Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P09958 (FURIN_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 174. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Furin

EC=3.4.21.75
Alternative name(s):
Dibasic-processing enzyme
Paired basic amino acid residue-cleaving enzyme
Short name=PACE
Gene names
Name:FURIN
Synonyms:FUR, PACE, PCSK3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length794 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (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. Ref.7

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 structure

Interacts with FLNA By similarity. Binds to PACS1 which mediates TGN localization and connection to clathrin adapters. Ref.12

Subcellular location

Golgi apparatustrans-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. Ref.10

Post-translational modification

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.

Phosphorylation is required for TGN localization of the endoprotease. In vivo, exists as di-, mono- and non-phosphorylated forms. Ref.11

Sequence similarities

Belongs to the peptidase S8 family. Furin subfamily.

Contains 1 homo B/P domain.

Ontologies

Keywords
   Cellular componentCell membrane
Golgi apparatus
Membrane
   Coding sequence diversityPolymorphism
   DomainSignal
Transmembrane
Transmembrane helix
   LigandCalcium
Metal-binding
   Molecular functionHydrolase
Protease
Serine protease
   PTMAutocatalytic cleavage
Cleavage on pair of basic residues
Disulfide bond
Glycoprotein
Phosphoprotein
Zymogen
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processNotch signaling pathway

Traceable author statement. Source: Reactome

cell proliferation

Inferred from mutant phenotype PubMed 15899807. Source: BHF-UCL

cellular protein metabolic process

Traceable author statement. Source: Reactome

collagen catabolic process

Traceable author statement. Source: Reactome

extracellular matrix disassembly

Traceable author statement. Source: Reactome

extracellular matrix organization

Traceable author statement. Source: Reactome

negative regulation of endopeptidase activity

Inferred from direct assay PubMed 10567353. Source: GOC

negative regulation of low-density lipoprotein particle receptor catabolic process

Inferred from direct assay PubMed 16912035. Source: HGNC

negative regulation of transforming growth factor beta1 production

Inferred from mutant phenotype PubMed 15899807. Source: BHF-UCL

nerve growth factor processing

Traceable author statement. Source: Reactome

nerve growth factor production

Inferred from direct assay PubMed 8615794. Source: BHF-UCL

neurotrophin TRK receptor signaling pathway

Traceable author statement. Source: Reactome

peptide biosynthetic process

Inferred from direct assay PubMed 8262946. Source: BHF-UCL

peptide hormone processing

Inferred from direct assay PubMed 9242664. Source: BHF-UCL

peptidyl-glutamic acid carboxylation

Traceable author statement. Source: Reactome

positive regulation of membrane protein ectodomain proteolysis

Inferred by curator PubMed 17010968. Source: BHF-UCL

post-translational protein modification

Traceable author statement. Source: Reactome

protein processing

Inferred from direct assay PubMed 10526337. Source: UniProtKB

proteolysis

Traceable author statement. Source: Reactome

regulation of endopeptidase activity

Inferred from direct assay PubMed 14744861. Source: BHF-UCL

regulation of protein catabolic process

Inferred from mutant phenotype PubMed 15899807. Source: BHF-UCL

regulation of signal transduction

Inferred from electronic annotation. Source: Ensembl

secretion by cell

Inferred from direct assay PubMed 8615794. Source: BHF-UCL

signal peptide processing

Inferred from direct assay PubMed 16912035. Source: HGNC

transforming growth factor beta receptor signaling pathway

Traceable author statement. Source: Reactome

viral life cycle

Inferred from expression pattern PubMed 8940009. Source: BHF-UCL

viral process

Traceable author statement. Source: Reactome

viral protein processing

Traceable author statement. Source: Reactome

virion assembly

Traceable author statement. Source: Reactome

   Cellular_componentGolgi lumen

Traceable author statement. Source: Reactome

Golgi membrane

Traceable author statement. Source: Reactome

cell surface

Inferred from direct assay PubMed 16537537. Source: BHF-UCL

extracellular vesicular exosome

Inferred from direct assay PubMed 19199708. Source: UniProt

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

membrane raft

Inferred from direct assay PubMed 17010968. Source: BHF-UCL

plasma membrane

Traceable author statement. Source: Reactome

trans-Golgi network

Inferred from direct assay PubMed 14744861. Source: BHF-UCL

trans-Golgi network transport vesicle

Inferred from direct assay PubMed 15078902. Source: MGI

   Molecular_functionendopeptidase activity

Inferred from direct assay PubMed 17010968PubMed 9242664. Source: BHF-UCL

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

nerve growth factor binding

Inferred from direct assay PubMed 8615794. Source: BHF-UCL

peptidase activity

Inferred from direct assay PubMed 10526337. Source: UniProtKB

peptide binding

Inferred from direct assay PubMed 8940009. Source: BHF-UCL

protease binding

Inferred from physical interaction PubMed 14744861. Source: BHF-UCL

serine-type endopeptidase activity

Inferred from direct assay PubMed 10567353PubMed 8615794. Source: BHF-UCL

serine-type endopeptidase inhibitor activity

Inferred from direct assay PubMed 10567353. Source: BHF-UCL

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2424 Potential
Propeptide25 – 10783Inhibition peptide
PRO_0000027028
Chain108 – 794687Furin
PRO_0000027029

