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P23188

- FURIN_MOUSE

UniProt

P23188 - FURIN_MOUSE

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Protein

Furin

Gene
Furin, Fur, Pcsk3
Organism
Mus musculus (Mouse)
Status
Reviewed - 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 vWF from their respective precursors.

Cofactori

Binds 2 calcium ions per subunit.

Enzyme regulationi

Could be inhibited by the not secondly cleaved propeptide.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei75 – 762Cleavage, second; by autolysis By similarity
Sitei107 – 1082Cleavage, first; by autolysis By similarity
Metal bindingi115 – 1151Calcium 1
Active sitei153 – 1531Charge relay system
Metal bindingi162 – 1621Calcium 1
Active sitei194 – 1941Charge relay system
Metal bindingi208 – 2081Calcium 1
Metal bindingi258 – 2581Calcium 2
Metal bindingi301 – 3011Calcium 2
Metal bindingi331 – 3311Calcium 2
Active sitei368 – 3681Charge relay system

GO - Molecular functioni

  1. metal ion binding Source: UniProtKB-KW
  2. peptidase activity Source: MGI
  3. peptide binding Source: Ensembl
  4. protein binding Source: MGI
  5. serine-type endopeptidase activity Source: RefGenome
  6. serine-type endopeptidase inhibitor activity Source: Ensembl

GO - Biological processi

  1. cell proliferation Source: Ensembl
  2. negative regulation of low-density lipoprotein particle receptor catabolic process Source: Ensembl
  3. negative regulation of transforming growth factor beta1 production Source: Ensembl
  4. nerve growth factor production Source: Ensembl
  5. peptide biosynthetic process Source: Ensembl
  6. peptide hormone processing Source: Ensembl
  7. protein processing Source: MGI
  8. regulation of signal transduction Source: MGI
  9. secretion by cell Source: Ensembl
  10. signal peptide processing Source: Ensembl
  11. viral life cycle Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Serine protease

Keywords - Ligandi

Calcium, Metal-binding

Enzyme and pathway databases

ReactomeiREACT_196517. Pre-NOTCH Processing in Golgi.
REACT_198996. Elastic fibre formation.
REACT_199000. Activation of Matrix Metalloproteinases.
REACT_199055. Collagen degradation.
REACT_203510. TGF-beta receptor signaling activates SMADs.
REACT_206713. NGF processing.
REACT_220645. Signaling by NODAL.

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
ProteomesiUP000000589: Chromosome 7

Organism-specific databases

MGIiMGI:97513. Furin.

Subcellular locationi

Golgi apparatustrans-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.

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei715 – 73521Helical; Reviewed predictionAdd
BLAST

GO - Cellular componenti

  1. cell surface Source: Ensembl
  2. early endosome Source: MGI
  3. endoplasmic reticulum lumen Source: Reactome
  4. extracellular region Source: Reactome
  5. extracellular space Source: RefGenome
  6. Golgi apparatus Source: RefGenome
  7. integral component of membrane Source: MGI
  8. membrane raft Source: Ensembl
  9. plasma membrane Source: UniProtKB-SubCell
  10. trans-Golgi network Source: Ensembl
  11. trans-Golgi network transport vesicle Source: MGI
  12. trans-Golgi network transport vesicle membrane Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Golgi apparatus, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2424 Reviewed predictionAdd
BLAST
Propeptidei25 – 10783Inhibition peptide By similarityPRO_0000027030Add
BLAST
Chaini108 – 793686FurinPRO_0000027031Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi211 ↔ 360
Disulfide bondi303 ↔ 333
Glycosylationi387 – 3871N-linked (GlcNAc...)
Glycosylationi440 – 4401N-linked (GlcNAc...)
Disulfide bondi450 ↔ 474
Glycosylationi553 – 5531N-linked (GlcNAc...) Reviewed prediction
Modified residuei772 – 7721Phosphoserine; by CK2 By similarity
Modified residuei774 – 7741Phosphoserine; by CK2 By 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.
Phosphorylation is required for TGN localization of the endoprotease. In vivo, exists as di-, mono- and non-phosphorylated forms By similarity.

Keywords - PTMi

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

Proteomic databases

MaxQBiP23188.
PaxDbiP23188.
PRIDEiP23188.

PTM databases

PhosphoSiteiP23188.

Miscellaneous databases

PMAP-CutDBQ6GTN6.

Expressioni

Tissue specificityi

Seems to be expressed ubiquitously.

Gene expression databases

ArrayExpressiP23188.
BgeeiP23188.
CleanExiMM_FURIN.
GenevestigatoriP23188.

