Affinage

STRA6

Receptor for retinol uptake STRA6 · UniProt Q9BX79

Length
667 aa
Mass
73.5 kDa
Annotated
2026-06-10
82 papers in source corpus 33 papers cited in narrative 33 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

STRA6 is a polytopic plasma-membrane protein that serves as the cell-surface receptor for circulating holo-retinol-binding protein (RBP4) and catalyzes facilitated, bidirectional retinol transport across blood-tissue barriers, coupling vitamin A homeostasis to retinoic acid signaling (PMID:18316031, PMID:22815070, PMID:24852372). Cryo-EM of zebrafish STRA6 established a homodimer of protomers each containing nine transmembrane and one intramembrane helix, with an arch-like RBP-binding surface covering a deep lipophilic cleft open to the bilayer, supporting retinol internalization by diffusion into the membrane; calmodulin is tightly bound in a noncanonical arrangement (PMID:27563101), an interaction mediated by the intracellular BP2 helix in a Ca2+-dependent manner (PMID:34592217). Directionality is set by intracellular acceptors: influx from holo-RBP requires coupling to CRBP-I or to lecithin:retinol acyltransferase (LRAT)-driven esterification, while apo-RBP drives efflux of free retinol (PMID:22815070, PMID:23959802). Beyond transport, STRA6 functions as a ligand-activated cytokine receptor whose phosphorylation and JAK2/STAT3/STAT5 signaling are triggered specifically by retinol translocation into CRBP-I, making transport and signaling interdependent (PMID:22665496, PMID:25237067). This signaling arm couples circulating RBP4 to insulin action and is suppressed by transthyretin, which blocks holo-RBP association with STRA6 (PMID:22826435, PMID:24036882, PMID:23839944). STRA6 transcription is directly RA-inducible through a RARE bound by RARγ/RXRα with accompanying p300/H3K27ac changes (PMID:25544292). The transporter is essential for ocular vitamin A uptake, visual chromophore/opsin stoichiometry, and outer blood-retinal barrier integrity, and for retinoid supply to brain and testis under dietary limitation (PMID:24852372, PMID:34508587, PMID:27189978, PMID:41135684). Loss-of-function STRA6 mutations cause colobomatous microphthalmia, with mislocalizing mutants showing abolished uptake activity (PMID:17273977, PMID:21901792). STRA6-dependent RA signaling additionally drives vascular smooth muscle lineage induction during cardiogenesis via an RARα/RXRα–TBX1 interaction (PMID:36635482), and its JAK/STAT and ILK/AKT-mTOR outputs promote proliferation, lipogenesis, and survival across multiple cancers (PMID:28689994, PMID:36592123, PMID:23449393).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1997 Medium

    Established STRA6 as a novel hydrophobic membrane protein concentrated at blood-organ barriers and under retinoid-receptor control, framing it as candidate retinoid transport machinery.

    Evidence Subtractive hybridization cloning and in situ hybridization in RAR-alpha null mice

    PMID:9203140

    Open questions at the time
    • No biochemical transport activity demonstrated
    • No direct ligand or partner identified
  2. 2001 Low

    Linked Stra6 expression to combined Wnt and RA inputs, hinting at transcriptional integration of developmental signals at the STRA6 locus.

    Evidence mRNA screening in Wnt-1-stimulated mammary cells and RA-treated colorectal lines

    PMID:11358845

    Open questions at the time
    • Correlative expression only; no mechanism of Wnt-RA synergy reconstituted
    • STRA6 protein function not addressed
  3. 2007 Medium

    Tied STRA6 loss-of-function to human disease and pinpointed functional residues, establishing topology-critical loop and C-terminal signaling motifs.

    Evidence Homozygosity mapping, mutational analysis, and topology modeling in patients

    PMID:17273977

    Open questions at the time
    • No in vitro reconstitution of mutant transport defects
    • SH2/phospho-motif function inferred from sequence, not assayed
  4. 2008 High

    Demonstrated that STRA6 mediates bidirectional retinol transfer from RBP4 into cells, enhanced by LRAT, and is required for vitamin A delivery to the developing eye.