Regions

Transmembrane716 – 73823Helical; Potential
Region759 – 7624Cell surface signal
Motif498 – 5003Cell attachment site Potential
Motif773 – 7797Trans Golgi network signal
Compositional bias556 – 705150Cys-rich

Sites

Active site1531Charge relay system By similarity
Active site1941Charge relay system By similarity
Active site3681Charge relay system By similarity
Metal binding1151Calcium 1 By similarity
Metal binding1621Calcium 1 By similarity
Metal binding2081Calcium 1 By similarity
Metal binding2581Calcium 2 By similarity
Metal binding3011Calcium 2 By similarity
Metal binding3311Calcium 2 By similarity
Site75 – 762Cleavage, second; by autolysis
Site107 – 1082Cleavage, first; by autolysis

Amino acid modifications

Modified residue7731Phosphoserine; by CK2 Ref.11
Modified residue7751Phosphoserine; by CK2 Ref.11
Glycosylation3871N-linked (GlcNAc...) Potential
Glycosylation4401N-linked (GlcNAc...) Potential
Glycosylation5531N-linked (GlcNAc...) Potential
Disulfide bond211 ↔ 360 By similarity
Disulfide bond303 ↔ 333 By similarity
Disulfide bond450 ↔ 474 By similarity

Natural variations

Natural variant431A → V.
Corresponds to variant rs16944971 [ dbSNP | Ensembl ].
VAR_051821
Natural variant5471W → R in cell line LoVo; does not undergo autocatalytic activation and is not transported to the Golgi apparatus. Ref.8
VAR_055343

Sequences

Sequence LengthMass (Da)Tools
P09958 [UniParc].

Last modified April 1, 1990. Version 2.
Checksum: 10C44DD5892EF85D

FASTA79486,678
        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 

« Hide

References

« Hide 'large scale' references
[1]"Structural homology between the human fur gene product and the subtilisin-like protease encoded by yeast KEX2."
van den Ouweland A.M.W., van Duijnhoven H.L.P., Keizer G.D., Dorssers L.C.J., van de Ven W.J.M.
Nucleic Acids Res. 18:664-664(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Blood.
[2]"Expression of a human proprotein processing enzyme: correct cleavage of the von Willebrand factor precursor at a paired basic amino acid site."
Wise R.J., Barr P.J., Wong P.A., Kiefer M.C., Brake A.J., Kaufman R.J.
Proc. Natl. Acad. Sci. U.S.A. 87:9378-9382(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"cDNA and gene structure for a human subtilisin-like protease with cleavage specificity for paired basic amino acid residues."
Barr P.J., Mason O.B., Landsberg K.E., Wong P.A., Kiefer M.C., Brake A.J.
DNA Cell Biol. 10:319-328(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Lung.
[5]"Nucleotide sequence analysis of the human fur gene."
Van den Ouweland A.M.W., van Groningen J.J.M., Roebrock A.J.M., Onnekink C., Van de Ven W.J.M.
Nucleic Acids Res. 17:7101-7102(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-280.
[6]"Evolutionary conserved close linkage of the c-fes/fps proto-oncogene and genetic sequences encoding a receptor-like protein."
Roebroek A.J.M., Schalken J.A., Leunissen J.A.M., Onnekink C., Bloemers H.P.J., van de Ven W.J.M.
EMBO J. 5:2197-2202(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 296-794.
[7]"A mutation of furin causes the lack of precursor-processing activity in human colon carcinoma LoVo cells."
Takahashi S., Kasai K., Hatsuzawa K., Kitamura N., Misumi Y., Ikehara Y., Murakami K., Nakayama K.
Biochem. Biophys. Res. Commun. 195:1019-1026(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 402-428, FUNCTION.
Tissue: Colon carcinoma.
[8]"A second mutant allele of furin in the processing-incompetent cell line, LoVo. Evidence for involvement of the homo B domain in autocatalytic activation."
Takahashi S., Nakagawa T., Kasai K., Banno T., Duguay S.J., Van de Ven W.J.M., Murakami K., Nakayama K.
J. Biol. Chem. 270:26565-26569(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 527-553, VARIANT ARG-547.
Tissue: Colon carcinoma.
[9]"Activation of human furin precursor processing endoprotease occurs by an intramolecular autoproteolytic cleavage."
Leduc R., Molloy S.S., Thorne B.A., Thomas G.
J. Biol. Chem. 267:14304-14308(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEOLYTIC PROCESSING.
[10]"Homology modelling of the catalytic domain of human furin. A model for the eukaryotic subtilisin-like proprotein convertases."
Siezen R.J., Creemers J.W.M., van de Ven W.J.M.
Eur. J. Biochem. 222:255-266(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: 3D-STRUCTURE MODELING OF CATALYTIC DOMAIN.
[11]"Intracellular trafficking of furin is modulated by the phosphorylation state of a casein kinase II site in its cytoplasmic tail."
Jones B.G., Thomas L., Molloy S.S., Thulin C.D., Fry M.D., Walsh K.A., Thomas G.
EMBO J. 14:5869-5883(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-773 AND SER-775.
[12]"PACS-1 binding to adaptors is required for acidic cluster motif-mediated protein traffic."
Crump C.M., Xiang Y., Thomas L., Gu F., Austin C., Tooze S.A., Thomas G.
EMBO J. 20:2191-2201(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PACS1.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X17094 mRNA. Translation: CAA34948.1.
BC012181 mRNA. Translation: AAH12181.1.
X15723 Genomic DNA. Translation: CAA33745.1.
X04329 Genomic DNA. Translation: CAA27860.1.
PIRKXHUF. A39552.
RefSeqNP_002560.1. NM_002569.3.
UniGeneHs.513153.

