Affinage

SCAP

SH2 domain-containing protein 2A · UniProt Q9NP31

Length
389 aa
Mass
42.9 kDa
Annotated
2026-06-10
100 papers in source corpus 46 papers cited in narrative 46 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SCAP is an octahelical ER membrane protein that serves as the cell's principal cholesterol sensor and the escort that controls activation of the SREBP family of lipogenic transcription factors (PMID:15260976, PMID:11358865). In sterol-depleted cells SCAP packages SREBP into COPII-coated vesicles via the MELADL sorting signal in a cytosolic loop, driving ER-to-Golgi transport where SREBPs are proteolytically processed to their active nuclear forms (PMID:12193656, PMID:15899885). Cholesterol binds directly and specifically to SCAP's membrane domain, with the 245-residue luminal Loop 1 constituting the cholesterol-binding site, and binding is transmitted through an intertwined Loop 1–Loop 7 luminal platform and the sterol-sensing domain to reposition cytosolic Loop 6, abrogating COPII recruitment (PMID:15260976, PMID:21454655, PMID:23564452, PMID:34139175). Sterol loading triggers SCAP binding to the ER-resident retention proteins INSIG-1 and INSIG-2, which captures the complex in the ER; oxysterols such as 25-hydroxycholesterol instead bind at the SCAP–INSIG interface, as resolved by cryo-EM of the SCAP/INSIG-2 complex (PMID:12202038, PMID:12242332, PMID:15452130, PMID:33446483). Point mutations in the sterol-sensing domain (Y298C, D443N, L315F) lock SCAP in a sterol-resistant, constitutively exporting state, and a transgenic SCAP(D443N) liver produces unrestrained lipogenesis and fatty liver, establishing SCAP as the in vivo rate-limiting sensor for hepatic cholesterol and fatty-acid synthesis (PMID:9789003, PMID:12482938, PMID:9854040, PMID:11358865). SCAP activity is further tuned by post-translational and trafficking inputs—N-glycosylation downstream of growth-factor/glucose signaling stabilizes SCAP and reduces INSIG association, and ubiquitination, S-acylation, and accessory factors modulate its stability and export (PMID:26555173, PMID:29068315, PMID:32054686, PMID:39522165, PMID:30858281). Beyond lipid metabolism, SCAP scaffolds innate-immune signaling, recruiting IRF3 to the STING signalosome through its cytosolic WD40 domain and coordinating STING/TBK1-driven NF-κB activation at the Golgi (PMID:26900919, PMID:35367665).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1998 High

    Established that specific residues in SCAP constitute a functional sterol sensor, by showing point mutations that uncouple SREBP processing from sterol levels.

    Evidence CHO sterol-resistant mutant cells (Y298C, D443N) with endoglycosidase H sensitivity and SREBP processing assays

    PMID:9789003

    Open questions at the time
    • Did not identify the retention factor that wild-type SCAP engages
    • Mechanism of cholesterol detection not defined
  2. 1998 High

    Demonstrated in vivo that the SCAP sterol sensor governs whole-organism lipogenesis, by expressing a sterol-resistant mutant in liver.

    Evidence Transgenic mice with liver-specific SCAP(D443N), dietary cholesterol challenge, nuclear SREBP and lipid analysis

    PMID:9854040

    Open questions at the time
    • Did not resolve the molecular retention mechanism
    • Loss-of-function in vivo not yet tested
  3. 1999 High

    Showed that sterol regulation operates at the level of SCAP trafficking between ER and Golgi, defining the transport step as the regulated event.

    Evidence Glycosidase sensitivity, glycosylation-defective mutants, density fractionation, brefeldin A in cells

    PMID:10500160

    Open questions at the time
    • Retention protein not identified
    • Vesicle machinery for export not defined
  4. 2001 High

    Established SCAP as physiologically required for hepatic lipid synthesis using conditional loss-of-function.

    Evidence Inducible Cre-mediated hepatic Scap knockout in mice with mRNA and lipid synthesis readouts

    PMID:11358865

    Open questions at the time
    • Did not address SCAP roles outside liver
    • Molecular sensing mechanism not addressed
  5. 2002 High

    Identified INSIG-1 and INSIG-2 as the sterol-regulated ER retention proteins that bind SCAP's sterol-sensing domain, resolving how sterols halt SREBP export.

    Evidence Reciprocal co-IP, mass spectrometry, blue native-PAGE, SREBP processing assays, mutant SCAP(Y298C)

    PMID:12202038 PMID:12242332

    Open questions at the time
    • Whether cholesterol acts directly on SCAP or via membrane not resolved
    • Structural basis of binding unknown
  6. 2002 High

    Connected the molecular events by showing sterols induce a SCAP conformational change and block COPII (Sec23/24) incorporation, with sterol-resistant mutants refractory.

    Evidence In vitro trypsin conformational assay on ER membranes, in vitro vesicle reconstitution with recombinant COPII, mutant analysis

    PMID:12191470 PMID:12193656 PMID:12482938

    Open questions at the time
    • Direct ligand binding not yet demonstrated
    • Sorting signal recognized by COPII not mapped
  7. 2003 High

    Defined the minimal sterol-regulated transport module and showed INSIG sensitizes the SCAP conformational switch, refining how the sensor reads membrane composition.

    Evidence Heterologous reconstitution in Drosophila cells; in vitro conformational assay with INSIG co-expression and cationic amphiphiles

    PMID:12842885 PMID:12963821

    Open questions at the time
    • Direct cholesterol receptor activity not yet proven
    • 25-HC mechanism distinct from cholesterol unresolved
  8. 2004 High

    Proved SCAP is a direct cholesterol receptor and distinguished cholesterol (direct binding) from 25-HC (indirect) as separate regulatory inputs.

    Evidence Purified recombinant SCAP membrane domain direct binding, photoaffinity cross-linking, analytical ultracentrifugation, INSIG co-IP

    PMID:15260976 PMID:15452130

    Open questions at the time
    • Precise cholesterol-binding subdomain not localized
    • How conformational change reaches the sorting signal unknown
  9. 2005 High

    Mapped the MELADL hexapeptide as the COPII sorting signal and defined Asp-428 as essential for sterol-dependent INSIG dissociation.

    Evidence In vitro microsomal pulldowns with INSIG dependency, MELADL mutagenesis, D428A co-IP and transport assay

    PMID:15728349 PMID:15899885

    Open questions at the time
    • Spatial relationship of MELADL to membrane not resolved
    • Path of signal from sensor to MELADL undefined
  10. 2007 High

    Resolved that cholesterol (on SCAP) and oxysterols (on INSIG) converge on a conformational change near MELADL that excludes COPII.