    Evidence Cell-based retinol transfer assays with LRAT and zebrafish morpholino knockdown

    PMID:18316031

    Open questions at the time
    • Mechanism of coupling to intracellular acceptors not yet resolved
    • Signaling function not addressed
  5. 2012 High

    Reconstituted STRA6 catalytic logic and showed transport and signaling are interdependent: retinol translocation to CRBP-I, not mere holo-RBP binding, triggers STRA6 phosphorylation and JAK/STAT signaling, and phosphorylation is required for uptake.

    Evidence In vitro transport assays with purified components, phosphorylation-deficient mutants, CRBP-I coupling, and TTR competition assays with mouse insulin-resistance models

    PMID:22665496 PMID:22815070 PMID:22826435

    Open questions at the time
    • Identity of the kinase phosphorylating STRA6 not defined
    • Structural basis of signaling-competent state unknown
  6. 2013 High

    Defined STRA6's primary systemic role as coupling circulating holo-RBP to JAK/STAT signaling that suppresses insulin action, with retinol delivery dispensable outside the eye, and showed LRAT-dependent esterification drives the inward transport that activates signaling.

    Evidence Stra6-null and LRAT-null mouse models, HPLC retinoid quantification, JAK2/STAT5 assays, glucose tolerance tests; adipocyte differentiation and oncogenic transformation/xenograft assays

    PMID:23839944 PMID:23959802 PMID:24036882 PMID:25237067

    Open questions at the time
    • Why eye retinoid homeostasis is uniquely STRA6-dependent unexplained at this stage
    • Tissue-specific signaling outputs not fully mapped
  7. 2013 Medium

    Identified a retinoid-independent, p53-driven pro-apoptotic role for STRA6 acting via mitochondrial depolarization and ROS, broadening its function beyond retinoid transport/signaling.

    Evidence DNA damage and p53-dependent transcription assays, ROS and mitochondrial membrane potential measurements with Stra6 knockdown

    PMID:23449393

    Open questions at the time
    • Molecular mechanism linking STRA6 to mitochondria undefined
    • How a plasma-membrane transporter drives ROS unclear
  8. 2014 High

    Cemented STRA6 as a bona fide ocular vitamin A transporter and dissected the RA-responsive promoter, showing knockout causes RPE/choroid malformation and cone death, and that an endogenous RARE bound by RARγ/RXRα controls its RA-induced transcription.

    Evidence Stra6-knockout mice (HPLC, ERG, histology, rescue), G304K mislocalization assays, zebrafish RA-inhibition models, CRISPR editing of the RARE plus ChIP-seq

    PMID:21901792 PMID:24852372 PMID:25544292

    Open questions at the time
    • Mechanism of STRA6 trafficking to the membrane not detailed
    • Cone-specific vulnerability mechanism unresolved
  9. 2016 High

    Provided the structural foundation—a homodimer with a lipophilic cleft open to the membrane and tightly bound calmodulin—rationalizing retinol release into the bilayer and RBP docking, and confirmed STRA6's barrier role in eye, brain, and testis.

    Evidence 3.9 Å cryo-EM of zebrafish STRA6 with RBP-binding residue mapping; Stra6-knockout mice under dietary vitamin A control with multi-tissue retinoid quantification

    PMID:27189978 PMID:27563101

    Open questions at the time
    • Conformational cycle of transport not captured
    • Functional role of bound calmodulin not established structurally
  10. 2017 Medium

    Extended STRA6 signaling to metabolic and oncogenic contexts—β-cell insulin synthesis via JAK2/STAT1/ISL-1, circadian insulin action via REV-ERBα, and colon cancer stem cell maintenance via JAK2/STAT3.

