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Reviewed, UniProtKB/Swiss-Prot P23188 (FURIN_MOUSE)

Last modified June 16, 2009. Version 97. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
    Furin
    EC=3.4.21.75
Alternative name(s):
    Paired basic amino acid residue cleaving enzyme
      Short name=PACE
    Dibasic-processing enzyme
    Prohormone convertase 3
Gene names
Name: Furin
Synonyms: Fur, Pcsk3
OrganismMus musculus (Mouse)
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

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Protein attributes

Sequence length793 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

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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.

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 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.

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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 – 73521 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 conflict7461M → V in AAA37643. Ref.2

Secondary structure

1 ................................................................................... 793
Helix Strand Turn

Details...

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Sequences

Sequence LengthMass (Da)Tools
P23188-1 [UniParc].

Last modified November 1, 1991. Version 1.
Checksum: 5F121C3DE2E1A42D

FASTA79386,804
        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 FSFRGMKVYT MDRGLISYKG LPPEAWQEEC PSDSEEDEGR 

       790 
GERTAFIKDQ SAL

« Hide

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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: 2266110] [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]"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: 9412467] [Abstract]
Cited for: INTERACTION WITH FLNA.
[4]"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: 12794637] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 108-578 IN COMPLEX WITH INHIBITOR.
+Additional computationally mapped references.

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Cross-references

Sequence databases

X54056 mRNA. Translation: CAA37988.1.
L26489 mRNA. Translation: AAA37643.1.
IPIIPI00314624.
PIRKXMSF. A23679.
UniGeneMm.5241

3D structure databases

EntryMethodResolution (Å)ChainPositionsPDBsum
1P8JX-ray2.60A/B/C/D/E/F/G/H108-578[»]
ModBaseSearch...

Protein family/group databases

MEROPSS08.071.

PTM databases

PhosphoSiteP23188.

Genome annotation databases

EnsemblENSMUSG00000030530. Mus musculus. [Contig view]

Organism-specific databases

MGIMGI:97513. Furin.

Phylogenomic databases

HOGENOMP23188.
HOVERGENP23188.

Enzyme and pathway databases

BRENDA3.4.21.75. 244.

Gene expression databases

ArrayExpressP23188.
BgeeP23188.
CleanExMM_FURIN.
GermOnlineENSMUSG00000030530. Mus musculus.

Family and domain databases

InterProIPR006212. Furin_repeat.
IPR000209. Pept_S8_S53.
IPR015500. Peptidase_S8_subtilisin-rel.
IPR002884. PrprotnconvertsP.
[Graphical view]
Gene3DG3DSA:3.40.50.200. Pept_S8_S53. 1 hit.
PANTHERPTHR10795. SubtilSerProt. 1 hit.
PfamPF01483. P_proprotein. 1 hit.
PF00082. Peptidase_S8. 1 hit.
[Graphical view]
PRINTSPR00723. SUBTILISIN.
ProDomPD000717. PrprotnconvertsP. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTSM00261. FU. 2 hits.
[Graphical view]
PROSITEPS00136. SUBTILASE_ASP. 1 hit.
PS00137. SUBTILASE_HIS. 1 hit.
PS00138. SUBTILASE_SER. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

SOURCESearch...

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Entry information

Entry nameFURIN_MOUSE
AccessionPrimary (citable) accession number: P23188
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1991
Last sequence update: November 1, 1991
Last modified: June 16, 2009
This is version 97 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

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Relevant documents

MGD cross-references

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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

Peptidase families

Classification of peptidase families and list of entries

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents