LOCUS       NM_002569               4247 bp    mRNA    linear   PRI 09-FEB-2025
DEFINITION  Homo sapiens furin, paired basic amino acid cleaving enzyme
            (FURIN), transcript variant 1, mRNA.
ACCESSION   NM_002569
VERSION     NM_002569.4
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 1 to 4247)
  AUTHORS   Kubo,Y., Hans,M.B., Nakamura,T. and Hayashi,H.
  TITLE     The Furin Protease Dependence and Antiviral GBP2 Sensitivity of
            Murine Leukemia Virus Infection Are Determined by the Amino Acid
            Sequence at the Envelope Glycoprotein Cleavage Site
  JOURNAL   Int J Mol Sci 25 (18), 9987 (2024)
   PUBMED   39337476
  REMARK    GeneRIF: The Furin Protease Dependence and Antiviral GBP2
            Sensitivity of Murine Leukemia Virus Infection Are Determined by
            the Amino Acid Sequence at the Envelope Glycoprotein Cleavage Site.
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 4247)
  AUTHORS   Su,W., Ahmad,I., Wu,Y., Tang,L., Khan,I., Ye,B., Liang,J., Li,S.
            and Zheng,Y.H.
  TITLE     Furin Egress from the TGN is Regulated by Membrane-Associated
            RING-CH Finger (MARCHF) Proteins and Ubiquitin-Specific Protease 32
            (USP32) via Nondegradable K33-Polyubiquitination
  JOURNAL   Adv Sci (Weinh) 11 (35), e2403732 (2024)
   PUBMED   39031635
  REMARK    GeneRIF: Furin Egress from the TGN is Regulated by
            Membrane-Associated RING-CH Finger (MARCHF) Proteins and
            Ubiquitin-Specific Protease 32 (USP32) via Nondegradable
            K33-Polyubiquitination.
REFERENCE   3  (bases 1 to 4247)
  AUTHORS   Pandey,R.K., Srivastava,A., Mishra,R.K., Singh,P.P. and Chaubey,G.
  TITLE     Novel genetic association of the Furin gene polymorphism rs1981458
            with COVID-19 severity among Indian populations
  JOURNAL   Sci Rep 14 (1), 7822 (2024)
   PUBMED   38570613
  REMARK    GeneRIF: Novel genetic association of the Furin gene polymorphism
            rs1981458 with COVID-19 severity among Indian populations.
            Erratum:[Sci Rep. 2024 Apr 25;14(1):9523. doi:
            10.1038/s41598-024-60182-8.. PMID: 38664564]
            Publication Status: Online-Only
REFERENCE   4  (bases 1 to 4247)
  AUTHORS   Grinstein-Koren,O., Lusthaus,M., Tabibian-Keissar,H., Kaplan,I.,
            Buchner,A., Ilatov,R., Vered,M. and Zlotogorski-Hurvitz,A.
  TITLE     Pathological changes in oral epithelium and the expression of
            SARS-CoV-2 entry receptors, ACE2 and furin
  JOURNAL   PLoS One 19 (3), e0300269 (2024)
   PUBMED   38489333
  REMARK    GeneRIF: Pathological changes in oral epithelium and the expression
            of SARS-CoV-2 entry receptors, ACE2 and furin.
            Publication Status: Online-Only
REFERENCE   5  (bases 1 to 4247)
  AUTHORS   Shang,J., Wan,Y., Luo,C., Ye,G., Geng,Q., Auerbach,A. and Li,F.
  TITLE     Cell entry mechanisms of SARS-CoV-2
  JOURNAL   Proc Natl Acad Sci U S A 117 (21), 11727-11734 (2020)
   PUBMED   32376634
REFERENCE   6  (bases 1 to 4247)
  AUTHORS   Hoffmann,M., Kleine-Weber,H. and Pohlmann,S.
  TITLE     A Multibasic Cleavage Site in the Spike Protein of SARS-CoV-2 Is
            Essential for Infection of Human Lung Cells
  JOURNAL   Mol Cell 78 (4), 779-784 (2020)
   PUBMED   32362314
REFERENCE   7  (bases 1 to 4247)
  AUTHORS   Klimpel,K.R., Molloy,S.S., Thomas,G. and Leppla,S.H.
  TITLE     Anthrax toxin protective antigen is activated by a cell surface
            protease with the sequence specificity and catalytic properties of
            furin
  JOURNAL   Proc Natl Acad Sci U S A 89 (21), 10277-10281 (1992)
   PUBMED   1438214
REFERENCE   8  (bases 1 to 4247)
  AUTHORS   Molloy,S.S., Bresnahan,P.A., Leppla,S.H., Klimpel,K.R. and
            Thomas,G.
