LOCUS       NM_174936               3637 bp    mRNA    linear   PRI 10-FEB-2025
DEFINITION  Homo sapiens proprotein convertase subtilisin/kexin type 9 (PCSK9),
            transcript variant 1, mRNA.
ACCESSION   NM_174936
VERSION     NM_174936.4
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 3637)
  AUTHORS   Lorca,R., Aparicio,A., Gutierrez,L., Alvarez-Velasco,R.,
            Gonzalez-Urbistondo,F., Pascual,I., Gomez,J., Vazquez-Coto,D.,
            Garcia-Lago,C., Avanzas,P. and Coto,E.
  TITLE     PCSK9 gene variations in the clinical setting of premature
            cardiovascular disease: A critical appraisal
  JOURNAL   Int J Cardiol 413, 132402 (2024)
   PUBMED   39074621
  REMARK    GeneRIF: PCSK9 gene variations in the clinical setting of premature
            cardiovascular disease: A critical appraisal.
REFERENCE   2  (bases 1 to 3637)
  AUTHORS   Ghalali,A., Alhamdan,F., Upadhyay,S., Ganguly,K., Larsson,K.,
            Palmberg,L. and Rahman,M.
  TITLE     Contrasting effects of intracellular and extracellular human PCSK9
            on inflammation, lipid alteration and cell death
  JOURNAL   Commun Biol 7 (1), 985 (2024)
   PUBMED   39138259
  REMARK    GeneRIF: Contrasting effects of intracellular and extracellular
            human PCSK9 on inflammation, lipid alteration and cell death.
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 3637)
  AUTHORS   Mahboobnia,K., Pirro,M., Marini,E., Grignani,F., Bezsonov,E.E.,
            Jamialahmadi,T. and Sahebkar,A.
  TITLE     PCSK9 and cancer: Rethinking the link
  JOURNAL   Biomed Pharmacother 140, 111758 (2021)
   PUBMED   34058443
  REMARK    Review article
REFERENCE   4  (bases 1 to 3637)
  AUTHORS   Guo,Y., Yan,B., Tai,S., Zhou,S. and Zheng,X.L.
  TITLE     PCSK9: Associated with cardiac diseases and their risk factors?
  JOURNAL   Arch Biochem Biophys 704, 108717 (2021)
   PUBMED   33307067
  REMARK    GeneRIF: PCSK9: Associated with cardiac diseases and their risk
            factors?
            Review article
REFERENCE   5  (bases 1 to 3637)
  AUTHORS   Barale,C., Melchionda,E., Morotti,A. and Russo,I.
  TITLE     PCSK9 Biology and Its Role in Atherothrombosis
  JOURNAL   Int J Mol Sci 22 (11), 5880 (2021)
   PUBMED   34070931
  REMARK    GeneRIF: PCSK9 Biology and Its Role in Atherothrombosis.
            Review article
            Publication Status: Online-Only
REFERENCE   6  (bases 1 to 3637)
  AUTHORS   Ogura,M.
  TITLE     PCSK9 inhibition in the management of familial hypercholesterolemia
  JOURNAL   J Cardiol 71 (1), 1-7 (2018)
   PUBMED   28784313
  REMARK    Review article
REFERENCE   7  (bases 1 to 3637)
  AUTHORS   Seidah,N.G. and Prat,A.
  TITLE     The biology and therapeutic targeting of the proprotein convertases
  JOURNAL   Nat Rev Drug Discov 11 (5), 367-383 (2012)
   PUBMED   22679642
  REMARK    Review article
REFERENCE   8  (bases 1 to 3637)
  AUTHORS   Seidah,N.G., Benjannet,S., Wickham,L., Marcinkiewicz,J.,
            Jasmin,S.B., Stifani,S., Basak,A., Prat,A. and Chretien,M.
