Affinage

SCG5

Neuroendocrine protein 7B2 · UniProt P05408

Length
212 aa
Mass
23.7 kDa
Annotated
2026-06-10
100 papers in source corpus 35 papers cited in narrative 34 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SCG5/7B2 is a neuroendocrine secretory protein that functions as a dedicated, bifunctional partner of prohormone convertase 2 (PC2), coupling chaperone-assisted activation of PC2 with timed inhibition of its activity within the regulated secretory pathway (PMID:7913882, PMID:7790360, PMID:10089884). Its N-terminal domain binds the proPC2 precursor specifically (not furin, PC1, PACE4, or PC5) in a Ca2+-dependent manner that does not require proPC2 glycosylation, acting after proPC2 has folded to stabilize it against unfolding and aggregation, escort it from the ER to the Golgi, and render it competent for activation at acidic pH (PMID:7722516, PMID:9348280, PMID:18467442). A minimal 36-residue internal segment containing a polyproline-II helix, an adjacent alpha-helix, and the single disulfide bond carries all the information required for proPC2 activation, and interaction depends on PC2 catalytic-domain determinants including Tyr194, Asp309, and residues 242–248 (PMID:8798569, PMID:10409712, PMID:9422782, PMID:9645470, PMID:10799554). The C-terminal CT peptide is a potent, PC2-specific inhibitor (Ki ~57 nM) requiring an internal Lys-Lys pair, and inhibition is self-terminating: PC2 cleaves the CT peptide at this Lys-Lys site followed by carboxypeptidase E trimming to abolish inhibitory potency (PMID:8016065, PMID:7782286, PMID:7727407, PMID:8643504, PMID:10673395). Pro-7B2 is itself matured by furin-like cleavage at a pentabasic site in the TGN, a step required for PC2 to efficiently inactivate the CT peptide, while phosphorylation at Ser115 by Golgi kinases blocks proPC2 binding and inactivates the activating function (PMID:8034690, PMID:11677272, PMID:16286464). 7B2 is absolutely required for PC2 activation in vivo, with 7B2-null mice showing no PC2 activity, defective islet hormone processing, and lethal Cushing's syndrome from intermediate-lobe ACTH hypersecretion (PMID:10089884, PMID:11854475). Beyond PC2, 7B2 acts as a broader secretory anti-aggregation chaperone, suppressing fibrillation of Aβ, α-synuclein, and IAPP and protecting neuronal cells from their cytotoxicity (PMID:23172224, PMID:24042052).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1986 Medium

    Established that 7B2 resides in neuroendocrine secretory granules and is released by regulated exocytosis, defining its subcellular setting before any enzymatic role was known.

    Evidence Immuno-EM of pituitary cells and stimulated catecholamine co-release from bovine chromaffin cells

    PMID:3115588 PMID:3681297

    Open questions at the time
    • No molecular function assigned at this stage
    • Granule targeting determinants not defined
  2. 1990 Medium

    Identified 7B2 as a precursor processed at its C-terminus, with only the processed form secreted in a regulated manner, framing the precursor/product distinction central to its later dual functions.

    Evidence Pulse-chase immunoprecipitation and peptide mapping in Xenopus neurointermediate lobe

    PMID:2394742

    Open questions at the time
    • Functional consequence of processing unknown
    • Processing enzyme not identified
  3. 1994 High

    Resolved 7B2's core dual identity: it specifically and transiently binds the proPC2 precursor as a chaperone while its intact form potently and selectively inhibits PC2 but not PC1/PC3.

    Evidence Co-IP and pulse-chase in pituitary/Xenopus cells plus in vitro inhibition assays with recombinant 7B2; furin-mediated TGN maturation of pro-7B2 also defined

    PMID:7913882 PMID:8016065 PMID:8034690

    Open questions at the time
    • Domains responsible for each activity not yet mapped
    • Mechanism terminating inhibition unknown
  4. 1995 High

    Mapped the bifunctional architecture and kinetics: the C-terminal CT peptide (Ki ~57 nM, requiring a Lys171-Lys172 site) confers inhibition while the 21-kDa product facilitates proPC2 maturation, and proPC2 binding is Ca2+-dependent via the pro-7B2 pentabasic site.

