ID FURIN_HUMAN Reviewed; 794 AA.
AC P09958; Q14336; Q6LBS3; Q9UCZ5;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1990, sequence version 2.
DT 27-MAR-2024, entry version 258.
DE RecName: Full=Furin {ECO:0000303|PubMed:7690548};
DE EC=3.4.21.75 {ECO:0000269|PubMed:11799113, ECO:0000269|PubMed:1629222, ECO:0000269|PubMed:1713771, ECO:0000269|PubMed:2251280, ECO:0000269|PubMed:25974265, ECO:0000269|PubMed:7592877, ECO:0000269|PubMed:7690548, ECO:0000269|PubMed:9130696};
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 {ECO:0000303|PubMed:7690548, ECO:0000312|HGNC:HGNC:8568};
GN Synonyms=FUR {ECO:0000303|PubMed:2408021}, PACE, PCSK3;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Blood;
RX PubMed=2408021; DOI=10.1093/nar/18.3.664;
RA van den Ouweland A.M.W., van Duijnhoven H.L.P., Keizer G.D.,
RA Dorssers L.C.J., van de Ven W.J.M.;
RT "Structural homology between the human fur gene product and the subtilisin-
RT like protease encoded by yeast KEX2.";
RL Nucleic Acids Res. 18:664-664(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=2251280; DOI=10.1073/pnas.87.23.9378;
RA Wise R.J., Barr P.J., Wong P.A., Kiefer M.C., Brake A.J., Kaufman R.J.;
RT "Expression of a human proprotein processing enzyme: correct cleavage of
RT the von Willebrand factor precursor at a paired basic amino acid site.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:9378-9382(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, AND TISSUE
RP SPECIFICITY.
RX PubMed=1713771; DOI=10.1089/dna.1991.10.319;
RA Barr P.J., Mason O.B., Landsberg K.E., Wong P.A., Kiefer M.C., Brake A.J.;
RT "cDNA and gene structure for a human subtilisin-like protease with cleavage
RT specificity for paired basic amino acid residues.";
RL DNA Cell Biol. 10:319-328(1991).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-280.
RX PubMed=2674906; DOI=10.1093/nar/17.17.7101;
RA Van den Ouweland A.M.W., van Groningen J.J.M., Roebrock A.J.M.,
RA Onnekink C., Van de Ven W.J.M.;
RT "Nucleotide sequence analysis of the human fur gene.";
RL Nucleic Acids Res. 17:7101-7102(1989).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 296-794.
RX PubMed=3023061; DOI=10.1002/j.1460-2075.1986.tb04484.x;
RA Roebroek A.J.M., Schalken J.A., Leunissen J.A.M., Onnekink C.,
RA Bloemers H.P.J., van de Ven W.J.M.;
RT "Evolutionary conserved close linkage of the c-fes/fps proto-oncogene and
RT genetic sequences encoding a receptor-like protein.";
RL EMBO J. 5:2197-2202(1986).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 402-428, FUNCTION, AND CATALYTIC ACTIVITY.
RC TISSUE=Colon carcinoma;
RX PubMed=7690548; DOI=10.1006/bbrc.1993.2146;
RA Takahashi S., Kasai K., Hatsuzawa K., Kitamura N., Misumi Y., Ikehara Y.,
RA Murakami K., Nakayama K.;
RT "A mutation of furin causes the lack of precursor-processing activity in
RT human colon carcinoma LoVo cells.";
RL Biochem. Biophys. Res. Commun. 195:1019-1026(1993).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 527-553, FUNCTION, CATALYTIC ACTIVITY, AND
RP VARIANT ARG-547.
RC TISSUE=Colon carcinoma;
RX PubMed=7592877; DOI=10.1074/jbc.270.44.26565;
RA Takahashi S., Nakagawa T., Kasai K., Banno T., Duguay S.J.,
RA Van de Ven W.J.M., Murakami K., Nakayama K.;
RT "A second mutant allele of furin in the processing-incompetent cell line,
RT LoVo. Evidence for involvement of the homo B domain in autocatalytic
RT activation.";
RL J. Biol. Chem. 270:26565-26569(1995).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, AND PROTEOLYTIC PROCESSING.
RX PubMed=1629222; DOI=10.1016/s0021-9258(19)49712-3;
RA Leduc R., Molloy S.S., Thorne B.A., Thomas G.;
RT "Activation of human furin precursor processing endoprotease occurs by an
RT intramolecular autoproteolytic cleavage.";
RL J. Biol. Chem. 267:14304-14308(1992).
RN [10]
RP FUNCTION (MICROBIAL INFECTION), CATALYTIC ACTIVITY, AND COFACTOR.
RX PubMed=1644824; DOI=10.1016/s0021-9258(18)42016-9;
RA Molloy S.S., Bresnahan P.A., Leppla S.H., Klimpel K.R., Thomas G.;
RT "Human furin is a calcium-dependent serine endoprotease that recognizes the
RT sequence Arg-X-X-Arg and efficiently cleaves anthrax toxin protective
RT antigen.";
RL J. Biol. Chem. 267:16396-16402(1992).
RN [11]
RP FUNCTION (MICROBIAL INFECTION), AND CATALYTIC ACTIVITY.
RX PubMed=1438214; DOI=10.1073/pnas.89.21.10277;
RA Klimpel K.R., Molloy S.S., Thomas G., Leppla S.H.;
RT "Anthrax toxin protective antigen is activated by a cell surface protease
RT with the sequence specificity and catalytic properties of furin.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:10277-10281(1992).
RN [12]
RP FUNCTION (MICROBIAL INFECTION).
RX PubMed=8253774; DOI=10.1016/s0021-9258(19)74337-3;
RA Tsuneoka M., Nakayama K., Hatsuzawa K., Komada M., Kitamura N., Mekada E.;
RT "Evidence for involvement of furin in cleavage and activation of diphtheria
RT toxin.";
RL J. Biol. Chem. 268:26461-26465(1993).
RN [13]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=7737999; DOI=10.1074/jbc.270.18.10618;
RA Dubois C.M., Laprise M.H., Blanchette F., Gentry L.E., Leduc R.;
RT "Processing of transforming growth factor beta 1 precursor by human furin
RT convertase.";
RL J. Biol. Chem. 270:10618-10624(1995).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [15]
RP FUNCTION (MICROBIAL INFECTION), AND CATALYTIC ACTIVITY.
RX PubMed=31091448; DOI=10.1016/j.celrep.2019.04.063;
RA Braun E., Hotter D., Koepke L., Zech F., Gross R., Sparrer K.M.J.,
RA Mueller J.A., Pfaller C.K., Heusinger E., Wombacher R., Sutter K.,
RA Dittmer U., Winkler M., Simmons G., Jakobsen M.R., Conzelmann K.K.,
RA Poehlmann S., Muench J., Fackler O.T., Kirchhoff F., Sauter D.;
RT "Guanylate-binding proteins 2 and 5 exert broad antiviral activity by
RT inhibiting furin-mediated processing of viral envelope proteins.";
RL Cell Rep. 27:2092-2104(2019).
