ID CATC_HUMAN Reviewed; 463 AA. AC P53634; A8K7V2; Q53G93; Q71E75; Q71E76; Q7M4N9; Q7Z3G7; Q8WY99; AC Q8WYA7; Q8WYA8; DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-1996, sequence version 1. DT 13-JUL-2010, entry version 112. DE RecName: Full=Dipeptidyl peptidase 1; DE EC=3.4.14.1; DE AltName: Full=Dipeptidyl peptidase I; DE Short=DPP-I; DE Short=DPPI; DE AltName: Full=Cathepsin C; DE AltName: Full=Cathepsin J; 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; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Ileum; RX MEDLINE=95377428; 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, AND TISSUE SPECIFICITY. RX MEDLINE=97248590; 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, RT and expression."; RL J. Biol. Chem. 272:10260-10265(1997). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT ILE-153, AND VARIANTS RP PLS TYR-236; ARG-286 AND TYR-291. RC TISSUE=Blood; RX MEDLINE=21113227; PubMed=11180601; RX DOI=10.1002/1098-1004(200102)17:2<152::AID-HUMU10>3.3.CO;2-R; 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 VARIANT PLS HIS-294. RC TISSUE=Blood; RX MEDLINE=22695588; 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- RT Lefevre syndrome."; RL Mol. Genet. Metab. 79:146-148(2003). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=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., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA 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., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., 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). 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., RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., RA Ottenwaelder B., Poustka A., 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], AND VARIANT ILE-153. 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., RA Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., RA FitzGerald M.G., Jaffe D.B., LaButti K., Nicol R., Park H.-S., RA Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., RA Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., RA 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]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [10] RP PROTEIN SEQUENCE OF 25-71; 122-143; 231-235 AND 395-399, RP CHARACTERIZATION 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 [11] 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 RT cathepsin C."; RL J. Biol. Chem. 270:21626-21631(1995). RN [12] RP PROTEIN SEQUENCE OF 25-28; 51-61; 114-117 AND 133-139, RP CHARACTERIZATION OF 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 RT for an intramolecular chaperone in folding and stabilizing the human RT proenzyme."; RL Biochemistry 39:12382-12390(2000). RN [13] RP PROTEIN SEQUENCE OF 231-290; 310-328 AND 340-383, FUNCTION, ENZYME RP REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, AND GLYCOSYLATION. RC TISSUE=Spleen; RX MEDLINE=92264725; 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 RT human spleen."; RL Arch. Biochem. Biophys. 295:280-288(1992). RN [14] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RA Colinge J., Superti-Furga G., Bennett K.L.; RL Submitted (OCT-2008) to UniProtKB. RN [15] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-53, AND MASS SPECTROMETRY. 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 RT multiple enzyme digestion and hydrazide chemistry."; RL J. Proteome Res. 8:651-661(2009). RN [16] RP X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) OF 25-143 AND 231-463 IN RP COMPLEX WITH CHLORIDE IONS, SUBUNIT, DISULFIDE BONDS, AND RP GLYCOSYLATION AT ASN-29. RX MEDLINE=21583324; 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 RT domain added to an endopeptidase framework creates the machine for RT activation of granular serine proteases."; RL EMBO J. 20:6570-6582(2001). RN [17] RP VARIANTS PLS PHE-249; LEU-252; PRO-272; SER-301; CYS-339 AND CYS-347. RX MEDLINE=20047769; PubMed=10581027; DOI=10.1038/70525; RA Toomes C., James J., Wood A.J., Wu C.L., McCormick D., Lench N., RA Hewitt C., Moynihan L., Roberts E., Woods C.G., Markham A., Wong M., RA Widmer R., Ghaffar K.A., Pemberton M., Hussein I.R., Temtamy S.A., RA Davies R., Read A.P., Sloan P., Dixon M.J., Thakker N.S.; RT "Loss-of-function mutations in the cathepsin C gene result in RT periodontal disease and palmoplantar keratosis."; RL Nat. Genet. 23:421-424(1999). RN [18] RP VARIANT HMS ARG-286. RX MEDLINE=20130333; PubMed=10662807; DOI=10.1136/jmg.37.2.88; RA Hart T.C., Hart P.S., Michalec M.D., Zhang Y., Firatli E., RA Van Dyke T.E., Stabholz A., Zlotogorski A., Shapira L., Soskolne W.A.; RT "Haim-Munk syndrome and Papillon-Lefevre syndrome are allelic RT mutations in cathepsin C."; RL J. Med. Genet. 37:88-94(2000). RN [19] RP VARIANTS PLS CYS-339 AND CYS-340, AND VARIANT JPD 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., RA Cooper M., Yassin O.M., Nusier M., Walker S.; RT "Localisation of a gene for prepubertal periodontitis to chromosome RT 11q14 and identification of a cathepsin C gene mutation."; RL J. Med. Genet. 37:95-101(2000). RN [20] 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 ILE-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 RT Papillon-Lefevre syndrome patients."; RL J. Med. Genet. 37:927-932(2000). RN [21] RP VARIANTS PLS SER-39 AND SER-301, AND VARIANT VAL-453. RX MEDLINE=21103486; PubMed=11180012; RX 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 RT cathepsin C gene."; RL J. Invest. Dermatol. 116:339-343(2001). RN [22] RP VARIANTS PLS PRO-127; PRO-272; CYS-339 AND CYS-429, AND VARIANTS RP ILE-153 AND LYS-401. RX MEDLINE=21884204; PubMed=11886537; RX 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 RT C gene in nine families from Europe and North Africa with Papillon- RT Lefevre syndrome."; RL J. Invest. Dermatol. 117:1657-1661(2001). RN [23] 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 [24] RP VARIANTS PLS ARG-139 AND PRO-272, AND VARIANT ILE-153. RX PubMed=12112662; DOI=10.1002/humu.9040; RA Zhang Y., Hart P.S., Moretti A.J., Bouwsma O.J., Fisher E.M., RA Dudlicek L., 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 [25] RP VARIANTS PLS GLU-129; ARG-139; TYR-236; PHE-249; LEU-252; HIS-272; RP SER-301; ARG-312; CYS-339; CYS-347 AND GLY-447, VARIANTS JPD HIS-272 RP AND CYS-412, AND VARIANT ILE-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., RA Hattab F., Al-Hamed M., Sloan P., Toomes C., Dixon M.J., James J., RA Read A.P., 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 [26] 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 RT Papillon-Lefevre syndrome are associated with deficiency of serine RT proteinases in PMNs."; RL Hum. Mutat. 