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P23188 (FURIN_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 142. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·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
Prohormone convertase 3
Gene names
Name:Furin
Synonyms:Fur, Pcsk3
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length793 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.

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

Binds 2 calcium ions per subunit.

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 By similarity. Ref.5

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 By similarity.

Tissue specificity

Seems to be expressed ubiquitously.

Domain

Contains a cytoplasmic domain responsible for its TGN localization and recycling from the cell surface.

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 By similarity.

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

Sequence similarities

Belongs to the peptidase S8 family. Furin subfamily.

Contains 1 homo B/P domain.

Ontologies

Keywords
   Cellular componentCell membrane
Golgi apparatus
Membrane
   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 term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcell proliferation

Inferred from electronic annotation. Source: Ensembl

negative regulation of low-density lipoprotein particle receptor catabolic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of transforming growth factor beta1 production

Inferred from electronic annotation. Source: Ensembl

nerve growth factor production

Inferred from electronic annotation. Source: Ensembl

peptide biosynthetic process

Inferred from electronic annotation. Source: Ensembl

peptide hormone processing

Inferred from electronic annotation. Source: Ensembl

protein processing

Inferred from direct assay PubMed 20530870. Source: MGI

proteolysis

Inferred from electronic annotation. Source: UniProtKB-KW

regulation of signal transduction

Inferred from direct assay PubMed 17936261. Source: MGI

secretion by cell

Inferred from electronic annotation. Source: Ensembl

signal peptide processing

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentGolgi apparatus

Inferred from Biological aspect of Ancestor. Source: RefGenome

cell surface

Inferred from electronic annotation. Source: Ensembl

early endosome

Traceable author statement PubMed 12360192. Source: MGI

endoplasmic reticulum lumen

Traceable author statement. Source: Reactome

extracellular region

Traceable author statement. Source: Reactome

extracellular space

Inferred from Biological aspect of Ancestor. Source: RefGenome

integral component of membrane

Traceable author statement PubMed 12360192. Source: MGI

membrane raft

Inferred from electronic annotation. Source: Ensembl

plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

trans-Golgi network

Inferred from electronic annotation. Source: Ensembl

trans-Golgi network transport vesicle

Inferred from sequence orthology PubMed 15078902. Source: MGI

trans-Golgi network transport vesicle membrane

Traceable author statement PubMed 12360192. Source: MGI

   Molecular_functionmetal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

peptidase activity

Inferred from sequence orthology PubMed 15082773. Source: MGI

peptide binding

Inferred from electronic annotation. Source: Ensembl

serine-type endopeptidase activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

serine-type endopeptidase inhibitor activity

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2424 Potential
Propeptide25 – 10783Inhibition peptide By similarity
PRO_0000027030
Chain108 – 793686Furin
PRO_0000027031

Regions

Transmembrane715 – 73521Helical; Potential
Region109 – 445337Catalytic
Region446 – 578133P-domain
Region758 – 7614Cell surface signal
Motif498 – 5003Cell attachment site Potential
Motif772 – 7787Trans Golgi network signal
Compositional bias556 – 705150Cys-rich

Sites

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

Amino acid modifications

Modified residue7721Phosphoserine; by CK2 By similarity
Modified residue7741Phosphoserine; by CK2 By similarity
Glycosylation3871N-linked (GlcNAc...)
Glycosylation4401N-linked (GlcNAc...)
Glycosylation5531N-linked (GlcNAc...) Potential
Disulfide bond211 ↔ 360
Disulfide bond303 ↔ 333
Disulfide bond450 ↔ 474

Experimental info

Sequence conflict7461V → M in CAA37988. Ref.1

Secondary structure

................................................................................... 793
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P23188 [UniParc].

Last modified July 27, 2011. Version 2.
Checksum: 0F120C2DE2E1A431

FASTA79386,772
        10         20         30         40         50         60 
MELRSWLLWV VAAAGAVVLL AADAQGQKIF TNTWAVHIPG GPAVADRVAQ KHGFHNLGQI 

        70         80         90        100        110        120 
FGDYYHFWHR AVTKRSLSPH RPRHSRLQRE PQVKWLEQQV AKRRAKRDVY QEPTDPKFPQ 

       130        140        150        160        170        180 
QWYLSGVTQR DLNVKEAWAQ GFTGHGIVVS 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 SKPAHLNADD WATNGVGRKV 

       430        440        450        460        470        480 
SHSYGYGLLD AGAMVALAQN WTTVAPQRKC IVEILVEPKD IGKRLEVRKA VTACLGEPNH 

       490        500        510        520        530        540 
ITRLEHVQAR LTLSYNRRGD LAIHLISPMG TRSTLLAARP HDYSADGFND WAFMTTHSWD 

