Affinage

STRA6

Receptor for retinol uptake STRA6 · UniProt Q9BX79

Length
667 aa
Mass
73.5 kDa
Annotated
2026-04-28
82 papers in source corpus 33 papers cited in narrative 33 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

STRA6 is a multitransmembrane cell-surface receptor and bidirectional retinol transporter that couples vitamin A (retinol) delivery from plasma retinol-binding protein (RBP4) to intracellular JAK/STAT signaling. Structurally, STRA6 forms a homodimer with nine transmembrane helices per protomer and a deep lipophilic cleft open to the membrane through which retinol enters the bilayer after release from holo-RBP; calmodulin is constitutively bound intracellularly in a Ca²⁺-dependent manner (PMID:27563101, PMID:34592217). STRA6 mediates retinol influx coupled to LRAT-catalyzed esterification and CRBP-I, and retinol efflux into apo-RBP; retinol translocation to CRBP-I triggers STRA6 phosphorylation and activation of JAK2/STAT3/STAT5 cascades that regulate insulin signaling, adipogenesis, cancer stem cell maintenance, and muscle homeostasis, while transthyretin blocks holo-RBP access to suppress both transport and signaling (PMID:22665496, PMID:22826435, PMID:22815070, PMID:28689994, PMID:39031684). Loss-of-function mutations in STRA6 cause Matthew-Wood syndrome, characterized by anophthalmia and congenital heart defects, and STRA6 knockout in mice confirms its essential role in ocular retinoid homeostasis and photoreceptor chromophore supply (PMID:17273977, PMID:22467576, PMID:34508587).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1997 Medium

    Before STRA6's function was known, its identification as a retinoic acid-responsive gene encoding a novel integral membrane protein at blood–organ barriers established the molecular starting point and predicted a role in retinoid transport.

    Evidence Subtractive hybridization cloning and in situ hybridization in wild-type and RARα-null mice

    PMID:9203140

    Open questions at the time
    • No biochemical activity assigned
    • Membrane topology unknown
    • No binding partner identified
  2. 2007 High

    The central question of STRA6's biochemical function was resolved by demonstrating it is the high-affinity cell-surface receptor for plasma RBP that mediates cellular retinol uptake, and simultaneously, human loss-of-function mutations established its physiological necessity for eye and heart development.

    Evidence Transfected-cell retinol uptake assays with RBP binding (Cell Metabolism); homozygosity mapping and patient fibroblast analysis showing protein absence (Am J Hum Genet)

    PMID:17273977 PMID:17339024

    Open questions at the time
    • Directionality of transport not yet tested
    • Structural basis unknown
    • Signaling capacity not suspected
  3. 2008 High

    The transport mechanism was shown to be bidirectional and LRAT-coupled, and zebrafish loss-of-function confirmed that STRA6 gates vitamin A specifically to the developing eye rather than acting as a general cellular uptake channel.

    Evidence In vitro retinol influx/efflux assays plus zebrafish morpholino knockdown with pharmacological rescue

    PMID:18316031

    Open questions at the time
    • Efflux coupling partners not fully defined
    • Structural mechanism of bidirectionality unknown
  4. 2012 High

    A paradigm shift occurred when STRA6 was revealed to function simultaneously as a cytokine receptor: retinol translocation to CRBP-I triggers STRA6 phosphorylation and JAK2/STAT3-5 activation, transthyretin blocks holo-RBP access to suppress both transport and signaling, and STRA6 catalyzes retinol exchange between intracellular CRBPs and extracellular RBP.

    Evidence Phosphorylation/retinol uptake assays with dominant-negative mutants; TTR binding competition in vitro and insulin resistance protection in mice; purified-component exchange assays

    PMID:22665496 PMID:22815070 PMID:22826435

    Open questions at the time
    • Phosphorylation site(s) on STRA6 not mapped biochemically
    • How TTR sterically excludes holo-RBP structurally unknown
    • Calmodulin's role in signaling vs transport not dissected
  5. 2012 High

    Stra6-knockout mice established that STRA6 is essential for ocular retinoid homeostasis and photoreceptor maintenance but dispensable for retinol uptake in most non-ocular tissues, delineating tissue-specific dependence.

    Evidence Stra6-null mice with HPLC retinoid quantification, ERG, and histology across tissues

    PMID:22467576 PMID:23839944

    Open questions at the time
    • Alternative retinol uptake pathways in non-ocular tissues not identified
    • Whether STRA6 loss affects brain and testis long-term not fully addressed
  6. 2013 High

    LRAT was shown to be required for STRA6/JAK2/STAT5 activation, demonstrating that retinol metabolism is mechanistically coupled to the signaling output, and bidirectional transport through STRA6 was shown to regulate adipogenesis by controlling cellular retinoid levels and RARα activity.

    Evidence LRAT-null mice protected from holo-RBP-induced insulin suppression; adipocyte differentiation assays with apo- vs holo-RBP4

    PMID:23959802 PMID:24036882

    Open questions at the time
    • Whether LRAT and CRBP-I compete or cooperate at STRA6 unknown
    • Relative contribution of transport vs signaling to adipogenesis unclear
  7. 2014 High

    STRA6 transcription was shown to be regulated by a dual-promoter system driven by a half-site RARE occupied by RARγ/RXRα, with vitamin A status controlling promoter switching, and STRA6/JAK2/STAT3 signaling was linked to oncogenic transformation in breast and colon tumors.

