LOCUS       NM_001025200             870 bp    mRNA    linear   PRI 05-APR-2024
DEFINITION  Homo sapiens chymotrypsinogen B2 (CTRB2), mRNA.
ACCESSION   NM_001025200 XM_496169
VERSION     NM_001025200.4
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 870)
  AUTHORS   Nemeth,B.Z., Demcsak,A., Micsonai,A., Kiss,B., Schlosser,G.,
            Geisz,A., Hegyi,E., Sahin-Toth,M. and Pal,G.
  TITLE     Arg236 in human chymotrypsin B2 (CTRB2) is a key determinant of
            high enzyme activity, trypsinogen degradation capacity, and
            protection against pancreatitis
  JOURNAL   Biochim Biophys Acta Proteins Proteom 1870 (9), 140831 (2022)
   PUBMED   35934298
  REMARK    GeneRIF: Arg236 in human chymotrypsin B2 (CTRB2) is a key
            determinant of high enzyme activity, trypsinogen degradation
            capacity, and protection against pancreatitis.
REFERENCE   2  (bases 1 to 870)
  AUTHORS   Jermusyk,A., Zhong,J., Connelly,K.E., Gordon,N., Perera,S.,
            Abdolalizadeh,E., Zhang,T., O'Brien,A., Hoskins,J.W., Collins,I.,
            Eiser,D., Yuan,C., Risch,H.A., Jacobs,E.J., Li,D., Du,M.,
            Stolzenberg-Solomon,R.Z., Klein,A.P., Smith,J.P., Wolpin,B.M.,
            Chanock,S.J., Shi,J., Petersen,G.M., Westlake,C.J. and
            Amundadottir,L.T.
  CONSRTM   PanScan Consortium; PanC4 Consortium
  TITLE     A 584 bp deletion in CTRB2 inhibits chymotrypsin B2 activity and
            secretion and confers risk of pancreatic cancer
  JOURNAL   Am J Hum Genet 108 (10), 1852-1865 (2021)
   PUBMED   34559995
  REMARK    GeneRIF: A 584 bp deletion in CTRB2 inhibits chymotrypsin B2
            activity and secretion and confers risk of pancreatic cancer.
REFERENCE   3  (bases 1 to 870)
  AUTHORS   Seltsam,K., Pentner,C., Weigl,F., Sutedjo,S., Zimmer,C., Beer,S.,
            Bugert,P., Ewers,M., Ruffert,C., Michl,P., Laumen,H., Witt,H. and
            Rosendahl,J.
  TITLE     Sequencing of the complex CTRB1-CTRB2 locus in chronic pancreatitis
  JOURNAL   Pancreatology 20 (8), 1598-1603 (2020)
   PUBMED   33036922
  REMARK    GeneRIF: Sequencing of the complex CTRB1-CTRB2 locus in chronic
            pancreatitis.
REFERENCE   4  (bases 1 to 870)
  AUTHORS   Rosendahl,J., Kirsten,H., Hegyi,E., Kovacs,P., Weiss,F.U.,
            Laumen,H., Lichtner,P., Ruffert,C., Chen,J.M., Masson,E., Beer,S.,
            Zimmer,C., Seltsam,K., Algul,H., Buhler,F., Bruno,M.J., Bugert,P.,
            Burkhardt,R., Cavestro,G.M., Cichoz-Lach,H., Farre,A., Frank,J.,
            Gambaro,G., Gimpfl,S., Grallert,H., Griesmann,H., Grutzmann,R.,
            Hellerbrand,C., Hegyi,P., Hollenbach,M., Iordache,S., Jurkowska,G.,
            Keim,V., Kiefer,F., Krug,S., Landt,O., Leo,M.D., Lerch,M.M.,
            Levy,P., Loffler,M., Lohr,M., Ludwig,M., Macek,M., Malats,N.,
            Malecka-Panas,E., Malerba,G., Mann,K., Mayerle,J., Mohr,S., Te
            Morsche,R.H.M., Motyka,M., Mueller,S., Muller,T., Nothen,M.M.,
            Pedrazzoli,S., Pereira,S.P., Peters,A., Pfutzer,R., Real,F.X.,
            Rebours,V., Ridinger,M., Rietschel,M., Rosmann,E., Saftoiu,A.,
            Schneider,A., Schulz,H.U., Soranzo,N., Soyka,M., Simon,P.,
            Skipworth,J., Stickel,F., Strauch,K., Stumvoll,M., Testoni,P.A.,
            Tonjes,A., Werner,L., Werner,J., Wodarz,N., Ziegler,M.,
            Masamune,A., Mossner,J., Ferec,C., Michl,P., P H Drenth,J.,
            Witt,H., Scholz,M. and Sahin-Toth,M.
  CONSRTM   all members of the PanEuropean Working group on ACP
  TITLE     Genome-wide association study identifies inversion in the
            CTRB1-CTRB2 locus to modify risk for alcoholic and non-alcoholic
            chronic pancreatitis
  JOURNAL   Gut 67 (10), 1855-1863 (2018)
   PUBMED   28754779
  REMARK    GeneRIF: An inversion in the CTRB1-CTRB2 locus modifies risk for
            Alcoholic and Non-alcoholic Chronic Pancreatitis indicating that
            common pathomechanisms are involved in these inflammatory
            disorders.