  TITLE     Human furin is a calcium-dependent serine endoprotease that
            recognizes the sequence Arg-X-X-Arg and efficiently cleaves anthrax
            toxin protective antigen
  JOURNAL   J Biol Chem 267 (23), 16396-16402 (1992)
   PUBMED   1644824
REFERENCE   9  (bases 1 to 4247)
  AUTHORS   Leduc,R., Molloy,S.S., Thorne,B.A. and Thomas,G.
  TITLE     Activation of human furin precursor processing endoprotease occurs
            by an intramolecular autoproteolytic cleavage
  JOURNAL   J Biol Chem 267 (20), 14304-14308 (1992)
   PUBMED   1629222
REFERENCE   10 (bases 1 to 4247)
  AUTHORS   Rehemtulla,A. and Kaufman,R.J.
  TITLE     Preferred sequence requirements for cleavage of pro-von Willebrand
            factor by propeptide-processing enzymes
  JOURNAL   Blood 79 (9), 2349-2355 (1992)
   PUBMED   1571548
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC124248.6, BP283962.1,
            X17094.1, BC012181.1 and BM043834.1.
            
            On Nov 22, 2018 this sequence version replaced NM_002569.3.
            
            Summary: This gene encodes a member of the subtilisin-like
            proprotein convertase family, which includes proteases that process
            protein and peptide precursors trafficking through regulated or
            constitutive branches of the secretory pathway. It encodes a type 1
            membrane bound protease that is expressed in many tissues,
            including neuroendocrine, liver, gut, and brain. The encoded
            protein undergoes an initial autocatalytic processing event in the
            ER and then sorts to the trans-Golgi network through endosomes
            where a second autocatalytic event takes place and the catalytic
            activity is acquired. Like other members of this convertase family,
            the product of this gene specifically cleaves substrates at single
            or paired basic residues. Some of its substrates include
            proparathyroid hormone, transforming growth factor beta 1
            precursor, proalbumin, pro-beta-secretase, membrane type-1 matrix
            metalloproteinase, beta subunit of pro-nerve growth factor and von
            Willebrand factor. It is thought to be one of the proteases
            responsible for the activation of HIV envelope glycoproteins gp160
            and gp140, and may play a role in tumor progression. Unlike
            SARS-CoV and other coronaviruses, the spike protein of SARS-CoV-2
            is thought to be uniquely cleaved by this protease. Alternative
            splicing results in multiple transcript variants. [provided by
            RefSeq, Aug 2020].
            
            Transcript Variant: This variant (1) represents the predominant
            transcript. Variants 1, 2, and 3 encode the same protein.
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: X17094.1, SRR11853565.10208.1
                                           [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1968540, SAMEA1968832
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            coronavirus related    :: involved in SARS-CoV-2 infection
            MANE Ensembl match     :: ENST00000268171.8/ ENSP00000268171.2
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-4                 AC124248.6         111068-111071
            5-67                BP283962.1         2-64
            68-230              X17094.1           1-163
            231-586             BP283962.1         228-583
            587-2133            BC012181.1         353-1899
            2134-2535           BM043834.1         268-669
            2536-4247           BC012181.1         2302-4013
FEATURES             Location/Qualifiers
     source          1..4247
