FURI1_XENLA
ID FURI1_XENLA Reviewed; 783 AA.
AC P29119;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-1992, sequence version 1.
DT 03-AUG-2022, entry version 130.
DE RecName: Full=Furin-1;
DE EC=3.4.21.75 {ECO:0000250|UniProtKB:P09958};
DE AltName: Full=Dibasic-processing enzyme;
DE AltName: Full=Paired basic amino acid residue-cleaving enzyme;
DE Short=PACE;
DE Flags: Precursor;
GN Name=furin;
OS Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=1722329; DOI=10.1073/pnas.88.24.11393;
RA Korner J., Chun J., O'Bryan L., Axel R.;
RT "Prohormone processing in Xenopus oocytes: characterization of cleavage
RT signals and cleavage enzymes.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:11393-11397(1991).
CC -!- FUNCTION: Ubiquitous endoprotease within constitutive secretory
CC pathways capable of cleavage at the RX(K/R)R consensus motif.
CC {ECO:0000250|UniProtKB:P09958}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Release of mature proteins from their proproteins by cleavage
CC of -Arg-Xaa-Yaa-Arg-|-Zaa- bonds, where Xaa can be any amino acid and
CC Yaa is Arg or Lys. Releases albumin, complement component C3 and von
CC Willebrand factor from their respective precursors.; EC=3.4.21.75;
CC Evidence={ECO:0000250|UniProtKB:P09958};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000250|UniProtKB:P09958};
CC Note=Binds 3 calcium ions per subunit. {ECO:0000250|UniProtKB:P09958};
CC -!- ACTIVITY REGULATION: Inhibited by the not secondly cleaved propeptide.
CC Inhibited by m-guanidinomethyl-phenylacetyl-Arg-Val-Arg-(amidomethyl)-
CC benzamidine (m-guanidinomethyl-Phac-RVR-Amb) and 4-guanidinomethyl-
CC phenylacetyl-Arg-Tle-Arg-4-amidinobenzylamide (MI-1148).
CC {ECO:0000250|UniProtKB:P09958}.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus, trans-Golgi network membrane
CC {ECO:0000250|UniProtKB:P09958}; Single-pass type I membrane protein
CC {ECO:0000305}. Cell membrane {ECO:0000250|UniProtKB:P09958}; Single-
CC pass type I membrane protein {ECO:0000305}. Secreted
CC {ECO:0000250|UniProtKB:Q28193}. Endosome membrane
CC {ECO:0000250|UniProtKB:P09958}; Single-pass type I membrane protein
CC {ECO:0000305}. Note=Shuttles between the trans-Golgi network and the
CC cell surface. Propeptide cleavage is a prerequisite for exit of furin
CC molecules out of the endoplasmic reticulum (ER). A second cleavage
CC within the propeptide occurs in the trans Golgi network (TGN), followed
CC by the release of the propeptide and the activation of furin.
CC {ECO:0000250|UniProtKB:P09958}.
CC -!- TISSUE SPECIFICITY: In all tissues analyzed.
CC {ECO:0000269|PubMed:1722329}.
CC -!- SIMILARITY: Belongs to the peptidase S8 family. Furin subfamily.
CC {ECO:0000305}.
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DR EMBL; M80471; AAA49717.1; -; mRNA.
DR PIR; A41627; A41627.
DR PIR; B41627; B41627.
DR AlphaFoldDB; P29119; -.
DR SMR; P29119; -.
DR MEROPS; S08.071; -.
DR Proteomes; UP000186698; Genome assembly.
DR GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004252; F:serine-type endopeptidase activity; ISS:UniProtKB.
DR GO; GO:1901394; P:positive regulation of transforming growth factor beta1 activation; ISS:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR CDD; cd00064; FU; 2.
DR CDD; cd04059; Peptidases_S8_Protein_convertases_Kexins_Furin-like; 1.
DR Gene3D; 3.30.70.850; -; 1.
DR Gene3D; 3.40.50.200; -; 1.
DR InterPro; IPR006212; Furin_repeat.
DR InterPro; IPR008979; Galactose-bd-like_sf.
DR InterPro; IPR009030; Growth_fac_rcpt_cys_sf.
DR InterPro; IPR034182; Kexin/furin.
DR InterPro; IPR002884; P_dom.
DR InterPro; IPR000209; Peptidase_S8/S53_dom.
DR InterPro; IPR036852; Peptidase_S8/S53_dom_sf.
DR InterPro; IPR023827; Peptidase_S8_Asp-AS.
DR InterPro; IPR022398; Peptidase_S8_His-AS.
DR InterPro; IPR023828; Peptidase_S8_Ser-AS.
DR InterPro; IPR015500; Peptidase_S8_subtilisin-rel.
DR InterPro; IPR032815; S8_pro-domain.
DR InterPro; IPR038466; S8_pro-domain_sf.
DR Pfam; PF01483; P_proprotein; 1.
DR Pfam; PF00082; Peptidase_S8; 1.
DR Pfam; PF16470; S8_pro-domain; 1.
DR PRINTS; PR00723; SUBTILISIN.
DR SMART; SM00261; FU; 2.