RN [16]
RP 3D-STRUCTURE MODELING OF CATALYTIC DOMAIN.
RX PubMed=8020465; DOI=10.1111/j.1432-1033.1994.tb18864.x;
RA Siezen R.J., Creemers J.W.M., van de Ven W.J.M.;
RT "Homology modelling of the catalytic domain of human furin. A model for the
RT eukaryotic subtilisin-like proprotein convertases.";
RL Eur. J. Biochem. 222:255-266(1994).
RN [17]
RP SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-773 AND SER-775, MOTIF, AND
RP MUTAGENESIS OF SER-773 AND SER-775.
RX PubMed=8846780; DOI=10.1002/j.1460-2075.1995.tb00275.x;
RA Jones B.G., Thomas L., Molloy S.S., Thulin C.D., Fry M.D., Walsh K.A.,
RA Thomas G.;
RT "Intracellular trafficking of furin is modulated by the phosphorylation
RT state of a casein kinase II site in its cytoplasmic tail.";
RL EMBO J. 14:5869-5883(1995).
RN [18]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY REGULATION,
RP BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION, PROTEOLYTIC CLEAVAGE,
RP IDENTIFICATION BY MASS SPECTROMETRY, AND MUTAGENESIS OF ASP-153.
RX PubMed=9130696; DOI=10.1093/emboj/16.7.1508;
RA Anderson E.D., VanSlyke J.K., Thulin C.D., Jean F., Thomas G.;
RT "Activation of the furin endoprotease is a multiple-step process:
RT requirements for acidification and internal propeptide cleavage.";
RL EMBO J. 16:1508-1518(1997).
RN [19]
RP SUBCELLULAR LOCATION.
RX PubMed=9412467; DOI=10.1083/jcb.139.7.1719;
RA Liu G., Thomas L., Warren R.A., Enns C.A., Cunningham C.C., Hartwig J.H.,
RA Thomas G.;
RT "Cytoskeletal protein ABP-280 directs the intracellular trafficking of
RT furin and modulates proprotein processing in the endocytic pathway.";
RL J. Cell Biol. 139:1719-1733(1997).
RN [20]
RP INTERACTION WITH PACS1, AND SUBCELLULAR LOCATION.
RX PubMed=11331585; DOI=10.1093/emboj/20.9.2191;
RA Crump C.M., Xiang Y., Thomas L., Gu F., Austin C., Tooze S.A., Thomas G.;
RT "PACS-1 binding to adaptors is required for acidic cluster motif-mediated
RT protein traffic.";
RL EMBO J. 20:2191-2201(2001).
RN [21]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, SUBCELLULAR LOCATION,
RP AND MUTAGENESIS OF VAL-72; ARG-75 AND ASP-153.
RX PubMed=11799113; DOI=10.1074/jbc.m108740200;
RA Anderson E.D., Molloy S.S., Jean F., Fei H., Shimamura S., Thomas G.;
RT "The ordered and compartment-specfific autoproteolytic removal of the furin
RT intramolecular chaperone is required for enzyme activation.";
RL J. Biol. Chem. 277:12879-12890(2002).
RN [22]
RP FUNCTION.
RX PubMed=20489134; DOI=10.1373/clinchem.2010.143883;
RA Semenov A.G., Tamm N.N., Seferian K.R., Postnikov A.B., Karpova N.S.,
RA Serebryanaya D.V., Koshkina E.V., Krasnoselsky M.I., Katrukha A.G.;
RT "Processing of pro-B-type natriuretic peptide: furin and corin as candidate
RT convertases.";
RL Clin. Chem. 56:1166-1176(2010).
RN [23]
RP FUNCTION.
RX PubMed=21763278; DOI=10.1016/j.bbrc.2011.06.192;
RA Peng J., Jiang J., Wang W., Qi X., Sun X.L., Wu Q.;
RT "Glycosylation and processing of pro-B-type natriuretic peptide in
RT cardiomyocytes.";
RL Biochem. Biophys. Res. Commun. 411:593-598(2011).
RN [24]
RP FUNCTION (MICROBIAL INFECTION).
RX PubMed=27582320; DOI=10.1038/srep32371;
RA Schulte T., Mikaelsson C., Beaussart A., Kikhney A., Deshmukh M.,
RA Wolniak S., Pathak A., Ebel C., Lofling J., Fogolari F.,
RA Henriques-Normark B., Dufrene Y.F., Svergun D., Nygren P.A., Achour A.;
RT "The BR domain of PsrP interacts with extracellular DNA to promote
RT bacterial aggregation; structural insights into pneumococcal biofilm
RT formation.";
RL Sci. Rep. 6:32371-32371(2016).
RN [25]
RP FUNCTION (MICROBIAL INFECTION), AND CATALYTIC ACTIVITY.
RX PubMed=32703818; DOI=10.26508/lsa.202000786;
RA Bestle D., Heindl M.R., Limburg H., Van Lam van T., Pilgram O., Moulton H.,
RA Stein D.A., Hardes K., Eickmann M., Dolnik O., Rohde C., Klenk H.D.,
RA Garten W., Steinmetzer T., Boettcher-Friebertshaeuser E.;
RT "TMPRSS2 and furin are both essential for proteolytic activation of SARS-
RT CoV-2 in human airway cells.";
RL Life. Sci Alliance 3:1-14(2020).
RN [26]
RP FUNCTION (MICROBIAL INFECTION), ACTIVITY REGULATION, AND CATALYTIC
RP ACTIVITY.
RX PubMed=32362314; DOI=10.1016/j.molcel.2020.04.022;
RA Hoffmann M., Kleine-Weber H., Poehlmann S.;
RT "A multibasic cleavage site in the Spike protein of SARS-CoV-2 is essential
RT for infection of human lung cells.";
RL Mol. Cell 78:779-784(2020).
RN [27]
RP FUNCTION (MICROBIAL INFECTION), AND INTERACTION WITH LAMP1; LAMP2 AND
RP LAMP3.
RX PubMed=32295904; DOI=10.1128/jvi.00050-20;
RA Ueo A., Kubota M., Shirogane Y., Ohno S., Hashiguchi T., Yanagi Y.;
RT "Lysosome-Associated Membrane Proteins Support the Furin-Mediated
RT Processing of the Mumps Virus Fusion Protein.";
RL J. Virol. 94:0-0(2020).
RN [28]
RP ACTIVITY REGULATION.
RX PubMed=34699015; DOI=10.1007/s10719-021-10018-8;
RA Zeng J., Meng Y., Chen S.Y., Zhao G., Wang L., Zhang E.X., Qiu H.;
RT "Structural characteristics of Heparan sulfate required for the binding
RT with the virus processing Enzyme Furin.";
RL Glycoconj. J. 0:0-0(2021).
RN [29] {ECO:0007744|PDB:4OMC, ECO:0007744|PDB:4OMD}
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 108-574 IN COMPLEX WITH CALCIUM
RP AND INHIBITOR, FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND
RP DISULFIDE BONDS.
