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FURIN (furin, paired basic amino acid cleaving enzyme)

Gene

5045

Furin, paired basic amino acid cleaving enzyme

FURIN

FUR, PACE, PCSK3, SPC1

15q26.1

This gene encodes a member of the subtilisin-like proprotein convertase family, which includes proteases that process protein and peptide precursors trafficking through regulated or constitutive branches of the secretory pathway. It encodes a type 1 membrane bound protease that is expressed in many tissues, including neuroendocrine, liver, gut, and brain. The encoded protein undergoes an initial autocatalytic processing event in the ER and then sorts to the trans-Golgi network through endosomes where a second autocatalytic event takes place and the catalytic activity is acquired. Like other members of this convertase family, the product of this gene specifically cleaves substrates at single or paired basic residues. Some of its substrates include proparathyroid hormone, transforming growth factor beta 1 precursor, proalbumin, pro-beta-secretase, membrane type-1 matrix metalloproteinase, beta subunit of pro-nerve growth factor and von Willebrand factor. It is thought to be one of the proteases responsible for the activation of HIV envelope glycoproteins gp160 and gp140, and may play a role in tumor progression. Unlike SARS-CoV and other coronaviruses, the spike protein of SARS-CoV-2 is thought to be uniquely cleaved by this protease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2020]

Show/Hide all(98)