  TITLE     The secretory proprotein convertase neural apoptosis-regulated
            convertase 1 (NARC-1): liver regeneration and neuronal
            differentiation
  JOURNAL   Proc Natl Acad Sci U S A 100 (3), 928-933 (2003)
   PUBMED   12552133
REFERENCE   9  (bases 1 to 3637)
  AUTHORS   Varret,M., Rabes,J.P., Saint-Jore,B., Cenarro,A., Marinoni,J.C.,
            Civeira,F., Devillers,M., Krempf,M., Coulon,M., Thiart,R.,
            Kotze,M.J., Schmidt,H., Buzzi,J.C., Kostner,G.M., Bertolini,S.,
            Pocovi,M., Rosa,A., Farnier,M., Martinez,M., Junien,C. and
            Boileau,C.
  TITLE     A third major locus for autosomal dominant hypercholesterolemia
            maps to 1p34.1-p32
  JOURNAL   Am J Hum Genet 64 (5), 1378-1387 (1999)
   PUBMED   10205269
REFERENCE   10 (bases 1 to 3637)
  AUTHORS   Ison,H.E., Clarke,S.L. and Knowles,J.W.
  TITLE     Familial Hypercholesterolemia
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   24404629
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from DA738424.1, AL589790.22,
            EF692496.1, AC091609.2 and BC042095.1.
            
            On Aug 31, 2019 this sequence version replaced NM_174936.3.
            
            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. The encoded protein
            undergoes an autocatalytic processing event with its prosegment in
            the ER and is constitutively secreted as an inactive protease into
            the extracellular matrix and trans-Golgi network. It is expressed
            in liver, intestine and kidney tissues and escorts specific
            receptors for lysosomal degradation. It plays a role in cholesterol
            and fatty acid metabolism. Mutations in this gene have been
            associated with autosomal dominant familial hypercholesterolemia.
            Alternative splicing results in multiple transcript variants.
            [provided by RefSeq, Feb 2014].
            
            Transcript Variant: This variant (1) represents the longer
            transcript and encodes the functional protein.
            
            Sequence Note: This RefSeq record was created from transcript and
            genomic sequence data to make the sequence consistent with the
            reference genome assembly. The genomic coordinates used for the
            transcript record were based on transcript alignments.
            
            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 :: AK075365.1, EF692496.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA2144333, SAMEA2147920
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000302118.5/ ENSP00000303208.5
            RefSeq Select criteria :: based on conservation, expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-26                DA738424.1         73-98
            27-27               AL589790.22        39449-39449
            28-290              DA738424.1         100-362
            291-1315            EF692496.1         1-1025
            1316-1316           AC091609.2         170358-170358       c
            1317-1669           EF692496.1         1027-1379
            1670-1710           AC091609.2         169154-169194       c
            1711-2298           EF692496.1         1421-2008
            2299-2940           AC091609.2         163563-164204       c
            2941-3637           BC042095.1         1551-2247