RX PubMed=24666235; DOI=10.1021/cb500087x;
RA Dahms S.O., Hardes K., Becker G.L., Steinmetzer T., Brandstetter H.,
RA Than M.E.;
RT "X-ray structures of human furin in complex with competitive inhibitors.";
RL ACS Chem. Biol. 9:1113-1118(2014).
RN [30] {ECO:0007744|PDB:4RYD}
RP X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) OF 108-574 IN COMPLEX WITH CALCIUM
RP AND INHIBITOR, FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND
RP DISULFIDE BONDS.
RX PubMed=25974265; DOI=10.1002/cmdc.201500103;
RA Hardes K., Becker G.L., Lu Y., Dahms S.O., Kohler S., Beyer W., Sandvig K.,
RA Yamamoto H., Lindberg I., Walz L., von Messling V., Than M.E., Garten W.,
RA Steinmetzer T.;
RT "Novel Furin inhibitors with potent anti-infectious activity.";
RL ChemMedChem 10:1218-1231(2015).
RN [31]
RP VARIANTS VAL-43; SER-146; GLN-298 AND VAL-636.
RX PubMed=32867305; DOI=10.3390/genes11091010;
RA Latini A., Agolini E., Novelli A., Borgiani P., Giannini R., Gravina P.,
RA Smarrazzo A., Dauri M., Andreoni M., Rogliani P., Bernardini S.,
RA Helmer-Citterich M., Biancolella M., Novelli G.;
RT "COVID-19 and Genetic Variants of Protein Involved in the SARS-CoV-2 Entry
RT into the Host Cells.";
RL Genes (Basel) 11:0-0(2020).
CC -!- FUNCTION: Ubiquitous endoprotease within constitutive secretory
CC pathways capable of cleavage at the RX(K/R)R consensus motif
CC (PubMed:11799113, PubMed:1629222, PubMed:1713771, PubMed:2251280,
CC PubMed:24666235, PubMed:25974265, PubMed:7592877, PubMed:7690548,
CC PubMed:9130696). Mediates processing of TGFB1, an essential step in
CC TGF-beta-1 activation (PubMed:7737999). Converts through proteolytic
CC cleavage the non-functional Brain natriuretic factor prohormone into
CC its active hormone BNP(1-32) (PubMed:20489134, PubMed:21763278). By
CC mediating processing of accessory subunit ATP6AP1/Ac45 of the V-ATPase,
CC regulates the acidification of dense-core secretory granules in islets
CC of Langerhans cells (By similarity). {ECO:0000250|UniProtKB:P23188,
CC ECO:0000269|PubMed:11799113, ECO:0000269|PubMed:1629222,
CC ECO:0000269|PubMed:1713771, ECO:0000269|PubMed:20489134,
CC ECO:0000269|PubMed:21763278, ECO:0000269|PubMed:2251280,
CC ECO:0000269|PubMed:24666235, ECO:0000269|PubMed:25974265,
CC ECO:0000269|PubMed:7592877, ECO:0000269|PubMed:7690548,
CC ECO:0000269|PubMed:7737999, ECO:0000269|PubMed:9130696}.
CC -!- FUNCTION: (Microbial infection) Cleaves and activates diphtheria toxin
CC DT. {ECO:0000269|PubMed:8253774}.
CC -!- FUNCTION: (Microbial infection) Cleaves and activates anthrax toxin
CC protective antigen (PA). {ECO:0000269|PubMed:1438214,
CC ECO:0000269|PubMed:1644824}.
CC -!- FUNCTION: (Microbial infection) Cleaves and activates HIV-1 virus
CC Envelope glycoprotein gp160. {ECO:0000269|PubMed:31091448}.
CC -!- FUNCTION: (Microbial infection) Required for H7N1 and H5N1 influenza
CC virus infection probably by cleaving hemagglutinin.
CC {ECO:0000269|PubMed:25974265}.
CC -!- FUNCTION: (Microbial infection) Able to cleave S.pneumoniae serine-rich
CC repeat protein PsrP. {ECO:0000269|PubMed:27582320}.
CC -!- FUNCTION: (Microbial infection) Facilitates human coronaviruses EMC and
CC SARS-CoV-2 infections by proteolytically cleaving the spike protein at
CC the monobasic S1/S2 cleavage site. This cleavage is essential for spike
CC protein-mediated cell-cell fusion and entry into human lung cells.
CC {ECO:0000269|PubMed:32362314, ECO:0000269|PubMed:32703818}.
CC -!- FUNCTION: (Microbial infection) Facilitates mumps virus infection by
CC proteolytically cleaving the viral fusion protein F.
CC {ECO:0000269|PubMed:32295904}.
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:0000269|PubMed:11799113, ECO:0000269|PubMed:1438214,
CC ECO:0000269|PubMed:1629222, ECO:0000269|PubMed:1644824,
CC ECO:0000269|PubMed:1713771, ECO:0000269|PubMed:2251280,
CC ECO:0000269|PubMed:24666235, ECO:0000269|PubMed:25974265,
CC ECO:0000269|PubMed:31091448, ECO:0000269|PubMed:32362314,
CC ECO:0000269|PubMed:32703818, ECO:0000269|PubMed:7592877,
CC ECO:0000269|PubMed:7690548, ECO:0000269|PubMed:7737999,
CC ECO:0000269|PubMed:8253774, ECO:0000269|PubMed:9130696};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000269|PubMed:1644824, ECO:0000269|PubMed:24666235,
CC ECO:0000269|PubMed:25974265, ECO:0000269|PubMed:9130696};
CC Note=Binds 3 calcium ions per subunit. {ECO:0000269|PubMed:24666235,
CC ECO:0000269|PubMed:25974265, ECO:0000269|PubMed:9130696};
CC -!- ACTIVITY REGULATION: Inhibited by the not secondly cleaved propeptide
CC (PubMed:9130696, PubMed:11799113). Inhibited by m-guanidinomethyl-
CC phenylacetyl-Arg-Val-Arg-(amidomethyl)-benzamidine (m-guanidinomethyl-
CC Phac-RVR-Amb) and 4-guanidinomethyl-phenylacetyl-Arg-Tle-Arg-4-
CC amidinobenzylamide (MI-1148) (PubMed:24666235, PubMed:25974265).
CC Inhibited by Decanoyl-Arg-Val-Lys-Arg-chloromethylketone (decanoyl-
CC RVKR-CMK) (PubMed:32362314). Inhibited by heparin/heparan sulfate-
CC binding (PubMed:2408021). {ECO:0000269|PubMed:11799113,
CC ECO:0000269|PubMed:2408021, ECO:0000269|PubMed:24666235,
CC ECO:0000269|PubMed:25974265, ECO:0000269|PubMed:32362314,
CC ECO:0000269|PubMed:9130696}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 6.0. {ECO:0000269|PubMed:9130696};
CC -!- SUBUNIT: Interacts with FLNA (By similarity). Binds to PACS1 which
CC mediates TGN localization and connection to clathrin adapters
CC (PubMed:11331585). Interacts with LAMP1, LAMP2 and LAMP3
CC (PubMed:32295904). {ECO:0000250|UniProtKB:P23188,
CC ECO:0000269|PubMed:11331585, ECO:0000269|PubMed:32295904}.
