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Protein

Furin

Gene

FURIN

Organism
Bos taurus (Bovine)
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.1 Publication

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.1 Publication

Cofactori

Ca2+1 PublicationNote: Binds 3 calcium ions per subunit.By similarity

Enzyme regulationi

Inhibited by the not secondly cleaved propeptide. Inhibited by m-guanidinomethyl-phenylacetyl-Arg-Val-Arg-(amidomethyl)-benzamidine (m-guanidinomethyl-Phac-RVR-Amb) and 4-guanidinomethyl-phenylacteyl-Arg-Tle-Arg-4-amidinobenzylamide (MI-1148).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi115Calcium 1By similarity1
Active sitei153Charge relay systemPROSITE-ProRule annotation1
Binding sitei154SubstrateBy similarity1
Metal bindingi162Calcium 1By similarity1
Metal bindingi174Calcium 2By similarity1
Metal bindingi179Calcium 2By similarity1
Metal bindingi181Calcium 2; via carbonyl oxygenBy similarity1
Active sitei194Charge relay systemPROSITE-ProRule annotation1
Metal bindingi205Calcium 1; via carbonyl oxygenBy similarity1
Metal bindingi208Calcium 1By similarity1
Metal bindingi210Calcium 1; via carbonyl oxygenBy similarity1
Metal bindingi212Calcium 1; via carbonyl oxygenBy similarity1
Binding sitei231inhibitor; via carbonyl oxygenBy similarity1
Binding sitei236inhibitorBy similarity1
Binding sitei236SubstrateBy similarity1
Metal bindingi258Calcium 3By similarity1
Binding sitei264SubstrateBy similarity1
Metal bindingi301Calcium 3By similarity1
Binding sitei306SubstrateBy similarity1
Binding sitei308SubstrateBy similarity1
Metal bindingi331Calcium 3By similarity1
Active sitei368Charge relay systemBy similarity1
Binding sitei368SubstrateBy similarity1

GO - Molecular functioni

Keywordsi

Molecular functionHydrolase, Protease, Serine protease
LigandCalcium, Metal-binding

Protein family/group databases

MEROPSiS08.071.

Names & Taxonomyi

Protein namesi
Recommended name:
Furin (EC:3.4.21.751 Publication)
Alternative name(s):
Dibasic-processing enzyme
Paired basic amino acid residue-cleaving enzyme
Short name:
PACE
Trans Golgi network protease furin
Gene namesi
Name:FURIN
Synonyms:FUR, PACE
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Unplaced

Subcellular locationi

  • Golgi apparatustrans-Golgi network membrane 1 Publication; Single-pass type I membrane protein Curated
  • Cell membrane 1 Publication; Single-pass type I membrane protein Curated
  • Secreted 1 Publication
  • Endosome membrane By similarity; Single-pass type I membrane protein Curated

  • 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.1 Publication

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini108 – 718LumenalCuratedAdd BLAST611
Transmembranei719 – 739HelicalSequence analysisAdd BLAST21
Topological domaini740 – 797CytoplasmicCuratedAdd BLAST58

GO - Cellular componenti

Keywords - Cellular componenti

Cell membrane, Endosome, Golgi apparatus, Membrane, Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 26Sequence analysisAdd BLAST26
PropeptideiPRO_000002702627 – 107Inhibition peptideBy similarityAdd BLAST81
ChainiPRO_0000027027108 – 797FurinAdd BLAST690

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi211 ↔ 360By similarity
Disulfide bondi303 ↔ 333By similarity
Glycosylationi387N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi440N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi450 ↔ 474By similarity
Glycosylationi553N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei776PhosphoserineBy similarity1
Modified residuei778PhosphoserineBy 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.1 Publication
Phosphorylation is required for TGN localization of the endoprotease. In vivo, exists as di-, mono- and non-phosphorylated forms.By similarity
N-glycosylated.1 Publication

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

PaxDbiQ28193.
PRIDEiQ28193.

Miscellaneous databases

PMAP-CutDBiQ28193.

Interactioni

Subunit structurei

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

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000003826.

Structurei

3D structure databases

ProteinModelPortaliQ28193.
SMRiQ28193.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini144 – 427Peptidase S8Sequence analysisAdd BLAST284
Domaini444 – 576P/Homo BPROSITE-ProRule annotationAdd BLAST133
Repeati577 – 620FU 1Sequence analysisAdd BLAST44
Repeati638 – 681FU 2Sequence analysisAdd BLAST44

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni191 – 192Substrate bindingBy similarity2
Regioni253 – 258Substrate bindingBy similarity6
Regioni292 – 295Substrate bindingBy similarity4
Regioni762 – 765Cell surface signalBy similarity4

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi498 – 500Cell attachment sitePROSITE-ProRule annotation3
Motifi776 – 782Trans Golgi network signalBy similarity7

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi690 – 698Poly-ProSequence analysis9

Domaini

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

Sequence similaritiesi

Belongs to the peptidase S8 family. Furin subfamily.Curated

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3525. Eukaryota.
COG1404. LUCA.
COG4935. LUCA.
HOGENOMiHOG000192536.
HOVERGENiHBG008705.
InParanoidiQ28193.
KOiK01349.

