	67.53	810
HSA-MIR-4464	98.95	67.73	820
HSA-MIR-6871-5P	98.90	66.67	671
HSA-MIR-760	98.81	66.65	1392
HSA-MIR-532-5P	98.43	67.53	760
HSA-MIR-939-5P	97.10	65.80	1579
HSA-MIR-1343-5P	96.48	66.06	1506
HSA-MIR-4296	96.35	63.55	1233
HSA-MIR-4265	96.18	64.68	557
HSA-MIR-4322	96.18	64.85	539
HSA-MIR-3675-5P	95.90	65.80	474

Literature-anchored findings (GeneRIF, showing 11)

• retinoic acid responsiveness of the human CRBP II promoter is mediated by an indirect mechanism and that this mechanism is associated with enterocyte differentiation. (PMID:12016134)
• We report here the X-ray structures of human apo and holo CRBP II solved at 1.2 A resolution and compare the two structures between them and with the structures of zebrafish and rat CRBP II. (PMID:18076076)
• HNF-4alpha is an important transcriptional factor that regulates human CRBPII gene expression; possibility for a novel function of HNF-4alpha in the regulation of human intestinal vitamin A absorption and metabolism (PMID:19147806)
• Data show that CRBPI and CRBPII bind 9-cis-retinol and 9-cis-retinal with high affinities, albeit with affinities somewhat lower than for all-trans-retinol and all-trans-retinal. (PMID:21382444)
• With only nine point mutations, the hCRBPII mutants induced a systematic shift in the absorption profile of all-trans-retinal of more than 200 nanometers across the visible spectrum. (PMID:23224553)
• The structure of retinal-bound human CRBPII and the structure of retinol-bound CRBPII with retinol fully occupying the binding pocket are reported. (PMID:25478840)
• Domain-swapped dimers of RBP2 provides evidence for ordered folding intermediates. (PMID:27524203)
• study demonstrates that Piasy may prevent exaggerated transcription of IFNI by Rbp2-mediated demethylation of H3K4me3 of IFNI, avoiding excessive immune responses (PMID:28970247)
• molecular dynamics simulations for the uptake of retinol by CRBP 1 and 2 (PMID:29567208)
• Molecular basis for the interaction of cellular retinol binding protein 2 (CRBP2) with nonretinoid ligands. (PMID:33631211)
• [Effect of RBP2 gene silencing on proliferation, migration and invasion of ovarian epithelial cancer SKOV3/DDP cells and its mechanism]. (PMID:35184457)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	rbp2a	ENSDARG00000070038
danio_rerio	rbp2b	ENSDARG00000093774
mus_musculus	Rbp2	ENSMUSG00000032454
rattus_norvegicus	Rbp1	ENSRNOG00000013794
drosophila_melanogaster	fabp	FBGN0037913
caenorhabditis_elegans		WBGENE00002259
caenorhabditis_elegans		WBGENE00002260

Paralogs (15): RBP1 (ENSG00000114115), FABP3 (ENSG00000121769), RBP5 (ENSG00000139194), CRABP2 (ENSG00000143320), FABP2 (ENSG00000145384), PMP2 (ENSG00000147588), RBP7 (ENSG00000162444), FABP1 (ENSG00000163586), FABP7 (ENSG00000164434), FABP5 (ENSG00000164687), CRABP1 (ENSG00000166426), FABP6 (ENSG00000170231), FABP4 (ENSG00000170323), FABP12 (ENSG00000197416), FABP9 (ENSG00000205186)

Protein

Protein identifiers

Retinol-binding protein 2 — P50120 (reviewed: P50120)

Alternative names: Cellular retinol-binding protein II

All UniProt accessions (3): P50120, D6RB89, D6RGE6

UniProt curated annotations — full annotation on UniProt →

Function. Intracellular transport of retinol.

Subcellular location. Cytoplasm.

Tissue specificity. Higher expression in adult small intestine and to a much lesser extent in fetal kidney.

Domain organisation. Forms a beta-barrel structure that accommodates hydrophobic ligands in its interior.

Similarity. Belongs to the calycin superfamily. Fatty-acid binding protein (FABP) family.

