FURIN furin, paired basic amino acid cleaving enzyme [Homo sapiens (human)] - Gene

Summary

Official Symbol: FURINprovided by HGNC
Official Full Name: furin, paired basic amino acid cleaving enzymeprovided by HGNC
Primary source: HGNC:HGNC:8568
See related: Ensembl:ENSG00000140564 MIM:136950; AllianceGenome:HGNC:8568
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: FUR; PACE; SPC1; PCSK3
Summary: 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]
Annotation information: Note: This gene has been reviewed for its involvement in coronavirus biology, and is involved in SARS-CoV-2 infection.
Expression: Ubiquitous expression in salivary gland (RPKM 50.5), liver (RPKM 36.0) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 15q26.1

Exon count:: 20

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	15	NC_000015.10 (90868588..90883457)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	15	NC_060939.1 (88627830..88643054)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	15	NC_000015.9 (91411818..91426687)

Chromosome 15 - NC_000015.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

The Furin Protease Dependence and Antiviral GBP2 Sensitivity of Murine Leukemia Virus Infection Are Determined by the Amino Acid Sequence at the Envelope Glycoprotein Cleavage Site.
Title: The Furin Protease Dependence and Antiviral GBP2 Sensitivity of Murine Leukemia Virus Infection Are Determined by the Amino Acid Sequence at the Envelope Glycoprotein Cleavage Site.
Furin Egress from the TGN is Regulated by Membrane-Associated RING-CH Finger (MARCHF) Proteins and Ubiquitin-Specific Protease 32 (USP32) via Nondegradable K33-Polyubiquitination.
Title: Furin Egress from the TGN is Regulated by Membrane-Associated RING-CH Finger (MARCHF) Proteins and Ubiquitin-Specific Protease 32 (USP32) via Nondegradable K33-Polyubiquitination.
The proprotein convertase furin in cancer: more than an oncogene.
Title: The proprotein convertase furin in cancer: more than an oncogene.
The impact of wound-healing assay, phorbol myristate acetate (PMA) stimulation and siRNA-mediated FURIN gene silencing on endogenous retroviral ERVW-1 expression level in U87-MG astrocytoma cells.
Title: The impact of wound-healing assay, phorbol myristate acetate (PMA) stimulation and siRNA-mediated FURIN gene silencing on endogenous retroviral ERVW-1 expression level in U87-MG astrocytoma cells.
Novel genetic association of the Furin gene polymorphism rs1981458 with COVID-19 severity among Indian populations.
Title: Novel genetic association of the Furin gene polymorphism rs1981458 with COVID-19 severity among Indian populations.
Pathological changes in oral epithelium and the expression of SARS-CoV-2 entry receptors, ACE2 and furin.
Title: Pathological changes in oral epithelium and the expression of SARS-CoV-2 entry receptors, ACE2 and furin.
The subtilisin-like protease furin regulates hemin-induced CD63 surface expression on platelets.
Title: The subtilisin-like protease furin regulates hemin-induced CD63 surface expression on platelets.
An Overview of the Role of Furin in Type 2 Diabetes.
Title: An Overview of the Role of Furin in Type 2 Diabetes.
Allele-Specific Epigenetic Regulation of FURIN Expression at a Coronary Artery Disease Susceptibility Locus.
Title: Allele-Specific Epigenetic Regulation of FURIN Expression at a Coronary Artery Disease Susceptibility Locus.
Overexpression of the pro-protein convertase furin predicts prognosis and promotes papillary thyroid carcinoma progression and metastasis through RAF/MEK signaling.
Title: Overexpression of the pro-protein convertase furin predicts prognosis and promotes papillary thyroid carcinoma progression and metastasis through RAF/MEK signaling.