Family and domain databases

CDDicd04059. Peptidases_S8_Protein_converta. 1 hit.
Gene3Di2.60.120.260. 1 hit.
3.40.50.200. 1 hit.
InterProiView protein in InterPro
IPR006212. Furin_repeat.
IPR008979. Galactose-bd-like.
IPR009030. Growth_fac_rcpt_.
IPR034182. Kexin/furin.
IPR009020. Peptidase/Inhibitor_I9.
IPR000209. Peptidase_S8/S53_dom.
IPR023827. Peptidase_S8_Asp-AS.
IPR022398. Peptidase_S8_His-AS.
IPR015500. Peptidase_S8_subtilisin-rel.
IPR002884. PrprotnconvertsP.
IPR032815. S8_pro-domain.
PfamiView protein in Pfam
PF01483. P_proprotein. 1 hit.
PF00082. Peptidase_S8. 1 hit.
PF16470. S8_pro-domain. 1 hit.
PRINTSiPR00723. SUBTILISIN.
SMARTiView protein in SMART
SM00261. FU. 2 hits.
SUPFAMiSSF49785. SSF49785. 1 hit.
SSF52743. SSF52743. 1 hit.
SSF54897. SSF54897. 1 hit.
SSF57184. SSF57184. 1 hit.
PROSITEiView protein in PROSITE
PS51829. P_HOMO_B. 1 hit.
PS00136. SUBTILASE_ASP. 1 hit.
PS00137. SUBTILASE_HIS. 1 hit.

Sequencei

Sequence statusi: Complete.

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

Q28193-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MELRPWLFWV VAAAGALVLL VADARGEKVF TNTWAVHIPG GPAVADRVAR
60 70 80 90 100
KHGFLNLGQI FGDYYHFWHR AVTKRSLSPH RLGHNRLQRE PQVKWLEQQV
110 120 130 140 150
AKRRAKRDIY QEPTDPKFPQ QWYLSGVTQR DLNVKEAWAQ GYTGRGIVVS
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 KTVDGPAHLA EEAFFRGVSQ GRGGLGSIFV WASGNGGREH
310 320 330 340 350
DSCNCDGYTN SIYTLSISSA TQFGNVPWYS EACSSTLATT YSSGNQNEKQ
360 370 380 390 400
IVTTDLRQKC TESHTGTSAF APLAAGIIAL TLEANKNLTW RDMQHLVVRT
410 420 430 440 450
SKPAHLNAND WATNGVGRKV SHSYGYGLLD AGAMVALAQN WTTVAPQRKC
460 470 480 490 500
TIDILTEPKD IGKRLEVRKT VTACLGEPSH ITRLEHAQAR LTLSYNRRGD
510 520 530 540 550
LAIHLVSPMG TRSTLLAARP HDYSADGFND WAFMTTHSWD EDPSGEWVLE
560 570 580 590 600
IENTSEANNY GTLTKFTLVL YGTAPEGLPT PPESIGCKTL TSSQACVVCE
610 620 630 640 650
EGFSLHQKNC VQHCPPGFAP QVLDTHYSTE NDVEIIRASV CTPCHASCAT
660 670 680 690 700
CQGPAPTDCL SCPSHASLDP VEQTCSRQSQ SSRESHQQQP PPPPRPPPAE
710 720 730 740 750
VATEPRLRAD LLPSHLPEVV AGLSCAFIVL VFVTVFLVLQ LRSGFSFRGV
760 770 780 790
KVYTMDRGLI SYKGLPPEAW QEECPSDSEE DEGRGERTAF IKDQSAL
Length:797
Mass (Da):87,251
Last modified:November 1, 1997 - v1
Checksum:i466F28EC0246C3D2
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X75956 mRNA. Translation: CAA53569.1.
PIRiI46044.
RefSeqiNP_776561.1. NM_174136.2.
UniGeneiBt.21338.

Genome annotation databases

GeneIDi281374.
KEGGibta:281374.

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.

Entry informationi

Entry nameiFURIN_BOVIN
AccessioniPrimary (citable) accession number: Q28193
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1997
Last modified: May 10, 2017
This is version 140 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Peptidase families
    Classification of peptidase families and list of entries
  2. SIMILARITY comments
    Index of protein domains and families