23:524-524(2004). RN [27] 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 [28] RP ERRATUM. RA de Haar S.F., Mir M., Nguyen M., Kazemi B., Ramezani G.H., Everts V.; RL Hum. Genet. 118:533-533(2005). CC -!- FUNCTION: Thiol protease. Has dipeptidylpeptidase activity. Active CC against a broad range of dipeptide substrates composed of both CC polar and hydrophobic amino acids. Proline cannot occupy the P1 CC position and arginine cannot occupy the P2 position of the CC substrate. Can act as both an exopeptidase and endopeptidase. CC Activates serine proteases such as elastase, cathepsin G and CC granzymes A and B. Can also activate neuraminidase and factor CC XIII. CC -!- CATALYTIC ACTIVITY: Release of an N-terminal dipeptide, Xaa-Yaa-|- CC Zaa-, except when Xaa is Arg or Lys, or Yaa or Zaa is Pro. CC -!- COFACTOR: Binds 1 chloride ion per heavy chain. CC -!- ENZYME REGULATION: Strongly inhibited by the cysteine peptidase CC inhibitors mersalyl acid, iodoacetic acid and cystatin. Inhibited CC by N-ethylmaleimide, Gly-Phe-diazomethane, TLCK, TPCK and, at low CC pH, by dithiodipyridine. Not inhibited by the serine peptidase CC inhibitor PMSF, the aminopeptidase inhibitor bestatin, or metal CC ion chelators. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC pH dependence: CC High activity at pH 4.5-6.8; CC -!- SUBUNIT: Tetramer of heterotrimers consisting of exclusion domain, CC heavy- and light chains. CC -!- SUBCELLULAR LOCATION: Lysosome. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P53634-1; Sequence=Displayed; CC Name=2; CC IsoId=P53634-2; Sequence=VSP_039123, VSP_039124; CC -!- TISSUE SPECIFICITY: Ubiquitous. Highly expressed in lung, kidney CC and placenta. Detected at intermediate levels in colon, small CC intestine, spleen and pancreas. CC -!- INDUCTION: Up-regulated in lymphocytes by IL2. CC -!- PTM: N-glycosylated. 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 CC domain are held together by a disulfide bond. CC -!- DISEASE: Defects in CTSC are a cause of Papillon-Lefevre syndrome CC (PLS) [MIM:245000]; also known as keratosis palmoplantaris with CC periodontopathia. PLS is an autosomal recessive disorder CC characterized by palmoplantar keratosis and severe periodontitis CC affecting deciduous and permanent dentitions and resulting in CC premature tooth loss. The palmoplantar keratotic phenotype vary CC from mild psoriasiform scaly skin to overt hyperkeratosis. CC Keratosis also affects other sites such as elbows and knees. CC -!- DISEASE: Defects in CTSC are a cause of Haim-Munk syndrome (HMS) CC [MIM:245010]; also known as keratosis palmoplantaris with CC periodontopathia and onychogryposis or Cochin Jewish disorder. HMS CC is an autosomal recessive disorder characterized by palmoplantar CC keratosis, onychogryphosis and periodontitis. Additional features CC are pes planus, arachnodactyly, and acroosteolysis. CC -!