Submit: New GeneRIF Correction See all GeneRIFs (180)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Biological insights from 108 schizophrenia-associated genetic loci. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	HIV-1 gp120 upregulates the expression of furin (paired basic amino acid cleaving enzyme) in human B cells	PubMed
Envelope surface glycoprotein gp160, precursor	env	PAR1 inhibits the cleavage of HIV-1 gp160 to gp41 by furin	PubMed
	env	Furin, a subtilisin-like eukaryotic endoprotease, is able to process HIV-1 gp160/gp140 to the cleavage products gp120 and gp41 at the cleavage site with the consensus amino acid sequence Arg-X-Lys/Arg-Arg	PubMed
	env	Interaction between gp120 C5 region and gp41 disulfide loop in unprocessed HIV-1 Env glycoprotein is required for Env processing by furin	PubMed
	env	V38M + N43T-N44K mutations impairs gPr160 cleavage by furin	PubMed
Tat	tat	Furin cleaves HIV-1 Tat at amino acid residue 56, resulting in greatly reduced Tat transactivation activity	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH1636 (e-PCR)
- UniSTS:24856

FURIN (e-PCR)
- UniSTS:503074

FURIN_659 (e-PCR)
- UniSTS:462201

FURIN_V45 (e-PCR)
- UniSTS:462201

FURIN (e-PCR)
- UniSTS:265098

G54068 (e-PCR)
- UniSTS:109450

G06349 (e-PCR)
- UniSTS:54186

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables endopeptidase activity	IDA Inferred from Direct Assay more info	PubMed
enables endopeptidase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables endopeptidase activity	TAS Traceable Author Statement more info
enables heparan sulfate binding	IDA Inferred from Direct Assay more info	PubMed
enables heparin binding	IDA Inferred from Direct Assay more info	PubMed
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables nerve growth factor binding	IDA Inferred from Direct Assay more info	PubMed
enables peptidase activity	IDA Inferred from Direct Assay more info	PubMed
enables peptide binding	IDA Inferred from Direct Assay more info	PubMed
enables protease binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables serine-type endopeptidase activity	IBA Inferred from Biological aspect of Ancestor more info
enables serine-type endopeptidase activity	IDA Inferred from Direct Assay more info	PubMed
enables serine-type endopeptidase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables serine-type endopeptidase activity	TAS Traceable Author Statement more info
enables serine-type endopeptidase inhibitor activity	IDA Inferred from Direct Assay more info	PubMed
enables serine-type peptidase activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in amyloid fibril formation	TAS Traceable Author Statement more info
involved_in blastocyst formation	IEA Inferred from Electronic Annotation more info
involved_in collagen catabolic process	TAS Traceable Author Statement more info
involved_in cytokine precursor processing	IDA Inferred from Direct Assay more info	PubMed
involved_in dibasic protein processing	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in extracellular matrix disassembly	TAS Traceable Author Statement more info
involved_in extracellular matrix organization	TAS Traceable Author Statement more info
involved_in negative regulation of inflammatory response to antigenic stimulus	TAS Traceable Author Statement more info
involved_in negative regulation of low-density lipoprotein particle receptor catabolic process	IDA Inferred from Direct Assay more info	PubMed
NOT involved_in negative regulation of nerve growth factor production	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of transforming growth factor beta1 production	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in nerve growth factor production	IDA Inferred from Direct Assay more info	PubMed
involved_in peptide biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
involved_in peptide hormone processing	IBA Inferred from Biological aspect of Ancestor more info
involved_in peptide hormone processing	IDA Inferred from Direct Assay more info	PubMed
involved_in plasma lipoprotein particle remodeling	TAS Traceable Author Statement more info
involved_in positive regulation of membrane protein ectodomain proteolysis	IC Inferred by Curator more info	PubMed
involved_in positive regulation of viral entry into host cell	IDA Inferred from Direct Assay more info	PubMed
involved_in protein maturation	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within protein processing	IDA Inferred from Direct Assay more info	PubMed
involved_in protein processing	IDA Inferred from Direct Assay more info	PubMed
involved_in protein processing	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of cholesterol transport	IEA Inferred from Electronic Annotation more info
involved_in regulation of endopeptidase activity	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of protein catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of signal transduction	IEA Inferred from Electronic Annotation more info
involved_in secretion by cell	IDA Inferred from Direct Assay more info	PubMed
involved_in signal peptide processing	IDA Inferred from Direct Assay more info	PubMed
involved_in signal peptide processing	TAS Traceable Author Statement more info
involved_in transforming growth factor beta receptor signaling pathway	TAS Traceable Author Statement more info
involved_in viral life cycle	IEP Inferred from Expression Pattern more info	PubMed
involved_in viral protein processing	TAS Traceable Author Statement more info
acts_upstream_of viral translation	TAS Traceable Author Statement more info	PubMed
involved_in zymogen activation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in zymogen inhibition	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in Golgi lumen	TAS Traceable Author Statement more info
is_active_in Golgi membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in Golgi membrane	IMP Inferred from Mutant Phenotype more info	PubMed
located_in Golgi membrane	TAS Traceable Author Statement more info
located_in cell surface	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum	IGI Inferred from Genetic Interaction more info	PubMed
located_in endosome membrane	IEA Inferred from Electronic Annotation more info
located_in extracellular exosome	HDA more info	PubMed
located_in extracellular region	TAS Traceable Author Statement more info
NOT located_in extracellular space	IDA Inferred from Direct Assay more info	PubMed
located_in membrane	HDA more info	PubMed
located_in membrane raft	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info
is_active_in trans-Golgi network	IBA Inferred from Biological aspect of Ancestor more info
located_in trans-Golgi network	IDA Inferred from Direct Assay more info	PubMed
located_in trans-Golgi network transport vesicle	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: furin

