LOCUS       NM_017573               2603 bp    mRNA    linear   PRI 22-SEP-2024
DEFINITION  Homo sapiens proprotein convertase subtilisin/kexin type 4 (PCSK4),
            transcript variant 1, mRNA.
ACCESSION   NM_017573
VERSION     NM_017573.5
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 2603)
  AUTHORS   Haenig,C., Atias,N., Taylor,A.K., Mazza,A., Schaefer,M.H., Russ,J.,
            Riechers,S.P., Jain,S., Coughlin,M., Fontaine,J.F., Freibaum,B.D.,
            Brusendorf,L., Zenkner,M., Porras,P., Stroedicke,M., Schnoegl,S.,
            Arnsburg,K., Boeddrich,A., Pigazzini,L., Heutink,P., Taylor,J.P.,
            Kirstein,J., Andrade-Navarro,M.A., Sharan,R. and Wanker,E.E.
  TITLE     Interactome Mapping Provides a Network of Neurodegenerative Disease
            Proteins and Uncovers Widespread Protein Aggregation in Affected
            Brains
  JOURNAL   Cell Rep 32 (7), 108050 (2020)
   PUBMED   32814053
REFERENCE   2  (bases 1 to 2603)
  AUTHORS   Luck,K., Kim,D.K., Lambourne,L., Spirohn,K., Begg,B.E., Bian,W.,
            Brignall,R., Cafarelli,T., Campos-Laborie,F.J., Charloteaux,B.,
            Choi,D., Cote,A.G., Daley,M., Deimling,S., Desbuleux,A., Dricot,A.,
            Gebbia,M., Hardy,M.F., Kishore,N., Knapp,J.J., Kovacs,I.A.,
            Lemmens,I., Mee,M.W., Mellor,J.C., Pollis,C., Pons,C.,
            Richardson,A.D., Schlabach,S., Teeking,B., Yadav,A., Babor,M.,
            Balcha,D., Basha,O., Bowman-Colin,C., Chin,S.F., Choi,S.G.,
            Colabella,C., Coppin,G., D'Amata,C., De Ridder,D., De Rouck,S.,
            Duran-Frigola,M., Ennajdaoui,H., Goebels,F., Goehring,L., Gopal,A.,
            Haddad,G., Hatchi,E., Helmy,M., Jacob,Y., Kassa,Y., Landini,S.,
            Li,R., van Lieshout,N., MacWilliams,A., Markey,D., Paulson,J.N.,
            Rangarajan,S., Rasla,J., Rayhan,A., Rolland,T., San-Miguel,A.,
            Shen,Y., Sheykhkarimli,D., Sheynkman,G.M., Simonovsky,E., Tasan,M.,
            Tejeda,A., Tropepe,V., Twizere,J.C., Wang,Y., Weatheritt,R.J.,
            Weile,J., Xia,Y., Yang,X., Yeger-Lotem,E., Zhong,Q., Aloy,P.,
            Bader,G.D., De Las Rivas,J., Gaudet,S., Hao,T., Rak,J.,
            Tavernier,J., Hill,D.E., Vidal,M., Roth,F.P. and Calderwood,M.A.
  TITLE     A reference map of the human binary protein interactome
  JOURNAL   Nature 580 (7803), 402-408 (2020)
   PUBMED   32296183
REFERENCE   3  (bases 1 to 2603)
  AUTHORS   Seidah,N.G., Sadr,M.S., Chretien,M. and Mbikay,M.
  TITLE     The multifaceted proprotein convertases: their unique, redundant,
            complementary, and opposite functions
  JOURNAL   J Biol Chem 288 (30), 21473-21481 (2013)
   PUBMED   23775089
  REMARK    Review article
REFERENCE   4  (bases 1 to 2603)
  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   5  (bases 1 to 2603)
  AUTHORS   Seidah,N.G.
  TITLE     The proprotein convertases, 20 years later
  JOURNAL   Methods Mol Biol 768, 23-57 (2011)
   PUBMED   21805237
  REMARK    Review article
REFERENCE   6  (bases 1 to 2603)
  AUTHORS   Gyamera-Acheampong,C. and Mbikay,M.
  TITLE     Proprotein convertase subtilisin/kexin type 4 in mammalian
            fertility: a review
  JOURNAL   Hum Reprod Update 15 (2), 237-247 (2009)
   PUBMED   19109312
  REMARK    Review article
REFERENCE   7  (bases 1 to 2603)
  AUTHORS   Tadros,H., Chretien,M. and Mbikay,M.