miRTarBase ID	miRNA	Experiments	Reference
MIRT005919	hsa-miR-24-3p	Luciferase reporter assay, Microarray, qRT-PCR, Western blot	20945401
MIRT005919	hsa-miR-24-3p	qRT-PCR, Western blot	22260784
MIRT027060	hsa-miR-103a-3p	Sequencing	20371350
MIRT027060	hsa-miR-103a-3p	PAR-CLIP	23592263
MIRT027060	hsa-miR-103a-3p	PAR-CLIP	26701625
MIRT031785	hsa-miR-16-5p	Sequencing	20371350
MIRT031785	hsa-miR-16-5p	PAR-CLIP	23592263
MIRT031785	hsa-miR-16-5p	PAR-CLIP	26701625
MIRT039979	hsa-miR-615-3p	CLASH	23622248
MIRT042240	hsa-miR-484	CLASH	23622248
MIRT476678	hsa-miR-6778-5p	PAR-CLIP	23592263
MIRT476678	hsa-miR-6778-5p	PAR-CLIP	26701625
MIRT476679	hsa-miR-1233-5p	PAR-CLIP	23592263
MIRT476679	hsa-miR-1233-5p	PAR-CLIP	26701625
MIRT476680	hsa-miR-6766-5p	PAR-CLIP	23592263
MIRT476680	hsa-miR-6766-5p	PAR-CLIP	26701625
MIRT476681	hsa-miR-6756-5p	PAR-CLIP	23592263
MIRT476681	hsa-miR-6756-5p	PAR-CLIP	26701625
MIRT476682	hsa-miR-6508-3p	PAR-CLIP	23592263
MIRT476682	hsa-miR-6508-3p	PAR-CLIP	26701625
MIRT476683	hsa-miR-6739-5p	PAR-CLIP	23592263
MIRT476683	hsa-miR-6739-5p	PAR-CLIP	26701625
MIRT476684	hsa-miR-6733-5p	PAR-CLIP	23592263
MIRT476684	hsa-miR-6733-5p	PAR-CLIP	26701625
MIRT476685	hsa-miR-3153	PAR-CLIP	23592263
MIRT476685	hsa-miR-3153	PAR-CLIP	26701625
MIRT476686	hsa-miR-4505	PAR-CLIP	23592263
MIRT476686	hsa-miR-4505	PAR-CLIP	26701625
MIRT476687	hsa-miR-5787	PAR-CLIP	23592263
MIRT476687	hsa-miR-5787	PAR-CLIP	26701625
MIRT476688	hsa-miR-6089	PAR-CLIP	23592263
MIRT476688	hsa-miR-6089	PAR-CLIP	26701625
MIRT476689	hsa-miR-4286	PAR-CLIP	23592263
MIRT476689	hsa-miR-4286	PAR-CLIP	26701625
MIRT476690	hsa-miR-6783-5p	PAR-CLIP	23592263
MIRT476690	hsa-miR-6783-5p	PAR-CLIP	26701625
MIRT476691	hsa-miR-6856-5p	PAR-CLIP	23592263
MIRT476691	hsa-miR-6856-5p	PAR-CLIP	26701625
MIRT476692	hsa-miR-6758-5p	PAR-CLIP	23592263
MIRT476692	hsa-miR-6758-5p	PAR-CLIP	26701625
MIRT476693	hsa-miR-140-3p	PAR-CLIP	23592263
MIRT476693	hsa-miR-140-3p	PAR-CLIP	26701625
MIRT476694	hsa-miR-6838-5p	PAR-CLIP	23592263
MIRT476694	hsa-miR-6838-5p	PAR-CLIP	26701625
MIRT476695	hsa-miR-497-5p	PAR-CLIP	23592263
MIRT476695	hsa-miR-497-5p	PAR-CLIP	26701625
MIRT476696	hsa-miR-424-5p	PAR-CLIP	23592263
MIRT476696	hsa-miR-424-5p	PAR-CLIP	26701625
MIRT476697	hsa-miR-195-5p	PAR-CLIP	23592263
MIRT476697	hsa-miR-195-5p	PAR-CLIP	26701625
MIRT476698	hsa-miR-15a-5p	PAR-CLIP	23592263
MIRT476698	hsa-miR-15a-5p	PAR-CLIP	26701625
MIRT476699	hsa-miR-15b-5p	PAR-CLIP	23592263
MIRT476699	hsa-miR-15b-5p	PAR-CLIP	26701625
MIRT476700	hsa-miR-107	PAR-CLIP	23592263
MIRT476700	hsa-miR-107	PAR-CLIP	26701625
MIRT736863	hsa-miR-1273h-5p	PAR-CLIP	26701625
MIRT737667	hsa-miR-148a-3p	PAR-CLIP	26701625
MIRT737680	hsa-miR-148b-3p	PAR-CLIP	26701625
MIRT737728	hsa-miR-149-3p	PAR-CLIP	26701625
MIRT737869	hsa-miR-152-3p	PAR-CLIP	26701625
MIRT739648	hsa-miR-302c-3p	PAR-CLIP	26701625
MIRT739753	hsa-miR-30b-3p	PAR-CLIP	26701625
MIRT741288	hsa-miR-328-5p	PAR-CLIP	26701625
MIRT742255	hsa-miR-3689a-3p	PAR-CLIP	26701625
MIRT742325	hsa-miR-3689b-3p	PAR-CLIP	26701625
MIRT742395	hsa-miR-3689c	PAR-CLIP	26701625
MIRT743354	hsa-miR-4253	PAR-CLIP	26701625
MIRT746326	hsa-miR-4640-5p	PAR-CLIP	26701625
MIRT747219	hsa-miR-4697-3p	PAR-CLIP	26701625
MIRT747755	hsa-miR-4726-5p	PAR-CLIP	26701625
MIRT747824	hsa-miR-4728-5p	PAR-CLIP	26701625
MIRT748023	hsa-miR-4738-5p	PAR-CLIP	26701625
MIRT750242	hsa-miR-520f-3p	PAR-CLIP	26701625
MIRT751689	hsa-miR-6076	PAR-CLIP	26701625
MIRT755494	hsa-miR-6779-5p	PAR-CLIP	26701625
MIRT755570	hsa-miR-6780a-5p	PAR-CLIP	26701625
MIRT755819	hsa-miR-6785-5p	PAR-CLIP	26701625
MIRT756168	hsa-miR-6797-3p	PAR-CLIP	26701625
MIRT756299	hsa-miR-6799-5p	PAR-CLIP	26701625
MIRT757890	hsa-miR-6862-5p	PAR-CLIP	26701625
MIRT758404	hsa-miR-6883-5p	PAR-CLIP	26701625
MIRT758538	hsa-miR-6885-5p	PAR-CLIP	26701625
MIRT758851	hsa-miR-7106-5p	PAR-CLIP	26701625
MIRT790082	hsa-miR-1285-3p	HITS-CLIP	28735896
MIRT790257	hsa-miR-3187-5p	HITS-CLIP	28735896
MIRT790286	hsa-miR-331-3p	HITS-CLIP	28735896
MIRT790412	hsa-miR-4292	HITS-CLIP	28735896
MIRT790635	hsa-miR-4779	HITS-CLIP	28735896
MIRT790706	hsa-miR-5189-5p	HITS-CLIP	28735896
MIRT790823	hsa-miR-612	HITS-CLIP	28735896
MIRT790886	hsa-miR-6721-5p	HITS-CLIP	28735896
MIRT790899	hsa-miR-6731-5p	HITS-CLIP	28735896
MIRT790963	hsa-miR-6791-5p	HITS-CLIP	28735896
MIRT790977	hsa-miR-6805-5p	HITS-CLIP	28735896
MIRT791047	hsa-miR-6860	HITS-CLIP	28735896
MIRT791140	hsa-miR-8085	HITS-CLIP	28735896
MIRT791165	hsa-miR-939-3p	HITS-CLIP	28735896

