LOCUS       NM_002594               4691 bp    mRNA    linear   PRI 04-APR-2024
DEFINITION  Homo sapiens proprotein convertase subtilisin/kexin type 2 (PCSK2),
            transcript variant 1, mRNA.
ACCESSION   NM_002594
VERSION     NM_002594.5
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 4691)
  AUTHORS   Remes,S.M., Leijon,H., Vesterinen,T., Louhimo,J., Pulkkinen,V.,
            Ezer,S., Kere,J., Haglund,C. and Arola,J.
  TITLE     PCSK2 expression in neuroendocrine tumors points to a midgut,
            pulmonary, or pheochromocytoma-paraganglioma origin
  JOURNAL   APMIS 128 (11), 563-572 (2020)
   PUBMED   32794589
  REMARK    GeneRIF: PCSK2 expression in neuroendocrine tumors points to a
            midgut, pulmonary, or pheochromocytoma-paraganglioma origin.
REFERENCE   2  (bases 1 to 4691)
  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   3  (bases 1 to 4691)
  AUTHORS   Fujimaki,T., Kato,K., Yokoi,K., Oguri,M., Yoshida,T., Watanabe,S.,
            Metoki,N., Yoshida,H., Satoh,K., Aoyagi,Y., Nozawa,Y., Kimura,G.
            and Yamada,Y.
  TITLE     Association of genetic variants in SEMA3F, CLEC16A, LAMA3, and
            PCSK2 with myocardial infarction in Japanese individuals
  JOURNAL   Atherosclerosis 210 (2), 468-473 (2010)
   PUBMED   20036365
  REMARK    GeneRIF: SEMA3F, CLEC16A, LAMA3, and PCSK2 variants have roles in
            myocardial infarction in Japanese individuals
REFERENCE   4  (bases 1 to 4691)
  AUTHORS   Leak,T.S., Keene,K.L., Langefeld,C.D., Gallagher,C.J.,
            Mychaleckyj,J.C., Freedman,B.I., Bowden,D.W., Rich,S.S. and
            Sale,M.M.
  TITLE     Association of the proprotein convertase subtilisin/kexin-type 2
            (PCSK2) gene with type 2 diabetes in an African American population
  JOURNAL   Mol Genet Metab 92 (1-2), 145-150 (2007)
   PUBMED   17618154
  REMARK    GeneRIF: Single nucleotide polymorphisms in PCSK2 is associated
            with type 2 diabetes
            GeneRIF: Observational study of gene-disease association. (HuGE
            Navigator)
REFERENCE   5  (bases 1 to 4691)
  AUTHORS   Taylor,N.A., Shennan,K.I., Cutler,D.F. and Docherty,K.
  TITLE     Mutations within the propeptide, the primary cleavage site or the
            catalytic site, or deletion of C-terminal sequences, prevents
            secretion of proPC2 from transfected COS-7 cells
  JOURNAL   Biochem J 321 (Pt 2) (Pt 2), 367-373 (1997)
   PUBMED   9020868
REFERENCE   6  (bases 1 to 4691)
  AUTHORS   Bailyes,E.M., Shennan,K.I., Usac,E.F., Arden,S.D., Guest,P.C.,
            Docherty,K. and Hutton,J.C.
  TITLE     Differences between the catalytic properties of recombinant human
            PC2 and endogenous rat PC2
  JOURNAL   Biochem J 309 (Pt 2) (Pt 2), 587-594 (1995)
   PUBMED   7626024
REFERENCE   7  (bases 1 to 4691)
  AUTHORS   Ohagi,S., LaMendola,J., LeBeau,M.M., Espinosa,R. 3rd, Takeda,J.,
            Smeekens,S.P., Chan,S.J. and Steiner,D.F.
  TITLE     Identification and analysis of the gene encoding human PC2, a
            prohormone convertase expressed in neuroendocrine tissues
  JOURNAL   Proc Natl Acad Sci U S A 89 (11), 4977-4981 (1992)
   PUBMED   1594602
REFERENCE   8  (bases 1 to 4691)
  AUTHORS   Seidah,N.G., Mattei,M.G., Gaspar,L., Benjannet,S., Mbikay,M. and
            Chretien,M.
  TITLE     Chromosomal assignments of the genes for neuroendocrine convertase
            PC1 (NEC1) to human 5q15-21, neuroendocrine convertase PC2 (NEC2)
            to human 20p11.1-11.2, and furin (mouse 7[D1-E2] region)
  JOURNAL   Genomics 11 (1), 103-107 (1991)
   PUBMED   1765368
REFERENCE   9  (bases 1 to 4691)
  AUTHORS   Smeekens,S.P. and Steiner,D.F.