    Evidence Islet/INS-1E and RBP4-transgenic models, adipose-specific Stra6 knockout with circadian profiling, colon cancer knockdown with sphere/tumor-initiation assays

    PMID:28689994 PMID:28733465 PMID:33199363

    Open questions at the time
    • Tissue specificity of STAT effector usage unexplained
    • Direct connection of circadian regulation to transport vs signaling unclear
  11. 2021 Medium

    Resolved how calmodulin engages STRA6—via the BP2 helix in a Ca2+-tunable bilobal manner—and showed STRA6-mediated retinol transfer between hepatic stellate cells and hepatocytes drives fibrogenic lipogenesis.

    Evidence NMR/ITC/kinetic analysis of BP2-calmodulin binding; STRA6 knockdown in vitro and in vivo fibrosis models with TIF1γ manipulation

    PMID:33407858 PMID:34592217

    Open questions at the time
    • Functional effect of Ca2+-calmodulin on transport not directly demonstrated
    • How interorgan retinol shuttling is triggered in fibrosis unresolved
  12. 2022 High

    Showed STRA6 controls chromophore/opsin stoichiometry in photoreceptors and replenishes retinoids lost to visual-cycle side reactions, explaining the differential rod versus cone dependence on vitamin A.

    Evidence Stra6-knockout mice with retinoid quantification, opsin expression/immunolocalization, light-bleaching, and vitamin A rescue

    PMID:34508587 PMID:38395306

    Open questions at the time
    • Why cone phenotype resists vitamin A supplementation unexplained
    • Quantitative flux of byproduct recycling not defined
  13. 2023 Medium

    Established STRA6 as required for vascular smooth muscle lineage induction from human cardiac progenitors, acting through an RARα/RXRα–TBX1 transcriptional interaction.

    Evidence STRA6-knockout hESC differentiation, RNA-seq, RARα/RXRα-TBX1 Co-IP, cross-species scRNA-seq

    PMID:36635482

    Open questions at the time
    • Direct transcriptional targets of the RAR-TBX1 complex not enumerated
    • Whether transport or signaling activity is the relevant STRA6 function not distinguished
  14. 2024 Medium

    Expanded STRA6's disease roles—RBP4/STRA6/JAK2/STAT3-driven muscle atrophy, ILK/AKT-mTOR/SREBP1 signaling in thyroid carcinoma, and m6A-mediated (VIRMA/IGF2BP2) STRA6 mRNA stabilization driving glycolysis in pancreatic cancer.

    Evidence C2C12/RBP4-knockout and denervation models; STRA6-ILK Co-IP with knockdown/xenograft; m6A-seq, RIP-seq, and mRNA stability assays in PDAC

    PMID:36592123 PMID:38604311 PMID:39031684

    Open questions at the time
    • Whether ILK binding is direct and how it relates to JAK/STAT arm unclear
    • Generalizability of STRA6-driven lipogenesis across tumor types untested
  15. 2025 High

    Mechanistically linked STRA6 loss to outer blood-retinal barrier failure via impaired retinoid signaling, showing RAR agonist rescues tight-junction gene expression and barrier function.

    Evidence Albino Stra6-knockout mice with retinoid quantification, tight-junction protein analysis, ERG, and TTNPB pharmacological rescue

    PMID:41135684

    Open questions at the time
    • Synergy mechanism between melanin and STRA6 not molecularly defined
    • Which RA-target genes directly maintain junctions not pinpointed

Open questions

Synthesis pass · forward-looking unresolved questions
  • How STRA6 mechanically couples retinol translocation to its phosphorylation-dependent switch into a JAK/STAT-competent receptor—and what role bound calmodulin plays in gating transport—remains unresolved.
  • No structure of a signaling-active or substrate-bound human STRA6 conformer
  • Functional consequence of Ca2+-calmodulin binding on transport untested
  • Kinase responsible for STRA6 phosphorylation unidentified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 4 GO:0001618 virus receptor activity 3 GO:0060089 molecular transducer activity 2 GO:0140104 molecular carrier activity 2 GO:0008289 lipid binding 1
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-382551 Transport of small molecules 3 R-HSA-9709957 Sensory Perception 3 R-HSA-1266738 Developmental Biology 2 R-HSA-74160 Gene expression (Transcription) 1
Partners
CALM1CRBP1IGF2BP2ILKJAK2LRATRBP4TTR

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 STRA6 was identified as a novel multi-transmembrane integral membrane protein. Structural analysis of missense mutations (P90L, P293L, T321P) suggested significant effects on the geometry of loops connecting transmembrane helices. Two C-terminal variations (T644M and R655C) alter an SH2-binding motif and a phosphorylation site, respectively, indicating these are functional sites. Homozygosity mapping, mutational analysis, structural modeling of transmembrane topology American journal of human genetics Medium 17273977
1997 STRA6 encodes a highly hydrophobic membrane protein of a new type with no similarity to previously characterized integral membrane proteins. It is strongly expressed at blood-organ barriers (e.g., blood-testis barrier in Sertoli cells) with a spermatogenic cycle-dependent expression that is lost in RAR-alpha null mutants, suggesting it is a component of a retinoid transport machinery. Subtractive hybridization cDNA cloning, in situ hybridization, analysis of RAR-alpha null mutants Mechanisms of development Medium 9203140
2008 STRA6-dependent transfer of retinol from RBP4 into NIH 3T3 fibroblasts was enhanced by lecithin:retinol acyltransferase (LRAT). Retinol transfer was shown to be bidirectional, establishing that STRA6 acts as a retinol channel/transporter. Loss-of-function in zebrafish revealed that Stra6 deficiency caused vitamin A deprivation of developing eyes. In the absence of Stra6, holo-Rbp4 provoked non-specific vitamin A excess in embryonic tissues, impairing retinoic acid receptor signaling. Cell-based retinol transfer assay with LRAT co-expression, zebrafish morpholino knockdown, pharmacological and morpholino RBP4 reduction Cell metabolism High 18316031
2012 STRA6 functions as both a retinol transporter and a cytokine receptor. Activation of STRA6 signaling (JAK/STAT cascade) is triggered not simply by holo-RBP binding but by STRA6-mediated translocation of retinol from serum RBP to the intracellular acceptor CRBP-I. STRA6 phosphorylation is required for retinol uptake to proceed, demonstrating that signaling and transport are critically interdependent. Phosphorylation assays, CRBP-I interaction studies, retinol uptake assays with phosphorylation-deficient STRA6 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 cell signaling. TTR protects mice from RBP-induced insulin resistance. STRA6 functions only when plasma RBP levels exceed TTR levels. Cell-based retinol uptake assay, JAK/STAT signaling assays, glucose tolerance tests in mice with TTR manipulation Molecular and cellular biology High 22826435
2012 STRA6 catalyzes bidirectional retinol transport: (1) influx — retinol release from holo-RBP coupled to CRBP-I or LRAT; (2) efflux — loading of free retinol into apo-RBP, driven by CRBP-I. Holo-RBP blocks STRA6-mediated efflux by competing with apo-RBP binding. STRA6 also catalyzes efficient retinol exchange between intracellular CRBP-I and extracellular RBP. In vitro retinol transport assays with purified components, competition binding assays The Journal of membrane biology High 22815070
2013 Lecithin:retinol acyl transferase (LRAT), which esterifies retinol to retinyl esters, is necessary for activation of the STRA6/JAK2/STAT5 signaling cascade by holo-RBP. LRAT-null mice are protected from holo-RBP-induced suppression of insulin responses, establishing that STRA6 signaling requires retinol esterification to drive inward transport. LRAT-null mouse model, JAK2/STAT5 phosphorylation assays, insulin response measurements FASEB journal High 24036882
2013 STRA6 functions as a cytokine receptor activating JAK2 and the transcription factors STAT3 and STAT5 upon holo-RBP binding. This signaling promotes oncogenic transformation and is critical for tumor formation by colon carcinoma cells in vivo. JAK2/STAT3/STAT5 phosphorylation assays, oncogenic transformation assay in fibroblasts, xenograft mouse model with STRA6 knockdown Cancer research Medium 25237067
2013 STRA6 mediates bidirectional retinol transport in adipocyte precursors: holo-RBP4 triggers retinol influx and blocks adipocyte differentiation by activating RARα, while apo-RBP4 triggers retinol efflux, reducing cellular retinoids and RARα activity, thereby enhancing adipogenesis. Ectopic STRA6 synergized with apo-RBP4 to enhance adipogenesis. Cell-based retinol efflux/influx assays, RARα reporter assays, adipocyte differentiation assays, mouse liver RBP4 mobilization experiment Molecular and cellular biology High 23959802
