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Protein

Furin

Gene

Furin

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -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.By similarity

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.By similarity

Cofactori

Ca2+By similarityNote: 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 systemPROSITE-ProRule annotation1
Binding sitei368SubstrateBy similarity1

GO - Molecular functioni

  • metal ion binding Source: UniProtKB-KW
  • serine-type endopeptidase activity Source: RGD

GO - Biological processi

  • aging Source: RGD
  • positive regulation of cell migration Source: RGD
  • positive regulation of transforming growth factor beta receptor signaling pathway Source: RGD
  • protein processing Source: RGD

Keywordsi

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

Protein family/group databases

MEROPSiS08.071

Names & Taxonomyi

Protein namesi
Recommended name:
Furin (EC:3.4.21.75By similarity)
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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi3274 Furin

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini108 – 714LumenalCuratedAdd BLAST607
Transmembranei715 – 735HelicalSequence analysisAdd BLAST21
Topological domaini736 – 793CytoplasmicCuratedAdd BLAST58

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_000002703227 – 107Inhibition peptideBy similarityAdd BLAST81
ChainiPRO_0000027033108 – 793FurinAdd BLAST686

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 residuei772PhosphoserineBy similarity1
Modified residuei774PhosphoserineBy 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
Phosphorylation is required for TGN localization of the endoprotease. In vivo, exists as di-, mono- and non-phosphorylated forms.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

PaxDbiP23377
PRIDEiP23377

Interactioni

Subunit structurei

Interacts with FLNA (By similarity). Binds to PACS1 which mediates TGN localization and connection to clathrin adapters (PubMed:9695949).By similarity1 Publication

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000015521

Structurei

3D structure databases

ProteinModelPortaliP23377
SMRiP23377
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini148 – 435Peptidase S8Sequence analysisAdd BLAST288
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
Regioni758 – 761Cell surface signalBy similarity4

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi498 – 500Cell attachment sitePROSITE-ProRule annotation3
Motifi772 – 778Trans Golgi network signalBy similarity7

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
InParanoidiP23377
KOiK01349
PhylomeDBiP23377

Family and domain databases

CDDicd04059 Peptidases_S8_Protein_converta, 1 hit
Gene3Di2.60.120.260, 1 hit
3.30.70.850, 1 hit
3.40.50.200, 1 hit
InterProiView protein in InterPro
IPR006212 Furin_repeat
IPR008979 Galactose-bd-like_sf
IPR009030 Growth_fac_rcpt_cys_sf
IPR034182 Kexin/furin
IPR002884 P_dom
IPR000209 Peptidase_S8/S53_dom
IPR036852 Peptidase_S8/S53_dom_sf
IPR023827 Peptidase_S8_Asp-AS
IPR022398 Peptidase_S8_His-AS
IPR023828 Peptidase_S8_Ser-AS
IPR015500 Peptidase_S8_subtilisin-rel
IPR032815 S8_pro-domain
IPR038466 S8_pro-domain_sf
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
SSF57184 SSF57184, 1 hit
PROSITEiView protein in PROSITE
PS51829 P_HOMO_B, 1 hit
PS00136 SUBTILASE_ASP, 1 hit
PS00137 SUBTILASE_HIS, 1 hit
PS00138 SUBTILASE_SER, 1 hit

Sequencei

Sequence statusi: Complete.

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

P23377-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MELRPWLLWV VAAAGALVLL AAEARGQKIF TNTWAVHISG GPAVADSVAR
60 70 80 90 100
KHGFHNLGQI FGDYYHFWHR AVTKRSLSPH RPRHSRLQRV PQVKWLEQQV
110 120 130 140 150
AKQRAKRDVY QEPTDPKFPQ QWYLSGVTQR DLNVKEAWAQ GFTGRGIVVS
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
SKPAHLNAND WATNGVGRKV SHSYGYGLLD AGAMVALAQN WTTVAPQRKC
460 470 480 490 500
IIEILAEPKD IGKRLEVRKT VTACLGEPNH ISRLEHVQAR LTLSYNRRGD
510 520 530 540 550
LAIHLISPMG TRSTLLAARP HDYSADGFND WAFMTTHSWD EDPSGEWVLE
560 570 580 590 600
IENTSEANNY GTLTKFTLVL YGTASEGLSA PPESSGCKTL TSSQACVVCE
610 620 630 640 650
EGFSLHQKSC VQRCPPGFTP QVLDTHYSTE NDVEIIRASV CTPCHASCAT
660 670 680 690 700
CQGPAPTDCL SCPSHASLDP VEQTCSRQSQ SSRESRPQQP PPALRPEVEV
710 720 730 740 750
EPRLRAGLAS HLPEVLAGLS CLIIALIFGI VFLFLHRCSG FSFRGVKVYT
760 770 780 790
MDRGLISYKG LPPEAWQEEC PSDSEEDEGR GERTAFIKDQ SAL
Length:793
Mass (Da):86,653
Last modified:November 1, 1991 - v1
Checksum:i87C22C345AE0A25C
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X55660 mRNA Translation: CAA39193.1
PIRiS13106 KXRTF
RefSeqiNP_062204.1, NM_019331.1
UniGeneiRn.3220

Genome annotation databases

GeneIDi54281
KEGGirno:54281
UCSCiRGD:3274 rat

Similar proteinsi

Entry informationi

Entry nameiFURIN_RAT
AccessioniPrimary (citable) accession number: P23377
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1991
Last sequence update: November 1, 1991
Last modified: May 23, 2018
This is version 156 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

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