  TITLE     Identification of a human insulinoma cDNA encoding a novel
            mammalian protein structurally related to the yeast dibasic
            processing protease Kex2
  JOURNAL   J Biol Chem 265 (6), 2997-3000 (1990)
   PUBMED   2154467
REFERENCE   10 (bases 1 to 4691)
  AUTHORS   Sanke,T., Bell,G.I., Sample,C., Rubenstein,A.H. and Steiner,D.F.
  TITLE     An islet amyloid peptide is derived from an 89-amino acid precursor
            by proteolytic processing
  JOURNAL   J Biol Chem 263 (33), 17243-17246 (1988)
   PUBMED   3053705
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from HY137524.1, BC001905.1,
            BC005815.2, BC040546.1, DA148468.1, CD519990.1 and BP384064.1.
            
            On Nov 22, 2018 this sequence version replaced NM_002594.4.
            
            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 protein
            undergoes an initial autocatalytic processing event and interacts
            with a neuroendocrine secretory protein in the ER, exits the ER and
            sorts to secretory granules, where it is cleaved and catalytically
            activated during intracellular transport. The encoded protease is
            packaged into and activated in dense core secretory granules and
            expressed in the neuroendocrine system and brain. This gene encodes
            one of the seven basic amino acid-specific members which cleave
            their substrates at single or paired basic residues. It functions
            in the proteolytic activation of polypeptide hormones and
            neuropeptides precursors. Single nucleotide polymorphisms in this
            gene may increase susceptibility to myocardial infarction and type
            2 diabetes. This gene may also play a role in tumor development and
            progression. Alternatively spliced transcript variants encoding
            multiple isoforms have been observed for this gene. [provided by
            RefSeq, Jan 2014].
            
            Transcript Variant: This variant (1) represents the longest
            transcript and encodes the longest isoform (1).
            
            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 :: SRR1803614.72025.1,
                                           SRR1660809.4612.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1968540, SAMEA1968832
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000262545.7/ ENSP00000262545.2
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-36                HY137524.1         117-152
            37-644              BC001905.1         52-659
            645-2394            BC005815.2         634-2383
            2395-2475           BC040546.1         2379-2459
            2476-2927           DA148468.1         119-570
            2928-3153           BC040546.1         2911-3136
            3154-3404           CD519990.1         360-610
            3405-4210           BC040546.1         3387-4192
            4211-4439           BP384064.1         178-406
            4440-4691           BC040546.1         4422-4673
FEATURES             Location/Qualifiers
     source          1..4691
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="20"
                     /map="20p12.1"
     gene            1..4691
                     /gene="PCSK2"
                     /gene_synonym="NEC 2; NEC-2; NEC2; PC2; SPC2"
                     /note="proprotein convertase subtilisin/kexin type 2"
                     /db_xref="GeneID:5126"
                     /db_xref="HGNC:HGNC:8744"
                     /db_xref="MIM:162151"
     exon            1..443
                     /gene="PCSK2"
