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P23188

- FURIN_MOUSE

UniProt

P23188 - FURIN_MOUSE

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Protein

Furin

Gene

Furin

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

Ca2+Note: 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 autolysisBy similarity
Sitei107 – 1082Cleavage, first; by autolysisBy 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. serine-type endopeptidase activity Source: RefGenome
  5. 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.
REACT_255710. Removal of aminoterminal propeptides from gamma-carboxylated proteins.
REACT_263353. Signaling by PDGF.

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).By similarity

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei715 – 73521HelicalSequence AnalysisAdd
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. extracellular vesicular exosome Source: Ensembl
  7. Golgi apparatus Source: RefGenome
  8. integral component of membrane Source: MGI
  9. membrane raft Source: Ensembl
  10. plasma membrane Source: UniProtKB-KW
  11. trans-Golgi network Source: Ensembl
  12. trans-Golgi network transport vesicle Source: MGI
  13. 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 – 2424Sequence AnalysisAdd
BLAST
Propeptidei25 – 10783Inhibition peptideBy 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...)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

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

BgeeiP23188.
CleanExiMM_FURIN.
ExpressionAtlasiP23188. baseline and differential.
GenevestigatoriP23188.

Interactioni

Subunit structurei

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

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000113370.

Structurei

Secondary structure

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

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1P8JX-ray2.60A/B/C/D/E/F/G/H108-578[»]
ProteinModelPortaliP23188.
SMRiP23188. Positions 30-99, 109-578.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP23188.

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

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

eggNOGiCOG4935.
GeneTreeiENSGT00750000117358.
HOGENOMiHOG000192536.
HOVERGENiHBG008705.
InParanoidiP23188.
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

        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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti746 – 7461V → M in CAA37988. (PubMed:2266110)Curated

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_001081454.1.
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:
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 .
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:
PDBei
RCSB PDBi
PDBji
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.
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 P23188.
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.
REACT_255710. Removal of aminoterminal propeptides from gamma-carboxylated proteins.
REACT_263353. Signaling by PDGF.

Miscellaneous databases

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

Gene expression databases

Bgeei P23188.
CleanExi MM_FURIN.
ExpressionAtlasi P23188. baseline and differential.
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: November 26, 2014
This is version 149 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