    Evidence Anti-MELADL blocking in vitro, intracellular Fab microinjection, cysteine-labeling conformational assay

    PMID:17428919

    Open questions at the time
    • Luminal determinants of cholesterol binding not yet localized
    • Structural model absent
  11. 2013 High

    Localized the cholesterol-binding site to luminal Loop 1 and showed Loop 1–Loop 7 interaction maintains the COPII-permissive Loop 6 conformation, building the intramolecular signal-relay model.

    Evidence Recombinant Loop 1 binding, Y234A and Y640S mutations, conformational assays, co-IP of N- and C-terminal fragments

    PMID:21454655 PMID:23564452 PMID:28377508

    Open questions at the time
    • Atomic structure of luminal domain still lacking
    • Quantitative coupling between loops not defined
  12. 2021 High

    Provided the structural basis of sterol sensing with cryo-EM of SCAP free, SCAP/INSIG, and the 25HC-bound complex, defining the luminal platform and ligand pocket.

    Evidence Cryo-EM of human SCAP/INSIG-2 with 25HC, full-length chicken SCAP in two states, AI-assisted comparative analysis

    PMID:33446483 PMID:34139175 PMID:34192549

    Open questions at the time
    • Dynamics of the conformational transition not captured
    • Structure of the SREBP-bound exporting state unresolved
  13. 2016 High

    Defined the structural basis of the SCAP C-terminus–SREBP interaction via the ortholog complex, explaining how SCAP engages its cargo.

    Evidence Crystal and cryo-EM structures of fission yeast Sre1-CTD/Scp1 4:4 oligomer with biochemical and cellular validation

    PMID:27811944

    Open questions at the time
    • Mammalian SCAP WD40–SREBP complex structure not solved
    • Relationship of oligomer to vesicle loading unclear
  14. 2009 Medium

    Showed hormonal/signaling inputs override sterol control: insulin and PI3K/Akt promote SCAP/SREBP export, broadening regulation beyond sterols.

    Evidence Insig-2a mRNA decay and siRNA in hepatocytes; PI3K inhibitor and dominant-negative Akt with SCAP localization imaging

    PMID:16571675 PMID:19759400

    Open questions at the time
    • Direct kinase target on SCAP not defined
    • PI3K/Akt mechanism on trafficking not fully resolved
  15. 2017 Medium

    Established post-translational control of SCAP stability and trafficking via glycosylation and ubiquitination, linking growth-factor signaling and LXR to lipogenesis.

    Evidence N-glycosylation mutagenesis with xenografts; RNF145 KO/overexpression with ubiquitination assays; 25OHD-induced degradation; RNF5 K305 mapping

    PMID:26555173 PMID:28132894 PMID:29068315 PMID:32054686

    Open questions at the time
    • Interplay among competing E3 ligases unresolved
    • Quantitative contribution of each modification in vivo unknown
  16. 2020 Medium

    Identified additional stability and trafficking modulators of SCAP, including SQSTM1-mediated lysosomal degradation, S-acylation, and accessory tethering/loading factors.

    Evidence SQSTM1 domain-mapped pulldown and degradation; ZDHHC3 palmitoylation at C264; PAQR3 Golgi tethering; Cideb-Sec12 COPII loading; SREBP-cleavage-dependent recycling

    PMID:24478315 PMID:26311497 PMID:30858281 PMID:32432943 PMID:39522165

    Open questions at the time
    • Hierarchy among these modulators undefined
    • Most validated in single labs without reciprocal confirmation
  17. 2012 High

    Established SCAP as required for diet- and insulin-resistance-driven hepatic steatosis, defining it as a therapeutic node in metabolic disease.

    Evidence Conditional hepatic Scap KO in ob/ob and high-fat-diet mice; siRNA in hamster; fatostatin direct binding and transport block

    PMID:22326225 PMID:27324795

    Open questions at the time
    • Fatostatin shows SCAP-independent effects, limiting selectivity
    • On-target small-molecule pharmacology incomplete
  18. 2016 Medium

    Revealed SCAP functions beyond lipid metabolism by scaffolding innate-immune signaling and coordinating NF-κB activation.

    Evidence Co-IP of SCAP-STING and SCAP-IRF3 with domain mapping and HSV-1 infection; SCAP-NS2B binding; macrophage-specific KO with STING/TBK1 co-IP; Scap-SREBP1-IκBα super-complex; Tim-4 disruption of Insig1-SCAP

    PMID:26900919 PMID:28228593 PMID:35367665 PMID:36450259 PMID:37267109

    Open questions at the time
    • Whether immune scaffolding requires sterol-sensing activity unclear
    • Most findings from single labs without independent replication
  19. 2024 Medium

    Identified transcriptional control of the SCAP gene itself by BRG1/Sp1 and STAT3, linking chromatin and oncogenic signaling to SCAP abundance.

    Evidence ChIP of BRG1 and STAT3 at the SCAP promoter, knockdown/KO with rescue, pharmacological inhibition in cancer cells

    PMID:33718362 PMID:38718868

    Open questions at the time
    • Integration of transcriptional and post-translational control not modeled
    • In vivo relevance of these transcriptional inputs incompletely tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the multiple competing regulatory layers—sterol sensing, ammonia and hormonal inputs, ubiquitination/acylation, and immune scaffolding—are integrated on a single SCAP molecule, and the structure of the active SREBP-bound exporting complex, remain unresolved.
  • No structure of SCAP–SREBP–COPII exporting complex
  • Quantitative crosstalk among regulatory modifications undefined
  • In vivo significance of non-lipid SCAP functions incompletely established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140299 molecular sensor activity 4 GO:0008289 lipid binding 3 GO:0038024 cargo receptor activity 2 GO:0060090 molecular adaptor activity 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005783 endoplasmic reticulum 3 GO:0005794 Golgi apparatus 3 GO:0005886 plasma membrane 1
Pathway
R-HSA-1430728 Metabolism 3 R-HSA-168256 Immune System 3 R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-74160 Gene expression (Transcription) 2 R-HSA-9609507 Protein localization 2
Partners
INSIG1INSIG2IRF3PAQR3RNF145RNF5SREBF2STING1
Complex memberships
SCAP/INSIG complexSCAP/SREBP complexSTING signalosomeScap-SREBP1-IκBα super-complex