CC -!- INTERACTION:
CC P09958; P05067: APP; NbExp=3; IntAct=EBI-1056807, EBI-77613;
CC P09958; P50281: MMP14; NbExp=3; IntAct=EBI-1056807, EBI-992788;
CC P09958; Q9H239: MMP28; NbExp=3; IntAct=EBI-1056807, EBI-20858485;
CC P09958; O14793: MSTN; NbExp=2; IntAct=EBI-1056807, EBI-8542977;
CC P09958; K9N5Q8: S; Xeno; NbExp=3; IntAct=EBI-1056807, EBI-25474996;
CC P09958; P0DTC2: S; Xeno; NbExp=5; IntAct=EBI-1056807, EBI-25474821;
CC P09958; Q91QT1: s; Xeno; NbExp=2; IntAct=EBI-1056807, EBI-25690542;
CC -!- SUBCELLULAR LOCATION: Golgi apparatus, trans-Golgi network membrane
CC {ECO:0000269|PubMed:11331585, ECO:0000269|PubMed:11799113,
CC ECO:0000269|PubMed:8846780, ECO:0000269|PubMed:9130696,
CC ECO:0000269|PubMed:9412467}; Single-pass type I membrane protein
CC {ECO:0000305}. Cell membrane {ECO:0000269|PubMed:11799113,
CC ECO:0000269|PubMed:9130696, ECO:0000269|PubMed:9412467}; Single-pass
CC type I membrane protein {ECO:0000305}. Secreted
CC {ECO:0000305|PubMed:11799113}. Endosome membrane
CC {ECO:0000269|PubMed:9412467}; Single-pass type I membrane protein
CC {ECO:0000305}. Note=Shuttles between the trans-Golgi network and the
CC cell surface (PubMed:9412467, PubMed:11799113). Propeptide cleavage is
CC a prerequisite for exit of furin molecules out of the endoplasmic
CC reticulum (ER). A second cleavage within the propeptide occurs in the
CC trans Golgi network (TGN), followed by the release of the propeptide
CC and the activation of furin (PubMed:11799113).
CC {ECO:0000269|PubMed:11799113, ECO:0000269|PubMed:9412467}.
CC -!- TISSUE SPECIFICITY: Seems to be expressed ubiquitously.
CC {ECO:0000269|PubMed:1713771}.
CC -!- DOMAIN: Contains a cytoplasmic domain responsible for its TGN
CC localization and recycling from the cell surface.
CC {ECO:0000269|PubMed:8846780}.
CC -!- PTM: The inhibition peptide, which plays the role of an intramolecular
CC chaperone, is autocatalytically removed in the endoplasmic reticulum
CC (ER) and remains non-covalently bound to furin as a potent
CC autoinhibitor. Following transport to the trans Golgi, a second
CC cleavage within the inhibition propeptide results in propeptide
CC dissociation and furin activation. {ECO:0000269|PubMed:1629222,
CC ECO:0000269|PubMed:9130696}.
CC -!- PTM: Phosphorylation is required for TGN localization of the
CC endoprotease. In vivo, exists as di-, mono- and non-phosphorylated
CC forms. {ECO:0000269|PubMed:8846780}.
CC -!- SIMILARITY: Belongs to the peptidase S8 family. Furin subfamily.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="https://atlasgeneticsoncology.org/gene/40646/FURIN";
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DR EMBL; X17094; CAA34948.1; -; mRNA.
DR EMBL; BC012181; AAH12181.1; -; mRNA.
DR EMBL; X15723; CAA33745.1; -; Genomic_DNA.
DR EMBL; X04329; CAA27860.1; -; Genomic_DNA.
DR CCDS; CCDS10364.1; -.
DR PIR; A39552; KXHUF.
DR RefSeq; NP_001276752.1; NM_001289823.1.
DR RefSeq; NP_001276753.1; NM_001289824.1.
DR RefSeq; NP_002560.1; NM_002569.3.
DR PDB; 4OMC; X-ray; 2.30 A; A/B/C/D/E/F=108-574.
DR PDB; 4OMD; X-ray; 2.70 A; A/B/C/D/E/F=108-574.
DR PDB; 4RYD; X-ray; 2.15 A; A/B/C/D/E/F=108-574.
DR PDB; 4Z2A; X-ray; 1.89 A; A=110-574.
DR PDB; 5JMO; X-ray; 2.00 A; A/B=108-574.
DR PDB; 5JXG; X-ray; 1.80 A; A=108-574.
DR PDB; 5JXH; X-ray; 2.00 A; A=108-574.
DR PDB; 5JXI; X-ray; 2.00 A; A=108-574.
DR PDB; 5JXJ; X-ray; 2.00 A; A=108-574.
DR PDB; 5MIM; X-ray; 1.90 A; A=108-574.
DR PDB; 6A8Y; NMR; -; A=64-89.
DR PDB; 6EQV; X-ray; 1.90 A; A=108-574.
DR PDB; 6EQW; X-ray; 1.99 A; A=108-574.
DR PDB; 6EQX; X-ray; 1.99 A; A=108-567.
DR PDB; 6HLB; X-ray; 2.00 A; A=108-574.
DR PDB; 6HLD; X-ray; 2.10 A; A=108-574.
DR PDB; 6HLE; X-ray; 1.99 A; A=108-574.
DR PDB; 6HZA; X-ray; 1.90 A; A=108-574.
DR PDB; 6HZB; X-ray; 1.90 A; A=108-574.
DR PDB; 6HZC; X-ray; 1.90 A; A=108-574.
DR PDB; 6HZD; X-ray; 1.90 A; A=108-574.
DR PDB; 6YD2; X-ray; 1.80 A; A=108-574.
DR PDB; 6YD3; X-ray; 2.00 A; A=108-574.
DR PDB; 6YD4; X-ray; 1.70 A; A=108-574.
DR PDB; 6YD7; X-ray; 1.80 A; A=108-574.
DR PDB; 7LCU; X-ray; 1.24 A; A=108-574.
DR PDB; 7O1U; X-ray; 1.70 A; A=108-574.
DR PDB; 7O1W; X-ray; 1.80 A; A=108-574.
DR PDB; 7O1Y; X-ray; 1.70 A; A=108-574.
DR PDB; 7O20; X-ray; 1.80 A; A=108-574.
DR PDB; 7O22; X-ray; 1.80 A; A=108-574.
DR PDB; 7QXY; X-ray; 1.48 A; A=108-574.
DR PDB; 7QXZ; X-ray; 1.80 A; A=108-574.
DR PDB; 7QY0; X-ray; 1.54 A; A=108-574.
DR PDB; 7QY1; X-ray; 1.45 A; A=108-574.
DR PDB; 7QY2; X-ray; 1.55 A; A=108-574.
DR PDB; 8B4V; X-ray; 1.60 A; A=108-574.
DR PDB; 8B4W; X-ray; 1.60 A; A=108-574.
DR PDB; 8B4X; X-ray; 1.60 A; A=108-574.
DR PDBsum; 4OMC; -.
