ID CBPA1_BOVIN Reviewed; 419 AA. AC P00730; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1991, sequence version 3. DT 04-NOV-2026, entry version 201. DE RecName: Full=Carboxypeptidase A1 {ECO:0000305}; DE EC=3.4.17.1 {ECO:0000250|UniProtKB:P15085}; DE Flags: Precursor; GN Name=CPA1; Synonyms=CPA; OS Bos taurus (Bovine). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae; OC Bovinae; Bos. OX NCBI_TaxID=9913; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Pancreas; RX PubMed=1998496; DOI=10.1016/s0006-291x(05)81207-0; RA le Hueerou I., Guilloteau P., Toullec R., Puigserver A., Wicker C.; RT "Cloning and nucleotide sequence of a bovine pancreatic RT preprocarboxypeptidase A cDNA."; RL Biochem. Biophys. Res. Commun. 175:110-116(1991). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Pancreas; RX PubMed=8522204; DOI=10.1016/0378-1119(95)00454-e; RA Goo J.H., Kim K.H., Choi K.Y.; RT "Cloning, sequencing and expression of the gene encoding a major allotypic RT preprocarboxypeptidase A from bovine pancreas."; RL Gene 165:333-334(1995). RN [3] RP PROTEIN SEQUENCE OF 111-417. RX PubMed=5102489; DOI=10.1021/bi00782a004; RA Bradshaw R.A., Walsh K.A., Neurath H.; RT "Amino acid sequence of bovine carboxypeptidase A. Tryptic and chymotryptic RT peptides of the cyanogen bromide fragment F-I."; RL Biochemistry 10:938-950(1971). RN [4] RP SEQUENCE REVISION TO 138 AND 141. RX PubMed=5143102; DOI=10.1021/bi00798a600; RA Petra P.H., Hermodson M.A., Walsh K.A., Neurath H.; RT "Characterization of bovine carboxypeptidase A (Allan)."; RL Biochemistry 10:4023-4025(1971). RN [5] RP PROTEIN SEQUENCE OF 17-120. RX PubMed=3147705; DOI=10.1016/0300-9084(88)90178-2; RA Wade R.D., Hass G.M., Kumar S., Walsh K.A., Neurath H.; RT "The amino acid sequence of the activation peptide of bovine pro- RT carboxypeptidase A."; RL Biochimie 70:1137-1142(1988). RN [6] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=12729612; DOI=10.1016/s0003-9861(03)00080-8; RA Reddanna P., Prabhu K.S., Whelan J., Reddy C.C.; RT "Carboxypeptidase A-catalyzed direct conversion of leukotriene C4 to RT leukotriene F4."; RL Arch. Biochem. Biophys. 413:158-163(2003). RN [7] RP ACTIVITY REGULATION. RX PubMed=23746805; DOI=10.1016/j.str.2013.04.021; RA Alonso del Rivero M., Reytor M.L., Trejo S.A., Chavez M.A., Aviles F.X., RA Reverter D.; RT "A noncanonical mechanism of carboxypeptidase inhibition revealed by the RT crystal structure of the Tri-Kunitz SmCI in complex with human CPA4."; RL Structure 21:1118-1126(2013). RN [8] RP X-RAY CRYSTALLOGRAPHY. RX PubMed=6887246; DOI=10.1016/s0022-2836(83)80024-2; RA Rees D.C., Lewis M., Lipscomb W.N.; RT "Refined crystal structure of carboxypeptidase A at 1.54-A resolution."; RL J. Mol. Biol. 168:367-387(1983). RN [9] RP X-RAY CRYSTALLOGRAPHY IN COMPLEX WITH ZINC IONS AND SUBSTRATE ANALOG. RX PubMed=15299490; DOI=10.1107/s0907444993007267; RA Teplyakov A., Wilson K.S., Orioli P., Mangani S.; RT "High-resolution structure of the complex between carboxypeptidase A and L- RT phenyl lactate."; RL Acta Crystallogr. D 49:534-540(1993). RN [10] RP X-RAY CRYSTALLOGRAPHY OF COMPLEX WITH CPA1 AND CTRC, AND TISSUE RP SPECIFICITY. RX PubMed=7556081; DOI=10.1002/j.1460-2075.1995.tb00117.x; RA Gomis-Rueth F.-X., Gomez M., Bode W., Huber R., Aviles F.X.; RT "The three-dimensional structure of the native ternary complex of bovine RT pancreatic procarboxypeptidase A with proproteinase E and chymotrypsinogen RT C."; RL EMBO J. 14:4387-4394(1995). RN [11] RP X-RAY CRYSTALLOGRAPHY OF APOENZYME AND IN COMPLEX WITH ZINC IONS. RX PubMed=9867434; DOI=10.1107/s0907444997010445; RA Greenblatt H.M., Feinberg H., Tucker P.A., Shoham G.; RT "Carboxypeptidase A: native, zinc-removed and mercury-replaced forms."; RL Acta Crystallogr. D 54:289-305(1998). RN [12] RP X-RAY CRYSTALLOGRAPHY IN COMPLEX WITH ZINC IONS AND INHIBITOR. RX PubMed=10955996; DOI=10.1021/bi000952h; RA van Aalten D.M.F., Chong C.R., Joshua-Tor L.; RT "Crystal structure of carboxypeptidase A complexed with D-cysteine at 1.75 RT A -- inhibitor-induced conformational changes."; RL Biochemistry 39:10082-10089(2000). RN [13] RP X-RAY CRYSTALLOGRAPHY IN COMPLEX WITH ZINC IONS AND SUBSTRATE ANALOG. RX PubMed=11937361; DOI=10.1016/s0968-0896(01)00429-1; RA Cho J.H., Kim D.H., Chung S.J., Ha N.