RET4_HUMAN
ID RET4_HUMAN Reviewed; 201 AA.
AC P02753; D3DR38; O43478; O43479; Q5VY24; Q8WWA3; Q9P178;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 29-MAR-2005, sequence version 3.
DT 03-AUG-2022, entry version 235.
DE RecName: Full=Retinol-binding protein 4;
DE AltName: Full=Plasma retinol-binding protein;
DE Short=PRBP;
DE Short=RBP;
DE Contains:
DE RecName: Full=Plasma retinol-binding protein(1-182);
DE Contains:
DE RecName: Full=Plasma retinol-binding protein(1-181);
DE Contains:
DE RecName: Full=Plasma retinol-binding protein(1-179);
DE Contains:
DE RecName: Full=Plasma retinol-binding protein(1-176);
DE Flags: Precursor;
GN Name=RBP4; ORFNames=PRO2222;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=6316270; DOI=10.1093/nar/11.22.7769;
RA Colantuoni V., Romano V., Bensi G., Santoro C., Costanzo F., Raugei G.,
RA Cortese R.;
RT "Cloning and sequencing of a full length cDNA coding for human retinol-
RT binding protein.";
RL Nucleic Acids Res. 11:7769-7776(1983).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Liver;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-189.
RX PubMed=2998779; DOI=10.1002/j.1460-2075.1985.tb03881.x;
RA D'Onofrio C., Colantuoni V., Cortese R.;
RT "Structure and cell-specific expression of a cloned human retinol binding
RT protein gene: the 5'-flanking region contains hepatoma specific
RT transcriptional signals.";
RL EMBO J. 4:1981-1989(1985).
RN [6]
RP PROTEIN SEQUENCE OF 19-201, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND
RP DISULFIDE BONDS.
RX PubMed=2444024; DOI=10.3109/03009738709178685;
RA Rask L., Anundi H., Fohlman J., Peterson P.A.;
RT "The complete amino acid sequence of human serum retinol-binding protein.";
RL Ups. J. Med. Sci. 92:115-146(1987).
RN [7]
RP PROTEIN SEQUENCE OF 19-201.
RX PubMed=6942701; DOI=10.1111/j.1749-6632.1981.tb12739.x;
RA Rask L., Anundi H., Boehme J., Eriksson U., Ronne H., Sege K.,
RA Peterson P.A.;
RT "Structural and functional studies of vitamin A-binding proteins.";
RL Ann. N. Y. Acad. Sci. 359:79-90(1981).
RN [8]
RP PROTEIN SEQUENCE OF 19-183.
RX PubMed=573217; DOI=10.1016/0014-5793(79)81084-4;
RA Rask L., Anundi H., Peterson P.A.;
RT "The primary structure of the human retinol-binding protein.";
RL FEBS Lett. 104:55-58(1979).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 18-201.
RC TISSUE=Fetal liver;
RA Zhang C., Yu Y., Zhang S., Wei H., Zhang Y., Zhou G., Bi J., Liu M., He F.;
RT "Functional prediction of the coding sequences of 79 new genes deduced by
RT analysis of cDNA clones from human fetal liver.";
RL Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP PARTIAL PROTEIN SEQUENCE, AND MASS SPECTROMETRY.
RX PubMed=7666002;
RA Jaconi S., Rose K., Hughes G.J., Saurat J.-H., Siegenthaler G.;
RT "Characterization of two post-translationally processed forms of human
RT serum retinol-binding protein: altered ratios in chronic renal failure.";
RL J. Lipid Res. 36:1247-1253(1995).
RN [11]
RP SUBCELLULAR LOCATION, FUNCTION, TISSUE SPECIFICITY, AND INTERACTION WITH
RP TTR.
RX PubMed=5541771; DOI=10.1016/s0021-9258(18)62529-3;
RA Peterson P.A.;
RT "Studies on the interaction between prealbumin, retinol-binding protein,
RT and vitamin A.";
RL J. Biol. Chem. 246:44-49(1971).