  TITLE     The testicular germ-cell protease PC4 is also expressed in
            macrophage-like cells of the ovary
  JOURNAL   J Reprod Immunol 49 (2), 133-152 (2001)
   PUBMED   11164898
REFERENCE   8  (bases 1 to 2603)
  AUTHORS   Zhou,A., Webb,G., Zhu,X. and Steiner,D.F.
  TITLE     Proteolytic processing in the secretory pathway
  JOURNAL   J Biol Chem 274 (30), 20745-20748 (1999)
   PUBMED   10409610
  REMARK    Review article
REFERENCE   9  (bases 1 to 2603)
  AUTHORS   Mbikay,M., Seidah,N.G., Chretien,M. and Simpson,E.M.
  TITLE     Chromosomal assignment of the genes for proprotein convertases PC4,
            PC5, and PACE 4 in mouse and human
  JOURNAL   Genomics 26 (1), 123-129 (1995)
   PUBMED   7782070
REFERENCE   10 (bases 1 to 2603)
  AUTHORS   Seidah,N.G., Chretien,M. and Day,R.
  TITLE     The family of subtilisin/kexin like pro-protein and pro-hormone
            convertases: divergent or shared functions
  JOURNAL   Biochimie 76 (3-4), 197-209 (1994)
   PUBMED   7819324
  REMARK    Review article
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC027307.5.
            
            On Jun 19, 2021 this sequence version replaced NM_017573.4.
            
            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 initial autocatalytic processing event in the ER to
            generate a heterodimer which exits the ER and sorts to subcellular
            compartments where a second autocatalytic even takes place and the
            catalytic activity is acquired. This gene encodes one of the seven
            basic amino acid-specific members which cleave their substrates at
            single or paired basic residues. The protease is expressed only in
            the testis, placenta, and ovary. It plays a critical role in
            fertilization, fetoplacental growth, and embryonic development and
            processes multiple prohormones including pro-pituitary adenylate
            cyclase-activating protein and pro-insulin-like growth factor II.
            [provided by RefSeq, Jan 2014].
            
            Transcript Variant: This variant (1) represents the longer
            transcript and encodes the longer isoform (1).
            
            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 :: AY358963.1, HM005448.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000300954.10/ ENSP00000300954.5
            RefSeq Select criteria :: based on manual assertion, conservation,
                                      expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-193               AC027307.5         79981-80173         c
            194-298             AC027307.5         79616-79720         c
            299-391             AC027307.5         78011-78103         c
            392-520             AC027307.5         77787-77915         c
            521-597             AC027307.5         77608-77684         c
            598-686             AC027307.5         77426-77514         c
            687-859             AC027307.5         76964-77136         c
            860-1072            AC027307.5         76676-76888         c
            1073-1173           AC027307.5         73850-73950         c
            1174-1277           AC027307.5         73661-73764         c
            1278-1395           AC027307.5         73473-73590         c
            1396-1575           AC027307.5         73107-73286         c
            1576-1700           AC027307.5         72719-72843         c
            1701-1823           AC027307.5         72176-72298         c
            1824-2603           AC027307.5         71251-72030         c
FEATURES             Location/Qualifiers
     source          1..2603
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="19"
                     /map="19p13.3"
     gene            1..2603
                     /gene="PCSK4"
                     /gene_synonym="PC4; SPC5"
                     /note="proprotein convertase subtilisin/kexin type 4"
                     /db_xref="GeneID:54760"
