ID CATC_RAT Reviewed; 462 AA. AC P80067; P80068; DT 01-MAY-1992, integrated into UniProtKB/Swiss-Prot. DT 05-SEP-2006, sequence version 3. DT 24-JAN-2024, entry version 184. DE RecName: Full=Dipeptidyl peptidase 1; DE EC=3.4.14.1 {ECO:0000269|PubMed:1740150}; 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; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=1885565; DOI=10.1016/s0021-9258(18)55298-4; RA Ishidoh K., Muno D., Sato N., Kominami E.; RT "Molecular cloning of cDNA for rat cathepsin C. Cathepsin C, a cysteine RT proteinase with an extremely long propeptide."; RL J. Biol. Chem. 266:16312-16317(1991). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY. RC STRAIN=Wistar; TISSUE=Kidney; RX PubMed=1515062; DOI=10.1515/bchm3.1992.373.2.367; RA Kominami E., Ishidoh K., Muno D., Sato N.; RT "The primary structure and tissue distribution of cathepsin C."; RL Biol. Chem. Hoppe-Seyler 373:367-373(1992). RN [3] RP PROTEIN SEQUENCE OF 25-47; 230-251 AND 393-427, FUNCTION, CATALYTIC RP ACTIVITY, AND SUBCELLULAR LOCATION. RC TISSUE=Liver; RX PubMed=1740150; DOI=10.1111/j.1432-1033.1992.tb16647.x; RA Nikawa T., Towatari T., Katunuma N.; RT "Purification and characterization of cathepsin J from rat liver."; RL Eur. J. Biochem. 204:381-393(1992). RN [4] RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 25-462, SUBUNIT, GLYCOSYLATION AT RP ASN-29 AND ASN-275, AND DISULFIDE BONDS. RX PubMed=11602245; DOI=10.1016/s0014-5793(01)02911-8; RA Olsen J.G., Kadziola A., Lauritzen C., Pedersen J., Larsen S., Dahl S.W.; RT "Tetrameric dipeptidyl peptidase I directs substrate specificity by use of RT the residual pro-part domain."; RL FEBS Lett. 506:201-206(2001). CC -!- FUNCTION: Thiol protease (PubMed:1740150). Has dipeptidylpeptidase CC activity (PubMed:1740150). Active against a broad range of dipeptide CC substrates composed of both polar and hydrophobic amino acids. Proline CC cannot occupy the P1 position and arginine cannot occupy the P2 CC position of the substrate (PubMed:1740150). Can act as both an CC exopeptidase and endopeptidase (By similarity). Activates serine CC proteases such as elastase, cathepsin G and granzymes A and B (By CC similarity). {ECO:0000250|UniProtKB:P53634, CC ECO:0000269|PubMed:1740150}. 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:1740150}; CC -!- COFACTOR: CC Name=chloride; Xref=ChEBI:CHEBI:17996; CC Evidence={ECO:0000250|UniProtKB:P53634}; CC Note=Binds 1 Cl(-) ion per heavy chain. {ECO:0000250|UniProtKB:P53634}; CC -!- SUBUNIT: Tetramer of heterotrimers consisting of exclusion domain, CC heavy- and light chains. {ECO:0000269|PubMed:11602245}. CC -!- SUBCELLULAR LOCATION: Lysosome {ECO:0000269|PubMed:1740150}. CC -!- TISSUE SPECIFICITY: Broadly distributed, but higher levels found in CC liver, spleen, intestine, lung and kidney. CC {ECO:0000269|PubMed:1515062}. 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 --------------------------------------------------------------------------- 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; D90404; BAA14400.1; -; mRNA. DR PIR; A41158; A41158. DR RefSeq; NP_058793.1; NM_017097.1. DR PDB; 1JQP; X-ray; 2.40 A; A=25-462. DR PDBsum; 1JQP; -. DR AlphaFoldDB; P80067; -. DR SMR; P80067; -. DR STRING; 10116.ENSRNOP00000022342; -. DR BindingDB; P80067; -. DR ChEMBL; CHEMBL3308944; -. DR GuidetoPHARMACOLOGY; 2344; -. DR MEROPS; C01.070; -. DR GlyCosmos; P80067; 4 sites, No reported glycans. DR GlyGen; P80067; 4 sites. DR iPTMnet; P80067; -. DR PhosphoSitePlus; P80067; -. DR