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FLASH GENE

Symbol

PCSK2

contributors: mct - updated : 26-08-2015

HGNC name	proprotein convertase subtilisin/kexin type 2
HGNC id	8744

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	258.47 kb     12 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

Y

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001201528 13 - 4687 NP_001188457 - 619 - - NM_002594 12 - 4787 NP_002585 - 638 - - NM_001201529 11 - 4682 NP_001188458 - 603 - -

EXPRESSION

Type

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Endocrine thyroid         nervous brain diencephalon       Visual eye uvea choroid

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial barrier/lining retinal pigment epithelium (RPE)

cells

System Cell Pubmed Species Stage Rna symbol Endocrine islet cell (alpha,beta...) Nervous neuron Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

fetal

Text

eye

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a preprodomain,a subtilisin-like catalytic,serine protease domain Ca2+ dependent
	conserved P an (hemo B) domain
	a furin cysteine-rich region
	a transmembrane anchor and a catalytic domain with D/H/S catalytic triad

isoforms

Precursor

autocatalytically activated

HOMOLOGY

Homologene

FAMILY

proprotein convertase subtilisin kexin-like (SPC) subtilase family

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	extracellular
	plasma membrane
	intracellular
	intracellular,cytoplasm,cytosolic,granule
text	secretory granules

basic FUNCTION	involved in the processing of hormone and other protein precursors at sites comprised of pairs of basic amino acid residues
	requires interaction with the neuroendocrine protein SCG5 for the production of an activatable zymogen
	is the essential enzyme for pancreatic proinsulin processing
	activation of the hypothalamic FFAR1 signaling pathway may regulate beta-endorphin release via PCSK2, and regulate the endogenous pain control system

CELLULAR PROCESS

protein, degradation

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	proinsulin processing enzyme playing a key role in regulating insulin biosynthesis
	SCG5 is required for the production of active prohormone convertase 2 (PCSK2), an enzyme involved in the synthesis of peptide hormones, such as glucagon and POMC
	SCG5 is a prohormone convertase 2 (PCSK2)-binding protein
	PAX6 directly bound to and activated the prohormone convertase 1/3 (PCSK1, PCSK2, FURIN) gene promoter and subsequently regulated proinsulin processing
	activation of the hypothalamic FFAR1 signaling pathway may regulate beta-endorphin release via PCSK2, and regulate the endogenous pain control system

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --low   decreased hypothalamic PCSK1, PCSK2, FURIN in huntington disease patients

Susceptibility

to type 2 diabetes

Variant & Polymorphism	variant of the PCSK2 gene associated with reduced glucose-stimulated insulin secretion, but also with lower glucagon levels, which could potentially counteract the effects of decreased insulin secretion on the risk of type 2 diabetes

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

Pcsk2-null mice exhibit delayed intestinal motility, reduced refeeding response and altered plasma levels of several regulatory peptides