Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Furin

Gene

Furin

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 activityi

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.

Cofactori

Ca2+Note: Binds 2 calcium ions per subunit.

Enzyme regulationi

Could be inhibited by the not secondly cleaved propeptide.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi115Calcium 11
Active sitei153Charge relay system1
Metal bindingi162Calcium 11
Active sitei194Charge relay system1
Metal bindingi208Calcium 11
Metal bindingi258Calcium 21
Metal bindingi301Calcium 21
Metal bindingi331Calcium 21
Active sitei368Charge relay system1

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Serine protease

Keywords - Ligandi

Calcium, Metal-binding

Enzyme and pathway databases

ReactomeiR-MMU-1181150. Signaling by NODAL.
R-MMU-1442490. Collagen degradation.
R-MMU-1566948. Elastic fibre formation.
R-MMU-1592389. Activation of Matrix Metalloproteinases.
R-MMU-159782. Removal of aminoterminal propeptides from gamma-carboxylated proteins.
R-MMU-167060. NGF processing.
R-MMU-174800. Chylomicron-mediated lipid transport.
R-MMU-186797. Signaling by PDGF.
R-MMU-1912420. Pre-NOTCH Processing in Golgi.
R-MMU-2173789. TGF-beta receptor signaling activates SMADs.

Protein family/group databases

MEROPSiS08.071.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:Furin
Synonyms:Fur, Pcsk3
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:97513. Furin.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transmembranei715 – 735HelicalSequence analysisAdd BLAST21

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Golgi apparatus, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 24Sequence analysisAdd BLAST24
PropeptideiPRO_000002703025 – 107Inhibition peptideBy similarityAdd BLAST83
ChainiPRO_0000027031108 – 793FurinAdd BLAST686

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi211 ↔ 360
Disulfide bondi303 ↔ 333
Glycosylationi387N-linked (GlcNAc...)1
Glycosylationi440N-linked (GlcNAc...)1
Disulfide bondi450 ↔ 474
Glycosylationi553N-linked (GlcNAc...)Sequence analysis1
Modified residuei772Phosphoserine; by CK2By similarity1
Modified residuei774Phosphoserine; by CK2By similarity1

Post-translational modificationi

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei75 – 76Cleavage, second; by autolysisBy similarity2
Sitei107 – 108Cleavage, first; by autolysisBy similarity2

Keywords - PTMi

Autocatalytic cleavage, Cleavage on pair of basic residues, Disulfide bond, Glycoprotein, Phosphoprotein, Zymogen

Proteomic databases

EPDiP23188.
MaxQBiP23188.
PaxDbiP23188.
PeptideAtlasiP23188.
PRIDEiP23188.

PTM databases

iPTMnetiP23188.
PhosphoSitePlusiP23188.

Miscellaneous databases

PMAP-CutDBQ6GTN6.

Expressioni

Tissue specificityi

Seems to be expressed ubiquitously.

Gene expression databases

BgeeiENSMUSG00000030530.
CleanExiMM_FURIN.
ExpressionAtlasiP23188. baseline and differential.
GenevisibleiP23188. MM.

Interactioni

Subunit structurei

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

GO - Molecular functioni

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000102985.

Structurei

Secondary structure

1793
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi118 – 120Combined sources3
Turni122 – 124Combined sources3
Helixi135 – 139Combined sources5
Beta strandi148 – 154Combined sources7
Turni161 – 163Combined sources3
Helixi164 – 166Combined sources3
Helixi169 – 171Combined sources3
Turni175 – 178Combined sources4
Helixi194 – 203Combined sources10
Beta strandi206 – 211Combined sources6
Turni215 – 218Combined sources4
Beta strandi219 – 225Combined sources7
Beta strandi227 – 229Combined sources3
Helixi233 – 240Combined sources8
Turni244 – 246Combined sources3
Beta strandi249 – 252Combined sources4
Beta strandi259 – 261Combined sources3
Helixi268 – 280Combined sources13
Helixi282 – 284Combined sources3
Beta strandi288 – 292Combined sources5
Helixi297 – 299Combined sources3
Helixi303 – 305Combined sources3
Turni307 – 310Combined sources4
Beta strandi314 – 320Combined sources7
Beta strandi338 – 341Combined sources4
Beta strandi351 – 355Combined sources5
Turni356 – 358Combined sources3
Beta strandi359 – 364Combined sources6
Helixi367 – 384Combined sources18
Helixi390 – 400Combined sources11
Beta strandi419 – 421Combined sources3
Turni422 – 424Combined sources3
Helixi431 – 438Combined sources8
Beta strandi448 – 455Combined sources8
Beta strandi464 – 471Combined sources8
Beta strandi482 – 496Combined sources15
Helixi498 – 500Combined sources3
Beta strandi501 – 506Combined sources6
Beta strandi512 – 516Combined sources5
Beta strandi528 – 535Combined sources8
Turni537 – 540Combined sources4
Beta strandi545 – 553Combined sources9
Beta strandi555 – 557Combined sources3
Beta strandi561 – 573Combined sources13

