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UniProtKB/Swiss-Prot entry P09958


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name FURIN_HUMAN
Primary accession number P09958
Secondary accession numbers Q14336 Q6LBS3
Integrated into Swiss-Prot on July 1, 1989
Sequence was last modified on April 1, 1990 (Sequence version 2)
Annotations were last modified on    November 25, 2008 (Entry version 113)
Name and origin of the protein
Protein name Furin [Precursor]
Synonyms EC 3.4.21.75
Paired basic amino acid residue cleaving enzyme
PACE
Dibasic-processing enzyme
Gene name
Name: FURIN
Synonyms: FUR, PACE, PCSK3
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [MRNA].
TISSUE=Blood;
DOI=10.1093/nar/18.3.664; PubMed=2408021 [NCBI, ExPASy, EBI, Israel, Japan]
van den Ouweland A.M.W., van Duijnhoven H.L.P., Keizer G.D., Dorssers L.C.J., van de Ven W.J.M.;
"Structural homology between the human fur gene product and the subtilisin-like protease encoded by yeast KEX2.";
Nucleic Acids Res. 18:664-664(1990).
[2]
NUCLEOTIDE SEQUENCE.
PubMed=2251280 [NCBI, ExPASy, EBI, Israel, Japan]
Wise R.J., Barr P.J., Wong P.A., Kiefer M.C., Brake A.J., Kaufman R.J.;
"Expression of a human proprotein processing enzyme: correct cleavage of the von Willebrand factor precursor at a paired basic amino acid site.";
Proc. Natl. Acad. Sci. U.S.A. 87:9378-9382(1990).
[3]
NUCLEOTIDE SEQUENCE.
PubMed=1713771 [NCBI, ExPASy, EBI, Israel, Japan]
Barr P.J., Mason O.B., Landsberg K.E., Wong P.A., Kiefer M.C., Brake A.J.;
"cDNA and gene structure for a human subtilisin-like protease with cleavage specificity for paired basic amino acid residues.";
DNA Cell Biol. 10:319-328(1991).
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Lung;
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[5]
NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-280.
DOI=10.1093/nar/17.17.7101; PubMed=2674906 [NCBI, ExPASy, EBI, Israel, Japan]
Van den Ouweland A.M.W., van Groningen J.J.M., Roebrock A.J.M., Onnekink C., Van de Ven W.J.M.;
"Nucleotide sequence analysis of the human fur gene.";
Nucleic Acids Res. 17:7101-7102(1989).
[6]
NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 296-794.
PubMed=3023061 [NCBI, ExPASy, EBI, Israel, Japan]
Roebroek A.J.M., Schalken J.A., Leunissen J.A.M., Onnekink C., Bloemers H.P.J., van de Ven W.J.M.;
"Evolutionary conserved close linkage of the c-fes/fps proto-oncogene and genetic sequences encoding a receptor-like protein.";
EMBO J. 5:2197-2202(1986).
[7]
NUCLEOTIDE SEQUENCE OF 402-428, AND FUNCTION.
DOI=10.1006/bbrc.1993.2146; PubMed=7690548 [NCBI, ExPASy, EBI, Israel, Japan]
Takahashi S., Kasai K., Hatsuzawa K., Kitamura N., Misumi Y., Ikehara Y., Murakami K., Nakayama K.;
"A mutation of furin causes the lack of precursor-processing activity in human colon carcinoma LoVo cells.";
Biochem. Biophys. Res. Commun. 195:1019-1026(1993).
[8]
3D-STRUCTURE MODELING OF CATALYTIC DOMAIN.
PubMed=8020465 [NCBI, ExPASy, EBI, Israel, Japan]
Siezen R.J., Creemers J.W.M., van de Ven W.J.M.;
"Homology modelling of the catalytic domain of human furin. A model for the eukaryotic subtilisin-like proprotein convertases.";
Eur. J. Biochem. 222:255-266(1994).
[9]
PROTEOLYTIC PROCESSING.
PubMed=1629222 [NCBI, ExPASy, EBI, Israel, Japan]
Leduc R., Molloy S.S., Thorne B.A., Thomas G.;
"Activation of human furin precursor processing endoprotease occurs by an intramolecular autoproteolytic cleavage.";
J. Biol. Chem. 267:14304-14308(1992).
[10]
PHOSPHORYLATION AT SER-773 AND SER-775.
PubMed=8846780 [NCBI, ExPASy, EBI, Israel, Japan]
Jones B.G., Thomas L., Molloy S.S., Thulin C.D., Fry M.D., Walsh K.A., Thomas G.;
"Intracellular trafficking of furin is modulated by the phosphorylation state of a casein kinase II site in its cytoplasmic tail.";
EMBO J. 14:5869-5883(1995).
[11]
INTERACTION WITH PACS1.
DOI=10.1093/emboj/20.9.2191; PubMed=11331585 [NCBI, ExPASy, EBI, Israel, Japan]
Crump C.M., Xiang Y., Thomas L., Gu F., Austin C., Tooze S.A., Thomas G.;
"PACS-1 binding to adaptors is required for acidic cluster motif-mediated protein traffic.";
EMBO J. 20:2191-2201(2001).
Comments
  • 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 von Willebrand factor 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 [view classification].
  • SIMILARITY: Contains 1 homo B/P domain.
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
X17094; CAA34948.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
X04329; CAA27860.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC012181; AAH12181.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
X15723; CAA33745.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
PIR A39552; KXHUF.
RefSeq NP_002560.1; -.
UniGene Hs.513153
3D structure databases
HSSP P23188; 1P8J. [HSSP ENTRY / PDB]
SMR P09958; 109-578.
ModBase P09958.
Protein family/group databases
MEROPS S08.071; -.
PTM databases
PhosphoSite P09958; -.
Enzyme and pathway databases
Reactome REACT_1069; Post-translational protein modification.
REACT_11061; Signalling by NGF.
REACT_299; Signaling by Notch.
REACT_6844; Signaling by TGF beta.
2D gel databases
OGP P09958; -.
Organism-specific databases
H-InvDB HIX0012578; -.
HGNC HGNC:8568; FURIN.
GenAtlas FURIN.
HPA CAB009499; -.
MIM 136950; gene. [NCBI / EBI]
PharmGKB PA32894; -.
GeneCards P09958.
Gene expression databases
ArrayExpress P09958; -.
CleanEx HS_FURIN; -.
GermOnline ENSG00000140564; Homo sapiens.
Ontologies
GO
GO:0009986; Cellular component: cell surface (inferred from direct assay from UniProtKB).
GO:0000139; Cellular component: Golgi membrane (inferred from experiment from Reactome).
GO:0016021; Cellular component: integral to membrane (inferred from electronic annotation from UniProtKB-KW).
GO:0005886; Cellular component: plasma membrane (inferred from electronic annotation from UniProtKB-KW).
GO:0005802; Cellular component: trans-Golgi network (inferred from direct assay from UniProtKB).
GO:0030140; Cellular component: trans-Golgi network transport vesicle (inferred from direct assay from MGI).
GO:0005509; Molecular function: calcium ion binding (inferred from electronic annotation from UniProtKB-KW).
GO:0004276; Molecular function: furin activity (inferred from direct assay from UniProtKB).
GO:0048406; Molecular function: nerve growth factor binding (inferred from direct assay from UniProtKB).
GO:0042277; Molecular function: peptide binding (inferred from direct assay from UniProtKB).
GO:0016808; Molecular function: proprotein convertase activity (inferred from direct assay from UniProtKB).
GO:0002020; Molecular function: protease binding (inferred from physical interaction from UniProtKB).
GO:0004252; Molecular function: serine-type endopeptidase activity (inferred from electronic annotation from InterPro).
GO:0004867; Molecular function: serine-type endopeptidase inhibitor activity (inferred from direct assay from UniProtKB).
GO:0008283; Biological process: cell proliferation (inferred from mutant phenotype from UniProtKB).
GO:0032804; Biological process: negative regulation of low-density lipoprotein receptor catabolic process (inferred from direct assay from HGNC).
GO:0032911; Biological process: negative regulation of transforming growth factor-beta1 production (inferred from mutant phenotype from UniProtKB).
GO:0032455; Biological process: nerve growth factor processing (inferred from experiment from Reactome).
GO:0032902; Biological process: nerve growth factor production (inferred from direct assay from UniProtKB).
GO:0043043; Biological process: peptide biosynthetic process (inferred from direct assay from UniProtKB).
GO:0052548; Biological process: regulation of endopeptidase activity (inferred from direct assay from UniProtKB).
GO:0042176; Biological process: regulation of protein catabolic process (inferred from mutant phenotype from UniProtKB).
GO:0032940; Biological process: secretion by cell (inferred from direct assay from UniProtKB).
GO:0006465; Biological process: signal peptide processing (inferred from direct assay from HGNC).
GO:0019067; Biological process: viral assembly, maturation, egress, and release (inferred from expression pattern from UniProtKB).
QuickGo view.
Family and domain databases
InterPro IPR006212; Furin_repeat.
IPR000209; Pept_S8_S53.
IPR015500; Peptidase_S8_subtilisin-rel.
IPR002884; PrprotnconvertsP.
Graphical view of domain structure.
Gene3D G3DSA:3.40.50.200; Pept_S8_S53; 1.
PANTHER PTHR10795; SubtilSerProt; 1.
Pfam PF01483; P_proprotein; 1.
PF00082; Peptidase_S8; 1.
Pfam graphical view of domain structure.
PRINTS PR00723; SUBTILISIN.
ProDom PD000717; PrprotnconvertsP; 1.
[Domain structure / List of seq. sharing at least 1 domain]
SMART SM00261; FU; 2.
SMART graphical view of domain structure.
PROSITE PS00136; SUBTILASE_ASP; 1.
PS00137; SUBTILASE_HIS; 1.
PS00138; SUBTILASE_SER; 1.
ProtoNet P09958.
Proteomic databases
PeptideAtlas P09958; -.
Genome annotation databases
Ensembl ENSG00000140564; Homo sapiens. [Contig view]
GeneID 5045; -.
KEGG hsa:5045; -.
Phylogenomic databases
HOGENOM P09958; -.
HOVERGEN P09958; -.
Other
NextBio 19422; -.
SOURCE FURIN; Homo sapiens.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
Autocatalytic cleavage; Calcium; Cell membrane; Cleavage on pair of basic residues; Glycoprotein; Golgi apparatus; Hydrolase; Membrane; Metal-binding; Phosphoprotein; Protease; Serine protease; Signal; Transmembrane; Zymogen.
Features
SEVIEWER logo Feature table viewer FT aligner logo Feature aligner
KeyFrom   To Length Description FTId
SIGNAL   1    24  24     Potential. 
PROPEP   25   107  83     Inhibition peptide. PRO_0000027028
CHAIN   108   794  687     Furin. PRO_0000027029
TRANSMEM   716   738  23     Potential. 
REGION   759   762  4     Cell surface signal. 
MOTIF   498   500  3     Cell attachment site (Potential). 
MOTIF   773   779  7     Trans Golgi network signal. 
COMPBIAS   556   705  150     Cys-rich. 
ACT_SITE   153   153        Charge relay system (By similarity). 
ACT_SITE   194   194        Charge relay system (By similarity). 
ACT_SITE   368   368        Charge relay system (By similarity). 
METAL   115   115        Calcium 1 (By similarity). 
METAL   162   162        Calcium 1 (By similarity). 
METAL   208   208        Calcium 1 (By similarity). 
METAL   258   258        Calcium 2 (By similarity). 
METAL   301   301        Calcium 2 (By similarity). 
METAL   331   331        Calcium 2 (By similarity). 
SITE   75    76  2     Cleavage, second; by autolysis. 
SITE   107   108  2     Cleavage, first; by autolysis. 
MOD_RES   773   773        Phosphoserine; by CK2. 
MOD_RES   775   775        Phosphoserine; by CK2. 
CARBOHYD   387   387        N-linked (GlcNAc...) (Potential). 
CARBOHYD   440   440        N-linked (GlcNAc...) (Potential). 
CARBOHYD   553   553        N-linked (GlcNAc...) (Potential). 
DISULFID   211   360        By similarity. 
DISULFID   303   333        By similarity. 
DISULFID   450   474        By similarity. 
Sequence information
Length: 794 AA [This is the length of the unprocessed precursor] Molecular weight: 86678 Da [This is the MW of the unprocessed precursor] CRC64: 10C44DD5892EF85D [This is a checksum on the sequence]
        10         20         30         40         50         60 
MELRPWLLWV VAATGTLVLL AADAQGQKVF TNTWAVRIPG GPAVANSVAR KHGFLNLGQI 

        70         80         90        100        110        120 
FGDYYHFWHR GVTKRSLSPH RPRHSRLQRE PQVQWLEQQV AKRRTKRDVY QEPTDPKFPQ 

       130        140        150        160        170        180 
QWYLSGVTQR DLNVKAAWAQ GYTGHGIVVS ILDDGIEKNH PDLAGNYDPG ASFDVNDQDP 

       190        200        210        220        230        240 
DPQPRYTQMN DNRHGTRCAG EVAAVANNGV CGVGVAYNAR IGGVRMLDGE VTDAVEARSL 

       250        260        270        280        290        300 
GLNPNHIHIY SASWGPEDDG KTVDGPARLA EEAFFRGVSQ GRGGLGSIFV WASGNGGREH 

       310        320        330        340        350        360 
DSCNCDGYTN SIYTLSISSA TQFGNVPWYS EACSSTLATT YSSGNQNEKQ IVTTDLRQKC 

       370        380        390        400        410        420 
TESHTGTSAS APLAAGIIAL TLEANKNLTW RDMQHLVVQT SKPAHLNAND WATNGVGRKV 

       430        440        450        460        470        480 
SHSYGYGLLD AGAMVALAQN WTTVAPQRKC IIDILTEPKD IGKRLEVRKT VTACLGEPNH 

       490        500        510        520        530        540 
ITRLEHAQAR LTLSYNRRGD LAIHLVSPMG TRSTLLAARP HDYSADGFND WAFMTTHSWD 

       550        560        570        580        590        600 
EDPSGEWVLE IENTSEANNY GTLTKFTLVL YGTAPEGLPV PPESSGCKTL TSSQACVVCE 

       610        620        630        640        650        660 
EGFSLHQKSC VQHCPPGFAP QVLDTHYSTE NDVETIRASV CAPCHASCAT CQGPALTDCL 

       670        680        690        700        710        720 
SCPSHASLDP VEQTCSRQSQ SSRESPPQQQ PPRLPPEVEA GQRLRAGLLP SHLPEVVAGL 

       730        740        750        760        770        780 
SCAFIVLVFV TVFLVLQLRS GFSFRGVKVY TMDRGLISYK GLPPEAWQEE CPSDSEEDEG 

       790 
RGERTAFIKD QSAL 

P09958 in FASTA format

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