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Details on Person UniProt:P09958 FURIN
| Class:Id | ReferenceGeneProduct:55032 |
|---|---|
| _chainChangeLog | signal peptide:1-24 added on Fri February 6 2015;propeptide:25-107 added on Fri February 6 2015;chain:108-794 added on Fri February 6 2015 |
| _displayName | UniProt:P09958 FURIN |
| _timestamp | 2024-11-03 20:14:30 |
| chain | signal peptide:1-26 propeptide:27-107 chain:108-794 |
| checksum | 10C44DD5892EF85D |
| comment | 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). By mediating processing of accessory subunit ATP6AP1/Ac45 of the V-ATPase, regulates the acidification of dense-core secretory granules in islets of Langerhans cells (By similarity).FUNCTION (Microbial infection) Cleaves and activates diphtheria toxin DT.FUNCTION (Microbial infection) Cleaves and activates anthrax toxin protective antigen (PA).FUNCTION (Microbial infection) Cleaves and activates HIV-1 virus Envelope glycoprotein gp160.FUNCTION (Microbial infection) Required for H7N1 and H5N1 influenza virus infection probably by cleaving hemagglutinin.FUNCTION (Microbial infection) Able to cleave S.pneumoniae serine-rich repeat protein PsrP.FUNCTION (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.FUNCTION (Microbial infection) Facilitates mumps virus infection by proteolytically cleaving the viral fusion protein F.CATALYTIC ACTIVITY Release of mature proteins from their proproteins by cleavage of -Arg-Xaa-Yaa-Arg-|-Zaa- bonds, where Xaa can be any amino acid and Yaa is Arg or Lys. Releases albumin, complement component C3 and von Willebrand factor from their respective precursors.COFACTOR Binds 3 calcium ions per subunit.ACTIVITY REGULATION Inhibited by the not secondly cleaved propeptide (PubMed:11799113, PubMed:9130696). Inhibited by m-guanidinomethyl-phenylacetyl-Arg-Val-Arg-(amidomethyl)-benzamidine (m-guanidinomethyl-Phac-RVR-Amb) and 4-guanidinomethyl-phenylacetyl-Arg-Tle-Arg-4-amidinobenzylamide (MI-1148) (PubMed:24666235, PubMed:25974265). Inhibited by Decanoyl-Arg-Val-Lys-Arg-chloromethylketone (decanoyl-RVKR-CMK) (PubMed:32362314). Inhibited by heparin/heparan sulfate-binding (PubMed:2408021).BIOPHYSICOCHEMICAL PROPERTIES Optimum pH is 6.0.SUBUNIT Interacts with FLNA (By similarity). Binds to PACS1 which mediates TGN localization and connection to clathrin adapters (PubMed:11331585). Interacts with LAMP1, LAMP2 and LAMP3 (PubMed:32295904).INTERACTION Shuttles between the trans-Golgi network and the cell surface (PubMed:11799113, PubMed:9412467). Propeptide cleavage is a prerequisite for exit of furin molecules out of the endoplasmic reticulum (ER). A second cleavage within the propeptide occurs in the trans Golgi network (TGN), followed by the release of the propeptide and the activation of furin (PubMed:11799113).TISSUE SPECIFICITY Seems to be expressed ubiquitously.DOMAIN Contains a cytoplasmic domain responsible for its TGN localization and recycling from the cell surface.PTM The inhibition peptide, which plays the role of an intramolecular chaperone, is autocatalytically removed in the endoplasmic reticulum (ER) and remains non-covalently bound to furin as a potent autoinhibitor. Following transport to the trans Golgi, a second cleavage within the inhibition propeptide results in propeptide dissociation and furin activation.PTM Phosphorylation is required for TGN localization of the endoprotease. In vivo, exists as di-, mono- and non-phosphorylated forms.SIMILARITY Belongs to the peptidase S8 family. Furin subfamily. |
| description | recommendedName: fullName evidence="32"Furin ecNumber evidence="7 9 11 14 17 24 25 29"3.4.21.75 alternativeName: Dibasic-processing enzyme alternativeName: Paired basic amino acid residue-cleaving enzyme shortName: PACE |
| geneName | FURIN FUR PACE PCSK3 |
| identifier | P09958 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure 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 Proteomics identification Reference proteome Repeat Secreted Serine protease Signal Transmembrane Transmembrane helix Zymogen |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 |
| name | FURIN |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:8980996] ENSEMBL:ENSG00000140564 FURIN [Homo sapiens] |
| secondaryIdentifier | FURIN_HUMAN Q14336 Q6LBS3 Q9UCZ5 |
| sequenceLength | 794 |
| species | [Species:48887] Homo sapiens |
| (referenceEntity) | [EntityWithAccessionedSequence:157049] FURIN [Golgi membrane] [Homo sapiens] [EntityWithAccessionedSequence:448351] FURIN [Golgi lumen] [Homo sapiens] [EntityWithAccessionedSequence:1181103] FURIN [extracellular region] [Homo sapiens] [EntityWithAccessionedSequence:2159856] FURIN [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:9832627] FURIN [trans-Golgi network membrane] [Homo sapiens] [EntityWithAccessionedSequence:9837714] FURIN [macropinosome membrane] [Homo sapiens] [EntityWithAccessionedSequence:9922501] FURIN [endosome membrane] [Homo sapiens] [EntityWithAccessionedSequence:9923830] FURIN [exocytic vesicle] [Homo sapiens] |
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No pathways have been reviewed or authored by UniProt:P09958 FURIN (55032)