2013 STRA6 is essential for RBP-induced suppression of insulin signaling in vivo; Stra6-null mice are protected from RBP-induced insulin resistance. However, with the exception of the eye, ablation of Stra6 had only a modest effect on retinoid homeostasis in other tissues, demonstrating that STRA6's primary systemic function (outside the eye) is coupling circulating holo-RBP to JAK/STAT cell signaling rather than retinol delivery. Stra6-null mouse model, retinoid quantification by HPLC, insulin signaling assays, glucose tolerance tests The Journal of biological chemistry High 23839944
2013 Stra6 can be upregulated by DNA damage in a p53-dependent manner and plays a role in p53-induced apoptosis. Stra6 expression induced mitochondrial depolarization and accumulation of reactive oxygen species; inhibition of Stra6 compromised p53-induced apoptosis. These functions did not require downstream activation of retinoic acid signaling. DNA damage assays, p53-dependent transcriptional analysis, apoptosis assays, ROS measurement, mitochondrial membrane potential assay, 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 show markedly reduced ocular retinoids, malformations in the choroid and RPE, early cone photoreceptor cell death, and reduced rod outer segment length. STRA6-mediated uptake in the eye is a regulated process mandatory when RBP4 is the only transport mode. Vitamin A transport through the blood-CSF barrier in the choroid plexus was also impaired. Stra6-knockout mouse model, HPLC retinoid quantification, ophthalmic imaging, histology, electroretinography, pharmacological vitamin A rescue Human molecular genetics High 24852372
2014 The STRA6 G304K mutant protein is mislocalized and has severely reduced vitamin A uptake activity, establishing that membrane localization is required for STRA6 function. Inhibiting retinoic acid synthesis in zebrafish reproduced the colobomatous microanophthalmia phenotype, confirming diminished RA levels underlie the eye malformations. STRA6 G304K mutant expression and localization analysis, retinol uptake assay, zebrafish RA synthesis inhibition model Human mutation Medium 21901792
2016 Cryo-EM structure of zebrafish STRA6 determined at 3.9 Å resolution revealed: (1) STRA6 has one intramembrane and nine transmembrane helices in a homodimeric assembly; (2) calmodulin is tightly bound to STRA6 in a noncanonical arrangement; (3) residues involved in RBP binding map to an arch-like structure covering a deep lipophilic cleft; (4) the cleft is open to the membrane, suggesting retinol internalization via direct diffusion into the lipid bilayer. Single-particle cryo-electron microscopy at 3.9 Å resolution Science High 27563101
2016 STRA6 is critical for vitamin A transport across blood-tissue barriers in the eyes, brain, and testis. In Stra6-knockout mice under vitamin A-deficient conditions, retinoid homeostasis in the eye, brain, and testis (but not in fat or lung) was severely impaired. Stra6 expression in testis and brain was regulated by vitamin A supply, reducing consumption when dietary supply was limited. Stra6-knockout mouse model with controlled dietary vitamin A, retinoid quantification in multiple tissues, retinoid-dependent physiological assays FASEB journal High 27189978
2017 STRA6 mediates the inhibitory effect of RBP4 on insulin synthesis in pancreatic β-cells through the JAK2/STAT1/ISL-1 signaling pathway. STRA6 is expressed in β-cells and its activation by RBP4 suppresses glucose-stimulated insulin secretion. Primary islet isolation, INS-1E cell culture, RBP4 transgenic mouse model, JAK2/STAT1/ISL-1 pathway analysis, siRNA knockdown of STRA6 Diabetes Medium 33199363
2017 STRA6 activates JAK2-STAT3 signaling to promote colon cancer stem cell maintenance. Downregulation of STRA6 or RBP4 decreased cancer stem cell fraction and sphere and tumor initiation frequency. High-fat diet increased STRA6 levels and promoted tumor growth. STRA6 knockdown in colon cancer cells, sphere formation assay, xenograft tumor initiation assay, JAK2-STAT3 signaling analysis Stem cell reports Medium 28689994
