Gene Report

Basic Information

Approved Symbol	PCSK2
Approved Name	proprotein convertase subtilisin/kexin type 2
Previous Symbol	NEC2
Symbol Alias	PC2, SPC2
Name Alias	"neuroendocrine convertase 2", "KEX2-like endoprotease 2"
Location	20p11.2
Position	chr20:17462716-17465223 (+)
External Links	Entrez Gene: 5126 Ensembl: ENSG00000125851 UCSC: uc002wpm.3 HGNC ID: 8744
No. of Studies (Positive/Negative)	1(1/0)
Type	Literature-origin

Positive relationships between PCSK2 and MDD (count: 1)

Name in Literature	Reference	Research Type	Statistical Result	Relation Description
PCSK2	Aston, 2005	patients and normal controls		Genes altered in major depressive disorder Genes altered in major depressive disorder

Positive relationships between PCSK2 and other components at different levels (count: 0)

Positive relationship network of PCSK2 in MK4MDD

Network loading ...

Note:
1. The different color of the nodes denotes the level of the nodes.

Genetic/Epigenetic Locus	Protein and Other Molecule	Cell and Molecular Pathway	Neural System	Cognition and Behavior	Symptoms and Signs	Environment	MDD

2. Besides the component related relationships from literature, gene mapped protein and protein mapped gene are also shown in the network. If the mapped gene or protein is not from literature, square node would be used instead of Circle node. Accordingly, the relationship is marked with dot line.
2. User can drag the nodes to rearrange the layout of the network. Click the node will enter the report page of the node. Right-click will show also the menus to link to the report page of the node and remove the node and related edges. Hover the node will show the level of the node and hover the edge will show the evidence/description of the edge.
3. The network is generated using Cytoscape Web

Negative relationships between PCSK2 and MDD (count: 0)

Negative relationships between PCSK2 and other components at different levels (count: 0)

PCSK2 related SNPs in MK4MDD (count: 0)

PCSK2 related proteins in MK4MDD (count: 0)

PCSK2 related GO terms (count: 16)

ID	Name	Type	Evidence
Gene mapped GO terms
GO:0043204	perikaryon	cellular component	IEA
GO:0004252	serine-type endopeptidase activity	molecular function	IDA[7626024]
GO:0006508	proteolysis	biological process	IDA[7626024]
GO:0030133	transport vesicle	cellular component	IEA
GO:0005515	protein binding	molecular function	IPI[7913882]
GO:0030425	dendrite	cellular component	IEA
GO:0007399	nervous system development	biological process	IEA
GO:0034230	enkephalin processing	biological process	ISS
GO:0005615	extracellular space	cellular component	IDA[9020868]
GO:0030070	insulin processing	biological process	IDA[7626024]
GO:0044267	cellular protein metabolic process	biological process	TAS
GO:0016540	protein autoprocessing	biological process	IEA
GO:0016020	membrane	cellular component	IDA[8034613]
GO:0034774	secretory granule lumen	cellular component	TAS
GO:0032403	protein complex binding	molecular function	IEA
GO:0034231	islet amyloid polypeptide processing	biological process	ISS

PCSK2 related KEGG pathways (count: 0)

PCSK2 related BioCarta pathways (count: 0)

PCSK2 related Reactome pathways (count: 2)

ID	Name	Description
Gene mapped Reactome pathways
REACT_15550	insulin synthesis_and_secretion	Synthesis of insulin-containing secretory granules can be de...... Synthesis of insulin-containing secretory granules can be described in 6 steps: transcription of preproinsulin genes, translation of preproinsulin mRNA with concomitant removal of the signal peptide, formation of intramolecular disulfide bonds, formation of proinsulin-zinc-calcium complexes, proteolytic cleavage of proinsulin to yield insulin, translocation of the granules across the cytosol to the plasma membrane. Transcription of the human insulin gene INS is activated by 4 important transcription factors: Pdx-1, MafA, Beta2/NeuroD1, and E47. The transcription factors interact with each other at the promoters of the insulin gene and act synergistically to promote transcription. Expression of the transcription factors is upregulated in response to glucose. The preproinsulin mRNA is translated by ribosomes at the rough endoplasmic reticulum (ER) and the preproinsulin enters the secretion pathway by virtue of its signal peptide, which is cleaved during translation to yield proinsulin. Evidence indicates that the preproinsulin mRNA is stabilized by glucose. Within the ER, three intramolecular disulfide bonds form between cysteine residues in the proinsulin. Formation of the bonds is the spontaneous result of the conformation of proinsulin and the oxidizing environment of the ER, which is maintained by Ero1-like alpha The cystine bonded proinsulin then moves via vesicles from the ER to the Golgi Complex. High concentrations of zinc are maintained in the Golgi by zinc transporters ZnT5, ZnT6, and ZnT7 and the proinsulin forms complexes with zinc and calcium. Proinsulin-zinc-calcium complexes bud in vesicles from the trans-Golgi to form immature secretory vesicles (secretory granules) in the cytosol. Within the immature granules the endoproteases Prohormone Convertase 1/3 and Prohormone Convertase 2 cleave at two sites of the proinsulin and Carboxypeptidase E removes a further 4 amino acid residues to yield the cystine-bonded A and B chains of mature insulin and the C peptide, which will also be secreted with the insulin. The insulin-zinc-calcium complexes form insoluble crystals within the granule The insulin-containing secretory granules are then translocated across the cytosol to the inner surface of the plasma membrane. Translocation occurs initially by attachment of the granules to Kinesin-1, which motors along microtubules, and then by attachment to Myosin Va, which motors along the microfilaments of the cortical actin network. A pancreatic beta cell contains about 10000 insulin granules of which about 1000 are docked at the plasma membrane and 50 are readily releasable in immediate response to stimulation by glucose or other secretogogues. Docking is due to interaction between the Exocyst proteins EXOC3 on the granule membrane and EXOC4 on the plasma membrane. Exocytosis is accomplished by interaction between SNARE-type proteins Syntaxin 1A and Syntaxin 4 on the plasma membrane and Synaptobrevin-2/VAMP2 on the granule membrane. Exocytosis is a calcium-dependent process due to interaction of the calcium-binding membrane protein Synaptotagmin V/IX with the SNARE-type proteins. More...
REACT_15380	diabetes pathways

PCSK2 related interactors from protein-protein interaction data in HPRD (count: 3)

Gene	Interactor	Interactor in MK4MDD?	Experiment Type	PMID
PCSK2	SCG5	No	in vitro;in vivo	11439082 , 7722516
PCSK2	PMCH	No	in vivo	10037747
PCSK2	IAPP	No	in vitro;in vivo	3053705 , 8557106 , 11246872 , 10931181

Gene Report

Gene mapped GO terms

Gene mapped Reactome pathways