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Protein

Retinol-binding protein 4

Gene

RBP4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Delivers retinol from the liver stores to the peripheral tissues. In plasma, the RBP-retinol complex interacts with transthyretin, this prevents its loss by filtration through the kidney glomeruli.

GO - Molecular functioni

  • retinal binding Source: UniProtKB-KW
  • retinol binding Source: BHF-UCL
  • retinol transporter activity Source: BHF-UCL

GO - Biological processi

  • cardiac muscle tissue development Source: BHF-UCL
  • embryonic organ morphogenesis Source: BHF-UCL
  • embryonic retina morphogenesis in camera-type eye Source: BHF-UCL
  • embryonic skeletal system development Source: BHF-UCL
  • eye development Source: BHF-UCL
  • female genitalia morphogenesis Source: BHF-UCL
  • gluconeogenesis Source: BHF-UCL
  • glucose homeostasis Source: BHF-UCL
  • heart development Source: BHF-UCL
  • heart trabecula formation Source: BHF-UCL
  • lung development Source: BHF-UCL
  • maintenance of gastrointestinal epithelium Source: BHF-UCL
  • negative regulation of cardiac muscle cell proliferation Source: BHF-UCL
  • positive regulation of immunoglobulin secretion Source: BHF-UCL
  • positive regulation of insulin secretion Source: BHF-UCL
  • response to ethanol Source: Ensembl
  • response to retinoic acid Source: BHF-UCL
  • retinoid metabolic process Source: Reactome
  • retinol metabolic process Source: BHF-UCL
  • retinol transport Source: BHF-UCL
  • urinary bladder development Source: BHF-UCL
  • uterus development Source: BHF-UCL
  • vagina development Source: BHF-UCL
  • visual perception Source: UniProtKB-KW
Complete GO annotation...

Keywords - Biological processi

Sensory transduction, Transport, Vision

Keywords - Ligandi

Retinol-binding, Vitamin A

Enzyme and pathway databases

BioCyciMetaCyc:ENSG00000138207-MONOMER.
ReactomeiR-HSA-2453864. Retinoid cycle disease events.
R-HSA-2453902. The canonical retinoid cycle in rods (twilight vision).
R-HSA-6809583. Retinoid metabolism disease events.
R-HSA-975634. Retinoid metabolism and transport.

Names & Taxonomyi

Protein namesi
Recommended name:
Retinol-binding protein 4
Alternative name(s):
Plasma retinol-binding protein
Short name:
PRBP
Short name:
RBP
Cleaved into the following 4 chains:
Gene namesi
Name:RBP4
ORF Names:PRO2222
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

HGNCiHGNC:9922. RBP4.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: Reactome
  • extracellular exosome Source: UniProtKB
  • extracellular region Source: Reactome
  • extracellular space Source: BHF-UCL
  • protein complex Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Involvement in diseasei

Retinal dystrophy, iris coloboma, and comedogenic acne syndrome (RDCCAS)2 Publications
The disease is caused by mutations affecting the gene represented in this entry. Loss of functional RBP4 protein results in serum retinol deficiency. Lack of normal levels of retinol impairs the visual cycle leading to night blindness at early stages; prolonged deficiency may lead to retinal degeneration. Additionally, retinol deficiency may result in dry skin, increased susceptibility to infection and acne (PubMed:23189188).1 Publication
Disease descriptionA disease characterized by retinal degeneration, ocular colobomas involving both the anterior and posterior segment, impaired night vision and loss of visual acuity. Additional characteristic features include developmental abnormalities and severe acne.
See also OMIM:615147
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti59 – 591I → N in RDCCAS. 2 Publications
Corresponds to variant rs121918584 [ dbSNP | Ensembl ].
VAR_009276
Natural varianti93 – 931G → D in RDCCAS. 2 Publications
Corresponds to variant rs121918585 [ dbSNP | Ensembl ].
VAR_009277
Microphthalmia, isolated, with coloboma, 10 (MCOPCB10)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues. Ocular abnormalities like opacities of the cornea and lens, scaring of the retina and choroid, and other abnormalities may also be present. Ocular colobomas are a set of malformations resulting from abnormal morphogenesis of the optic cup and stalk, and the fusion of the fetal fissure (optic fissure).
See also OMIM:616428
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti73 – 731A → T in MCOPCB10; dramatic reduction in retinol binding; has greater affinity for the STRA6 receptor. 1 Publication
Corresponds to variant rs794726862 [ dbSNP | Ensembl ].
VAR_073856
Natural varianti75 – 751A → T in MCOPCB10; dramatic reduction in retinol binding; has greater affinity for the STRA6 receptor. 1 Publication
Corresponds to variant rs794726861 [ dbSNP | Ensembl ].
VAR_073857

Keywords - Diseasei

Disease mutation, Microphthalmia

Organism-specific databases

MalaCardsiRBP4.
MIMi615147. phenotype.
616428. phenotype.
Orphaneti352718. Progressive retinal dystrophy due to retinol transport defect.
PharmGKBiPA34289.