Evidence

Reading pass · 46 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 INSIG-1 is an ER protein that binds the sterol-sensing domain of SCAP in a sterol-dependent manner, retaining the SCAP/SREBP complex in the ER and preventing SREBP transport to the Golgi for proteolytic processing. Mutant SCAP(Y298C) fails to bind INSIG-1 and is resistant to sterol-mediated ER retention. Coimmunoprecipitation, tandem mass spectrometry, blue native-PAGE, mutant SCAP analysis Cell High 12202038
2002 INSIG-2, a second ER protein with 59% sequence identity to INSIG-1, binds SCAP in a sterol-regulated fashion and blocks SCAP/SREBP export from the ER to the Golgi, thereby preventing proteolytic SREBP processing. Unlike INSIG-1, INSIG-2 expression does not require nuclear SREBPs. Coimmunoprecipitation, sterol-regulated binding assays, SREBP processing assays Proceedings of the National Academy of Sciences of the United States of America High 12242332
2002 Cholesterol addition to ER membranes in vitro causes a conformational change in SCAP detectable by trypsin cleavage site unmasking. Two sterol-resistant mutants, SCAP(Y298C) and SCAP(D443N), are refractory to this cholesterol-induced conformational change in vitro. In vitro trypsin cleavage/protease protection assay on ER membranes, mutant SCAP analysis Molecular cell High 12191470
1999 Sterols regulate cycling of SCAP between the ER and Golgi: in sterol-depleted cells, N-linked carbohydrates of SCAP are modified by Golgi enzymes (becoming endoglycosidase H-resistant), and SCAP returns to the ER; in sterol-overloaded cells, SCAP fails to leave the ER and Golgi modifications do not occur. Glycosidase treatment, glycosidase inhibitors, glycosylation-defective mutant cell lines, density gradient fractionation, brefeldin A treatment Proceedings of the National Academy of Sciences of the United States of America High 10500160
2002 Sterols block incorporation of SCAP into COPII-coated vesicles by blocking Sar1-dependent binding of COPII proteins (Sec23/24) to SCAP. SCAP-containing vesicles formed in vitro also contain VSVG (a COPII marker), and sterols selectively block SCAP but not VSVG incorporation. Immunoisolation of vesicles formed in vitro, reconstitution with recombinant yeast COPII proteins, pulldown assays Proceedings of the National Academy of Sciences of the United States of America High 12193656
2004 Cholesterol directly binds with high affinity and specificity to the purified 767 amino acid octahelical membrane region of SCAP. The membrane domain of SCAP forms a tetramer, and cholesterol binding is inhibited by cationic amphiphiles. Cholesterol acts through direct receptor-ligand interaction rather than by changing membrane physical properties. Recombinant SCAP purification in detergent, direct cholesterol binding assay, analytical ultracentrifugation (tetramer determination) Molecular cell High 15260976
2004 Cholesterol and 25-hydroxycholesterol (25-HC) inhibit SCAP/SREBP transport by two distinct mechanisms: cholesterol directly binds SCAP (demonstrated by photoactivated cholesterol cross-linking to SCAP membrane domain) and induces a conformational change causing SCAP to bind Insigs; 25-HC does not cross-link to SCAP and does not produce a detectable SCAP conformational change, suggesting it acts indirectly through a separate sensor. Methyl-β-cyclodextrin cholesterol delivery, trypsin conformational assay, photoactivated cholesterol cross-linking, coimmunoprecipitation with Insigs The Journal of biological chemistry High 15452130
2005 Insig proteins are required for sterol-mediated inhibition of Sec23/24 binding to SCAP in vitro. The hexapeptide sequence MELADL in a cytoplasmic loop of SCAP is required for Sec23/24 binding and acts as a sterol-regulated ER sorting signal. Protein pulldown assays with microsomal membranes, Insig-1 dependency experiments, MELADL mutagenesis The Journal of biological chemistry High 15899885
2007 Sterols block COPII binding to the MELADL sorting signal in SCAP by two mechanisms: cholesterol binds directly to SCAP causing a conformational change near MELADL, and oxysterols bind to Insig (not SCAP directly), also producing a conformational change near MELADL. Both conformational changes abrogate COPII binding but not anti-MELADL antibody binding. The distance of MELADL from the ER membrane is implicated as crucial for COPII binding. Anti-MELADL blocking of COPII binding in vitro, microinjection of Fab anti-MELADL into cells, cysteine labeling conformational assay, mutagenesis Proceedings of the National Academy of Sciences of the United States of America High 17428919
1998 Point mutations Y298C and D443N within the putative sterol-sensing domain of SCAP render it resistant to sterol-mediated inhibition. In sterol-resistant mutant cells, N-linked carbohydrates of SCAP remain in the endoglycosidase H-resistant (Golgi-processed) form even in the presence of 25-hydroxycholesterol, confirming that these residues are required for sterol-regulated ER retention. Isolation of CHO mutant cells, endoglycosidase H sensitivity assay, SREBP processing assay Proceedings of the National Academy of Sciences of the United States of America High 9789003
2002 Three independent point mutations in the sterol-sensing domain of SCAP (Y298C, D443N, L315F) each prevent sterol-induced binding of SCAP to Insig-1 and Insig-2, abolishing feedback regulation of SREBP processing. Sterols also fail to inhibit SCAP(L315F)/SREBP packaging into COPII vesicles in vitro. CHO mutant cell isolation, co-immunoprecipitation with Insigs, in vitro vesicle budding assay Proceedings of the National Academy of Sciences of the United States of America High 12482938
2003 Insig proteins lower the concentration of cholesterol required to produce the conformational change in SCAP in vitro. Cationic amphiphiles (chlorpromazine, trifluoperazine, imipramine) also induce this conformational change and are enhanced by Insig proteins, suggesting SCAP monitors the composition of the cytoplasmic leaflet of the ER membrane. In vitro trypsin cleavage conformational assay with Insig co-expression, cationic amphiphile treatment Proceedings of the National Academy of Sciences of the United States of America High 12963821
2000 Overexpression of the membrane domain of SCAP (TM1-6, containing the sterol-sensing domain) prevents sterol-mediated ER retention of SCAP/SREBP, consistent with competition for a putative ER retention protein. The Y298C mutation in TM1-6 abolishes this dominant-negative effect. Transfection of truncated SCAP(TM1-6), SREBP processing assay, Y298C point mutation abolishing competition The Journal of biological chemistry High 10896675
2011 Luminal Loop 1 of Scap (245 aa projecting into the ER lumen) is the cholesterol-binding site: recombinant Loop 1 binds sterols with specificity identical to the full membrane domain. Mutation Y234A in Loop 1 locks Loop 6 in the cholesterol-bound conformation even in sterol-depleted cells, preventing SREBP processing. Recombinant Loop 1 cholesterol binding assay, Y234A point mutation, SREBP processing assay in transfected cells The Journal of biological chemistry High 21454655
2005 Conserved Asp-428 in the sixth transmembrane helix of SCAP is essential for SCAP dissociation from Insigs. SCAP(D428A) mutant remains in the Insig-binding conformation even in sterol-depleted cells, failing to transport SREBPs to the Golgi. Transfection of D428A point mutant, co-immunoprecipitation with Insigs, SREBP transport assay Proceedings of the National Academy of Sciences of the United States of America High 15728349
