Affinage

SCG5

Neuroendocrine protein 7B2 · UniProt P05408

Length
212 aa
Mass
23.7 kDa
Annotated
2026-04-28
100 papers in source corpus 31 papers cited in narrative 31 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SCG5 (7B2) is an obligate neuroendocrine chaperone for prohormone convertase 2 (PC2) that also functions as a broad anti-aggregation factor in the secretory pathway. The 21-kDa N-terminal domain of 7B2 binds proPC2 in the ER via a polyproline helix and disulfide-stabilized alpha-helix, preventing proPC2 aggregation and stabilizing a transport- and activation-competent conformation that is essential for proPC2 zymogen activation at acidic pH in the TGN; 7B2-null mice completely lack PC2 activity, exhibit hyperproinsulinemia, ACTH hypersecretion, and die of Cushing's syndrome (PMID:10089884, PMID:7913882, PMID:10409712, PMID:18467442). Furin cleaves pro-7B2 in the TGN to release a C-terminal peptide that potently and specifically inhibits mature PC2 (Ki ~57 nM) through a Lys171-Lys172-dependent competitive mechanism, until PC2 itself cleaves this inhibitory peptide at an internal dibasic site to relieve inhibition (PMID:7727407, PMID:8643504, PMID:11677272). Beyond PC2, 7B2 suppresses fibrillation of Aβ, α-synuclein, and IAPP at substoichiometric ratios, and phosphorylation at Ser115 by Golgi kinases inactivates its chaperone function (PMID:23172224, PMID:24042052, PMID:16286464).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1990 High

    Establishing that 7B2 is a regulated secretory pathway protein that undergoes C-terminal processing prior to secretion resolved its identity as an intracellularly processed neuroendocrine protein rather than a constitutively released factor.

    Evidence Pulse-chase immunoprecipitation and secretion assays in Xenopus neurointermediate lobe

    PMID:2394742

    Open questions at the time
    • Processing enzyme not identified
    • Functional significance of processing unknown
    • No binding partner identified
  2. 1994 High

    Discovery that 7B2 specifically and transiently associates with proPC2 beginning in the ER — and that furin cleaves pro-7B2 in the TGN — established 7B2 as a dedicated secretory pathway chaperone for PC2 and identified the protease responsible for 7B2 maturation.

    Evidence Co-immunoprecipitation, pulse-chase in Xenopus intermediate lobe cells, and complementation in furin-deficient LoVo cells

    PMID:7913882 PMID:8034690

    Open questions at the time
    • Binding determinants on 7B2 unknown
    • Mechanism of chaperone action versus inhibition not resolved
  3. 1995 High

    Demonstration that 7B2 is bifunctional — the N-terminal 21-kDa domain facilitates proPC2 maturation while the C-terminal peptide inhibits mature PC2 with Ki ~57 nM via a Lys171-Lys172-dependent mechanism — resolved the paradox of how one protein could both activate and inhibit the same enzyme.

    Evidence Quantitative in vitro enzyme inhibition with synthetic peptides, systematic mutagenesis, and cell-based maturation assays in AtT-20, Rin5f, and CHO cells

    PMID:7672117 PMID:7727407 PMID:7782286 PMID:7790360

    Open questions at the time
    • Structural basis of dual function unresolved
    • How CT peptide inhibition is relieved in vivo unknown
    • Minimal active domain not mapped
  4. 1996 High

    Identification that PC2 itself cleaves the inhibitory CT peptide at an internal Lys-Lys site — with further inactivation by CPE — revealed a self-derepression mechanism ensuring timed release of PC2 activity within secretory granules, while the polyproline helix (Pro90-95) was mapped as the key structural motif mediating proPC2 interaction.

    Evidence In vitro cleavage of radiolabeled CT peptide by purified PC2; site-directed mutagenesis of PPII prolines with four orthogonal functional assays; thermal stabilization assays

    PMID:8643504 PMID:8660652 PMID:8798569

    Open questions at the time
    • Three-dimensional structure of the 7B2–proPC2 complex unknown
    • Whether 7B2 acts only post-folding not established
  5. 1998 High

    Mapping the 7B2-binding surface on PC2 to a catalytic-domain loop (Tyr194 and residues 242-248) and demonstrating that 7B2 acts after proPC2 folding to stabilize a transport-competent conformation — not to assist folding per se — refined the chaperone mechanism and showed 7B2 is rate-limiting for proPC2 activation at acidic pH.

    Evidence Domain-swap chimeras and site-directed mutagenesis of PC2 in AtT-20 and BSC40 cells; pulse-chase with subcellular fractionation and cell-free activation in Golgi-enriched fractions; cross-species conservation with C. elegans 7B2

    PMID:9348280 PMID:9422782 PMID:9645470 PMID:9726255

    Open questions at the time
    • Atomic-resolution structure still lacking
    • Mechanism by which 7B2 prevents premature proPC2 activation in ER not explained
  6. 1999 High

    The 7B2-null mouse proved that 7B2 is absolutely required for PC2 activity in vivo and revealed an additional PC2-independent role in ACTH regulation: nulls develop lethal Cushing's syndrome with ACTH hypersecretion not seen in PC2-null mice. The minimal 36-residue domain containing the PPII helix, alpha-helix, and disulfide bond was shown to be sufficient for proPC2 activation.