FEATURES             Location/Qualifiers
     source          1..3637
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="1"
                     /map="1p32.3"
     gene            1..3637
                     /gene="PCSK9"
                     /gene_synonym="FH3; FHCL3; HCHOLA3; LDLCQ1; NARC-1; NARC1;
                     PC9"
                     /note="proprotein convertase subtilisin/kexin type 9"
                     /db_xref="GeneID:255738"
                     /db_xref="HGNC:HGNC:20001"
                     /db_xref="MIM:607786"
     exon            1..497
                     /gene="PCSK9"
                     /gene_synonym="FH3; FHCL3; HCHOLA3; LDLCQ1; NARC-1; NARC1;
                     PC9"
                     /inference="alignment:Splign:2.1.0"
     CDS             291..2369
                     /gene="PCSK9"
                     /gene_synonym="FH3; FHCL3; HCHOLA3; LDLCQ1; NARC-1; NARC1;
                     PC9"
                     /note="isoform 1 preproprotein is encoded by transcript
                     variant 1; neural apoptosis regulated convertase 1;
                     convertase subtilisin/kexin type 9 preproprotein;
                     subtilisin/kexin-like protease PC9"
                     /codon_start=1
                     /product="proprotein convertase subtilisin/kexin type 9
                     isoform 1 preproprotein"
                     /protein_id="NP_777596.2"
                     /db_xref="CCDS:CCDS603.1"
                     /db_xref="GeneID:255738"
                     /db_xref="HGNC:HGNC:20001"
                     /db_xref="MIM:607786"
                     /translation="MGTVSSRRSWWPLPLLLLLLLLLGPAGARAQEDEDGDYEELVLA
                     LRSEEDGLAEAPEHGTTATFHRCAKDPWRLPGTYVVVLKEETHLSQSERTARRLQAQA
                     ARRGYLTKILHVFHGLLPGFLVKMSGDLLELALKLPHVDYIEEDSSVFAQSIPWNLER
                     ITPPRYRADEYQPPDGGSLVEVYLLDTSIQSDHREIEGRVMVTDFENVPEEDGTRFHR
                     QASKCDSHGTHLAGVVSGRDAGVAKGASMRSLRVLNCQGKGTVSGTLIGLEFIRKSQL
                     VQPVGPLVVLLPLAGGYSRVLNAACQRLARAGVVLVTAAGNFRDDACLYSPASAPEVI
                     TVGATNAQDQPVTLGTLGTNFGRCVDLFAPGEDIIGASSDCSTCFVSQSGTSQAAAHV
                     AGIAAMMLSAEPELTLAELRQRLIHFSAKDVINEAWFPEDQRVLTPNLVAALPPSTHG
                     AGWQLFCRTVWSAHSGPTRMATAVARCAPDEELLSCSSFSRSGKRRGERMEAQGGKLV
                     CRAHNAFGGEGVYAIARCCLLPQANCSVHTAPPAEASMGTRVHCHQQGHVLTGCSSHW
                     EVEDLGTHKPPVLRPRGQPNQCVGHREASIHASCCHAPGLECKVKEHGIPAPQEQVTV
                     ACEEGWTLTGCSALPGTSHVLGAYAVDNTCVVRSRDVSTTGSTSEGAVTAVAICCRSR
                     HLAQASQELQ"
     exon            498..689
                     /gene="PCSK9"
                     /gene_synonym="FH3; FHCL3; HCHOLA3; LDLCQ1; NARC-1; NARC1;
                     PC9"
                     /inference="alignment:Splign:2.1.0"
     exon            690..813
                     /gene="PCSK9"
                     /gene_synonym="FH3; FHCL3; HCHOLA3; LDLCQ1; NARC-1; NARC1;
                     PC9"
                     /inference="alignment:Splign:2.1.0"
     exon            814..947
                     /gene="PCSK9"
                     /gene_synonym="FH3; FHCL3; HCHOLA3; LDLCQ1; NARC-1; NARC1;
                     PC9"
                     /inference="alignment:Splign:2.1.0"
     exon            948..1089
                     /gene="PCSK9"
                     /gene_synonym="FH3; FHCL3; HCHOLA3; LDLCQ1; NARC-1; NARC1;