                     /gene_synonym="NEC 2; NEC-2; NEC2; PC2; SPC2"
                     /inference="alignment:Splign:2.1.0"
     CDS             267..2183
                     /gene="PCSK2"
                     /gene_synonym="NEC 2; NEC-2; NEC2; PC2; SPC2"
                     /EC_number="3.4.21.94"
                     /note="isoform 1 preproprotein is encoded by transcript
                     variant 1; prohormone convertase 2; neuroendocrine
                     convertase 2; KEX2-like endoprotease 2"
                     /codon_start=1
                     /product="neuroendocrine convertase 2 isoform 1
                     preproprotein"
                     /protein_id="NP_002585.2"
                     /db_xref="CCDS:CCDS13125.1"
                     /db_xref="GeneID:5126"
                     /db_xref="HGNC:HGNC:8744"
                     /db_xref="MIM:162151"
                     /translation="MKGGCVSQWKAAAGFLFCVMVFASAERPVFTNHFLVELHKGGED
                     KARQVAAEHGFGVRKLPFAEGLYHFYHNGLAKAKRRRSLHHKQQLERDPRVKMALQQE
                     GFDRKKRGYRDINEIDINMNDPLFTKQWYLINTGQADGTPGLDLNVAEAWELGYTGKG
                     VTIGIMDDGIDYLHPDLASNYNAEASYDFSSNDPYPYPRYTDDWFNSHGTRCAGEVSA
                     AANNNICGVGVAYNSKVAGIRMLDQPFMTDIIEASSISHMPQLIDIYSASWGPTDNGK
                     TVDGPRELTLQAMADGVNKGRGGKGSIYVWASGDGGSYDDCNCDGYASSMWTISINSA
                     INDGRTALYDESCSSTLASTFSNGRKRNPEAGVATTDLYGNCTLRHSGTSAAAPEAAG
                     VFALALEANLGLTWRDMQHLTVLTSKRNQLHDEVHQWRRNGVGLEFNHLFGYGVLDAG
                     AMVKMAKDWKTVPERFHCVGGSVQDPEKIPSTGKLVLTLTTDACEGKENFVRYLEHVQ
                     AVITVNATRRGDLNINMTSPMGTKSILLSRRPRDDDSKVGFDKWPFMTTHTWGEDARG
                     TWTLELGFVGSAPQKGVLKEWTLMLHGTQSAPYIDQVVRDYQSKLAMSKKEELEEELD
                     EAVERSLKSILNKN"
     exon            444..548
                     /gene="PCSK2"
                     /gene_synonym="NEC 2; NEC-2; NEC2; PC2; SPC2"
                     /inference="alignment:Splign:2.1.0"
     exon            549..662
                     /gene="PCSK2"
                     /gene_synonym="NEC 2; NEC-2; NEC2; PC2; SPC2"
                     /inference="alignment:Splign:2.1.0"
     exon            663..771
                     /gene="PCSK2"
                     /gene_synonym="NEC 2; NEC-2; NEC2; PC2; SPC2"
                     /inference="alignment:Splign:2.1.0"
     exon            772..809
                     /gene="PCSK2"
                     /gene_synonym="NEC 2; NEC-2; NEC2; PC2; SPC2"
                     /inference="alignment:Splign:2.1.0"
     exon            810..886
                     /gene="PCSK2"
                     /gene_synonym="NEC 2; NEC-2; NEC2; PC2; SPC2"
                     /inference="alignment:Splign:2.1.0"
     exon            887..975
                     /gene="PCSK2"
                     /gene_synonym="NEC 2; NEC-2; NEC2; PC2; SPC2"
                     /inference="alignment:Splign:2.1.0"
     exon            976..1151
                     /gene="PCSK2"
                     /gene_synonym="NEC 2; NEC-2; NEC2; PC2; SPC2"
                     /inference="alignment:Splign:2.1.0"
     exon            1152..1367
                     /gene="PCSK2"
                     /gene_synonym="NEC 2; NEC-2; NEC2; PC2; SPC2"
                     /inference="alignment:Splign:2.1.0"
     exon            1368..1468
                     /gene="PCSK2"
                     /gene_synonym="NEC 2; NEC-2; NEC2; PC2; SPC2"
                     /inference="alignment:Splign:2.1.0"
     exon            1469..1696
                     /gene="PCSK2"
                     /gene_synonym="NEC 2; NEC-2; NEC2; PC2; SPC2"
                     /inference="alignment:Splign:2.1.0"