    Evidence Gene-targeted 7B2-null mice with hormone RIAs and enzymatic assays; antisense knockdown in rMTC 6-23 cells; systematic 7B2 deletion constructs in activation assays

    PMID:10089884 PMID:10198237 PMID:10409712

    Open questions at the time
    • Mechanism of PC2-independent ACTH hypersecretion unclear
    • Whether 7B2 has additional substrates beyond PC2 not resolved
  7. 2000 High

    Structure-activity analysis of the CT peptide and identification of PC2 residues 242-248 as essential for CT peptide binding established that inhibition depends on both side-chain and backbone stereochemistry, while evolutionary conservation was confirmed by functional reconstitution with Drosophila 7B2 and amontillado/dPC2.

    Evidence Stereoisomeric peptide analogues in PC2 inhibition assays; PC2 mutagenesis with co-IP and enzymatic readouts; cross-species reconstitution in Drosophila S2 cells

    PMID:10673395 PMID:10749852 PMID:10799554

    Open questions at the time
    • No co-crystal structure of CT peptide with PC2
    • Role in non-neuroendocrine contexts not explored
  8. 2001 High

    Furin cleavage of pro-7B2 is prerequisite for PC2-mediated destruction of the CT peptide: a furin-site blockade mutant retains CT peptide inhibitory activity and fails to support secretion of active PC2, establishing the ordered processing cascade (furin → 7B2 cleavage → PC2 activation → CT peptide destruction).

    Evidence Bacterial expression of 7B2 furin-site mutants; cell-free and HEK293-based proPC2 activation assays

    PMID:11677272

    Open questions at the time
    • Kinetics of the cascade in vivo not measured
    • Whether incomplete furin cleavage serves a regulatory role unknown
  9. 2002 High

    Adrenalectomy rescue of 7B2-null mice demonstrated that the lethal Cushing's phenotype is driven by corticosterone-mediated suppression of pituitary dopamine, linking 7B2 to dopaminergic regulation of ACTH secretion beyond its canonical PC2 chaperone role.

    Evidence Adrenalectomy of 7B2-null mice with dopamine measurements and hormone RIAs

    PMID:11854475

    Open questions at the time
    • Direct molecular target of 7B2 in dopaminergic pathway unknown
    • Whether this is PC2-dependent or independent remains ambiguous
  10. 2005 High

    Phosphorylation of 7B2 at Ser115 by Golgi kinases abolishes proPC2 binding and chaperone function, revealing a post-translational switch that can tune PC2 activation efficiency within the secretory pathway.

    Evidence Metabolic 32P-labeling in Rin and chromaffin cells; phosphoamino acid analysis; Ser115 mutagenesis; co-IP and cell-free activation assays; kinase inhibitor studies

    PMID:16286464

    Open questions at the time
    • Identity of the responsible Golgi kinase not definitively established
    • Physiological conditions triggering phosphorylation unknown
    • Stoichiometry of phosphorylated vs. unphosphorylated 7B2 in vivo not measured
  11. 2008 High

    Demonstration that 7B2 prevents proPC2 unfolding and disaggregates proPC2 oligomers in a dose-dependent manner established it as a bona fide anti-aggregation chaperone, not merely a folding escort.

    Evidence Cross-linking, sucrose density gradients, and velocity sedimentation with recombinant 7B2 added to CHO cells expressing proPC2

    PMID:18467442

    Open questions at the time
    • Whether anti-aggregation extends to substrates other than proPC2 not tested
    • Structural mechanism of disaggregation unknown
  12. 2012 High

    Extension of 7B2's anti-aggregation function to disease-associated amyloidogenic proteins — Aβ(1-42), Aβ(1-40), and α-synuclein — at substoichiometric ratios established 7B2 as a general secretory anti-fibrillation chaperone with potential neuroprotective roles.

    Evidence ThT fibrillation assays; Neuro-2A viability assays with 7B2 overexpression and RNAi; co-localization with amyloid plaques in APP/PSEN1 mouse and human AD brain

    PMID:23172224

    Open questions at the time
    • In vivo relevance to neurodegeneration not established by genetic models
    • Structural basis of broad substrate recognition unknown
    • Whether endogenous 7B2 levels are sufficient for neuroprotection in brain
  13. 2013 Medium

    7B2 also blocks IAPP fibrillation and cytotoxicity and, in a distinct physiological context, the 7B2•PC2 complex participates in FGF-23 cleavage in osteoblasts, broadening 7B2's functional scope beyond classical neuroendocrine hormone processing.

    Evidence ThT assays with hIAPP and 7B2 truncations; RNAi of Sgne1 in osteoblasts with FGF-23 cleavage readout; Hexa-D-Arg rescue of hyp-mouse bone phenotype

    PMID:22886699 PMID:24042052

    Open questions at the time
    • Whether 7B2 anti-IAPP activity operates in pancreatic beta cells in vivo unknown
    • FGF-23 cleavage link from single laboratory
    • Structural determinants of anti-IAPP versus anti-Aβ activity not distinguished

Open questions

Synthesis pass · forward-looking unresolved questions
  • No atomic-resolution structure of the 7B2–proPC2 complex exists, and the molecular basis by which 7B2 exerts PC2-independent effects (e.g., ACTH hypersecretion in nulls beyond PC2-null phenotype, broad anti-amyloid activity) remains mechanistically unresolved.
  • No crystal or cryo-EM structure of the 7B2–proPC2 or 7B2–PC2 complex
  • PC2-independent functions not assigned to a specific molecular target
  • In vivo relevance of anti-amyloid chaperone activity not tested genetically