2013 Luminal Loop 7 of Scap must interact with Loop 1 to maintain Loop 6 in a COPII-binding permissive conformation. Point mutation Y640S in Loop 7 prevents Loop 1–Loop 7 interaction (co-immunoprecipitation of separately expressed N- and C-terminal Scap fragments) and locks Loop 6 in the COPII-excluding conformation even without cholesterol. Y640S point mutation, trypsin cleavage conformational assay, co-immunoprecipitation of Scap N- and C-terminal fragments The Journal of biological chemistry High 23564452
2003 Reconstitution in Drosophila cells shows that mammalian SCAP and Insig-1 or Insig-2 are the minimal requirements for sterol-regulated ER-to-Golgi transport of SREBP-2. Without mammalian SCAP, mammalian SREBP-2 is not transported to the Golgi in insect cells. Sterols block transport only when mammalian Insig is co-expressed. Heterologous reconstitution in Drosophila cells, co-expression of mammalian SCAP and Insig The Journal of biological chemistry High 12842885
2001 SCAP is required in vivo for hepatic lipid synthesis: conditional SCAP deficiency in mouse liver reduces basal cholesterol and fatty acid synthesis by 80% (due to decreases in biosynthetic enzyme mRNAs) and abolishes normal adaptive increases in response to cholesterol deprivation and insulin elevation. Conditional hepatic Scap knockout via inducible Cre recombinase in mice, mRNA quantification, lipid synthesis measurement Genes & development High 11358865
2021 Cryo-EM structure of human Scap bound to Insig-2 in the presence of 25-hydroxycholesterol (25HC) reveals that a 25HC molecule is sandwiched between S4–S6 segments of Scap and TM3–4 of Insig-2 in the luminal leaflet of the membrane. Unwinding of the middle of the Scap-S4 segment is crucial for 25HC binding and Insig association. Cryo-electron microscopy of human Scap/Insig-2 complex, resolution 3.7 Å for transmembrane domains Science (New York, N.Y.) High 33446483
2021 Cryo-EM structures of full-length chicken Scap (wild-type free of Insig, and mutant bound to chicken Insig without cholesterol) reveal that luminal loops L1 and L7 intertwine tightly to form a globular domain (luminal platform) connecting the sterol-sensing domain to the rest of Scap. In the presence of Insig, this platform undergoes a large rotation accompanied by rearrangement of transmembrane helices. Cryo-EM of full-length chicken Scap in two states; structural comparison of Insig-bound vs. free forms Cell High 34139175
2015 EGFR signaling, by increasing glucose uptake, promotes N-glycosylation of SCAP, which stabilizes SCAP and reduces its association with Insig-1, allowing SCAP/SREBP movement to the Golgi and proteolytic SREBP-1 activation. Blocking SCAP N-glycosylation inhibits SCAP/SREBP trafficking and ameliorates EGFRvIII-driven glioblastoma xenograft growth. N-glycosylation site mutagenesis, co-immunoprecipitation (SCAP/Insig-1), Golgi trafficking assay, xenograft tumor studies Cancer cell High 26555173
2017 25-hydroxyvitamin D (25OHD) inhibits SREBP activation by inducing proteolytic processing and ubiquitin-mediated degradation of SCAP, thereby decreasing SREBP levels. This mechanism is independent of the vitamin D receptor. Chemical library screen, ubiquitination assay, proteolytic processing assay, SCAP degradation measurement Cell chemical biology Medium 28132894
2017 RNF145, an ER membrane ubiquitin E3 ligase induced by LXR activation, triggers ubiquitination of SCAP on lysine residues within the cytoplasmic loop essential for COPII binding, potentially inhibiting SCAP transport to Golgi and subsequent SREBP-2 processing. RNF145 knockdown or knockout potentiates cholesterol biosynthetic gene expression. RNF145 overexpression and shRNA knockdown in mouse liver, genetic deletion, ubiquitination assay on SCAP eLife Medium 29068315
2020 SCAP interacts with SQSTM1 (p62) via its WD40 domain (SCAP) and the TB domain (SQSTM1), and lycorine promotes SCAP lysosomal degradation via an autophagy-independent SQSTM1-mediated pathway (SMAILD), distinct from sterol-dependent ER retention mechanisms. Pulldown assay, domain mapping, lysosomal degradation assay, autophagy-independent pathway determination Autophagy Medium 32432943
2014 SCAP Golgi-to-ER recycling requires cleavage of SREBP at site-1. When SREBP cleavage is reduced, SCAP is degraded in lysosomes. SREBP actively prevents premature recycling of the SCAP-SREBP complex until initiation of SREBP cleavage, representing an ancient regulatory mechanism conserved between human cells and yeast. Inhibition of site-1 protease, lysosomal degradation assays, yeast genetic experiments The Journal of biological chemistry Medium 24478315
2015 PAQR3, a Golgi-localized membrane protein, interacts with SCAP and SREBP and tethers them to the Golgi, promoting SCAP/SREBP complex formation and SREBP processing. The interaction between Scap and PAQR3 or Insig-1 is mutually exclusive and regulated by cholesterol level. Co-immunoprecipitation, PAQR3 knockdown in liver, synthetic peptide disruption of SCAP-PAQR3 interaction Nature communications Medium 26311497
2019 Cideb, an ER/lipid droplet-associated protein, selectively promotes loading of SREBP/SCAP into COPII vesicles by interacting with SCAP (interaction enhanced by sterol deprivation) and binding to the guanine nucleotide exchange factor Sec12 to enrich SCAP/SREBP at ER exit sites. Loss of Cideb inhibits SREBP activation. Co-immunoprecipitation (SCAP-Cideb, Cideb-Sec12), COPII vesicle loading assay, Cideb knockout The EMBO journal Medium 30858281
2016 SCAP translocates from ER via Golgi to perinuclear microsome in a STING-dependent manner upon cytosolic microbial DNA sensing. The N-terminal transmembrane domain of SCAP interacts with STING, and the C-terminal cytosolic (WD40) domain of SCAP binds IRF3, recruiting IRF3 to the STING signalosome. SCAP knockdown mice are more susceptible to HSV-1 infection. Co-immunoprecipitation (SCAP-STING, SCAP-IRF3), SCAP knockdown (siRNA), HSV-1 infection of knockdown mice, localization by fluorescence microscopy PLoS pathogens Medium 26900919
2017 SCAP binds dengue virus NS2B protein (via its N-terminal transmembrane domain), inhibiting K27-linked polyubiquitination of NS3 and thereby preventing NS2B3 protease complex formation and STING cleavage. Ectopic SCAP impairs DENV infection; SCAP silencing potentiates it. Co-immunoprecipitation (SCAP-NS2B), ubiquitination assay, SCAP overexpression and knockdown with viral replication readout Journal of virology Medium 28228593
2022 Ammonia (released from glutamine) promotes SCAP-Insig dissociation and SREBP-1 activation independently of sterols. Ammonia binds to SCAP at a site blocked by 25-hydroxycholesterol. Mutating aspartate D428 to alanine prevents ammonia binding to SCAP and abolishes SREBP-1 activation. SCAP-Insig co-immunoprecipitation with ammonia treatment, D428A point mutation, ammonia binding assay, tumor xenograft Nature metabolism Medium 35534729
2006 PI3K/Akt pathway is involved in SCAP/SREBP-2 transport from the ER to the Golgi: PI3K inhibition (LY294002) or dominant-negative Akt expression disrupts SCAP trafficking to the Golgi as shown by fluorescence microscopy, blunting SREBP-2 processing. PI3K inhibitor (LY294002), dominant-negative Akt expression, immunofluorescence microscopy of SCAP localization Molecular biology of the cell Medium 16571675