Interactioni

Subunit structurei

Interacts with FLNA By similarity. Binds to PACS1 which mediates TGN localization and connection to clathrin adapters By similarity.1 Publication

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000113370.

Structurei

Secondary structure

1
793
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi118 – 1203
Turni122 – 1243
Helixi135 – 1395
Beta strandi148 – 1547
Turni161 – 1633
Helixi164 – 1663
Helixi169 – 1713
Turni175 – 1784
Helixi194 – 20310
Beta strandi206 – 2116
Turni215 – 2184
Beta strandi219 – 2257
Beta strandi227 – 2293
Helixi233 – 2408
Turni244 – 2463
Beta strandi249 – 2524
Beta strandi259 – 2613
Helixi268 – 28013
Helixi282 – 2843
Beta strandi288 – 2925
Helixi297 – 2993
Helixi303 – 3053
Turni307 – 3104
Beta strandi314 – 3207
Beta strandi338 – 3414
Beta strandi351 – 3555
Turni356 – 3583
Beta strandi359 – 3646
Helixi367 – 38418
Helixi390 – 40011
Beta strandi419 – 4213
Turni422 – 4243
Helixi431 – 4388
Beta strandi448 – 4558
Beta strandi464 – 4718
Beta strandi482 – 49615
Helixi498 – 5003
Beta strandi501 – 5066
Beta strandi512 – 5165
Beta strandi528 – 5358
Turni537 – 5404
Beta strandi545 – 5539
Beta strandi555 – 5573
Beta strandi561 – 57313

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1P8JX-ray2.60A/B/C/D/E/F/G/H108-578[»]
ProteinModelPortaliP23188.
SMRiP23188. Positions 30-99, 109-578, 585-648.

Miscellaneous databases

EvolutionaryTraceiP23188.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni109 – 445337CatalyticAdd
BLAST
Regioni446 – 578133P-domainAdd
BLAST
Regioni758 – 7614Cell surface signal

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi498 – 5003Cell attachment site Reviewed prediction
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

Contains 1 homo B/P domain.

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG4935.
GeneTreeiENSGT00750000117358.
HOGENOMiHOG000192536.
HOVERGENiHBG008705.
InParanoidiQ6GTN6.
KOiK01349.
OMAiTWAVRIP.
OrthoDBiEOG7BW0JD.
TreeFamiTF314277.

Family and domain databases

Gene3Di2.60.120.260. 1 hit.
3.40.50.200. 1 hit.
InterProiIPR006212. Furin_repeat.
IPR008979. Galactose-bd-like.
IPR009030. Growth_fac_rcpt_N_dom.
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. Prot_inh_propept.
IPR002884. PrprotnconvertsP.
[Graphical view]
PANTHERiPTHR10795. PTHR10795. 1 hit.
PfamiPF01483. P_proprotein. 1 hit.
PF00082. Peptidase_S8. 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

MELRSWLLWV VAAAGAVVLL AADAQGQKIF TNTWAVHIPG GPAVADRVAQ    50
KHGFHNLGQI FGDYYHFWHR AVTKRSLSPH RPRHSRLQRE PQVKWLEQQV 100
AKRRAKRDVY QEPTDPKFPQ QWYLSGVTQR DLNVKEAWAQ GFTGHGIVVS 150
ILDDGIEKNH PDLAGNYDPG ASFDVNDQDP DPQPRYTQMN DNRHGTRCAG 200
EVAAVANNGV CGVGVAYNAR IGGVRMLDGE VTDAVEARSL GLNPNHIHIY 250
SASWGPEDDG KTVDGPARLA EEAFFRGVSQ GRGGLGSIFV WASGNGGREH 300
DSCNCDGYTN SIYTLSISSA TQFGNVPWYS EACSSTLATT YSSGNQNEKQ 350
IVTTDLRQKC TESHTGTSAS APLAAGIIAL TLEANKNLTW RDMQHLVVQT 400
SKPAHLNADD WATNGVGRKV SHSYGYGLLD AGAMVALAQN WTTVAPQRKC 450
IVEILVEPKD IGKRLEVRKA VTACLGEPNH ITRLEHVQAR LTLSYNRRGD 500
LAIHLISPMG TRSTLLAARP HDYSADGFND WAFMTTHSWD EDPAGEWVLE 550
IENTSEANNY GTLTKFTLVL YGTAPEGLST PPESSGCKTL TSSQACVVCE 600
EGYSLHQKSC VQHCPPGFIP QVLDTHYSTE NDVEIIRASV CTPCHASCAT 650
CQGPAPTDCL SCPSHASLDP VEQTCSRQSQ SSRESRPQQQ PPALRPEVEM 700
EPRLQAGLAS HLPEVLAGLS CLIIVLIFGI VFLFLHRCSG FSFRGVKVYT 750
MDRGLISYKG LPPEAWQEEC PSDSEEDEGR GERTAFIKDQ SAL 793
Length:793
Mass (Da):86,772
Last modified:July 27, 2011 - v2
Checksum:i0F120C2DE2E1A431
GO

