Reviewed, UniProtKB/Swiss-Prot P02753 (RET4_HUMAN)

Names and origin

Protein names

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:
    1- Recommended name:
            Plasma retinol-binding protein(1-182)
    2- Recommended name:
            Plasma retinol-binding protein(1-181)
    3- Recommended name:
            Plasma retinol-binding protein(1-179)
    4- Recommended name:
            Plasma retinol-binding protein(1-176)

Gene names

Name:	RBP4
ORF Names:	PRO2222

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	201 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	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.
Subcellular location	Secreted.
Involvement in disease	Defects in RBP4 are a cause of retinol-binding protein deficiency [MIM:180250]. This condition causes night vision problems. It produces a typical 'fundus xerophthalmicus', featuring a progressed atrophy of the retinal pigment epithelium. A deficiency of vitamin A blocks secretion of the binding protein post-translationally and results in defective delivery and supply of vitamin to the epidermal cells (a condition associated with a dermatosis).
Sequence similarities	Belongs to the calycin superfamily. Lipocalin family.
Mass spectrometry	Molecular mass is 21063.46±1.88 Da from positions 17 - 199. Determined by ESI. Ref.9 Molecular mass is 20534 Da from positions 19 - 197. Determined by MALDI. Ref.11 Molecular mass is 20162 Da from positions 19 - 194. Determined by MALDI. Ref.11

Ontologies

Keywords
Biological process	Sensory transduction Transport Vision
Cellular component	Secreted
Disease	Disease mutation
Domain	Signal
Ligand	Retinol-binding Vitamin A
PTM	Disulfide bond
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	cardiac muscle tissue development Inferred from sequence or structural similarity. Source: UniProtKB embryonic organ morphogenesis Inferred from sequence or structural similarity. Source: UniProtKB embryonic retina morphogenesis in camera-type eye Inferred from sequence or structural similarity. Source: UniProtKB embryonic skeletal system development Inferred from sequence or structural similarity. Source: UniProtKB female genitalia morphogenesis Inferred from sequence or structural similarity. Source: UniProtKB gluconeogenesis Inferred from mutant phenotype. Source: UniProtKB glucose homeostasis Inferred from direct assay. Source: UniProtKB heart trabecula formation Inferred from sequence or structural similarity. Source: UniProtKB lung development Inferred from sequence or structural similarity. Source: UniProtKB maintenance of gastrointestinal epithelium Inferred from direct assay. Source: UniProtKB negative regulation of cardiac muscle cell proliferation Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of immunoglobulin secretion Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of insulin secretion Inferred from mutant phenotype. Source: UniProtKB response to retinoic acid Inferred from direct assay. Source: UniProtKB retinol metabolic process Ref.17 Inferred from mutant phenotype. Source: UniProtKB retinol transport Inferred by curator. Source: UniProtKB urinary bladder development Inferred from sequence or structural similarity. Source: UniProtKB uterus development Inferred from sequence or structural similarity. Source: UniProtKB vagina development Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	extracellular space Inferred from direct assay. Source: UniProtKB
Molecular function	protein binding Inferred from physical interaction. Source: UniProtKB retinal binding Inferred from electronic annotation. Source: UniProtKB-KW retinol binding Inferred from direct assay. Source: UniProtKB retinol transporter activity Inferred by curator. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 18

18

Ref.5 Ref.6 Ref.7

Chain

19 – 201

183

Retinol-binding protein 4

PRO_0000017961

Chain

19 – 200

182

Plasma retinol-binding protein(1-182)

PRO_0000017962

Chain

19 – 199

181

Plasma retinol-binding protein(1-181)

PRO_0000017963

Chain

19 – 197

179

Plasma retinol-binding protein(1-179)

PRO_0000017964

Chain

19 – 194

176

Plasma retinol-binding protein(1-176)

PRO_0000017965

Amino acid modifications

Disulfide bond

22 ↔ 178

Ref.5

Disulfide bond

88 ↔ 192

Ref.5

Disulfide bond

138 ↔ 147

Ref.5

Natural variations

Natural variant

59

1

I → N in RBP deficiency. Ref.16 Ref.17

VAR_009276

Natural variant

93

1

G → D in RBP deficiency. Ref.16 Ref.17

VAR_009277

Experimental info

Sequence conflict

8

1

L → F in AAH20633. Ref.3

Sequence conflict

13 – 17

5

LGSGR → WAA Ref.1

Sequence conflict

13 – 17

5

LGSGR → WAA Ref.4

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

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.

.

.

.

.

.

201

Helix Strand Turn

Details...

