Human Gene FURIN (ENST00000268171.8) from GENCODE V44
Description: Homo sapiens furin, paired basic amino acid cleaving enzyme (FURIN), transcript variant 1, mRNA. (from RefSeq NM_002569) RefSeq Summary (NM_002569): 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. The product of this gene is one of the seven basic amino acid-specific members which cleave their 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, May 2020]. Gencode Transcript: ENST00000268171.8 Gencode Gene: ENSG00000140564.13 Transcript (Including UTRs) Position: hg38 chr15:90,868,588-90,883,457 Size: 14,870 Total Exon Count: 16 Strand: + Coding Region Position: hg38 chr15:90,875,741-90,881,878 Size: 6,138 Coding Exon Count: 15
ID:FURIN_HUMAN DESCRIPTION: RecName: Full=Furin; EC=3.4.21.75; AltName: Full=Dibasic-processing enzyme; AltName: Full=Paired basic amino acid residue-cleaving enzyme; Short=PACE; Flags: Precursor; FUNCTION: Furin is likely to represent the ubiquitous endoprotease activity within constitutive secretory pathways and capable of cleavage at the RX(K/R)R consensus motif. 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 vWF from their respective precursors. COFACTOR: Calcium. ENZYME REGULATION: Could be inhibited by the not secondly cleaved propeptide. SUBUNIT: Interacts with FLNA (By similarity). Binds to PACS1 which mediates TGN localization and connection to clathrin adapters. SUBCELLULAR LOCATION: Golgi apparatus, trans-Golgi network membrane; Single-pass type I membrane protein. Cell membrane; Single-pass type I membrane protein. Note=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. 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. SIMILARITY: Contains 1 homo B/P domain.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P09958
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
US Server
