LOCUS       NM_001873               2582 bp    mRNA    linear   PRI 09-FEB-2025
DEFINITION  Homo sapiens carboxypeptidase E (CPE), mRNA.
ACCESSION   NM_001873
VERSION     NM_001873.4
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 2582)
  AUTHORS   Minchenko,O.H., Abramchuk,A.I., Khita,O.O., Sliusar,M.Y.,
            Viletska,Y.M. and Minchenko,D.O.
  TITLE     Endoplasmic reticulum stress-dependent regulation of
            carboxypeptidase E expression in glioblastoma cells
  JOURNAL   Endocr Regul 58 (1), 206-214 (2024)
   PUBMED   39352777
  REMARK    GeneRIF: Endoplasmic reticulum stress-dependent regulation of
            carboxypeptidase E expression in glioblastoma cells.
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 2582)
  AUTHORS   Fan,F.C., Du,Y., Zheng,W.H., Loh,Y.P. and Cheng,Y.
  TITLE     Carboxypeptidase E conditional knockout mice exhibit learning and
            memory deficits and neurodegeneration
  JOURNAL   Transl Psychiatry 13 (1), 135 (2023)
   PUBMED   37100779
  REMARK    GeneRIF: Carboxypeptidase E conditional knockout mice exhibit
            learning and memory deficits and neurodegeneration.
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 2582)
  AUTHORS   Sharma,V.K., Yang,X., Kim,S.K., Mafi,A., Saiz-Sanchez,D.,
            Villanueva-Anguita,P., Xiao,L., Inoue,A., Goddard,W.A. 3rd and
            Loh,Y.P.
  TITLE     Novel interaction between neurotrophic
            factor-alpha1/carboxypeptidase E and serotonin receptor, 5-HTR1E,
            protects human neurons against oxidative/neuroexcitotoxic stress
            via beta-arrestin/ERK signaling
  JOURNAL   Cell Mol Life Sci 79 (1), 24 (2021)
   PUBMED   34966948
  REMARK    GeneRIF: Novel interaction between neurotrophic
            factor-alpha1/carboxypeptidase E and serotonin receptor, 5-HTR1E,
            protects human neurons against oxidative/neuroexcitotoxic stress
            via beta-arrestin/ERK signaling.
            Erratum:[Cell Mol Life Sci. 2023 Feb 20;80(3):65. doi:
            10.1007/s00018-023-04711-0.. PMID: 36808009]
            Publication Status: Online-Only
REFERENCE   4  (bases 1 to 2582)
  AUTHORS   Lou,H. and Loh,Y.P.
  TITLE     Silencing of Carboxypeptidase E expression inhibits proliferation
            and invasion of Panc-1 pancreatic cancer cells
  JOURNAL   F1000Res 10, 489 (2021)
   PUBMED   35528956
  REMARK    GeneRIF: Silencing of Carboxypeptidase E expression inhibits
            proliferation and invasion of Panc-1 pancreatic cancer cells.
            Publication Status: Online-Only
REFERENCE   5  (bases 1 to 2582)
  AUTHORS   Sapio,M.R. and Fricker,L.D.
  TITLE     Carboxypeptidases in disease: insights from peptidomic studies
  JOURNAL   Proteomics Clin Appl 8 (5-6), 327-337 (2014)
   PUBMED   24470285
  REMARK    Review article
REFERENCE   6  (bases 1 to 2582)
  AUTHORS   O'Rahilly,S., Gray,H., Humphreys,P.J., Krook,A., Polonsky,K.S.,
            White,A., Gibson,S., Taylor,K. and Carr,C.
  TITLE     Brief report: impaired processing of prohormones associated with
            abnormalities of glucose homeostasis and adrenal function
  JOURNAL   N Engl J Med 333 (21), 1386-1390 (1995)
   PUBMED   7477119
REFERENCE   7  (bases 1 to 2582)
  AUTHORS   Song,L. and Fricker,L.