    Evidence Stable transfection in multiple neuroendocrine lines, mutagenesis, fluorogenic inhibitor kinetics with purified PC2, calcium-chelation co-IP

    PMID:7672117 PMID:7722516 PMID:7727407 PMID:7782286 PMID:7790360

    Open questions at the time
    • Structural basis of PPII/helix interaction not yet defined
    • Order of folding vs binding unresolved
  5. 1996 High

    Defined the N-terminal interaction surface and the inhibitory shutoff mechanism: a polyproline helix is required for proPC2 binding, and PC2 itself cleaves the CT peptide at an internal Lys-Lys site (with CPE trimming) to terminate inhibition.

    Evidence Proline point mutagenesis with four functional assays; in vitro CT peptide cleavage with purified PC2 plus CPE; thermal stabilization assays on purified PC2

    PMID:8643504 PMID:8660652 PMID:8681965 PMID:8798569

    Open questions at the time
    • Precise sequence of dissociation vs maturation events partially unresolved
    • Atomic structure of complex absent
  6. 1997 High

    Clarified mechanism timing: proPC2 must fold before binding 7B2, after which 7B2 enables ER-to-Golgi transport and acidic-pH activation, reconstitutable in Golgi-enriched fractions.

    Evidence Pulse-chase, glycanase sensitivity, subcellular fractionation, and in vitro activation in Golgi fractions

    PMID:9348280

    Open questions at the time
    • Conformational nature of the activation-competent state not structurally defined
  7. 1998 High

    Identified PC2 determinants of binding and proved in vivo necessity: PC2 proregion plus Tyr194 and Asp309 are required for 7B2 binding, and PC2-expressing cells lacking 7B2 contain only inactive proPC2 until rescued by 7B2.

    Evidence Domain-swap chimeras and point mutagenesis of PC2; stable 7B2 transfection rescue in PC2-expressing cells; hypoglycemic shock model

    PMID:9422782 PMID:9645470 PMID:9881669

    Open questions at the time
    • Whether these residues form a contiguous binding epitope not structurally confirmed
  8. 1999 High

    Genetic ablation established 7B2 as absolutely required for PC2 activation in vivo and revealed PC2-independent endocrine functions, including a lethal ACTH hypersecretion phenotype, and the minimal 36-residue activation unit was defined.

    Evidence 7B2 null mouse with hormonal/histological phenotyping versus PC2 null; sequential deletion/mutagenesis mapping the 36-residue activation core; antisense suppression in rMTC cells

    PMID:10089884 PMID:10198237 PMID:10409712

    Open questions at the time
    • Molecular basis of PC2-independent pituitary functions unresolved
    • Secretory-granule sorting partner unknown
  9. 2000 High

    Refined the inhibitory and binding interfaces: CT peptide residues 3–18 with a Lys-Lys pair and both main- and side-chain contacts drive inhibition, and PC2 residues 242–248 govern 7B2 binding and CT-peptide inhibition.

    Evidence Alanine scanning and stereo-isomer CT analogues; PC2 catalytic-domain mutagenesis with binding and processing readouts

    PMID:10673395 PMID:10799554

    Open questions at the time
    • No co-crystal structure of CT peptide bound to PC2 active site
  10. 2001 High

    Connected pro-7B2 maturation to inhibition control: furin cleavage of the pentabasic site is needed to produce PC2 capable of efficiently inactivating the CT peptide, decoupling activation from inhibitor turnover.

    Evidence CT-peptide and furin-site mutants tested in cell-free activation and HEK293 transfection assays

    PMID:11677272

    Open questions at the time
    • Structural reason furin cleavage gates CT inactivation unclear
  11. 2002 High

    Mechanistically linked the 7B2-null lethality to a dopaminergic deficiency: reduced pituitary dopamine drives ACTH/corticosterone excess, and adrenalectomy rescues survival.

    Evidence Adrenalectomy rescue of 7B2 null mice with ACTH, corticosterone, and dopamine measurements

    PMID:11854475

    Open questions at the time
    • How 7B2 loss lowers pituitary dopamine mechanistically not resolved
  12. 2005 High

    Revealed phospho-regulation: Golgi-kinase phosphorylation at Ser115 abolishes proPC2 binding and activation, providing a post-translational off-switch for the chaperone function.