DR SUPFAM; SSF49785; SSF49785; 1.
DR SUPFAM; SSF52743; SSF52743; 1.
DR SUPFAM; SSF57184; SSF57184; 1.
DR PROSITE; PS51829; P_HOMO_B; 1.
DR PROSITE; PS51892; SUBTILASE; 1.
DR PROSITE; PS00136; SUBTILASE_ASP; 1.
DR PROSITE; PS00137; SUBTILASE_HIS; 1.
DR PROSITE; PS00138; SUBTILASE_SER; 1.
PE 2: Evidence at transcript level;
KW Cell membrane; Cleavage on pair of basic residues; Disulfide bond;
KW Endosome; Glycoprotein; Golgi apparatus; Hydrolase; Membrane;
KW Metal-binding; Protease; Reference proteome; Repeat; Secreted;
KW Serine protease; Signal; Transmembrane; Transmembrane helix; Zymogen.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT PROPEP 25..105
FT /evidence="ECO:0000255"
FT /id="PRO_0000027034"
FT CHAIN 106..783
FT /note="Furin-1"
FT /id="PRO_0000027035"
FT TOPO_DOM 106..701
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 702..722
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 723..783
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT DOMAIN 119..433
FT /note="Peptidase S8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT DOMAIN 442..574
FT /note="P/Homo B"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01173"
FT REPEAT 585..618
FT /note="FU 1"
FT /evidence="ECO:0000255"
FT REPEAT 636..679
FT /note="FU 2"
FT /evidence="ECO:0000255"
FT REGION 158..189
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 746..749
FT /note="Cell surface signal"
FT /evidence="ECO:0000250|UniProtKB:P09958"
FT REGION 760..783
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 496..498
FT /note="Cell attachment site"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00293"
FT ACT_SITE 151
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT ACT_SITE 192
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT ACT_SITE 366
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT BINDING 113
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P09958"
FT BINDING 152
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P09958"
FT BINDING 160
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P09958"
FT BINDING 172
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P09958"
FT BINDING 177
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P09958"
FT BINDING 179
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P09958"
FT BINDING 189..190
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P09958"
FT BINDING 203
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P09958"
FT BINDING 206
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P09958"
FT BINDING 210
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P09958"
FT BINDING 234
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P09958"
FT BINDING 251..256
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P09958"
FT BINDING 256
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P09958"
FT BINDING 262
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P09958"
FT BINDING 290..293
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P09958"
FT BINDING 299
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P09958"
FT BINDING 304
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P09958"
FT BINDING 306
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P09958"
FT BINDING 329
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P09958"
FT BINDING 366
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P09958"
FT SITE 73..74
FT /note="Cleavage, second; by autolysis"
FT /evidence="ECO:0000250|UniProtKB:P09958"
FT SITE 105..106
FT /note="Cleavage, first; by autolysis"
FT /evidence="ECO:0000250|UniProtKB:P09958"
FT CARBOHYD 385
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 551
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 209..358
FT /evidence="ECO:0000250|UniProtKB:P09958"
FT DISULFID 301..331
FT /evidence="ECO:0000250|UniProtKB:P09958"
SQ SEQUENCE 783 AA; 86444 MW; 02476FD3247AF2C7 CRC64;
MDLSPSLLLM LWTLLSVLVE EITGQKVYTN TWAAHISGGS AEADRLCKKY GFINHGLIFE
DHYHFSHRAV MKRSLTPKRT RQVLLKREPQ VHWLEQQVAK KRKKRDIYTD PTDPKFMQQW
YLLDTNRHDL HVKEAWEQGF TGKGIVVSIL DDGIEKNHPD LQANYDPAAS YDVNDQDPDP
QPRYTQLNDN RHGTRCAGEV AAVANNGICG VGIAYNANIG GVRMLDGEVT DAVEARSLGL
NPNHIHIYSA SWGPEDDGKT VDGPAKLAEE AFYRGVTQGR GGLGSIYVWA SGNGGREHDS
CNCDGYTNSI YTLSISSTTQ MGNVPWYSEA CSSTLATTYS SGNQNEKQIV TTDLRQKCTD
SHTGTSASAP LAAGIIALAL EANKNLTWRD MQHLVVQTSN PAGLNANDWI TNGVGRKVSH
SYGYGLLDAG AMVAMAKTWV TVGPQRKYVI DILSEPKDIG KALEVRRKVE PCAGMSNYIS
TLEHVQARLS LSYNCRGDLA IYLTSPMGTR SCLLAPRPHD YSADGFNDWS FMTTHSWDED
PAGEWVLEIE NVSNNNNYGT LTQFVLVLYG TASEGLSRKF DGDGSRNVAS SQSCIVCEEG
YFLHQKSCIK SCPQGFTSSI QNIHYTLDNN IEPLLVNVCV PCHVSCATCK GTTINDCLTC
PAHSHYNLLD YSCTHQTQRS RESPTLKDSS HDYVARTSNL PFIVAILSCL FIIVVFGSIF
LFLQLRSGGV LGRKRLYMLD SGIISYKGIP SGAWQEEGFS ESETEETAAH SERTAFLKQQ
STL
