ID CTRC_HUMAN Reviewed; 268 AA. AC Q99895; A8K082; O00765; Q9NUH5; DT 01-JUN-2001, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-2001, sequence version 2. DT 24-JAN-2024, entry version 180. DE RecName: Full=Chymotrypsin-C; DE EC=3.4.21.2; DE AltName: Full=Caldecrin; DE Flags: Precursor; GN Name=CTRC; Synonyms=CLCR; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT TRP-80. RC TISSUE=Pancreas; RX PubMed=8635596; DOI=10.1016/0014-5793(96)00377-8; RA Tomomura A., Akiyama M., Itoh H., Yoshino I., Tomomura M., Nishii Y., RA Noikura T., Saheki T.; RT "Molecular cloning and expression of human caldecrin."; RL FEBS Lett. 386:26-28(1996). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Urinary bladder; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Pancreas; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] OF 17-268. RC TISSUE=Pancreas; RA Sziegoleit A.; RT "A human pancreatic chymotrypsin: biochemical and molecular RT characterization."; RL Submitted (JUN-1997) to the EMBL/GenBank/DDBJ databases. RN [7] RP CHARACTERIZATION. RX PubMed=9538241; DOI=10.1093/oxfordjournals.jbchem.a021971; RA Yoshino-Yasuda I., Kobayashi K., Akiyama M., Itoh H., Tomomura A., RA Saheki T.; RT "Caldecrin is a novel-type serine protease expressed in pancreas, but its RT homologue, elastase IV, is an artifact during cloning derived from RT caldecrin gene."; RL J. Biochem. 123:546-554(1998). RN [8] RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 17-268 IN COMPLEX WITH INHIBITOR, RP FUNCTION, AND DISULFIDE BONDS. RX PubMed=23430245; DOI=10.1074/jbc.m113.457382; RA Batra J., Szabo A., Caulfield T.R., Soares A.S., Sahin-Toth M., RA Radisky E.S.; RT "Long-range electrostatic complementarity governs substrate recognition by RT human chymotrypsin C, a key regulator of digestive enzyme activation."; RL J. Biol. Chem. 288:9848-9859(2013). RN [9] RP VARIANTS PCTT THR-73; TYR-155; SER-217; ARG-217; ILE-235; 247-LYS--ARG-254 RP DEL AND TRP-254, AND VARIANTS HIS-162; GLU-172 AND VAL-200. RX PubMed=18172691; DOI=10.1007/s00439-007-0459-3; RA Masson E., Chen J.M., Scotet V., Le Marechal C., Ferec C.; RT "Association of rare chymotrypsinogen C (CTRC) gene variations in patients RT with idiopathic chronic pancreatitis."; RL Hum. Genet. 123:83-91(2008). RN [10] RP VARIANTS PCTT THR-73; SER-217; ARG-217; ILE-235 AND TRP-254, VARIANTS RP HIS-35; ASN-35; GLN-37; ARG-48; GLU-172; SER-218; ARG-220; ALA-225; LEU-249 RP AND ASN-260, CHARACTERIZATION OF VARIANTS PCTT THR-73; SER-217; ILE-235 AND RP TRP-254, AND CHARACTERIZATION OF VARIANTS GLN-37 AND ARG-48. RX PubMed=18059268; DOI=10.1038/ng.2007.44; RA Rosendahl J., Witt H., Szmola R., Bhatia E., Ozsvari B., Landt O., RA Schulz H.-U., Gress T.M., Pfuetzer R., Loehr M., Kovacs P., Blueher M., RA Stumvoll M., Choudhuri G., Hegyi P., te Morsche R.H.M., Drenth J.P.H., RA Truninger K., Macek M. Jr., Puhl G., Witt U., Schmidt H., Buening C., RA Ockenga J., Kage A., Groneberg D.A., Nickel R., Berg T., Wiedenmann B., RA Boedeker H., Keim V., Moessner J., Teich N., Sahin-Toth M.; RT "Chymotrypsin C (CTRC) variants that diminish activity or secretion are RT associated with chronic pancreatitis."; RL Nat. Genet. 