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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

Corresponding disease	BDIAS Blue diaper syndrome OBS10 extreme obesity with a defective prohormone processing
Location	5q15      Physical location : 95.726.039 - 95.768.985
Synonym name	neuroendocrine convertase 1,protein convertase 1/3
Synonym symbol(s)	NEC1, PC1, PC3, SKI1, PCSK, BMIQ12, SPC3
EC.number	3.4.21.93

DNA

TYPE	functioning gene
STRUCTURE	42.92 kb     14 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

confirmed

RNA

TRANSCRIPTS	type	messenger

text	multiple alternatively spliced transcript variants

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_000439 14 - 5136 NP_000430 - 753 - 2016 28271036 NM_001177875 14 - 4824 NP_001171346 - 706 - 2016 28271036

EXPRESSION

Type

widely

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 neuroendocrine pituitary     highly   pancreas       highly nervous brain diencephalon       Nervous nerve spinal nerve sciatic     Visual eye retina

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective bone       Epithelial secretory glandular endocrine

cells

System Cell Pubmed Species Stage Rna symbol Nervous neuron Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

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