    Evidence 32P labeling, phosphoamino acid analysis, Ser115 mutagenesis, co-IP, and cell-free activation assays

    PMID:16286464

    Open questions at the time
    • Identity of the responsible Golgi kinase not pinned down
    • Physiological trigger for phosphorylation unknown
  13. 2008 High

    Demonstrated 7B2 acts as an anti-aggregation chaperone toward proPC2 itself, solubilizing oligomers and maintaining an activation-competent conformation.

    Evidence Cross-linking, sucrose gradients, velocity sedimentation, and exogenous recombinant 7B2 addition to proPC2-expressing cells

    PMID:18467442

    Open questions at the time
    • Whether anti-aggregation and activation are separable activities unresolved
  14. 2011 High

    Showed 7B2 modulates PC2-mediated processing in a cell-type-specific manner, notably boosting glucagon production in alpha cells by routing PC2 to secretory granules.

    Evidence Adenoviral overexpression and siRNA knockdown across alpha, beta, and pituitary cells with in vivo glucagon corroboration

    PMID:22013069

    Open questions at the time
    • Basis of cell-type specificity not defined
  15. 2012 High

    Broadened 7B2's chaperone role beyond PC2 to general amyloid suppression, blocking Aβ and α-synuclein fibrillation and cytotoxicity and co-localizing with disease deposits.

    Evidence In vitro ThT fibrillation assays, gain/loss-of-function in Neuro-2A cells, and immunofluorescence in mouse and human brain

    PMID:23172224

    Open questions at the time
    • In vivo significance of anti-amyloid activity unestablished
    • Region mediating broad chaperone activity not mapped
  16. 2013 High

    Extended the anti-aggregation activity to IAPP and tied reduced 7B2•PC2 activity to X-linked hypophosphatemia pathogenesis, with pharmacological rescue in the hyp-mouse.

    Evidence In vitro hIAPP fibrillation and cell-protection assays with deletion mapping; osteoblast gain/loss-of-function and Hexa-D-Arginine rescue in hyp-mice

    PMID:22886699 PMID:24042052

    Open questions at the time
    • Whether anti-aggregation contributes to bone phenotype unclear
    • Generality of disease relevance not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • The atomic structure of the 7B2–proPC2 complex and the molecular basis of 7B2's PC2-independent and broad anti-amyloid functions remain to be resolved.
  • No co-crystal/cryo-EM structure of the chaperone or inhibitory complex
  • PC2-independent endocrine roles mechanistically undefined
  • Physiological role of broad anti-aggregation activity in vivo unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 5 GO:0044183 protein folding chaperone 4 GO:0098772 molecular function regulator activity 4 GO:0140313 molecular sequestering activity 3
Localization
GO:0005783 endoplasmic reticulum 3 GO:0005794 Golgi apparatus 3 GO:0031410 cytoplasmic vesicle 3
Pathway
R-HSA-392499 Metabolism of proteins 4 R-HSA-9609507 Protein localization 3
Partners
PCSK2