RN [12]
RP MASS SPECTROMETRY, AND SUBCELLULAR LOCATION.
RX PubMed=12237133; DOI=10.1016/s0006-291x(02)02212-x;
RA Kiernan U.A., Tubbs K.A., Nedelkov D., Niederkofler E.E., Nelson R.W.;
RT "Comparative phenotypic analyses of human plasma and urinary retinol
RT binding protein using mass spectrometric immunoassay.";
RL Biochem. Biophys. Res. Commun. 297:401-405(2002).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=12716133; DOI=10.1021/pr025574c;
RA Kiernan U.A., Tubbs K.A., Nedelkov D., Niederkofler E.E., McConnell E.,
RA Nelson R.W.;
RT "Comparative urine protein phenotyping using mass spectrometric
RT immunoassay.";
RL J. Proteome Res. 2:191-197(2003).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [15]
RP INTERACTION WITH STRA6, AND FUNCTION.
RX PubMed=22665496; DOI=10.1128/mcb.00505-12;
RA Berry D.C., O'Byrne S.M., Vreeland A.C., Blaner W.S., Noy N.;
RT "Cross talk between signaling and vitamin A transport by the retinol-
RT binding protein receptor STRA6.";
RL Mol. Cell. Biol. 32:3164-3175(2012).
RN [16]
RP INVOLVEMENT IN RDCCAS.
RX PubMed=23189188; DOI=10.1371/journal.pone.0050205;
RA Cukras C., Gaasterland T., Lee P., Gudiseva H.V., Chavali V.R.,
RA Pullakhandam R., Maranhao B., Edsall L., Soares S., Reddy G.B.,
RA Sieving P.A., Ayyagari R.;
RT "Exome analysis identified a novel mutation in the RBP4 gene in a
RT consanguineous pedigree with retinal dystrophy and developmental
RT abnormalities.";
RL PLoS ONE 7:E50205-E50205(2012).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [18]
RP INVOLVEMENT IN MCOPCB10, VARIANTS MCOPCB10 THR-73 AND THR-75,
RP CHARACTERIZATION OF VARIANTS MCOPCB10 THR-73 AND THR-75, AND INTERACTION
RP WITH STRA6.
RX PubMed=25910211; DOI=10.1016/j.cell.2015.03.006;
RA Chou C.M., Nelson C., Tarle S.A., Pribila J.T., Bardakjian T., Woods S.,
RA Schneider A., Glaser T.;
RT "Biochemical basis for dominant inheritance, variable penetrance, and
RT maternal effects in RBP4 congenital eye disease.";
RL Cell 161:634-646(2015).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS).
RX PubMed=6540172; DOI=10.1002/j.1460-2075.1984.tb01995.x;
RA Newcomer M.E., Jones T.A., Aqvist J., Sundelin J., Eriksson U., Rask L.,
RA Peterson P.A.;
RT "The three-dimensional structure of retinol-binding protein.";
RL EMBO J. 3:1451-1454(1984).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
RX PubMed=2217163; DOI=10.1002/prot.340080108;
RA Cowan S.W., Newcomer M.E., Jones T.A.;
RT "Crystallographic refinement of human serum retinol binding protein at 2-A
RT resolution.";
RL Proteins 8:44-61(1990).
RN [21]
RP COMPARISON OF X-RAY STRUCTURES.
RX PubMed=1623143; DOI=10.1002/bip.360320425;
RA Monaco H.L., Zanotti G.;
RT "Three-dimensional structure and active site of three hydrophobic molecule-
RT binding proteins with significant amino acid sequence similarity.";
RL Biopolymers 32:457-465(1992).
RN [22] {ECO:0007744|PDB:1RLB}
RP X-RAY CRYSTALLOGRAPHY (3.10 ANGSTROMS) OF 19-192 IN COMPLEX WITH TTR,
RP INTERACTION WITH TTR, AND DISULFIDE BONDS.