       550        560        570        580        590        600 
EDPAGEWVLE IENTSEANNY GTLTKFTLVL YGTAPEGLST PPESSGCKTL TSSQACVVCE 

       610        620        630        640        650        660 
EGYSLHQKSC VQHCPPGFIP QVLDTHYSTE NDVEIIRASV CTPCHASCAT CQGPAPTDCL 

       670        680        690        700        710        720 
SCPSHASLDP VEQTCSRQSQ SSRESRPQQQ PPALRPEVEM EPRLQAGLAS HLPEVLAGLS 

       730        740        750        760        770        780 
CLIIVLIFGI VFLFLHRCSG FSFRGVKVYT MDRGLISYKG LPPEAWQEEC PSDSEEDEGR 

       790 
GERTAFIKDQ SAL 

« Hide

References

« Hide 'large scale' references
[1]"Structure and expression of mouse furin, a yeast Kex2-related protease. Lack of processing of coexpressed prorenin in GH4C1 cells."
Hatsuzawa K., Hosaka M., Nakagawa T., Nagase M., Shoda A., Murakami K., Nakayama K.
J. Biol. Chem. 265:22075-22078(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Cloning and functional expression of a 4.3 kbp mouse fur cDNA: evidence for differential expression."
Creemers J.W.M., Roebroek A.J.M., van den Ouweland A.M.W., van Duijnhoven H.L.P., van de Ven W.J.M.
Life Sci. Adv. (Mol. Biol.) 11:127-138(1992)
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Liver.
[3]Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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: Eye.
[5]"Cytoskeletal protein ABP-280 directs the intracellular trafficking of furin and modulates proprotein processing in the endocytic pathway."
Liu G., Thomas L., Warren R.A., Enns C.A., Cunningham C.C., Hartwig J.H., Thomas G.
J. Cell Biol. 139:1719-1733(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH FLNA.
[6]"The crystal structure of the proprotein processing proteinase furin explains its stringent specificity."
Henrich S., Cameron A., Bourenkov G.P., Kiefersauer R., Huber R., Lindberg I., Bode W., Than M.E.
Nat. Struct. Biol. 10:520-526(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 108-578 IN COMPLEX WITH INHIBITOR.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X54056 mRNA. Translation: CAA37988.1.
L26489 mRNA. Translation: AAA37643.1.
CH466543 Genomic DNA. Translation: EDL06988.1.
BC048234 mRNA. Translation: AAH48234.1.
PIRKXMSF. A23679.
RefSeqNP_001074923.1. NM_001081454.1.
NP_035176.1. NM_011046.2.
XP_006540765.1. XM_006540702.1.
XP_006540766.1. XM_006540703.1.
XP_006540767.1. XM_006540704.1.
XP_006540768.1. XM_006540705.1.
UniGeneMm.5241.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1P8JX-ray2.60A/B/C/D/E/F/G/H108-578[»]
ProteinModelPortalP23188.
SMRP23188. Positions 30-99, 109-578, 593-679.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING10090.ENSMUSP00000113370.

Protein family/group databases

MEROPSS08.071.

PTM databases

PhosphoSiteP23188.

Proteomic databases

PaxDbP23188.
PRIDEP23188.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000107362; ENSMUSP00000102985; ENSMUSG00000030530.
ENSMUST00000120753; ENSMUSP00000113793; ENSMUSG00000030530.
ENSMUST00000122232; ENSMUSP00000113370; ENSMUSG00000030530.
GeneID18550.
KEGGmmu:18550.
UCSCuc009iau.1. mouse.

Organism-specific databases

CTD5045.
MGIMGI:97513. Furin.

Phylogenomic databases

eggNOGCOG4935.
GeneTreeENSGT00750000117358.
HOGENOMHOG000192536.
HOVERGENHBG008705.
InParanoidQ6GTN6.
KOK01349.
OMAASCATCQ.
OrthoDBEOG7BW0JD.
TreeFamTF314277.

Enzyme and pathway databases

ReactomeREACT_188257. Signal Transduction.
REACT_188576. Developmental Biology.

Gene expression databases

ArrayExpressP23188.
BgeeP23188.
CleanExMM_FURIN.
GenevestigatorP23188.

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

EvolutionaryTraceP23188.
NextBio294346.
PMAP-CutDBQ6GTN6.
PROP23188.
SOURCESearch...

Entry information

Entry nameFURIN_MOUSE
AccessionPrimary (citable) accession number: P23188
Secondary accession number(s): Q6GTN6
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1991
Last sequence update: July 27, 2011
Last modified: April 16, 2014
This is version 142 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot