CATC_HUMAN
ID CATC_HUMAN Reviewed; 463 AA.
AC P53634; A8K7V2; B5MDD5; Q2HIY8; Q53G93; Q71E75; Q71E76; Q7M4N9; Q7Z3G7;
AC Q7Z5U7; Q8WY99; Q8WYA7; Q8WYA8;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2011, sequence version 2.
DT 03-AUG-2022, entry version 215.
DE RecName: Full=Dipeptidyl peptidase 1;
DE EC=3.4.14.1;
DE AltName: Full=Cathepsin C;
DE AltName: Full=Cathepsin J;
DE AltName: Full=Dipeptidyl peptidase I;
DE Short=DPP-I;
DE Short=DPPI;
DE AltName: Full=Dipeptidyl transferase;
DE Contains:
DE RecName: Full=Dipeptidyl peptidase 1 exclusion domain chain;
DE AltName: Full=Dipeptidyl peptidase I exclusion domain chain;
DE Contains:
DE RecName: Full=Dipeptidyl peptidase 1 heavy chain;
DE AltName: Full=Dipeptidyl peptidase I heavy chain;
DE Contains:
DE RecName: Full=Dipeptidyl peptidase 1 light chain;
DE AltName: Full=Dipeptidyl peptidase I light chain;
DE Flags: Precursor;
GN Name=CTSC; Synonyms=CPPI;
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] (ISOFORM 1), AND VARIANT THR-153.
RC TISSUE=Ileum;
RX PubMed=7649281; DOI=10.1016/0014-5793(95)00777-7;
RA Paris A., Strukelj B., Pungercar J., Renko M., Dolenc I., Turk V.;
RT "Molecular cloning and sequence analysis of human preprocathepsin C.";
RL FEBS Lett. 369:326-330(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], INDUCTION, TISSUE SPECIFICITY, AND
RP VARIANT THR-153.
RX PubMed=9092576; DOI=10.1074/jbc.272.15.10260;
RA Rao N.V., Rao G.V., Hoidal J.R.;
RT "Human dipeptidyl-peptidase I. Gene characterization, localization, and
RT expression.";
RL J. Biol. Chem. 272:10260-10265(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS PLS TYR-236; ARG-286 AND
RP TYR-291, AND VARIANT THR-153.
RC TISSUE=Blood;
RX PubMed=11180601;
RX DOI=10.1002/1098-1004(200102)17:2<152::aid-humu10>3.0.co;2-#;
RA Allende L.M., Garcia-Perez M.A., Moreno A., Corell A., Carasol M.,
RA Martinez-Canut P., Arnaiz-Villena A.;
RT "Cathepsin C gene: first compound heterozygous patient with Papillon-
RT Lefevre syndrome and a novel symptomless mutation.";
RL Hum. Mutat. 17:152-153(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS THR-153 AND PLS
RP HIS-294.
RC TISSUE=Blood;
RX PubMed=12809647; DOI=10.1016/s1096-7192(03)00070-2;
RA Allende L.M., Moreno A., de Unamuno P.;
RT "A genetic study of cathepsin C gene in two families with Papillon-Lefevre
RT syndrome.";
RL Mol. Genet. Metab. 79:146-148(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
RP THR-153.
RC TISSUE=Cerebellum, and Rheumatoid arthritic synovial fluid;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT THR-153.
RC TISSUE=Thyroid;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Fetal kidney;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT THR-153.
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 [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
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 [11]
RP PROTEIN SEQUENCE OF 25-71; 122-143; 231-235 AND 395-399, CHARACTERIZATION
RP OF EXCLUSION DOMAIN, AND GLYCOSYLATION.
RX PubMed=9507095; DOI=10.1016/s0167-4838(97)00173-8;
RA Cigic B., Krizaj I., Kralj B., Turk V., Pain R.H.;
RT "Stoichiometry and heterogeneity of the pro-region chain in tetrameric
RT human cathepsin C.";
RL Biochim. Biophys. Acta 1382:143-150(1998).
RN [12]
RP PROTEIN SEQUENCE OF 25-34; 231-239 AND 395-404, AND CHARACTERIZATION.
RX PubMed=7665576; DOI=10.1074/jbc.270.37.21626;
RA Dolenc I., Turk B., Pungercic G., Ritonja A., Turk V.;
RT "Oligomeric structure and substrate induced inhibition of human cathepsin
RT C.";
RL J. Biol. Chem. 270:21626-21631(1995).
RN [13]
RP PROTEIN SEQUENCE OF 25-28; 51-61; 114-117 AND 133-139, CHARACTERIZATION OF
RP EXCLUSION DOMAIN, AND DISULFIDE BONDS.
RX PubMed=11015218; DOI=10.1021/bi0008837;
RA Cigic B., Dahl S.W., Pain R.H.;
RT "The residual pro-part of cathepsin C fulfills the criteria required for an
RT intramolecular chaperone in folding and stabilizing the human proenzyme.";
RL Biochemistry 39:12382-12390(2000).
RN [14]
RP PROTEIN SEQUENCE OF 231-290; 310-328 AND 340-383, FUNCTION, ACTIVITY
RP REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, GLYCOSYLATION, AND
RP VARIANT THR-153.
RC TISSUE=Spleen;
RX PubMed=1586157; DOI=10.1016/0003-9861(92)90519-3;
RA McGuire M.J., Lipsky P.E., Thiele D.L.;
RT "Purification and characterization of dipeptidyl peptidase I from human
RT spleen.";
RL Arch. Biochem. Biophys. 295:280-288(1992).
RN [15]
RP GLYCOSYLATION AT ASN-29; ASN-53; ASN-119 AND ASN-276.
RX PubMed=19167329; DOI=10.1016/j.cell.2008.11.047;
RA Ruiz-Canada C., Kelleher D.J., Gilmore R.;
RT "Cotranslational and posttranslational N-glycosylation of polypeptides by
RT distinct mammalian OST isoforms.";
RL Cell 136:272-283(2009).
