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P23188

- FURIN_MOUSE

UniProt

P23188 - FURIN_MOUSE

Protein

Furin

Gene

Furin

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 147 (01 Oct 2014)
      Sequence version 2 (27 Jul 2011)
      Previous versions | rss
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    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 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. 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

    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.By similarity

    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

    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

    ArrayExpressiP23188.
    BgeeiP23188.
    CleanExiMM_FURIN.
    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 – 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.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP23188.

    Transmembrane

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

    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.
    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

    Experimental Info

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

    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

    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: October 1, 2014
    This is version 147 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