Disease relevance of SCG5

• Identification and localization of 7B2 protein in human, porcine, and rat thyroid gland and in human medullary carcinoma [1].
• Three of nineteen human medullary carcinoma cases showed immunoreactive 7B2 within the early and late hyperplasia stages and neoplasia [1].
• The vasopressin precursor is not processed in the hypothalamus of Wolfram syndrome patients with diabetes insipidus: evidence for the involvement of PC2 and 7B2 [2].
• Finally, the human neuroepithelioma SK-N-MCIXC expresses PC2 but not 7B2 [3].
• Differential expression of the gene encoding the novel pituitary polypeptide 7B2 in human lung cancer cells [4].

Psychiatry related information on SCG5

• Evidence for a novel pituitary protein (7B2) in human brain, cerebrospinal fluid and plasma: brain concentrations in controls and patients with Alzheimer's disease [5].

High impact information on SCG5

• When incubated in vitro with newly synthesized pituitary proteins, recombinant 7B2 specifically associates with prohormone convertase PC2 [6].
• Internal cleavage of the inhibitory 7B2 carboxyl-terminal peptide by PC2: a potential mechanism for its inactivation [7].
• Once the proPC2/7B2 complex arrives at the trans-Golgi network, 7B2 is internally cleaved into two domains, the 21-kDa fragment and a carboxy-terminal 31 residue peptide [8].
• The protein designated 7B2 is a recently discovered pituitary polypeptide which is selectively expressed in cells containing secretory granules, such as neurons and endocrine cells [4].
• In only one of four non-SCLC cell lines tested, 7B2 was expressed [4].

Chemical compound and disease context of SCG5

• Secretory protein 7B2 response to oral glucose loading and intravenous glucagon injection in patients with diabetes mellitus [9].
• Thyrotropin releasing hormone (TRH)-induced release of 7B2 (neuroendocrine polypeptide) in vivo and in vitro using adenoma cells of a patient with acromegaly [10].

Biological context of SCG5

• Two types of mRNAs for neuroendocrine protein 7B2 were deduced from the sequence of cDNAs clones isolated from a human pituitary cDNA library [11].
• The production by alternate splicing of two mRNAs differing by one codon could be an intrinsic property of neuroendocrine protein 7B2 gene expression in man [11].
• This report describes the genomic organization of the 7B2 gene which consists of six exons [12].
• Of further interest is the finding of two DNA elements which are common to the promoter regions of the 7B2 gene and other genes selectively expressed in neuroendocrine tissues [12].
• Primer-extension analysis showed that the human 7B2 gene is transcribed from multiple transcription-initiation sites [12].

Anatomical context of SCG5

• By immunocytochemistry 7B2 was colocalized with calcitonin in parafollicular cells and identified within secretory granules by electron microscopy [1].
• The novel, highly conserved polypeptide 7B2, which belongs to a new protein superfamily, was isolated from human and porcine hypophysis [1].
• As in previous reports concerning the brain, adenohypophysis, and thyroid gland, IR-7B2 could be detected by electron microscopy within secretory granules of alpha- and beta-like cells in islets [13].
• Attenuation of the polypeptide 7B2, prohormone convertase PC2, and vasopressin in the hypothalamus of some Prader-Willi patients: indications for a processing defect [14].
• In a previous study we were able to show 7B2 immunoreactivity in the supraoptic nucleus (SON) or the paraventricular nucleus (PVN) in only three of five PWS patients [14].

Associations of SCG5 with chemical compounds

• Involvement of a polyproline helix-like structure in the interaction of 7B2 with prohormone convertase 2 [15].
• We conclude that both the proline-rich region and the alpha-helix contribute to 7B2 activity [15].
• Site-directed mutagenesis of pro-PC2 further showed that a single residue replacement in the catalytic domain, Tyr-194 --> Asp, prevented pro-PC2 from binding 7B2 and blocked activation [16].
• The response of circulating IR-7B2 to oral glucose was also evaluated [17].
• Except for a few cells which were simultaneously positive for 5-hydroxytryptamine, and a few others showing Grimelius's reaction, "7B2" cells do not exhibit argentaffin and/or argyrophil character [18].

Physical interactions of SCG5

• 7B2 is a neuroendocrine chaperone that transiently interacts with prohormone convertase PC2 in the secretory pathway [6].
• Interestingly, both 7B2 and the molecular chaperone DnaK interact with IGF1 in the yeast two-hybrid system [19].
• Like DnaK, 7B2 also binds the tumor suppressor protein p53 [19].

Regulatory relationships of SCG5

• None of the 7B2 mutant proteins inhibited PC1/PC3 activity [20].
• Previous studies have demonstrated that while the carboxyl-terminal portion of 7B2 (residues 155-186) regulates the enzymatic activity of PC2, the amino terminus of the molecule (residues 1-151) is required for maturation of proPC2 [15].

Other interactions of SCG5

• The human 7B2 gene promoter contains a cAMP-responsive element, an AP-1 site, and several Pit-1/GHF-1-binding domains and heat-shock-element-like sequences but no obvious TATA or CAAT boxes [12].
• We conclude that cleavage at the 7B2 furin consensus site is required to produce PC2 capable of efficient proteolytic inactivation of the CT peptide [21].
• It is conceivable that 7B2 participates in an analogous manner in the dissociation of non-covalently linked multimers of IGF1 [19].
• Inactivation of the 7B2 inhibitory CT peptide depends on a functional furin cleavage site [21].
• Unlike 7B2, proSAAS-(1-225) was able to slow convertase-mediated processing of proopiomelanocortin and proenkephalin; however, similarly to 7B2, proSAAS expression did not result in any accumulated differences in the content of cellular processed peptide [22].

Analytical, diagnostic and therapeutic context of SCG5

• 7B2 was purified from thyroid homogenates by HPLC chromatography and characterized by gel permeation chromatography (dimeric mol wt, approximately 40,000) and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (monomeric mol wt, 20,750) [1].
• Cloning and sequence analysis of human pituitary cDNA encoding the novel polypeptide 7B2 [23].
• Regional mapping of the human gene encoding the novel pituitary polypeptide 7B2 to chromosome 15q13----q14 by in situ hybridization [24].
• In this study we employed four different experimental approaches (co-immunoprecipitation with proPC2, facilitation of pro-PC2 maturation, acquisition of enzymatic activity, and thermal protection assays) to identify structural elements of 7B2 important for bioactivity [15].
• Based upon migration on SDS-PAGE, the apparent molecular weight of the major form of 7B2 extracted from different brain regions was found to be 22,000, identical to that of the pituitary form [25].

References