40:78-82(2008). RN [11] RP VARIANTS LYS-225; GLN-254 AND SER-263. RX PubMed=19407484; DOI=10.1159/000199437; RA Chang M.C., Chang Y.T., Wei S.C., Liang P.C., Jan I.S., Su Y.N., Kuo C.H., RA Wong J.M.; RT "Association of novel chymotrypsin C gene variations and haplotypes in RT patients with chronic pancreatitis in Chinese in Taiwan."; RL Pancreatology 9:287-292(2009). RN [12] RP VARIANTS GLN-29; MET-209; ALA-239; CYS-239; GLU-247 AND TRP-254. RX PubMed=23135764; DOI=10.1136/gutjnl-2012-303860; RA Masamune A., Nakano E., Kume K., Kakuta Y., Ariga H., Shimosegawa T.; RT "Identification of novel missense CTRC variants in Japanese patients with RT chronic pancreatitis."; RL Gut 62:653-654(2013). RN [13] RP VARIANTS ARG-48; GLU-172; CYS-246 AND THR-257, AND VARIANTS PCTT THR-73; RP ILE-235 AND TRP-254. RX PubMed=22580415; DOI=10.1136/gutjnl-2012-302448; RA Paliwal S., Bhaskar S., Mani K.R., Reddy D.N., Rao G.V., Singh S.P., RA Thomas V., Chandak G.R.; RT "Comprehensive screening of chymotrypsin C (CTRC) gene in tropical calcific RT pancreatitis identifies novel variants."; RL Gut 62:1602-1606(2013). RN [14] RP VARIANTS ARG-18; TYR-35 AND SER-227, VARIANTS PCTT ARG-178 AND GLU-250, RP CHARACTERIZATION OF VARIANTS ARG-18; TYR-35; ARG-48; ARG-61; ARG-220 AND RP GLN-254, AND CHARACTERIZATION OF VARIANTS PCTT VAL-32; THR-73; TYR-155; RP ARG-178; ARG-217; SER-217; ILE-235; 247-LYS--ARG-254 DEL; LEU-249; GLU-250 RP AND TRP-254. RX PubMed=22942235; DOI=10.1136/gutjnl-2012-303090; RA Beer S., Zhou J., Szabo A., Keiles S., Chandak G.R., Witt H., RA Sahin-Toth M.; RT "Comprehensive functional analysis of chymotrypsin C (CTRC) variants RT reveals distinct loss-of-function mechanisms associated with pancreatitis RT risk."; RL Gut 62:1616-1624(2013). CC -!- FUNCTION: Regulates activation and degradation of trypsinogens and CC procarboxypeptidases by targeting specific cleavage sites within their CC zymogen precursors. Has chymotrypsin-type protease activity and CC hypocalcemic activity. {ECO:0000269|PubMed:23430245}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Preferential cleavage: Leu-|-Xaa, Tyr-|-Xaa, Phe-|-Xaa, Met-|- CC Xaa, Trp-|-Xaa, Gln-|-Xaa, Asn-|-Xaa.; EC=3.4.21.2; CC -!- INTERACTION: CC Q99895; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-10295404, EBI-3867333; CC Q99895; Q8TF65: GIPC2; NbExp=3; IntAct=EBI-10295404, EBI-712067; CC Q99895; O76011: KRT34; NbExp=3; IntAct=EBI-10295404, EBI-1047093; CC Q99895; Q07627: KRTAP1-1; NbExp=3; IntAct=EBI-10295404, EBI-11959885; CC Q99895; P60409: KRTAP10-7; NbExp=3; IntAct=EBI-10295404, EBI-10172290; CC Q99895; P60410: KRTAP10-8; NbExp=3; IntAct=EBI-10295404, EBI-10171774; CC Q99895; Q9BYR8: KRTAP3-1; NbExp=3; IntAct=EBI-10295404, EBI-9996449; CC Q99895; Q3LI66: KRTAP6-2; NbExp=3; IntAct=EBI-10295404, EBI-11962084; CC Q99895; Q9BYQ4: KRTAP9-2; NbExp=3; IntAct=EBI-10295404, EBI-1044640; CC Q99895; Q99750: MDFI; NbExp=3; IntAct=EBI-10295404, EBI-724076; CC Q99895; Q8NI38: NFKBID; NbExp=3; IntAct=EBI-10295404, EBI-10271199; CC Q99895; Q96LM6: SPMIP9; NbExp=3; IntAct=EBI-10295404, EBI-743976; CC Q99895; A8MV65-2: VGLL3; NbExp=3; IntAct=EBI-10295404, EBI-11957216; CC -!- TISSUE SPECIFICITY: Pancreas. CC -!- DISEASE: Pancreatitis, hereditary (PCTT) [MIM:167800]: A disease CC characterized by pancreas inflammation, permanent destruction of the CC pancreatic parenchyma, maldigestion, and severe abdominal pain attacks. CC {ECO:0000269|PubMed:18059268, ECO:0000269|PubMed:18172691, CC ECO:0000269|PubMed:22580415, ECO:0000269|PubMed:22942235}. Note=Disease CC susceptibility is associated with variants affecting the gene CC represented in this entry. Loss-of-function CTRC variants predispose to CC pancreatitis by diminishing its protective trypsin-degrading activity CC (PubMed:18059268). They cause loss of function by one or more of three CC mechanisms: reduced secretion, catalytic defect and increased CC degradation by trypsin (PubMed:22942235). {ECO:0000269|PubMed:18059268, CC ECO:0000269|PubMed:22942235}. CC -!- SIMILARITY: Belongs to the peptidase S1 family. Elastase subfamily. CC {ECO:0000255|PROSITE-ProRule:PRU00274}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; S82198; AAB47104.2; ALT_SEQ; mRNA. DR EMBL; AK289447; BAF82136.1; -; mRNA. DR EMBL; AL031283; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471167; EAW51726.1; -; Genomic_DNA. DR EMBL; BC015118; AAH15118.1; -; mRNA. DR EMBL; Y13697; CAA74031.1; -; mRNA. DR CCDS; CCDS156.1; -. DR PIR; S68825; S68825. DR PIR; S68826; S68826. DR RefSeq; NP_009203.2; NM_007272.2. DR PDB; 4H4F; X-ray; 1.90 A; A=30-268, Q=17-26. DR PDBsum; 4H4F; -. DR AlphaFoldDB; Q99895; -. DR SMR; Q99895; -. DR BioGRID; 116458; 19. DR IntAct; Q99895; 14. DR STRING; 9606.ENSP00000365116; -. DR BindingDB; Q99895; -. DR ChEMBL; CHEMBL2386; -. DR DrugCentral; Q99895; -. DR GuidetoPHARMACOLOGY; 2341; -. DR MEROPS; S01.157; -. DR GlyCosmos; Q99895; 3 sites, No reported glycans. DR GlyGen; Q99895; 3 sites. DR BioMuta; CTRC; -. DR DMDM; 14194504; -. DR MassIVE; Q99895; -. DR PaxDb; 9606-ENSP00000365116; -. DR PeptideAtlas; Q99895; -. DR ProteomicsDB; 78519; -. DR Antibodypedia; 28845; 192 antibodies from 23 providers. DR DNASU; 11330; -. DR Ensembl; ENST00000375949.5; ENSP00000365116.4; ENSG00000162438.12. DR GeneID; 11330; -. DR KEGG; hsa:11330; -. DR MANE-Select; ENST00000375949.5; ENSP00000365116.4; NM_007272.3; NP_009203.2. DR UCSC; uc001awi.2; human. DR AGR; HGNC:2523; -. DR CTD; 11330; -. DR DisGeNET; 11330; -. DR GeneCards; CTRC; -. DR GeneReviews; CTRC; -. DR HGNC; HGNC:2523; CTRC. DR HPA; ENSG00000162438; Tissue enriched (pancreas). DR MalaCards; CTRC; -. DR MIM; 167800; phenotype. DR MIM; 601405; gene. DR neXtProt; NX_Q99895; -. DR OpenTargets; ENSG00000162438; -. DR Orphanet; 676; Hereditary chronic pancreatitis. DR Orphanet; 64740; NON RARE IN EUROPE: Recurrent acute pancreatitis. DR Orphanet; 103918; Tropical