     exon            1697..4691
                     /gene="PCSK2"
                     /gene_synonym="NEC 2; NEC-2; NEC2; PC2; SPC2"
                     /inference="alignment:Splign:2.1.0"
     regulatory      2374..2379
                     /regulatory_class="polyA_signal_sequence"
                     /gene="PCSK2"
                     /gene_synonym="NEC 2; NEC-2; NEC2; PC2; SPC2"
                     /note="hexamer: AATATA"
     polyA_site      2398
                     /gene="PCSK2"
                     /gene_synonym="NEC 2; NEC-2; NEC2; PC2; SPC2"
                     /note="major polyA site"
     regulatory      4275..4280
                     /regulatory_class="polyA_signal_sequence"
                     /gene="PCSK2"
                     /gene_synonym="NEC 2; NEC-2; NEC2; PC2; SPC2"
                     /note="hexamer: ATTAAA"
     polyA_site      4301
                     /gene="PCSK2"
                     /gene_synonym="NEC 2; NEC-2; NEC2; PC2; SPC2"
     regulatory      4669..4674
                     /regulatory_class="polyA_signal_sequence"
                     /gene="PCSK2"
                     /gene_synonym="NEC 2; NEC-2; NEC2; PC2; SPC2"
                     /note="hexamer: AATAAA"
     polyA_site      4691
                     /gene="PCSK2"
                     /gene_synonym="NEC 2; NEC-2; NEC2; PC2; SPC2"
                     /note="major polyA site"
ORIGIN      
        1 gctctttctc tccggtacac acagctcccc acattcgcac ccctgcccgc gcgccgggcc
       61 gcctgactgc acggcttccc ctccagccag atgctggaga acacacactg attcgctgct
      121 ttccaagacc ctgttcagtc tctttctcta tacaaagatt tttttaaaaa ctatatataa
      181 gaattcttta tttgcaccct ccctccgagt cccctgctcc gccagcctgc gcgcctccta
      241 gcaccacttt tcactcccaa agaaggatga agggtggttg tgtctcccag tggaaggcgg
      301 ccgccgggtt cctcttctgt gtcatggttt ttgcatctgc tgagcgaccg gtcttcacga
      361 atcattttct tgtggagttg cataaagggg gagaggacaa agctcgccaa gttgcagcag
      421 aacacggctt tggagtccga aagcttccct ttgctgaagg tctgtaccac ttttatcaca
      481 atggccttgc aaaggccaag agaagacgca gcctacacca caagcagcag ctggagagag
      541 accccagggt aaagatggct ttgcagcagg aaggatttga ccgaaaaaag cgaggttaca
      601 gagacatcaa tgagatcgac atcaacatga acgatcctct ttttacaaag cagtggtatc
      661 tgatcaatac tgggcaagct gatggcactc ctggccttga tttgaatgtg gctgaagcct
      721 gggagctggg atacacaggg aaaggtgtta ccattggaat tatggatgat gggattgact
      781 atctccaccc ggacctggcc tccaactata atgccgaagc aagttacgac ttcagcagca
      841 acgaccccta tccttaccct cggtacacag atgactggtt taacagccac gggacccgat
      901 gtgcaggaga agtttctgct gccgccaaca acaatatctg tggagttgga gtagcataca
      961 actccaaggt tgcaggcatc cggatgctgg accagccatt catgacagac atcatcgagg
     1021 cctcctccat cagtcatatg ccacagctga ttgacatcta cagcgccagc tggggcccca
     1081 cagacaacgg caagacagtg gatgggcccc gggagctcac gctgcaggcc atggccgatg
     1141 gcgtgaacaa gggccgcggc ggcaaaggca gcatctacgt gtgggcctcc ggggacggcg
     1201 gcagctatga cgactgcaac tgcgacggct acgcctccag catgtggacc atctccatca
     1261 actcagccat caacgacggc aggactgccc tgtacgacga gagctgctct tccaccttgg
     1321 cttccacctt cagcaacggg aggaaaagga accccgaggc cggtgtggca accacagatt
     1381 tgtacggcaa ctgcactctg aggcattctg ggacatctgc agctgccccc gaggcagctg
     1441 gtgtgtttgc actggctctg gaggctaacc tgggtctgac ctggcgggac atgcagcatc
     1501 tgactgtgct cacctccaaa cggaaccagc ttcacgacga ggtccatcag tggcggcgca
     1561 atggggtcgg cctggaattt aatcacctct ttggctacgg ggtccttgat gcaggtgcca
     1621 tggtgaaaat ggctaaagac tggaaaaccg tgcctgagag attccactgt gtgggaggct
     1681 ccgtgcagga ccctgagaaa ataccatcca ctggcaagtt ggtgctgaca ctcacaaccg
     1741 acgcctgtga ggggaaggaa aattttgtcc gctacctgga gcatgtccag gctgtcatca