Evidence

Reading pass · 34 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 7B2 (SCG5) acts as a neuroendocrine chaperone that specifically associates with the precursor form of prohormone convertase PC2 (proPC2) in the early secretory pathway; the interaction is transient, commencing in the ER and dissociating in later compartments coincident with cleavages of 7B2, proPC2, and prohormone. The amino-terminal half of 7B2 is distantly related to chaperonins. In vitro incubation with recombinant 7B2 and newly synthesized pituitary proteins; metabolic cell labeling and co-immunoprecipitation; pulse-chase analysis in Xenopus intermediate lobe cells Cell High 7913882
1994 Intact recombinant 7B2 is a potent, specific inhibitor of PC2 enzymatic activity in vitro but does not inhibit the related convertase PC1/PC3. The 7B2 cleavage product (C-terminal half removed) is virtually inactive as an inhibitor. The carboxyl-terminal half of 7B2 is distantly related to the potato inhibitor I family of subtilisin inhibitors. In vitro enzyme inhibition assays using recombinant 7B2 against PC2 and PC1/PC3; sequence homology analysis Proceedings of the National Academy of Sciences of the United States of America High 8016065
1995 Overexpression of 21-kDa 7B2 (the naturally occurring maturation product of 27-kDa pro-7B2) greatly facilitates the kinetics of proPC2 maturation and is required for the generation of enzymatic activity; the N-terminal 'chaperone' domain alone was insufficient. PC2 enzymatic activity was inhibited by the 7B2 carboxyl-terminal peptide, confirming specificity. Stable transfection of neuroendocrine cell lines (AtT-20/PC2, Rin5f, CHO/PC2) with 7B2 constructs; pulse-chase metabolic labeling; fluorogenic substrate enzyme activity assay; inhibition by 7B2 CT peptide The Journal of cell biology High 7790360
1995 Within the ER, pro-7B2 specifically binds proPC2 but not other convertases (furin, PC1, PACE4, PC5). This binding is Ca2+-dependent and does not require N-glycosylation of proPC2. Mutagenesis of the pentabasic RRKRRS site in pro-7B2 (critical residues R152, R151, S156) abolished or greatly diminished binding. After furin cleavage in the TGN, 7B2 remains bound to PC2, suggesting a second Ca2+-dependent binding site. Biosynthetic pulse-chase analysis; co-immunoprecipitation; site-directed mutagenesis of pro-7B2; calcium chelation experiments in neuroendocrine cells Journal of neurochemistry High 7722516
1995 The carboxyl-terminal portion of 7B2 (CT peptide, residues ~155–185) is responsible for PC2 inhibition. A short segment containing a Lys171-Lys172 dibasic site is critical; single and double mutations at this site strongly diminished or abolished inhibitory potency. No 7B2 mutant inhibited PC1/PC3. In vitro mutagenesis; prokaryotic expression of mutant 7B2 proteins; in vitro enzyme activity assays against PC1/PC3 and PC2 The Journal of biological chemistry High 7782286
1995 Immunopurified PC2 cleaves the fluorogenic substrate Cbz-Arg-Ser-Lys-Arg-AMC in a Ca2+-dependent manner (half-maximal stimulation at 75 µM Ca2+, pH optimum 5.0). The 27-kDa 7B2 is a tight-binding inhibitor of PC2 with Kd = 7.3 nM. The 7B2 CT peptide (residues ~155–185) is a potent inhibitor (Ki = 57 nM) and can block PC2-mediated proenkephalin processing; 21-kDa 7B2 is functionally inactive as a proteinase inhibitor. Immunopurification of PC2 from mouse insulinoma cell conditioned medium; fluorogenic substrate assay; inhibitor kinetics with recombinant 27-kDa 7B2 and synthetic CT peptides; in vitro cleavage of recombinant proenkephalin Biochemistry High 7727407
1996 Active recombinant PC2 was purified to homogeneity from conditioned medium of CHO cells co-expressing PC2 and 21-kDa 7B2. 21-kDa 7B2 copurifies with activated PC2 and provides significant stabilization against thermal denaturation in a Ca2+- and pH-dependent manner (optimal at millimolar Ca2+, pH 5–6), consistent with a role for 7B2 in stabilizing PC2 activity within secretory granules. Purification of recombinant PC2; thermal denaturation assays; enzyme activity assays; gel filtration to remove associated 7B2 followed by re-addition Archives of biochemistry and biophysics High 8660652
1994 Pro-7B2 is tyrosine-sulfated in the trans-Golgi network and cleaved by a furin-like convertase at the RXKR/RRKRR site within the TGN to generate the 23-kDa form; PC1 and PC2 cannot process pro-7B2. Protein transport to Golgi compartments is required for this processing (blocked by monensin, brefeldin A, or low temperature). Recombinant vaccinia virus expression in multiple cell lines (AtT-20, PC12, GH4C1, Ltk-); mutagenesis of P4 Arg; co-expression with PC1, PC2, furin; expression in furin-deficient LoVo cells; [35S]SO4 pulse-chase; monensin/brefeldin A treatments The Journal of biological chemistry High 8034690