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0044183 protein folding chaperone 6 GO:0098772 molecular function regulator activity 6
Localization
GO:0031410 cytoplasmic vesicle 4 GO:0005783 endoplasmic reticulum 3 GO:0005794 Golgi apparatus 2 GO:0005576 extracellular region 1
Pathway
R-HSA-392499 Metabolism of proteins 7 R-HSA-162582 Signal Transduction 3 R-HSA-9609507 Protein localization 3
Partners
CPEFURINPCSK2
Complex memberships
proPC2–7B2 chaperone complex

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 7B2 (SCG5) acts as a neuroendocrine chaperone that transiently and specifically associates with the precursor form of prohormone convertase PC2 (proPC2) early in the secretory pathway; the interaction commences in the ER and dissociation in later compartments coincides with cleavages of both 7B2 and proPC2, preventing premature activation of proPC2. In vitro incubation of recombinant 7B2 with newly synthesized pituitary proteins; metabolic cell labeling with co-immunoprecipitation; pulse-chase analysis in Xenopus intermediate lobe cells Cell High 7913882
1994 Intact recombinant 7B2 is a potent inhibitor of PC2 enzymatic activity and prevents proPC2 cleavage in vitro, while the processed (C-terminal cleavage) product of 7B2 is virtually inactive; 7B2 does not inhibit PC1/PC3. The C-terminal half of 7B2 is distantly related to the potato inhibitor I family of subtilisin inhibitors. In vitro enzyme inhibition assays with recombinant 7B2 proteins; sequence analysis Proceedings of the National Academy of Sciences of the United States of America High 8016065
1995 7B2 is bifunctional: the amino-terminal domain (21-kDa form) facilitates transport and maturation of proPC2 (reducing its half-life of conversion), while the C-terminal peptide of 7B2 is a potent and specific inhibitor of PC2. 21-kDa 7B2 overexpression in CHO cells enabled generation of enzymatically active PC2 from proPC2. Stable transfection of neuroendocrine cell lines (AtT-20/PC2, Rin5f, CHO) with 7B2 constructs; pulse-chase analysis; fluorogenic substrate enzyme assays; inhibition by CT peptide The Journal of cell biology High 7790360
1995 7B2 specifically binds proPC2 but not furin, PC1, PACE4, or PC5 in the ER; this binding is Ca2+-dependent and does not require N-glycosylation of proPC2. Mutagenesis of the pentabasic RRKRR site in 7B2 (especially RR152) abolished binding. After cleavage of both precursors in the TGN, 7B2 remains associated with PC2, suggesting a second Ca2+-dependent binding site. Co-immunoprecipitation; biosynthetic pulse-chase; site-directed mutagenesis of pro-7B2; expression in heterologous cells Journal of neurochemistry High 7722516
1995 The 7B2 C-terminal peptide (CT peptide) is a potent competitive inhibitor of PC2 with Ki = 57 nM and the Lys171-Lys172 dibasic site is critical for inhibition. 27-kDa intact 7B2 inhibits PC2 with Kd = 7.3 nM. The CT peptide blocks proPC2-to-PC2 conversion and PC2-mediated proenkephalin cleavage in vitro. Immunopurification of PC2; fluorogenic substrate enzyme assay; synthetic peptide inhibition assays; in vitro cleavage of proenkephalin Biochemistry High 7727407
1995 The region within 7B2 responsible for PC2 inhibition maps to a short C-terminal segment containing Lys171-Lys172; single or double mutations at this dibasic site strongly diminish or abolish PC2 inhibitory potency. No 7B2 mutant inhibited PC1/PC3. In vitro mutagenesis; prokaryotic expression of mutant proteins; in vitro PC1 and PC2 enzyme assays The Journal of biological chemistry High 7782286
1996 Recombinant PC2 purified from CHO cells co-expressing 21-kDa 7B2 is enzymatically active; 21-kDa 7B2 co-purifies with PC2 and provides thermal stabilization of PC2 activity in a Ca2+-dependent manner at acidic pH, consistent with a stabilizing role within secretory granules. Affinity purification of recombinant PC2; SDS-PAGE; fluorogenic substrate kinetic assays; thermal denaturation assays; gel filtration Archives of biochemistry and biophysics High 8660652
1996 PC2 itself cleaves the 7B2 CT peptide at an internal Lys-Lys site within secretory granules; the resulting cleavage product is non-inhibitory and further deactivated by carboxypeptidase E (CPE) removal of terminal lysines, providing a mechanism for intracellular inactivation of the CT peptide inhibitor. Immunoprecipitation of radiolabeled CT peptide from multiple cell lines; gel filtration; RIA; in vitro incubation of 125I-CT peptide with purified PC2; synthetic CT peptide derivative inhibition assays including with CPE Proceedings of the National Academy of Sciences of the United States of America High 8643504
1996 Prolines at positions 90, 91, 93, and 95 of 7B2 form a polyproline helix-like (PPII) structure that mediates interaction with proPC2; mutagenesis of these prolines severely impairs or abolishes 7B2 bioactivity as measured by co-immunoprecipitation with proPC2, facilitation of proPC2 maturation, acquisition of PC2 enzymatic activity, and thermal protection assays. Site-directed mutagenesis; co-immunoprecipitation; proPC2 maturation assays; PC2 enzymatic activity assays; thermal protection assays The Journal of biological chemistry High 8798569
1997 7B2 does not facilitate early proPC2 folding (proPC2 must fold before binding 7B2); instead, 7B2 acts after folding to stabilize a transport-competent conformation and is required for proPC2 activation at acidic pH in Golgi-enriched fractions. ProPC2 exits the ER more slowly than 7B2 and its capacity to bind 7B2 is rate-limiting. Pulse-chase analysis; subcellular fractionation; in vitro proPC2 activation assay in Golgi-enriched fractions; N-glycanase sensitivity; propeptide cleavage block experiments The Journal of cell biology High 9348280