     1801 cggtcaacgc aaccagaaga ggagacctga acatcaacat gacttcccct atgggcacca
     1861 agtccatttt gctgagccgg cgtccaaggg atgacgactc caaggtgggc tttgacaagt
     1921 ggcctttcat gaccactcac acgtgggggg aagacgcccg aggcacctgg accctggagc
     1981 tgggatttgt cggcagcgcc ccgcagaagg gggtgctgaa ggagtggacc ctgatgctgc
     2041 atggcactca gagtgccccg tacatcgacc aggtggtgcg ggattaccag tccaagttgg
     2101 ccatgtccaa gaaagaggag ctggaggaag agctggacga agccgtggag agaagcctga
     2161 aaagcatcct taacaagaac tagcgctgca catccgcctt tcccaccgcc ctccctcccc
     2221 agctccgcct ctgtcctcgc tccacgtttc aggcaggcac ctagcaattc catcacccgt
     2281 acaggcaatt ccgtcttctt aatctgaagc ttcactcact gtcaatgatt attttcatta
     2341 caatggaaac aatctttttt actctatgcc ccaaatatag cgttcccaac aacatccatg
     2401 tcctatgtgt gactctaaat tctttatttc tgtcattcaa atgggtgata tcctgaaaaa
     2461 aaaaaaaaaa aaaaaactgg gacagctttc ccctcatttt tttttttgtt tctgagaaaa
     2521 gaacgtattt taaaagccac atagagtgac tccaagaaca attgtccatg gtctcaaaca
     2581 aggggctgtt acataacaag aaaatcaaag ctgaggacag ggtgtgagcg ccacatctct
     2641 gaaagcacag gagacactgt gctataaatc ctttggggag cgatgttttg aatttagtga
     2701 gatttaccag ggatgtagat taaggtgatg tgattcaaaa gatgccattc atagagagcc
     2761 ctagttactg catggggaaa gagatccagg aagcatgagt gctggatatt ttactaccaa
     2821 tgccaagata attcactcta ctcagccggc gtggcaaata taaaacttac agagcgtggc
     2881 tgtgctctca ccagctgctg ctctgagtta tgttaaaatc cgctagagca gcccaaattt
     2941 ttctcagttt gtatagagtt catcccagcc ccaattttct ggggctcctc acatagctac
     3001 ccaaaagaga aaaaaaatta agacaagcct ggcaacacac ctggtgaaga gtagtttact
     3061 agcttttcaa acaagaatgt cccttttcct aagtcacttt gaggtgtctc aatctgatct
     3121 gagtgagagg cgacaggagt attttttttt ttttacagct ttacacacac agatgtgggc
     3181 tttgatttcc aagtaatata atggaagaga aatctcatac tcccccacag tttgatgtca
     3241 ttaatgtgtt gggaaaaagg cctctgtccc ggaagagtca tgggaggtga aaggggcacg
     3301 tttgaagatg cgagcgctat cttcacatag ttctccagtt gtatggagcc tcttctgcca
     3361 agagagggcc atgcaattca tcccagagga acctgaggcc tgaaggaggt gagagaagac
     3421 ctctgtgagg aaagcacaca gtcaccttct cggcaactaa gcagtccctg agaccattta
     3481 acatgcaacc cgaaggttat ggtcaatccc aaaagtcacc actccattcc caactagaca
     3541 ttaccaaagt gacctaccca gagattgctt ctcatcccca gtcccaatgc acatccattc
     3601 ccaagaaatg ctttgtcttc agcctctcca ggcaccatct cccttcctgt gggagcagag
     3661 agcttagcct ggagcacctt tccttcaagc cagcaacaca gagcactagg ttcaattccc
     3721 tgaaggtggc cactttaaga gagaaatctg aaaaccccat ttgctttctt ttctcccata
     3781 ttggcatgga tttctgtctt ctctaacacc ttgtgacctt ctctatatca tgctttaaag
     3841 tgtaataata tgatttttta aaagaaattt attacttgtt gcaaaggtct ttttaaacca
     3901 gtttagattt caagaaaaaa taaatggaaa tcatcgaaaa ttcatttcac attaatggtc
     3961 taaaaataaa ccaaaggaca ttatgtgtgc atgtgtgtat aagtgcacac agaaatatat
     4021 atacatatgt agactatata catgtgtgta tatatgtgta tatatacata cacttgtata
     4081 aatgtatata cacatatacc tataatgtgt gtatgtgtat ttattgaaga aacagatacc
     4141 atactcattt ctaaaagaat attcagagaa tatcaagatg attctggctg aaaaaggcca
     4201 gtggaaattc aggtgaaaat gttcatcaat tcccattgca tcacctctgt aatttttcag
     4261 ctctctgtat aaacattaaa tgtcttatat agcagcaaaa atataaaata gttgtccata
     4321 ttttcacagg tgtggtgtaa tttataaaat tagaaagcaa cttatcagct acttaagaga
     4381 aatggcaagt tttgatatga gtatacaata tataaaaata tatatagtgc tatatatata
     4441 aatatttggt ctctatttca ttttttgcat cagtattaat actaaaatat gtctcgctag
     4501 tgatgttttt atgatatccc tgatcctaac tgaagagaca gttatttata gtcatttatt
     4561 ttaaaaaatg aaaataagtg aataataatt aggttaacat tgttgctccc tgtgacaaaa
     4621 ttttataagc aaatttcaaa agacatgttg taaattagga ggctcaacaa taaaacatta
     4681 tgctccagaa a
//