Chemistry

ChEMBLiCHEMBL3100.
DrugBankiDB00162. Vitamin A.
GuidetoPHARMACOLOGYi2549.

Polymorphism and mutation databases

BioMutaiRBP4.
DMDMi62298174.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 18183 PublicationsAdd
BLAST
Chaini19 – 201183Retinol-binding protein 4PRO_0000017961Add
BLAST
Chaini19 – 200182Plasma retinol-binding protein(1-182)PRO_0000017962Add
BLAST
Chaini19 – 199181Plasma retinol-binding protein(1-181)PRO_0000017963Add
BLAST
Chaini19 – 197179Plasma retinol-binding protein(1-179)PRO_0000017964Add
BLAST
Chaini19 – 194176Plasma retinol-binding protein(1-176)PRO_0000017965Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi22 ↔ 1781 Publication
Disulfide bondi88 ↔ 1921 Publication
Disulfide bondi138 ↔ 1471 Publication

Keywords - PTMi

Disulfide bond

Proteomic databases

EPDiP02753.
MaxQBiP02753.
PaxDbiP02753.
PeptideAtlasiP02753.
PRIDEiP02753.

2D gel databases

SWISS-2DPAGEP02753.

PTM databases

iPTMnetiP02753.
PhosphoSiteiP02753.

Expressioni

Gene expression databases

BgeeiENSG00000138207.
CleanExiHS_RBP4.
ExpressionAtlasiP02753. baseline and differential.
GenevisibleiP02753. HS.

Organism-specific databases

HPAiCAB004555.
HPA001641.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
TTRO552452EBI-2116134,EBI-7038226From a different organism.

Protein-protein interaction databases

BioGridi111884. 13 interactions.
IntActiP02753. 4 interactions.
STRINGi9606.ENSP00000360519.

Chemistry

BindingDBiP02753.

Structurei

Secondary structure

1
201
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi24 – 263Combined sources
Helixi35 – 384Combined sources
Beta strandi40 – 489Combined sources
Beta strandi51 – 533Combined sources
Beta strandi55 – 6511Combined sources
Beta strandi67 – 693Combined sources
Beta strandi71 – 8010Combined sources
Beta strandi82 – 843Combined sources
Beta strandi86 – 9712Combined sources
Beta strandi103 – 11210Combined sources
Beta strandi118 – 12710Combined sources
Beta strandi129 – 14113Combined sources
Beta strandi145 – 15814Combined sources
Helixi164 – 17613Combined sources
Turni180 – 1823Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1BRPX-ray2.50A19-200[»]
1BRQX-ray2.50A19-200[»]
1JYDX-ray1.70A19-200[»]
1JYJX-ray2.00A19-200[»]
1QABX-ray3.20E/F22-201[»]
1RBPX-ray2.00A19-200[»]
1RLBX-ray3.10E/F19-192[»]
2WQ9X-ray1.65A19-192[»]
2WQAX-ray2.85E/F19-194[»]
2WR6X-ray1.80A19-192[»]
3BSZX-ray3.38E/F19-194[»]
3FMZX-ray2.90A/B19-201[»]
4O9SX-ray2.30A/B19-201[»]
4PSQX-ray2.40A/B19-201[»]
ProteinModelPortaliP02753.
SMRiP02753. Positions 19-192.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP02753.

Family & Domainsi

Sequence similaritiesi

Belongs to the calycin superfamily. Lipocalin family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IJHC. Eukaryota.
ENOG4111K1Y. LUCA.
GeneTreeiENSGT00510000047107.
HOVERGENiHBG004493.
InParanoidiP02753.
KOiK18271.
OMAiGHMSATA.
OrthoDBiEOG091G0KIM.
PhylomeDBiP02753.
TreeFamiTF331445.