1994 Pro-7B2 is processed by a furin-like convertase (not PC1 or PC2) within the trans-Golgi network at an Arg-Xaa-Arg/Lys-Arg site; mutation of the P4 Arg abolishes cleavage. Pro-7B2 is tyrosine-sulfated in the TGN before cleavage. Brefeldin A and monensin block processing, confirming TGN as the processing site. Recombinant vaccinia virus expression in multiple cell lines including furin-deficient LoVo cells; co-expression with individual convertases; metabolic labeling with 35S-sulfate; subcellular transport inhibitors The Journal of biological chemistry High 8034690
1998 PC2 requires 7B2 for proteolytic conversion and activation in vivo: in a human neuroepithelioma cell line (SK-N-MCIXC) expressing PC2 but not 7B2, only inactive pro-PC2 accumulates; stable transfection of pro-7B2 restores secretion of mature, active PC2. In hypoglycemic shock where adrenomedullary 7B2 is decreased, the pro-PC2:mature PC2 ratio increases. Stable transfection of SK-N-MCIXC cells; Western blotting; in vivo animal model of hypoglycemic shock; in situ hybridization DNA and cell biology High 9881669
1998 The PC2 proregion is required but not sufficient for 7B2 binding; the P domain is required for PC2 structural stability and is not exchangeable with PC1's P domain; the C-terminal domain is not involved in 7B2 binding. A single residue Tyr194→Asp in the PC2 catalytic domain prevents 7B2 binding and blocks activation, identifying a surface loop rich in aromatic residues as the primary 7B2 recognition site on PC2. Sequential deletions, site-directed mutagenesis, and domain swapping of PC2/PC1 chimeras expressed in AtT-20 cells; 7B2 binding assays; maturation and enzymatic activity assays The Journal of biological chemistry High 9422782
1998 Mutagenesis of PC2 Tyr194→Asp enables PC2 to acquire activity in the absence of 7B2 in BSC40 cells; this residue participates in 7B2 binding. The oxyanion hole Asp309 is critical for binding of proPC2 to pro-7B2. Site-directed mutagenesis of PC2; expression in BSC40 and other cells; co-immunoprecipitation; fluorogenic substrate enzyme assays; POMC processing assay FEBS letters High 9645470
1999 A minimal 36-residue internal peptide of 7B2 (containing the proline-rich PPII sequence, an alpha-helix, and the sole disulfide bond) contains all information required for proPC2 activation; deletion of the alpha-helix or mutation of the cysteines abolishes activation. The N-terminal half of 21-kDa 7B2 is dispensable for proPC2 activation. Sequential deletions of 7B2; in vivo and in vitro proPC2 activation assays; co-immunoprecipitation; maturation assays The Journal of biological chemistry High 10409712
1999 7B2 is required for the sorting and activation of PC2 into the regulated secretory pathway of rMTC 6-23 endocrine cells; antisense-mediated knockdown of 7B2 (>90% reduction) results in constitutive release of an inactive PC2 form not stored in secretory granules and unable to process pro-neurotensin/neuromedin N. Stable antisense transfection; Western blotting; secretion assays; pro-neurotensin processing assay Biochemical and biophysical research communications High 10198237
1999 7B2 null mice have no demonstrable PC2 activity and are deficient in processing islet hormones (hyperproinsulinemia, hypoglucagonemia), confirming that 7B2 is absolutely required for PC2 activation in vivo. In contrast to PC2 nulls, 7B2 null mice also exhibit ACTH hypersecretion and die of Cushing's syndrome, indicating 7B2 has additional roles beyond PC2 activation. Gene targeting (transposon-facilitated null mutation); RIA and ELISA for hormones; PC2 enzyme activity assay; comparison with PC2 null phenotype Cell High 10089884
2000 Drosophila 7B2 (d7B2) interacts with Drosophila PC2 (dPC2/amontillado) and is required for secretion and activity of dPC2; however, dPC2 activation requires insect cell-specific processing events not present in mammalian HEK-293 cells. In insect S2 cells, coexpression of dPC2 with either d7B2 or rat 7B2 yields secreted active dPC2. Heterologous expression in HEK-293 and Drosophila S2 cells; immunoblotting; PC2 enzymatic activity assay; metabolic labeling The Journal of biological chemistry High 10749852
2000 Structure-function analysis of the 7B2 CT peptide shows that residues 3-18 (including Lys-Lys at positions 17-18) are required for PC2 inhibition; all-D, all-D-retro-inverso, and all-L-inverso analogues are completely inactive, indicating that both side-chain and main-chain interactions with PC2 are required. CT peptide inhibition cannot be competitively blocked by truncated inactive forms. Synthetic peptide N-terminal truncations; alanine scanning; stereo-isomeric analogues; in vitro PC2 enzyme inhibition assays Biochemical and biophysical research communications High 10673395
2000 PC2-specific residues 242-248 in the catalytic domain are required for binding 21-kDa 7B2 and for inhibition by the 7B2 CT peptide, but do not substantially affect substrate specificity. Replacement of these residues with corresponding PC1 residues greatly reduces 7B2 binding and abolishes CT peptide inhibition. Site-directed mutagenesis; co-immunoprecipitation with 7B2; in vivo proenkephalin and POMC processing; in vitro fluorogenic substrate assay; CT peptide inhibition assay The Journal of biological chemistry High 10799554
