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Protein

Furin

Gene

Furin

Organism
Rattus norvegicus (Rat)
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+By similarity

Enzyme regulationi

Could be inhibited by the not secondly cleaved propeptide.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi115 – 1151Calcium 1By similarity
Active sitei153 – 1531Charge relay systemBy similarity
Metal bindingi162 – 1621Calcium 1By similarity
Active sitei194 – 1941Charge relay systemBy similarity
Metal bindingi208 – 2081Calcium 1By similarity
Metal bindingi258 – 2581Calcium 2By similarity
Metal bindingi301 – 3011Calcium 2By similarity
Metal bindingi331 – 3311Calcium 2By similarity
Active sitei368 – 3681Charge relay systemBy similarity

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
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Serine protease

Keywords - Ligandi

Calcium, Metal-binding

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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi3274. Furin.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei715 – 73521HelicalSequence analysisAdd
BLAST

GO - Cellular componenti

  • endoplasmic reticulum membrane Source: RGD
  • extracellular space Source: GO_Central
  • Golgi cisterna Source: RGD
  • integral component of membrane Source: UniProtKB-KW
  • plasma membrane Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Golgi apparatus, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2424Sequence analysisAdd
BLAST
Propeptidei25 – 10783Inhibition peptideBy similarityPRO_0000027032Add
BLAST
Chaini108 – 793686FurinPRO_0000027033Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi211 ↔ 360By similarity
Disulfide bondi303 ↔ 333By similarity
Glycosylationi387 – 3871N-linked (GlcNAc...)Sequence analysis
Glycosylationi440 – 4401N-linked (GlcNAc...)Sequence analysis
Disulfide bondi450 ↔ 474By similarity
Glycosylationi553 – 5531N-linked (GlcNAc...)Sequence analysis
Modified residuei772 – 7721Phosphoserine; by CK2By similarity
Modified residuei774 – 7741Phosphoserine; by CK2By similarity

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)LengthDescriptionGraphical viewFeature identifierActions
Sitei75 – 762Cleavage, second; by autolysisBy similarity
Sitei107 – 1082Cleavage, first; by autolysisBy similarity

Keywords - PTMi

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

Proteomic databases

PaxDbiP23377.
PRIDEiP23377.

Expressioni

Tissue specificityi

Seems to be expressed ubiquitously.

Developmental stagei

Expressed at E7 day in endoderm and mesoderm, uniformly expressed until E10, when expression is higher in heart and liver primordia. In mid- and late-gestational stages, widely expressed.

Interactioni

Subunit structurei

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

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000015521.

Structurei

3D structure databases

ProteinModelPortaliP23377.
SMRiP23377. Positions 108-574.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini148 – 435288Peptidase S8Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni758 – 7614Cell surface signal

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi498 – 5003Cell attachment siteSequence analysis
Motifi772 – 7787Trans Golgi network signal

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi556 – 705150Cys-richAdd
BLAST

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.
HOGENOMiHOG000192536.
HOVERGENiHBG008705.
InParanoidiP23377.
KOiK01349.
PhylomeDBiP23377.

Family and domain databases

Gene3Di2.60.120.260. 1 hit.
3.30.70.850. 1 hit.
3.40.50.200. 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.
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.

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.

Cross-referencesi

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.

3D structure databases

ProteinModelPortaliP23377.
SMRiP23377. Positions 108-574.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000015521.

Protein family/group databases

MEROPSiS08.071.

Proteomic databases

PaxDbiP23377.
PRIDEiP23377.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi54281.
KEGGirno:54281.
UCSCiRGD:3274. rat.

Organism-specific databases

CTDi5045.
RGDi3274. Furin.

Phylogenomic databases

eggNOGiKOG3525. Eukaryota.
COG1404. LUCA.
COG4935. LUCA.
HOGENOMiHOG000192536.
HOVERGENiHBG008705.
InParanoidiP23377.
KOiK01349.
PhylomeDBiP23377.

Miscellaneous databases

PROiP23377.

Family and domain databases

Gene3Di2.60.120.260. 1 hit.
3.30.70.850. 1 hit.
3.40.50.200. 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.
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...

Publicationsi

  1. "Sequence of the cDNA encoding rat furin, a possible propeptide-processing endoprotease."
    Misumi Y., Sohoda M., Ikehara Y.
    Nucleic Acids Res. 18:6719-6719(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: Wistar.
    Tissue: Liver.
  2. "PACS-1 defines a novel gene family of cytosolic sorting proteins required for trans-Golgi network localization."
    Wan L., Molloy S.S., Thomas L., Liu G., Xiang Y., Rybak S.L., Thomas G.
    Cell 94:205-216(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH PACS1.
    Tissue: Brain.

Entry informationi

Entry nameiFURIN_RAT
AccessioniPrimary (citable) accession number: P23377
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1991
Last sequence update: November 1, 1991
Last modified: July 6, 2016
This is version 145 of the entry and version 1 of the sequence. [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

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.