Names: FES upstream region; dibasic processing enzyme; furin, membrane associated receptor protein; paired basic amino acid residue-cleaving enzyme; proprotein convertase subtilisin/kexin 3; proprotein convertase subtilisin/kexin type 3; subtilisin-like proprotein convertase 1

NP_001276752.1

EC 3.4.21.75

NP_001276753.1

EC 3.4.21.75

NP_001369548.1

EC 3.4.21.75

NP_001369549.1

EC 3.4.21.75

NP_001369550.1

EC 3.4.21.75

NP_001369551.1

EC 3.4.21.75

NP_002560.1

EC 3.4.21.75

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001289823.2 → NP_001276752.1 furin isoform 1 preproprotein

See identical proteins and their annotated locations for NP_001276752.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR, compared to variant 1. Variants 1, 2, and 3 encode the same protein.

Source sequence(s)

AC124248

Consensus CDS

CCDS10364.1

UniProtKB/Swiss-Prot

P09958, Q14336, Q6LBS3, Q9UCZ5

UniProtKB/TrEMBL

A0A7P0T8U2

Related

ENSP00000484952.1, ENST00000610579.4

Conserved Domains (4) summary

cd04059
Location:113 → 402

Peptidases_S8_Protein_convertases_Kexins_Furin-lik; Peptidase S8 family domain in Protein convertases

smart00261
Location:638 → 675

FU; Furin-like repeats

pfam01483
Location:484 → 570

P_proprotein; Proprotein convertase P-domain

pfam16470
Location:33 → 107

S8_pro-domain; Peptidase S8 pro-domain
NM_001289824.2 → NP_001276753.1 furin isoform 1 preproprotein

See identical proteins and their annotated locations for NP_001276753.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) differs in the 5' UTR, compared to variant 1. Variants 1, 2, and 3 encode the same protein.

Source sequence(s)

AC124248

Consensus CDS

CCDS10364.1

UniProtKB/Swiss-Prot

P09958, Q14336, Q6LBS3, Q9UCZ5

UniProtKB/TrEMBL

A0A7P0T8U2

Related

ENSP00000483552.1, ENST00000618099.4

Conserved Domains (4) summary

cd04059
Location:113 → 402

Peptidases_S8_Protein_convertases_Kexins_Furin-lik; Peptidase S8 family domain in Protein convertases

smart00261
Location:638 → 675

FU; Furin-like repeats

pfam01483
Location:484 → 570

P_proprotein; Proprotein convertase P-domain

pfam16470
Location:33 → 107

S8_pro-domain; Peptidase S8 pro-domain
NM_001382619.1 → NP_001369548.1 furin isoform 1 preproprotein