    Evidence CRISPR-Cas9 RARE deletion and ChIP in mouse tissues; STRA6 knockdown in xenograft tumor models

    PMID:25237067 PMID:25544292

    Open questions at the time
    • Whether the two promoter-derived isoforms have distinct signaling properties unknown
    • Oncogenic role observed in limited tumor types
  8. 2016 High

    The cryo-EM structure at 3.9 Å resolution revealed STRA6's unprecedented homodimeric architecture with a deep lipophilic cleft open to the membrane, explaining how retinol is released from RBP and diffuses into the bilayer, and constitutively bound calmodulin was identified intracellularly.

    Evidence Single-particle cryo-EM of zebrafish STRA6 with mutagenesis of RBP-binding residues

    PMID:27563101

    Open questions at the time
    • No structure of STRA6–RBP complex available
    • How retinol traverses from the cleft to intracellular acceptors unresolved
    • Calmodulin's functional role in transport not demonstrated structurally
  9. 2017 Medium

    STRA6 was placed in the circadian regulatory network, with REV-ERBα driving its diurnal expression in adipose tissue, and STRA6/JAK2/STAT3 signaling was shown to maintain cancer stem cell self-renewal in colon carcinoma.

    Evidence Circadian expression analysis in Stra6-KO mice; cancer stem cell sphere-formation and xenograft assays with STRA6 knockdown

    PMID:28689994 PMID:28733465

    Open questions at the time
    • Whether circadian STRA6 oscillation directly modulates retinol flux or only signaling is unclear
    • Cancer stem cell mechanism may be tissue-specific
  10. 2019 Medium

    O-GlcNAcylation was identified as a post-translational modification of STRA6 in diabetic kidneys that suppresses RBP4 binding and disrupts downstream retinol signaling, providing a molecular link between hyperglycemia and impaired vitamin A homeostasis.

    Evidence Immunoprecipitation, proximity ligation assay, OGT/OGA manipulation in high-glucose-treated cells

    PMID:30905621

    Open questions at the time
    • Specific O-GlcNAcylation sites on STRA6 not mapped
    • Whether this modification affects STRA6 signaling independently of transport unknown
    • Single-lab finding awaits independent confirmation
  11. 2021 High

    NMR studies defined the Ca²⁺-dependent calmodulin–STRA6 interaction in molecular detail: at resting Ca²⁺, only the CaM C-lobe engages the BP2 peptide, while signaling-level Ca²⁺ recruits both lobes, suggesting Ca²⁺ transients regulate STRA6 transport activity.

    Evidence NMR chemical shift perturbation, thermodynamic Ca²⁺-binding and kinetic dissociation measurements

    PMID:34592217

    Open questions at the time
    • Functional effect of CaM engagement on retinol transport rate not measured in cells
    • No structure of full-length CaM–STRA6 complex at atomic resolution
  12. 2022 High

    STRA6 was shown to be essential for maintaining chromophore–opsin stoichiometry throughout life; its absence causes persistent chromophore deficit, opsin downregulation, and cone opsin mislocalization that pharmacological vitamin A only partially rescues.

    Evidence Stra6-KO mice with lifelong retinoid quantification, ERG, immunohistochemistry, and vitamin A supplementation

    PMID:34508587

    Open questions at the time
    • Why cones are more sensitive than rods to STRA6 loss not mechanistically explained
    • Alternative chromophore delivery routes to cones not identified
  13. 2023 Medium

    STRA6 was linked to cardiac outflow tract development through its role in supplying retinol for retinoic acid signaling to RAR/RXR–TBX1 complexes, and independently shown to interact with ILK to activate AKT/mTOR signaling in thyroid cancer.

    Evidence STRA6-KO hESC differentiation with scRNA-seq and Co-IP of RARα/RXRα–TBX1; Co-IP of STRA6–ILK in thyroid carcinoma cells with knockdown and xenograft assays

    PMID:36592123 PMID:36635482

    Open questions at the time
    • STRA6–ILK interaction awaits reciprocal validation and structural characterization
    • Whether the cardiac SMC phenotype reflects retinol transport or STRA6 signaling is undetermined
  14. 2024 Medium

    STRA6/JAK2/STAT3 signaling was extended to muscle atrophy (via Atrogin-1/MuRF1 induction) and pancreatic cancer glycolysis (via STAT3/HIF-1α), and STRA6 mRNA was shown to be stabilized by VIRMA-mediated m⁶A modification read by IGF2BP2, adding epitranscriptomic regulation.