                     PC9"
                     /inference="alignment:Splign:2.1.0"
     exon            1090..1286
                     /gene="PCSK9"
                     /gene_synonym="FH3; FHCL3; HCHOLA3; LDLCQ1; NARC-1; NARC1;
                     PC9"
                     /inference="alignment:Splign:2.1.0"
     exon            1287..1470
                     /gene="PCSK9"
                     /gene_synonym="FH3; FHCL3; HCHOLA3; LDLCQ1; NARC-1; NARC1;
                     PC9"
                     /inference="alignment:Splign:2.1.0"
     exon            1471..1644
                     /gene="PCSK9"
                     /gene_synonym="FH3; FHCL3; HCHOLA3; LDLCQ1; NARC-1; NARC1;
                     PC9"
                     /inference="alignment:Splign:2.1.0"
     exon            1645..1793
                     /gene="PCSK9"
                     /gene_synonym="FH3; FHCL3; HCHOLA3; LDLCQ1; NARC-1; NARC1;
                     PC9"
                     /inference="alignment:Splign:2.1.0"
     exon            1794..1971
                     /gene="PCSK9"
                     /gene_synonym="FH3; FHCL3; HCHOLA3; LDLCQ1; NARC-1; NARC1;
                     PC9"
                     /inference="alignment:Splign:2.1.0"
     exon            1972..2153
                     /gene="PCSK9"
                     /gene_synonym="FH3; FHCL3; HCHOLA3; LDLCQ1; NARC-1; NARC1;
                     PC9"
                     /inference="alignment:Splign:2.1.0"
     exon            2154..3637
                     /gene="PCSK9"
                     /gene_synonym="FH3; FHCL3; HCHOLA3; LDLCQ1; NARC-1; NARC1;
                     PC9"
                     /inference="alignment:Splign:2.1.0"
     regulatory      3621..3626
                     /regulatory_class="polyA_signal_sequence"
                     /gene="PCSK9"
                     /gene_synonym="FH3; FHCL3; HCHOLA3; LDLCQ1; NARC-1; NARC1;
                     PC9"
                     /note="hexamer: AACAAA"
     polyA_site      3637
                     /gene="PCSK9"
                     /gene_synonym="FH3; FHCL3; HCHOLA3; LDLCQ1; NARC-1; NARC1;
                     PC9"
                     /note="major polyA site"
ORIGIN      
        1 agcgacgtcg aggcgctcat ggttgcaggc gggcgccgcc gttcagttca gggtctgagc
       61 ctggaggagt gagccaggca gtgagactgg ctcgggcggg ccgggacgcg tcgttgcagc
      121 agcggctccc agctcccagc caggattccg cgcgcccctt cacgcgccct gctcctgaac
      181 ttcagctcct gcacagtcct ccccaccgca aggctcaagg cgccgccggc gtggaccgcg
      241 cacggcctct aggtctcctc gccaggacag caacctctcc cctggccctc atgggcaccg
      301 tcagctccag gcggtcctgg tggccgctgc cactgctgct gctgctgctg ctgctcctgg
      361 gtcccgcggg cgcccgtgcg caggaggacg aggacggcga ctacgaggag ctggtgctag
      421 ccttgcgttc cgaggaggac ggcctggccg aagcacccga gcacggaacc acagccacct
      481 tccaccgctg cgccaaggat ccgtggaggt tgcctggcac ctacgtggtg gtgctgaagg
      541 aggagaccca cctctcgcag tcagagcgca ctgcccgccg cctgcaggcc caggctgccc
      601 gccggggata cctcaccaag atcctgcatg tcttccatgg ccttcttcct ggcttcctgg
      661 tgaagatgag tggcgacctg ctggagctgg ccttgaagtt gccccatgtc gactacatcg
      721 aggaggactc ctctgtcttt gcccagagca tcccgtggaa cctggagcgg attacccctc
      781 cacggtaccg ggcggatgaa taccagcccc ccgacggagg cagcctggtg gaggtgtatc
      841 tcctagacac cagcatacag agtgaccacc gggaaatcga gggcagggtc atggtcaccg
      901 acttcgagaa tgtgcccgag gaggacggga cccgcttcca cagacaggcc agcaagtgtg