RN [16]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-53.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [20] {ECO:0007744|PDB:1K3B}
RP X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) OF 25-143 AND 231-463 IN COMPLEX
RP WITH CHLORIDE IONS, SUBUNIT, DISULFIDE BONDS, AND GLYCOSYLATION AT ASN-29.
RX PubMed=11726493; DOI=10.1093/emboj/20.23.6570;
RA Turk D., Janjic V., Stern I., Podobnik M., Lamba D., Dahl S.W.,
RA Lauritzen C., Pedersen J., Turk V., Turk B.;
RT "Structure of human dipeptidyl peptidase I (cathepsin C): exclusion domain
RT added to an endopeptidase framework creates the machine for activation of
RT granular serine proteases.";
RL EMBO J. 20:6570-6582(2001).
RN [21]
RP VARIANTS PLS PHE-249; LEU-252; PRO-272; SER-301; CYS-339 AND CYS-347.
RX PubMed=10581027; DOI=10.1038/70525;
RA Toomes C., James J., Wood A.J., Wu C.L., McCormick D., Lench N., Hewitt C.,
RA Moynihan L., Roberts E., Woods C.G., Markham A., Wong M., Widmer R.,
RA Ghaffar K.A., Pemberton M., Hussein I.R., Temtamy S.A., Davies R.,
RA Read A.P., Sloan P., Dixon M.J., Thakker N.S.;
RT "Loss-of-function mutations in the cathepsin C gene result in periodontal
RT disease and palmoplantar keratosis.";
RL Nat. Genet. 23:421-424(1999).
RN [22]
RP VARIANT HMS ARG-286.
RX PubMed=10662807; DOI=10.1136/jmg.37.2.88;
RA Hart T.C., Hart P.S., Michalec M.D., Zhang Y., Firatli E., Van Dyke T.E.,
RA Stabholz A., Zlotogorski A., Shapira L., Soskolne W.A.;
RT "Haim-Munk syndrome and Papillon-Lefevre syndrome are allelic mutations in
RT cathepsin C.";
RL J. Med. Genet. 37:88-94(2000).
RN [23]
RP VARIANTS PLS CYS-339 AND CYS-340, AND VARIANT AP1 CYS-347.
RX PubMed=10662808; DOI=10.1136/jmg.37.2.95;
RA Hart T.C., Hart P.S., Michalec M.D., Zhang Y., Marazita M.L., Cooper M.,
RA Yassin O.M., Nusier M., Walker S.;
RT "Localisation of a gene for prepubertal periodontitis to chromosome 11q14
RT and identification of a cathepsin C gene mutation.";
RL J. Med. Genet. 37:95-101(2000).
RN [24]
RP VARIANTS PLS 67-TYR--ALA-74 DEL; PRO-272; SER-300; VAL-301; SER-301;
RP ASN-304; GLY-319; CYS-339; CYS-340 AND GLY-447, AND VARIANT THR-153.
RX PubMed=11106356; DOI=10.1136/jmg.37.12.927;
RA Hart P.S., Zhang Y., Firatli E., Uygur C., Lotfazar M., Michalec M.D.,
RA Marks J.J., Lu X., Coates B.J., Seow W.K., Marshall R., Williams D.,
RA Reed J.B., Wright J.T., Hart T.C.;
RT "Identification of cathepsin C mutations in ethnically diverse Papillon-
RT Lefevre syndrome patients.";
RL J. Med. Genet. 37:927-932(2000).
RN [25]
RP VARIANTS PLS SER-39 AND SER-301, AND VARIANT VAL-453.
RX PubMed=11180012; DOI=10.1046/j.1523-1747.2001.01244.x;
RA Nakano A., Nomura K., Nakano H., Ono Y., LaForgia S., Pulkkinen L.,
RA Hashimoto I., Uitto J.;
RT "Papillon-Lefevre syndrome: mutations and polymorphisms in the cathepsin C
RT gene.";
RL J. Invest. Dermatol. 116:339-343(2001).
RN [26]
RP VARIANTS PLS PRO-127; PRO-272; CYS-339 AND CYS-429, AND VARIANTS THR-153
RP AND LYS-401.
RX PubMed=11886537; DOI=10.1046/j.0022-202x.2001.01595.x;
RA Lefevre C., Blanchet-Bardon C., Jobard F., Bouadjar B., Stalder J.-F.,
RA Cure S., Hoffmann A., Prud'Homme J.-F., Fischer J.;
RT "Novel point mutations, deletions, and polymorphisms in the cathepsin C
RT gene in nine families from Europe and North Africa with Papillon-Lefevre
RT syndrome.";
RL J. Invest. Dermatol. 117:1657-1661(2001).
RN [27]
RP VARIANTS PLS PRO-272 AND ASP-300.
RX PubMed=11158173; DOI=10.1136/jmg.38.2.96;
RA Zhang Y., Lundgren T., Renvert S., Tatakis D.N., Firatli E., Uygur C.,
RA Hart P.S., Gorry M.C., Marks J.J., Hart T.C.;
RT "Evidence of a founder effect for four cathepsin C gene mutations in
RT Papillon-Lefevre syndrome patients.";
RL J. Med. Genet. 38:96-101(2001).
RN [28]
RP VARIANTS PLS ARG-139 AND PRO-272, AND VARIANT THR-153.
RX PubMed=12112662; DOI=10.1002/humu.9040;
RA Zhang Y., Hart P.S., Moretti A.J., Bouwsma O.J., Fisher E.M., Dudlicek L.,
RA Pettenati M.J., Hart T.C.;
RT "Biochemical and mutational analyses of the cathepsin c gene (CTSC) in
RT three North American families with Papillon Lefevre syndrome.";
RL Hum. Mutat. 20:75-75(2002).