2009 Insulin promotes SCAP/SREBP-1c transport to the Golgi by selectively reducing Insig-2a protein levels via accelerated mRNA decay (through the 3'-UTR of Insig-2a mRNA), releasing the SCAP/SREBP-1c complex from ER retention. siRNA knockdown of Insig-2a mimics insulin-induced SREBP-1c proteolysis. Insig-2a mRNA decay assay, siRNA knockdown, exogenous Insig-2a expression, SCAP-COPII association assay in primary hepatocytes The Journal of biological chemistry Medium 19759400
2016 Complex structure of fission yeast SREBP C-terminus (Sre1-CTD) and SCAP C-terminus (Scp1) shows they form a functional 4:4 oligomer with Sre1-CTD forming a dimer of dimers. Three distinct regions in Sre1-CTD mediate Scp1 binding, Sre1-CTD dimerization, and tetrameric formation; proper oligomeric complex formation is required for Sre1 activation. Crystal structure of Sre1-CTD at 3.5 Å, cryo-EM of complex at 5.4 Å, in vitro biochemical assembly assays, functional validation in cells Cell research High 27811944
2017 Cholesterol binding to Loop 1 of Scap alters the conformation of the sterol-sensing domain (SSD): in the absence of cholesterol, cytosolic loop 4 is cleaved by trypsin/proteinase K generating a protected fragment; upon cholesterol addition, cleavage of loop 4 is abolished. This conformational change in the SSD is proposed to transmit the cholesterol signal from Loop 1 to Loop 7. Protease protection assay in sealed membrane vesicles using trypsin or proteinase K, monoclonal antibody detection of protected fragment The Journal of biological chemistry Medium 28377508
2020 RNF5, an ER-anchored E3 ubiquitin ligase, mediates Lys-29-linked polyubiquitination of SCAP at K305 in cytosolic loop 2. This ubiquitination enhances interaction between SCAP luminal loop 1 and loop 7, activating SREBP2. K305R SCAP fails to restore the SREBP2 pathway in SCAP-deficient cells. RNF5 knockdown and overexpression, ubiquitination site mapping (K305), co-immunoprecipitation (loop 1–loop 7 interaction), SREBP2 activation assay The Journal of biological chemistry Medium 32054686
2021 ZDHHC3 S-acylates (palmitoylates) SCAP at cysteine C264, which antagonizes HACE1-mediated SCAP ubiquitination and proteasomal degradation. ABHD17A acts as the depalmitoylase. SREBP2 transcriptionally upregulates ZDHHC3, forming a positive feedback loop that sustains SCAP/SREBP2 signaling in HCC. Palmitoylation assay, ZDHHC3 knockdown/overexpression, co-immunoprecipitation, ubiquitination assay, chromatin immunoprecipitation for SREBP2 at ZDHHC3 promoter Cell reports Medium 39522165
2021 In cholesterol-fed cells, ER-localized SCAP interacts with Sac1 PI4P phosphatase through a VAP-OSBP complex at ER-Golgi membrane contact sites (MCSs), facilitating PI4P turnover and CARTS biogenesis. SCAP knockdown inhibits PI4P turnover and CARTS biogenesis; this is reversed by wild-type SCAP or a Golgi-transport-defective mutant but not by cholesterol-sensing-defective mutants. Co-immunoprecipitation (SCAP-Sac1, VAP-OSBP), SCAP knockdown, rescue with WT and mutant SCAP, CARTS biogenesis assay The Journal of cell biology Medium 33156328
2023 Scap and SREBP1 form a super-complex with IκBα that associates NF-κB near the ER. Upon LPS stimulation, Scap transports this complex to the Golgi where SREBP1 is cleaved by S1P/S2P, liberating IκBα for IKK-mediated phosphorylation and NF-κB activation. Loss of Scap diminishes LPS-induced NF-κB activation. Co-immunoprecipitation (Scap-SREBP1-IκBα), Scap knockout, S1P/S2P inhibition, NF-κB activation assays, Golgi localization by imaging Cell reports Medium 37267109
2021 Chromatin remodeling protein BRG1 binds the SCAP promoter in complex with Sp1 to activate SCAP transcription in hepatocytes. BRG1 deficiency reduces SCAP expression and SREBP processing; forced exogenous SCAP expression partially rescues SREBP target gene expression in BRG1-null hepatocytes. ChIP (BRG1 at SCAP promoter), BRG1 knockdown/KO, exogenous SCAP rescue experiment, SREBP processing assay Frontiers in cell and developmental biology Medium 33718362
2022 Macrophage SCAP specifically recruits STING and TBK1 onto the Golgi apparatus to activate NF-κB, promoting inflammatory factor release. Macrophage-specific SCAP knockout attenuates STING-NF-κB pathway activation and reduces metaflammation. Macrophage-specific SCAP knockout mice, co-immunoprecipitation (SCAP-STING-TBK1), NF-κB activation assay, Golgi localization imaging Cellular and molecular gastroenterology and hepatology Medium 35367665
2024 STAT3 directly binds the promoter of the SCAP gene to activate its transcription across multiple cancer cell types, and simultaneously activates SREBF1 transcription, cooperatively enhancing fatty acid synthesis. ChIP (STAT3 at SCAP promoter), STAT3 pharmacological inhibition, SCAP/SREBP-1 expression assays in cancer cells and clinical samples The Journal of biological chemistry Medium 38718868
1998 Transgenic mice expressing sterol-resistant SCAP(D443N) in liver show increased nuclear SREBP-1 and -2, elevated lipogenic gene mRNAs, and fatty livers. These livers show blunted feedback suppression of SREBP processing in response to high dietary cholesterol, confirming SCAP's sterol-sensing role in vivo. Transgenic mouse model with liver-specific SCAP(D443N), dietary cholesterol challenge, nuclear SREBP quantification, lipid analysis The Journal of clinical investigation High 9854040
2012 Scap is required for hepatic steatosis in insulin-resistant ob/ob mice and high-fat diet mice: deletion of Scap in liver abolishes fatty liver despite persistent obesity, hyperinsulinemia, and hyperglycemia. siRNA silencing of Scap in sucrose-fed hamster livers prevents sucrose-induced hypertriglyceridemia by reducing all three nuclear SREBPs. Conditional hepatic Scap knockout in ob/ob mice, siRNA silencing in hamsters, lipid synthesis measurement, SREBP nuclear levels Cell metabolism High 22326225
2016 Fatostatin directly binds SCAP and blocks its ER-to-Golgi transport independently of Insig proteins. However, fatostatin also inhibits cell growth via SCAP-independent mechanisms and delays ER-to-Golgi transport of VSVG protein, indicating general ER-to-Golgi transport inhibition beyond SCAP. VSVG trafficking assay, SCAP-null cell growth assay, fatostatin direct binding to SCAP, ER exit assay Journal of lipid research Medium 27324795
2021 Combined cryo-EM and AI-facilitated structural prediction reveals that luminal loop 1 and a co-folded segment in loop 7 of Scap resemble the luminal/extracellular domain in NPC1 and related proteins. An additional luminal interface between Scap and Insig-2 is observed. SCAP(D428A) shows identical conformation with wild-type when complexed with Insig-2, suggesting constitutive suppression may involve a later trafficking step. Cryo-EM of human Scap/Insig-2 complex in digitonin, AI structural prediction, comparative structural analysis Cell reports High 34192549
2022 Tim-4 disturbs the Insig1-SCAP interaction and promotes SCAP-SREBP2 complex translocation to the Golgi, upregulating cholesterol biosynthesis in macrophages and limiting type I IFN responses. Co-immunoprecipitation (Insig1-SCAP with/without Tim-4), Tim-4 deficiency, SREBP2 activation assay, IFN signaling measurement Cell reports Medium 36450259