Helix

24 – 26

3

Helix

35 – 38

4

Beta strand

40 – 48

9

Beta strand

55 – 65

11

Beta strand

71 – 80

10

Beta strand

82 – 84

3

Beta strand

86 – 96

11

Beta strand

103 – 112

10

Beta strand

118 – 127

10

Beta strand

129 – 141

13

Beta strand

145 – 158

14

Helix

164 – 176

13

Sequences

	Sequence		Length	Mass (Da)
	P02753-1 [UniParc]. Last modified March 29, 2005. Version 3. Checksum: 660C6DD8CC9B811A	FASTA	201	23,010
	10 20 30 40 50 60 MKWVWALLLL AALGSGRAER DCRVSSFRVK ENFDKARFSG TWYAMAKKDP EGLFLQDNIV 70 80 90 100 110 120 AEFSVDETGQ MSATAKGRVR LLNNWDVCAD MVGTFTDTED PAKFKMKYWG VASFLQKGND 130 140 150 160 170 180 DHWIVDTDYD TYAVQYSCRL LNLDGTCADS YSFVFSRDPN GLPPEAQKIV RQRQEELCLA 190 200 RQYRLIVHNG YCDGRSERNL L

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and sequencing of a full length cDNA coding for human retinol-binding protein." Colantuoni V., Romano V., Bensi G., Santoro C., Costanzo F., Raugei G., Cortese R. Nucleic Acids Res. 11:7769-7776(1983) [PubMed: 6316270] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J. Nature 429:375-381(2004) [PubMed: 15164054] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Liver.
[4]	"Structure and cell-specific expression of a cloned human retinol binding protein gene: the 5'-flanking region contains hepatoma specific transcriptional signals." D'Onofrio C., Colantuoni V., Cortese R. EMBO J. 4:1981-1989(1985) [PubMed: 2998779] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-189.
[5]	"The complete amino acid sequence of human serum retinol-binding protein." Rask L., Anundi H., Fohlman J., Peterson P.A. Ups. J. Med. Sci. 92:115-146(1987) [PubMed: 2444024] [Abstract] Cited for: PROTEIN SEQUENCE OF 19-201, DISULFIDE BONDS.
[6]	"Structural and functional studies of vitamin A-binding proteins." Rask L., Anundi H., Boehme J., Eriksson U., Ronne H., Sege K., Peterson P.A. Ann. N. Y. Acad. Sci. 359:79-90(1981) [PubMed: 6942701] [Abstract] Cited for: PROTEIN SEQUENCE OF 19-201.
[7]	"The primary structure of the human retinol-binding protein." Rask L., Anundi H., Peterson P.A. FEBS Lett. 104:55-58(1979) [PubMed: 573217] [Abstract] Cited for: PROTEIN SEQUENCE OF 19-183.
[8]	"Functional prediction of the coding sequences of 79 new genes deduced by analysis of cDNA clones from human fetal liver." Zhang C., Yu Y., Zhang S., Wei H., Zhang Y., Zhou G., Bi J., Liu M., He F. Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 18-201. Tissue: Fetal liver.
[9]	"Characterization of two post-translationally processed forms of human serum retinol-binding protein: altered ratios in chronic renal failure." Jaconi S., Rose K., Hughes G.J., Saurat J.-H., Siegenthaler G. J. Lipid Res. 36:1247-1253(1995) [PubMed: 7666002] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE, MASS SPECTROMETRY.
[10]	"Comparative urine protein phenotyping using mass spectrometric immunoassay." Kiernan U.A., Tubbs K.A., Nedelkov D., Niederkofler E.E., McConnell E., Nelson R.W. J. Proteome Res. 2:191-197(2003) [PubMed: 12716133] [Abstract] Cited for: MASS SPECTROMETRY.
[11]	"Comparative phenotypic analyses of human plasma and urinary retinol binding protein using mass spectrometric immunoassay." Kiernan U.A., Tubbs K.A., Nedelkov D., Niederkofler E.E., Nelson R.W. Biochem. Biophys. Res. Commun. 297:401-405(2002) [PubMed: 12237133] [Abstract] Cited for: MASS SPECTROMETRY.
[12]	"The three-dimensional structure of retinol-binding protein." Newcomer M.E., Jones T.A., Aqvist J., Sundelin J., Eriksson U., Rask L., Peterson P.A. EMBO J. 3:1451-1454(1984) [PubMed: 6540172] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS).
[13]	"Crystallographic refinement of human serum retinol binding protein at 2-A resolution." Cowan S.W., Newcomer M.E., Jones T.A. Proteins 8:44-61(1990) [PubMed: 2217163] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
[14]	"Three-dimensional structure and active site of three hydrophobic molecule-binding proteins with significant amino acid sequence similarity." Monaco H.L., Zanotti G. Biopolymers 32:457-465(1992) [PubMed: 1623143] [Abstract] Cited for: COMPARISON OF X-RAY STRUCTURES.
[15]	"The structure of human retinol-binding protein (RBP) with its carrier protein transthyretin reveals an interaction with the carboxy terminus of RBP." Naylor H.M., Newcomer M.E. Biochemistry 38:2647-2653(1999) [PubMed: 10052934] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) OF COMPLEX WITH TTR.
[16]	"Phenotype in retinol deficiency due to a hereditary defect in retinol binding protein synthesis." Seeliger M.W., Biesalski H.K., Wissinger B., Gollnick H., Gielen S., Frank J., Beck S.C., Zrenner E. Invest. Ophthalmol. Vis. Sci. 40:3-11(1999) [PubMed: 9888420] [Abstract] Cited for: VARIANTS RBP DEFICIENCY ASN-59 AND ASP-93.
[17]	"Biochemical but not clinical vitamin A deficiency results from mutations in the gene for retinol binding protein." Biesalski H.K., Frank J., Beck S.C., Heinrich F., Illek B., Reifen R., Gollnick H., Seeliger M.W., Wissinger B., Zrenner E. Am. J. Clin. Nutr. 69:931-936(1999) [PubMed: 10232633] [Abstract] Cited for: CHARACTERIZATION OF VARIANTS ASN-59 AND ASP-93.
+	Additional computationally mapped references.