2001 Cleavage at the 7B2 furin consensus pentabasic site is required for PC2 to efficiently inactivate the CT peptide; a blockade mutant preventing furin cleavage retains CT peptide inhibitory activity and, when coexpressed with PC2, fails to support secretion of active PC2 from HEK293 cells. Bacterial expression of 7B2 mutants; cell-free proPC2 activation assay; transient transfection in HEK293 cells; PC2 enzymatic activity assay; CT peptide RIA Journal of neurochemistry High 11677272
2002 7B2 null mice have 13-fold elevated neurointermediate lobe ACTH and greatly reduced pituitary dopamine (one-fourth of wild-type), contributing to ACTH hypersecretion; adrenalectomy rescues the lethal phenotype and normalizes dopamine and ACTH, indicating that elevated corticosterone drives the lethal syndrome and that 7B2 has a role in pituitary dopaminergic function. Comparison of 7B2 null and PC2 null mice; dopamine measurement in pituitary; adrenalectomy rescue experiment; circulating hormone RIA Proceedings of the National Academy of Sciences of the United States of America High 11854475
2005 7B2 can be phosphorylated at Ser115 (and other serine/threonine residues) by endogenous Golgi kinases (partially PKC-dependent) within the secretory pathway; phosphorylated 7B2 cannot bind proPC2 and is impaired in facilitating proPC2 activation, indicating phosphorylation inactivates 7B2's chaperone function. Metabolic phosphate labeling in Rin cells and chromaffin cells; phosphoamino acid analysis; Ser115 mutagenesis; co-immunoprecipitation; cell-free proPC2 activation assay; in vitro Golgi kinase assay with kinase inhibitors The Journal of biological chemistry High 16286464
2008 7B2 prevents unfolding and aggregation of proPC2; exogenous recombinant 7B2 added to CHO cells expressing proPC2 reduces higher-order proPC2 oligomers and solubilizes aggregated PC2 species in a dose-dependent manner. 7B2 must be present before or very shortly after proPC2 secretion to confer activation competence, suggesting it blocks loss of the catalytically competent conformer. Aggregation assays; cross-linking experiments; sucrose density gradients; velocity sedimentation; PC2 activity assays; dose-response addition of recombinant 7B2 Endocrinology High 18467442
2012 7B2 suppresses fibrillation and aggregation of Aβ(1-42), Aβ(1-40), and α-synuclein in vitro at a 1:10 molar ratio; recombinant 7B2 in medium or intracellular 7B2 overexpression blocks Aβ(1-42)-induced neurocytotoxicity in Neuro-2A cells, while 7B2 knockdown increases cytotoxicity. In APP/PSEN1 mouse brains, 7B2 co-localizes with amyloid aggregates. In vitro fibrillation assays (ThT fluorescence); cell viability assays; adenoviral 7B2 overexpression; RNAi knockdown; immunofluorescence co-localization in transgenic mouse and human AD/PD brain The Journal of biological chemistry High 23172224
2013 21-kDa 7B2 and proSAAS block hIAPP fibrillation in vitro; structure-function studies show a central region within 21-kDa 7B2 is important for anti-fibrillation activity. Both proteins block hIAPP cytotoxicity in Rin5f cells; 7B2 generated by overexpression is also effective. In vitro ThT fibrillation assays; cell viability assays; truncation/domain analysis of 7B2; 7B2 overexpression in Rin5f cells FEBS letters Medium 24042052
1990 7B2 is biosynthesized as a 25-kDa precursor that is processed to an 18-kDa form; only the processed 18-kDa product is secreted (via the regulated pathway, blocked by dopamine agonist apomorphine), while the 25-kDa precursor remains intracellular. Processing occurs in the C-terminal region and 7B2 is not glycosylated. Pulse-chase immunoprecipitation in Xenopus neurointermediate lobe; chemical and enzymatic peptide mapping; tunicamycin treatment; secretion assay with apomorphine The Journal of biological chemistry High 2394742
2013 7B2•PC2 activity in osteoblasts cleaves FGF-23; RNAi knockdown of 7B2 (Sgne1) in murine osteoblasts decreases FGF-23 degradation and increases Fgf-23 mRNA via reduced BMP1-mediated cleavage of DMP1. Hyp-mouse bone has decreased 7B2 mRNA and protein with impaired proPC2 maturation; Hexa-D-Arginine treatment enhances bone 7B2•PC2 activity and rescues the HYP phenotype. Transfection of osteoblasts with PC2 and 7B2; RNAi knockdown; Hexa-D-Arginine pharmacological treatment of hyp-mice; FGF-23 and DMP1 cleavage assays; Western blotting Journal of bone and mineral research Medium 22886699
1995 Processed 7B2 (but not intact 7B2) can enhance in vitro cleavage of POMC by immunopurified Xenopus PC2 in cell lysates; intact 7B2 abolishes this enhancing effect by inhibiting PC2, demonstrating that the processed N-terminal domain acts as a positive chaperone while intact 7B2 inhibits PC2. In vitro POMC cleavage assay using Xenopus intermediate pituitary cell lysates; immunopurified Xenopus PC2; recombinant processed and intact 7B2 FEBS letters Medium 7672117
1998 The minimal active domain of 7B2 for proPC2 activation maps to residues roughly corresponding to 7B2's proline-rich region, as demonstrated using C. elegans 7B2 (only 23% similar to vertebrate sequence) which retains the PPNPCP signature motif and inhibits vertebrate PC2 with IC50 ~130 nM, and whose N-terminal domain facilitates proPC2 activation. Cloning of C. elegans 7B2; in vitro PC2 inhibition assay; proPC2 activation functional assays DNA and cell biology Medium 9726255
2009 Pax6 transcription factor directly and indirectly (via cMaf and Beta2/NeuroD1) activates the 7B2 gene promoter in pancreatic alpha cells; Pax6 also controls PC2 gene transcription, thereby regulating glucagon biosynthesis and processing. Pax6 siRNA knockdown in InR1G9 cells; dominant-negative Pax6 expression; binding studies (EMSA/ChIP implied) and transactivation assays Molecular and cellular biology Medium 19223471

