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Details on Person UniProt:P23188 Furin
| Class:Id | ReferenceGeneProduct:90654 |
|---|---|
| _chainChangeLog | signal peptide:1-24 added on Fri February 6 2015;propeptide:25-107 added on Fri February 6 2015;chain:108-793 added on Fri February 6 2015 |
| _displayName | UniProt:P23188 Furin |
| _timestamp | 2023-11-03 15:16:54 |
| chain | signal peptide:1-24 propeptide:25-107 chain:108-793 |
| checksum | 0F120C2DE2E1A431 |
| comment | FUNCTION Ubiquitous endoprotease within constitutive secretory pathways capable of cleavage at the RX(K/R)R consensus motif (PubMed:18713856). Mediates processing of TGFB1, an essential step in TGF-beta-1 activation (By similarity). Converts through proteolytic cleavage the non-functional Brain natriuretic factor prohormone into its active hormone BNP(1-45) (By similarity). 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 (PubMed:18713856).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. 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). Inhibited by Decanoyl-Arg-Val-Lys-Arg-chloromethylketone (decanoyl-RVKR-CMK). Inhibited by heparin/heparan sulfate-binding.SUBUNIT Interacts with FLNA (PubMed:9412467). Binds to PACS1 which mediates TGN localization and connection to clathrin adapters (By similarity).SUBCELLULAR LOCATION Shuttles between the trans-Golgi network and the cell surface. 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.TISSUE SPECIFICITY Seems to be expressed ubiquitously (PubMed:2266110). Expressed in islets of Langerhans (PubMed:18713856).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.DISRUPTION PHENOTYPE Conditional knockout in pancreas causes mild glucose intolerance (PubMed:18713856). Insulin secretion by islets of Langerhans cells is reduced (PubMed:18713856). In islets of Langerhans cells, processing of pro-proteins including Pcsk2, Ins2/proinsulin II and Gcg/proglucagon and acidification of dense-core secretory granules are reduced (PubMed:18713856). Islets of Langerhans are normal (PubMed:18713856).SIMILARITY Belongs to the peptidase S8 family. Furin subfamily. |
| description | recommendedName: Furin ecNumber evidence="9"3.4.21.75 alternativeName: Dibasic-processing enzyme alternativeName: Paired basic amino acid residue-cleaving enzyme shortName: PACE alternativeName: Prohormone convertase 3 |
| geneName | Furin Fur Pcsk3 |
| identifier | P23188 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Autocatalytic cleavage Calcium Cell membrane Cleavage on pair of basic residues Disulfide bond Endosome Glycoprotein Golgi apparatus Heparin-binding Hydrolase Membrane Metal-binding Phosphoprotein Protease Reference proteome Repeat Secreted Serine protease Signal Transmembrane Transmembrane helix Zymogen |
| modified | [InstanceEdit:143527] Schmidt, EE, 2004-11-12 07:45:10 [InstanceEdit:217385] Schmidt, EE, 2008-03-27 06:23:53 [InstanceEdit:354386] Schmidt, EE, 2008-06-18 04:45:12 [InstanceEdit:384350] Kanapin, AA, 2008-11-26 14:00:39 [InstanceEdit:392885] Kanapin, AA, 2009-03-09 12:07:18 [InstanceEdit:400710] Schmidt, EE, 2009-03-25 05:33:35 [InstanceEdit:423310] Kanapin, AA [InstanceEdit:435478] Kanapin, AA [InstanceEdit:435871] Kanapin, AA [InstanceEdit:447347] Kanapin, AA [InstanceEdit:525883] Kanapin, AA [InstanceEdit:613449] Kanapin, AA [InstanceEdit:797602] Kanapin, AA [InstanceEdit:937368] Yung, CK [InstanceEdit:1042053] Yung, CK [InstanceEdit:1220657] Yung, CK [InstanceEdit:1300696] Yung, CK [InstanceEdit:1301627] Yung, CK [InstanceEdit:1551960] Weiser, JD [InstanceEdit:1995863] Weiser, JD [InstanceEdit:2132304] Weiser, JD [InstanceEdit:2265580] Weiser, JD [InstanceEdit:5433710] Weiser, JD [InstanceEdit:5618415] Weiser, JD [InstanceEdit:5634237] Weiser, JD [InstanceEdit:5673015] Weiser, JD [InstanceEdit:6807888] Weiser, JD [InstanceEdit:8987656] Weiser, JD [InstanceEdit:9037114] Weiser, JD [InstanceEdit:9627708] Weiser, JD [InstanceEdit:9637257] Weiser, JD [InstanceEdit:9657908] Weiser, JD [InstanceEdit:9676415] Weiser, JD [InstanceEdit:9715482] Weiser, JD [InstanceEdit:9730071] Weiser, JD [InstanceEdit:9773244] Weiser, Joel [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 |
| name | Furin |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| secondaryIdentifier | FURIN_MOUSE Q6GTN6 |
| sequenceLength | 793 |
| species | [Species:48892] Mus musculus |
| (referenceEntity) | [EntityWithAccessionedSequence:181833] Furin [endoplasmic reticulum lumen] [Mus musculus] [EntityWithAccessionedSequence:1181112] Furin [extracellular region] [Mus musculus] |
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No pathways have been reviewed or authored by UniProt:P23188 Furin (90654)