    Evidence Denervation and RBP4-KO mouse models for atrophy; m⁶A-seq and RIP assays for epitranscriptomic control; knockdown and xenograft assays for pancreatic cancer

    PMID:38604311 PMID:39031684 PMID:39168951

    Open questions at the time
    • Whether m⁶A regulation of STRA6 operates in non-cancer contexts unknown
    • Relative contribution of STRA6 transport vs signaling to muscle atrophy not dissected

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the atomic-resolution structure of the STRA6–holo-RBP complex, the identity of specific phosphorylation and O-GlcNAcylation sites, how calmodulin binding functionally modulates retinol transport in cells, the mechanism by which retinol traverses from the lipophilic cleft to intracellular acceptors, and the molecular basis for tissue-specific dependence on STRA6 versus alternative retinol uptake pathways.
  • No atomic STRA6–RBP co-structure
  • Phosphorylation sites not mapped by mass spectrometry
  • Alternative retinol uptake pathways in non-ocular tissues molecularly unidentified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 4 GO:0060089 molecular transducer activity 4 GO:0008289 lipid binding 2 GO:0038024 cargo receptor activity 2
Localization
GO:0005886 plasma membrane 4
Pathway
R-HSA-382551 Transport of small molecules 6 R-HSA-1643685 Disease 5 R-HSA-1266738 Developmental Biology 4
Partners
CAMCRBP1ILKJAK2LRATRBP4TTR
Complex memberships
STRA6 homodimerSTRA6–calmodulin complex