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1994 7B2 is a neuroendocrine chaperone that transiently interacts with prohormone convertase PC2 in the secretory pathway. Cell 191 7913882
1999 The neuroendocrine protein 7B2 is required for peptide hormone processing in vivo and provides a novel mechanism for pituitary Cushing's disease. Cell 151 10089884
2001 Neuroendocrine secretory protein 7B2: structure, expression and functions. The Biochemical journal 149 11439082
1995 7B2 facilitates the maturation of proPC2 in neuroendocrine cells and is required for the expression of enzymatic activity. The Journal of cell biology 148 7790360
1994 The neuroendocrine polypeptide 7B2 is an endogenous inhibitor of prohormone convertase PC2. Proceedings of the National Academy of Sciences of the United States of America 146 8016065
1988 Localization of 7B2, neuromedin B, and neuromedin U in specific cell types of rat, mouse, and human pituitary, in rat hypothalamus, and in 30 human pituitary and extrapituitary tumors. Endocrinology 117 3335208
1999 The subtilisin/kexin family of precursor convertases. Emphasis on PC1, PC2/7B2, POMC and the novel enzyme SKI-1. Annals of the New York Academy of Sciences 108 10816641
1995 7B2 is a specific intracellular binding protein of the prohormone convertase PC2. Journal of neurochemistry 89 7722516
1997 Mechanism of the facilitation of PC2 maturation by 7B2: involvement in ProPC2 transport and activation but not folding. The Journal of cell biology 87 9348280
1996 Purification and enzymatic characterization of recombinant prohormone convertase 2: stabilization of activity by 21 kDa 7B2. Archives of biochemistry and biophysics 84 8660652
1994 The neuroendocrine precursor 7B2 is a sulfated protein proteolytically processed by a ubiquitous furin-like convertase. The Journal of biological chemistry 80 8034690
1988 Cloning and sequence analysis of human pituitary cDNA encoding the novel polypeptide 7B2. FEBS letters 79 3134253
1992 Pituitary adenylate cyclase-activating polypeptide releases 7B2, adrenocorticotrophin, growth hormone and prolactin from the mouse and rat clonal pituitary cell lines AtT-20 and GH3. The Journal of endocrinology 77 1310712
1995 Enzymatic characterization of immunopurified prohormone convertase 2: potent inhibition by a 7B2 peptide fragment. Biochemistry 76 7727407
1996 Internal cleavage of the inhibitory 7B2 carboxyl-terminal peptide by PC2: a potential mechanism for its inactivation. Proceedings of the National Academy of Sciences of the United States of America 75 8643504
2000 The SAAS granin exhibits structural and functional homology to 7B2 and contains a highly potent hexapeptide inhibitor of PC1. FEBS letters 64 10812060
1995 Identification of the region within the neuroendocrine polypeptide 7B2 responsible for the inhibition of prohormone convertase PC2. The Journal of biological chemistry 64 7782286
1990 The neuroendocrine polypeptide 7B2 is a precursor protein. The Journal of biological chemistry 64 2394742
1986 Production of pituitary protein 7B2 immunoreactivity by endocrine tumors and its possible diagnostic value. The Journal of clinical endocrinology and metabolism 63 3525602
1985 Immunocytochemical localization of a novel pituitary protein (7B2) within the rat brain and hypophysis. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 60 4067275
1989 cDNA sequence of neuroendocrine protein 7B2 expressed in beta cell tumors of transgenic mice. International journal of peptide and protein research 56 2542174
2003 Biosynthesis of proopiomelanocortin-derived peptides in prohormone convertase 2 and 7B2 null mice. Endocrinology 53 14576186
2002 Mortality in 7B2 null mice can be rescued by adrenalectomy: involvement of dopamine in ACTH hypersecretion. Proceedings of the National Academy of Sciences of the United States of America 53 11854475
1989 The novel pituitary polypeptide 7B2 is a highly-conserved protein coexpressed with proopiomelanocortin. European journal of biochemistry 53 2714283
1998 Attenuation of the polypeptide 7B2, prohormone convertase PC2, and vasopressin in the hypothalamus of some Prader-Willi patients: indications for a processing defect. The Journal of clinical endocrinology and metabolism 52 9467579
1987 The pituitary polypeptide "7B2" is associated with LH/FSH and TSH cells and is localized within secretory vesicles. Cell and tissue research 52 3115588
1986 CNS distribution of a novel pituitary protein '7B2': localization in secretory and synaptic vesicles. Brain research 51 3530373
2013 Hexa-D-arginine treatment increases 7B2•PC2 activity in hyp-mouse osteoblasts and rescues the HYP phenotype. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 49 22886699
2000 Pro-opiomelanocortin-related peptides, prohormone convertases 1 and 2 and the regulatory peptide 7B2 are present in melanosomes of human melanocytes. The Journal of investigative dermatology 47 10692100
1998 Neuroendocrine protein 7B2 is essential for proteolytic conversion and activation of proprotein convertase 2 in vivo. DNA and cell biology 47 9881669
2012 The neuroendocrine protein 7B2 suppresses the aggregation of neurodegenerative disease-related proteins. The Journal of biological chemistry 42 23172224
1987 Evidence for a novel pituitary protein (7B2) in human brain, cerebrospinal fluid and plasma: brain concentrations in controls and patients with Alzheimer's disease. Peptides 42 3628077