DR PDBsum; 4OMD; -.
DR PDBsum; 4RYD; -.
DR PDBsum; 4Z2A; -.
DR PDBsum; 5JMO; -.
DR PDBsum; 5JXG; -.
DR PDBsum; 5JXH; -.
DR PDBsum; 5JXI; -.
DR PDBsum; 5JXJ; -.
DR PDBsum; 5MIM; -.
DR PDBsum; 6A8Y; -.
DR PDBsum; 6EQV; -.
DR PDBsum; 6EQW; -.
DR PDBsum; 6EQX; -.
DR PDBsum; 6HLB; -.
DR PDBsum; 6HLD; -.
DR PDBsum; 6HLE; -.
DR PDBsum; 6HZA; -.
DR PDBsum; 6HZB; -.
DR PDBsum; 6HZC; -.
DR PDBsum; 6HZD; -.
DR PDBsum; 6YD2; -.
DR PDBsum; 6YD3; -.
DR PDBsum; 6YD4; -.
DR PDBsum; 6YD7; -.
DR PDBsum; 7LCU; -.
DR PDBsum; 7O1U; -.
DR PDBsum; 7O1W; -.
DR PDBsum; 7O1Y; -.
DR PDBsum; 7O20; -.
DR PDBsum; 7O22; -.
DR PDBsum; 7QXY; -.
DR PDBsum; 7QXZ; -.
DR PDBsum; 7QY0; -.
DR PDBsum; 7QY1; -.
DR PDBsum; 7QY2; -.
DR PDBsum; 8B4V; -.
DR PDBsum; 8B4W; -.
DR PDBsum; 8B4X; -.
DR AlphaFoldDB; P09958; -.
DR SMR; P09958; -.
DR BioGRID; 111082; 250.
DR CORUM; P09958; -.
DR DIP; DIP-29904N; -.
DR ELM; P09958; -.
DR IntAct; P09958; 25.
DR MINT; P09958; -.
DR STRING; 9606.ENSP00000483552; -.
DR BindingDB; P09958; -.
DR ChEMBL; CHEMBL2611; -.
DR DrugBank; DB03600; Capric acid.
DR GuidetoPHARMACOLOGY; 2366; -.
DR MEROPS; S08.071; -.
DR TCDB; 1.A.9.1.24; the neurotransmitter receptor, cys loop, ligand-gated ion channel (lic) family.
DR TCDB; 9.B.355.2.1; the dentilisin (dentilisin) family.
DR GlyCosmos; P09958; 3 sites, No reported glycans.
DR GlyGen; P09958; 3 sites.
DR iPTMnet; P09958; -.
DR PhosphoSitePlus; P09958; -.
DR SwissPalm; P09958; -.
DR BioMuta; FURIN; -.
DR DMDM; 120611; -.
DR OGP; P09958; -.
DR EPD; P09958; -.
DR jPOST; P09958; -.
DR MassIVE; P09958; -.
DR MaxQB; P09958; -.
DR PaxDb; 9606-ENSP00000483552; -.
DR PeptideAtlas; P09958; -.
DR ProteomicsDB; 52283; -.
DR Pumba; P09958; -.
DR ABCD; P09958; 1 sequenced antibody.
DR Antibodypedia; 4013; 496 antibodies from 39 providers.
DR DNASU; 5045; -.
DR Ensembl; ENST00000268171.8; ENSP00000268171.2; ENSG00000140564.13.
DR Ensembl; ENST00000610579.4; ENSP00000484952.1; ENSG00000140564.13.
DR Ensembl; ENST00000618099.4; ENSP00000483552.1; ENSG00000140564.13.
DR Ensembl; ENST00000680053.1; ENSP00000506143.1; ENSG00000140564.13.
DR GeneID; 5045; -.
DR KEGG; hsa:5045; -.
DR MANE-Select; ENST00000268171.8; ENSP00000268171.2; NM_002569.4; NP_002560.1.
DR UCSC; uc002bpu.2; human.
DR AGR; HGNC:8568; -.
DR CTD; 5045; -.
DR DisGeNET; 5045; -.
DR GeneCards; FURIN; -.
DR HGNC; HGNC:8568; FURIN.
DR HPA; ENSG00000140564; Tissue enhanced (liver, salivary gland).
DR MIM; 136950; gene.
DR neXtProt; NX_P09958; -.
DR OpenTargets; ENSG00000140564; -.
DR PharmGKB; PA32894; -.
DR VEuPathDB; HostDB:ENSG00000140564; -.
DR eggNOG; KOG3525; Eukaryota.
DR GeneTree; ENSGT00940000157220; -.
DR HOGENOM; CLU_002976_4_0_1; -.
DR InParanoid; P09958; -.
DR OMA; FREWAFM; -.
DR OrthoDB; 5474719at2759; -.
DR PhylomeDB; P09958; -.
DR TreeFam; TF314277; -.
DR BRENDA; 3.4.21.75; 2681.
DR PathwayCommons; P09958; -.
DR Reactome; R-HSA-1181150; Signaling by NODAL.
DR Reactome; R-HSA-1442490; Collagen degradation.
DR Reactome; R-HSA-1566948; Elastic fibre formation.
DR Reactome; R-HSA-1592389; Activation of Matrix Metalloproteinases.
DR Reactome; R-HSA-159782; Removal of aminoterminal propeptides from gamma-carboxylated proteins.
DR Reactome; R-HSA-167060; NGF processing.
DR Reactome; R-HSA-171286; Synthesis and processing of ENV and VPU.
DR Reactome; R-HSA-186797; Signaling by PDGF.
DR Reactome; R-HSA-1912420; Pre-NOTCH Processing in Golgi.
DR Reactome; R-HSA-2173789; TGF-beta receptor signaling activates SMADs.
DR Reactome; R-HSA-2173796; SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription.
DR Reactome; R-HSA-5210891; Uptake and function of anthrax toxins.
DR Reactome; R-HSA-6809371; Formation of the cornified envelope.
DR Reactome; R-HSA-8963889; Assembly of active LPL and LIPC lipase complexes.
DR Reactome; R-HSA-9662834; CD163 mediating an anti-inflammatory response.
DR Reactome; R-HSA-9679191; Potential therapeutics for SARS.
DR Reactome; R-HSA-9694614; Attachment and Entry.
DR Reactome; R-HSA-9733458; Induction of Cell-Cell Fusion.
DR Reactome; R-HSA-977225; Amyloid fiber formation.
DR SignaLink; P09958; -.
DR SIGNOR; P09958; -.
DR BioGRID-ORCS; 5045; 166 hits in 1183 CRISPR screens.
DR ChiTaRS; FURIN; human.
DR GeneWiki; Furin; -.
DR GenomeRNAi; 5045; -.
DR Pharos; P09958; Tchem.
DR PRO; PR:P09958; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; P09958; Protein.
DR Bgee; ENSG00000140564; Expressed in right lobe of liver and 192 other cell types or tissues.
DR ExpressionAtlas; P09958; baseline and differential.
DR Genevisible; P09958; HS.
DR GO; GO:0009986; C:cell surface; IDA:BHF-UCL.