RN [29]
RP VARIANTS PLS GLU-129; ARG-139; TYR-236; PHE-249; LEU-252; HIS-272; SER-301;
RP ARG-312; CYS-339; CYS-347 AND GLY-447, VARIANTS AP1 HIS-272 AND CYS-412,
RP AND VARIANT THR-153.
RX PubMed=14974080; DOI=10.1002/humu.10314;
RA Hewitt C., McCormick D., Linden G., Turk D., Stern I., Wallace I.,
RA Southern L., Zhang L., Howard R., Bullon P., Wong M., Widmer R.,
RA Gaffar K.A., Awawdeh L., Briggs J., Yaghmai R., Jabs E.W., Hoeger P.,
RA Bleck O., Rudiger S.G., Petersilka G., Battino M., Brett P., Hattab F.,
RA Al-Hamed M., Sloan P., Toomes C., Dixon M.J., James J., Read A.P.,
RA Thakker N.S.;
RT "The role of cathepsin C in Papillon-Lefevre syndrome, prepubertal
RT periodontitis, and aggressive periodontitis.";
RL Hum. Mutat. 23:222-228(2004).
RN [30]
RP VARIANT PLS ASN-405.
RX PubMed=15108292; DOI=10.1002/humu.9243;
RA de Haar S.F., Jansen D.C., Schoenmaker T., De Vree H., Everts V.,
RA Beertsen W.;
RT "Loss-of-function mutations in cathepsin C in two families with Papillon-
RT Lefevre syndrome are associated with deficiency of serine proteinases in
RT PMNs.";
RL Hum. Mutat. 23:524-524(2004).
RN [31]
RP VARIANT PLS ARG-405.
RX PubMed=15991336;
RA de Haar S.F., Mir M., Nguyen M., Kazemi B., Ramezani G.H., Everts V.;
RT "Gene symbol: CTSC. Disease: Papillon-Lefevre syndrome.";
RL Hum. Genet. 116:545-545(2005).
RN [32]
RP ERRATUM OF PUBMED:15991336.
RA de Haar S.F., Mir M., Nguyen M., Kazemi B., Ramezani G.H., Everts V.;
RL Hum. Genet. 118:533-533(2005).
RN [33]
RP VARIANT PLS ASP-300.
RX PubMed=25799584; DOI=10.1371/journal.pone.0121351;
RA Erzurumluoglu A.M., Alsaadi M.M., Rodriguez S., Alotaibi T.S.,
RA Guthrie P.A., Lewis S., Ginwalla A., Gaunt T.R., Alharbi K.K., Alsaif F.M.,
RA Alsaadi B.M., Day I.N.;
RT "Proxy molecular diagnosis from whole-exome sequencing reveals Papillon-
RT Lefevre syndrome caused by a missense mutation in CTSC.";
RL PLoS ONE 10:E0121351-E0121351(2015).
CC -!- FUNCTION: Thiol protease. Has dipeptidylpeptidase activity. Active
CC against a broad range of dipeptide substrates composed of both polar
CC and hydrophobic amino acids. Proline cannot occupy the P1 position and
CC arginine cannot occupy the P2 position of the substrate. Can act as
CC both an exopeptidase and endopeptidase. Activates serine proteases such
CC as elastase, cathepsin G and granzymes A and B. Can also activate
CC neuraminidase and factor XIII. {ECO:0000269|PubMed:1586157}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Release of an N-terminal dipeptide, Xaa-Yaa-|-Zaa-, except
CC when Xaa is Arg or Lys, or Yaa or Zaa is Pro.; EC=3.4.14.1;
CC -!- COFACTOR:
CC Name=chloride; Xref=ChEBI:CHEBI:17996;
CC Evidence={ECO:0000269|PubMed:11726493};
CC Note=Binds 1 Cl(-) ion per heavy chain. {ECO:0000269|PubMed:11726493};
CC -!- ACTIVITY REGULATION: Strongly inhibited by the cysteine peptidase
CC inhibitors mersalyl acid, iodoacetic acid and cystatin. Inhibited by N-
CC ethylmaleimide, Gly-Phe-diazomethane, TLCK, TPCK and, at low pH, by
CC dithiodipyridine. Not inhibited by the serine peptidase inhibitor PMSF,
CC the aminopeptidase inhibitor bestatin, or metal ion chelators.
CC {ECO:0000269|PubMed:1586157}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC High activity at pH 4.5-6.8. {ECO:0000269|PubMed:1586157};
CC -!- SUBUNIT: Tetramer of heterotrimers consisting of exclusion domain,
CC heavy- and light chains. {ECO:0000269|PubMed:11726493,
CC ECO:0000269|PubMed:1586157}.
CC -!- INTERACTION:
CC P53634; O76096: CST7; NbExp=2; IntAct=EBI-1047323, EBI-2807448;
CC P53634; G5E9A7: DMWD; NbExp=3; IntAct=EBI-1047323, EBI-10976677;
CC P53634; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-1047323, EBI-5235340;
CC -!- SUBCELLULAR LOCATION: Lysosome.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P53634-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P53634-2; Sequence=VSP_039123, VSP_039124;
CC Name=3;
CC IsoId=P53634-3; Sequence=VSP_043232, VSP_043233;
CC -!- TISSUE SPECIFICITY: Ubiquitous. Highly expressed in lung, kidney and
CC placenta. Detected at intermediate levels in colon, small intestine,
CC spleen and pancreas. {ECO:0000269|PubMed:9092576}.
CC -!- INDUCTION: Up-regulated in lymphocytes by IL2/interleukin-2.
CC {ECO:0000269|PubMed:9092576}.