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 STRA6 encodes a highly hydrophobic integral membrane protein of a novel type with no similarity to previously characterized integral membrane proteins; it is strongly expressed at blood-organ barriers and its expression in testis Sertoli cells is spermatogenic cycle-dependent and lost in RAR-alpha null mutants, suggesting a role in retinoid transport machinery. Subtractive hybridization cDNA cloning, in situ hybridization, expression analysis in RAR-alpha null mutants Mechanisms of development Medium 9203140
2007 STRA6 functions as the high-affinity cell-surface receptor for plasma retinol-binding protein (RBP) and mediates cellular uptake of retinol (vitamin A) from holo-RBP; STRA6 couples with LRAT to facilitate retinol transfer into cells. Biochemical retinol uptake assays in transfected cells, RBP binding studies Cell metabolism High 17339024
2007 Loss-of-function mutations in STRA6 cause pleiotropic developmental malformations (anophthalmia, heart defects, diaphragmatic hernia); missense mutations alter the geometry of transmembrane helix-connecting loops, and C-terminal mutations disrupt an SH2-binding motif (T644M) and a phosphorylation site (R655C), indicating these functional sites are essential for STRA6 activity. Homozygosity mapping, sequencing, immunoblot of patient fibroblasts, structural modeling American journal of human genetics High 17273977
2008 STRA6-dependent retinol transfer from RBP4 into NIH 3T3 fibroblasts is enhanced by LRAT and is bidirectional, indicating STRA6 acts as a retinol channel/transporter; in zebrafish, stra6 loss-of-function causes vitamin A deprivation of developing eyes, and in stra6-deficient embryos, holo-Rbp4 provokes nonspecific vitamin A excess in other tissues impairing RA receptor signaling. In vitro retinol transfer assays, zebrafish morpholino knockdown, pharmacological rescue Cell metabolism High 18316031
2012 STRA6 functions as a cytokine receptor that activates JAK/STAT signaling upon binding of holo-RBP; receptor phosphorylation is triggered not simply by extracellular ligand binding, but by STRA6-mediated translocation of retinol from serum RBP to the intracellular acceptor CRBP-I, and STRA6 phosphorylation is required for retinol uptake to proceed, demonstrating that transport and signaling are critically interdependent. Phosphorylation assays, retinol uptake assays, CRBP-I interaction studies, dominant-negative mutants Molecular and cellular biology High 22665496
2012 Transthyretin (TTR) blocks the ability of holo-RBP to associate with STRA6, thereby suppressing both STRA6-mediated retinol uptake and STRA6-initiated JAK/STAT signaling; TTR protects mice from RBP-induced insulin resistance. In vitro binding assays, cell-based retinol uptake and signaling assays, mouse glucose tolerance tests Molecular and cellular biology High 22826435
2012 STRA6 catalyzes bidirectional retinol transport: retinol influx from holo-RBP (coupled to CRBP-I and LRAT) and retinol efflux into apo-RBP (strongly coupled to both CRBP-I and CRBP-II); STRA6 also catalyzes retinol exchange between intracellular CRBP-I and extracellular RBP. In vitro retinol influx, efflux, and exchange assays with purified components The Journal of membrane biology High 22815070
2012 STRA6 deficiency in mice (stra6-/- null) results in severe reduction of retinoid content in the RPE and retina, impaired retinol uptake, shortened rod outer/inner segments, reduced cone photoreceptor number, reduced scotopic and photopic ERG responses, and persistent primary hyperplastic vitreous; however, STRA6 is not the only pathway for RPE retinol uptake. Stra6 knockout mouse, HPLC retinoid quantification, ERG, histology, immunocytochemistry Investigative ophthalmology & visual science High 22467576
2013 STRA6 ablation in mice effectively protects from RBP-induced suppression of insulin signaling (JAK/STAT pathway), demonstrating that STRA6 couples circulating holo-RBP levels to cell signaling and insulin resistance; contribution of STRA6 to retinol uptake by non-ocular tissues in vivo is small, and only the eye is critically dependent on STRA6 for retinoid homeostasis. Stra6 knockout mouse, insulin signaling assays, retinoid quantification, glucose tolerance tests The Journal of biological chemistry High 23839944
2013 LRAT (lecithin:retinol acyl transferase), by esterifying retinol, is necessary for activation of the STRA6/JAK2/STAT5 cascade by holo-RBP; LRAT-null mice are protected from holo-RBP-induced suppression of insulin responses, demonstrating that STRA6 signaling requires STRA6-mediated retinol transport supported by LRAT-catalyzed retinol metabolism. LRAT-null mice, cell-based JAK2/STAT5 signaling assays, insulin response measurements FASEB journal High 24036882
2013 STRA6 is expressed in adipocyte precursor cells and mediates bidirectional retinol transport dictated by apo- and holo-RBP4 isoforms; holo-RBP4 blocks adipocyte differentiation via RARα activation, while apo-RBP4 triggers retinol efflux reducing cellular retinoids and RARα activity, enhancing adipogenesis synergistically with ectopic STRA6. Cell-based retinol transport assays, adipocyte differentiation assays, RARα reporter assays, in vivo retinoid mobilization Molecular and cellular biology High 23959802