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1P8JX-ray2.60A/B/C/D/E/F/G/H108-578[»]
ProteinModelPortaliP23188.
SMRiP23188.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP23188.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini148 – 435Peptidase S8Add BLAST288

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni758 – 761Cell surface signal4

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi498 – 500Cell attachment siteSequence analysis3
Motifi772 – 778Trans Golgi network signal7

Domaini

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

Sequence similaritiesi

Belongs to the peptidase S8 family. Furin subfamily.Curated
Contains 1 peptidase S8 domain.Curated

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3525. Eukaryota.
COG1404. LUCA.
COG4935. LUCA.
GeneTreeiENSGT00750000117358.
HOGENOMiHOG000192536.
HOVERGENiHBG008705.
InParanoidiP23188.
KOiK01349.
OMAiIIRASVC.
OrthoDBiEOG091G05HI.
TreeFamiTF314277.

Family and domain databases

Gene3Di2.60.120.260. 1 hit.
3.30.70.850. 1 hit.
3.40.50.200. 1 hit.
3.80.20.20. 1 hit.
InterProiIPR006212. Furin_repeat.
IPR008979. Galactose-bd-like.
IPR009030. Growth_fac_rcpt_.
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. Propept_inh.
IPR002884. PrprotnconvertsP.
IPR000494. Rcpt_L-dom.
IPR032815. S8_pro-domain.
[Graphical view]
PANTHERiPTHR10795. PTHR10795. 3 hits.
PfamiPF01483. P_proprotein. 1 hit.
PF00082. Peptidase_S8. 1 hit.
PF16470. S8_pro-domain. 1 hit.
[Graphical view]
PRINTSiPR00723. SUBTILISIN.
SMARTiSM00261. FU. 2 hits.
[Graphical view]
SUPFAMiSSF49785. SSF49785. 1 hit.
SSF52743. SSF52743. 1 hit.
SSF54897. SSF54897. 1 hit.
SSF57184. SSF57184. 1 hit.
PROSITEiPS00136. SUBTILASE_ASP. 1 hit.
PS00137. SUBTILASE_HIS. 1 hit.
PS00138. SUBTILASE_SER. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P23188-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MELRSWLLWV VAAAGAVVLL AADAQGQKIF TNTWAVHIPG GPAVADRVAQ
60 70 80 90 100
KHGFHNLGQI FGDYYHFWHR AVTKRSLSPH RPRHSRLQRE PQVKWLEQQV
110 120 130 140 150
AKRRAKRDVY QEPTDPKFPQ QWYLSGVTQR DLNVKEAWAQ GFTGHGIVVS
160 170 180 190 200
ILDDGIEKNH PDLAGNYDPG ASFDVNDQDP DPQPRYTQMN DNRHGTRCAG
210 220 230 240 250
EVAAVANNGV CGVGVAYNAR IGGVRMLDGE VTDAVEARSL GLNPNHIHIY
260 270 280 290 300
SASWGPEDDG KTVDGPARLA EEAFFRGVSQ GRGGLGSIFV WASGNGGREH
310 320 330 340 350
DSCNCDGYTN SIYTLSISSA TQFGNVPWYS EACSSTLATT YSSGNQNEKQ
360 370 380 390 400
IVTTDLRQKC TESHTGTSAS APLAAGIIAL TLEANKNLTW RDMQHLVVQT
410 420 430 440 450
SKPAHLNADD WATNGVGRKV SHSYGYGLLD AGAMVALAQN WTTVAPQRKC
460 470 480 490 500
IVEILVEPKD IGKRLEVRKA VTACLGEPNH ITRLEHVQAR LTLSYNRRGD
510 520 530 540 550
LAIHLISPMG TRSTLLAARP HDYSADGFND WAFMTTHSWD EDPAGEWVLE
560 570 580 590 600
IENTSEANNY GTLTKFTLVL YGTAPEGLST PPESSGCKTL TSSQACVVCE
610 620 630 640 650
EGYSLHQKSC VQHCPPGFIP QVLDTHYSTE NDVEIIRASV CTPCHASCAT
660 670 680 690 700
CQGPAPTDCL SCPSHASLDP VEQTCSRQSQ SSRESRPQQQ PPALRPEVEM
710 720 730 740 750
EPRLQAGLAS HLPEVLAGLS CLIIVLIFGI VFLFLHRCSG FSFRGVKVYT
760 770 780 790
MDRGLISYKG LPPEAWQEEC PSDSEEDEGR GERTAFIKDQ SAL
Length:793
Mass (Da):86,772
Last modified:July 27, 2011 - v2
Checksum:i0F120C2DE2E1A431
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti746V → M in CAA37988 (PubMed:2266110).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X54056 mRNA. Translation: CAA37988.1.
L26489 mRNA. Translation: AAA37643.1.
CH466543 Genomic DNA. Translation: EDL06988.1.
BC048234 mRNA. Translation: AAH48234.1.
CCDSiCCDS21397.1.
PIRiA23679. KXMSF.
RefSeqiNP_001074923.1. NM_001081454.2.
NP_035176.1. NM_011046.3.
UniGeneiMm.5241.