3D structure databases

ProteinModelPortalP09958.
SMRP09958. Positions 30-99, 109-578, 592-682.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111082. 8 interactions.
DIPDIP-29904N.
IntActP09958. 7 interactions.
MINTMINT-1209355.
STRING9606.ENSP00000268171.

Chemistry

BindingDBP09958.
ChEMBLCHEMBL2611.
GuidetoPHARMACOLOGY2366.

Protein family/group databases

MEROPSS08.071.

PTM databases

PhosphoSiteP09958.

Polymorphism databases

DMDM120611.

2D gel databases

OGPP09958.

Proteomic databases

PaxDbP09958.
PeptideAtlasP09958.
PRIDEP09958.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000268171; ENSP00000268171; ENSG00000140564.
GeneID5045.
KEGGhsa:5045.
UCSCuc002bpu.1. human.

Organism-specific databases

CTD5045.
GeneCardsGC15P091411.
HGNCHGNC:8568. FURIN.
HPACAB009499.
MIM136950. gene.
neXtProtNX_P09958.
PharmGKBPA32894.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG4935.
HOGENOMHOG000192536.
HOVERGENHBG008705.
InParanoidP09958.
KOK01349.
OMAASCATCQ.
OrthoDBEOG7BW0JD.
PhylomeDBP09958.
TreeFamTF314277.

Enzyme and pathway databases

ReactomeREACT_111045. Developmental Biology.
REACT_111102. Signal Transduction.
REACT_116125. Disease.
REACT_118779. Extracellular matrix organization.
REACT_17015. Metabolism of proteins.
SignaLinkP09958.

Gene expression databases

ArrayExpressP09958.
BgeeP09958.
CleanExHS_FURIN.
GenevestigatorP09958.

Family and domain databases

Gene3D2.60.120.260. 1 hit.
3.40.50.200. 1 hit.
InterProIPR006212. Furin_repeat.
IPR008979. Galactose-bd-like.
IPR009030. Growth_fac_rcpt_N_dom.
IPR000209. Peptidase_S8/S53_dom.
IPR023827. Peptidase_S8_Asp-AS.
IPR022398. Peptidase_S8_His-AS.
IPR023828. Peptidase_S8_Ser-AS.
IPR015500. Peptidase_S8_subtilisin-rel.
IPR009020. Prot_inh_propept.
IPR002884. PrprotnconvertsP.
[Graphical view]
PANTHERPTHR10795. PTHR10795. 1 hit.
PfamPF01483. P_proprotein. 1 hit.
PF00082. Peptidase_S8. 1 hit.
[Graphical view]
PRINTSPR00723. SUBTILISIN.
SMARTSM00261. FU. 2 hits.
[Graphical view]
SUPFAMSSF49785. SSF49785. 1 hit.
SSF52743. SSF52743. 1 hit.
SSF54897. SSF54897. 1 hit.
SSF57184. SSF57184. 1 hit.
PROSITEPS00136. SUBTILASE_ASP. 1 hit.
PS00137. SUBTILASE_HIS. 1 hit.
PS00138. SUBTILASE_SER. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSFURIN. human.
GeneWikiFurin.
GenomeRNAi5045.
NextBio19422.
PMAP-CutDBP09958.
PROP09958.
SOURCESearch...

Entry information

Entry nameFURIN_HUMAN
AccessionPrimary (citable) accession number: P09958
Secondary accession number(s): Q14336, Q6LBS3, Q9UCZ5
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: April 1, 1990
Last modified: April 16, 2014
This is version 174 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 15

Human chromosome 15: entries, gene names and cross-references to MIM