1996 PC2 itself cleaves the 7B2 CT peptide at an internal Lys-Lys site in secretory granules; the resulting cleavage product is non-inhibitory after removal of terminal lysines by carboxypeptidase E (CPE). This provides a mechanism for intracellular inactivation of the CT peptide inhibitor. Metabolic labeling ([3H]valine) and immunoprecipitation in multiple cell lines; RIA against CT peptide carboxyl terminus; in vitro incubation of 125I-CT peptide with purified recombinant PC2; synthetic CT peptide derivative inhibitory assays; inclusion of CPE in reactions Proceedings of the National Academy of Sciences of the United States of America High 8643504
1997 7B2 does not promote early proPC2 folding; instead, proPC2 must fold before it can bind 7B2. Once bound, 7B2 facilitates proPC2 transport from the ER to the Golgi and is required for proPC2 activation at acidic pH. ProPC2 activation could be reconstituted in Golgi-enriched subcellular fractions in vitro and required 7B2. Pulse-chase labeling; N-glycanase F sensitivity assay; inhibition of proPC2 folding experiments; co-immunoprecipitation; subcellular fractionation; in vitro proPC2 activation assay in Golgi-enriched fractions The Journal of cell biology High 9348280
1996 A polyproline helix-like (PPII) structure within the N-terminal domain of 7B2 (around Pro90, Pro91, Pro93, Pro95) is required for interaction with proPC2. Point mutagenesis of critical prolines severely impaired or abolished 7B2 bioactivity as measured by four assays: co-immunoprecipitation with proPC2, facilitation of proPC2 maturation, acquisition of PC2 enzymatic activity, and thermal protection of PC2. An adjacent predicted alpha-helix (residues 107–123) also contributes. Site-directed point mutagenesis; co-immunoprecipitation; proPC2 maturation assay; PC2 enzymatic activity assay; thermal protection assay The Journal of biological chemistry High 8798569
1998 The PC2 proregion is required but not sufficient for 7B2 binding; the P domain stabilizes PC2 structure and is not interchangeable with PC1's P domain; the C-terminal domain is not involved in 7B2 binding. A single residue in the PC2 catalytic domain, Tyr-194, is required for 7B2 binding and proPC2 activation; Y194 is located within a surface-exposed loop rich in aromatic amino acids. Sequential domain deletions, site-directed mutagenesis, and PC2/PC1 domain-swapping chimeras expressed in AtT-20 cells; co-immunoprecipitation; maturation assay; enzymatic activity assay The Journal of biological chemistry High 9422782
1998 7B2 is essential for proteolytic conversion and activation of proPC2 in vivo: cells expressing PC2 but not 7B2 (SK-N-MCIXC neuroepithelioma) contain only inactive proPC2 forms; stable transfection with pro-7B2 rescued secretion of mature, active 68-kDa PC2. In a model of hypoglycemic shock, decreased adrenomedullary 7B2 expression correlated with increased proPC2:PC2 ratio. Immunoblotting of cell fractions; stable transfection of 7B2 cDNA into PC2-expressing cells; insulin-induced hypoglycemic shock animal model; comparison of developing rat brain PC2 forms DNA and cell biology High 9881669
1999 7B2 null mice have no demonstrable PC2 activity, are deficient in processing islet hormones (hyperproinsulinemia, hypoglucagonemia), and develop lethal Cushing's syndrome from pituitary intermediate lobe ACTH hypersecretion. This establishes that 7B2 is absolutely required for PC2 activation in vivo and has additional functions in regulating pituitary hormone secretion beyond PC2. 7B2 null mouse (knockout via transposon-facilitated technique); comparison with PC2 null phenotype; measurement of circulating hormones (ACTH, corticosterone, insulin, glucagon); histology Cell High 10089884
1999 A minimal 36-residue internal peptide of 7B2 (containing the proline-rich sequence, an alpha-helix, and the only disulfide bond) contains all information required for proPC2 activation. Mutation of the alpha-helix or the cysteines forming the disulfide bond abolished proPC2 activation activity. Sequential deletions of 7B2; mutagenesis of alpha-helix and cysteine residues; four functional assays: proPC2 binding, maturation facilitation, in vivo and in vitro proPC2 activation The Journal of biological chemistry High 10409712
1996 Dissociation of the N-terminal 7B2 fragment from proPC2 precedes (and is not directly linked to) proPC2 maturation; proPC2 maturation does not occur while associated with intact 7B2 precursor. The C-terminal region of 7B2 is necessary and sufficient for inhibition of proPC2 conversion in vitro. Pulse-chase analysis in Xenopus and mouse intermediate pituitary cells; in vitro conversion assay with recombinant 7B2 and truncation mutants European journal of biochemistry High 8681965
2000 Residues 242–248 in the PC2 catalytic domain (PC2-specific sequence) are required for binding to 21-kDa 7B2 and for inhibition by the 7B2 CT peptide; replacement with corresponding PC1 residues greatly reduced 7B2 binding and nearly abolished CT peptide inhibition, without profoundly altering substrate cleavage specificity. Site-directed mutagenesis of PC2 catalytic domain; co-immunoprecipitation with 7B2; in vivo proenkephalin and POMC cleavage assays; in vitro fluorogenic substrate assay; CT peptide inhibition assay The Journal of biological chemistry High 10799554
