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 27-MAR-2024, entry version 224. DE RecName: Full=Dipeptidyl peptidase 1; DE EC=3.4.14.1 {ECO:0000269|PubMed:1586157}; 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), VARIANT THR-153, AND VARIANT 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 SUBCELLULAR LOCATION. 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, CATALYTIC RP ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, RP GLYCOSYLATION, AND 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 FUNCTION. RX PubMed=8428921; DOI=10.1016/s0021-9258(18)53798-4; RA McGuire M.J., Lipsky P.E., Thiele D.L.; RT "Generation of active myeloid and lymphoid granule serine proteases RT requires processing by the granule thiol protease dipeptidyl peptidase I."; RL J. Biol. Chem. 268:2458-2467(1993). RN [16] 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 [17] 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 [18] 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 [19] 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 [20] 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 [21] {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 [22] 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 [23] 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 [24] 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 [25] 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 [26] 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 [27] 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 [28] 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 [29] 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 [30] 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 [31] 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 [32] 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 [33] 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 [34] 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 (PubMed:1586157). Has dipeptidylpeptidase CC activity (PubMed:1586157). Active against a broad range of dipeptide CC substrates composed of both polar and hydrophobic amino acids CC (PubMed:1586157). Proline cannot occupy the P1 position and arginine CC cannot occupy the P2 position of the substrate (PubMed:1586157). Can CC act as both an exopeptidase and endopeptidase (PubMed:1586157). CC Activates serine proteases such as elastase, cathepsin G and granzymes CC A and B (PubMed:8428921). {ECO:0000269|PubMed:1586157, CC ECO:0000269|PubMed:8428921}. 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 Evidence={ECO:0000269|PubMed:1586157}; 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 {ECO:0000305|PubMed:7665576}. 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 --------------------------------------------------------------------------- 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; 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; 61. DR IntAct; P53634; 28. 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 GlyCosmos; P53634; 4 sites, 57 glycans. DR GlyGen; P53634; 6 sites, 57 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; 9606-ENSP00000227266; -. DR PeptideAtlas; P53634; -. DR ProteomicsDB; 56595; -. [P53634-1] DR ProteomicsDB; 56596; -. [P53634-2] DR ProteomicsDB; 56597; -. [P53634-3] DR Pumba; P53634; -. DR TopDownProteomics; P53634-1; -. [P53634-1] DR Antibodypedia; 31473; 317 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 AGR; HGNC:2528; -. 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; HWDWRNV; -. DR OrthoDB; 5475703at2759; -. DR PhylomeDB; P53634; -. DR TreeFam; TF313225; -. DR BioCyc; MetaCyc:HS03265-MONOMER; -. 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; 13 hits in 1164 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 203 other cell types or tissues. DR ExpressionAtlas; P53634; baseline and differential. 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: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: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:0051087; F:protein-folding chaperone binding; ISS:BHF-UCL. DR GO; GO:0004252; F:serine-type endopeptidase activity; 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; Cathepsin C, exclusion domain; 1. DR Gene3D; 3.90.70.10; Cysteine proteinases; 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; IPR013128; Peptidase_C1A. DR InterPro; IPR000668; Peptidase_C1A_C. DR PANTHER; PTHR12411; CYSTEINE PROTEASE FAMILY C1-RELATED; 1. DR PANTHER; PTHR12411:SF942; DIPEPTIDYL PEPTIDASE 1; 1. 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; Cysteine proteinases; 1. DR SUPFAM; SSF75001; Dipeptidyl peptidase I (cathepsin C), exclusion domain; 1. DR PROSITE; PS00640; THIOL_PROTEASE_ASN; 1. DR PROSITE; PS00139; THIOL_PROTEASE_CYS; 1. DR PROSITE; PS00639; THIOL_PROTEASE_HIS; 1. DR Genevisible; P53634; HS. 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 //