CC -!- PTM: N-glycosylated. While glycosylation at Asn-53, Asn-119 and Asn-276
CC is mediated by STT3A-containing complexes, glycosylation at Asn-29 is
CC mediated STT3B-containing complexes. {ECO:0000269|PubMed:11726493,
CC ECO:0000269|PubMed:1586157, ECO:0000269|PubMed:19159218,
CC ECO:0000269|PubMed:19167329, ECO:0000269|PubMed:9507095}.
CC -!- PTM: In approximately 50% of the complexes the exclusion domain is
CC cleaved at position 58 or 61. The two parts of the exclusion domain are
CC held together by a disulfide bond.
CC -!- DISEASE: Papillon-Lefevre syndrome (PLS) [MIM:245000]: An autosomal
CC recessive disorder characterized by palmoplantar keratosis and severe
CC periodontitis affecting deciduous and permanent dentitions and
CC resulting in premature tooth loss. The palmoplantar keratotic phenotype
CC vary from mild psoriasiform scaly skin to overt hyperkeratosis.
CC Keratosis also affects other sites such as elbows and knees.
CC {ECO:0000269|PubMed:10581027, ECO:0000269|PubMed:10662808,
CC ECO:0000269|PubMed:11106356, ECO:0000269|PubMed:11158173,
CC ECO:0000269|PubMed:11180012, ECO:0000269|PubMed:11180601,
CC ECO:0000269|PubMed:11886537, ECO:0000269|PubMed:12112662,
CC ECO:0000269|PubMed:12809647, ECO:0000269|PubMed:14974080,
CC ECO:0000269|PubMed:15108292, ECO:0000269|PubMed:15991336,
CC ECO:0000269|PubMed:25799584}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Haim-Munk syndrome (HMS) [MIM:245010]: An autosomal recessive
CC disorder characterized by palmoplantar keratosis, onychogryphosis and
CC periodontitis. Additional features are pes planus, arachnodactyly, and
CC acroosteolysis. {ECO:0000269|PubMed:10662807}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- DISEASE: Periodontititis, aggressive, 1 (AP1) [MIM:170650]: A disease
CC characterized by severe and protracted gingival infections, generalized
CC or localized, leading to tooth loss. Amounts of microbial deposits are
CC generally inconsistent with the severity of periodontal tissue
CC destruction and the progression of attachment and bone loss may be self
CC arresting. {ECO:0000269|PubMed:10662808, ECO:0000269|PubMed:14974080}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- SIMILARITY: Belongs to the peptidase C1 family. {ECO:0000255|PROSITE-
CC ProRule:PRU10088, ECO:0000255|PROSITE-ProRule:PRU10089,
CC ECO:0000255|PROSITE-ProRule:PRU10090}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAD97897.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=CTSCbase; Note=CTSC mutation db;
CC URL="http://structure.bmc.lu.se/idbase/CTSCbase/";
CC ---------------------------------------------------------------------------
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CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
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DR EMBL; X87212; CAA60671.1; -; mRNA.
DR EMBL; U79415; AAC51341.1; -; Genomic_DNA.
DR EMBL; AF234263; AAL48191.1; -; mRNA.
DR EMBL; AF234264; AAL48192.1; -; mRNA.
DR EMBL; AF254757; AAL48195.1; -; mRNA.
DR EMBL; AF525032; AAQ08887.1; -; mRNA.
DR EMBL; AF525033; AAQ08888.1; -; mRNA.
DR EMBL; AK292117; BAF84806.1; -; mRNA.
DR EMBL; AK311923; BAG34864.1; -; mRNA.
DR EMBL; AK223038; BAD96758.1; -; mRNA.
DR EMBL; BX537913; CAD97897.1; ALT_INIT; mRNA.
DR EMBL; AC011088; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471185; EAW59364.1; -; Genomic_DNA.
DR EMBL; BC054028; AAH54028.1; -; mRNA.
DR EMBL; BC100891; AAI00892.1; -; mRNA.
DR EMBL; BC100892; AAI00893.1; -; mRNA.
DR EMBL; BC100893; AAI00894.1; -; mRNA.
DR EMBL; BC100894; AAI00895.1; -; mRNA.
DR EMBL; BC109386; AAI09387.1; -; mRNA.
DR EMBL; BC110071; AAI10072.1; -; mRNA.
DR EMBL; BC113850; AAI13851.1; -; mRNA.
DR EMBL; BC113897; AAI13898.1; -; mRNA.
DR CCDS; CCDS31654.1; -. [P53634-2]
DR CCDS; CCDS44693.1; -. [P53634-3]
DR CCDS; CCDS8282.1; -. [P53634-1]
DR PIR; S23941; S23941.
DR PIR; S66504; S66504.
DR RefSeq; NP_001107645.1; NM_001114173.2. [P53634-3]
DR RefSeq; NP_001805.3; NM_001814.5. [P53634-1]
DR RefSeq; NP_680475.1; NM_148170.4. [P53634-2]
DR PDB; 1K3B; X-ray; 2.15 A; A=25-143, B=231-394, C=395-463.
DR PDB; 2DJF; X-ray; 2.00 A; A=25-143, B=231-394, C=395-463.
DR PDB; 2DJG; X-ray; 2.05 A; A=25-143, B=231-394, C=395-463.
DR PDB; 3PDF; X-ray; 1.85 A; A=25-463.
DR PDB; 4CDC; X-ray; 2.40 A; A/D/G/J=25-143, B/E/H/K=230-394, C/F/I/L=395-463.
DR PDB; 4CDD; X-ray; 2.35 A; A/D=25-144, B/E=230-394, C/F=395-463.
DR PDB; 4CDE; X-ray; 2.40 A; A/D=25-143, B/E=230-394, C/F=395-463.
DR PDB; 4CDF; X-ray; 2.20 A; A/D=25-144, B/E=229-394, C/F=395-463.
DR PDB; 4OEL; X-ray; 1.40 A; A=25-394, B=395-463.