2000 Drosophila 7B2 (d7B2) and rat 7B2 can both support dPC2 (amontillado) secretion and activity in Drosophila S2 insect cells but not in HEK-293 cells, demonstrating that dPC2 requires insect cell-specific posttranslational processing events for maturation and secretion, and that 7B2–PC2 interaction is evolutionarily conserved. Transfection of dPC2 and d7B2/r7B2 cDNAs into HEK-293 and S2 cells; PC2 activity assays; immunoblotting; pulse-chase labeling The Journal of biological chemistry Medium 10749852
2001 Cleavage at the 7B2 furin consensus pentabasic site is required for production of PC2 capable of efficiently cleaving the inhibitory CT peptide. When the furin site is blocked (blockade mutant), intact 27-kDa 7B2 accumulates and PC2 secreted with it lacks ability to inactivate the CT peptide, although proPC2 activation per se does not require furin cleavage when the CT peptide is non-inhibitory. Construction of 7B2 mutants (CT peptide KK→SS; furin site blockade; double mutant); cell-free proPC2 activation assay; transient transfection into HEK293 cells; measurement of PC2 activity and CT peptide forms in conditioned medium Journal of neurochemistry High 11677272
2002 Mortality in 7B2 null mice is caused by elevated corticosterone secondary to ACTH hypersecretion; adrenalectomy rescues survival and normalizes pituitary dopamine (which is reduced to ~25% of WT in 7B2 nulls), circulating ACTH, and corticosterone. This indicates a 7B2-mediated dopaminergic deficiency contributes to ACTH hypersecretion. Adrenalectomy of 7B2 null mice; measurement of circulating ACTH, corticosterone, pituitary dopamine; comparison with PC2 null mice Proceedings of the National Academy of Sciences of the United States of America High 11854475
2005 7B2 can be phosphorylated at Ser115 (and additional serine/threonine residues) by Golgi kinases in Rin cells and chromaffin cells but not AtT-20 cells. Phosphorylated 7B2 is unable to bind proPC2 (co-immunoprecipitation) and is impaired in facilitating proPC2 activation (cell-free assay), functionally inactivating it in a manner analogous to BiP phosphorylation. Metabolic 32P labeling; phosphoamino acid analysis; site-directed mutagenesis of Ser115; co-immunoprecipitation of phospho-7B2 with proPC2; cell-free proPC2 activation assay; in vitro Golgi kinase phosphorylation with kinase inhibitors The Journal of biological chemistry High 16286464
2008 7B2 possesses chaperone activity that prevents unfolding and aggregation of proPC2; addition of exogenous recombinant 7B2 to CHO cells expressing proPC2 prevented secreted PC2 aggregation in a dose-dependent manner. Intracellular proPC2 exists in part as higher-order oligomers, reduced by co-expressed 7B2. Velocity sedimentation showed 7B2 solubilizes three PC2 species from precipitable aggregates. An activation-competent PC2 conformation cannot be maintained without 7B2. Aggregation assays; enzymatic activity assays; chemical cross-linking; sucrose density gradients; velocity sedimentation; addition of exogenous recombinant 7B2 to cells Endocrinology High 18467442
2012 7B2 suppresses fibrillation and aggregation of Aβ(1-42), Aβ(1-40), and α-synuclein in vitro at 1:10 molar ratio. In Neuro-2A cell culture, extracellular or adenovirally overexpressed 7B2 blocked neurocytotoxicity of Aβ(1-42) and increased cell viability; RNAi knockdown of 7B2 increased Aβ(1-42)-induced cytotoxicity. In APP/PSEN1 mouse brains and human AD/PD brains, 7B2 co-localizes with Aβ plaques and α-synuclein deposits. In vitro fibrillation/aggregation assays (ThT fluorescence); adenoviral overexpression; RNAi knockdown; cell viability assays; immunofluorescence co-localization in mouse model and human postmortem brain The Journal of biological chemistry High 23172224
2013 21-kDa 7B2 blocks hIAPP (islet amyloid polypeptide) fibrillation in vitro and protects Rin5f cells from hIAPP cytotoxicity. Structure-function studies identified a central region within 21-kDa 7B2 as important for this anti-aggregation effect. In vitro hIAPP fibrillation assays; cell viability assays; structure-function deletion analysis of 7B2 regions FEBS letters Medium 24042052
1999 7B2 protein is essential for targeting and activation of PC2 into the regulated secretory pathway: antisense suppression of 7B2 in rMTC 6-23 cells (~90% reduction) caused proPC2 to be constitutively released (not stored in secretory granules) and rendered it unable to process proNT/NN, without affecting proPC2 expression levels. Stable transfection with 7B2 antisense cDNA in endocrine rMTC 6-23 cells; immunoblotting; measurement of PC2 activity; pro-neurotensin processing assay; secretion pathway fractionation Biochemical and biophysical research communications High 10198237