RefSeq proteins (1): NP_004155* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000463	Fatty_acid-bd	Domain
IPR000566	Lipocln_cytosolic_FA-bd_dom	Domain
IPR012674	Calycin	Homologous_superfamily
IPR031259	ILBP	Family

Pfam: PF00061

UniProt features (19 total): strand 10, binding site 2, turn 2, sequence conflict 2, helix 2, chain 1

Structure

Experimental structures (PDB)

102 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
7UCZ	X-RAY DIFFRACTION	1.08
4QYN	X-RAY DIFFRACTION	1.19
2RCQ	X-RAY DIFFRACTION	1.2
2RCT	X-RAY DIFFRACTION	1.2
7K3I	X-RAY DIFFRACTION	1.2
9D8M	X-RAY DIFFRACTION	1.2
8VZZ	X-RAY DIFFRACTION	1.22
8W00	X-RAY DIFFRACTION	1.23
7LHJ	X-RAY DIFFRACTION	1.26
7MFY	X-RAY DIFFRACTION	1.26
9PSX	X-RAY DIFFRACTION	1.29
4GKC	X-RAY DIFFRACTION	1.3
7JVY	X-RAY DIFFRACTION	1.3
7JWR	X-RAY DIFFRACTION	1.3
9D8N	X-RAY DIFFRACTION	1.3
5F6B	X-RAY DIFFRACTION	1.31
7UD1	X-RAY DIFFRACTION	1.32
8DN1	X-RAY DIFFRACTION	1.32
9D8O	X-RAY DIFFRACTION	1.32
8VZY	X-RAY DIFFRACTION	1.34
6BTH	X-RAY DIFFRACTION	1.35
7JWD	X-RAY DIFFRACTION	1.35
12AK	X-RAY DIFFRACTION	1.37
4EDE	X-RAY DIFFRACTION	1.4
4RUU	X-RAY DIFFRACTION	1.4
5FAZ	X-RAY DIFFRACTION	1.4
7JVG	X-RAY DIFFRACTION	1.4
7LHO	X-RAY DIFFRACTION	1.4
9DE1	X-RAY DIFFRACTION	1.4
6C7Z	X-RAY DIFFRACTION	1.42

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P50120-F1	96.49	0.94

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (2): 41; 109

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-975634	Retinoid metabolism and transport

MSigDB gene sets: 84 (showing top): GOBP_ORGANIC_ACID_TRANSPORT, COUP_01, NF1_Q6_01, GOBP_ORGANIC_ANION_TRANSPORT, HFH3_01, HNF4_01, PPAR_DR1_Q2, GOBP_EPIDERMIS_DEVELOPMENT, GOBP_LIPID_METABOLIC_PROCESS, SANSOM_APC_TARGETS_DN, TATA_C, GOBP_MONOCARBOXYLIC_ACID_TRANSPORT, AACTTT_UNKNOWN, VECCHI_GASTRIC_CANCER_EARLY_DN, GOBP_LIPID_LOCALIZATION

GO Biological Process (5): vitamin A metabolic process (GO:0006776), epidermis development (GO:0008544), fatty acid transport (GO:0015908), triglyceride biosynthetic process (GO:0019432), retinoid metabolic process (GO:0001523)

GO Molecular Function (6): retinoid binding (GO:0005501), fatty acid binding (GO:0005504), retinal binding (GO:0016918), retinol binding (GO:0019841), molecular carrier activity (GO:0140104), lipid binding (GO:0008289)

GO Cellular Component (3): nucleus (GO:0005634), cytosol (GO:0005829), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Visual phototransduction	1
Metabolism of fat-soluble vitamins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
retinoid binding	2
vitamin binding	2
binding	2
cellular anatomical structure	2
retinoid metabolic process	1
tissue development	1
lipid transport	1
monocarboxylic acid transport	1
triglyceride metabolic process	1
acylglycerol biosynthetic process	1
diterpenoid metabolic process	1
isoprenoid binding	1
lipid binding	1
monocarboxylic acid binding	1
alcohol binding	1
molecular_function	1
intracellular membrane-bounded organelle	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

594 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RBP2	CYP26A1	O43174	811
RBP2	RARA	P10276	738
RBP2	GOT2	P00505	724
RBP2	RBP3	P10745	724
RBP2	RARS1	P54136	700
RBP2	LRAT	O95237	665
RBP2	CYP26C1	Q6V0L0	634
RBP2	RHO	P08100	633
RBP2	RARB	P10826	632
RBP2	RARG	P13631	618
RBP2	STRA6	Q9BX79	587
RBP2	TGIF2	Q9GZN2	585
RBP2	ANXA4	P09525	542
RBP2	PPARD	Q03181	521
RBP2	PGM3	O95394	520

