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FLASH GENE

Symbol

PCSK1

contributors: mct - updated : 12-06-2020

HGNC name	proprotein convertase subtilisin/kexin type 1
HGNC id	8743

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a preprodomain, a subtilisin-like catalytic, serine protease domain Ca2+ dependent,
	conserved P(hemo B) domain,
	a furin cysteine-rich region,
	a transmembrane anchor and a cytoplasmic domain
	C-terminus translocated across the endoplasmic reticulum membrane

isoforms

Precursor

autocatalytically activated

HOMOLOGY

Homologene

FAMILY	proprotein convertase subtilisin kexin-like (SPC) subtilase family
	mammalian subtilisin-like proprotein convertase family

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	extracellular
	intracellular
	intracellular,cytoplasm,cytosolic,granule
text	secretory granules
	its propeptide is rapidly and autocatalytically cleaved in the endoplasmic reticulum; the mature protein is sorted and stored in dense-core secretory vesicles, together with its substrates

basic FUNCTION	endopeptidase involved in proteolytic processing of peptide hormone precursors in granules of the regulated secretory pathway of endocrine cells
	specifically cleaving BDNF, processing of hormones and other proteins
	type I proinsulin-processing enzyme that plays a key role in regulating insulin biosynthesis
	involved in the endoproteolytic cleavage of a large number of precursor proteins including prohormones, proneuropeptides, zymogens, and proreceptors
	is a serine endoprotease that is involved in the processing of a variety of proneuropeptides and prohormones

CELLULAR PROCESS

protein, degradation

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

signal transduction

cell-cell signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	PAX6 directly bound to and activated the prohormone convertase 1/3 (PCSK1, PCSK2, FURIN) gene promoter and subsequently regulated proinsulin processing
	NHLH2 has been shown to promote PCSK1 expression
	ANGPTL4 promotes PCSK1-mediated intracellular cleavage of LPL in adipocytes, likely contributing to regulation of LPL in adipose tissue

cell & other

REGULATION

activated by

upregulated during early phase of liver regeneration

ASSOCIATED DISORDERS

corresponding disease(s)

OBS10 , BDIAS

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --low   decreased hypothalamic PCSK1, PCSK2, FURIN in huntington disease patients constitutional       loss of function impairs prohormone processing in Prader-Willi syndrome

Susceptibility

to non insulin dependent diabetes (type II) and coronary artery disease to obesity to hypertension

Variant & Polymorphism other	N221D, and Q665E-S690T pair, associated with obesity in adults and children
	more common variants in the PCSK1 gene have been found to be associated with alterations in body mass index, increased circulating proinsulin levels, and defects in glucose homeostasis
	association of genetic variation in the PCSK1 gene with blood pressure and hypertension

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS