ID PAPA3_CARPA Reviewed; 348 AA. AC P10056; DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-1996, sequence version 2. DT 04-NOV-2026, entry version 133. DE RecName: Full=Caricain; DE EC=3.4.22.30 {ECO:0000269|PubMed:2404797}; DE AltName: Full=Papaya peptidase A; DE AltName: Full=Papaya proteinase III; DE Short=PPIII; DE AltName: Full=Papaya proteinase omega; DE Flags: Precursor; OS Carica papaya (Papaya). OC Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta; OC Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae; OC rosids; malvids; Brassicales; Caricaceae; Carica. OX NCBI_TaxID=3649; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Leaf; RA Baker K.C., Revell D.F., Cummings N.J., Collins M.E., Goodenough P.W.; RL Submitted (MAY-1995) to the EMBL/GenBank/DDBJ databases. RN [2] RP PROTEIN SEQUENCE OF 133-348, AND CATALYTIC ACTIVITY. RC TISSUE=Latex; RX PubMed=3063283; DOI=10.1515/bchm3.1988.369.2.741; RA Dubois T., Kleinschmidt T., Schnek A.G., Looze Y., Braunitzer G.; RT "The thiol proteinases from the latex of Carica papaya L. II. The primary RT structure of proteinase omega."; RL Biol. Chem. Hoppe-Seyler 369:741-754(1988). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] OF 237-348. RC TISSUE=Leaf; RA Collins M.E., Revell D.F., Sumner I.G., Pickersgill R.W., Goodenough P.W.; RL Submitted (FEB-1990) to the EMBL/GenBank/DDBJ databases. RN [4] RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=2404797; DOI=10.1016/0014-5793(90)80101-n; RA Buttle D.J., Ritonja A., Pearl L.H., Turk V., Barrett A.J.; RT "Selective cleavage of glycyl bonds by papaya proteinase IV."; RL FEBS Lett. 260:195-197(1990). RN [5] RP X-RAY CRYSTALLOGRAPHY, AND DISULFIDE BONDS. RA Pickersgill R.W., Rizkallah P., Harris G.W., Goodenough P.W.; RT "Determination of the structure of papaya protease omega."; RL Acta Crystallogr. B 47:766-771(1991). RN [6] RP X-RAY CRYSTALLOGRAPHY OF MUTANT GLU-290 IN COMPLEX WITH E64, DISULFIDE RP BONDS, AND ACTIVITY REGULATION. RX PubMed=8769310; DOI=10.1016/0014-5793(96)00697-7; RA Katerelos N.A., Taylor M.A.J., Scott M., Goodenough P.W., Pickersgill R.W.; RT "Crystal structure of a caricain D158E mutant in complex with E-64."; RL FEBS Lett. 392:35-39(1996). RN [7] RP X-RAY CRYSTALLOGRAPHY, AND DISULFIDE BONDS. RX PubMed=8939744; DOI=10.1016/s0969-2126(96)00127-x; RA Groves M.R., Taylor M.A., Scott M., Cummings N.J., Pickersgill R.W., RA Jenkins J.A.; RT "The prosequence of procaricain forms an alpha-helical domain that prevents RT access to the substrate-binding cleft."; RL Structure 4:1193-1203(1996). CC -!- FUNCTION: Cysteine proteinase with a high level of diversity in CC substrate specificity. {ECO:0000269|PubMed:2404797}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Hydrolysis of proteins with broad specificity for peptide CC bonds, similar to those of papain and chymopapain.; EC=3.4.22.30; CC Evidence={ECO:0000269|PubMed:2404797}; CC -!