CTRC_HUMAN
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 03-AUG-2022, entry version 172.
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: TEX37; 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}.
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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 GlyGen; Q99895; 3 sites.
DR BioMuta; CTRC; -.
DR DMDM; 14194504; -.
DR MassIVE; Q99895; -.
DR PaxDb; Q99895; -.
DR PeptideAtlas; Q99895; -.
DR PRIDE; Q99895; -.
DR ProteomicsDB; 78519; -.
DR Antibodypedia; 28845; 161 antibodies from 22 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 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; PDWWGSQ; -.
DR OrthoDB; 1314811at2759; -.
DR PhylomeDB; Q99895; -.
DR TreeFam; TF330455; -.
DR BRENDA; 3.4.21.2; 2681.
DR PathwayCommons; Q99895; -.
DR SignaLink; Q99895; -.
DR BioGRID-ORCS; 11330; 15 hits in 1069 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 109 other tissues.
DR ExpressionAtlas; Q99895; baseline and differential.
DR Genevisible; Q99895; HS.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
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:cellular calcium ion homeostasis; IDA:MGI.
DR GO; GO:0009235; P:cobalamin metabolic process; TAS:Reactome.
DR GO; GO:0006508; P:proteolysis; IDA:MGI.
DR CDD; cd00190; Tryp_SPc; 1.
DR Gene3D; 2.40.10.10; -; 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 Pfam; PF00089; Trypsin; 1.
DR PRINTS; PR00722; CHYMOTRYPSIN.
DR SMART; SM00020; Tryp_SPc; 1.
DR SUPFAM; SSF50494; SSF50494; 1.
DR PROSITE; PS50240; TRYPSIN_DOM; 1.
DR PROSITE; PS00134; TRYPSIN_HIS; 1.
DR PROSITE; PS00135; TRYPSIN_SER; 1.
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; unknown pathological significance; catalytic
FT activity comparable to that of wild type; the mutant
FT undergoes proteolytic degradation during trypsin-mediated
FT activation; 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 unknown pathological significance; dbSNP:rs772024986)"
FT /evidence="ECO:0000269|PubMed:23135764"
FT /id="VAR_070521"
FT VARIANT 32
FT /note="G -> V (in PCTT; associated with disease
FT susceptibility; highly reduced catalytic 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; unknown pathological significance; catalytic
FT activity 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 associated with
FT susceptibility to pancreatitis; results in markedly reduced
FT protein 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; unknown pathological significance; the mutant
FT is not secreted; dbSNP:rs769482036)"
FT /evidence="ECO:0000269|PubMed:22942235"
FT /id="VAR_070524"
FT VARIANT 73
FT /note="A -> T (in PCTT; associated with susceptibility to
FT disease; results in markedly reduced protein secretion;
FT 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; unknown pathological significance)"
FT /id="VAR_070525"
FT VARIANT 155
FT /note="C -> Y (in PCTT; associated with susceptibility to
FT disease; 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; unknown pathological 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; associated with disease
FT susceptibility; impaired catalytic activity;
FT dbSNP:rs200678111)"
FT /evidence="ECO:0000269|PubMed:22942235"
FT /id="VAR_070528"
FT VARIANT 200
FT /note="M -> V (rare variant; found in a patient with
FT chronic pancreatitis; unknown pathological significance;
FT 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; associated with susceptibility to
FT disease; results in markedly reduced protein secretion and
FT 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; associated with susceptibility to
FT disease; reduced protein secretion; impaired catalytic
FT 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; unknown pathological 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; associated with susceptibility to
FT disease; slightly reduced activity; 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 unknown pathological 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 unknown pathological 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; associated with disease
FT susceptibility; results in reduced protein secretion and
FT 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 unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:23135764"
FT /id="VAR_070537"
FT VARIANT 249
FT /note="P -> L (in PCTT; associated with disease
FT susceptibility; results in reduced protein secretion and
FT 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; associated with disease
FT susceptibility; results in altered enzyme specificity and
FT 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; unknown pathological significance; mutant
FT protein secretion, activity and trypsin-mediated
FT degradation are comparable to those of wild-type;
FT 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; associated with susceptibility to
FT disease; results in reduced secretion; normal activity; the
FT mutant undergoes proteolytic degradation during trypsin-
FT mediated activation; 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 unknown pathological 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; unknown pathological significance;
FT 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
