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FLASH GENE

Symbol

FURIN

contributors: mct - updated : 29-11-2014

HGNC name	furin (paired basic amino acid cleaving enzyme)
HGNC id	8568

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	15.17 kb     16 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_002569 16 - 4180 NP_002560 - 794 - 2006 16942750 preproprotein NM_001289823 - - 4198 NP_001276752 - 794 - 2006 16942750 NM_001289824 - - 4352 NP_001276753 - 794 - 2006 16942750

EXPRESSION

Type	ubiquitous

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 Digestive intestine small intestine     highly   liver       highly Endocrine pancreas       highly Reproductive female system placenta     highly Homo sapiens   male system testis     lowly Respiratory lung       lowly Urinary kidney       highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Muscular striatum cardiac   lowly

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 an (hemo B) domain
	a cysteine-rich region
	a transmembrane anchor and a cytoplasmic domain

conjugated

GlycoP , PhosphoP

isoforms

Precursor

autocatalytically activated

HOMOLOGY

interspecies	homolog to murine Furin (93.9pc)
	homolog to rattus Furin (93.8pc)

intraspecies

homolog to PCSK5,PCSK4

Homologene

FAMILY	subtilisin-like proprotein convertase family
	peptidase S8 family
	furin subfamily

CATEGORY

enzyme , signaling

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,lumen
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,Golgi
text	membrane associated protein circulating between the trans-Golgi network and cell surface
	highly expressed in syncytial trophoblast in the first trimester human placenta

basic FUNCTION	paired basic amino-acid residue cleaving enzyme
	involved in processing of pro-parathyroid hormone, von Willebrand factor, insulin receptor, TGF1B, hepatocyte growth factor, C propeptide of collagen type V, alpha 1, NOTCH signaling proteins, certain viral enveloppe glycoproteins, ED1
	protease
	cleaving CD109 and thus involved in the regulation of TGF-beta signaling
	may be responsible for the activation of HIV envelope glycoproteins gp160 and gp140
	may play a role in tumor progression
	cleaving hemojuvelin
	mediating the posttranslational processing of hepcidin
	proprotein convertase that cycles between the plasma membrane, endosomes and the trans-Golgi network (TGN), maintaining a predominant distribution in the latter
	involved in the signaling and trafficking of membrane proteins
	may control hepcidin expression
	SRC and FURIN play crucial roles in tumorigenesis
	FURIN function is required for the development of syncytiotrophoblast structure in the labyrinth layer, as well as for normal embryonic development
	is the primary convertase of ANGPTL3 and endothelial lipase in hepatocytes
	FURIN, PCSK5, and PCSK6 process two triglyceride lipase family members, endothelial lipase and lipoprotein lipase, which are important for HDL remodeling

CELLULAR PROCESS

protein, degradation

PHYSIOLOGICAL PROCESS

development

text	required for ventral closure and axial rotation

PATHWAY

metabolism

signaling

signal transduction

cell-cell signaling

a component

INTERACTION

DNA

RNA

small molecule	metal binding,
	Ca2+

protein	binding to PACS1 which mediates its TGN localization and connection to clathrin adapters
	interacting with FLNA
	interacting with TFR2 and HFE (TFR2 and HFE are involved in holotransferrin-dependent signaling for the regulation of FURIN which involved Erk phosphorylation)
	interaction between the PTB domain of APBA3 and the acidic peptide signal of FURIN regulates the specific localization of FURIN in the TGN
	important role for FURIN in regulated secretion, particularly in intragranular acidification most likely due to impaired processing of ATP6AP1
	MMP14 and FURIN were found to co-localize with Golgi reassembly stacking protein 55 (GORASP2)
	SERPINE1 is an intracellular inhibitor of furin, having an active role in the development of metabolic disorders
	association between FURIN and MMP14 is regulated by the tyrosine kinase SRC
	NOTCH1-FURIN interaction is regulated by the non-receptor tyrosine kinase, SRC
	PCSK3/FURIN was identified as the major proprotein convertase expressed by adipocytes that mediates the endogenous cleavage of C1QTNF12
	SERPINE2 inhibits FURIN, a serine protease that activates MMP17 involved in the shedding of endothelial PROCR, suggesting a direct interaction between SERPINE2 and FURIN in endothelial cells
	PAX6 directly bound to and activated the prohormone convertase 1/3 (PCSK1, PCSK2, FURIN) gene promoter and subsequently regulated proinsulin processing
	FURIN appears to be the essential enzyme for the generation of kisspeptin (KISS1)

cell & other

REGULATION

induced by

leukotriene D4

inhibited by

the not secondly cleaved propeptide

Other	up-regulated by TGFB1
	oxidation by H2O2 disrupts its Ca2+-binding capacity in vitiligo

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral         no expression in small cell lung cancers tumoral     --over   overexpressed in non small cell lung cancers constitutional     --low   decreased hypothalamic PCSK1, PCSK2, FURIN in huntington disease patients constitutional     --low   in the syncytiotrophoblast is significantly lower in the placentas from pre-eclamptic patients as compared with their gestational age-matched control placentas

Susceptibility

to (PACE) insulin-resistent diabetes (INSR), hemophilia B (F9) and Marfan syndrome (FBN1)

Variant & Polymorphism SNP	SNP in the P1 promoter of FURIN affects furin transcription activity and hepatitis B virus infection outcome

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

mutant-/- embryomic lethal,failing to undergo looping and embryonic turning