2013 STRA6 upregulation by DNA damage occurs in a p53-dependent manner; STRA6 expression induces apoptosis and influences p53-mediated cell fate decisions by converting arrest to cell death, induces mitochondria depolarization and ROS accumulation, and is present not only at the cell membrane but also in the cytosol; these functions are independent of downstream RA signaling. p53 overexpression and knockdown, flow cytometry (apoptosis, ROS, mitochondrial potential), subcellular fractionation, STRA6 knockdown Cell death and differentiation Medium 23449393
2014 STRA6 is a bona fide vitamin A transporter critical for ocular vitamin A uptake; Stra6 knockout mice on vitamin A-sufficient diets show markedly reduced ocular retinoids, choroid/RPE malformations, early cone photoreceptor cell death, and reduced rod outer segment length; pharmacological doses of vitamin A restore transport across blood-retinal and blood-CSF barriers and rescue vision. Stra6 knockout mouse, HPLC retinoid quantification, ophthalmic imaging, histology, pharmacological rescue Human molecular genetics High 24852372
2014 Holo-RBP/STRA6 signaling activates a JAK2-STAT3/STAT5 cascade that promotes oncogenic transformation; expression of RBP and STRA6 is markedly upregulated in human breast and colon tumors; STRA6 expression is critical for tumor formation by colon carcinoma cells in vivo, and holo-RBP/STRA6 signaling efficiently induces fibroblast oncogenic transformation. STRA6 knockdown/overexpression, xenograft mouse models, JAK2/STAT signaling assays, tumor formation assays Cancer research High 25237067
2014 An alternative Stra6 promoter driven by a half-site retinoic acid response element (RARE) is used in embryonic stem cells and some tissues; both RARγ and RXRα occupy the STRA6 RARE; RA increases p300 binding and H3K27 acetylation and decreases Suz12/H3K27me3 at both promoters; in vitamin A-deficient kidneys, differential promoter usage occurs, with the longer transcript (Stra6L) greatly increased while the shorter (Stra6S) decreases. CRISPR-Cas9 RARE deletion, luciferase reporter assays, ChIP, mouse models of vitamin A deficiency, RARγ null mice The Journal of biological chemistry High 25544292
2015 G304K mutant STRA6 protein is mislocalized and has severely reduced vitamin A uptake activity; inhibition of retinoic acid synthesis in zebrafish reproduces the colobomatous microanophthalmia phenotype, indicating diminished RA levels account for eye malformations in STRA6 p.G304K patients. Functional vitamin A uptake assays, localization studies in transfected cells, zebrafish RA synthesis inhibition model Human mutation High 21901792
2016 Cryo-EM structure of zebrafish STRA6 at 3.9 Å resolution reveals: (1) a novel topology with one intramembrane and nine transmembrane helices forming an intricate homodimer; (2) calmodulin tightly bound in a noncanonical arrangement; (3) an arch-like extracellular structure covering a deep lipophilic cleft that is open to the membrane, suggesting retinol internalization by direct diffusion into the lipid bilayer after release from RBP. Single-particle cryo-electron microscopy, structural analysis, mutagenesis of RBP-binding residues Science High 27563101
2016 STRA6 is critical for transport of vitamin A across blood-tissue barriers in eyes, brain, and testis; fat and lung rely instead on dietary vitamin A; in testis and brain, Stra6 expression is regulated by vitamin A levels, which reduces vitamin A consumption under dietary limitation to sequester it for the eye. Stra6 knockout mice on vitamin A-sufficient and -deficient diets, tissue retinoid quantification, retinoid-dependent process analysis FASEB journal High 27189978
2017 STRA6 undergoes circadian patterning in adipose tissue driven in part by the nuclear transcription factor REV-ERBα; STRA6 is necessary for diurnal rhythmicity of insulin action and JAK/STAT signaling in adipose tissue, establishing holo-RBP/STRA6 as a regulator of diurnal insulin responses. Circadian expression analysis, Stra6 knockout mice, adipose tissue insulin signaling assays The Journal of biological chemistry Medium 28733465
2017 RBP4 activation of STRA6 transduces a JAK2-STAT3 signaling cascade that promotes colon cancer stem cell maintenance and sphere/tumor initiation frequency; downregulation of STRA6 or RBP4 decreases cancer stem cell fraction and tumor growth in vivo. STRA6/RBP4 knockdown, cancer stem cell assays, sphere formation, xenograft mouse model Stem cell reports High 28689994
2019 miR-873 directly targets STRA6, downregulating its expression; STRA6 activates the Wnt/β-catenin signaling pathway in gastric cancer cells, promoting proliferation and metastasis. Dual-luciferase reporter assay, rescue experiments, STRA6 knockdown/overexpression, in vitro and in vivo tumor assays Journal of experimental & clinical cancer research Medium 31694721
2019 O-GlcNAcylation directly modifies STRA6 in diabetic kidneys, suppressing RBP4 binding activity and disrupting downstream retinol signaling (CRBP1, LRAT, ADH, retinoic acid, RARs); inhibition of O-GlcNAcylation rescues STRA6-retinol signals and reverses increases in TGFβ1 and collagen in high-glucose-treated cells. Immunoprecipitation, proximity ligation assay, OGT/OGA knockdown and transfection, HPLC retinoid quantification, Western blot Biochimica et biophysica acta. General subjects Medium 30905621
2020 STRA6 expressed in pancreatic β-cells mediates RBP4's inhibitory effect on insulin synthesis through a JAK2/STAT1/ISL-1 signaling pathway; RBP4 directly suppresses glucose-stimulated insulin secretion via STRA6 in a dose- and time-dependent manner. Primary islet isolation, INS-1E cell assays, siRNA knockdown of STRA6, JAK2/STAT1 inhibitors, RBP4 transgenic mice Diabetes High 33199363
2021 Calmodulin binding to STRA6 via the BP2 region is Ca2+-dependent: at resting intracellular Ca2+ (<100 nM), BP2 interacts with the C-lobe of CaM; as Ca2+ rises to ~1000 nM (signaling event level), BP2 interacts with both N- and C-lobes of Ca2+-loaded CaM; BP2 binding increases CaM's Ca2+-binding affinity and slows Ca2+ dissociation, suggesting Ca2+-dependent regulation of vitamin A transport by STRA6. NMR chemical shift perturbations, thermodynamic Ca2+ binding studies, kinetic koff measurements Journal of molecular biology High 34592217
2021 Retinol from hepatic stellate cells is transferred to hepatocytes via STRA6-mediated transport; TIF1γ suppression in HSCs upregulates STRA6 and promotes retinol release, and STRA6 knockdown in HSCs blocks retinol transfer to hepatocytes, reducing lipogenesis-related gene upregulation and triglyceride accumulation; in vivo STRA6 blocking reduces liver fibrosis. siRNA knockdown of STRA6, HSC isolation from transgenic mice, HepG2 cell retinol uptake assays, in vivo fibrosis model Cell & bioscience Medium 33407858
2022 STRA6 is critical to adjust the stoichiometry of chromophore and opsins in rod and cone photoreceptors; STRA6-deficient mice show decreased chromophore throughout life, downregulation of opsin genes, mislocalized cone opsins, and significant amounts of chromophore-free opsins in rods; pharmacological vitamin A ameliorates the rod phenotype but does not restore cone visual pigment synthesis. Stra6 knockout mice, HPLC retinoid quantification, histology, ERG, immunohistochemistry, pharmacological rescue Human molecular genetics High 34508587
2023 STRA6 is required for proper induction of vascular smooth muscle cell (SMC) lineages in human cardiac outflow tract development; STRA6-knockout human embryonic stem cells can differentiate into cardiomyocytes but cannot differentiate into mesodermal or neural crest-derived SMCs; an interaction between RA nuclear receptors RARα/RXRα and TBX1 (OFT-specific transcription factor) was identified as downstream of STRA6-mediated RA signaling. STRA6-knockout hESCs, single-cell RNA-seq comparison, population RNA-seq, in vitro differentiation assays, co-immunoprecipitation (RARα/RXRα-TBX1) Cardiovascular research High 36635482
2023 STRA6 interacts with integrin-linked kinase (ILK) and activates downstream AKT/mTOR signaling in thyroid carcinoma cells; STRA6 also activates STAT3-mediated SREBP1 expression to reprogram lipid metabolism, promoting tumor metastasis. Co-immunoprecipitation, RNA sequencing, STRA6 knockdown, in vitro and in vivo tumor assays, siRNA-LNP delivery Endocrinology Medium 36592123
2024 Holo-RBP4 activates STRA6 to promote phosphorylation of downstream JAK2 and STAT3, causing muscle atrophy; inhibition of STRA6/JAK2/STAT3 pathway by siRNA or specific inhibitors reduces atrophy marker expression (Atrogin-1, MuRF1) and rescues myogenesis markers (MyoD, MyoG) in C2C12 myotubes treated with holo-RBP4. siRNA knockdown, pathway inhibitors, denervation mouse model, RBP4 knockout mice, C2C12 myotube assays Journal of cachexia, sarcopenia and muscle High 39031684
2024 VIRMA-mediated m6A modification of STRA6 mRNA (at the 3' UTR) stabilizes STRA6 mRNA via the m6A reader IGF2BP2, upregulating STRA6 expression; STRA6 then activates STAT3/HIF-1α signaling to promote glycolysis in pancreatic ductal adenocarcinoma. RNA-seq, m6A-seq, RIP assay, luciferase assay, mRNA stability assay, STRA6/VIRMA knockdown in vitro and in vivo Cancer letters Medium 38604311
2024 STRA6 knockdown in NSCLC cells suppresses proliferation, migration, and invasion by reducing lipid synthesis; mechanistically, STRA6 activates JAK2/STAT3 signaling, which induces SREBP-1 expression to promote adipogenesis and provide energy for tumor growth. STRA6 knockdown, in vitro and in vivo tumor assays, JAK2/STAT3 pathway analysis, lipid metabolism assays Molecular and cellular biochemistry Medium 39168951
2015 Purified STRA6 protein interacts with RBP in a retinol-independent manner with a stoichiometry consistent with 1 mole RBP per mole STRA6 monomer, as shown by surface plasmon resonance; STRA6-GFP correctly localizes to the cell surface and retains RBP binding. Surface plasmon resonance, GFP fusion expression and purification, cell surface localization assay PloS one Medium 25816144
2020 Reconstitution of purified zebrafish STRA6 in liposomes demonstrates STRA6-mediated retinol uptake activity in a defined in vitro proteoliposome assay; the cryo-EM structure shows STRA6 in lipid-filled nanodiscs maintaining its homodimeric topology. Cryo-EM, proteoliposome reconstitution, in vitro retinol uptake assay Methods in enzymology High 32359662