DR GO; GO:0005783; C:endoplasmic reticulum; IGI:BHF-UCL.
DR GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005796; C:Golgi lumen; TAS:Reactome.
DR GO; GO:0000139; C:Golgi membrane; IMP:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0045121; C:membrane raft; IDA:BHF-UCL.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0005802; C:trans-Golgi network; IDA:BHF-UCL.
DR GO; GO:0030140; C:trans-Golgi network transport vesicle; IDA:MGI.
DR GO; GO:0004175; F:endopeptidase activity; IDA:UniProtKB.
DR GO; GO:1904399; F:heparan sulfate binding; IDA:UniProtKB.
DR GO; GO:0008201; F:heparin binding; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0048406; F:nerve growth factor binding; IDA:BHF-UCL.
DR GO; GO:0008233; F:peptidase activity; IDA:UniProtKB.
DR GO; GO:0042277; F:peptide binding; IDA:BHF-UCL.
DR GO; GO:0002020; F:protease binding; IPI:BHF-UCL.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IDA:UniProtKB.
DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IDA:BHF-UCL.
DR GO; GO:0008236; F:serine-type peptidase activity; IDA:UniProt.
DR GO; GO:1990000; P:amyloid fibril formation; TAS:Reactome.
DR GO; GO:0001825; P:blastocyst formation; IEA:Ensembl.
DR GO; GO:0030574; P:collagen catabolic process; TAS:Reactome.
DR GO; GO:0140447; P:cytokine precursor processing; IDA:UniProtKB.
DR GO; GO:0090472; P:dibasic protein processing; IMP:UniProtKB.
DR GO; GO:0022617; P:extracellular matrix disassembly; TAS:Reactome.
DR GO; GO:0030198; P:extracellular matrix organization; TAS:Reactome.
DR GO; GO:0002862; P:negative regulation of inflammatory response to antigenic stimulus; TAS:Reactome.
DR GO; GO:0032804; P:negative regulation of low-density lipoprotein particle receptor catabolic process; IDA:HGNC-UCL.
DR GO; GO:0032911; P:negative regulation of transforming growth factor beta1 production; IMP:BHF-UCL.
DR GO; GO:0032902; P:nerve growth factor production; IDA:BHF-UCL.
DR GO; GO:0043043; P:peptide biosynthetic process; IDA:BHF-UCL.
DR GO; GO:0016486; P:peptide hormone processing; IDA:BHF-UCL.
DR GO; GO:0034369; P:plasma lipoprotein particle remodeling; TAS:Reactome.
DR GO; GO:0051044; P:positive regulation of membrane protein ectodomain proteolysis; IC:BHF-UCL.
DR GO; GO:0046598; P:positive regulation of viral entry into host cell; IDA:UniProtKB.
DR GO; GO:0051604; P:protein maturation; IDA:UniProt.
DR GO; GO:0016485; P:protein processing; IDA:UniProtKB.
DR GO; GO:0032374; P:regulation of cholesterol transport; IEA:Ensembl.
DR GO; GO:0052548; P:regulation of endopeptidase activity; IDA:BHF-UCL.
DR GO; GO:0042176; P:regulation of protein catabolic process; IMP:BHF-UCL.
DR GO; GO:0009966; P:regulation of signal transduction; IEA:Ensembl.
DR GO; GO:0032940; P:secretion by cell; IDA:BHF-UCL.
DR GO; GO:0006465; P:signal peptide processing; IDA:HGNC-UCL.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; TAS:Reactome.
DR GO; GO:0019058; P:viral life cycle; IEP:BHF-UCL.
DR GO; GO:0019082; P:viral protein processing; TAS:Reactome.
DR GO; GO:0019081; P:viral translation; TAS:UniProt.
DR GO; GO:0031638; P:zymogen activation; IMP:UniProtKB.
DR CDD; cd00064; FU; 2.
DR CDD; cd04059; Peptidases_S8_Protein_convertases_Kexins_Furin-like; 1.
DR Gene3D; 2.60.120.260; Galactose-binding domain-like; 1.
DR Gene3D; 3.30.70.850; Peptidase S8, pro-domain; 1.
DR Gene3D; 3.40.50.200; Peptidase S8/S53 domain; 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 PANTHER; PTHR42884:SF1; FURIN; 1.
DR PANTHER; PTHR42884; PROPROTEIN CONVERTASE SUBTILISIN/KEXIN-RELATED; 1.
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; Galactose-binding domain-like; 1.
DR SUPFAM; SSF57184; Growth factor receptor domain; 1.
DR SUPFAM; SSF54897; Protease propeptides/inhibitors; 1.
DR SUPFAM; SSF52743; Subtilisin-like; 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 1: Evidence at protein level;
KW 3D-structure; Autocatalytic cleavage; Calcium; Cell membrane;
KW Cleavage on pair of basic residues; Disulfide bond; Endosome; Glycoprotein;
KW Golgi apparatus; Heparin-binding; Host-virus interaction; Hydrolase;
KW Membrane; Metal-binding; Phosphoprotein; Protease; Reference proteome;
KW Repeat; Secreted; Serine protease; Signal; Transmembrane;
KW Transmembrane helix; Zymogen.