                     /db_xref="HGNC:HGNC:8746"
                     /db_xref="MIM:600487"
     exon            1..193
                     /gene="PCSK4"
                     /gene_synonym="PC4; SPC5"
                     /inference="alignment:Splign:2.1.0"
     CDS             5..2272
                     /gene="PCSK4"
                     /gene_synonym="PC4; SPC5"
                     /note="isoform 1 preproprotein is encoded by transcript
                     variant 1; testicular tissue protein Li 135"
                     /codon_start=1
                     /product="proprotein convertase subtilisin/kexin type 4
                     isoform 1 preproprotein"
                     /protein_id="NP_060043.2"
                     /db_xref="CCDS:CCDS12069.2"
                     /db_xref="GeneID:54760"
                     /db_xref="HGNC:HGNC:8746"
                     /db_xref="MIM:600487"
                     /translation="MRPAPIALWLRLVLALALVRPRAVGWAPVRAPIYVSSWAVQVSQ
                     GNREVERLARKFGFVNLGPIFPDGQYFHLRHRGVVQQSLTPHWGHRLHLKKNPKVQWF
                     QQQTLQRRVKRSVVVPTDPWFSKQWYMNSEAQPDLSILQAWSQGLSGQGIVVSVLDDG
                     IEKDHPDLWANYDPLASYDFNDYDPDPQPRYTPSKENRHGTRCAGEVAAMANNGFCGV
                     GVAFNARIGGVRMLDGTITDVIEAQSLSLQPQHIHIYSASWGPEDDGRTVDGPGILTR
                     EAFRRGVTKGRGGLGTLFIWASGNGGLHYDNCNCDGYTNSIHTLSVGSTTQQGRVPWY
                     SEACASTLTTTYSSGVATDPQIVTTDLHHGCTDQHTGTSASAPLAAGMIALALEANPF
                     LTWRDMQHLVVRASKPAHLQAEDWRTNGVGRQVSHHYGYGLLDAGLLVDTARTWLPTQ
                     PQRKCAVRVQSRPTPILPLIYIRENVSACAGLHNSIRSLEHVQAQLTLSYSRRGDLEI
                     SLTSPMGTRSTLVAIRPLDVSTEGYNNWVFMSTHFWDENPQGVWTLGLENKGYYFNTG
                     TLYRYTLLLYGTAEDMTARPTGPQVTSSACVQRDTEGLCQACDGPAYILGQLCLAYCP
                     PRFFNHTRLVTAGPGHTAAPALRVCSSCHASCYTCRGGSPRDCTSCPPSSTLDQQQGS
                     CMGPTTPDSRPRLRAAACPHHRCPASAMVLSLLAVTLGGPVLCGMSMDLPLYAWLSRA
                     RATPTKPQVWLPAGT"
     exon            194..298
                     /gene="PCSK4"
                     /gene_synonym="PC4; SPC5"
                     /inference="alignment:Splign:2.1.0"
     exon            299..391
                     /gene="PCSK4"
                     /gene_synonym="PC4; SPC5"
                     /inference="alignment:Splign:2.1.0"
     exon            392..520
                     /gene="PCSK4"
                     /gene_synonym="PC4; SPC5"
                     /inference="alignment:Splign:2.1.0"
     exon            521..597
                     /gene="PCSK4"
                     /gene_synonym="PC4; SPC5"
                     /inference="alignment:Splign:2.1.0"
     exon            598..686
                     /gene="PCSK4"
                     /gene_synonym="PC4; SPC5"
                     /inference="alignment:Splign:2.1.0"
     exon            687..859
                     /gene="PCSK4"
                     /gene_synonym="PC4; SPC5"
                     /inference="alignment:Splign:2.1.0"
     exon            860..1072
                     /gene="PCSK4"
                     /gene_synonym="PC4; SPC5"
                     /inference="alignment:Splign:2.1.0"
     exon            1073..1173
                     /gene="PCSK4"
                     /gene_synonym="PC4; SPC5"
                     /inference="alignment:Splign:2.1.0"
     exon            1174..1277
                     /gene="PCSK4"
                     /gene_synonym="PC4; SPC5"
                     /inference="alignment:Splign:2.1.0"
     exon            1278..1395
                     /gene="PCSK4"
                     /gene_synonym="PC4; SPC5"
                     /inference="alignment:Splign:2.1.0"
     exon            1396..1575
                     /gene="PCSK4"
                     /gene_synonym="PC4; SPC5"
                     /inference="alignment:Splign:2.1.0"
     exon            1576..1700
                     /gene="PCSK4"
                     /gene_synonym="PC4; SPC5"
                     /inference="alignment:Splign:2.1.0"