DR PDB; 4OEM; X-ray; 1.52 A; A=25-394, B=395-463.
DR PDBsum; 1K3B; -.
DR PDBsum; 2DJF; -.
DR PDBsum; 2DJG; -.
DR PDBsum; 3PDF; -.
DR PDBsum; 4CDC; -.
DR PDBsum; 4CDD; -.
DR PDBsum; 4CDE; -.
DR PDBsum; 4CDF; -.
DR PDBsum; 4OEL; -.
DR PDBsum; 4OEM; -.
DR AlphaFoldDB; P53634; -.
DR SMR; P53634; -.
DR BioGRID; 107502; 46.
DR IntAct; P53634; 26.
DR MINT; P53634; -.
DR STRING; 9606.ENSP00000227266; -.
DR BindingDB; P53634; -.
DR ChEMBL; CHEMBL2252; -.
DR GuidetoPHARMACOLOGY; 2344; -.
DR MEROPS; C01.070; -.
DR GlyConnect; 1175; 60 N-Linked glycans (4 sites).
DR GlyGen; P53634; 6 sites, 56 N-linked glycans (4 sites), 1 O-linked glycan (1 site).
DR iPTMnet; P53634; -.
DR PhosphoSitePlus; P53634; -.
DR SwissPalm; P53634; -.
DR BioMuta; CTSC; -.
DR DMDM; 317373330; -.
DR EPD; P53634; -.
DR jPOST; P53634; -.
DR MassIVE; P53634; -.
DR MaxQB; P53634; -.
DR PaxDb; P53634; -.
DR PeptideAtlas; P53634; -.
DR PRIDE; P53634; -.
DR ProteomicsDB; 56595; -. [P53634-1]
DR ProteomicsDB; 56596; -. [P53634-2]
DR ProteomicsDB; 56597; -. [P53634-3]
DR TopDownProteomics; P53634-1; -. [P53634-1]
DR Antibodypedia; 31473; 289 antibodies from 31 providers.
DR DNASU; 1075; -.
DR Ensembl; ENST00000227266.10; ENSP00000227266.4; ENSG00000109861.17. [P53634-1]
DR Ensembl; ENST00000524463.6; ENSP00000432541.1; ENSG00000109861.17. [P53634-2]
DR Ensembl; ENST00000529974.2; ENSP00000433539.1; ENSG00000109861.17. [P53634-3]
DR Ensembl; ENST00000677106.1; ENSP00000504568.1; ENSG00000109861.17. [P53634-2]
DR GeneID; 1075; -.
DR KEGG; hsa:1075; -.
DR MANE-Select; ENST00000227266.10; ENSP00000227266.4; NM_001814.6; NP_001805.4.
DR UCSC; uc001pck.5; human. [P53634-1]
DR CTD; 1075; -.
DR DisGeNET; 1075; -.
DR GeneCards; CTSC; -.
DR HGNC; HGNC:2528; CTSC.
DR HPA; ENSG00000109861; Low tissue specificity.
DR MalaCards; CTSC; -.
DR MIM; 170650; phenotype.
DR MIM; 245000; phenotype.
DR MIM; 245010; phenotype.
DR MIM; 602365; gene.
DR neXtProt; NX_P53634; -.
DR OpenTargets; ENSG00000109861; -.
DR Orphanet; 2342; Haim-Munk syndrome.
DR Orphanet; 678; Papillon-Lefevre syndrome.
DR PharmGKB; PA27028; -.
DR VEuPathDB; HostDB:ENSG00000109861; -.
DR eggNOG; KOG1543; Eukaryota.
DR GeneTree; ENSGT00940000155787; -.
DR HOGENOM; CLU_048219_0_0_1; -.
DR InParanoid; P53634; -.
DR OMA; HDKTVNC; -.
DR OrthoDB; 1275401at2759; -.
DR PhylomeDB; P53634; -.
DR TreeFam; TF313225; -.
DR BioCyc; MetaCyc:HS03265-MON; -.
DR BRENDA; 3.4.14.1; 2681.
DR PathwayCommons; P53634; -.
DR Reactome; R-HSA-204005; COPII-mediated vesicle transport.
DR Reactome; R-HSA-2132295; MHC class II antigen presentation.
DR Reactome; R-HSA-5694530; Cargo concentration in the ER.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR SABIO-RK; P53634; -.
DR SignaLink; P53634; -.
DR BioGRID-ORCS; 1075; 11 hits in 1084 CRISPR screens.
DR ChiTaRS; CTSC; human.
DR EvolutionaryTrace; P53634; -.
DR GeneWiki; Cathepsin_C; -.
DR GenomeRNAi; 1075; -.
DR Pharos; P53634; Tchem.
DR PRO; PR:P53634; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; P53634; protein.
DR Bgee; ENSG00000109861; Expressed in palpebral conjunctiva and 201 other tissues.
DR ExpressionAtlas; P53634; baseline and differential.
DR Genevisible; P53634; HS.
DR GO; GO:0035578; C:azurophil granule lumen; TAS:Reactome.
DR GO; GO:0005813; C:centrosome; IDA:HPA.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
DR GO; GO:0030134; C:COPII-coated ER to Golgi transport vesicle; TAS:Reactome.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR GO; GO:0033116; C:endoplasmic reticulum-Golgi intermediate compartment membrane; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; HDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IEA:Ensembl.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005764; C:lysosome; ISS:BHF-UCL.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0051087; F:chaperone binding; ISS:BHF-UCL.
DR GO; GO:0031404; F:chloride ion binding; IEA:Ensembl.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IBA:GO_Central.
DR GO; GO:0008234; F:cysteine-type peptidase activity; IDA:UniProtKB.
DR GO; GO:0008239; F:dipeptidyl-peptidase activity; IEA:UniProtKB-EC.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0016505; F:peptidase activator activity involved in apoptotic process; IEA:Ensembl.
DR GO; GO:0019902; F:phosphatase binding; ISS:BHF-UCL.
DR GO; GO:0043621; F:protein self-association; IEA:Ensembl.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IEA:Ensembl.
DR GO; GO:0007568; P:aging; IEA:Ensembl.
DR GO; GO:0006955; P:immune response; TAS:ProtInc.
DR GO; GO:0031642; P:negative regulation of myelination; IEA:Ensembl.
DR GO; GO:2001235; P:positive regulation of apoptotic signaling pathway; IEA:Ensembl.
DR GO; GO:1903980; P:positive regulation of microglial cell activation; IEA:Ensembl.
DR GO; GO:1903052; P:positive regulation of proteolysis involved in protein catabolic process; ISS:BHF-UCL.
DR GO; GO:0006508; P:proteolysis; IDA:UniProtKB.
DR GO; GO:0051603; P:proteolysis involved in protein catabolic process; IBA:GO_Central.
DR GO; GO:0010033; P:response to organic substance; IEA:Ensembl.
DR GO; GO:0001913; P:T cell mediated cytotoxicity; IEA:Ensembl.
DR CDD; cd02621; Peptidase_C1A_CathepsinC; 1.
DR Gene3D; 2.40.128.80; -; 1.
DR InterPro; IPR039412; CatC.
DR InterPro; IPR014882; CathepsinC_exc.
DR InterPro; IPR036496; CathepsinC_exc_dom_sf.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR025661; Pept_asp_AS.
DR InterPro; IPR000169; Pept_cys_AS.
DR InterPro; IPR025660; Pept_his_AS.
DR InterPro; IPR000668; Peptidase_C1A_C.
DR Pfam; PF08773; CathepsinC_exc; 1.
DR Pfam; PF00112; Peptidase_C1; 1.
DR PRINTS; PR00705; PAPAIN.
DR SMART; SM00645; Pept_C1; 1.
DR SUPFAM; SSF54001; SSF54001; 1.
DR SUPFAM; SSF75001; SSF75001; 1.
DR PROSITE; PS00640; THIOL_PROTEASE_ASN; 1.
DR PROSITE; PS00139; THIOL_PROTEASE_CYS; 1.
DR PROSITE; PS00639; THIOL_PROTEASE_HIS; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Chloride; Direct protein sequencing;
KW Disease variant; Disulfide bond; Glycoprotein; Hydrolase; Lysosome;
KW Palmoplantar keratoderma; Protease; Reference proteome; Signal;
KW Thiol protease; Zymogen.
FT SIGNAL 1..24
FT /evidence="ECO:0000269|PubMed:11015218,
FT ECO:0000269|PubMed:7665576, ECO:0000269|PubMed:9507095"
FT CHAIN 25..134
FT /note="Dipeptidyl peptidase 1 exclusion domain chain"
FT /id="PRO_0000026338"
FT PROPEP 135..230
FT /evidence="ECO:0000269|PubMed:1586157,
FT ECO:0000269|PubMed:7665576, ECO:0000269|PubMed:9507095"
FT /id="PRO_0000026339"
FT CHAIN 231..394
FT /note="Dipeptidyl peptidase 1 heavy chain"
FT /id="PRO_0000026340"
FT CHAIN 395..463
FT /note="Dipeptidyl peptidase 1 light chain"
FT /id="PRO_0000026341"
FT ACT_SITE 258
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10088"
FT ACT_SITE 405
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10089"
FT ACT_SITE 427
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10090"
FT BINDING 302
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000269|PubMed:11726493,
FT ECO:0007744|PDB:1K3B"
FT BINDING 304
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000269|PubMed:11726493,
FT ECO:0007744|PDB:1K3B"
FT BINDING 347
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000269|PubMed:11726493,
FT ECO:0007744|PDB:1K3B"
FT CARBOHYD 29
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:11726493,
FT ECO:0000269|PubMed:19167329"
FT CARBOHYD 53
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218,
FT ECO:0000269|PubMed:19167329"
FT CARBOHYD 119
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19167329"
FT CARBOHYD 276
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19167329"
FT DISULFID 30..118
FT /evidence="ECO:0000269|PubMed:11726493,
FT ECO:0007744|PDB:1K3B"
FT DISULFID 54..136
FT /evidence="ECO:0000269|PubMed:11726493,
FT ECO:0007744|PDB:1K3B"
FT DISULFID 255..298
FT /evidence="ECO:0000269|PubMed:11726493,
FT ECO:0007744|PDB:1K3B"
FT DISULFID 291..331
FT /evidence="ECO:0000269|PubMed:11726493,
FT ECO:0007744|PDB:1K3B"
FT DISULFID 321..337
FT /evidence="ECO:0000269|PubMed:11726493,
FT ECO:0007744|PDB:1K3B"
FT VAR_SEQ 107..141
FT /note="YKEEGSKVTTYCNETMTGWVHDVLGRNWACFTGKK -> DVTDFISHLFMQL
FT GTVGIYDLPHLRNKLAMNRRWG (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_043232"
FT VAR_SEQ 107..137