PaxDb; 10116-ENSRNOP00000022342; -. DR Ensembl; ENSRNOT00000022342.6; ENSRNOP00000022342.3; ENSRNOG00000016496.8. DR GeneID; 25423; -. DR KEGG; rno:25423; -. DR AGR; RGD:2445; -. DR CTD; 1075; -. DR RGD; 2445; Ctsc. DR eggNOG; KOG1543; Eukaryota. DR GeneTree; ENSGT00940000155787; -. DR HOGENOM; CLU_048219_0_0_1; -. DR InParanoid; P80067; -. DR OMA; HWDWRNV; -. DR OrthoDB; 5475703at2759; -. DR PhylomeDB; P80067; -. DR TreeFam; TF313225; -. DR BRENDA; 3.4.14.1; 5301. DR Reactome; R-RNO-204005; COPII-mediated vesicle transport. DR Reactome; R-RNO-2132295; MHC class II antigen presentation. DR Reactome; R-RNO-5694530; Cargo concentration in the ER. DR Reactome; R-RNO-6798695; Neutrophil degranulation. DR SABIO-RK; P80067; -. DR EvolutionaryTrace; P80067; -. DR PRO; PR:P80067; -. DR Proteomes; UP000002494; Chromosome 1. DR Bgee; ENSRNOG00000016496; Expressed in liver and 19 other cell types or tissues. DR GO; GO:0005813; C:centrosome; IEA:Ensembl. DR GO; GO:0005737; C:cytoplasm; ISO:RGD. DR GO; GO:0005615; C:extracellular space; IBA:GO_Central. DR GO; GO:0005764; C:lysosome; IDA:ParkinsonsUK-UCL. DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl. DR GO; GO:0031404; F:chloride ion binding; IDA:RGD. DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IBA:GO_Central. DR GO; GO:0008234; F:cysteine-type peptidase activity; ISO:RGD. DR GO; GO:0008239; F:dipeptidyl-peptidase activity; IEA:UniProtKB-EC. DR GO; GO:0042802; F:identical protein binding; IDA:RGD. DR GO; GO:0016505; F:peptidase activator activity involved in apoptotic process; ISO:RGD. DR GO; GO:0019902; F:phosphatase binding; IPI:ParkinsonsUK-UCL. DR GO; GO:0043621; F:protein self-association; IDA:RGD. DR GO; GO:0051087; F:protein-folding chaperone binding; IPI:ParkinsonsUK-UCL. DR GO; GO:0004252; F:serine-type endopeptidase activity; ISO:RGD. DR GO; GO:0031642; P:negative regulation of myelination; ISO:RGD. DR GO; GO:2001235; P:positive regulation of apoptotic signaling pathway; ISO:RGD. DR GO; GO:1903980; P:positive regulation of microglial cell activation; ISO:RGD. DR GO; GO:1903052; P:positive regulation of proteolysis involved in protein catabolic process; IDA:ParkinsonsUK-UCL. DR GO; GO:0006508; P:proteolysis; ISO:RGD. DR GO; GO:0051603; P:proteolysis involved in protein catabolic process; IBA:GO_Central. DR GO; GO:0010033; P:response to organic substance; IDA:RGD. DR GO; GO:0001913; P:T cell mediated cytotoxicity; ISO:RGD. 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; P80067; RN. PE 1: Evidence at protein level; KW 3D-structure; Chloride; Direct protein sequencing; Disulfide bond; KW Glycoprotein; Hydrolase; Lysosome; Protease; Reference proteome; Signal; KW Thiol protease; Zymogen. FT SIGNAL 1..24 FT /evidence="ECO:0000269|PubMed:1740150" FT CHAIN 25..134 FT /note="Dipeptidyl peptidase 1 exclusion domain chain" FT /evidence="ECO:0000250|UniProtKB:P53634" FT /id="PRO_0000026350" FT PROPEP 135..229 FT /evidence="ECO:0000250|UniProtKB:P53634" FT /id="PRO_0000026351" FT CHAIN 230..393 FT /note="Dipeptidyl peptidase 1 heavy chain" FT /id="PRO_0000026352" FT CHAIN 394..462 FT /note="Dipeptidyl peptidase 1 light chain" FT /id="PRO_0000026353" FT ACT_SITE 257 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10088" FT ACT_SITE 404 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10089" FT ACT_SITE 426 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10090" FT BINDING 301 FT /ligand="chloride" FT /ligand_id="ChEBI:CHEBI:17996" FT /evidence="ECO:0000250|UniProtKB:P53634" FT