     exon            1701..1823
                     /gene="PCSK4"
                     /gene_synonym="PC4; SPC5"
                     /inference="alignment:Splign:2.1.0"
     exon            1824..2603
                     /gene="PCSK4"
                     /gene_synonym="PC4; SPC5"
                     /inference="alignment:Splign:2.1.0"
     regulatory      2582..2587
                     /regulatory_class="polyA_signal_sequence"
                     /gene="PCSK4"
                     /gene_synonym="PC4; SPC5"
                     /note="hexamer: AATAAA"
     polyA_site      2603
                     /gene="PCSK4"
                     /gene_synonym="PC4; SPC5"
                     /note="major polyA site"
ORIGIN      
        1 ctccatgcgg cccgccccga ttgcgctgtg gctgcgcctg gtcttggccc tggcccttgt
       61 ccgcccccgg gctgtggggt gggccccggt ccgagccccc atctatgtca gcagctgggc
      121 cgtccaggtg tcccagggta accgggaggt cgagcgcctg gcacgcaaat tcggcttcgt
      181 caacctgggg ccgatcttcc ctgacgggca gtactttcac ctgcggcacc ggggcgtggt
      241 ccagcagtcc ctgaccccgc actggggcca ccgcctgcac ctgaagaaaa accccaaggt
      301 gcagtggttc cagcagcaga cgctgcagcg gcgggtgaaa cgctctgtcg tggtgcccac
      361 ggacccctgg ttctccaagc agtggtacat gaacagcgag gcccaaccag acctgagcat
      421 cctgcaggcc tggagtcagg ggctgtcagg ccagggcatc gtggtctctg tgctggacga
      481 tggcatcgag aaggaccacc cggacctctg ggccaactac gaccccctgg ccagctatga
      541 cttcaatgac tacgacccgg acccccagcc ccgctacacc cccagcaaag agaaccggca
      601 cgggacccgc tgtgctgggg aggtggccgc gatggccaac aatggcttct gtggtgtggg
      661 ggtcgctttc aacgcccgaa tcggaggcgt acggatgctg gacggtacca tcaccgatgt
      721 catcgaggcc cagtcgctga gcctgcagcc gcagcacatc cacatttaca gcgccagctg
      781 gggtcccgag gacgacggcc gcacggtgga cggccccggc atcctcaccc gcgaggcctt
      841 ccggcgtggt gtgaccaagg gccgcggcgg gctgggcacg ctcttcatct gggcctcggg
      901 caacggcggc ctgcactacg acaactgcaa ctgcgacggc tacaccaaca gcatccacac
      961 gctttccgtg ggcagcacca cccagcaggg ccgcgtgccc tggtacagcg aagcctgcgc
     1021 ctccaccctc accaccacct acagcagcgg cgtggccacc gacccccaga tcgtcaccac
     1081 ggacctgcat cacgggtgca cagaccagca cacgggcacc tcggcctcag ccccactggc
     1141 ggccggcatg atcgccctag cgctggaggc caacccgttc ctgacgtgga gagacatgca
     1201 gcacctggtg gtccgcgcgt ccaagccggc gcacctgcag gccgaggact ggaggaccaa
     1261 cggcgtgggg cgccaagtga gccatcacta cggatacggg ctgctggacg ccgggctgct
     1321 ggtggacacc gcccgcacct ggctgcccac ccagccgcag aggaagtgcg ccgtccgggt
     1381 ccagagccgc cccaccccca tcctgccgct gatctacatc agggaaaacg tatcggcctg
     1441 cgccggcctc cacaactcca tccgctcgct ggagcacgtg caggcgcagc tgacgctgtc
     1501 ctacagccgg cgcggagacc tggagatctc gctcaccagc cccatgggca cgcgctccac
     1561 actcgtggcc atacgaccct tggacgtcag cactgaaggc tacaacaact gggtcttcat
     1621 gtccacccac ttctgggatg agaacccaca gggcgtgtgg accctgggcc tagagaacaa
     1681 gggctactat ttcaacacgg ggacgttgta ccgctacacg ctgctgctct atgggacggc
     1741 cgaggacatg acagcgcggc ctacaggccc ccaggtgacc agcagcgcgt gtgtgcagcg
     1801 ggacacagag gggctgtgcc aggcgtgtga cggccccgcc tacatcctgg gacagctctg
     1861 cctggcctac tgccccccgc ggttcttcaa ccacacaagg ctggtgaccg ctgggcctgg
     1921 gcacacggcg gcgcccgcgc tgagggtctg ctccagctgc catgcctcct gctacacctg
     1981 ccgcggcggc tccccgaggg actgcacctc ctgtccccca tcctccacgc tggaccagca
     2041 gcagggctcc tgcatgggac ccaccacccc cgacagccgc ccccggctta gagctgccgc
     2101 ctgtccccac caccgctgcc cagcctcggc catggtgctg agcctcctgg ccgtgaccct
     2161 cggaggcccc gtcctctgcg gcatgtccat ggacctccca ctatacgcct ggctctcccg
     2221 tgccagggcc acccccacca aaccccaggt ctggctgcca gctggaacct gaagttgtca
     2281 gctcagaaag cgaccttgcc cccgcctggg tccctgacag gcactgctgc catgctgcct
     2341 ccccaggctg gccccagagg agcgagcacc agcacccgac gcctggcctg ccagggatgg
     2401 gccccgtgga accccgaagc ctggcgggag agagagagag agaagtctcc tctgcatttt
     2461 gggtttgggc gggagtgggc tggggggaga ggctggagca ccccaaaagc caggggaaag
     2521 tggagggaga gaaacgtgac actgtccgcc tcgggcaccg cgtccaacct cagagtttgc
     2581 aaataaaggt tgcttagaag gtg
//