  TITLE     Processing of procarboxypeptidase E into carboxypeptidase E occurs
            in secretory vesicles
  JOURNAL   J Neurochem 65 (1), 444-453 (1995)
   PUBMED   7790890
REFERENCE   8  (bases 1 to 2582)
  AUTHORS   Naggert,J.K., Fricker,L.D., Varlamov,O., Nishina,P.M., Rouille,Y.,
            Steiner,D.F., Carroll,R.J., Paigen,B.J. and Leiter,E.H.
  TITLE     Hyperproinsulinaemia in obese fat/fat mice associated with a
            carboxypeptidase E mutation which reduces enzyme activity
  JOURNAL   Nat Genet 10 (2), 135-142 (1995)
   PUBMED   7663508
REFERENCE   9  (bases 1 to 2582)
  AUTHORS   Manser,E., Fernandez,D., Loo,L., Goh,P.Y., Monfries,C., Hall,C. and
            Lim,L.
  TITLE     Human carboxypeptidase E. Isolation and characterization of the
            cDNA, sequence conservation, expression and processing in vitro
  JOURNAL   Biochem J 267 (2), 517-525 (1990)
   PUBMED   2334405
REFERENCE   10 (bases 1 to 2582)
  AUTHORS   Fricker,L.D. and Snyder,S.H.
  TITLE     Enkephalin convertase: purification and characterization of a
            specific enkephalin-synthesizing carboxypeptidase localized to
            adrenal chromaffin granules
  JOURNAL   Proc Natl Acad Sci U S A 79 (12), 3886-3890 (1982)
   PUBMED   6808517
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from X51405.1, AA683379.1,
            AC012504.7 and AA883804.1.
            
            On Nov 23, 2018 this sequence version replaced NM_001873.3.
            
            Summary: This gene encodes a member of the M14 family of
            metallocarboxypeptidases. The encoded preproprotein is
            proteolytically processed to generate the mature peptidase. This
            peripheral membrane protein cleaves C-terminal amino acid residues
            and is involved in the biosynthesis of peptide hormones and
            neurotransmitters, including insulin. This protein may also
            function independently of its peptidase activity, as a neurotrophic
            factor that promotes neuronal survival, and as a sorting receptor
            that binds to regulated secretory pathway proteins, including
            prohormones. Mutations in this gene are implicated in type 2
            diabetes. [provided by RefSeq, Nov 2015].
            
            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 :: SRR1803611.83919.1,
                                           SRR3476690.1065405.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000402744.9/ ENSP00000386104.4
            RefSeq Select criteria :: based on single protein-coding transcript
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-2359              X51405.1           77-2435
            2360-2488           AA683379.1         80-208              c
            2489-2489           AC012504.7         175509-175509
            2490-2582           AA883804.1         3-95                c
FEATURES             Location/Qualifiers
     source          1..2582
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="4"
                     /map="4q32.3"
     gene            1..2582
                     /gene="CPE"
                     /gene_synonym="BDVS; CPH; IDDHH"
                     /note="carboxypeptidase E"
                     /db_xref="GeneID:1363"
                     /db_xref="HGNC:HGNC:2303"
                     /db_xref="MIM:114855"
     exon            1..521
                     /gene="CPE"
                     /gene_synonym="BDVS; CPH; IDDHH"
                     /inference="alignment:Splign:2.1.0"
     CDS             215..1645
                     /gene="CPE"