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti746 – 7461V → M in CAA37988. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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_001081454.1.
NP_035176.1. NM_011046.2.
XP_006540765.1. XM_006540702.1.
XP_006540766.1. XM_006540703.1.
XP_006540767.1. XM_006540704.1.
XP_006540768.1. XM_006540705.1.
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:
EMBL
GenBank
DDBJ
Links Updated
X54056 mRNA. Translation: CAA37988.1 .
L26489 mRNA. Translation: AAA37643.1 .
CH466543 Genomic DNA. Translation: EDL06988.1 .
BC048234 mRNA. Translation: AAH48234.1 .
CCDSi CCDS21397.1.
PIRi A23679. KXMSF.
RefSeqi NP_001074923.1. NM_001081454.1.
NP_035176.1. NM_011046.2.
XP_006540765.1. XM_006540702.1.
XP_006540766.1. XM_006540703.1.
XP_006540767.1. XM_006540704.1.
XP_006540768.1. XM_006540705.1.
UniGenei Mm.5241.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1P8J X-ray 2.60 A/B/C/D/E/F/G/H 108-578 [» ]
ProteinModelPortali P23188.
SMRi P23188. Positions 30-99, 109-578, 585-648.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

STRINGi 10090.ENSMUSP00000113370.

Protein family/group databases

MEROPSi S08.071.

PTM databases

PhosphoSitei P23188.

Proteomic databases

MaxQBi P23188.
PaxDbi P23188.
PRIDEi P23188.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000107362 ; ENSMUSP00000102985 ; ENSMUSG00000030530 .
ENSMUST00000120753 ; ENSMUSP00000113793 ; ENSMUSG00000030530 .
ENSMUST00000122232 ; ENSMUSP00000113370 ; ENSMUSG00000030530 .
GeneIDi 18550.
KEGGi mmu:18550.
UCSCi uc009iau.1. mouse.

Organism-specific databases

CTDi 5045.
MGIi MGI:97513. Furin.

Phylogenomic databases

eggNOGi COG4935.
GeneTreei ENSGT00750000117358.
HOGENOMi HOG000192536.
HOVERGENi HBG008705.
InParanoidi Q6GTN6.
KOi K01349.
OMAi TWAVRIP.
OrthoDBi EOG7BW0JD.
TreeFami TF314277.

Enzyme and pathway databases

Reactomei REACT_196517. Pre-NOTCH Processing in Golgi.
REACT_198996. Elastic fibre formation.
REACT_199000. Activation of Matrix Metalloproteinases.
REACT_199055. Collagen degradation.
REACT_203510. TGF-beta receptor signaling activates SMADs.
REACT_206713. NGF processing.
REACT_220645. Signaling by NODAL.

Miscellaneous databases

EvolutionaryTracei P23188.
NextBioi 294346.
PMAP-CutDB Q6GTN6.
PROi P23188.
SOURCEi Search...

Gene expression databases

ArrayExpressi P23188.
Bgeei P23188.
CleanExi MM_FURIN.
Genevestigatori P23188.

Family and domain databases

Gene3Di 2.60.120.260. 1 hit.
3.40.50.200. 1 hit.
InterProi IPR006212. Furin_repeat.
IPR008979. Galactose-bd-like.
IPR009030. Growth_fac_rcpt_N_dom.
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. Prot_inh_propept.
IPR002884. PrprotnconvertsP.
[Graphical view ]
PANTHERi PTHR10795. PTHR10795. 1 hit.
Pfami PF01483. P_proprotein. 1 hit.
PF00082. Peptidase_S8. 1 hit.
[Graphical view ]
PRINTSi PR00723. SUBTILISIN.
SMARTi SM00261. FU. 2 hits.
[Graphical view ]
SUPFAMi SSF49785. SSF49785. 1 hit.
SSF52743. SSF52743. 1 hit.
SSF54897. SSF54897. 1 hit.
SSF57184. SSF57184. 1 hit.
PROSITEi PS00136. SUBTILASE_ASP. 1 hit.
PS00137. SUBTILASE_HIS. 1 hit.
PS00138. SUBTILASE_SER. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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] [Europe PMC] [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. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
    Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Eye.
  5. "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] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH FLNA.
  6. "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] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 108-578 IN COMPLEX WITH INHIBITOR.

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: September 3, 2014
This is version 146 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

External Data

Dasty 3

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