FT SIGNAL 1..26
FT /evidence="ECO:0000255"
FT PROPEP 27..107
FT /note="Inhibition peptide"
FT /evidence="ECO:0000269|PubMed:9130696"
FT /id="PRO_0000027028"
FT CHAIN 108..794
FT /note="Furin"
FT /id="PRO_0000027029"
FT TOPO_DOM 108..715
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 716..738
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 739..794
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT DOMAIN 121..435
FT /note="Peptidase S8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT DOMAIN 444..576
FT /note="P/Homo B"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01173"
FT REPEAT 577..620
FT /note="FU 1"
FT /evidence="ECO:0000255"
FT REPEAT 638..681
FT /note="FU 2"
FT /evidence="ECO:0000255"
FT REGION 162..183
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 673..696
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 759..762
FT /note="Cell surface signal"
FT /evidence="ECO:0000303|PubMed:9412467"
FT REGION 767..794
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 498..500
FT /note="Cell attachment site"
FT /evidence="ECO:0000255"
FT MOTIF 773..779
FT /note="Trans Golgi network signal"
FT /evidence="ECO:0000269|PubMed:8846780"
FT COMPBIAS 673..687
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 153
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT ACT_SITE 194
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT ACT_SITE 368
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT BINDING 115
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:24666235,
FT ECO:0000269|PubMed:25974265, ECO:0007744|PDB:4OMC,
FT ECO:0007744|PDB:4OMD, ECO:0007744|PDB:4RYD"
FT BINDING 154
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:24666235,
FT ECO:0000305|PubMed:25974265, ECO:0007744|PDB:4OMC,
FT ECO:0007744|PDB:4OMD, ECO:0007744|PDB:4RYD"
FT BINDING 162
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:24666235,
FT ECO:0000269|PubMed:25974265, ECO:0007744|PDB:4OMC,
FT ECO:0007744|PDB:4OMD, ECO:0007744|PDB:4RYD"
FT BINDING 174
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:24666235,
FT ECO:0000269|PubMed:25974265, ECO:0007744|PDB:4OMC,
FT ECO:0007744|PDB:4OMD, ECO:0007744|PDB:4RYD"
FT BINDING 179
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:24666235,
FT ECO:0000269|PubMed:25974265, ECO:0007744|PDB:4OMC,
FT ECO:0007744|PDB:4OMD, ECO:0007744|PDB:4RYD"
FT BINDING 181
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:24666235,
FT ECO:0000269|PubMed:25974265, ECO:0007744|PDB:4OMC,
FT ECO:0007744|PDB:4OMD, ECO:0007744|PDB:4RYD"
FT BINDING 191..192
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:24666235,
FT ECO:0000305|PubMed:25974265, ECO:0007744|PDB:4OMC,
FT ECO:0007744|PDB:4OMD, ECO:0007744|PDB:4RYD"
FT BINDING 205
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:24666235,
FT ECO:0000269|PubMed:25974265, ECO:0007744|PDB:4OMC,
FT ECO:0007744|PDB:4OMD, ECO:0007744|PDB:4RYD"
FT BINDING 208
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:24666235,
FT ECO:0000269|PubMed:25974265, ECO:0007744|PDB:4OMC,
FT ECO:0007744|PDB:4OMD, ECO:0007744|PDB:4RYD"
FT BINDING 210
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:24666235,
FT ECO:0000269|PubMed:25974265, ECO:0007744|PDB:4OMC,
FT ECO:0007744|PDB:4OMD, ECO:0007744|PDB:4RYD"
FT BINDING 212
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:24666235,
FT ECO:0000269|PubMed:25974265, ECO:0007744|PDB:4OMC,
FT ECO:0007744|PDB:4OMD, ECO:0007744|PDB:4RYD"
FT BINDING 236
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:24666235,
FT ECO:0000305|PubMed:25974265, ECO:0007744|PDB:4OMC,
FT ECO:0007744|PDB:4OMD, ECO:0007744|PDB:4RYD"
FT BINDING 253..258
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:24666235,
FT ECO:0000305|PubMed:25974265, ECO:0007744|PDB:4OMC,
FT ECO:0007744|PDB:4OMD, ECO:0007744|PDB:4RYD"
FT BINDING 258
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000269|PubMed:24666235,
FT ECO:0000269|PubMed:25974265, ECO:0007744|PDB:4OMC,
FT ECO:0007744|PDB:4OMD, ECO:0007744|PDB:4RYD"
FT BINDING 264
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:24666235,
FT ECO:0000305|PubMed:25974265, ECO:0007744|PDB:4OMC,
FT ECO:0007744|PDB:4OMD, ECO:0007744|PDB:4RYD"
FT BINDING 292..295
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:24666235,
FT ECO:0000305|PubMed:25974265, ECO:0007744|PDB:4OMC,
FT ECO:0007744|PDB:4OMD, ECO:0007744|PDB:4RYD"
FT BINDING 301
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000269|PubMed:24666235,
FT ECO:0000269|PubMed:25974265, ECO:0007744|PDB:4OMC,
FT ECO:0007744|PDB:4OMD, ECO:0007744|PDB:4RYD"
FT BINDING 306
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:24666235,
FT ECO:0000305|PubMed:25974265, ECO:0007744|PDB:4OMC,
FT ECO:0007744|PDB:4OMD, ECO:0007744|PDB:4RYD"
FT BINDING 308
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:24666235,
FT ECO:0000305|PubMed:25974265, ECO:0007744|PDB:4OMC,
FT ECO:0007744|PDB:4OMD, ECO:0007744|PDB:4RYD"
FT BINDING 331
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000269|PubMed:24666235,
FT ECO:0000269|PubMed:25974265, ECO:0007744|PDB:4OMC,
FT ECO:0007744|PDB:4OMD, ECO:0007744|PDB:4RYD"
FT BINDING 368
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:24666235,
FT ECO:0000305|PubMed:25974265, ECO:0007744|PDB:4OMC,
FT ECO:0007744|PDB:4OMD, ECO:0007744|PDB:4RYD"
FT SITE 75..76
FT /note="Cleavage, second; by autolysis"
FT /evidence="ECO:0000269|PubMed:9130696"
FT SITE 107..108
FT /note="Cleavage, first; by autolysis"
FT /evidence="ECO:0000269|PubMed:1629222,
FT ECO:0000269|PubMed:9130696"
FT MOD_RES 773
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000269|PubMed:8846780"
FT MOD_RES 775
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000269|PubMed:8846780"
FT CARBOHYD 387
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 440
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 553
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 211..360
FT /evidence="ECO:0000269|PubMed:24666235,
FT ECO:0000269|PubMed:25974265"
FT DISULFID 303..333
FT /evidence="ECO:0000269|PubMed:24666235,
FT ECO:0000269|PubMed:25974265"
FT DISULFID 450..474
FT /evidence="ECO:0000269|PubMed:24666235,
FT ECO:0000269|PubMed:25974265"
FT VARIANT 43
FT /note="A -> V (in dbSNP:rs16944971)"
FT /evidence="ECO:0000269|PubMed:32867305"
FT /id="VAR_051821"
FT VARIANT 146
FT /note="G -> S"
FT /evidence="ECO:0000269|PubMed:32867305"
FT /id="VAR_084542"
FT VARIANT 298
FT /note="R -> Q"
FT /evidence="ECO:0000269|PubMed:32867305"
FT /id="VAR_084543"
FT VARIANT 547
FT /note="W -> R (in cell line LoVo; does not undergo
FT autocatalytic activation and is not transported to the
FT Golgi apparatus)"
FT /evidence="ECO:0000269|PubMed:7592877"
FT /id="VAR_055343"
FT VARIANT 636
FT /note="I -> V"
FT /evidence="ECO:0000269|PubMed:32867305"
FT /id="VAR_084544"
FT MUTAGEN 72
FT /note="V->R: Loss of catalytic activity and propeptide
FT second cleavage and removal. Abnormal accumulation in the
FT early secretory pathway."
FT /evidence="ECO:0000269|PubMed:11799113"
FT MUTAGEN 75
FT /note="R->A: Loss of catalytic activity and, propeptide
FT second cleavage and removal. Normal trafficking to the
FT Golgi."
FT /evidence="ECO:0000269|PubMed:11799113"
FT MUTAGEN 153
FT /note="D->N: Loss of catalytic activity and propeptide
FT first cleavage. Abnormal accumulation in the early
FT secretory pathway."
FT /evidence="ECO:0000269|PubMed:11799113,
FT ECO:0000269|PubMed:9130696"
FT MUTAGEN 773..775
FT /note="SDS->DDD: Phosphomimetic mutant. Localization in
FT early endosome is increased."
FT /evidence="ECO:0000269|PubMed:8846780"
FT MUTAGEN 773
FT /note="S->A: Slight reduction in phosphorylation. Loss of
FT phosphorylation and abnormal accumulation in the early
FT secretory pathway; when associated with A-775."