Source papers

Stage 0 corpus · 82 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 Mutations in STRA6 cause a broad spectrum of malformations including anophthalmia, congenital heart defects, diaphragmatic hernia, alveolar capillary dysplasia, lung hypoplasia, and mental retardation. American journal of human genetics 286 17273977
2007 Matthew-Wood syndrome is caused by truncating mutations in the retinol-binding protein receptor gene STRA6. American journal of human genetics 169 17503335
1997 Developmental expression pattern of Stra6, a retinoic acid-responsive gene encoding a new type of membrane protein. Mechanisms of development 165 9203140
2008 RBP4 disrupts vitamin A uptake homeostasis in a STRA6-deficient animal model for Matthew-Wood syndrome. Cell metabolism 154 18316031
2013 The STRA6 receptor is essential for retinol-binding protein-induced insulin resistance but not for maintaining vitamin A homeostasis in tissues other than the eye. The Journal of biological chemistry 118 23839944
2016 Structure of the STRA6 receptor for retinol uptake. Science (New York, N.Y.) 116 27563101
2014 STRA6 is critical for cellular vitamin A uptake and homeostasis. Human molecular genetics 115 24852372
2001 Overexpression of the retinoic acid-responsive gene Stra6 in human cancers and its synergistic induction by Wnt-1 and retinoic acid. Cancer research 94 11358845
2017 RBP4-STRA6 Pathway Drives Cancer Stem Cell Maintenance and Mediates High-Fat Diet-Induced Colon Carcinogenesis. Stem cell reports 89 28689994
2012 Retinoid content, visual responses, and ocular morphology are compromised in the retinas of mice lacking the retinol-binding protein receptor, STRA6. Investigative ophthalmology & visual science 88 22467576
2012 Cross talk between signaling and vitamin A transport by the retinol-binding protein receptor STRA6. Molecular and cellular biology 87 22665496
2009 Phenotypic spectrum of STRA6 mutations: from Matthew-Wood syndrome to non-lethal anophthalmia. Human mutation 86 19309693
2013 Retinol-binding protein 4 and its membrane receptor STRA6 control adipogenesis by regulating cellular retinoid homeostasis and retinoic acid receptor α activity. Molecular and cellular biology 84 23959802
2012 STRA6-catalyzed vitamin A influx, efflux, and exchange. The Journal of membrane biology 70 22815070
2011 First implication of STRA6 mutations in isolated anophthalmia, microphthalmia, and coloboma: a new dimension to the STRA6 phenotype. Human mutation 66 21901792
2007 STRA6, a cell-surface receptor for retinol-binding protein: the plot thickens. Cell metabolism 65 17339024
2012 Transthyretin blocks retinol uptake and cell signaling by the holo-retinol-binding protein receptor STRA6. Molecular and cellular biology 58 22826435
2015 Vitamin A Transport Mechanism of the Multitransmembrane Cell-Surface Receptor STRA6. Membranes 52 26343735
2015 STRA6: role in cellular retinol uptake and efflux. Hepatobiliary surgery and nutrition 51 26312242
2014 Holo-retinol-binding protein and its receptor STRA6 drive oncogenic transformation. Cancer research 51 25237067
2016 Transport of vitamin A across blood-tissue barriers is facilitated by STRA6. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 49 27189978
2009 Acidic retinoids synergize with vitamin A to enhance retinol uptake and STRA6, LRAT, and CYP26B1 expression in neonatal lung. Journal of lipid research 44 19700416
2010 Case-control analysis of SNPs in GLUT4, RBP4 and STRA6: association of SNPs in STRA6 with type 2 diabetes in a South Indian population. PloS one 41 20625434
2009 Pulmonary hypoplasia-diaphragmatic hernia-anophthalmia-cardiac defect (PDAC) syndrome due to STRA6 mutations--what are the minimal criteria? American journal of medical genetics. Part A 36 19839040
2019 STRA6 exerts oncogenic role in gastric tumorigenesis by acting as a crucial target of miR-873. Journal of experimental & clinical cancer research : CR 35 31694721
2020 Retinol-Binding Protein 4 Activates STRA6, Provoking Pancreatic β-Cell Dysfunction in Type 2 Diabetes. Diabetes 34 33199363
2012 Mutation analysis of the STRA6 gene in isolated and non-isolated anophthalmia/microphthalmia. Clinical genetics 34 22686418
2014 Downregulation of STRA6 in adipocytes and adipose stromovascular fraction in obesity and effects of adipocyte-specific STRA6 knockdown in vivo. Molecular and cellular biology 31 24421389
2008 Identification of STRA6 and SKI sequence variants in patients with anophthalmia/microphthalmia. Molecular vision 30 19112531
2013 Stra6, a retinoic acid-responsive gene, participates in p53-induced apoptosis after DNA damage. Cell death and differentiation 29 23449393
2014 An alternative retinoic acid-responsive Stra6 promoter regulated in response to retinol deficiency. The Journal of biological chemistry 28 25544292
2013 To investigate the necessity of STRA6 upregulation in T cells during T cell immune responses. PloS one 28 24391722
2017 The retinol-binding protein receptor STRA6 regulates diurnal insulin responses. The Journal of biological chemistry 26 28733465
2016 Vitamin A Transport and Cell Signaling by the Retinol-Binding Protein Receptor STRA6. Sub-cellular biochemistry 26 27830501
2013 The retinol esterifying enzyme LRAT supports cell signaling by retinol-binding protein and its receptor STRA6. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 23 24036882
2013 Downregulation of STRA6 expression in epidermal keratinocytes leads to hyperproliferation-associated differentiation in both in vitro and in vivo skin models. The Journal of investigative dermatology 22 24284421
2021 Retinol from hepatic stellate cells via STRA6 induces lipogenesis on hepatocytes during fibrosis. Cell & bioscience 21 33407858
2024 RBP4 promotes denervation-induced muscle atrophy through STRA6-dependent pathway. Journal of cachexia, sarcopenia and muscle 20 39031684
2010 The expression of Stra6 and Rdh10 in the avian embryo and their contribution to the generation of retinoid signatures. The International journal of developmental biology 20 20563989
2021 A master of all trades - linking retinoids to different signalling pathways through the multi-purpose receptor STRA6. Cell death discovery 18 34785649
2020 Retinol and vitamin A metabolites accumulate through RBP4 and STRA6 changes in a psoriasis murine model. Nutrition & metabolism 17 31956331
2015 A novel mutation in two Hmong families broadens the range of STRA6-related malformations to include contractures and camptodactyly. American journal of medical genetics. Part A 17 26373900