1998 The oxyanion hole residue Asp309 in PC2 is critical for binding pro-7B2: the D309N mutation abolished pro-7B2 co-immunoprecipitation and significantly reduced PC2-mediated POMC processing to beta-endorphin. Similarly, Tyr194 participates in the interaction of PC2 with 7B2. Site-directed mutagenesis of PC2; vaccinia virus expression in AtT-20 and GH3 cells; co-immunoprecipitation; POMC processing assay (beta-endorphin production) FEBS letters High 9645470
1995 Processed 7B2 (but not intact 27-kDa 7B2) can enhance in vitro POMC cleavage by PC2 in Xenopus intermediate pituitary cell lysates and with immunopurified Xenopus PC2; intact 7B2 abolished the enhancing effect (consistent with its known PC2 inhibitory activity), confirming that 7B2 displays chaperone/activating activity toward PC2. In vitro POMC cleavage assay in pituitary cell lysates; immunopurified PC2; addition of recombinant intact vs. processed 7B2 forms FEBS letters Medium 7672117
2009 Pax6 transcription factor directly and indirectly (through cMaf and Beta2/NeuroD1) activates the 7B2 gene promoter in pancreatic alpha cells, thereby regulating 7B2 and PC2 expression and glucagon biosynthesis. siRNA knockdown of Pax6 in InR1G9 alpha cells; dominant-negative Pax6 expression; transactivation/binding studies at 7B2 and PC2 promoters Molecular and cellular biology Medium 19223471
2013 Decreased 7B2•PC2 activity in hyp-mouse (XLH model) osteoblasts is central to pathogenesis: reduced 7B2 protein leads to impaired proPC2 activation, decreased FGF-23 cleavage, decreased active BMP1 (from decreased proBMP1 processing), increased DMP1, and elevated Fgf-23 mRNA/protein. Treatment with Hexa-D-Arginine increased 7B2•PC2 activity and rescued the HYP phenotype. Transfection of PC2 + 7B2 into murine osteoblasts; Sgne1 RNAi transfection; measurement of FGF-23, BMP1, DMP1; analysis of hyp-mouse bone (Sgne1 mRNA, 7B2 protein, proPC2 processing); Hexa-D-Arginine treatment of hyp-mice Journal of bone and mineral research High 22886699
2011 7B2 dynamically modulates PC2-mediated peptide processing in a cell type-specific manner: in pancreatic alpha cells (α-TC6), 7B2 overexpression increased glucagon production and intracellular PC2 activity by routing PC2 to secretory granules; siRNA knockdown of 7B2 decreased glucagon. In contrast, 7B2 overexpression did not affect peptide production in anterior pituitary or beta cell lines despite increased PC2 secretion. Adenoviral overexpression of 7B2 in α-TC6 cells; siRNA knockdown; rescue of 7B2 in 7B2 null primary pituitary cultures; measurement of glucagon, α-MSH, and PC2 activity; in vivo glucagon measurement in 7B2-overexpressing cast/cast mice The Journal of biological chemistry High 22013069
2000 Structure-function analysis of the 7B2 CT peptide showed that residues 3–18 are required for inhibitory potency; specific residues (Gln7, Gln9, Asp12) can be individually replaced by Ala without losing activity. All-D, all-L-inverso, and all-D analogues of CT peptide are completely inactive, indicating the main chain and side chains both interact with PC2. CT peptide inhibition requires a Lys-Lys pair for initial active-site binding. N-terminal truncation analysis; alanine scanning mutagenesis; stereo-isomer CT peptide analogues; competitive blockade with truncated peptides; in vitro PC2 inhibition assays Biochemical and biophysical research communications High 10673395
1990 7B2 is a precursor molecule that is processed to an 18-kDa form in the carboxyl-terminal region in Xenopus intermediate lobe. The processed 18-kDa product (but not intact 7B2) is secreted in a regulated (dopamine-inhibitable) manner. Neither form is N-glycosylated. Pulse-chase immunoprecipitation analysis in Xenopus neurointermediate lobe; chemical and enzymatic peptide mapping; tunicamycin treatment; apomorphine inhibition of secretion The Journal of biological chemistry Medium 2394742
1998 The C. elegans 7B2 ortholog, despite only 23% sequence similarity to mammalian 7B2, retains both functional domains: the CT peptide inhibits vertebrate PC2 (IC50 130 nM) and the N-terminal domain facilitates proPC2 activation. The conserved PPNPCP motif and a heptapeptide in the CT region are identified as critical conserved functional elements. cDNA cloning; in vitro PC2 inhibition assays; two functional activation assays for N-terminal domain DNA and cell biology Medium 9726255
1986 7B2 is localized within secretory granules of neuroendocrine cells (electron microscopy: small granules in gonadotrophs and thyrotrophs) and is co-released with catecholamines from bovine chromaffin cells upon nicotinic stimulation, indicating it undergoes regulated (exocytotic) secretion. Electron microscopy immunocytochemistry of pituitary cells; subcellular fractionation of chromaffin granules; RIA of 7B2 release from cultured bovine chromaffin cells stimulated with K+ and nicotine Journal of neurochemistry / Cell and tissue research Medium 3115588 3681297