pancreatitis. DR PharmGKB; PA27024; -. DR VEuPathDB; HostDB:ENSG00000162438; -. DR eggNOG; KOG3627; Eukaryota. DR GeneTree; ENSGT00940000153216; -. DR HOGENOM; CLU_006842_0_4_1; -. DR InParanoid; Q99895; -. DR OMA; DWISSKM; -. DR OrthoDB; 4629979at2759; -. DR PhylomeDB; Q99895; -. DR TreeFam; TF330455; -. DR BRENDA; 3.4.21.2; 2681. DR PathwayCommons; Q99895; -. DR SignaLink; Q99895; -. DR BioGRID-ORCS; 11330; 16 hits in 1147 CRISPR screens. DR ChiTaRS; CTRC; human. DR GeneWiki; Chymotrypsin-C; -. DR GenomeRNAi; 11330; -. DR Pharos; Q99895; Tchem. DR PRO; PR:Q99895; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; Q99895; Protein. DR Bgee; ENSG00000162438; Expressed in body of pancreas and 110 other cell types or tissues. DR ExpressionAtlas; Q99895; baseline and differential. DR GO; GO:0008233; F:peptidase activity; IDA:MGI. DR GO; GO:0004252; F:serine-type endopeptidase activity; IBA:GO_Central. DR GO; GO:0006874; P:intracellular calcium ion homeostasis; IDA:MGI. DR GO; GO:0006508; P:proteolysis; IDA:MGI. DR CDD; cd00190; Tryp_SPc; 1. DR Gene3D; 2.40.10.10; Trypsin-like serine proteases; 2. DR InterPro; IPR009003; Peptidase_S1_PA. DR InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin. DR InterPro; IPR001314; Peptidase_S1A. DR InterPro; IPR001254; Trypsin_dom. DR InterPro; IPR018114; TRYPSIN_HIS. DR InterPro; IPR033116; TRYPSIN_SER. DR PANTHER; PTHR24257:SF25; CHYMOTRYPSIN-C; 1. DR PANTHER; PTHR24257; CHYMOTRYPSIN-LIKE ELASTASE FAMILY MEMBER; 1. DR Pfam; PF00089; Trypsin; 1. DR PRINTS; PR00722; CHYMOTRYPSIN. DR SMART; SM00020; Tryp_SPc; 1. DR SUPFAM; SSF50494; Trypsin-like serine proteases; 1. DR PROSITE; PS50240; TRYPSIN_DOM; 1. DR PROSITE; PS00134; TRYPSIN_HIS; 1. DR PROSITE; PS00135; TRYPSIN_SER; 1. DR Genevisible; Q99895; HS. PE 1: Evidence at protein level; KW 3D-structure; Disease variant; Disulfide bond; Glycoprotein; Hydrolase; KW Protease; Reference proteome; Serine protease; Signal; Zymogen. FT SIGNAL 1..16 FT /evidence="ECO:0000255" FT PROPEP 17..29 FT /note="Activation peptide" FT /id="PRO_0000027713" FT CHAIN 30..268 FT /note="Chymotrypsin-C" FT /id="PRO_0000027714" FT DOMAIN 30..267 FT /note="Peptidase S1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274" FT ACT_SITE 74 FT /note="Charge relay system" FT /evidence="ECO:0000250" FT ACT_SITE 121 FT /note="Charge relay system" FT /evidence="ECO:0000250" FT ACT_SITE 216 FT /note="Charge relay system" FT /evidence="ECO:0000250" FT CARBOHYD 25 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 52 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 226 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 17..141 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274, FT ECO:0000269|PubMed:23430245" FT DISULFID 59..75 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274, FT ECO:0000269|PubMed:23430245" FT DISULFID 155..222 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274, FT ECO:0000269|PubMed:23430245" FT DISULFID 186..202 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274, FT