REFERENCE   5  (bases 1 to 870)
  AUTHORS   Tang,X.Y., Zou,W.B., Masson,E., Hu,L.H., Ferec,C., Chen,J.M.,
            Li,Z.S. and Liao,Z.
  TITLE     The CTRB1-CTRB2 risk allele for chronic pancreatitis discovered in
            European populations does not contribute to disease risk variation
            in the Chinese population due to near allele fixation
  JOURNAL   Gut 67 (7), 1368-1369 (2018)
   PUBMED   28951524
REFERENCE   6  (bases 1 to 870)
  AUTHORS   Wolpin,B.M., Rizzato,C., Kraft,P., Kooperberg,C., Petersen,G.M.,
            Wang,Z., Arslan,A.A., Beane-Freeman,L., Bracci,P.M., Buring,J.,
            Canzian,F., Duell,E.J., Gallinger,S., Giles,G.G., Goodman,G.E.,
            Goodman,P.J., Jacobs,E.J., Kamineni,A., Klein,A.P., Kolonel,L.N.,
            Kulke,M.H., Li,D., Malats,N., Olson,S.H., Risch,H.A., Sesso,H.D.,
            Visvanathan,K., White,E., Zheng,W., Abnet,C.C., Albanes,D.,
            Andreotti,G., Austin,M.A., Barfield,R., Basso,D., Berndt,S.I.,
            Boutron-Ruault,M.C., Brotzman,M., Buchler,M.W.,
            Bueno-de-Mesquita,H.B., Bugert,P., Burdette,L., Campa,D.,
            Caporaso,N.E., Capurso,G., Chung,C., Cotterchio,M., Costello,E.,
            Elena,J., Funel,N., Gaziano,J.M., Giese,N.A., Giovannucci,E.L.,
            Goggins,M., Gorman,M.J., Gross,M., Haiman,C.A., Hassan,M.,
            Helzlsouer,K.J., Henderson,B.E., Holly,E.A., Hu,N., Hunter,D.J.,
            Innocenti,F., Jenab,M., Kaaks,R., Key,T.J., Khaw,K.T., Klein,E.A.,
            Kogevinas,M., Krogh,V., Kupcinskas,J., Kurtz,R.C., LaCroix,A.,
            Landi,M.T., Landi,S., Le Marchand,L., Mambrini,A., Mannisto,S.,
            Milne,R.L., Nakamura,Y., Oberg,A.L., Owzar,K., Patel,A.V.,
            Peeters,P.H., Peters,U., Pezzilli,R., Piepoli,A., Porta,M.,
            Real,F.X., Riboli,E., Rothman,N., Scarpa,A., Shu,X.O.,
            Silverman,D.T., Soucek,P., Sund,M., Talar-Wojnarowska,R.,
            Taylor,P.R., Theodoropoulos,G.E., Thornquist,M., Tjonneland,A.,
            Tobias,G.S., Trichopoulos,D., Vodicka,P., Wactawski-Wende,J.,
            Wentzensen,N., Wu,C., Yu,H., Yu,K., Zeleniuch-Jacquotte,A.,
            Hoover,R., Hartge,P., Fuchs,C., Chanock,S.J.,
            Stolzenberg-Solomon,R.S. and Amundadottir,L.T.
  TITLE     Genome-wide association study identifies multiple susceptibility
            loci for pancreatic cancer
  JOURNAL   Nat Genet 46 (9), 994-1000 (2014)
   PUBMED   25086665
REFERENCE   7  (bases 1 to 870)
  AUTHORS   Hou,D.X., Ozawa,K., Tomita,N., Maeda,Y., Hashiguchi,T., Yokoyama,K.
            and Soeda,E.
  TITLE     Genomic cloning and partial characterization of human
            chymotrypsinogen gene
  JOURNAL   Jpn J Hum Genet 38 (4), 371-380 (1993)
   PUBMED   8186414
REFERENCE   8  (bases 1 to 870)
  AUTHORS   Tomita,N., Izumoto,Y., Horii,A., Doi,S., Yokouchi,H., Ogawa,M.,
            Mori,T. and Matsubara,K.
  TITLE     Molecular cloning and nucleotide sequence of human pancreatic
            prechymotrypsinogen cDNA
  JOURNAL   Biochem Biophys Res Commun 158 (2), 569-575 (1989)
   PUBMED   2917002
COMMENT     VALIDATED REFSEQ: This record has undergone validation or
            preliminary review. The reference sequence was derived from
            AK225933.1.
            
            On Nov 22, 2018 this sequence version replaced NM_001025200.3.