                     /gene_synonym="BDVS; CPH; IDDHH"
                     /EC_number="3.4.17.10"
                     /note="carboxypeptidase H; enkephalin convertase;
                     prohormone-processing carboxypeptidase; insulin
                     granule-associated carboxypeptidase; cobalt-stimulated
                     chromaffin granule carboxypeptidase; epididymis secretory
                     sperm binding protein; carbocypeptidase E"
                     /codon_start=1
                     /product="carboxypeptidase E preproprotein"
                     /protein_id="NP_001864.1"
                     /db_xref="CCDS:CCDS3810.1"
                     /db_xref="GeneID:1363"
                     /db_xref="HGNC:HGNC:2303"
                     /db_xref="MIM:114855"
                     /translation="MAGRGGSALLALCGALAACGWLLGAEAQEPGAPAAGMRRRRRLQ
                     QEDGISFEYHRYPELREALVSVWLQCTAISRIYTVGRSFEGRELLVIELSDNPGVHEP
                     GEPEFKYIGNMHGNEAVGRELLIFLAQYLCNEYQKGNETIVNLIHSTRIHIMPSLNPD
                     GFEKAASQPGELKDWFVGRSNAQGIDLNRNFPDLDRIVYVNEKEGGPNNHLLKNMKKI
                     VDQNTKLAPETKAVIHWIMDIPFVLSANLHGGDLVANYPYDETRSGSAHEYSSSPDDA
                     IFQSLARAYSSFNPAMSDPNRPPCRKNDDDSSFVDGTTNGGAWYSVPGGMQDFNYLSS
                     NCFEITVELSCEKFPPEETLKTYWEDNKNSLISYLEQIHRGVKGFVRDLQGNPIANAT
                     ISVEGIDHDVTSAKDGDYWRLLIPGNYKLTASAPGYLAITKKVAVPYSPAAGVDFELE
                     SFSERKEEEKEELMEWWKMMSETLNF"
     exon            522..718
                     /gene="CPE"
                     /gene_synonym="BDVS; CPH; IDDHH"
                     /inference="alignment:Splign:2.1.0"
     exon            719..886
                     /gene="CPE"
                     /gene_synonym="BDVS; CPH; IDDHH"
                     /inference="alignment:Splign:2.1.0"
     exon            887..1004
                     /gene="CPE"
                     /gene_synonym="BDVS; CPH; IDDHH"
                     /inference="alignment:Splign:2.1.0"
     exon            1005..1187
                     /gene="CPE"
                     /gene_synonym="BDVS; CPH; IDDHH"
                     /inference="alignment:Splign:2.1.0"
     exon            1188..1327
                     /gene="CPE"
                     /gene_synonym="BDVS; CPH; IDDHH"
                     /inference="alignment:Splign:2.1.0"
     exon            1328..1427
                     /gene="CPE"
                     /gene_synonym="BDVS; CPH; IDDHH"
                     /inference="alignment:Splign:2.1.0"
     exon            1428..1546
                     /gene="CPE"
                     /gene_synonym="BDVS; CPH; IDDHH"
                     /inference="alignment:Splign:2.1.0"
     exon            1547..2582
                     /gene="CPE"
                     /gene_synonym="BDVS; CPH; IDDHH"
                     /inference="alignment:Splign:2.1.0"
     regulatory      2205..2210
                     /regulatory_class="polyA_signal_sequence"
                     /gene="CPE"
                     /gene_synonym="BDVS; CPH; IDDHH"
                     /note="hexamer: AATAAA"
     polyA_site      2229
                     /gene="CPE"
                     /gene_synonym="BDVS; CPH; IDDHH"
                     /note="major polyA site"
     polyA_site      2381
                     /gene="CPE"
                     /gene_synonym="BDVS; CPH; IDDHH"
     polyA_site      2480
                     /gene="CPE"
                     /gene_synonym="BDVS; CPH; IDDHH"
     polyA_site      2500
                     /gene="CPE"
                     /gene_synonym="BDVS; CPH; IDDHH"
     regulatory      2562..2567