- DISEASE: Defects in CTSC are a cause of juvenile periodontitis CC (JPD) [MIM:170650]; also known as prepubertal periodontitis (PPP). CC JPD is characterized by severe and protracted gingival infections, CC leading to tooth loss. JPD inheritance is autosomal dominant. CC -!- SIMILARITY: Belongs to the peptidase C1 family. CC -!- SEQUENCE CAUTION: CC Sequence=CAD97897.1; Type=Erroneous initiation; Note=Translation N-terminally shortened; CC -!- WEB RESOURCE: Name=CTSCbase; Note=CTSC mutation db; CC URL="http://bioinf.uta.fi/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; 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 IPI; IPI00022810; -. DR PIR; S23941; S23941. DR PIR; S66504; S66504. DR RefSeq; NP_001805.3; -. DR UniGene; Hs.128065; -. 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 PDBsum; 1K3B; -. DR PDBsum; 2DJF; -. DR PDBsum; 2DJG; -. DR SMR; P53634; 25-463. DR IntAct; P53634; 2. DR MINT; MINT-4655964; -. DR STRING; P53634; -. DR MEROPS; C01.070; -. DR PRIDE; P53634; -. DR Ensembl; ENST00000227266; ENSP00000227266; ENSG00000109861; Homo sapiens. DR Ensembl; ENST00000415415; ENSP00000411027; ENSG00000109861; Homo sapiens. DR GeneID; 1075; -. DR UCSC; uc001pck.2; human. DR CTD; 1075; -. DR GeneCards; GC11M087666; -. DR H-InvDB; HIX0026143; -. DR HGNC; HGNC:2528; CTSC. DR HPA; CAB025364; -. DR MIM; 170650; phenotype. DR MIM; 245000; phenotype. DR MIM; 245010; phenotype. DR MIM; 602365; gene. DR Orphanet; 2342; Haim-Munk syndrome. DR Orphanet; 678; Papillon-Lefevre syndrome. DR PharmGKB; PA27028; -. DR eggNOG; prNOG11734; -. DR HOVERGEN; HBG005248; -. DR InParanoid; P53634; -. DR BRENDA; 3.4.14.1; 247. DR NextBio; 4488; -. DR PMAP-CutDB; P53634; -. DR ArrayExpress; P53634; -. DR Bgee; P53634; -. DR Genevestigator; P53634; -. DR GermOnline; ENSG00000109861; Homo sapiens. DR GO; GO:0005764; C:lysosome; TAS:UniProtKB. DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IEA:InterPro. DR GO; GO:0006955; P:immune response; TAS:ProtInc. DR GO; GO:0006508; P:proteolysis; IEA:InterPro. DR InterPro; IPR014882; CathepsinC_exc. DR InterPro; IPR000169; Pept_cys_AS. DR InterPro; IPR013128; Peptidase_C1A. DR InterPro; IPR000668; Peptidase_C1A_C. DR PANTHER; PTHR12411; Peptidase_C1A; 1. DR Pfam; PF08773; CathepsinC_exc; 1. DR Pfam; PF00112; Peptidase_C1; 1. DR PRINTS; PR00705; PAPAIN. DR SMART; SM00645; Pept_C1; 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; Complete proteome; KW Direct protein sequencing; Disease mutation; Disulfide bond; KW Glycoprotein; Hydrolase; Lysosome; Palmoplantar keratoderma; KW Polymorphism; Protease; Signal; Thiol protease; Zymogen. FT SIGNAL 1 24 FT CHAIN 25 134 Dipeptidyl peptidase 1 exclusion domain FT chain. FT /FTId=PRO_0000026338. FT PROPEP 135 230 FT /FTId=PRO_0000026339. FT CHAIN 231 394 Dipeptidyl peptidase 1 heavy chain. FT /FTId=PRO_0000026340. FT CHAIN 395 463 Dipeptidyl peptidase 1 light chain. FT /FTId=PRO_0000026341. FT ACT_SITE 258 258 FT ACT_SITE 405 405 FT ACT_SITE 427 427 FT BINDING 302 302 Chloride. FT BINDING 304 304 Chloride; via amide nitrogen. FT BINDING 347 347 Chloride. FT CARBOHYD 29 29 N-linked (GlcNAc...). FT CARBOHYD 53 53 N-linked (GlcNAc...). FT CARBOHYD 119 119 N-linked (GlcNAc...). FT CARBOHYD 276 276 N-linked (GlcNAc...). FT DISULFID 30 