BINDING 303 FT /ligand="chloride" FT /ligand_id="ChEBI:CHEBI:17996" FT /evidence="ECO:0000250|UniProtKB:P53634" FT BINDING 346 FT /ligand="chloride" FT /ligand_id="ChEBI:CHEBI:17996" FT /evidence="ECO:0000250|UniProtKB:P53634" FT CARBOHYD 29 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:11602245" FT CARBOHYD 53 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 144 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 275 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:11602245" FT DISULFID 30..118 FT /evidence="ECO:0000269|PubMed:11602245" FT DISULFID 54..136 FT /evidence="ECO:0000269|PubMed:11602245" FT DISULFID 254..297 FT /evidence="ECO:0000269|PubMed:11602245" FT DISULFID 290..330 FT /evidence="ECO:0000269|PubMed:11602245" FT DISULFID 320..336 FT /evidence="ECO:0000269|PubMed:11602245" FT CONFLICT 30 FT /note="C -> E (in Ref. 3; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 129 FT /note="V -> Y (in Ref. 2)" FT /evidence="ECO:0000305" FT CONFLICT 171 FT /note="N -> H (in Ref. 2)" FT /evidence="ECO:0000305" FT CONFLICT 191..192 FT /note="EE -> RR (in Ref. 2)" FT /evidence="ECO:0000305" FT CONFLICT 263 FT /note="L -> I (in Ref. 2)" FT /evidence="ECO:0000305" FT HELIX 32..35 FT /evidence="ECO:0007829|PDB:1JQP" FT STRAND 36..43 FT /evidence="ECO:0007829|PDB:1JQP" FT STRAND 62..69 FT /evidence="ECO:0007829|PDB:1JQP" FT TURN 70..72 FT /evidence="ECO:0007829|PDB:1JQP" FT STRAND 73..75 FT /evidence="ECO:0007829|PDB:1JQP" FT STRAND 77..79 FT /evidence="ECO:0007829|PDB:1JQP" FT STRAND 81..87 FT /evidence="ECO:0007829|PDB:1JQP" FT TURN 88..90 FT /evidence="ECO:0007829|PDB:1JQP" FT STRAND 91..96 FT /evidence="ECO:0007829|PDB:1JQP" FT STRAND 99..110 FT /evidence="ECO:0007829|PDB:1JQP" FT STRAND 113..121 FT /evidence="ECO:0007829|PDB:1JQP" FT STRAND 123..128 FT /evidence="ECO:0007829|PDB:1JQP" FT STRAND 133..141 FT /evidence="ECO:0007829|PDB:1JQP" FT STRAND 253..255 FT /evidence="ECO:0007829|PDB:1JQP" FT HELIX 257..273 FT /evidence="ECO:0007829|PDB:1JQP" FT TURN 274..276 FT /evidence="ECO:0007829|PDB:1JQP" FT HELIX 284..290 FT /evidence="ECO:0007829|PDB:1JQP" FT HELIX 302..305 FT /evidence="ECO:0007829|PDB:1JQP" FT HELIX 308..312 FT /evidence="ECO:0007829|PDB:1JQP" FT STRAND 315..317 FT /evidence="ECO:0007829|PDB:1JQP" FT HELIX 318..320 FT /evidence="ECO:0007829|PDB:1JQP" FT STRAND 338..346 FT /evidence="ECO:0007829|PDB:1JQP" FT HELIX 356..366 FT /evidence="ECO:0007829|PDB:1JQP" FT STRAND 369..373 FT /evidence="ECO:0007829|PDB:1JQP" FT HELIX 377..380 FT /evidence="ECO:0007829|PDB:1JQP" FT STRAND 384..387 FT /evidence="ECO:0007829|PDB:1JQP" FT STRAND 404..413 FT /evidence="ECO:0007829|PDB:1JQP" FT TURN 415..417 FT /evidence="ECO:0007829|PDB:1JQP" FT STRAND 420..425 FT /evidence="ECO:0007829|PDB:1JQP" FT STRAND 437..441 FT /evidence="ECO:0007829|PDB:1JQP" FT HELIX 446..448 FT /evidence="ECO:0007829|PDB:1JQP" FT STRAND 454..459 FT /evidence="ECO:0007829|PDB:1JQP" SQ SEQUENCE 462 AA; 52235 MW; F25F3953AA115D3C CRC64; MGPWTHSLRA ALLLVLLGVC TVSSDTPANC TYPDLLGTWV FQVGPRHPRS HINCSVMEPT EEKVVIHLKK LDTAYDEVGN SGYFTLIYNQ GFEIVLNDYK WFAFFKYEVK GSRAISYCHE TMTGWVHDVL GRNWACFVGK KMANHSEKVY VNVAHLGGLQ EKYSERLYSH NHNFVKAINS VQKSWTATTY EEYEKLSIRD LIRRSGHSGR ILRPKPAPIT DEIQQQILSL PESWDWRNVR GINFVSPVRN QESCGSCYSF ASLGMLEARI RILTNNSQTP ILSPQEVVSC SPYAQGCDGG FPYLIAGKYA QDFGVVEENC FPYTATDAPC KPKENCLRYY SSEYYYVGGF YGGCNEALMK LELVKHGPMA VAFEVHDDFL HYHSGIYHHT GLSDPFNPFE LTNHAVLLVG YGKDPVTGLD YWIVKNSWGS QWGESGYFRI RRGTDECAIE SIAMAAIPIP KL //