2017 Adipose tissue STRA6 undergoes circadian patterning 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. Circadian expression analysis of STRA6, REV-ERBα manipulation, adipose-specific STRA6 knockout mouse, insulin action and JAK/STAT signaling assays at different circadian time points The Journal of biological chemistry Medium 28733465
2021 Ca2+-calmodulin binding to STRA6 is mediated via the BP2 intracellular helix region. At resting intracellular Ca2+ levels (<100 nM), BP2 binds only the C-lobe of calmodulin. As Ca2+ approaches 1000 nM (signaling levels), BP2 interacts with both N- and C-lobes of Ca2+-loaded calmodulin. BP2 binding increases Ca2+-binding affinity of calmodulin and slows Ca2+ dissociation rates in both lobes. NMR chemical shift perturbation mapping, isothermal titration calorimetry, kinetic Ca2+ binding studies with BP2 peptide derived from STRA6 Journal of molecular biology High 34592217
2019 O-GlcNAcylation of STRA6 in diabetic kidneys significantly modifies STRA6, suppresses RBP4 binding activity, and disrupts retinol signals (CRBP1, LRAT, retinol, retinoic acid, RARs). Blocking O-GlcNAcylation with OSMI-1 or OGA overexpression restored STRA6 function and retinol signals. Co-immunoprecipitation, proximity ligation assay, Western blot, HPLC retinoid measurement, OGT/OGA siRNA, TMG/OSMI-1 pharmacological manipulation in db/db and ob/ob mice and HK-2 cells Biochimica et biophysica acta. General subjects Medium 30905621
2021 STRA6 mediates retinol transfer from hepatic stellate cells (HSCs) to hepatocytes during liver fibrosis. TIF1γ suppression in HSCs upregulates STRA6 and promotes retinol release; hepatocytes take up retinol via STRA6, leading to lipogenesis (upregulation of lipogenesis-related genes and triglyceride accumulation). STRA6 knockdown in vivo reduced liver fibrosis. siRNA knockdown of STRA6 in LX2 cells, HepG2 retinol uptake assay, RAR antagonist, in vivo siSTRA6 treatment in TAA fibrosis model, Lrat:Cas9-ERT2:sgTif1γ mice Cell & bioscience Medium 33407858
2023 STRA6 is essential for proper induction of vascular smooth muscle cell (SMC) lineages from human cardiac progenitors. STRA6-knockout hESCs could differentiate into cardiomyocytes normally but failed to differentiate into mesodermal- or neural crest-derived SMCs. A previously unrecognized interaction between RA nuclear receptors RARα/RXRα and TBX1 (an OFT-specific transcription factor) was identified as a downstream effector of STRA6-mediated RA signaling. STRA6-knockout hESC differentiation assays, population RNA-seq, co-immunoprecipitation of RARα/RXRα with TBX1, single-cell RNA-seq comparison of human and murine embryonic hearts Cardiovascular research Medium 36635482
2022 STRA6 is critical for adjusting the stoichiometry of chromophore and opsins in rod and cone photoreceptors. In STRA6-deficient mice, decreased chromophore led to downregulation of opsin genes in rods and absent/mislocalized opsins in cones. Rod photoreceptors entrapped available chromophore but showed significant amounts of chromophore-free opsins. Vitamin A supplementation ameliorated rod but not cone phenotype. Stra6-knockout mouse model, retinoid quantification, opsin gene expression analysis, immunolocalization of opsins, electroretinography, pharmacological vitamin A rescue Human molecular genetics High 34508587
2024 RBP4 promotes muscle atrophy through a STRA6-dependent JAK2/STAT3 pathway. Holo-RBP4 upregulated STRA6 expression (>3-fold) and promoted phosphorylation of JAK2 and STAT3. Inhibition of STRA6, JAK2, or STAT3 by siRNA or inhibitors decreased expression of atrophy markers Atrogin-1 and MuRF1, and decreased expression of myogenesis regulators MyoD and MyoG in holo-RBP4-treated C2C12 myotubes. siRNA knockdown of STRA6/JAK2/STAT3, specific signaling inhibitors, C2C12 myotube assays, RBP4-knockout mouse model, denervation-induced atrophy model, intramuscular injection of holo-RBP4 Journal of cachexia, sarcopenia and muscle Medium 39031684