Family and domain databases

Gene3Di2.40.128.20. 1 hit.
InterProiIPR012674. Calycin.
IPR011038. Calycin-like.
IPR002345. Lipocalin.
IPR022271. Lipocalin_ApoD.
IPR022272. Lipocalin_CS.
IPR000566. Lipocln_cytosolic_FA-bd_dom.
IPR002449. Retinol-bd/Purpurin.
[Graphical view]
PANTHERiPTHR11873. PTHR11873. 1 hit.
PfamiPF00061. Lipocalin. 1 hit.
[Graphical view]
PIRSFiPIRSF036893. Lipocalin_ApoD. 1 hit.
PIRSF500204. RBP_purpurin. 1 hit.
PRINTSiPR00179. LIPOCALIN.
PR01174. RETINOLBNDNG.
SUPFAMiSSF50814. SSF50814. 1 hit.
PROSITEiPS00213. LIPOCALIN. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P02753-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKWVWALLLL AALGSGRAER DCRVSSFRVK ENFDKARFSG TWYAMAKKDP
60 70 80 90 100
EGLFLQDNIV AEFSVDETGQ MSATAKGRVR LLNNWDVCAD MVGTFTDTED
110 120 130 140 150
PAKFKMKYWG VASFLQKGND DHWIVDTDYD TYAVQYSCRL LNLDGTCADS
160 170 180 190 200
YSFVFSRDPN GLPPEAQKIV RQRQEELCLA RQYRLIVHNG YCDGRSERNL

L
Length:201
Mass (Da):23,010
Last modified:March 29, 2005 - v3
Checksum:i660C6DD8CC9B811A
GO

Sequence cautioni

The sequence AAF69622 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti8 – 81L → F in AAH20633 (PubMed:15489334).Curated
Sequence conflicti13 – 175LGSGR → WAA in CAA24959 (PubMed:6316270).Curated
Sequence conflicti13 – 175LGSGR → WAA in CAA26553 (PubMed:2998779).Curated

Mass spectrometryi

Molecular mass is 21063.46±1.88 Da from positions 17 - 199. Determined by ESI. 1 Publication
Molecular mass is 20534 Da from positions 19 - 197. Determined by MALDI. 1 Publication
Molecular mass is 20162 Da from positions 19 - 194. Determined by MALDI. 1 Publication

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti59 – 591I → N in RDCCAS. 2 Publications
Corresponds to variant rs121918584 [ dbSNP | Ensembl ].
VAR_009276
Natural varianti73 – 731A → T in MCOPCB10; dramatic reduction in retinol binding; has greater affinity for the STRA6 receptor. 1 Publication
Corresponds to variant rs794726862 [ dbSNP | Ensembl ].
VAR_073856
Natural varianti75 – 751A → T in MCOPCB10; dramatic reduction in retinol binding; has greater affinity for the STRA6 receptor. 1 Publication
Corresponds to variant rs794726861 [ dbSNP | Ensembl ].
VAR_073857
Natural varianti93 – 931G → D in RDCCAS. 2 Publications
Corresponds to variant rs121918585 [ dbSNP | Ensembl ].
VAR_009277

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X00129 mRNA. Translation: CAA24959.1.
AL356214 Genomic DNA. Translation: CAH72328.1.
CH471066 Genomic DNA. Translation: EAW50065.1.
CH471066 Genomic DNA. Translation: EAW50066.1.
CH471066 Genomic DNA. Translation: EAW50067.1.
BC020633 mRNA. Translation: AAH20633.1.
X02775 Genomic DNA. Translation: CAA26553.1.
X02824 Genomic DNA. Translation: CAB46489.1.
AF119868 mRNA. Translation: AAF69622.1. Different initiation.
AF025334 Genomic DNA. Translation: AAC02945.1.
AF025335 Genomic DNA. Translation: AAC02946.1.
CCDSiCCDS31249.1.
PIRiA93494. VAHU.
RefSeqiNP_001310446.1. NM_001323517.1.
NP_001310447.1. NM_001323518.1.
NP_006735.2. NM_006744.3.
UniGeneiHs.50223.

Genome annotation databases

EnsembliENST00000371464; ENSP00000360519; ENSG00000138207.
ENST00000371467; ENSP00000360522; ENSG00000138207.
GeneIDi5950.
KEGGihsa:5950.
UCSCiuc001kit.4. human.

