FURIN

Protein identityUniProt · HPA

UniProt accession

P09958

Gene

FURIN

Ensembl

ENSG00000140564

Chromosome

15

Canonical length

794 aa

Protein class

Enzymes, Plasma proteins, Predicted membrane proteins

Subcellular location

Nucleoplasm,Golgi apparatus

Secretome location

Intracellular and membrane

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

794 residues, UniProt reviewed canonical sequence.

>P09958|FURIN
     1  MELRPWLLWV VAATGTLVLL AADAQGQKVF TNTWAVRIPG GPAVANSVAR KHGFLNLGQI
    61  FGDYYHFWHR GVTKRSLSPH RPRHSRLQRE PQVQWLEQQV AKRRTKRDVY QEPTDPKFPQ
   121  QWYLSGVTQR DLNVKAAWAQ GYTGHGIVVS ILDDGIEKNH PDLAGNYDPG ASFDVNDQDP
   181  DPQPRYTQMN DNRHGTRCAG EVAAVANNGV CGVGVAYNAR IGGVRMLDGE VTDAVEARSL
   241  GLNPNHIHIY SASWGPEDDG KTVDGPARLA EEAFFRGVSQ GRGGLGSIFV WASGNGGREH
   301  DSCNCDGYTN SIYTLSISSA TQFGNVPWYS EACSSTLATT YSSGNQNEKQ IVTTDLRQKC
   361  TESHTGTSAS APLAAGIIAL TLEANKNLTW RDMQHLVVQT SKPAHLNAND WATNGVGRKV
   421  SHSYGYGLLD AGAMVALAQN WTTVAPQRKC IIDILTEPKD IGKRLEVRKT VTACLGEPNH
   481  ITRLEHAQAR LTLSYNRRGD LAIHLVSPMG TRSTLLAARP HDYSADGFND WAFMTTHSWD
   541  EDPSGEWVLE IENTSEANNY GTLTKFTLVL YGTAPEGLPV PPESSGCKTL TSSQACVVCE
   601  EGFSLHQKSC VQHCPPGFAP QVLDTHYSTE NDVETIRASV CAPCHASCAT CQGPALTDCL
   661  SCPSHASLDP VEQTCSRQSQ SSRESPPQQQ PPRLPPEVEA GQRLRAGLLP SHLPEVVAGL
   721  SCAFIVLVFV TVFLVLQLRS GFSFRGVKVY TMDRGLISYK GLPPEAWQEE CPSDSEEDEG
   781  RGERTAFIKD QSAL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against FURIN can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.32

Highest tissue expression

208 nTPM

Expression across tissuesHPA

ReferencesPubMed · IEDB

Publications for FURIN from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.19

gnomAD pLI

1

gnomAD missense Z

2.5

DepMap mean gene effect

-0.24

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• amyloid fibril formation
• blastocyst formation
• cholesterol homeostasis
• collagen catabolic process
• cytokine precursor processing
• extracellular matrix disassembly
• extracellular matrix organization
• negative regulation of inflammatory response to antigenic stimulus
• negative regulation of low-density lipoprotein particle receptor catabolic process
• negative regulation of transforming growth factor beta1 production
• nerve growth factor production
• peptide biosynthetic process
• peptide hormone processing
• plasma lipoprotein particle remodeling
• positive regulation of membrane protein ectodomain proteolysis
• positive regulation of viral entry into host cell
• protein maturation
• protein processing
• regulation of cholesterol transport
• regulation of protein catabolic process
• regulation of signal transduction
• secretion by cell
• signal peptide processing
• transforming growth factor beta receptor signaling pathway
• viral life cycle
• viral protein processing
• zymogen activation
• dibasic protein processing

Molecular functions

• endopeptidase activator activity
• endopeptidase activity
• endopeptidase inhibitor activity
• heparan sulfate binding
• heparin binding
• metal ion binding
• nerve growth factor binding
• peptidase activity
• peptide binding
• protease binding
• serine-type endopeptidase activity
• serine-type endopeptidase inhibitor activity
• serine-type peptidase activity

Cellular components

• cell surface
• endoplasmic reticulum
• endosome membrane
• extracellular exosome
• extracellular region
• Golgi lumen
• Golgi membrane
• membrane
• membrane raft
• plasma membrane
• trans-Golgi network
• trans-Golgi network transport vesicle

Protein domainsUniProt · Pfam · InterPro

• Peptidase S8/S53 domain
• P domain
• Furin-like repeat
• Galactose-binding-like domain superfamily
• Growth factor receptor cysteine-rich domain superfamily
• Peptidase S8, subtilisin-related
• Peptidase S8, subtilisin, His-active site
• Peptidase S8, subtilisin, Asp-active site
• Peptidase S8, subtilisin, Ser-active site
• Peptidase S8, pro-domain
• Kexin/furin catalytic domain
• Peptidase S8/S53 domain superfamily
• Peptidase S8, pro-domain superfamily
• Subtilase family
• Proprotein convertase P-domain
• Peptidase S8 pro-domain

KeywordsUniProt

• Autocatalytic cleavage
• Calcium
• Cell membrane
• Cleavage on pair of basic residues
• Disulfide bond
• Endosome
• Glycoprotein
• Golgi apparatus
• Heparin-binding
• Host-virus interaction
• Hydrolase
• Membrane
• Metal-binding
• Phosphoprotein
• Protease
• Repeat
• Secreted
• Serine protease
• Signal
• Transmembrane
• Transmembrane helix
• Zymogen

InteractionsUniProt · HPA

Protein binding partners of FURIN in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• FLNA
• LAMP1
• LAMP2
• LAMP3
• PACS1
• MMP14