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="15"
                     /map="15q26.1"
     gene            1..4247
                     /gene="FURIN"
                     /gene_synonym="FUR; PACE; PCSK3; SPC1"
                     /note="furin, paired basic amino acid cleaving enzyme"
                     /db_xref="GeneID:5045"
                     /db_xref="HGNC:HGNC:8568"
                     /db_xref="MIM:136950"
     exon            1..124
                     /gene="FURIN"
                     /gene_synonym="FUR; PACE; PCSK3; SPC1"
                     /inference="alignment:Splign:2.1.0"
     exon            125..460
                     /gene="FURIN"
                     /gene_synonym="FUR; PACE; PCSK3; SPC1"
                     /inference="alignment:Splign:2.1.0"
     CDS             284..2668
                     /gene="FURIN"
                     /gene_synonym="FUR; PACE; PCSK3; SPC1"
                     /EC_number="3.4.21.75"
                     /note="isoform 1 preproprotein is encoded by transcript
                     variant 1; proprotein convertase subtilisin/kexin type 3;
                     dibasic processing enzyme; furin, membrane associated
                     receptor protein; FES upstream region; paired basic amino
                     acid residue-cleaving enzyme; proprotein convertase
                     subtilisin/kexin 3; subtilisin-like proprotein convertase
                     1"
                     /codon_start=1
                     /product="furin isoform 1 preproprotein"
                     /protein_id="NP_002560.1"
                     /db_xref="CCDS:CCDS10364.1"
                     /db_xref="GeneID:5045"
                     /db_xref="HGNC:HGNC:8568"
                     /db_xref="MIM:136950"
                     /translation="MELRPWLLWVVAATGTLVLLAADAQGQKVFTNTWAVRIPGGPAV
                     ANSVARKHGFLNLGQIFGDYYHFWHRGVTKRSLSPHRPRHSRLQREPQVQWLEQQVAK
                     RRTKRDVYQEPTDPKFPQQWYLSGVTQRDLNVKAAWAQGYTGHGIVVSILDDGIEKNH
                     PDLAGNYDPGASFDVNDQDPDPQPRYTQMNDNRHGTRCAGEVAAVANNGVCGVGVAYN
                     ARIGGVRMLDGEVTDAVEARSLGLNPNHIHIYSASWGPEDDGKTVDGPARLAEEAFFR
                     GVSQGRGGLGSIFVWASGNGGREHDSCNCDGYTNSIYTLSISSATQFGNVPWYSEACS
                     STLATTYSSGNQNEKQIVTTDLRQKCTESHTGTSASAPLAAGIIALTLEANKNLTWRD
                     MQHLVVQTSKPAHLNANDWATNGVGRKVSHSYGYGLLDAGAMVALAQNWTTVAPQRKC
                     IIDILTEPKDIGKRLEVRKTVTACLGEPNHITRLEHAQARLTLSYNRRGDLAIHLVSP
                     MGTRSTLLAARPHDYSADGFNDWAFMTTHSWDEDPSGEWVLEIENTSEANNYGTLTKF
                     TLVLYGTAPEGLPVPPESSGCKTLTSSQACVVCEEGFSLHQKSCVQHCPPGFAPQVLD
                     THYSTENDVETIRASVCAPCHASCATCQGPALTDCLSCPSHASLDPVEQTCSRQSQSS
                     RESPPQQQPPRLPPEVEAGQRLRAGLLPSHLPEVVAGLSCAFIVLVFVTVFLVLQLRS
                     GFSFRGVKVYTMDRGLISYKGLPPEAWQEECPSDSEEDEGRGERTAFIKDQSAL"
     exon            461..559
                     /gene="FURIN"
                     /gene_synonym="FUR; PACE; PCSK3; SPC1"
                     /inference="alignment:Splign:2.1.0"
     exon            560..655
                     /gene="FURIN"
                     /gene_synonym="FUR; PACE; PCSK3; SPC1"
                     /inference="alignment:Splign:2.1.0"
     exon            656..784
                     /gene="FURIN"
                     /gene_synonym="FUR; PACE; PCSK3; SPC1"
                     /inference="alignment:Splign:2.1.0"
     exon            785..861
                     /gene="FURIN"
                     /gene_synonym="FUR; PACE; PCSK3; SPC1"
                     /inference="alignment:Splign:2.1.0"
     exon            862..950
                     /gene="FURIN"
                     /gene_synonym="FUR; PACE; PCSK3; SPC1"