                     /regulatory_class="polyA_signal_sequence"
                     /gene="CPE"
                     /gene_synonym="BDVS; CPH; IDDHH"
                     /note="hexamer: TATAAA"
     polyA_site      2582
                     /gene="CPE"
                     /gene_synonym="BDVS; CPH; IDDHH"
ORIGIN      
        1 agtagtgcag cccgtggagc cgcggctttg cccgtctcct ctgggtggcc ccagtgcgcg
       61 ggctgacact cattcagccg gggaaggtga ggcgagtaga ggctggtgcg gaacttgccg
      121 cccccagcag cgccggcggg ctaagcccag ggccgggcag acaaaagagg ccgcccgcgt
      181 aggaaggcac ggccggcggc ggcggagcgc agcgatggcc gggcgagggg gcagcgcgct
      241 gctggctctg tgcggggcac tggctgcctg cgggtggctc ctgggcgccg aagcccagga
      301 gcccggggcg cccgcggcgg gcatgaggcg gcgccggcgg ctgcagcaag aggacggcat
      361 ctccttcgag taccaccgct accccgagct gcgcgaggcg ctcgtgtccg tgtggctgca
      421 gtgcaccgcc atcagcagga tttacacggt ggggcgcagc ttcgagggcc gggagctcct
      481 ggtcatcgag ctgtccgaca accctggcgt ccatgagcct ggtgagcctg aatttaaata
      541 cattgggaat atgcatggga atgaggctgt tggacgagaa ctgctcattt tcttggccca
      601 gtacctatgc aacgaatacc agaaggggaa cgagacaatt gtcaacctga tccacagtac
      661 ccgcattcac atcatgcctt ccctgaaccc agatggcttt gagaaggcag cgtctcagcc
      721 tggtgaactc aaggactggt ttgtgggtcg aagcaatgcc cagggaatag atctgaaccg
      781 gaactttcca gacctggata ggatagtgta cgtgaatgag aaagaaggtg gtccaaataa
      841 tcatctgttg aaaaatatga agaaaattgt ggatcaaaac acaaagcttg ctcctgagac
      901 caaggctgtc attcattgga ttatggatat tccttttgtg ctttctgcca atctccatgg
      961 aggagacctt gtggccaatt atccatatga tgagacgcgg agtggtagtg ctcacgaata
     1021 cagctcctcc ccagatgacg ccattttcca aagcttggcc cgggcatact cttctttcaa
     1081 cccggccatg tctgacccca atcggccacc atgtcgcaag aatgatgatg acagcagctt
     1141 tgtagatgga accaccaacg gtggtgcttg gtacagcgta cctggaggga tgcaagactt
     1201 caattacctt agcagcaact gttttgagat caccgtggag cttagctgtg agaagttccc
     1261 acctgaagag actctgaaga cctactggga ggataacaaa aactccctca ttagctacct
     1321 tgagcagata caccgaggag ttaaaggatt tgtccgagac cttcaaggta acccaattgc
     1381 gaatgccacc atctccgtgg aaggaataga ccacgatgtt acatccgcaa aggatggtga
     1441 ttactggaga ttgcttatac ctggaaacta taaacttaca gcctcagctc caggctatct
     1501 ggcaataaca aagaaagtgg cagttcctta cagccctgct gctggggttg attttgaact
     1561 ggagtcattt tctgaaagga aagaagagga gaaggaagaa ttgatggaat ggtggaaaat
     1621 gatgtcagaa actttaaatt tttaaaaagg cttctagtta gctgctttaa atctatctat
     1681 ataatgtagt atgatgtaat gtggtctttt ttttagattt tgtgcagtta atacttaaca
     1741 ttgatttatt ttttaatcat ttaaatatta atcaactttc cttaaaataa atagcctctt
     1801 aggtaaaaat ataagaactt gatatatttc attctcttat atagtattca ttttcctacc
     1861 tatattacac aaaaaagtat agaaaagatt taagtaattt tgccatccta ggcttaaatg
     1921 caatattcct ggtattattt acaatgcaga attttttgag taattctagc tttcaaaaat
     1981 tagtgaagtt cttttactgt aattggtgac aatgtcacat aatgaatgct attgaaaagg
     2041 ttaacagata cagctcggag ttgtgagcac tctactgcaa gacttaaata gttcagtata
     2101 aattgtcgtt tttttcttgt gctgactaac tataagcatg atcttgttaa tgcatttttg
     2161 atgggaagaa aaggtacatg tttacaaaga ggttttatga aaagaataaa aattgacttc
     2221 ttgcttgtac atataggagc aatactatta tattatgtag tccgttaaca ctacttaaaa
     2281 gtttagggtt ttctcttggt tgtagagtgg cccagaattg cattctgaat gaataaaggt
     2341 taaaaaaaaa tccccagtgc atgtatttca gttctctaag atttttggtc tggcattgtg
     2401 gtcttatgat gaaaacatgt atcctcttaa tggcggcttc tcatatattc atcctgtaca
     2461 ttttaaaatt tgttaagcaa ctactgtgtg ctaagcactg catagcctct atgtatgtta
     2521 ttgtggcagg caaaaggttc tgattttggg cacaaccttt atataaataa cacaaaaatt
     2581 aa
//