FT /note="YKEEGSKVTTYCNETMTGWVHDVLGRNWACF -> DVTDFISHLFMQLGTVG
FT IYDLPHLRNKLVIK (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:17974005"
FT /id="VSP_039123"
FT VAR_SEQ 138..463
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:17974005"
FT /id="VSP_039124"
FT VAR_SEQ 142..463
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_043233"
FT VARIANT 39
FT /note="W -> S (in PLS; dbSNP:rs104894210)"
FT /evidence="ECO:0000269|PubMed:11180012"
FT /id="VAR_016933"
FT VARIANT 67..74
FT /note="Missing (in PLS)"
FT /evidence="ECO:0000269|PubMed:11106356"
FT /id="VAR_019035"
FT VARIANT 127
FT /note="H -> P (in PLS; dbSNP:rs104894216)"
FT /evidence="ECO:0000269|PubMed:11886537"
FT /id="VAR_016934"
FT VARIANT 129
FT /note="V -> E (in PLS; dbSNP:rs760130711)"
FT /evidence="ECO:0000269|PubMed:14974080"
FT /id="VAR_019036"
FT VARIANT 139
FT /note="G -> R (in PLS; dbSNP:rs749103588)"
FT /evidence="ECO:0000269|PubMed:12112662,
FT ECO:0000269|PubMed:14974080"
FT /id="VAR_019037"
FT VARIANT 153
FT /note="I -> T (in dbSNP:rs217086)"
FT /evidence="ECO:0000269|PubMed:11106356,
FT ECO:0000269|PubMed:11180601, ECO:0000269|PubMed:11886537,
FT ECO:0000269|PubMed:12112662, ECO:0000269|PubMed:12809647,
FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:14974080,
FT ECO:0000269|PubMed:1586157, ECO:0000269|PubMed:7649281,
FT ECO:0000269|PubMed:9092576, ECO:0000269|Ref.6,
FT ECO:0000269|Ref.9"
FT /id="VAR_016943"
FT VARIANT 236
FT /note="D -> Y (in PLS; dbSNP:rs764724707)"
FT /evidence="ECO:0000269|PubMed:11180601,
FT ECO:0000269|PubMed:14974080"
FT /id="VAR_019038"
FT VARIANT 249
FT /note="V -> F (in PLS)"
FT /evidence="ECO:0000269|PubMed:10581027,
FT ECO:0000269|PubMed:14974080"
FT /id="VAR_009541"
FT VARIANT 252
FT /note="Q -> L (in PLS; dbSNP:rs104894207)"
FT /evidence="ECO:0000269|PubMed:10581027,
FT ECO:0000269|PubMed:14974080"
FT /id="VAR_009542"
FT VARIANT 272
FT /note="R -> H (in PLS; dbSNP:rs587777534)"
FT /evidence="ECO:0000269|PubMed:14974080"
FT /id="VAR_019039"
FT VARIANT 272
FT /note="R -> P (in PLS; dbSNP:rs587777534)"
FT /evidence="ECO:0000269|PubMed:10581027,
FT ECO:0000269|PubMed:11106356, ECO:0000269|PubMed:11158173,
FT ECO:0000269|PubMed:11886537, ECO:0000269|PubMed:12112662"
FT /id="VAR_009543"
FT VARIANT 286
FT /note="Q -> R (in HMS and PLS; dbSNP:rs104894208)"
FT /evidence="ECO:0000269|PubMed:10662807,
FT ECO:0000269|PubMed:11180601"
FT /id="VAR_016935"
FT VARIANT 291
FT /note="C -> Y (in PLS; dbSNP:rs748729285)"
FT /evidence="ECO:0000269|PubMed:11180601"
FT /id="VAR_019040"
FT VARIANT 294
FT /note="Y -> H (in PLS)"
FT /evidence="ECO:0000269|PubMed:12809647"
FT /id="VAR_039686"
FT VARIANT 300
FT /note="G -> D (in PLS)"
FT /evidence="ECO:0000269|PubMed:11158173,
FT ECO:0000269|PubMed:25799584"
FT /id="VAR_019041"
FT VARIANT 300
FT /note="G -> S (in PLS)"
FT /evidence="ECO:0000269|PubMed:11106356"
FT /id="VAR_019042"
FT VARIANT 301
FT /note="G -> S (in PLS; dbSNP:rs104894214)"
FT /evidence="ECO:0000269|PubMed:10581027,
FT ECO:0000269|PubMed:11106356, ECO:0000269|PubMed:11180012,
FT ECO:0000269|PubMed:14974080"
FT /id="VAR_009544"
FT VARIANT 301
FT /note="G -> V (in PLS)"
FT /evidence="ECO:0000269|PubMed:11106356"
FT /id="VAR_019043"
FT VARIANT 304
FT /note="Y -> N (in PLS)"
FT /evidence="ECO:0000269|PubMed:11106356"
FT /id="VAR_019044"
FT VARIANT 312
FT /note="Q -> R (in PLS; dbSNP:rs1484758757)"
FT /evidence="ECO:0000269|PubMed:14974080"
FT /id="VAR_019045"
FT VARIANT 319
FT /note="E -> G (in PLS; dbSNP:rs1294233227)"
FT /evidence="ECO:0000269|PubMed:11106356"
FT /id="VAR_019046"
FT VARIANT 339
FT /note="R -> C (in PLS; dbSNP:rs1044703733)"
FT /evidence="ECO:0000269|PubMed:10581027,
FT ECO:0000269|PubMed:10662808, ECO:0000269|PubMed:11106356,
FT ECO:0000269|PubMed:11886537, ECO:0000269|PubMed:14974080"
FT /id="VAR_009545"
FT VARIANT 340
FT /note="Y -> C (in PLS)"
FT /evidence="ECO:0000269|PubMed:10662808,
FT ECO:0000269|PubMed:11106356"
FT /id="VAR_016944"
FT VARIANT 347