- ACTIVITY REGULATION: Repressed by the active-site-directed cysteine CC protease inhibitor E64 (L-trans-epoxysuccinyl-leucylamide-(4-guanido)- CC butane) produced by Aspergillus japonicus. CC {ECO:0000269|PubMed:8769310}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=4.2 mM for Boc-Ala-Ala-Gly-NHPhNO(2) {ECO:0000269|PubMed:2404797}; CC KM=0.17 mM for Boc-Ala-Ala-Gly-NHMec {ECO:0000269|PubMed:2404797}; CC Note=kcat is 0.5 sec(-1) with Boc-Ala-Ala-Gly-NHPhNO(2) as substrate CC (PubMed:2404797). kcat is 0.1 sec(-1) with Boc-Ala-Ala-Gly-NHMec as CC substrate (PubMed:2404797). {ECO:0000269|PubMed:2404797}; CC -!- SUBUNIT: Monomer. 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; X66060; CAA46862.1; -; mRNA. DR EMBL; X51899; CAA36180.1; -; mRNA. DR PIR; JN0633; JN0633. DR PDB; 1MEG; X-ray; 2.00 A; A=133-348. DR PDB; 1PCI; X-ray; 3.20 A; A/B/C=27-348. DR PDB; 1PPO; X-ray; 1.80 A; A=133-348. DR AlphaFoldDB; P10056; -. DR MDposit; P10056; -. DR SMR; P10056; -. DR Allergome; 1539; Cari p Endoproteinase. DR MEROPS; C01.003; -. DR MEROPS; I29.003; -. DR GlyCosmos; P10056; 1 site, No reported glycans. DR KEGG; ag:CAA46862; -. DR BRENDA; 3.4.22.30; 1191. DR EvolutionaryTrace; P10056; -. DR GO; GO:0008234; F:cysteine-type peptidase activity; IEA:InterPro. DR GO; GO:0006508; P:proteolysis; IEA:InterPro. DR CDD; cd02248; Peptidase_C1A; 1. DR FunFam; 3.90.70.10:FF:000204; Papain; 1. DR Gene3D; 3.90.70.10; Cysteine proteinases; 1. 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 InterPro; IPR039417; Peptidase_C1A_papain-like. DR InterPro; IPR013201; Prot_inhib_I29. DR PANTHER; PTHR12411; CYSTEINE PROTEASE FAMILY C1-RELATED; 1. DR Pfam; PF08246; Inhibitor_I29; 1. DR Pfam; PF00112; Peptidase_C1; 1. DR PRINTS; PR00705; PAPAIN. DR SMART; SM00848; Inhibitor_I29; 1. DR SMART; SM00645; Pept_C1; 1. DR SUPFAM; SSF54001; Cysteine proteinases; 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; Direct protein sequencing; Disulfide bond; Glycoprotein; KW Hydrolase; Protease; Signal; Thiol protease; Zymogen. FT SIGNAL 1..16 FT /evidence="ECO:0000255" FT PROPEP 17..132 FT /note="Activation peptide" FT /evidence="ECO:0000269|PubMed:3063283" FT /id="PRO_0000026410" FT CHAIN 133..348 FT /note="Caricain" FT /id="PRO_0000026411" FT ACT_SITE 157 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10088, FT ECO:0000305|PubMed:8769310, ECO:0007744|PDB:1MEG" FT ACT_SITE 291 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10089" FT ACT_SITE 311 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10090" FT BINDING 157 FT /ligand="E64" FT /ligand_id="ChEBI:CHEBI:192370" FT /ligand_note="inhibitor; produced by Aspergillus