                     /inference="alignment:Splign:2.1.0"
     exon            951..1123
                     /gene="FURIN"
                     /gene_synonym="FUR; PACE; PCSK3; SPC1"
                     /inference="alignment:Splign:2.1.0"
     exon            1124..1336
                     /gene="FURIN"
                     /gene_synonym="FUR; PACE; PCSK3; SPC1"
                     /inference="alignment:Splign:2.1.0"
     exon            1337..1437
                     /gene="FURIN"
                     /gene_synonym="FUR; PACE; PCSK3; SPC1"
                     /inference="alignment:Splign:2.1.0"
     exon            1438..1541
                     /gene="FURIN"
                     /gene_synonym="FUR; PACE; PCSK3; SPC1"
                     /inference="alignment:Splign:2.1.0"
     exon            1542..1659
                     /gene="FURIN"
                     /gene_synonym="FUR; PACE; PCSK3; SPC1"
                     /inference="alignment:Splign:2.1.0"
     exon            1660..1839
                     /gene="FURIN"
                     /gene_synonym="FUR; PACE; PCSK3; SPC1"
                     /inference="alignment:Splign:2.1.0"
     exon            1840..1964
                     /gene="FURIN"
                     /gene_synonym="FUR; PACE; PCSK3; SPC1"
                     /inference="alignment:Splign:2.1.0"
     exon            1965..2075
                     /gene="FURIN"
                     /gene_synonym="FUR; PACE; PCSK3; SPC1"
                     /inference="alignment:Splign:2.1.0"
     exon            2076..4247
                     /gene="FURIN"
                     /gene_synonym="FUR; PACE; PCSK3; SPC1"
                     /inference="alignment:Splign:2.1.0"
     regulatory      4221..4226
                     /regulatory_class="polyA_signal_sequence"
                     /gene="FURIN"
                     /gene_synonym="FUR; PACE; PCSK3; SPC1"
                     /note="hexamer: ATTAAA"
     polyA_site      4247
                     /gene="FURIN"
                     /gene_synonym="FUR; PACE; PCSK3; SPC1"
                     /note="major polyA site"
ORIGIN      
        1 agccagaact ggaagggccc cgccctgtga agggatagga gcctgactgt tgcagctgca
       61 gtgagtggcg gggaagcagc agcggccagg atgaatccca ggtgctctgg agctggatgg
      121 tgaaggtcgg cactcttcac cctcccgagc cctgcccgtc tcggccccat gcccccacca
      181 gtcagccccg ggccacaggc agtgagcagg cacctgggag ccgaggccct gtgaccaggc
      241 caaggagacg ggcgctccag ggtcccagcc acctgtcccc cccatggagc tgaggccctg
      301 gttgctatgg gtggtagcag caacaggaac cttggtcctg ctagcagctg atgctcaggg
      361 ccagaaggtc ttcaccaaca cgtgggctgt gcgcatccct ggaggcccag cggtggccaa
      421 cagtgtggca cggaagcatg ggttcctcaa cctgggccag atcttcgggg actattacca
      481 cttctggcat cgaggagtga cgaagcggtc cctgtcgcct caccgcccgc ggcacagccg
      541 gctgcagagg gagcctcaag tacagtggct ggaacagcag gtggcaaagc gacggactaa
      601 acgggacgtg taccaggagc ccacagaccc caagtttcct cagcagtggt acctgtctgg
      661 tgtcactcag cgggacctga atgtgaaggc ggcctgggcg cagggctaca cagggcacgg
      721 cattgtggtc tccattctgg acgatggcat cgagaagaac cacccggact tggcaggcaa
      781 ttatgatcct ggggccagtt ttgatgtcaa tgaccaggac cctgaccccc agcctcggta
      841 cacacagatg aatgacaaca ggcacggcac acggtgtgcg ggggaagtgg ctgcggtggc
      901 caacaacggt gtctgtggtg taggtgtggc ctacaacgcc cgcattggag gggtgcgcat
      961 gctggatggc gaggtgacag atgcagtgga ggcacgctcg ctgggcctga accccaacca
     1021 catccacatc tacagtgcca gctggggccc cgaggatgac ggcaagacag tggatgggcc
     1081 agcccgcctc gccgaggagg ccttcttccg tggggttagc cagggccgag gggggctggg
     1141 ctccatcttt gtctgggcct cggggaacgg gggccgggaa catgacagct gcaactgcga
     1201 cggctacacc aacagtatct acacgctgtc catcagcagc gccacgcagt ttggcaacgt