RX PubMed=7754382; DOI=10.1126/science.7754382;
RA Monaco H.L., Rizzi M., Coda A.;
RT "Structure of a complex of two plasma proteins: transthyretin and retinol-
RT binding protein.";
RL Science 268:1039-1041(1995).
RN [23] {ECO:0007744|PDB:1QAB}
RP X-RAY CRYSTALLOGRAPHY (3.20 ANGSTROMS) OF 22-201 IN COMPLEX WITH TTR AND
RP 13-CIS-RETINOL, AND DISULFIDE BONDS.
RX PubMed=10052934; DOI=10.1021/bi982291i;
RA Naylor H.M., Newcomer M.E.;
RT "The structure of human retinol-binding protein (RBP) with its carrier
RT protein transthyretin reveals an interaction with the carboxy terminus of
RT RBP.";
RL Biochemistry 38:2647-2653(1999).
RN [24] {ECO:0007744|PDB:3BSZ}
RP X-RAY CRYSTALLOGRAPHY (3.38 ANGSTROMS) OF 19-194 IN COMPLEX WITH TTR AND
RP 13-CIS-RETINOL, INTERACTION WITH TTR, AND DISULFIDE BONDS.
RX PubMed=19021760; DOI=10.1111/j.1742-4658.2008.06705.x;
RA Zanotti G., Folli C., Cendron L., Alfieri B., Nishida S.K., Gliubich F.,
RA Pasquato N., Negro A., Berni R.;
RT "Structural and mutational analyses of protein-protein interactions between
RT transthyretin and retinol-binding protein.";
RL FEBS J. 275:5841-5854(2008).
RN [25]
RP VARIANTS RDCCAS ASN-59 AND ASP-93.
RX PubMed=9888420;
RA Seeliger M.W., Biesalski H.K., Wissinger B., Gollnick H., Gielen S.,
RA Frank J., Beck S.C., Zrenner E.;
RT "Phenotype in retinol deficiency due to a hereditary defect in retinol
RT binding protein synthesis.";
RL Invest. Ophthalmol. Vis. Sci. 40:3-11(1999).
RN [26]
RP CHARACTERIZATION OF VARIANTS RDCCAS ASN-59 AND ASP-93.
RX PubMed=10232633; DOI=10.1093/ajcn/69.5.931;
RA Biesalski H.K., Frank J., Beck S.C., Heinrich F., Illek B., Reifen R.,
RA Gollnick H., Seeliger M.W., Wissinger B., Zrenner E.;
RT "Biochemical but not clinical vitamin A deficiency results from mutations
RT in the gene for retinol binding protein.";
RL Am. J. Clin. Nutr. 69:931-936(1999).
CC -!- FUNCTION: Retinol-binding protein that mediates retinol transport in
CC blood plasma (PubMed:5541771). Delivers retinol from the liver stores
CC to the peripheral tissues (Probable). Transfers the bound all-trans
CC retinol to STRA6, that then facilitates retinol transport across the
CC cell membrane (PubMed:22665496). {ECO:0000269|PubMed:22665496,
CC ECO:0000305, ECO:0000305|PubMed:5541771}.
CC -!- SUBUNIT: Interacts with TTR (PubMed:5541771, PubMed:7754382,
CC PubMed:10052934, PubMed:19021760). Interaction with TTR prevents its
CC loss by filtration through the kidney glomeruli (Probable). Interacts
CC with STRA6 (PubMed:22665496, PubMed:25910211).
CC {ECO:0000269|PubMed:10052934, ECO:0000269|PubMed:19021760,
CC ECO:0000269|PubMed:22665496, ECO:0000269|PubMed:25910211,
CC ECO:0000269|PubMed:5541771, ECO:0000269|PubMed:7754382, ECO:0000305}.