Web resources

Mutations of the RBP4 gene

Retina International's Scientific Newsletter

Wikipedia

Retinol-binding protein 4 entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X00129 mRNA. Translation: CAA24959.1.
AL356214 Genomic DNA. Translation: CAH72328.1.
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.

IPI

IPI00022420.

PIR

VAHU. A93494.

RefSeq

NP_006735.2.

UniGene

Hs.50223

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1BRP	X-ray	2.50	A	19-198	[»]
1BRQ	X-ray	2.50	A	19-198	[»]
1JYD	X-ray	1.70	A	19-198	[»]
1JYJ	X-ray	2.00	A	19-198	[»]
1QAB	X-ray	3.20	E/F	24-201	[»]
1RBP	X-ray	2.00	A	19-200	[»]
1RLB	X-ray	3.10	E/F	19-190	[»]
3BSZ	X-ray	3.38	E/F	19-194	[»]
3FMZ	X-ray	2.90	A/B	19-201	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P02753. 1 interaction.

STRING

P02753.

2-D gel databases

SWISS-2DPAGE

P02753.

Siena-2DPAGE

P02753.

Proteomic databases

PRIDE

P02753.

Genome annotation databases

Ensembl

ENST00000371464; ENSP00000360519; ENSG00000138207; Homo sapiens. [Genome view]
ENST00000371467; ENSP00000360522; ENSG00000138207; Homo sapiens. [Genome view]

GeneID

5950.

KEGG

hsa:5950.

UCSC

uc001kit.1. human.

Organism-specific databases

CTD

5950.

GeneCards

GC10M095341.

H-InvDB

HIX0009047.

HGNC

HGNC:9922. RBP4.

HPA

CAB004555.
HPA001641.

MIM

180250. gene+phenotype.

PharmGKB

PA34289.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

HBG715497.

HOVERGEN

P02753.

InParanoid

P02753.

OMA

MEWVWAL.

PhylomeDB

P02753.

Gene expression databases

ArrayExpress

P02753.

Bgee

P02753.

CleanEx

HS_RBP4.

Genevestigator

P02753.

GermOnline

ENSG00000138207. Homo sapiens.

Family and domain databases

InterPro

IPR012674. Calycin.
IPR011038. Calycin-like.
IPR002345. Lipocalin.
IPR000566. Lipocln_cytosolic_FA_bd.
IPR002449. Retinol_bd.
[Graphical view]

Gene3D

G3DSA:2.40.128.20. Calycin. 1 hit.

PANTHER

PTHR11873. Retinol_bd. 1 hit.

Pfam

PF00061. Lipocalin. 1 hit.
[Graphical view]

PRINTS

PR00179. LIPOCALIN.
PR01174. RETINOLBNDNG.

PROSITE

PS00213. LIPOCALIN. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB00162. Vitamin A.

NextBio

23182.

SOURCE

Search...

Entry information

Entry name

RET4_HUMAN

Accession

Primary (citable) accession number: P02753
Secondary accession number(s): O43478 , O43479, Q5VY24, Q8WWA3, Q9P178

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	March 29, 2005
Last modified:	February 9, 2010
This is version 130 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any 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.