japonicus" FT /note="covalent" FT /evidence="ECO:0000269|PubMed:8769310, FT ECO:0007744|PDB:1MEG" FT CARBOHYD 86 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498" FT DISULFID 154..195 FT /evidence="ECO:0000269|PubMed:8769310, FT ECO:0000269|PubMed:8939744, ECO:0000269|Ref.5, FT ECO:0007744|PDB:1MEG, ECO:0007744|PDB:1PCI, FT ECO:0007744|PDB:1PPO" FT DISULFID 188..227 FT /evidence="ECO:0000269|PubMed:8769310, FT ECO:0000269|PubMed:8939744, ECO:0000269|Ref.5, FT ECO:0007744|PDB:1MEG, ECO:0007744|PDB:1PCI, FT ECO:0007744|PDB:1PPO" FT DISULFID 285..336 FT /evidence="ECO:0000269|PubMed:8769310, FT ECO:0000269|PubMed:8939744, ECO:0000269|Ref.5, FT ECO:0007744|PDB:1MEG, ECO:0007744|PDB:1PCI, FT ECO:0007744|PDB:1PPO" FT HELIX 40..53 FT /evidence="ECO:0007829|PDB:1PCI" FT TURN 54..56 FT /evidence="ECO:0007829|PDB:1PCI" FT HELIX 62..83 FT /evidence="ECO:0007829|PDB:1PCI" FT STRAND 88..91 FT /evidence="ECO:0007829|PDB:1PCI" FT TURN 95..98 FT /evidence="ECO:0007829|PDB:1PCI" FT HELIX 101..108 FT /evidence="ECO:0007829|PDB:1PCI" FT STRAND 122..124 FT /evidence="ECO:0007829|PDB:1PCI" FT TURN 139..143 FT /evidence="ECO:0007829|PDB:1PPO" FT STRAND 153..155 FT /evidence="ECO:0007829|PDB:1PPO" FT HELIX 157..174 FT /evidence="ECO:0007829|PDB:1PPO" FT HELIX 182..188 FT /evidence="ECO:0007829|PDB:1PPO" FT STRAND 190..192 FT /evidence="ECO:0007829|PDB:1PPO" FT HELIX 194..196 FT /evidence="ECO:0007829|PDB:1PCI" FT HELIX 200..210 FT /evidence="ECO:0007829|PDB:1PPO" FT STRAND 212..214 FT /evidence="ECO:0007829|PDB:1MEG" FT TURN 215..217 FT /evidence="ECO:0007829|PDB:1PPO" FT HELIX 229..231 FT /evidence="ECO:0007829|PDB:1PPO" FT STRAND 241..244 FT /evidence="ECO:0007829|PDB:1PPO" FT STRAND 247..249 FT /evidence="ECO:0007829|PDB:1MEG" FT HELIX 250..259 FT /evidence="ECO:0007829|PDB:1PPO" FT STRAND 262..266 FT /evidence="ECO:0007829|PDB:1PPO" FT HELIX 271..275 FT /evidence="ECO:0007829|PDB:1PPO" FT STRAND 278..281 FT /evidence="ECO:0007829|PDB:1PPO" FT STRAND 291..301 FT /evidence="ECO:0007829|PDB:1PPO" FT STRAND 304..310 FT /evidence="ECO:0007829|PDB:1PPO" FT STRAND 315..317 FT /evidence="ECO:0007829|PDB:1PPO" FT STRAND 322..326 FT /evidence="ECO:0007829|PDB:1PPO" FT STRAND 330..333 FT /evidence="ECO:0007829|PDB:1PPO" FT HELIX 335..337 FT /evidence="ECO:0007829|PDB:1PPO" FT STRAND 343..346 FT /evidence="ECO:0007829|PDB:1PPO" SQ SEQUENCE 348 AA; 38788 MW; 328F5C6BF45B4A07 CRC64; MAMIPSISKL LFVAICLFVH MSVSFGDFSI VGYSQDDLTS TERLIQLFNS WMLNHNKFYE NVDEKLYRFE IFKDNLNYID ETNKKNNSYW LGLNEFADLS NDEFNEKYVG SLIDATIEQS YDEEFINEDT VNLPENVDWR KKGAVTPVRH QGSCGSCWAF SAVATVEGIN KIRTGKLVEL SEQELVDCER RSHGCKGGYP PYALEYVAKN GIHLRSKYPY KAKQGTCRAK QVGGPIVKTS GVGRVQPNNE GNLLNAIAKQ PVSVVVESKG RPFQLYKGGI FEGPCGTKVD HAVTAVGYGK SGGKGYILIK NSWGTAWGEK GYIRIKRAPG NSPGVCGLYK SSYYPTKN //