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
2008 Overexpression of Scg5 increases enzymatic activity of PCSK2 and is inversely correlated with body weight in congenic mice. BMC genetics 17 18439298
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
2006 Differences of pancreatic expression of 7B2 between C57BL/6J and C3H/HeJ mice and genetic polymorphisms at its locus (Sgne1). Diabetes 16 16443780
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
2022 Association Between Maternal Adverse Childhood Experiences and Neonatal SCG5 DNA Methylation-Effect Modification by Prenatal Home Visiting. American journal of epidemiology 12 34791022
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
2016 Clinicopathological features of a kindred with SCG5-GREM1-associated hereditary mixed polyposis syndrome. Human pathology 11 27984123
2011 Dynamic modulation of prohormone convertase 2 (PC2)-mediated precursor processing by 7B2 protein: preferential effect on glucagon synthesis. The Journal of biological chemistry 11 22013069
2005 Neuroendocrine protein 7B2 can be inactivated by phosphorylation within the secretory pathway. The Journal of biological chemistry 11 16286464
1993 Depolarizing action of secretory granule protein 7B2 on rat supraoptic neurosecretory neurons. Journal of neuroendocrinology 11 8680421

Missed literature

Know a paper Affinage missed for SCG5? Flag it for the maintainers and the community.

No submissions yet.