1998 The vasopressin precursor is not processed in the hypothalamus of Wolfram syndrome patients with diabetes insipidus: evidence for the involvement of PC2 and 7B2. The Journal of clinical endocrinology and metabolism 41 9814487
1991 Cloning and characterization of the rat complementary deoxyribonucleic acid and gene encoding the neuroendocrine peptide 7B2. Endocrinology 41 1709861
1985 Regional distribution of a novel pituitary protein (7B2) in the rat brain. Brain research 41 4027592
2001 Functional characterization of ProSAAS: similarities and differences with 7B2. The Journal of biological chemistry 39 11719503
2008 7B2 prevents unfolding and aggregation of prohormone convertase 2. Endocrinology 37 18467442
2000 Interaction of Drosophila melanogaster prohormone convertase 2 and 7B2. Insect cell-specific processing and secretion. The Journal of biological chemistry 35 10749852
1998 Structural elements of PC2 required for interaction with its helper protein 7B2. The Journal of biological chemistry 35 9422782
1986 Specific release of a novel pituitary polypeptide, 7B2, from rat anterior pituitary cells in vitro by luteinizing hormone-releasing hormone. Neuroendocrinology 33 3100976
2013 Blockade of islet amyloid polypeptide fibrillation and cytotoxicity by the secretory chaperones 7B2 and proSAAS. FEBS letters 30 24042052
1995 The neuroendocrine chaperone 7B2 can enhance in vitro POMC cleavage by prohormone convertase PC2. FEBS letters 30 7672117
1996 Involvement of a polyproline helix-like structure in the interaction of 7B2 with prohormone convertase 2. The Journal of biological chemistry 29 8798569
2009 Pax6 regulates the proglucagon processing enzyme PC2 and its chaperone 7B2. Molecular and cellular biology 28 19223471
2007 Prohormone convertases 1/3, 2, furin and protein 7B2 (Secretogranin V) in endocrine cells of the human pancreas. Regulatory peptides 28 17959263
2005 Strain-dependent influences on the hypothalamo-pituitary-adrenal axis profoundly affect the 7B2 and PC2 null phenotypes. Endocrinology 28 15878971
1998 Residues unique to the pro-hormone convertase PC2 modulate its autoactivation, binding to 7B2 and enzymatic activity. FEBS letters 28 9645470
1997 Molecular characterization and differential gene induction of the neuroendocrine-specific genes neurotensin, neurotensin receptor, PC1, PC2, and 7B2 in the human ocular ciliary epithelium. Journal of neurochemistry 28 9349525
1998 Cloning and functional analysis of C. elegans 7B2. DNA and cell biology 27 9726255
1999 A 36-residue peptide contains all of the information required for 7B2-mediated activation of prohormone convertase 2. The Journal of biological chemistry 26 10409712
1999 The role of the 7B2 CT peptide in the inhibition of prohormone convertase 2 in endocrine cell lines. Journal of neurochemistry 26 10461888
2007 Altered neuropeptide profile of Caenorhabditis elegans lacking the chaperone protein 7B2 as analyzed by mass spectrometry. FEBS letters 25 17707816
1994 Differential expression of the neuroendocrine polypeptide 7B2 in hypothalami of Prader-(Labhart)-Willi syndrome patients. Brain research 25 7820629
1991 Immunological identification and sequence characterization of a peptide derived from the processing of neuroendocrine protein 7B2. FEBS letters 25 1743287
1988 Secretory protein 7B2 is associated with pancreatic hormones within normal islets and some experimentally induced tumors. Endocrinology 25 2840270
1996 Dissociation of the complex between the neuroendocrine chaperone 7B2 and prohormone convertase PC2 is not associated with proPC2 maturation. European journal of biochemistry 24 8681965
1995 Structure-function studies on the biosynthesis and bioactivity of the precursor convertase PC2 and the formation of the PC2/7B2 complex. FEBS letters 24 7720862
1991 Processed forms of neuroendocrine proteins 7B2 and secretogranin II are found in porcine pituitary extracts. International journal of peptide and protein research 24 1797712
1987 Presence of the novel pituitary protein "7B2" in bovine chromaffin granules: possible co-release of 7B2 and catecholamine as induced by nicotine. Journal of neurochemistry 24 3681297
1990 Assignment of the gene for neuroendocrine protein 7B2 (SGNE1 locus) to mouse chromosome region 2[E3-F3] and to human chromosome region 15q11-q15. Genomics 23 2328988
1997 Convertase PC2 and the neuroendocrine polypeptide 7B2 are co-induced and processed during neuronal differentiation of P19 embryonal carcinoma cells. DNA and cell biology 22 9364928
1989 Differential expression of the gene encoding the novel pituitary polypeptide 7B2 in human lung cancer cells. Cancer research 22 2545336
2002 Increased synthesis but decreased processing of neuronal proCCK in prohormone convertase 2 and 7B2 knockout animals. Journal of neurochemistry 21 12472887
1991 Application of recombinant DNA technology in epitope mapping and targeting. Development and characterization of a panel of monoclonal antibodies against the 7B2 neuroendocrine protein. Journal of immunological methods 21 1717598
1988 Identification and localization of 7B2 protein in human, porcine, and rat thyroid gland and in human medullary carcinoma. Endocrinology 21 3293987