CC -!- INTERACTION:
CC P02753; P02766: TTR; NbExp=4; IntAct=EBI-2116134, EBI-711909;
CC P02753; O55245: TTR; Xeno; NbExp=2; IntAct=EBI-2116134, EBI-7038226;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:12237133,
CC ECO:0000269|PubMed:2444024, ECO:0000269|PubMed:5541771}.
CC -!- TISSUE SPECIFICITY: Detected in blood plasma and in urine (at protein
CC level). {ECO:0000269|PubMed:2444024, ECO:0000269|PubMed:5541771}.
CC -!- MASS SPECTROMETRY: [Plasma retinol-binding protein(1-181)]:
CC Mass=21063.46; Mass_error=1.88; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:7666002};
CC -!- MASS SPECTROMETRY: [Plasma retinol-binding protein(1-179)]: Mass=20534;
CC Method=MALDI; Evidence={ECO:0000269|PubMed:12237133};
CC -!- MASS SPECTROMETRY: [Plasma retinol-binding protein(1-181)]: Mass=20162;
CC Method=MALDI; Evidence={ECO:0000269|PubMed:12237133};
CC -!- DISEASE: Retinal dystrophy, iris coloboma, and comedogenic acne
CC syndrome (RDCCAS) [MIM:615147]: A disease characterized by retinal
CC degeneration, ocular colobomas involving both the anterior and
CC posterior segment, impaired night vision and loss of visual acuity.
CC Additional characteristic features include developmental abnormalities
CC and severe acne. {ECO:0000269|PubMed:10232633,
CC ECO:0000269|PubMed:23189188, ECO:0000269|PubMed:9888420}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry. Loss of functional RBP4 protein results in serum retinol
CC deficiency. Lack of normal levels of retinol impairs the visual cycle
CC leading to night blindness at early stages; prolonged deficiency may
CC lead to retinal degeneration. Additionally, retinol deficiency may
CC result in dry skin, increased susceptibility to infection and acne
CC (PubMed:23189188). {ECO:0000269|PubMed:23189188}.
CC -!- DISEASE: Microphthalmia, isolated, with coloboma, 10 (MCOPCB10)
CC [MIM:616428]: A disorder of eye formation, ranging from small size of a
CC single eye to complete bilateral absence of ocular tissues. Ocular
CC abnormalities like opacities of the cornea and lens, scaring of the
CC retina and choroid, and other abnormalities may also be present. Ocular
CC colobomas are a set of malformations resulting from abnormal
CC morphogenesis of the optic cup and stalk, and the fusion of the fetal
CC fissure (optic fissure). {ECO:0000269|PubMed:25910211}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the calycin superfamily. Lipocalin family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAF69622.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Mutations of the RBP4 gene; Note=Retina
CC International's Scientific Newsletter;
CC URL="https://www.retina-international.org/files/sci-news/rbp4mut.htm";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Retinol-binding protein 4 entry;
CC URL="https://en.wikipedia.org/wiki/Retinol_binding_protein_4";
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DR EMBL; X00129; CAA24959.1; -; mRNA.
DR EMBL; AL356214; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471066; EAW50065.1; -; Genomic_DNA.
DR EMBL; CH471066; EAW50066.1; -; Genomic_DNA.
DR EMBL; CH471066; EAW50067.1; -; Genomic_DNA.
DR EMBL; BC020633; AAH20633.1; -; mRNA.
DR EMBL; X02775; CAA26553.1; -; Genomic_DNA.
DR EMBL; X02824; CAB46489.1; -; Genomic_DNA.
DR EMBL; AF119868; AAF69622.1; ALT_INIT; mRNA.
DR EMBL; AF025334; AAC02945.1; -; Genomic_DNA.
DR EMBL; AF025335; AAC02946.1; -; Genomic_DNA.
DR CCDS; CCDS31249.1; -.
DR PIR; A93494; VAHU.