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Crucial step in cholesterol homeostasis: sterols promote binding of SCAP to INSIG-1, a membrane protein that facilitates retention of SREBPs in ER. Cell 835 12202038
2002 Insig-2, a second endoplasmic reticulum protein that binds SCAP and blocks export of sterol regulatory element-binding proteins. Proceedings of the National Academy of Sciences of the United States of America 444 12242332
2017 Retrospective on Cholesterol Homeostasis: The Central Role of Scap. Annual review of biochemistry 394 28841344
2008 Cholesterol feedback: from Schoenheimer's bottle to Scap's MELADL. Journal of lipid research 386 18974038
2004 Cholesterol and 25-hydroxycholesterol inhibit activation of SREBPs by different mechanisms, both involving SCAP and Insigs. The Journal of biological chemistry 376 15452130
2002 Cholesterol addition to ER membranes alters conformation of SCAP, the SREBP escort protein that regulates cholesterol metabolism. Molecular cell 341 12191470
2004 Direct binding of cholesterol to the purified membrane region of SCAP: mechanism for a sterol-sensing domain. Molecular cell 282 15260976
2012 The Scap/SREBP pathway is essential for developing diabetic fatty liver and carbohydrate-induced hypertriglyceridemia in animals. Cell metabolism 276 22326225
2001 SREBP cleavage-activating protein (SCAP) is required for increased lipid synthesis in liver induced by cholesterol deprivation and insulin elevation. Genes & development 276 11358865
2015 Glucose-Mediated N-glycosylation of SCAP Is Essential for SREBP-1 Activation and Tumor Growth. Cancer cell 251 26555173
2007 Sterol-regulated transport of SREBPs from endoplasmic reticulum to Golgi: Insig renders sorting signal in Scap inaccessible to COPII proteins. Proceedings of the National Academy of Sciences of the United States of America 242 17428919
2011 Comparative analysis of in vitro osteo/odontogenic differentiation potential of human dental pulp stem cells (DPSCs) and stem cells from the apical papilla (SCAP). Archives of oral biology 236 21227403
1999 Sterols regulate cycling of SREBP cleavage-activating protein (SCAP) between endoplasmic reticulum and Golgi. Proceedings of the National Academy of Sciences of the United States of America 196 10500160
2005 Insig required for sterol-mediated inhibition of Scap/SREBP binding to COPII proteins in vitro. The Journal of biological chemistry 194 15899885
2013 An essential requirement for the SCAP/SREBP signaling axis to protect cancer cells from lipotoxicity. Cancer research 172 23440422
2006 Involvement of Akt in ER-to-Golgi transport of SCAP/SREBP: a link between a key cell proliferative pathway and membrane synthesis. Molecular biology of the cell 141 16571675
2002 Sterols block binding of COPII proteins to SCAP, thereby controlling SCAP sorting in ER. Proceedings of the National Academy of Sciences of the United States of America 126 12193656
2018 SCAP/SREBPs are Central Players in Lipid Metabolism and Novel Metabolic Targets in Cancer Therapy. Current topics in medicinal chemistry 121 29788888
2017 Vitamin D Metabolite, 25-Hydroxyvitamin D, Regulates Lipid Metabolism by Inducing Degradation of SREBP/SCAP. Cell chemical biology 115 28132894
2022 Ammonia stimulates SCAP/Insig dissociation and SREBP-1 activation to promote lipogenesis and tumour growth. Nature metabolism 111 35534729
1998 Sterols regulate processing of carbohydrate chains of wild-type SREBP cleavage-activating protein (SCAP), but not sterol-resistant mutants Y298C or D443N. Proceedings of the National Academy of Sciences of the United States of America 111 9789003
2022 Inhibiting SCAP/SREBP exacerbates liver injury and carcinogenesis in murine nonalcoholic steatohepatitis. The Journal of clinical investigation 99 35380992
2009 SCAP is required for timely and proper myelin membrane synthesis. Proceedings of the National Academy of Sciences of the United States of America 95 19948958
2003 Cholesterol-induced conformational change in SCAP enhanced by Insig proteins and mimicked by cationic amphiphiles. Proceedings of the National Academy of Sciences of the United States of America 93 12963821
2019 Berberine suppresses colon cancer cell proliferation by inhibiting the SCAP/SREBP-1 signaling pathway-mediated lipogenesis. Biochemical pharmacology 91 31874145
2004 Molecular regulation of SREBP function: the Insig-SCAP connection and isoform-specific modulation of lipid synthesis. Biochemistry and cell biology = Biochimie et biologie cellulaire 89 15052338
2017 The SCAP/SREBP Pathway: A Mediator of Hepatic Steatosis. Endocrinology and metabolism (Seoul, Korea) 85 28116873
2009 Insulin enhances the biogenesis of nuclear sterol regulatory element-binding protein (SREBP)-1c by posttranscriptional down-regulation of Insig-2A and its dissociation from SREBP cleavage-activating protein (SCAP).SREBP-1c complex. The Journal of biological chemistry 84 19759400
2020 The cellular function of SCAP in metabolic signaling. Experimental & molecular medicine 83 32385422
2020 Discovery of a potent SCAP degrader that ameliorates HFD-induced obesity, hyperlipidemia and insulin resistance via an autophagy-independent lysosomal pathway. Autophagy 79 32432943
2021 A structure of human Scap bound to Insig-2 suggests how their interaction is regulated by sterols. Science (New York, N.Y.) 78 33446483
2014 Sterol regulatory element-binding protein (SREBP) cleavage regulates Golgi-to-endoplasmic reticulum recycling of SREBP cleavage-activating protein (SCAP). The Journal of biological chemistry 75 24478315