Status: REVIEWED

Source sequence(s)

AC124248

Consensus CDS

CCDS10364.1

UniProtKB/Swiss-Prot

P09958, Q14336, Q6LBS3, Q9UCZ5

UniProtKB/TrEMBL

A0A7P0T8U2

Conserved Domains (4) summary

cd04059
Location:113 → 402

Peptidases_S8_Protein_convertases_Kexins_Furin-lik; Peptidase S8 family domain in Protein convertases

smart00261
Location:638 → 675

FU; Furin-like repeats

pfam01483
Location:484 → 570

P_proprotein; Proprotein convertase P-domain

pfam16470
Location:33 → 107

S8_pro-domain; Peptidase S8 pro-domain
NM_001382620.1 → NP_001369549.1 furin isoform 1 preproprotein

Status: REVIEWED

Source sequence(s)

AC124248

Consensus CDS

CCDS10364.1

UniProtKB/Swiss-Prot

P09958, Q14336, Q6LBS3, Q9UCZ5

UniProtKB/TrEMBL

A0A7P0T8U2

Related

ENSP00000506143.1, ENST00000680053.1

Conserved Domains (4) summary

cd04059
Location:113 → 402

Peptidases_S8_Protein_convertases_Kexins_Furin-lik; Peptidase S8 family domain in Protein convertases

smart00261
Location:638 → 675

FU; Furin-like repeats

pfam01483
Location:484 → 570

P_proprotein; Proprotein convertase P-domain

pfam16470
Location:33 → 107

S8_pro-domain; Peptidase S8 pro-domain
NM_001382621.1 → NP_001369550.1 furin isoform 1 preproprotein

Status: REVIEWED

Source sequence(s)

AC124248

Consensus CDS

CCDS10364.1

UniProtKB/Swiss-Prot

P09958, Q14336, Q6LBS3, Q9UCZ5

UniProtKB/TrEMBL

A0A7P0T8U2

Conserved Domains (4) summary

cd04059
Location:113 → 402

Peptidases_S8_Protein_convertases_Kexins_Furin-lik; Peptidase S8 family domain in Protein convertases

smart00261
Location:638 → 675

FU; Furin-like repeats

pfam01483
Location:484 → 570

P_proprotein; Proprotein convertase P-domain

pfam16470
Location:33 → 107

S8_pro-domain; Peptidase S8 pro-domain
NM_001382622.1 → NP_001369551.1 furin isoform 2 precursor

Status: REVIEWED

Source sequence(s)

AC124248

Conserved Domains (3) summary

cd04059
Location:113 → 402

Peptidases_S8_Protein_convertases_Kexins_Furin-lik; Peptidase S8 family domain in Protein convertases

pfam01483
Location:484 → 570

P_proprotein; Proprotein convertase P-domain

pfam16470
Location:33 → 107

S8_pro-domain; Peptidase S8 pro-domain
NM_002569.4 → NP_002560.1 furin isoform 1 preproprotein

See identical proteins and their annotated locations for NP_002560.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the predominant transcript. Variants 1, 2, and 3 encode the same protein.

Source sequence(s)

AC124248, BC012181, BM043834, BP283962, X17094

Consensus CDS

CCDS10364.1

UniProtKB/Swiss-Prot

P09958, Q14336, Q6LBS3, Q9UCZ5

UniProtKB/TrEMBL

A0A7P0T8U2

Related

ENSP00000268171.2, ENST00000268171.8

Conserved Domains (4) summary

cd04059
Location:113 → 402

Peptidases_S8_Protein_convertases_Kexins_Furin-lik; Peptidase S8 family domain in Protein convertases

smart00261
Location:638 → 675

FU; Furin-like repeats

pfam01483
Location:484 → 570

P_proprotein; Proprotein convertase P-domain

pfam16470
Location:33 → 107

S8_pro-domain; Peptidase S8 pro-domain