FT /evidence="ECO:0000269|PubMed:8846780"
FT MUTAGEN 775
FT /note="S->A: Slight reduction in phosphorylation. Loss of
FT phosphorylation and abnormal accumulation in the early
FT secretory pathway; when associated with A-773."
FT /evidence="ECO:0000269|PubMed:8846780"
FT HELIX 66..68
FT /evidence="ECO:0007829|PDB:6A8Y"
FT HELIX 73..77
FT /evidence="ECO:0007829|PDB:6A8Y"
FT STRAND 78..80
FT /evidence="ECO:0007829|PDB:6A8Y"
FT TURN 82..84
FT /evidence="ECO:0007829|PDB:6A8Y"
FT HELIX 85..88
FT /evidence="ECO:0007829|PDB:6A8Y"
FT HELIX 118..120
FT /evidence="ECO:0007829|PDB:7LCU"
FT HELIX 122..125
FT /evidence="ECO:0007829|PDB:7LCU"
FT STRAND 127..129
FT /evidence="ECO:0007829|PDB:7LCU"
FT HELIX 134..139
FT /evidence="ECO:0007829|PDB:7LCU"
FT STRAND 148..154
FT /evidence="ECO:0007829|PDB:7LCU"
FT TURN 161..163
FT /evidence="ECO:0007829|PDB:7LCU"
FT HELIX 164..166
FT /evidence="ECO:0007829|PDB:7LCU"
FT HELIX 169..171
FT /evidence="ECO:0007829|PDB:7LCU"
FT TURN 175..178
FT /evidence="ECO:0007829|PDB:7LCU"
FT HELIX 191..193
FT /evidence="ECO:0007829|PDB:6YD4"
FT HELIX 194..203
FT /evidence="ECO:0007829|PDB:7LCU"
FT STRAND 206..211
FT /evidence="ECO:0007829|PDB:7LCU"
FT TURN 215..218
FT /evidence="ECO:0007829|PDB:7LCU"
FT STRAND 219..225
FT /evidence="ECO:0007829|PDB:7LCU"
FT STRAND 227..229
FT /evidence="ECO:0007829|PDB:7LCU"
FT HELIX 233..240
FT /evidence="ECO:0007829|PDB:7LCU"
FT TURN 244..246
FT /evidence="ECO:0007829|PDB:7LCU"
FT STRAND 249..252
FT /evidence="ECO:0007829|PDB:7LCU"
FT STRAND 259..261
FT /evidence="ECO:0007829|PDB:7LCU"
FT HELIX 268..280
FT /evidence="ECO:0007829|PDB:7LCU"
FT HELIX 282..284
FT /evidence="ECO:0007829|PDB:7LCU"
FT STRAND 288..292
FT /evidence="ECO:0007829|PDB:7LCU"
FT HELIX 297..299
FT /evidence="ECO:0007829|PDB:7LCU"
FT HELIX 303..305
FT /evidence="ECO:0007829|PDB:7LCU"
FT TURN 307..310
FT /evidence="ECO:0007829|PDB:7LCU"
FT STRAND 314..320
FT /evidence="ECO:0007829|PDB:7LCU"
FT STRAND 338..341
FT /evidence="ECO:0007829|PDB:7LCU"
FT STRAND 351..355
FT /evidence="ECO:0007829|PDB:7LCU"
FT TURN 356..358
FT /evidence="ECO:0007829|PDB:7LCU"
FT STRAND 359..364
FT /evidence="ECO:0007829|PDB:7LCU"
FT HELIX 367..369
FT /evidence="ECO:0007829|PDB:7LCU"
FT HELIX 370..384
FT /evidence="ECO:0007829|PDB:7LCU"
FT HELIX 390..400
FT /evidence="ECO:0007829|PDB:7LCU"
FT STRAND 419..421
FT /evidence="ECO:0007829|PDB:7LCU"
FT TURN 422..424
FT /evidence="ECO:0007829|PDB:7LCU"
FT HELIX 431..438
FT /evidence="ECO:0007829|PDB:7LCU"
FT STRAND 448..453
FT /evidence="ECO:0007829|PDB:7LCU"
FT STRAND 464..471
FT /evidence="ECO:0007829|PDB:7LCU"
FT TURN 473..476
FT /evidence="ECO:0007829|PDB:7LCU"
FT STRAND 482..496
FT /evidence="ECO:0007829|PDB:7LCU"
FT HELIX 498..500
FT /evidence="ECO:0007829|PDB:7LCU"
FT STRAND 501..506
FT /evidence="ECO:0007829|PDB:7LCU"
FT STRAND 512..516
FT /evidence="ECO:0007829|PDB:7LCU"
FT STRAND 528..535
FT /evidence="ECO:0007829|PDB:7LCU"
FT TURN 537..540
FT /evidence="ECO:0007829|PDB:7LCU"
FT STRAND 545..553
FT /evidence="ECO:0007829|PDB:7LCU"
FT STRAND 555..557
FT /evidence="ECO:0007829|PDB:7LCU"
FT STRAND 561..573
FT /evidence="ECO:0007829|PDB:7LCU"
SQ SEQUENCE 794 AA; 86678 MW; 10C44DD5892EF85D CRC64;
MELRPWLLWV VAATGTLVLL AADAQGQKVF TNTWAVRIPG GPAVANSVAR KHGFLNLGQI
FGDYYHFWHR GVTKRSLSPH RPRHSRLQRE PQVQWLEQQV AKRRTKRDVY QEPTDPKFPQ
QWYLSGVTQR DLNVKAAWAQ GYTGHGIVVS ILDDGIEKNH PDLAGNYDPG ASFDVNDQDP
DPQPRYTQMN DNRHGTRCAG EVAAVANNGV CGVGVAYNAR IGGVRMLDGE VTDAVEARSL
GLNPNHIHIY SASWGPEDDG KTVDGPARLA EEAFFRGVSQ GRGGLGSIFV WASGNGGREH
DSCNCDGYTN SIYTLSISSA TQFGNVPWYS EACSSTLATT YSSGNQNEKQ IVTTDLRQKC
TESHTGTSAS APLAAGIIAL TLEANKNLTW RDMQHLVVQT SKPAHLNAND WATNGVGRKV
SHSYGYGLLD AGAMVALAQN WTTVAPQRKC IIDILTEPKD IGKRLEVRKT VTACLGEPNH
ITRLEHAQAR LTLSYNRRGD LAIHLVSPMG TRSTLLAARP HDYSADGFND WAFMTTHSWD
EDPSGEWVLE IENTSEANNY GTLTKFTLVL YGTAPEGLPV PPESSGCKTL TSSQACVVCE
EGFSLHQKSC VQHCPPGFAP QVLDTHYSTE NDVETIRASV CAPCHASCAT CQGPALTDCL
SCPSHASLDP VEQTCSRQSQ SSRESPPQQQ PPRLPPEVEA GQRLRAGLLP SHLPEVVAGL
SCAFIVLVFV TVFLVLQLRS GFSFRGVKVY TMDRGLISYK GLPPEAWQEE CPSDSEEDEG
RGERTAFIKD QSAL
//