118 FT DISULFID 54 136 FT DISULFID 255 298 FT DISULFID 291 331 FT DISULFID 321 337 FT VAR_SEQ 107 137 YKEEGSKVTTYCNETMTGWVHDVLGRNWACF -> DVTDFI FT SHLFMQLGTVGIYDLPHLRNKLVIK (in isoform 2). FT /FTId=VSP_039123. FT VAR_SEQ 138 463 Missing (in isoform 2). FT /FTId=VSP_039124. FT VARIANT 39 39 W -> S (in PLS). FT /FTId=VAR_016933. FT VARIANT 67 74 Missing (in PLS). FT /FTId=VAR_019035. FT VARIANT 127 127 H -> P (in PLS). FT /FTId=VAR_016934. FT VARIANT 129 129 V -> E (in PLS). FT /FTId=VAR_019036. FT VARIANT 139 139 G -> R (in PLS). FT /FTId=VAR_019037. FT VARIANT 153 153 T -> I (in dbSNP:rs217086). FT /FTId=VAR_016943. FT VARIANT 236 236 D -> Y (in PLS). FT /FTId=VAR_019038. FT VARIANT 249 249 V -> F (in PLS). FT /FTId=VAR_009541. FT VARIANT 252 252 Q -> L (in PLS). FT /FTId=VAR_009542. FT VARIANT 272 272 R -> H (in PLS). FT /FTId=VAR_019039. FT VARIANT 272 272 R -> P (in PLS). FT /FTId=VAR_009543. FT VARIANT 286 286 Q -> R (in HMS and PLS). FT /FTId=VAR_016935. FT VARIANT 291 291 C -> Y (in PLS). FT /FTId=VAR_019040. FT VARIANT 294 294 Y -> H (in PLS). FT /FTId=VAR_039686. FT VARIANT 300 300 G -> D (in PLS). FT /FTId=VAR_019041. FT VARIANT 300 300 G -> S (in PLS). FT /FTId=VAR_019042. FT VARIANT 301 301 G -> S (in PLS). FT /FTId=VAR_009544. FT VARIANT 301 301 G -> V (in PLS). FT /FTId=VAR_019043. FT VARIANT 304 304 Y -> N (in PLS). FT /FTId=VAR_019044. FT VARIANT 312 312 Q -> R (in PLS). FT /FTId=VAR_019045. FT VARIANT 319 319 E -> G (in PLS). FT /FTId=VAR_019046. FT VARIANT 339 339 R -> C (in PLS). FT /FTId=VAR_009545. FT VARIANT 340 340 Y -> C (in PLS). FT /FTId=VAR_016944. FT VARIANT 347 347 Y -> C (in PLS and JPD). FT /FTId=VAR_009546. FT VARIANT 401 401 E -> K. FT /FTId=VAR_016945. FT VARIANT 405 405 H -> N (in PLS). FT /FTId=VAR_027249. FT VARIANT 405 405 H -> R (in PLS). FT /FTId=VAR_027250. FT VARIANT 412 412 Y -> C (in JPD; dbSNP:rs28937571). FT /FTId=VAR_019047. FT VARIANT 429 429 W -> C (in PLS). FT /FTId=VAR_016936. FT VARIANT 447 447 E -> G (in PLS). FT /FTId=VAR_019048. FT VARIANT 453 453 I -> V (rare polymorphism; FT dbSNP:rs3888798). FT /FTId=VAR_016946. FT CONFLICT 63 63 K -> I (in Ref. 6; BAD96758). FT CONFLICT 237 237 W -> V (in Ref. 13; AA sequence). FT CONFLICT 321 321 C -> S (in Ref. 13; AA sequence). FT CONFLICT 355 355 C -> M (in Ref. 13; AA sequence). FT CONFLICT 366 366 H -> R (in Ref. 13; AA sequence). FT CONFLICT 376 378 VYD -> YVY (in Ref. 13; AA sequence). FT HELIX 32 35 FT STRAND 36 43 FT TURN 49 51 FT STRAND 62 69 FT TURN 70 72 FT STRAND 73 76 FT STRAND 81 87 FT TURN 88 90 FT STRAND 91 96 FT STRAND 99 112 FT STRAND 114 121 FT STRAND 123 128 FT STRAND 133 141 FT HELIX 258 274 FT TURN 275 277 FT HELIX 285 291 FT HELIX 303 306 FT HELIX 309 313 FT TURN 319 321 FT STRAND 342 347 FT HELIX 357 367 FT STRAND 370 374 FT HELIX 378 381 FT STRAND 385 388 FT STRAND 405 414 FT TURN 416 418 FT STRAND 421 426 FT STRAND 438 442 FT HELIX 447 449 FT STRAND 455 459 SQ SEQUENCE 463 AA; 51842 MW; 759B5EF1290C3771 CRC64; MGAGPSLLLA ALLLLLSGDG AVRCDTPANC TYLDLLGTWV FQVGSSGSQR DVNCSVMGPQ EKKVVVYLQK LDTAYDDLGN SGHFTIIYNQ GFEIVLNDYK WFAFFKYKEE GSKVTTYCNE TMTGWVHDVL GRNWACFTGK KVGTASENVY VNTAHLKNSQ 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 //