2024 STRA6 interacts with integrin-linked kinase (ILK) and subsequently activates the AKT/mTOR signaling pathway in thyroid carcinoma, promoting cell proliferation and metastasis. STRA6 also reprograms lipid metabolism through SREBP1 downstream of this axis. Co-immunoprecipitation of STRA6 with ILK, RNA sequencing, STRA6 stable knockdown, in vitro proliferation/metastasis assays, xenograft model, LNP-siRNA delivery Endocrinology Medium 36592123
2024 STRA6 mRNA stability is regulated by m6A modification: VIRMA (an m6A methyltransferase) targets the 3' UTR of STRA6 mRNA, and the m6A reader IGF2BP2 stabilizes STRA6 mRNA. VIRMA-driven STRA6 upregulation promotes STAT3 activation and HIF-1α-dependent glycolysis in pancreatic ductal adenocarcinoma. m6A sequencing, RNA sequencing, RIP-seq, mRNA stability assays, IGF2BP2 interaction studies, in vitro and in vivo PDAC models Cancer letters Medium 38604311
2014 STRA6 promotes Wnt/β-catenin signaling in gastric cancer. STRA6 knockdown inhibited the Wnt/β-catenin signaling pathway. STRA6 was confirmed as a direct target of miR-873, which suppresses GC tumor progression. STRA6 knockdown, Wnt/β-catenin pathway reporter assays, dual-luciferase reporter assay confirming miR-873 targeting of STRA6, rescue assays Journal of experimental & clinical cancer research Low 31694721
2015 Purified recombinant STRA6 interacts with RBP in a retinol-independent manner as determined by surface plasmon resonance, with binding data consistent with a transient interaction of 1 mole RBP per mole STRA6. Surface plasmon resonance-based binding analysis of purified STRA6-GFP produced in Pichia pastoris PloS one Medium 25816144
2020 STRA6 promotes NSCLC cell growth by activating JAK2/STAT3 signaling, which induces STAT3 target gene SREBP-1c expression, thereby promoting SREBP-1-mediated lipogenesis and providing energy for cancer cell growth. STRA6 knockdown in NSCLC cell lines and mouse xenograft, STAT3/SREBP-1 pathway analysis, lipid metabolism assays Molecular and cellular biochemistry Low 39168951
2025 STRA6 and melanin act synergistically to preserve the integrity of the outer blood-retinal barrier (oBRB). In albino Stra6-knockout mice, dietary vitamin A via chylomicrons failed to compensate for the loss of RBP4-mediated transport, leading to functional impairment of rod and cone responses and downregulation of tight junction proteins (ZO-1, Claudin-1, Claudin-3). Treatment with the pan-RAR agonist TTNPB restored junctional gene expression and oBRB function, demonstrating that barrier failure arises from impaired retinoid signaling. Albino Stra6-knockout mouse model, retinoid quantification, tight junction protein Western blot and immunofluorescence, electroretinography, TTNPB pharmacological rescue The Journal of biological chemistry High 41135684
2024 In STRA6-deficient mice, light-induced loss of ocular retinoids and visual impairment were correlated with generation of visual cycle byproducts (9-cis-retinal, 13-cis-retinal). 9-cis-retinal was recycled to all-trans-retinal via isorhodopsin. The absence of STRA6 impaired replenishment of retinoids lost through these chemical side reactions. Stra6-knockout mouse model, light bleaching experiments, HPLC retinoid quantification, rhodopsin spectrophotometry, electroretinography The Journal of biological chemistry Medium 38395306
2014 An alternative downstream promoter of Stra6 contains a half-site RA response element (RARE) required for RA-induced transcription. CRISPR-Cas9 editing of the endogenous RARE abolished RA-induced transcription of both Stra6 isoforms. RARγ and RXRα bind the Stra6 RARE; RA increases co-activator p300 binding and H3K27 acetylation while decreasing Suz12 and H3K27 trimethylation at both promoters, and these epigenetic changes depend on RARγ. CRISPR-Cas9 genome editing of endogenous RARE, ChIP-seq for RARγ/RXRα/p300/Suz12, luciferase reporter assay, analysis of RARγ-null mice and vitamin A-deficient mice The Journal of biological chemistry High 25544292
2001 Stra6 is synergistically induced by Wnt-1 signaling and retinoic acid in mammary cells. Wnt-1 upregulates retinoic acid receptor-gamma (RAR-gamma), which partly explains this synergy. Treatment of human colorectal cancer cell lines with retinoic acid led to accumulation of Stra6 protein at the cell membrane. mRNA screening of Wnt-1-stimulated C57MG cells, retinoic acid treatment of colorectal cancer cell lines, RAR-gamma upregulation analysis Cancer research Low 11358845