Genome annotation databases

EnsembliENSMUST00000107362; ENSMUSP00000102985; ENSMUSG00000030530.
ENSMUST00000120753; ENSMUSP00000113793; ENSMUSG00000030530.
ENSMUST00000122232; ENSMUSP00000113370; ENSMUSG00000030530.
GeneIDi18550.
KEGGimmu:18550.
UCSCiuc009iau.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X54056 mRNA. Translation: CAA37988.1.
L26489 mRNA. Translation: AAA37643.1.
CH466543 Genomic DNA. Translation: EDL06988.1.
BC048234 mRNA. Translation: AAH48234.1.
CCDSiCCDS21397.1.
PIRiA23679. KXMSF.
RefSeqiNP_001074923.1. NM_001081454.2.
NP_035176.1. NM_011046.3.
UniGeneiMm.5241.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1P8JX-ray2.60A/B/C/D/E/F/G/H108-578[»]
ProteinModelPortaliP23188.
SMRiP23188.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000102985.

Protein family/group databases

MEROPSiS08.071.

PTM databases

iPTMnetiP23188.
PhosphoSitePlusiP23188.

Proteomic databases

EPDiP23188.
MaxQBiP23188.
PaxDbiP23188.
PeptideAtlasiP23188.
PRIDEiP23188.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000107362; ENSMUSP00000102985; ENSMUSG00000030530.
ENSMUST00000120753; ENSMUSP00000113793; ENSMUSG00000030530.
ENSMUST00000122232; ENSMUSP00000113370; ENSMUSG00000030530.
GeneIDi18550.
KEGGimmu:18550.
UCSCiuc009iau.1. mouse.

Organism-specific databases

CTDi5045.
MGIiMGI:97513. Furin.

Phylogenomic databases

eggNOGiKOG3525. Eukaryota.
COG1404. LUCA.
COG4935. LUCA.
GeneTreeiENSGT00750000117358.
HOGENOMiHOG000192536.
HOVERGENiHBG008705.
InParanoidiP23188.
KOiK01349.
OMAiIIRASVC.
OrthoDBiEOG091G05HI.
TreeFamiTF314277.

Enzyme and pathway databases

ReactomeiR-MMU-1181150. Signaling by NODAL.
R-MMU-1442490. Collagen degradation.
R-MMU-1566948. Elastic fibre formation.
R-MMU-1592389. Activation of Matrix Metalloproteinases.
R-MMU-159782. Removal of aminoterminal propeptides from gamma-carboxylated proteins.
R-MMU-167060. NGF processing.
R-MMU-174800. Chylomicron-mediated lipid transport.
R-MMU-186797. Signaling by PDGF.
R-MMU-1912420. Pre-NOTCH Processing in Golgi.
R-MMU-2173789. TGF-beta receptor signaling activates SMADs.

Miscellaneous databases

EvolutionaryTraceiP23188.
PMAP-CutDBQ6GTN6.
PROiP23188.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000030530.
CleanExiMM_FURIN.
ExpressionAtlasiP23188. baseline and differential.
GenevisibleiP23188. MM.

Family and domain databases

Gene3Di2.60.120.260. 1 hit.
3.30.70.850. 1 hit.
3.40.50.200. 1 hit.
3.80.20.20. 1 hit.
InterProiIPR006212. Furin_repeat.
IPR008979. Galactose-bd-like.
IPR009030. Growth_fac_rcpt_.
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. Propept_inh.
IPR002884. PrprotnconvertsP.
IPR000494. Rcpt_L-dom.
IPR032815. S8_pro-domain.
[Graphical view]
PANTHERiPTHR10795. PTHR10795. 3 hits.
PfamiPF01483. P_proprotein. 1 hit.
PF00082. Peptidase_S8. 1 hit.
PF16470. S8_pro-domain. 1 hit.
[Graphical view]
PRINTSiPR00723. SUBTILISIN.
SMARTiSM00261. FU. 2 hits.
[Graphical view]
SUPFAMiSSF49785. SSF49785. 1 hit.
SSF52743. SSF52743. 1 hit.
SSF54897. SSF54897. 1 hit.
SSF57184. SSF57184. 1 hit.
PROSITEiPS00136. SUBTILASE_ASP. 1 hit.
PS00137. SUBTILASE_HIS. 1 hit.
PS00138. SUBTILASE_SER. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiFURIN_MOUSE
AccessioniPrimary (citable) accession number: P23188
Secondary accession number(s): Q6GTN6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1991
Last sequence update: July 27, 2011
Last modified: November 30, 2016
This is version 170 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. Peptidase families
    Classification of peptidase families and list of entries
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.