Transcription factors

Show/Hide all(2)

Transcription factor	Regulation	Reference
CEBPB	Activation	8132667
GATA1	Unknown	12411321

Show/Hide all(64)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000139	Component	Golgi membrane	IMP	9130696, 11799113
GO:0000139	Component	Golgi membrane	TAS
GO:0001825	Process	Blastocyst formation	IEA
GO:0002020	Function	Protease binding	IPI	14744861
GO:0004175	Function	Endopeptidase activity	IDA	9242664, 17010968
GO:0004175	Function	Endopeptidase activity	IMP	20489134
GO:0004175	Function	Endopeptidase activity	TAS
GO:0004252	Function	Serine-type endopeptidase activity	IBA	21873635
GO:0004252	Function	Serine-type endopeptidase activity	IDA	7737999, 8615794, 10567353, 21763278
GO:0004252	Function	Serine-type endopeptidase activity	IMP	9130696, 11799113
GO:0004252	Function	Serine-type endopeptidase activity	TAS
GO:0004867	Function	Serine-type endopeptidase inhibitor activity	IDA	10567353
GO:0005515	Function	Protein binding	IPI	20608975, 21152186, 23829672, 25543063, 32512386, 32703818, 32814053, 33037310, 33043282
GO:0005576	Component	Extracellular region	TAS
GO:0005615	Component	Extracellular space	IDA	10567353
GO:0005783	Component	Endoplasmic reticulum	IGI	17938254
GO:0005796	Component	Golgi lumen	TAS
GO:0005802	Component	Trans-Golgi network	IBA	21873635
GO:0005802	Component	Trans-Golgi network	IDA	14744861
GO:0005886	Component	Plasma membrane	TAS
GO:0006465	Process	Signal peptide processing	IDA	16912035
GO:0006465	Process	Signal peptide processing	TAS
GO:0007179	Process	Transforming growth factor beta receptor signaling pathway	TAS
GO:0008233	Function	Peptidase activity	IDA	10526337, 15082773, 15606899, 17938254
GO:0009966	Process	Regulation of signal transduction	IEA
GO:0009986	Component	Cell surface	IDA	16537537
GO:0010008	Component	Endosome membrane	IEA
GO:0010951	Process	Negative regulation of endopeptidase activity	IEA
GO:0016020	Component	Membrane	HDA	19946888
GO:0016020	Component	Membrane	IBA	21873635
GO:0016485	Process	Protein processing	IBA	21873635
GO:0016485	Process	Protein processing	IDA	9242664, 10526337, 10567353, 14744861, 15606899, 17938254
GO:0016485	Process	Protein processing	IMP	15899807
GO:0016486	Process	Peptide hormone processing	IBA	21873635
GO:0016486	Process	Peptide hormone processing	IDA	9242664
GO:0019058	Process	Viral life cycle	IEP	8940009
GO:0019082	Process	Viral protein processing	TAS
GO:0022617	Process	Extracellular matrix disassembly	TAS
GO:0030140	Component	Trans-Golgi network transport vesicle	IDA	15078902
GO:0030173	Component	Integral component of Golgi membrane	IBA	21873635
GO:0030198	Process	Extracellular matrix organization	TAS
GO:0030574	Process	Collagen catabolic process	TAS
GO:0031638	Process	Zymogen activation	IMP	9130696, 11799113
GO:0032374	Process	Regulation of cholesterol transport	IEA
GO:0032455	Process	Nerve growth factor processing	TAS
GO:0032804	Process	Negative regulation of low-density lipoprotein particle receptor catabolic process	IDA	16912035
GO:0032902	Process	Nerve growth factor production	IDA	8615794
GO:0032904	Process	Negative regulation of nerve growth factor production	IDA	10567353
GO:0032911	Process	Negative regulation of transforming growth factor beta1 production	IMP	15899807
GO:0032940	Process	Secretion by cell	IDA	8615794
GO:0042176	Process	Regulation of protein catabolic process	IMP	15899807
GO:0042277	Function	Peptide binding	IDA	8940009
GO:0043043	Process	Peptide biosynthetic process	IDA	8262946
GO:0044267	Process	Cellular protein metabolic process	TAS
GO:0045121	Component	Membrane raft	IDA	17010968
GO:0046872	Function	Metal ion binding	IEA
GO:0048406	Function	Nerve growth factor binding	IDA	8615794
GO:0051004	Process	Regulation of lipoprotein lipase activity	TAS
GO:0051044	Process	Positive regulation of membrane protein ectodomain proteolysis	IC	17010968
GO:0052548	Process	Regulation of endopeptidase activity	IDA	14744861
GO:0070062	Component	Extracellular exosome	HDA	19199708
GO:0070268	Process	Cornification	TAS
GO:0090472	Process	Dibasic protein processing	IMP	11799113
GO:1901394	Process	Positive regulation of transforming growth factor beta1 activation	IDA	7737999