DR RefSeq; NP_001310446.1; NM_001323517.1.
DR RefSeq; NP_001310447.1; NM_001323518.1.
DR RefSeq; NP_006735.2; NM_006744.3.
DR PDB; 1BRP; X-ray; 2.50 A; A=19-200.
DR PDB; 1BRQ; X-ray; 2.50 A; A=19-200.
DR PDB; 1JYD; X-ray; 1.70 A; A=19-200.
DR PDB; 1JYJ; X-ray; 2.00 A; A=19-200.
DR PDB; 1QAB; X-ray; 3.20 A; E/F=22-201.
DR PDB; 1RBP; X-ray; 2.00 A; A=19-200.
DR PDB; 1RLB; X-ray; 3.10 A; E/F=19-192.
DR PDB; 2WQ9; X-ray; 1.65 A; A=19-192.
DR PDB; 2WQA; X-ray; 2.85 A; E/F=19-194.
DR PDB; 2WR6; X-ray; 1.80 A; A=19-192.
DR PDB; 3BSZ; X-ray; 3.38 A; E/F=19-194.
DR PDB; 3FMZ; X-ray; 2.90 A; A/B=19-201.
DR PDB; 4O9S; X-ray; 2.30 A; A/B=19-201.
DR PDB; 4PSQ; X-ray; 2.40 A; A/B=19-201.
DR PDB; 5NTY; X-ray; 2.00 A; A=19-200.
DR PDB; 5NU2; X-ray; 1.50 A; A=19-200.
DR PDB; 5NU6; X-ray; 1.68 A; A=19-200.
DR PDB; 5NU7; X-ray; 1.50 A; A=19-200.
DR PDB; 5NU8; X-ray; 1.59 A; A=19-200.
DR PDB; 5NU9; X-ray; 1.50 A; A=19-200.
DR PDB; 5NUA; X-ray; 1.60 A; A=19-200.
DR PDB; 5NUB; X-ray; 1.60 A; A=19-200.
DR PDB; 6QBA; X-ray; 1.80 A; A=19-201.
DR PDBsum; 1BRP; -.
DR PDBsum; 1BRQ; -.
DR PDBsum; 1JYD; -.
DR PDBsum; 1JYJ; -.
DR PDBsum; 1QAB; -.
DR PDBsum; 1RBP; -.
DR PDBsum; 1RLB; -.
DR PDBsum; 2WQ9; -.
DR PDBsum; 2WQA; -.
DR PDBsum; 2WR6; -.
DR PDBsum; 3BSZ; -.
DR PDBsum; 3FMZ; -.
DR PDBsum; 4O9S; -.
DR PDBsum; 4PSQ; -.
DR PDBsum; 5NTY; -.
DR PDBsum; 5NU2; -.
DR PDBsum; 5NU6; -.
DR PDBsum; 5NU7; -.
DR PDBsum; 5NU8; -.
DR PDBsum; 5NU9; -.
DR PDBsum; 5NUA; -.
DR PDBsum; 5NUB; -.
DR PDBsum; 6QBA; -.
DR AlphaFoldDB; P02753; -.
DR BMRB; P02753; -.
DR SMR; P02753; -.
DR BioGRID; 111884; 23.
DR CORUM; P02753; -.
DR IntAct; P02753; 14.
DR MINT; P02753; -.
DR STRING; 9606.ENSP00000360522; -.
DR BindingDB; P02753; -.
DR ChEMBL; CHEMBL3100; -.
DR DrugBank; DB06985; 2-[({4-[2-(trifluoromethyl)phenyl]piperidin-1-yl}carbonyl)amino]benzoic acid.
DR DrugBank; DB06755; Beta carotene.
DR DrugBank; DB05076; Fenretinide.
DR DrugBank; DB03917; N-Ethylretinamide.
DR DrugBank; DB00755; Tretinoin.
DR DrugBank; DB00162; Vitamin A.
DR DrugCentral; P02753; -.
DR GuidetoPHARMACOLOGY; 2549; -.
DR TCDB; 8.A.180.1.1; the retinol-binding protein (rbp) family.
DR iPTMnet; P02753; -.
DR PhosphoSitePlus; P02753; -.
DR BioMuta; RBP4; -.
DR DMDM; 62298174; -.
DR SWISS-2DPAGE; P02753; -.
DR CPTAC; non-CPTAC-1156; -.
DR jPOST; P02753; -.
DR MassIVE; P02753; -.
DR MaxQB; P02753; -.
DR PaxDb; P02753; -.
DR PeptideAtlas; P02753; -.
DR PRIDE; P02753; -.
DR ProteomicsDB; 51582; -.
DR ABCD; P02753; 1 sequenced antibody.
DR Antibodypedia; 885; 1427 antibodies from 45 providers.
DR DNASU; 5950; -.
DR Ensembl; ENST00000371464.8; ENSP00000360519.3; ENSG00000138207.15.
DR Ensembl; ENST00000371467.5; ENSP00000360522.1; ENSG00000138207.15.
DR GeneID; 5950; -.
DR KEGG; hsa:5950; -.
DR MANE-Select; ENST00000371464.8; ENSP00000360519.3; NM_006744.4; NP_006735.2.
DR UCSC; uc001kit.4; human.
DR CTD; 5950; -.
DR DisGeNET; 5950; -.
DR GeneCards; RBP4; -.
DR HGNC; HGNC:9922; RBP4.
DR HPA; ENSG00000138207; Tissue enriched (liver).
DR MalaCards; RBP4; -.
DR MIM; 180250; gene.
DR MIM; 615147; phenotype.
DR MIM; 616428; phenotype.
DR neXtProt; NX_P02753; -.
DR OpenTargets; ENSG00000138207; -.
DR Orphanet; 98938; Colobomatous microphthalmia.
DR Orphanet; 352718; Progressive retinal dystrophy due to retinol transport defect.
DR PharmGKB; PA34289; -.
DR VEuPathDB; HostDB:ENSG00000138207; -.
DR eggNOG; ENOG502RXEW; Eukaryota.
DR GeneTree; ENSGT00510000047107; -.
DR HOGENOM; CLU_094618_0_0_1; -.
DR InParanoid; P02753; -.
DR OMA; FATFEDT; -.
DR OrthoDB; 1631943at2759; -.
DR PhylomeDB; P02753; -.
DR TreeFam; TF331445; -.
DR BioCyc; MetaCyc:ENSG00000138207-MON; -.
DR PathwayCommons; P02753; -.
DR Reactome; R-HSA-2453864; Retinoid cycle disease events.
DR Reactome; R-HSA-2453902; The canonical retinoid cycle in rods (twilight vision).
DR Reactome; R-HSA-6809583; Retinoid metabolism disease events.
DR Reactome; R-HSA-975634; Retinoid metabolism and transport.
DR SignaLink; P02753; -.
DR SIGNOR; P02753; -.
DR BioGRID-ORCS; 5950; 7 hits in 1070 CRISPR screens.
DR ChiTaRS; RBP4; human.
DR EvolutionaryTrace; P02753; -.
DR GeneWiki; Retinol_binding_protein_4; -.
DR GenomeRNAi; 5950; -.
DR Pharos; P02753; Tchem.
DR PRO; PR:P02753; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; P02753; protein.
DR Bgee; ENSG00000138207; Expressed in right lobe of liver and 165 other tissues.
DR ExpressionAtlas; P02753; baseline and differential.
DR Genevisible; P02753; HS.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0016918; F:retinal binding; IEA:UniProtKB-KW.
DR GO; GO:0019841; F:retinol binding; IDA:BHF-UCL.
DR GO; GO:0034632; F:retinol transmembrane transporter activity; IC:BHF-UCL.