ECO:0000269|PubMed:23430245" FT DISULFID 212..243 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274, FT ECO:0000269|PubMed:23430245" FT VARIANT 18 FT /note="G -> R (found in a patient with chronic FT pancreatitis; uncertain significance; catalytic activity FT comparable to that of wild type; the mutant undergoes FT proteolytic degradation during trypsin-mediated activation; FT dbSNP:rs200576965)" FT /evidence="ECO:0000269|PubMed:22942235" FT /id="VAR_070520" FT VARIANT 29 FT /note="R -> Q (found in patients with chronic pancreatitis; FT uncertain significance; dbSNP:rs772024986)" FT /evidence="ECO:0000269|PubMed:23135764" FT /id="VAR_070521" FT VARIANT 32 FT /note="G -> V (in PCTT; highly reduced catalytic FT efficiency)" FT /evidence="ECO:0000269|PubMed:22942235" FT /id="VAR_070522" FT VARIANT 35 FT /note="D -> H (in dbSNP:rs184977421)" FT /evidence="ECO:0000269|PubMed:18059268" FT /id="VAR_043516" FT VARIANT 35 FT /note="D -> N (in dbSNP:rs184977421)" FT /evidence="ECO:0000269|PubMed:18059268" FT /id="VAR_043517" FT VARIANT 35 FT /note="D -> Y (found in a patient with chronic FT pancreatitis; uncertain significance; catalytic activity FT comparable to that of wild type)" FT /evidence="ECO:0000269|PubMed:22942235" FT /id="VAR_070523" FT VARIANT 37 FT /note="R -> Q (rare variant; results in normal secretion FT and activity; dbSNP:rs145868278)" FT /evidence="ECO:0000269|PubMed:18059268" FT /id="VAR_043518" FT VARIANT 48 FT /note="Q -> R (rare variant that may be a risk factor for FT pancreatitis; results in markedly reduced protein FT secretion; dbSNP:rs536812916)" FT /evidence="ECO:0000269|PubMed:18059268, FT ECO:0000269|PubMed:22580415, ECO:0000269|PubMed:22942235" FT /id="VAR_043519" FT VARIANT 61 FT /note="G -> R (found in a patient with chronic FT pancreatitis; uncertain significance; the mutant is not FT secreted; dbSNP:rs769482036)" FT /evidence="ECO:0000269|PubMed:22942235" FT /id="VAR_070524" FT VARIANT 73 FT /note="A -> T (in PCTT; results in markedly reduced protein FT secretion; dbSNP:rs515726209)" FT /evidence="ECO:0000269|PubMed:18059268, FT ECO:0000269|PubMed:18172691, ECO:0000269|PubMed:22580415, FT ECO:0000269|PubMed:22942235" FT /id="VAR_043520" FT VARIANT 80 FT /note="R -> W (in dbSNP:rs779643710)" FT /evidence="ECO:0000269|PubMed:8635596" FT /id="VAR_010928" FT VARIANT 151 FT /note="K -> N (found in a patient with chronic FT pancreatitis; uncertain significance)" FT /id="VAR_070525" FT VARIANT 155 FT /note="C -> Y (in PCTT; the mutant is not secreted)" FT /evidence="ECO:0000269|PubMed:18172691, FT ECO:0000269|PubMed:22942235" FT /id="VAR_070526" FT VARIANT 162 FT /note="R -> H (rare variant; found in a patient with FT chronic pancreatitis; uncertain significance; FT dbSNP:rs775404479)" FT /evidence="ECO:0000269|PubMed:18172691" FT /id="VAR_070527" FT VARIANT 172 FT /note="K -> E (in dbSNP:rs34949635)" FT /evidence="ECO:0000269|PubMed:18059268, FT ECO:0000269|PubMed:18172691, ECO:0000269|PubMed:22580415" FT /id="VAR_043521" FT VARIANT 178 FT /note="Q -> R (in PCTT; impaired catalytic activity; FT dbSNP:rs200678111)" FT /evidence="ECO:0000269|PubMed:22942235" FT /id="VAR_070528" FT VARIANT 200 FT /note="M -> V (found in a patient with chronic FT pancreatitis; uncertain significance; dbSNP:rs146235499)" FT /evidence="ECO:0000269|PubMed:18172691" FT /id="VAR_070529" FT VARIANT 209 FT /note="I -> M" FT /evidence="ECO:0000269|PubMed:23135764" FT /id="VAR_070530" FT VARIANT 217 FT /note="G -> R (in PCTT; results in markedly reduced protein FT secretion and loss of activity; dbSNP:rs202058123)" FT /evidence="ECO:0000269|PubMed:18059268, FT ECO:0000269|PubMed:18172691, ECO:0000269|PubMed:22942235" FT /id="VAR_043522" FT VARIANT 217 FT /note="G -> S (in PCTT; reduced protein secretion; impaired FT catalytic activity; dbSNP:rs202058123)" FT /evidence="ECO:0000269|PubMed:18059268, FT ECO:0000269|PubMed:18172691, ECO:0000269|PubMed:22942235" FT /id="VAR_043523" FT VARIANT 218 FT /note="G -> S" FT /evidence="ECO:0000269|PubMed:18059268" FT /id="VAR_043524" FT VARIANT 220 FT /note="L -> R (rare variant; results in impaired protein FT secretion)" FT /evidence="ECO:0000269|PubMed:18059268, FT ECO:0000269|PubMed:22942235" FT /id="VAR_043525" FT VARIANT 225 FT /note="E -> A (in dbSNP:rs201486613)" FT /evidence="ECO:0000269|PubMed:18059268" FT /id="VAR_043526" FT VARIANT 225 FT /note="E -> K (found in a patient with chronic FT pancreatitis; uncertain significance)" FT /evidence="ECO:0000269|PubMed:19407484" FT /id="VAR_070531" FT VARIANT 227 FT /note="G -> S (in dbSNP:rs567745213)" FT /evidence="ECO:0000269|PubMed:22942235" FT /id="VAR_070532" FT VARIANT 235 FT /note="V -> I (in PCTT; slightly reduced activity; FT dbSNP:rs140993290)" FT /evidence="ECO:0000269|PubMed:18059268, FT ECO:0000269|PubMed:18172691, ECO:0000269|PubMed:22580415, FT ECO:0000269|PubMed:22942235" FT /id="VAR_043527" FT VARIANT 239 FT /note="S -> A (found in patients with chronic pancreatitis; FT uncertain significance)" FT /evidence="ECO:0000269|PubMed:23135764" FT /id="VAR_070533" FT VARIANT 239 FT /note="S -> C (found in patients with chronic pancreatitis; FT uncertain significance)" FT /evidence="ECO:0000269|PubMed:23135764" FT /id="VAR_070534" FT VARIANT 246 FT /note="R -> C (in dbSNP:rs200412314)" FT /evidence="ECO:0000269|PubMed:22580415" FT /id="VAR_070535" FT VARIANT 247..254 FT /note="Missing (in PCTT; results in reduced protein FT secretion and loss of activity)" FT /evidence="ECO:0000269|PubMed:18172691, FT ECO:0000269|PubMed:22942235" FT /id="VAR_070536" FT VARIANT 247 FT /note="K -> E (found in patients with chronic pancreatitis; FT uncertain significance)" FT /evidence="ECO:0000269|PubMed:23135764" FT /id="VAR_070537" FT VARIANT 249 FT /note="P -> L (in PCTT; results in reduced protein FT secretion and loss of activity; dbSNP:rs142560329)" FT /evidence="ECO:0000269|PubMed:18059268, FT ECO:0000269|PubMed:22942235" FT /id="VAR_043528" FT VARIANT 250 FT /note="V -> E (in PCTT; results in altered enzyme FT specificity and loss of activity)" FT /evidence="ECO:0000269|PubMed:22942235" FT /id="VAR_070538" FT VARIANT 254 FT /note="R -> Q (found in a patient with chronic FT pancreatitis; uncertain significance; mutant protein FT secretion, activity and trypsin-mediated degradation are FT comparable to those of wild-type; dbSNP:rs755811899)" FT /evidence="ECO:0000269|PubMed:19407484, FT ECO:0000269|PubMed:22942235" FT /id="VAR_070539" FT VARIANT 254 FT /note="R -> W (in PCTT; results in reduced secretion; FT normal activity; the mutant undergoes proteolytic FT degradation during trypsin-mediated activation; FT dbSNP:rs121909293)" FT /evidence="ECO:0000269|PubMed:18059268, FT ECO:0000269|PubMed:18172691, ECO:0000269|PubMed:22580415, FT ECO:0000269|PubMed:22942235, ECO:0000269|PubMed:23135764" FT /id="VAR_043529" FT VARIANT 257 FT /note="A -> T (found in patients with chronic pancreatitis; FT uncertain significance; dbSNP:rs200406696)" FT /evidence="ECO:0000269|PubMed:22580415" FT /id="VAR_070540" FT VARIANT 260 FT /note="D -> N (in dbSNP:rs540753875)" FT /evidence="ECO:0000269|PubMed:18059268" FT /id="VAR_043530" FT VARIANT 263 FT /note="N -> S (found in a patient with chronic FT pancreatitis; uncertain significance; dbSNP:rs769975164)" FT /evidence="ECO:0000269|PubMed:19407484" FT /id="VAR_070541" FT CONFLICT 16 FT /note="S -> T (in Ref. 1; AAB47104)" FT /evidence="ECO:0000305" FT CONFLICT 52 FT /note="N -> D (in Ref. 6; CAA74031)" FT /evidence="ECO:0000305" FT STRAND 44..51 FT /evidence="ECO:0007829|PDB:4H4F" FT STRAND 54..65 FT /evidence="ECO:0007829|PDB:4H4F" FT STRAND 68..71 FT /evidence="ECO:0007829|PDB:4H4F" FT HELIX 73..75 FT /evidence="ECO:0007829|PDB:4H4F" FT STRAND 82..87 FT /evidence="ECO:0007829|PDB:4H4F" FT STRAND 100..102 FT /evidence="ECO:0007829|PDB:4H4F" FT STRAND 104..109 FT /evidence="ECO:0007829|PDB:4H4F" FT TURN 115..117 FT /evidence="ECO:0007829|PDB:4H4F" FT STRAND 123..129 FT /evidence="ECO:0007829|PDB:4H4F" FT STRAND 155..160 FT /evidence="ECO:0007829|PDB:4H4F" FT STRAND 162..164 FT /evidence="ECO:0007829|PDB:4H4F" FT STRAND 174..177 FT /evidence="ECO:0007829|PDB:4H4F" FT HELIX 183..186 FT /evidence="ECO:0007829|PDB:4H4F" FT TURN 189..192 FT /evidence="ECO:0007829|PDB:4H4F" FT HELIX 193..195 FT /evidence="ECO:0007829|PDB:4H4F" FT STRAND 200..203 FT /evidence="ECO:0007829|PDB:4H4F" FT STRAND 206..210 FT /evidence="ECO:0007829|PDB:4H4F" FT STRAND 219..223 FT /evidence="ECO:0007829|PDB:4H4F" FT STRAND 229..239 FT /evidence="ECO:0007829|PDB:4H4F" FT STRAND 242..245 FT /evidence="ECO:0007829|PDB:4H4F" FT STRAND 250..254 FT /evidence="ECO:0007829|PDB:4H4F" FT HELIX 255..257 FT /evidence="ECO:0007829|PDB:4H4F" FT HELIX 259..265 FT /evidence="ECO:0007829|PDB:4H4F" SQ SEQUENCE 268 AA; 29484 MW; 460BF33B4A96516F CRC64; MLGITVLAAL LACASSCGVP SFPPNLSARV VGGEDARPHS WPWQISLQYL KNDTWRHTCG GTLIASNFVL TAAHCISNTR TYRVAVGKNN LEVEDEEGSL FVGVDTIHVH KRWNALLLRN DIALIKLAEH VELSDTIQVA CLPEKDSLLP KDYPCYVTGW GRLWTNGPIA DKLQQGLQPV VDHATCSRID WWGFRVKKTM VCAGGDGVIS ACNGDSGGPL NCQLENGSWE VFGIVSFGSR RGCNTRKKPV VYTRVSAYID WINEKMQL //