MIM	HGNC	e!Ensembl
136950	8568	ENSG00000140564

Protein

UniProt ID

P09958

Protein name

Furin (EC 3.4.21.75) (Dibasic-processing enzyme) (Paired basic amino acid residue-cleaving enzyme) (PACE)

Protein function

Ubiquitous endoprotease within constitutive secretory pathways capable of cleavage at the RX(K/R)R consensus motif (PubMed:11799113, PubMed:1629222, PubMed:1713771, PubMed:2251280, PubMed:24666235, PubMed:25974265, PubMed:7592877, PubMed:7690548, PubMed:9130696). Mediates processing of TGFB1, an essential step in TGF-beta-1 activation (PubMed:7737999). Converts through proteolytic cleavage the non-functional Brain natriuretic factor prohormone into its active hormone BNP(1-32) (PubMed:20489134, PubMed:21763278). ; (Microbial infection) Cleaves and activates diphtheria toxin DT. ; (Microbial infection) Cleaves and activates anthrax toxin protective antigen (PA). ; (Microbial infection) Required for H7N1 and H5N1 influenza virus infection probably by cleaving hemagglutinin. ; (Microbial infection) Able to cleave S.pneumoniae serine-rich repeat protein PsrP. ; (Microbial infection) Facilitates human coronaviruses EMC and SARS-CoV-2 infections by proteolytically cleaving the spike protein at the monobasic S1/S2 cleavage site. This cleavage is essential for spike protein-mediated cell-cell fusion and entry into human lung cells.

PDB

4OMC , 4OMD , 4RYD , 4Z2A , 5JMO , 5JXG , 5JXH , 5JXI , 5JXJ , 5MIM , 6A8Y , 6EQV , 6EQW , 6EQX , 6HLB , 6HLD , 6HLE , 6HZA , 6HZB , 6HZC , 6HZD , 6YD2 , 6YD3 , 6YD4 , 6YD7

Family and domains

Pfam

Accession	ID	Position in sequence	Description	Type
PF16470	S8_pro-domain	33 → 107	Peptidase S8 pro-domain	Domain
PF00082	Peptidase_S8	144 → 427	Subtilase family	Domain
PF01483	P_proprotein	484 → 570	Proprotein convertase P-domain	Family