2024 Glycolysis and tumor progression promoted by the m6A writer VIRMA via m6A-dependent upregulation of STRA6 in pancreatic ductal adenocarcinoma. Cancer letters 15 38604311
2022 The vitamin A transporter STRA6 adjusts the stoichiometry of chromophore and opsins in visual pigment synthesis and recycling. Human molecular genetics 15 34508587
2021 Augmentation of RBP4/STRA6 signaling leads to insulin resistance and inflammation and the plausible therapeutic role of vildagliptin and metformin. Molecular biology reports 15 34041677
2019 O-GlcNAcylation disrupts STRA6-retinol signals in kidneys of diabetes. Biochimica et biophysica acta. General subjects 15 30905621
2016 Electronegative low density lipoprotein induces renal apoptosis and fibrosis: STRA6 signaling involved. Journal of lipid research 14 27256691
2023 Genetic tuning of β-carotene oxygenase-1 activity rescues cone photoreceptor function in STRA6-deficient mice. Human molecular genetics 13 36150025
2012 A puzzle over several decades: eye anomalies with FRAS1 and STRA6 mutations in the same family. Clinical genetics 13 22283518
2016 Association of Polymorphisms in STRA6 and RARRES2 Genes with Type 2 Diabetes in Southern Han Chinese. BioMed research international 11 27446956
2021 Physiologically Relevant Free Ca2+ Ion Concentrations Regulate STRA6-Calmodulin Complex Formation via the BP2 Region of STRA6. Journal of molecular biology 10 34592217
2020 Plasma RBP4 Level in Association with Body Composition, Metabolic Profile, STRA6 and RBP4 Gene Polymorphisms in Obese Romanian Children. Diabetes, metabolic syndrome and obesity : targets and therapy 10 33273838
2020 STRA6 Polymorphisms Are Associated With EGFR Mutations in Locally-Advanced and Metastatic Non-Small Cell Lung Cancer Patients. Frontiers in oncology 9 33324556
2012 Oral vitamin A and retinoic acid supplementation stimulates antibody production and splenic Stra6 expression in tetanus toxoid-immunized mice. The Journal of nutrition 9 22739370
2023 STRA6 is essential for induction of vascular smooth muscle lineages in human embryonic cardiac outflow tract development. Cardiovascular research 8 36635482
2020 Overexpression of miR-455-5p affects retinol (vitamin A) absorption by downregulating STRA6 in a nitrofen-induced CDH with lung hypoplasia rat model. Pediatric pulmonology 8 32237270
2017 Both a frameshift and a missense mutation of the STRA6 gene observed in an infant with the Matthew-Wood syndrome. Birth defects research 8 28398665
2017 STRA6 as a possible candidate gene for pathogenesis of osteoporosis from RNA‑seq analysis of human mesenchymal stem cells. Molecular medicine reports 8 29067460
2024 ANLN Promotes the Proliferation and Migration of Gallbladder Cancer Cells via STRA6-Mediated Activation of PI3K/AKT Signaling. Cancers 7 38398143
2020 Expanding the phenotype of STRA6-related disorder to include left ventricular non-compaction. Molecular genetics & genomic medicine 6 32597569
2015 Production of functional human vitamin A transporter/RBP receptor (STRA6) for structure determination. PloS one 6 25816144
2024 Inhibition of STRA6 suppresses NSCLC growth via blocking STAT3/SREBP-1c axis-mediated lipogenesis. Molecular and cellular biochemistry 5 39168951
2019 Association of polymorphisms in STRA6 gene with gestational diabetes mellitus in a Chinese Han population. Medicine 5 30882700
2019 miR-455-5p Overexpression Reduces Rat Lung Alveolar Type II Cell Proliferation by Downregulating STRA6. Anatomical record (Hoboken, N.J. : 2007) 5 31087788
2014 Adaptive evolution of the STRA6 genes in mammalian. PloS one 5 25251323
2025 Targeting RBP4-STRA6 retinol signaling disrupts adipose-prostate crosstalk: A novel strategy to suppress basal cell plasticity in androgen deprivation. Metabolism: clinical and experimental 4 40340019
2024 Unraveling the mystery of ocular retinoid turnover: Insights from albino mice and the role of STRA6. The Journal of biological chemistry 4 38395306
2023 STRA6 Promotes Thyroid Carcinoma Progression via Activation of the ILK/AKT/mTOR Axis in Cells and Female Nude Mice. Endocrinology 4 36592123
2021 miR-363-3p inhibits rat lung alveolar type II cell proliferation by downregulating STRA6 expression and induces cell apoptosis via cellular oxidative stress and G1-phase cell cycle arrest. Translational pediatrics 4 34584880
2021 STRA6 and Placental Retinoid Metabolism in Gestational Diabetes Mellitus. Journal of personalized medicine 4 34945773
2020 Sample preparation for structural and functional analyses of the STRA6 receptor for retinol-binding protein. Methods in enzymology 4 32359662
2024 The Effects of STRA6 Regulation of the Circadian Rhythm on Choroidal Neovascularization. Investigative ophthalmology & visual science 3 39269368
2024 Identification of estrogen response-associated STRA6+ granulosa cells within high-grade serous ovarian carcinoma by single-cell sequencing. Heliyon 2 38509903
2019 1HN, 13C, and 15N resonance assignments of human calmodulin bound to a peptide derived from the STRA6 vitamin A transporter (CaMBP2). Biomolecular NMR assignments 2 30875027
2014 Crossing the barrier: STRA6 in epidermal differentiation. The Journal of investigative dermatology 2 24825059
2026 Beyond a gatekeeper: the non-classical signaling role of STRA6 in driving endothelial senescence and atherosclerosis. Frontiers in immunology 0 41782879
2025 Vitamin A deficiency attenuates cardiac rupture in Stra6-deficient hearts following ischemic injury. Frontiers in cardiovascular medicine 0 41035698
2025 ARNT2-driven transcriptional activation of STRA6 reprograms fatty acid metabolism to promote retroperitoneal liposarcoma progression. Journal of cancer research and clinical oncology 0 41108418
2025 The retinol-binding protein receptor STRA6 and melanin cooperatively sustain retinoid signaling and outer blood-retinal barrier integrity. The Journal of biological chemistry 0 41135684
2025 Aerobic exercise intervention improves angiotensin Ⅱ-induced cardiac remodeling by inhibiting RBP4-STRA6-Wnt/β-catenin pathway. Archives of biochemistry and biophysics 0 41205848
2025 1HN, 13C, and 15N resonance assignments of Ca2+-calmodulin bound to a BP2 peptide derived from the sheep STRA6 vitamin A transporter (residues 625-656). Biomolecular NMR assignments 0 41413324
2025 Correction: STRA6 polymorphisms are associated with EGFR mutations in locally-advanced and metastatic non-small cell lung cancer patients. Frontiers in oncology 0 41487564