Cross-referencesi

Web resourcesi

Mutations of the RBP4 gene

Retina International's Scientific Newsletter

Wikipedia

Retinol-binding protein 4 entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X00129 mRNA. Translation: CAA24959.1.
AL356214 Genomic DNA. Translation: CAH72328.1.
CH471066 Genomic DNA. Translation: EAW50065.1.
CH471066 Genomic DNA. Translation: EAW50066.1.
CH471066 Genomic DNA. Translation: EAW50067.1.
BC020633 mRNA. Translation: AAH20633.1.
X02775 Genomic DNA. Translation: CAA26553.1.
X02824 Genomic DNA. Translation: CAB46489.1.
AF119868 mRNA. Translation: AAF69622.1. Different initiation.
AF025334 Genomic DNA. Translation: AAC02945.1.
AF025335 Genomic DNA. Translation: AAC02946.1.
CCDSiCCDS31249.1.
PIRiA93494. VAHU.
RefSeqiNP_001310446.1. NM_001323517.1.
NP_001310447.1. NM_001323518.1.
NP_006735.2. NM_006744.3.
UniGeneiHs.50223.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1BRPX-ray2.50A19-200[»]
1BRQX-ray2.50A19-200[»]
1JYDX-ray1.70A19-200[»]
1JYJX-ray2.00A19-200[»]
1QABX-ray3.20E/F22-201[»]
1RBPX-ray2.00A19-200[»]
1RLBX-ray3.10E/F19-192[»]
2WQ9X-ray1.65A19-192[»]
2WQAX-ray2.85E/F19-194[»]
2WR6X-ray1.80A19-192[»]
3BSZX-ray3.38E/F19-194[»]
3FMZX-ray2.90A/B19-201[»]
4O9SX-ray2.30A/B19-201[»]
4PSQX-ray2.40A/B19-201[»]
ProteinModelPortaliP02753.
SMRiP02753. Positions 19-192.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111884. 13 interactions.
IntActiP02753. 4 interactions.
STRINGi9606.ENSP00000360519.

Chemistry

BindingDBiP02753.
ChEMBLiCHEMBL3100.
DrugBankiDB00162. Vitamin A.
GuidetoPHARMACOLOGYi2549.

PTM databases

iPTMnetiP02753.
PhosphoSiteiP02753.

Polymorphism and mutation databases

BioMutaiRBP4.
DMDMi62298174.

2D gel databases

SWISS-2DPAGEP02753.

Proteomic databases

EPDiP02753.
MaxQBiP02753.
PaxDbiP02753.
PeptideAtlasiP02753.
PRIDEiP02753.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000371464; ENSP00000360519; ENSG00000138207.
ENST00000371467; ENSP00000360522; ENSG00000138207.
GeneIDi5950.
KEGGihsa:5950.
UCSCiuc001kit.4. human.

Organism-specific databases

CTDi5950.
GeneCardsiRBP4.
H-InvDBHIX0009047.
HGNCiHGNC:9922. RBP4.
HPAiCAB004555.
HPA001641.
MalaCardsiRBP4.
MIMi180250. gene.
615147. phenotype.
616428. phenotype.
neXtProtiNX_P02753.
Orphaneti352718. Progressive retinal dystrophy due to retinol transport defect.
PharmGKBiPA34289.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IJHC. Eukaryota.
ENOG4111K1Y. LUCA.
GeneTreeiENSGT00510000047107.
HOVERGENiHBG004493.
InParanoidiP02753.
KOiK18271.
OMAiGHMSATA.
OrthoDBiEOG091G0KIM.
PhylomeDBiP02753.
TreeFamiTF331445.

Enzyme and pathway databases

BioCyciMetaCyc:ENSG00000138207-MONOMER.
ReactomeiR-HSA-2453864. Retinoid cycle disease events.
R-HSA-2453902. The canonical retinoid cycle in rods (twilight vision).
R-HSA-6809583. Retinoid metabolism disease events.
R-HSA-975634. Retinoid metabolism and transport.

Miscellaneous databases

ChiTaRSiRBP4. human.
EvolutionaryTraceiP02753.
GeneWikiiRetinol_binding_protein_4.
GenomeRNAii5950.
PROiP02753.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000138207.
CleanExiHS_RBP4.
ExpressionAtlasiP02753. baseline and differential.
GenevisibleiP02753. HS.

Family and domain databases

Gene3Di2.40.128.20. 1 hit.
InterProiIPR012674. Calycin.
IPR011038. Calycin-like.
IPR002345. Lipocalin.
IPR022271. Lipocalin_ApoD.
IPR022272. Lipocalin_CS.
IPR000566. Lipocln_cytosolic_FA-bd_dom.
IPR002449. Retinol-bd/Purpurin.
[Graphical view]
PANTHERiPTHR11873. PTHR11873. 1 hit.
PfamiPF00061. Lipocalin. 1 hit.
[Graphical view]
PIRSFiPIRSF036893. Lipocalin_ApoD. 1 hit.
PIRSF500204. RBP_purpurin. 1 hit.
PRINTSiPR00179. LIPOCALIN.
PR01174. RETINOLBNDNG.
SUPFAMiSSF50814. SSF50814. 1 hit.
PROSITEiPS00213. LIPOCALIN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiRET4_HUMAN
AccessioniPrimary (citable) accession number: P02753
Secondary accession number(s): D3DR38
, O43478, O43479, Q5VY24, Q8WWA3, Q9P178
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: March 29, 2005
Last modified: September 7, 2016
This is version 194 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.