Sequence

MELRPWLLWVVAATGTLVLLAADAQGQKVFTNTWAVRIPGGPAVANSVARKHGFLNLGQI
FGDYYHFWHRGVTKRSLSPHRPRHSRLQREPQVQWLEQQVAKRRTKRDVYQEPTDPKFPQ
QWYLSGVTQRDLNVKAAWAQGYTGHGIVVSILDDGIEKNHPDLAGNYDPGASFDVNDQDP
DPQPRYTQMNDNRHGTRCAGEVAAVANNGVCGVGVAYNARIGGVRMLDGEVTDAVEARSL
GLNPNHIHIYSASWGPEDDGKTVDGPARLAEEAFFRGVSQGRGGLGSIFVWASGNGGREH
DSCNCDGYTNSIYTLSISSATQFGNVPWYSEACSSTLATTYSSGNQNEKQIVTTDLRQKC
TESHTGTSASAPLAAGIIALTLEANKNLTWRDMQHLVVQTSKPAHLNANDWATNGVGRKV
SHSYGYGLLDAGAMVALAQNWTTVAPQRKCIIDILTEPKDIGKRLEVRKTVTACLGEPNH
ITRLEHAQARLTLSYNRRGDLAIHLVSPMGTRSTLLAARPHDYSADGFNDWAFMTTHSWD
EDPSGEWVLEIENTSEANNYGTLTKFTLVLYGTAPEGLPVPPESSGCKTLTSSQACVVCE
EGFSLHQKSCVQHCPPGFAPQVLDTHYSTENDVETIRASVCAPCHASCATCQGPALTDCL
SCPSHASLDPVEQTCSRQSQSSRESPPQQQPPRLPPEVEAGQRLRAGLLPSHLPEVVAGL
SCAFIVLVFVTVFLVLQLRSGFSFRGVKVYTMDRGLISYKGLPPEAWQEECPSDSEEDEG
RGERTAFIKDQSAL

Sequence length

794

Interactions

View interactions

	KEGG		Reactome
	Viral life cycle - HIV-1		Collagen degradation Elastic fibre formation Activation of Matrix Metalloproteinases Removal of aminoterminal propeptides from gamma-carboxylated proteins NGF processing Synthesis and processing of ENV and VPU Signaling by PDGF Pre-NOTCH Processing in Golgi TGF-beta receptor signaling activates SMADs Uptake and function of anthrax toxins Formation of the cornified envelope Assembly of active LPL and LIPC lipase complexes CD163 mediating an anti-inflammatory response Amyloid fiber formation

Associated diseases

Show/Hide Causal Diseases (4)

Causal
Disease name	Disease term	dbSNP ID	References
Schizophrenia	Schizophrenia	rs74315508, rs74315509, rs13447324, rs1558507406, rs387906932, rs387906933, rs-1, rs863223354, rs863223355, rs776061422, rs863223349, rs748809996, rs759748655, rs863223353, rs863223350, rs863223356, rs781821239, rs863223348, rs863223346, rs863223347, rs863223351, rs863223352, rs61734270, rs797045205, rs869312829, rs869312830, rs770913157, rs869312832, rs869312831, rs781720548, rs1262969313	25056061, 28540026, 31268507, 29483656, 26198764, 30285260, 31374203
Coronary artery disease	CORONARY ARTERY DISEASE, AUTOSOMAL DOMINANT, 1, Coronary Artery Disease	rs137852988, rs121918313, rs-1, rs121918529, rs121918531, rs137852340, rs405509, rs1555800701, rs1215189537	23202125, 26343387, 29212778
Carcinoma	Carcinoma, Carcinoma, Spindle-Cell, Undifferentiated carcinoma	rs121912654, rs555607708, rs786202962, rs1564055259	16316942, 12376462
Hypertension	Hypertensive disease	rs13306026	30487518

Show/Hide Unknown Diseases (2)

Unknown
Disease name	Disease term	dbSNP ID	References
Anaplastic carcinoma	Anaplastic carcinoma		12376462, 16316942
Development disorder	Child Development Disorders, Pervasive		28540026

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