     1261 gccgtggtac agcgaggcct gctcgtccac actggccacg acctacagca gtggcaacca
     1321 gaatgagaag cagatcgtga cgactgactt gcggcagaag tgcacggagt ctcacacggg
     1381 cacctcagcc tctgccccct tagcagccgg catcattgct ctcaccctgg aggccaataa
     1441 gaacctcaca tggcgggaca tgcaacacct ggtggtacag acctcgaagc cagcccacct
     1501 caatgccaac gactgggcca ccaatggtgt gggccggaaa gtgagccact catatggcta
     1561 cgggcttttg gacgcaggcg ccatggtggc cctggcccag aattggacca cagtggcccc
     1621 ccagcggaag tgcatcatcg acatcctcac cgagcccaaa gacatcggga aacggctcga
     1681 ggtgcggaag accgtgaccg cgtgcctggg cgagcccaac cacatcactc ggctggagca
     1741 cgctcaggcg cggctcaccc tgtcctataa tcgccgtggc gacctggcca tccacctggt
     1801 cagccccatg ggcacccgct ccaccctgct ggcagccagg ccacatgact actccgcaga
     1861 tgggtttaat gactgggcct tcatgacaac tcattcctgg gatgaggatc cctctggcga
     1921 gtgggtccta gagattgaaa acaccagcga agccaacaac tatgggacgc tgaccaagtt
     1981 caccctcgta ctctatggca ccgcccctga ggggctgccc gtacctccag aaagcagtgg
     2041 ctgcaagacc ctcacgtcca gtcaggcctg tgtggtgtgc gaggaaggct tctccctgca
     2101 ccagaagagc tgtgtccagc actgccctcc agggttcgcc ccccaagtcc tcgatacgca
     2161 ctatagcacc gagaatgacg tggagaccat ccgggccagc gtctgcgccc cctgccacgc
     2221 ctcatgtgcc acatgccagg ggccggccct gacagactgc ctcagctgcc ccagccacgc
     2281 ctccttggac cctgtggagc agacttgctc ccggcaaagc cagagcagcc gagagtcccc
     2341 gccacagcag cagccacctc ggctgccccc ggaggtggag gcggggcaac ggctgcgggc
     2401 agggctgctg ccctcacacc tgcctgaggt ggtggccggc ctcagctgcg ccttcatcgt
     2461 gctggtcttc gtcactgtct tcctggtcct gcagctgcgc tctggcttta gttttcgggg
     2521 ggtgaaggtg tacaccatgg accgtggcct catctcctac aaggggctgc cccctgaagc
     2581 ctggcaggag gagtgcccgt ctgactcaga agaggacgag ggccggggcg agaggaccgc
     2641 ctttatcaaa gaccagagcg ccctctgatg agcccactgc ccaccccctc aagccaatcc
     2701 cctccttggg cactttttaa ttcaccaaag tattttttta tcttgggact gggtttggac
     2761 cccagctggg aggcaagagg ggtggagact gcttcccatc ctaccctcgg gcccacctgg
     2821 ccacctgagg tgggcccagg accagctggg gcgtggggag ggccgtaccc caccctcagc
     2881 accccttcca tgtggagaaa ggagtgaaac ctttagggca gcttgccccg gccccggccc
     2941 cagccagagt tcctgcggag tgaagagggg cagcccttgc ttgttgggat tcctgaccca
     3001 ggccgcagct cttgcccttc cctgtccctc taaagcaata atggtcccat ccaggcagtc
     3061 gggggctggc ctaggagata tctgagggag gaggccacct ctccaagggc ttctgcaccc
     3121 tccaccctgt cccccagctc tggtgagtct tggcggcagc agccatcata ggaagggacc
     3181 aaggcaaggc aggtgcctcc aggtgtgcac gtggcatgtg gcctgtggcc tgtgtcccat
     3241 gacccacccc tgtgctccgt gcctccacca ccactggcca ccaggctggc gcagccaagg
     3301 ccgaagctct ggctgaaccc tgtgctggtg tcctgaccac cctcccctct cttgcacccg
     3361 cctctcccgt cagggcccaa gtccctgttt tctgagcccg ggctgcctgg gctgttggca
     3421 ctcacagacc tggagcccct gggtgggtgg tggggagggg cgctggccca gccggcctct
     3481 ctggcctccc acccgatgct gctttcccct gtggggatct caggggctgt ttgaggatat
     3541 attttcactt tgtgattatt tcactttaga tgctgatgat ttgtttttgt atttttaatg
     3601 ggggtagcag ctggactacc cacgttctca cacccaccgt ccgccctgct cctccctggc
     3661 tgccctggcc ctgaggtgtg ggggctgcag catgttgctg aggagtgagg aatagttgag
     3721 ccccaagtcc tgaagaggcg ggccagccag gcgggctcaa ggaaaggggg tcccagtggg
     3781 aggggcaggc tgacatctgt gtttcaagtg gggctcgcca tgccgggggt tcataggtca
     3841 ctggctctcc aagtgccaga ggtgggcagg tggtggcact gagccccccc aacactgtgc
     3901 cctggtggag aaagcactga cctgtcatgc ccccctcaaa cctcctcttc tgacgtgcct
     3961 tttgcacccc tcccattagg acaatcagtc ccctcccatc tgggagtccc cttttctttt
     4021 ctaccctagc cattcctggt acccagccat ctgcccaggg gtgccccctc ctctcccatc
     4081 cccctgccct cgtggccagc ccggctggtt ttgtaagatg ctgggttggt gcacagtgat
     4141 ttttttcttg taatttaaac aggcccagca ttgctggttc tatttaatgg acatgagata
     4201 atgttagagg ttttaaagtg attaaacgtg cagactatgc aaaccag
//