2000 Structure-function analysis of the 7B2 CT peptide. Biochemical and biophysical research communications 20 10673395
1995 The neuroendocrine protein 7B2 acts as a molecular chaperone in the in vitro folding of human insulin-like growth factor-1 secreted from yeast. Biochemical and biophysical research communications 20 7794252
1991 The secretory granule peptides 7B2 and CCB are sensitive biochemical markers of neuro-endocrine bronchial tumours in man. Clinical endocrinology 20 1752059
2002 The lethal form of Cushing's in 7B2 null mice is caused by multiple metabolic and hormonal abnormalities. Endocrinology 19 12021197
1994 Pan-neuronal mRNA expression of the secretory polypeptide 7B2. Neuroscience letters 19 7824189
1986 A novel pituitary protein (7B2)-like immunoreactivity is secreted by a rat phaeochromocytoma cell line (PC12). The Journal of endocrinology 19 3944535
1996 Structural organization of the gene encoding the neuroendocrine chaperone 7B2. European journal of biochemistry 18 8617287
1993 Expression of neuroendocrine secretory protein 7B2 mRNA in the mouse and rat pituitary gland. Neuroendocrinology 18 7505408
2007 SGNE1/7B2 is epigenetically altered and transcriptionally downregulated in human medulloblastomas. Oncogene 17 17334394
1992 Studies on co-localization of 7B2 and pancreatic hormones in normal and tumoural islet cells. Virchows Archiv. A, Pathological anatomy and histopathology 17 1466150
1989 Regional mapping of the human gene encoding the novel pituitary polypeptide 7B2 to chromosome 15q13----q14 by in situ hybridization. Cytogenetics and cell genetics 17 2776483
2008 Overexpression of Scg5 increases enzymatic activity of PCSK2 and is inversely correlated with body weight in congenic mice. BMC genetics 16 18439298
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1997 Identification of a molluscan homologue of the neuroendocrine polypeptide 7B2. The Journal of biological chemistry 16 9020122
1989 Elevation of a novel pituitary protein (7B2) in the plasma in small cell carcinoma of the lung. European journal of cancer & clinical oncology 16 2548871
1987 Developmental changes in immunoreactive content of novel pituitary protein 7B2 in human pancreas and its identification in pancreatic tumors. Diabetes 16 2822517
1985 Regional distribution of a novel pituitary protein (7B2) in the rat spinal cord: effect of neonatal capsaicin treatment and thoracic cord transection. Neuroscience letters 16 3858706
2001 Inactivation of the 7B2 inhibitory CT peptide depends on a functional furin cleavage site. Journal of neurochemistry 15 11677272
1994 Expression, intracellular localization, and gene transcription regulation of the secretory protein 7B2 in endocrine pancreatic cell lines and human insulinomas. Experimental cell research 15 7517367
1992 Dynamics of 7B2 and galanin expression in solitary magnocellular hypothalamic vasopressin neurons of the homozygous Brattleboro rat. Brain research 15 1380870
1989 Development of a monoclonal antibody against recombinant neuroendocrine 7B2 protein. FEBS letters 15 2676606
1988 Distribution of a novel pituitary protein (7B2) in mammalian gastrointestinal tract and pancreas. Digestive diseases and sciences 15 3286156
1999 Protein 7B2 is essential for the targeting and activation of PC2 into the regulated secretory pathway of rMTC 6-23 cells. Biochemical and biophysical research communications 14 10198237
1991 Coordinated expression of 7B2 and alpha MSH in the melanotrope cells of Xenopus laevis. An immunocytochemical and in situ hybridization study. Cell and tissue research 14 1652364
1988 7B2, a new protein secreted by human functionless pituitary tumours, in vitro. Acta endocrinologica 14 3400405
2000 Mutations in the catalytic domain of prohormone convertase 2 result in decreased binding to 7B2 and loss of inhibition with 7B2 C-terminal peptide. The Journal of biological chemistry 13 10799554
1992 Expression of the neuroendocrine cell marker 7B2 in human ACTH secreting tumours. Clinical endocrinology 13 1424185
1985 Immunoreactivity of vasopressin and a novel pituitary protein '7B2' in Long-Evans and Brattleboro rat hypothalamus and hypophysis. Neuroscience letters 13 3903556
2018 Highly deleterious variations in COX1, CYTB, SCG5, FK2, PRL and PGF genes are the potential adaptation of the immigrated African ostrich population. Computers in biology and medicine 12 29960146
2003 Regulation of cell growth and expression of 7B2, PC2, and PC1/3 by TGFbeta 1 and sodium butyrate in a human pituitary cell line (HP75). Endocrine 12 14709802
2022 Association Between Maternal Adverse Childhood Experiences and Neonatal SCG5 DNA Methylation-Effect Modification by Prenatal Home Visiting. American journal of epidemiology 11 34791022
2016 Clinicopathological features of a kindred with SCG5-GREM1-associated hereditary mixed polyposis syndrome. Human pathology 11 27984123
2005 Neuroendocrine protein 7B2 can be inactivated by phosphorylation within the secretory pathway. The Journal of biological chemistry 11 16286464
2003 Frequent appearance of autoantibodies against prohormone convertase 1/3 and neuroendocrine protein 7B2 in patients with nonfunctioning pituitary macroadenoma. Endocrine 11 14709807
1993 Depolarizing action of secretory granule protein 7B2 on rat supraoptic neurosecretory neurons. Journal of neuroendocrinology 11 8680421