DR GO; GO:0048738; P:cardiac muscle tissue development; ISS:BHF-UCL.
DR GO; GO:0048562; P:embryonic organ morphogenesis; ISS:BHF-UCL.
DR GO; GO:0060059; P:embryonic retina morphogenesis in camera-type eye; ISS:BHF-UCL.
DR GO; GO:0048706; P:embryonic skeletal system development; ISS:BHF-UCL.
DR GO; GO:0001654; P:eye development; IMP:BHF-UCL.
DR GO; GO:0048807; P:female genitalia morphogenesis; ISS:BHF-UCL.
DR GO; GO:0006094; P:gluconeogenesis; IMP:BHF-UCL.
DR GO; GO:0042593; P:glucose homeostasis; IDA:BHF-UCL.
DR GO; GO:0007507; P:heart development; ISS:BHF-UCL.
DR GO; GO:0060347; P:heart trabecula formation; ISS:BHF-UCL.
DR GO; GO:0030324; P:lung development; ISS:BHF-UCL.
DR GO; GO:0030277; P:maintenance of gastrointestinal epithelium; IDA:BHF-UCL.
DR GO; GO:0060044; P:negative regulation of cardiac muscle cell proliferation; ISS:BHF-UCL.
DR GO; GO:0002639; P:positive regulation of immunoglobulin production; ISS:BHF-UCL.
DR GO; GO:0032024; P:positive regulation of insulin secretion; IMP:BHF-UCL.
DR GO; GO:0032526; P:response to retinoic acid; IDA:BHF-UCL.
DR GO; GO:0042572; P:retinol metabolic process; IMP:BHF-UCL.
DR GO; GO:0034633; P:retinol transport; IBA:GO_Central.
DR GO; GO:0060157; P:urinary bladder development; ISS:BHF-UCL.
DR GO; GO:0060065; P:uterus development; ISS:BHF-UCL.
DR GO; GO:0060068; P:vagina development; ISS:BHF-UCL.
DR GO; GO:0007601; P:visual perception; IEA:UniProtKB-KW.
DR Gene3D; 2.40.128.20; -; 1.
DR InterPro; IPR012674; Calycin.
DR InterPro; IPR022271; Lipocalin_ApoD.
DR InterPro; IPR022272; Lipocalin_CS.
DR InterPro; IPR000566; Lipocln_cytosolic_FA-bd_dom.
DR InterPro; IPR002449; Retinol-bd/Purpurin.
DR PANTHER; PTHR11873; PTHR11873; 1.
DR Pfam; PF00061; Lipocalin; 1.
DR PIRSF; PIRSF036893; Lipocalin_ApoD; 1.
DR PIRSF; PIRSF500204; RBP_purpurin; 1.
DR PRINTS; PR01174; RETINOLBNDNG.
DR SUPFAM; SSF50814; SSF50814; 1.
DR PROSITE; PS00213; LIPOCALIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Disease variant; Disulfide bond;
KW Methylation; Microphthalmia; Reference proteome; Retinol-binding; Secreted;
KW Sensory transduction; Signal; Transport; Vision; Vitamin A.