IntAct

2 interactions, top by confidence:

A	B	Type	Score
RBP2	UBA1	psi-mi:“MI:0220”(ubiquitination reaction)	0.000

BioGRID (3): RBP2 (Affinity Capture-MS), RBP2 (Affinity Capture-MS), RBP2 (Affinity Capture-MS)

ESM2 similar proteins: A0A0K0MJ13, A0A0K0MJN3, A6YLM6, C4N147, O01812, O01814, O02772, O08716, O13008, O15540, O45035, O97788, P02689, P02690, P02691, P04117, P05413, P06768, P07483, P0C6G6, P10790, P11404, P15090, P24526, P29498, P41496, P41509, P48035, P50120, P50121, P51880, P55051, P55052, P55053, P70623, P80049, P86412, Q01469, Q02970, Q05423

Diamond homologs: A0A0K0MJ13, A0A0K0MJN3, A6NFH5, A6YLM6, A8MUU1, B7SUM8, C4N147, O01812, O01814, O02323, O02324, O02772, O08716, O13008, O15540, O42386, O45035, O76821, O97788, P02689, P02690, P02691, P02693, P02694, P02696, P04117, P05413, P06768, P07483, P09455, P0C241, P0C6G6, P0DM59, P10790, P11404, P12104, P15090, P22935, P24526, P29373

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
RBP2	“up-regulates quantity”	“all-trans-retinoic acid”	relocalization

Disease & clinical

Clinical variants and AI predictions

ClinVar

1 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	1
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

901 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:139462196:G:C	S56R	0.984
3:139462196:G:T	S56R	0.984
3:139462198:T:G	S56R	0.984
3:139462263:G:T	A34E	0.984
3:139453128:G:C	F131L	0.983
3:139453128:G:T	F131L	0.983
3:139453130:A:G	F131L	0.983
3:139462169:G:C	F65L	0.980
3:139462169:G:T	F65L	0.980
3:139462171:A:G	F65L	0.980
3:139476433:C:A	W9C	0.979
3:139476433:C:G	W9C	0.979
3:139462272:C:G	R31P	0.978
3:139476435:A:G	W9R	0.975
3:139476435:A:T	W9R	0.975
3:139462122:C:G	R81P	0.973
3:139453140:G:C	C127W	0.968
3:139454764:A:G	W107R	0.968
3:139454764:A:T	W107R	0.968
3:139462151:A:C	F71L	0.968
3:139462151:A:T	F71L	0.968
3:139462153:A:G	F71L	0.968
3:139454823:A:T	V87D	0.962
3:139462241:C:A	K41N	0.956
3:139462241:C:G	K41N	0.956
3:139454730:A:G	L118P	0.955
3:139454736:A:G	L116P	0.955
3:139453162:A:G	L120P	0.954
3:139454762:C:A	W107C	0.952
3:139454762:C:G	W107C	0.952

dbSNP variants (sampled 300 via entrez): RS1000026569 (3:139469271 A>G), RS1000188982 (3:139468423 C>A), RS1000386666 (3:139474955 C>G,T), RS1000410119 (3:139467677 A>C), RS1000453712 (3:139456544 A>G), RS1000479709 (3:139474748 G>A,C), RS1000649028 (3:139469564 G>A), RS1000745446 (3:139456795 A>G), RS1000771428 (3:139461799 G>A,T), RS1001117640 (3:139455227 T>C), RS1001183249 (3:139461593 G>A), RS1001350615 (3:139455282 A>T), RS1001482774 (3:139467750 T>C), RS1001605151 (3:139474247 A>G), RS1001880197 (3:139456908 G>C,T)

Disease associations

OMIM: gene MIM:180280 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: other protein — Fatty acid-binding proteins

CTD chemical–gene interactions

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, increases methylation, affects methylation	2
Tretinoin	affects expression, increases expression	2
fluorene-9-bisphenol	increases expression	1
dicrotophos	decreases expression	1
4-aminophenylarsenoxide	decreases reaction, affects binding	1
Resveratrol	affects cotreatment, decreases expression	1
Arsenic Trioxide	affects binding, decreases reaction	1
Cadmium	decreases expression	1
Ethinyl Estradiol	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Copper Sulfate	decreases expression	1
Lactic Acid	increases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.