2002 Three mutations in sterol-sensing domain of SCAP block interaction with insig and render SREBP cleavage insensitive to sterols. Proceedings of the National Academy of Sciences of the United States of America 74 12482938
2011 Identification of luminal Loop 1 of Scap protein as the sterol sensor that maintains cholesterol homeostasis. The Journal of biological chemistry 73 21454655
2000 Overexpression of membrane domain of SCAP prevents sterols from inhibiting SCAP.SREBP exit from endoplasmic reticulum. The Journal of biological chemistry 72 10896675
2015 PAQR3 modulates cholesterol homeostasis by anchoring Scap/SREBP complex to the Golgi apparatus. Nature communications 70 26311497
2016 Fatostatin blocks ER exit of SCAP but inhibits cell growth in a SCAP-independent manner. Journal of lipid research 68 27324795
2016 Physiological Suppression of Lipotoxic Liver Damage by Complementary Actions of HDAC3 and SCAP/SREBP. Cell metabolism 68 27866836
2015 Accumulation of advanced glycation end-products and activation of the SCAP/SREBP Lipogenetic pathway occur in diet-induced obese mouse skeletal muscle. PloS one 65 25750996
2016 Feedback Loop Regulation of SCAP/SREBP-1 by miR-29 Modulates EGFR Signaling-Driven Glioblastoma Growth. Cell reports 63 27477273
2013 Reduction of the cholesterol sensor SCAP in the brains of mice causes impaired synaptic transmission and altered cognitive function. PLoS biology 62 23585733
2005 Compensatory increase in fatty acid synthesis in adipose tissue of mice with conditional deficiency of SCAP in liver. Cell metabolism 59 16054043
1998 Blunted feedback suppression of SREBP processing by dietary cholesterol in transgenic mice expressing sterol-resistant SCAP(D443N). The Journal of clinical investigation 59 9854040
2016 ER Adaptor SCAP Translocates and Recruits IRF3 to Perinuclear Microsome Induced by Cytosolic Microbial DNAs. PLoS pathogens 58 26900919
2022 Macrophage SCAP Contributes to Metaflammation and Lean NAFLD by Activating STING-NF-κB Signaling Pathway. Cellular and molecular gastroenterology and hepatology 57 35367665
2001 SCAP ligands are potent new lipid-lowering drugs. Nature medicine 54 11726974
2024 The Role of SCAP/SREBP as Central Regulators of Lipid Metabolism in Hepatic Steatosis. International journal of molecular sciences 53 38256181
2008 Deletion of Scap in alveolar type II cells influences lung lipid homeostasis and identifies a compensatory role for pulmonary lipofibroblasts. The Journal of biological chemistry 53 19074148
2013 Cross-talk between TLR4-MyD88-NF-κB and SCAP-SREBP2 pathways mediates macrophage foam cell formation. American journal of physiology. Heart and circulatory physiology 52 23335792
2017 Inhibition of cholesterol biosynthesis through RNF145-dependent ubiquitination of SCAP. eLife 51 29068315
2013 Advanced glycation end products promote hepatosteatosis by interfering with SCAP-SREBP pathway in fructose-drinking mice. American journal of physiology. Gastrointestinal and liver physiology 51 23868406
2021 PKM2-TMEM33 axis regulates lipid homeostasis in cancer cells by controlling SCAP stability. The EMBO journal 50 34487377
2019 S-CAP extends pathogenicity prediction to genetic variants that affect RNA splicing. Nature genetics 49 30804562
2017 The antioxidative and hepatoprotective effects comparison of Chinese angelica polysaccharide(CAP)and selenizing CAP (sCAP) in CCl4 induced hepatic injury mice. International journal of biological macromolecules 48 28064055
2016 SCAP/SREBP pathway is required for the full steroidogenic response to cyclic AMP. Proceedings of the National Academy of Sciences of the United States of America 46 27601673
2013 Cholesterol Contributes to Diabetic Nephropathy through SCAP-SREBP-2 Pathway. International journal of endocrinology 46 24369464
2007 4-Methyl sterols regulate fission yeast SREBP-Scap under low oxygen and cell stress. The Journal of biological chemistry 46 17595166
2019 Cideb controls sterol-regulated ER export of SREBP/SCAP by promoting cargo loading at ER exit sites. The EMBO journal 44 30858281
2019 Quercetin improves lipid metabolism via SCAP-SREBP2-LDLr signaling pathway in early stage diabetic nephropathy. Diabetes, metabolic syndrome and obesity : targets and therapy 42 31239739
2011 Advanced glycation end products (AGEs) increase human mesangial foam cell formation by increasing Golgi SCAP glycosylation in vitro. American journal of physiology. Renal physiology 41 21511699
2022 Cholesterol sensor SCAP contributes to sorafenib resistance by regulating autophagy in hepatocellular carcinoma. Journal of experimental & clinical cancer research : CR 40 35354475
2002 Effects of SREBF-1a and SCAP polymorphisms on plasma levels of lipids, severity, progression and regression of coronary atherosclerosis and response to therapy with fluvastatin. Journal of molecular medicine (Berlin, Germany) 38 12436350
2017 Endoplasmic Reticulum Protein SCAP Inhibits Dengue Virus NS2B3 Protease by Suppressing Its K27-Linked Polyubiquitylation. Journal of virology 37 28228593
2013 Comparative analysis of in vitro periodontal characteristics of stem cells from apical papilla (SCAP) and periodontal ligament stem cells (PDLSCs). Archives of oral biology 37 23582988
2005 Intramembrane aspartic acid in SCAP protein governs cholesterol-induced conformational change. Proceedings of the National Academy of Sciences of the United States of America 35 15728349
2021 The ER cholesterol sensor SCAP promotes CARTS biogenesis at ER-Golgi membrane contact sites. The Journal of cell biology 34 33156328