      961 acagtcatgg cacccacctg gcaggggtgg tcagcggccg ggatgccggc gtggccaagg
     1021 gtgccagcat gcgcagcctg cgcgtgctca actgccaagg gaagggcacg gttagcggca
     1081 ccctcatagg cctggagttt attcggaaaa gccagctggt ccagcctgtg gggccactgg
     1141 tggtgctgct gcccctggcg ggtgggtaca gccgcgtcct caacgccgcc tgccagcgcc
     1201 tggcgagggc tggggtcgtg ctggtcaccg ctgccggcaa cttccgggac gatgcctgcc
     1261 tctactcccc agcctcagct cccgaggtca tcacagttgg ggccaccaat gcccaagacc
     1321 agccggtgac cctggggact ttggggacca actttggccg ctgtgtggac ctctttgccc
     1381 caggggagga catcattggt gcctccagcg actgcagcac ctgctttgtg tcacagagtg
     1441 ggacatcaca ggctgctgcc cacgtggctg gcattgcagc catgatgctg tctgccgagc
     1501 cggagctcac cctggccgag ttgaggcaga gactgatcca cttctctgcc aaagatgtca
     1561 tcaatgaggc ctggttccct gaggaccagc gggtactgac ccccaacctg gtggccgccc
     1621 tgccccccag cacccatggg gcaggttggc agctgttttg caggactgta tggtcagcac
     1681 actcggggcc tacacggatg gccacagccg tcgcccgctg cgccccagat gaggagctgc
     1741 tgagctgctc cagtttctcc aggagtggga agcggcgggg cgagcgcatg gaggcccaag
     1801 ggggcaagct ggtctgccgg gcccacaacg cttttggggg tgagggtgtc tacgccattg
     1861 ccaggtgctg cctgctaccc caggccaact gcagcgtcca cacagctcca ccagctgagg
     1921 ccagcatggg gacccgtgtc cactgccacc aacagggcca cgtcctcaca ggctgcagct
     1981 cccactggga ggtggaggac cttggcaccc acaagccgcc tgtgctgagg ccacgaggtc
     2041 agcccaacca gtgcgtgggc cacagggagg ccagcatcca cgcttcctgc tgccatgccc
     2101 caggtctgga atgcaaagtc aaggagcatg gaatcccggc ccctcaggag caggtgaccg
     2161 tggcctgcga ggagggctgg accctgactg gctgcagtgc cctccctggg acctcccacg
     2221 tcctgggggc ctacgccgta gacaacacgt gtgtagtcag gagccgggac gtcagcacta
     2281 caggcagcac cagcgaaggg gccgtgacag ccgttgccat ctgctgccgg agccggcacc
     2341 tggcgcaggc ctcccaggag ctccagtgac agccccatcc caggatgggt gtctggggag
     2401 ggtcaagggc tggggctgag ctttaaaatg gttccgactt gtccctctct cagccctcca
     2461 tggcctggca cgaggggatg gggatgcttc cgcctttccg gggctgctgg cctggccctt
     2521 gagtggggca gcctccttgc ctggaactca ctcactctgg gtgcctcctc cccaggtgga
     2581 ggtgccagga agctccctcc ctcactgtgg ggcatttcac cattcaaaca ggtcgagctg
     2641 tgctcgggtg ctgccagctg ctcccaatgt gccgatgtcc gtgggcagaa tgacttttat
     2701 tgagctcttg ttccgtgcca ggcattcaat cctcaggtct ccaccaagga ggcaggattc
     2761 ttcccatgga taggggaggg ggcggtaggg gctgcaggga caaacatcgt tggggggtga
     2821 gtgtgaaagg tgctgatggc cctcatctcc agctaactgt ggagaagccc ctgggggctc
     2881 cctgattaat ggaggcttag ctttctggat ggcatctagc cagaggctgg agacaggtgc
     2941 gcccctggtg gtcacaggct gtgccttggt ttcctgagcc acctttactc tgctctatgc
     3001 caggctgtgc tagcaacacc caaaggtggc ctgcggggag ccatcaccta ggactgactc
     3061 ggcagtgtgc agtggtgcat gcactgtctc agccaacccg ctccactacc cggcagggta
     3121 cacattcgca cccctacttc acagaggaag aaacctggaa ccagaggggg cgtgcctgcc
     3181 aagctcacac agcaggaact gagccagaaa cgcagattgg gctggctctg aagccaagcc
     3241 tcttcttact tcacccggct gggctcctca tttttacggg taacagtgag gctgggaagg
     3301 ggaacacaga ccaggaagct cggtgagtga tggcagaacg atgcctgcag gcatggaact
     3361 ttttccgtta tcacccaggc ctgattcact ggcctggcgg agatgcttct aaggcatggt
     3421 cgggggagag ggccaacaac tgtccctcct tgagcaccag ccccacccaa gcaagcagac
     3481 atttatcttt tgggtctgtc ctctctgttg cctttttaca gccaactttt ctagacctgt
     3541 tttgcttttg taacttgaag atatttattc tgggttttgt agcattttta ttaatatggt
     3601 gactttttaa aataaaaaca aacaaacgtt gtcctaa
//