            
            Summary: This gene encodes a member of the serine protease family
            of enzymes and forms a principal precursor of the pancreatic
            proteolytic enzymes. The encoded preproprotein is synthesized in
            the acinar cells of the pancreas and secreted into the small
            intestine where it undergoes proteolytic activation to generate a
            functional enzyme. This CTRB2 gene is located head-to-head with the
            related CTRB1 gene. Some human populations have an alternate
            haplotype which inverts a 16.6 Kb region containing portions of
            intron 1, exon 1, and the upstream sequence of the CTRB1 and CTRB2
            genes. In this inversion haplotype exon 1 and flanking sequence is
            swapped in CTRB1 and CTRB2. This inversion is associated with
            differential gene expression and increased risk for chronic
            pancreatitis. The GRCh38 assembly represents the minor allele for
            SNP rs8048956 of the CTRB1 gene. SNP rs8048956 is diagnostic for
            this inversion. [provided by RefSeq, Jan 2021].
            
            ##Evidence-Data-START##
            Transcript exon combination :: AK225933.1, AK291822.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA2142586, SAMEA2145245
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000303037.13/ ENSP00000303963.8
            RefSeq Select criteria :: based on single protein-coding transcript
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-870               AK225933.1         1-870
FEATURES             Location/Qualifiers
     source          1..870
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="16"
                     /map="16q23.1"
     gene            1..870
                     /gene="CTRB2"
                     /note="chymotrypsinogen B2"
                     /db_xref="GeneID:440387"
                     /db_xref="HGNC:HGNC:2522"
                     /db_xref="MIM:619620"
     exon            1..72
                     /gene="CTRB2"
                     /inference="alignment:Splign:2.1.0"
     CDS             21..812
                     /gene="CTRB2"
                     /EC_number="3.4.21.1"
                     /note="chymotrypsin B2"
                     /codon_start=1
                     /product="chymotrypsinogen B2 precursor"
                     /protein_id="NP_001020371.3"
                     /db_xref="CCDS:CCDS32489.1"
                     /db_xref="GeneID:440387"
                     /db_xref="HGNC:HGNC:2522"
                     /db_xref="MIM:619620"
                     /translation="MAFLWLLSCWALLGTTFGCGVPAIHPVLSGLSRIVNGEDAVPGS
                     WPWQVSLQDKTGFHFCGGSLISEDWVVTAAHCGVRTSDVVVAGEFDQGSDEENIQVLK
                     IAKVFKNPKFSILTVNNDITLLKLATPARFSQTVSAVCLPSADDDFPAGTLCATTGWG
                     KTKYNANKTPDKLQQAALPLLSNAECKKSWGRRITDVMICAGASGVSSCMGDSGGPLV
                     CQKDGAWTLVGIVSWGSRTCSTTTPAVYARVAKLIPWVQKILAAN"
     exon            73..176
                     /gene="CTRB2"
                     /inference="alignment:Splign:2.1.0"
     exon            177..256
                     /gene="CTRB2"
                     /inference="alignment:Splign:2.1.0"
     exon            257..335
                     /gene="CTRB2"
                     /inference="alignment:Splign:2.1.0"
     exon            336..516
                     /gene="CTRB2"
                     /inference="alignment:Splign:2.1.0"
     exon            517..650
                     /gene="CTRB2"
                     /inference="alignment:Splign:2.1.0"
     exon            651..870
                     /gene="CTRB2"
                     /inference="alignment:Splign:2.1.0"
     regulatory      850..855
                     /regulatory_class="polyA_signal_sequence"
                     /gene="CTRB2"
                     /note="hexamer: ATTAAA"
     polyA_site      870
                     /gene="CTRB2"
                     /note="major polyA site"
ORIGIN      
        1 acacccctgc cagcggcacc atggctttcc tctggctcct ctcctgctgg gccctcctgg
       61 gtaccacctt cggctgcggg gtccccgcca tccaccctgt gctcagcggc ctgtccagga
      121 tcgtgaatgg ggaggacgcc gtccccggct cctggccctg gcaggtgtcc ctgcaggaca
      181 aaaccggctt ccacttctgc gggggctccc tcatcagcga ggactgggtg gtcaccgctg
      241 cccactgcgg ggtcaggacc tccgacgtgg tcgtggctgg ggagtttgac cagggctctg
      301 acgaggagaa catccaggtc ctgaagatcg ccaaggtctt caagaacccc aagttcagca
      361 ttctgaccgt gaacaatgac atcaccctgc tgaagctggc cacacctgcc cgcttctccc
      421 agacagtgtc cgccgtgtgc ctgcccagcg ccgacgacga cttccccgcg gggacactgt
      481 gtgccaccac aggctggggc aagaccaagt acaacgccaa caagacccct gacaagctgc
      541 agcaggcagc cctgcccctc ctgtccaatg ccgaatgcaa gaagtcctgg ggcaggagga
      601 tcaccgacgt gatgatctgt gccggggcca gtggcgtctc ctcctgcatg ggtgactctg
      661 gaggccccct ggtctgccag aaggacggag cctggaccct ggtgggcatt gtgtcctggg
      721 gcagccgcac ctgctctacc accacgcccg ctgtgtacgc ccgtgtcgcc aagctcatac
      781 cctgggtgca gaagatcctg gccgccaact gagcccgcag ctcctgccac ccctgcctta
      841 agatttccca ttaaatgcat ctgtttagaa
//