FT /note="Y -> C (in PLS and AP1; dbSNP:rs104894211)"
FT /evidence="ECO:0000269|PubMed:10581027,
FT ECO:0000269|PubMed:10662808, ECO:0000269|PubMed:14974080"
FT /id="VAR_009546"
FT VARIANT 401
FT /note="E -> K (in dbSNP:rs200627023)"
FT /evidence="ECO:0000269|PubMed:11886537"
FT /id="VAR_016945"
FT VARIANT 405
FT /note="H -> N (in PLS)"
FT /evidence="ECO:0000269|PubMed:15108292"
FT /id="VAR_027249"
FT VARIANT 405
FT /note="H -> R (in PLS; dbSNP:rs151269219)"
FT /evidence="ECO:0000269|PubMed:15991336"
FT /id="VAR_027250"
FT VARIANT 412
FT /note="Y -> C (in AP1; dbSNP:rs28937571)"
FT /evidence="ECO:0000269|PubMed:14974080"
FT /id="VAR_019047"
FT VARIANT 429
FT /note="W -> C (in PLS; dbSNP:rs104894215)"
FT /evidence="ECO:0000269|PubMed:11886537"
FT /id="VAR_016936"
FT VARIANT 447
FT /note="E -> G (in PLS)"
FT /evidence="ECO:0000269|PubMed:11106356,
FT ECO:0000269|PubMed:14974080"
FT /id="VAR_019048"
FT VARIANT 453
FT /note="I -> V (in dbSNP:rs3888798)"
FT /evidence="ECO:0000269|PubMed:11180012"
FT /id="VAR_016946"
FT CONFLICT 63
FT /note="K -> I (in Ref. 6; BAD96758)"
FT /evidence="ECO:0000305"
FT CONFLICT 237
FT /note="W -> V (in Ref. 14; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 321
FT /note="C -> S (in Ref. 14; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 355
FT /note="C -> M (in Ref. 14; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 366
FT /note="H -> R (in Ref. 14; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 376..378
FT /note="VYD -> YVY (in Ref. 14; AA sequence)"
FT /evidence="ECO:0000305"
FT HELIX 32..35
FT /evidence="ECO:0007829|PDB:4OEL"
FT STRAND 37..48
FT /evidence="ECO:0007829|PDB:4OEL"
FT TURN 49..51
FT /evidence="ECO:0007829|PDB:1K3B"
FT HELIX 54..56
FT /evidence="ECO:0007829|PDB:4OEL"
FT STRAND 60..69
FT /evidence="ECO:0007829|PDB:4OEL"
FT TURN 70..72
FT /evidence="ECO:0007829|PDB:4OEL"
FT STRAND 73..75
FT /evidence="ECO:0007829|PDB:4OEL"
FT STRAND 81..87
FT /evidence="ECO:0007829|PDB:4OEL"
FT TURN 88..90
FT /evidence="ECO:0007829|PDB:4OEL"
FT STRAND 91..96
FT /evidence="ECO:0007829|PDB:4OEL"
FT STRAND 99..110
FT /evidence="ECO:0007829|PDB:4OEL"
FT STRAND 113..121
FT /evidence="ECO:0007829|PDB:4OEL"
FT STRAND 123..128
FT /evidence="ECO:0007829|PDB:4OEL"
FT STRAND 133..141
FT /evidence="ECO:0007829|PDB:4OEL"
FT STRAND 254..256
FT /evidence="ECO:0007829|PDB:2DJF"
FT HELIX 258..274
FT /evidence="ECO:0007829|PDB:4OEL"
FT TURN 275..277
FT /evidence="ECO:0007829|PDB:4OEL"
FT HELIX 285..291
FT /evidence="ECO:0007829|PDB:4OEL"
FT HELIX 297..299
FT /evidence="ECO:0007829|PDB:4OEM"
FT HELIX 303..306
FT /evidence="ECO:0007829|PDB:4OEL"
FT HELIX 309..313
FT /evidence="ECO:0007829|PDB:4OEL"
FT HELIX 319..321
FT /evidence="ECO:0007829|PDB:4OEL"
FT STRAND 342..347
FT /evidence="ECO:0007829|PDB:4OEL"
FT HELIX 357..367
FT /evidence="ECO:0007829|PDB:4OEL"
FT STRAND 370..374
FT /evidence="ECO:0007829|PDB:4OEL"
FT HELIX 378..382
FT /evidence="ECO:0007829|PDB:4OEL"
FT STRAND 385..388
FT /evidence="ECO:0007829|PDB:4OEL"
FT STRAND 405..414
FT /evidence="ECO:0007829|PDB:4OEL"
FT TURN 416..418
FT /evidence="ECO:0007829|PDB:4OEL"
FT STRAND 421..426
FT /evidence="ECO:0007829|PDB:4OEL"
FT STRAND 431..433
FT /evidence="ECO:0007829|PDB:2DJG"
FT STRAND 438..442
FT /evidence="ECO:0007829|PDB:4OEL"
FT TURN 443..446
FT /evidence="ECO:0007829|PDB:4CDE"
FT HELIX 447..449
FT /evidence="ECO:0007829|PDB:4OEL"
FT STRAND 455..459
FT /evidence="ECO:0007829|PDB:4OEL"
SQ SEQUENCE 463 AA; 51854 MW; 4C9C7C24D900CEE6 CRC64;
MGAGPSLLLA ALLLLLSGDG AVRCDTPANC TYLDLLGTWV FQVGSSGSQR DVNCSVMGPQ
EKKVVVYLQK LDTAYDDLGN SGHFTIIYNQ GFEIVLNDYK WFAFFKYKEE GSKVTTYCNE
TMTGWVHDVL GRNWACFTGK KVGTASENVY VNIAHLKNSQ EKYSNRLYKY DHNFVKAINA
IQKSWTATTY MEYETLTLGD MIRRSGGHSR KIPRPKPAPL TAEIQQKILH LPTSWDWRNV
HGINFVSPVR NQASCGSCYS FASMGMLEAR IRILTNNSQT PILSPQEVVS CSQYAQGCEG
GFPYLIAGKY AQDFGLVEEA CFPYTGTDSP CKMKEDCFRY YSSEYHYVGG FYGGCNEALM
KLELVHHGPM AVAFEVYDDF LHYKKGIYHH TGLRDPFNPF ELTNHAVLLV GYGTDSASGM
DYWIVKNSWG TGWGENGYFR IRRGTDECAI ESIAVAATPI PKL