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 167 9203140
2008 RBP4 disrupts vitamin A uptake homeostasis in a STRA6-deficient animal model for Matthew-Wood syndrome. Cell metabolism 155 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.) 117 27563101
2014 STRA6 is critical for cellular vitamin A uptake and homeostasis. Human molecular genetics 116 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 90 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 53 26343735
2015 STRA6: role in cellular retinol uptake and efflux. Hepatobiliary surgery and nutrition 52 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
2020 Retinol-Binding Protein 4 Activates STRA6, Provoking Pancreatic β-Cell Dysfunction in Type 2 Diabetes. Diabetes 35 33199363
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
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
2014 An alternative retinoic acid-responsive Stra6 promoter regulated in response to retinol deficiency. The Journal of biological chemistry 29 25544292
2013 Stra6, a retinoic acid-responsive gene, participates in p53-induced apoptosis after DNA damage. Cell death and differentiation 29 23449393
2013 To investigate the necessity of STRA6 upregulation in T cells during T cell immune responses. PloS one 28 24391722
2016 Vitamin A Transport and Cell Signaling by the Retinol-Binding Protein Receptor STRA6. Sub-cellular biochemistry 27 27830501
2017 The retinol-binding protein receptor STRA6 regulates diurnal insulin responses. The Journal of biological chemistry 26 28733465
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 16 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
2023 STRA6 is essential for induction of vascular smooth muscle lineages in human embryonic cardiac outflow tract development. Cardiovascular research 10 36635482
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
2012 Oral vitamin A and retinoic acid supplementation stimulates antibody production and splenic Stra6 expression in tetanus toxoid-immunized mice. The Journal of nutrition 10 22739370
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 9 32237270
2020 STRA6 Polymorphisms Are Associated With EGFR Mutations in Locally-Advanced and Metastatic Non-Small Cell Lung Cancer Patients. Frontiers in oncology 9 33324556
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
2015 Production of functional human vitamin A transporter/RBP receptor (STRA6) for structure determination. PloS one 7 25816144
2020 Expanding the phenotype of STRA6-related disorder to include left ventricular non-compaction. Molecular genetics & genomic medicine 6 32597569
2019 miR-455-5p Overexpression Reduces Rat Lung Alveolar Type II Cell Proliferation by Downregulating STRA6. Anatomical record (Hoboken, N.J. : 2007) 6 31087788
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
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

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