FT SIGNAL 1..18
FT /evidence="ECO:0000269|PubMed:2444024,
FT ECO:0000269|PubMed:573217, ECO:0000269|PubMed:6942701"
FT CHAIN 19..201
FT /note="Retinol-binding protein 4"
FT /id="PRO_0000017961"
FT CHAIN 19..200
FT /note="Plasma retinol-binding protein(1-182)"
FT /id="PRO_0000017962"
FT CHAIN 19..199
FT /note="Plasma retinol-binding protein(1-181)"
FT /id="PRO_0000017963"
FT CHAIN 19..197
FT /note="Plasma retinol-binding protein(1-179)"
FT /id="PRO_0000017964"
FT CHAIN 19..194
FT /note="Plasma retinol-binding protein(1-176)"
FT /id="PRO_0000017965"
FT BINDING 116
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P27485"
FT MOD_RES 139
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q00724"
FT DISULFID 22..178
FT /evidence="ECO:0000269|PubMed:2444024"
FT DISULFID 88..192
FT /evidence="ECO:0000269|PubMed:2444024"
FT DISULFID 138..147
FT /evidence="ECO:0000269|PubMed:2444024"
FT VARIANT 59
FT /note="I -> N (in RDCCAS; dbSNP:rs121918584)"
FT /evidence="ECO:0000269|PubMed:10232633,
FT ECO:0000269|PubMed:9888420"
FT /id="VAR_009276"
FT VARIANT 73
FT /note="A -> T (in MCOPCB10; dramatic reduction in retinol
FT binding; has greater affinity for the STRA6 receptor;
FT dbSNP:rs794726862)"
FT /evidence="ECO:0000269|PubMed:25910211"
FT /id="VAR_073856"
FT VARIANT 75
FT /note="A -> T (in MCOPCB10; dramatic reduction in retinol
FT binding; has greater affinity for the STRA6 receptor;
FT dbSNP:rs794726861)"
FT /evidence="ECO:0000269|PubMed:25910211"
FT /id="VAR_073857"
FT VARIANT 93
FT /note="G -> D (in RDCCAS; dbSNP:rs121918585)"
FT /evidence="ECO:0000269|PubMed:10232633,
FT ECO:0000269|PubMed:9888420"
FT /id="VAR_009277"
FT CONFLICT 8
FT /note="L -> F (in Ref. 4; AAH20633)"
FT /evidence="ECO:0000305"
FT CONFLICT 13..17
FT /note="LGSGR -> WAA (in Ref. 1; CAA24959 and 5; CAA26553)"
FT /evidence="ECO:0000305"
FT HELIX 24..26
FT /evidence="ECO:0007829|PDB:5NU2"
FT HELIX 35..38
FT /evidence="ECO:0007829|PDB:5NU2"
FT STRAND 40..48
FT /evidence="ECO:0007829|PDB:5NU2"
FT STRAND 51..53
FT /evidence="ECO:0007829|PDB:5NU7"
FT STRAND 55..65
FT /evidence="ECO:0007829|PDB:5NU2"
FT STRAND 67..69
FT /evidence="ECO:0007829|PDB:1RLB"
FT STRAND 71..81
FT /evidence="ECO:0007829|PDB:5NU2"
FT TURN 82..84
FT /evidence="ECO:0007829|PDB:5NU2"
FT STRAND 85..97
FT /evidence="ECO:0007829|PDB:5NU2"
FT STRAND 103..112
FT /evidence="ECO:0007829|PDB:5NU2"
FT STRAND 118..127
FT /evidence="ECO:0007829|PDB:5NU2"
FT STRAND 129..141
FT /evidence="ECO:0007829|PDB:5NU2"
FT STRAND 145..158
FT /evidence="ECO:0007829|PDB:5NU2"
FT HELIX 164..176
FT /evidence="ECO:0007829|PDB:5NU2"
FT TURN 180..182
FT /evidence="ECO:0007829|PDB:1BRP"
FT TURN 191..193
FT /evidence="ECO:0007829|PDB:6QBA"
SQ SEQUENCE 201 AA; 23010 MW; 660C6DD8CC9B811A CRC64;
MKWVWALLLL AALGSGRAER DCRVSSFRVK ENFDKARFSG TWYAMAKKDP EGLFLQDNIV
AEFSVDETGQ MSATAKGRVR LLNNWDVCAD MVGTFTDTED PAKFKMKYWG VASFLQKGND
DHWIVDTDYD TYAVQYSCRL LNLDGTCADS YSFVFSRDPN GLPPEAQKIV RQRQEELCLA
RQYRLIVHNG YCDGRSERNL L