2021 Structural basis for sterol sensing by Scap and Insig. Cell reports 34 34192549
2017 Cholesterol-induced conformational changes in the sterol-sensing domain of the Scap protein suggest feedback mechanism to control cholesterol synthesis. The Journal of biological chemistry 33 28377508
2015 Scap is required for sterol synthesis and crypt growth in intestinal mucosa. Journal of lipid research 32 25896350
2023 The Scap-SREBP1-S1P/S2P lipogenesis signal orchestrates the homeostasis and spatiotemporal activation of NF-κB. Cell reports 31 37267109
2021 The Chromatin Remodeling Protein BRG1 Regulates SREBP Maturation by Activating SCAP Transcription in Hepatocytes. Frontiers in cell and developmental biology 31 33718362
2005 Determinants of variable response to simvastatin treatment: the role of common variants of SCAP, SREBF-1a and SREBF-2 genes. The pharmacogenomics journal 31 16158080
2022 PIDDosome-SCAP crosstalk controls high-fructose-diet-dependent transition from simple steatosis to steatohepatitis. Cell metabolism 30 36041455
2020 Ring finger protein 5 activates sterol regulatory element-binding protein 2 (SREBP2) to promote cholesterol biosynthesis via inducing polyubiquitination of SREBP chaperone SCAP. The Journal of biological chemistry 30 32054686
2018 SCAP knockdown in vascular smooth muscle cells alleviates atherosclerosis plaque formation via up-regulating autophagy in ApoE-/- mice. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 30 30462530
2003 Reconstitution of sterol-regulated endoplasmic reticulum-to-Golgi transport of SREBP-2 in insect cells by co-expression of mammalian SCAP and Insigs. The Journal of biological chemistry 30 12842885
2024 ZDHHC3-mediated SCAP S-acylation promotes cholesterol biosynthesis and tumor immune escape in hepatocellular carcinoma. Cell reports 29 39522165
2021 DHT causes liver steatosis via transcriptional regulation of SCAP in normal weight female mice. The Journal of endocrinology 29 34060475
2021 Scap structures highlight key role for rotation of intertwined luminal loops in cholesterol sensing. Cell 29 34139175
2017 microRNA-29 mediates a novel negative feedback loop to regulate SCAP/SREBP-1 and lipid metabolism. RNA & disease (Houston, Tex.) 29 28664184
2015 Anti-Inflammatory Effects of Ang-(1-7) in Ameliorating HFD-Induced Renal Injury through LDLr-SREBP2-SCAP Pathway. PloS one 28 26291618
2022 Targeting the SREBP-1/Hsa-Mir-497/SCAP/FASN Oncometabolic Axis Inhibits the Cancer Stem-like and Chemoresistant Phenotype of Non-Small Cell Lung Carcinoma Cells. International journal of molecular sciences 27 35806291
2016 SCAP links glucose to lipid metabolism in cancer cells. Molecular & cellular oncology 27 27065222
2016 Complex structure of the fission yeast SREBP-SCAP binding domains reveals an oligomeric organization. Cell research 27 27811944
2022 SCAP deficiency facilitates obesity and insulin resistance through shifting adipose tissue macrophage polarization. Journal of advanced research 25 35659922
2021 Hyperphosphatemia in chronic kidney disease exacerbates atherosclerosis via a mannosidases-mediated complex-type conversion of SCAP N-glycans. Kidney international 24 33631226
2021 Sterol-resistant SCAP Overexpression in Vascular Smooth Muscle Cells Accelerates Atherosclerosis by Increasing Local Vascular Inflammation through Activation of the NLRP3 Inflammasome in Mice. Aging and disease 24 34094640
2016 Dose-dependent effects of siRNA-mediated inhibition of SCAP on PCSK9, LDLR, and plasma lipids in mouse and rhesus monkey. Journal of lipid research 24 27707816
2013 Point mutation in luminal loop 7 of Scap protein blocks interaction with loop 1 and abolishes movement to Golgi. The Journal of biological chemistry 23 23564452
2003 Synergistic activation of human LDL receptor expression by SCAP ligand and cytokine oncostatin M. Arteriosclerosis, thrombosis, and vascular biology 23 12524230
2017 Effect of Tetramethylpyrazine on Atherosclerosis and SCAP/SREBP-1c Signaling Pathway in ApoE-/- Mice Fed with a High-Fat Diet. Evidence-based complementary and alternative medicine : eCAM 22 28491104
2006 The discrete and combined effect of SREBP-2 and SCAP isoforms in the control of plasma lipids among familial hypercholesterolaemia patients. Atherosclerosis 21 16466730
1999 Genomic structure and chromosomal mapping of the human sterol regulatory element binding protein (SREBP) cleavage-activating protein (SCAP) gene. Journal of human genetics 21 10570913
2014 The gene-gene interaction of INSIG-SCAP-SREBP pathway on the risk of obesity in Chinese children. BioMed research international 20 25028659
1999 A common Ile796Val polymorphism of the human SREBP cleavage-activating protein (SCAP) gene. Journal of human genetics 20 10570919
2024 STAT3 activation of SCAP-SREBP-1 signaling upregulates fatty acid synthesis to promote tumor growth. The Journal of biological chemistry 19 38718868
2022 Tim-4 reprograms cholesterol metabolism to suppress antiviral innate immunity by disturbing the Insig1-SCAP interaction in macrophages. Cell reports 19 36450259
2007 SREBP-2 and SCAP isoforms and risk of early onset myocardial infarction. Atherosclerosis 19 17383658
2016 Analysis of SCAP N-glycosylation and Trafficking in Human Cells. Journal of visualized experiments : JoVE 18 27911384
2013 Overexpression of a key regulator of lipid homeostasis, Scap, promotes respiration in prostate cancer cells. FEBS letters 18 23454642

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