-C., Oh B.-H., Yong Choi K.; RT "Insight into the stereochemistry in the inhibition of carboxypeptidase A RT with N-(hydroxyaminocarbonyl)phenylalanine: binding modes of an RT enantiomeric pair of the inhibitor to carboxypeptidase A."; RL Bioorg. Med. Chem. 10:2015-2022(2002). RN [14] RP X-RAY CRYSTALLOGRAPHY IN COMPLEX WITH ZINC IONS AND SUBSTRATE ANALOG. RX PubMed=12431056; DOI=10.1021/jm020258v; RA Park J.D., Kim D.H., Kim S.-J., Woo J.-R., Ryu S.E.; RT "Sulfamide-based inhibitors for carboxypeptidase A. Novel type transition RT state analogue inhibitors for zinc proteases."; RL J. Med. Chem. 45:5295-5302(2002). RN [15] RP X-RAY CRYSTALLOGRAPHY IN COMPLEX WITH ZINC IONS. RX PubMed=12554943; DOI=10.1107/s0907444902015706; RA Kilshtain-Vardi A., Glick M., Greenblatt H.M., Goldblum A., Shoham G.; RT "Refined structure of bovine carboxypeptidase A at 1.25 A resolution."; RL Acta Crystallogr. D 59:323-333(2003). RN [16] RP VARIANTS ALLELIC VAL-289; ALA-338 AND VAL-415. RX PubMed=5817619; DOI=10.1021/bi00835a011; RA Petra P.H., Bradshaw R.A., Walsh K.A., Neurath H.; RT "Identification of the amino acid replacements characterizing the allotypic RT forms of bovine carboxypeptidase A."; RL Biochemistry 8:2762-2768(1969). CC -!- FUNCTION: Carboxypeptidase that catalyzes the release of a C-terminal CC amino acid, but has little or no action with -Asp, -Glu, -Arg, -Lys or CC -Pro (By similarity). Catalyzes the conversion of leukotriene C4 to CC leukotriene F4 via the hydrolysis of an amide bond (PubMed:12729612). CC {ECO:0000250|UniProtKB:P15085, ECO:0000269|PubMed:12729612}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Release of a C-terminal amino acid, but little or no action CC with -Asp, -Glu, -Arg, -Lys or -Pro.; EC=3.4.17.1; CC Evidence={ECO:0000250|UniProtKB:P15085}; CC -!- CATALYTIC ACTIVITY: CC Reaction=leukotriene C4 + H2O = leukotriene F4 + glycine; CC Xref=Rhea:RHEA:50740, ChEBI:CHEBI:15377, ChEBI:CHEBI:57305, CC ChEBI:CHEBI:57973, ChEBI:CHEBI:133618; CC Evidence={ECO:0000269|PubMed:12729612}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50741; CC Evidence={ECO:0000269|PubMed:12729612}; CC -!- COFACTOR: CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; CC Evidence={ECO:0000250|UniProtKB:P15085}; CC Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:P15085}; CC -!- ACTIVITY REGULATION: Inhibited by interaction with the S.magnifica CC carboxypeptidase inhibitor SmCI. {ECO:0000269|PubMed:23746805}. CC -!- SUBUNIT: Monomer. May form a complex with proelastase 2. CC {ECO:0000250|UniProtKB:P15085}. CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:Q9UI42}. CC -!- TISSUE SPECIFICITY: Pancreas. {ECO:0000269|PubMed:7556081}. CC -!- SIMILARITY: Belongs to the peptidase M14 family. {ECO:0000305}. 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; M61851; AAA30426.1; -; mRNA. DR EMBL; Z33906; CAA83955.1; -; mRNA. DR PIR; JN0126; CPBOA. DR RefSeq; NP_777175.1; NM_174750.2. DR PDB; 1ARL; X-ray; 1.88 A; A=111-417. DR PDB; 1ARM; X-ray; 1.76 A; A=111-419. DR PDB; 1BAV; X-ray; 1.60 A; A/B/C/D=111-419. DR PDB; 1CBX; X-ray; 2.00 A; A=111-417. DR PDB; 1CPS; X-ray; 2.25 A; A=111-417. DR PDB; 1CPX; X-ray; 2.00 A; A=111-417. DR PDB; 1EE3; X-ray; 1.70 A; P=111-419. DR PDB; 1ELL; X-ray; 1.76 A; P=111-419. DR PDB; 1ELM; X-ray; 2.00 A; P=111-419. DR PDB; 1F57; X-ray; 1.75 A; A=111-417. DR PDB; 1HDQ; X-ray; 2.30 A; A=111-417. DR PDB; 1HDU; X-ray; 1.75 A; A/B/D/E=111-417. DR PDB; 1HEE; X-ray; 1.75 A; A/B/D/E=111-417. DR PDB; 1IY7; X-ray; 2.00 A; A=111-417. DR PDB; 1M4L; X-ray; 1.25 A; A=111-417. DR PDB; 1PYT; X-ray; 2.35 A; A=17-110, B=111-419. DR PDB; 1YME; X-ray; 1.53 A; A=111-419. DR PDB; 1ZLH; X-ray; 1.70 A; A=111-419. DR PDB; 2ABZ; X-ray; 2.16 A; A/B=111-419. DR PDB; 2CTB; X-ray; 1.50 A; A=111-417. DR PDB; 2CTC; X-ray; 1.40 A; A=111-417. DR PDB; 2RFH; X-ray; 1.70 A; A=111-417. DR PDB; 3CPA; X-ray; 2.00 A; A=111-417. DR PDB; 3FVL; X-ray; 1.85 A; A/C/E=111-417. DR PDB; 3FX6; X-ray; 1.85 A; A/C/E=111-417. DR PDB; 3I1U; X-ray; 1.39 A; A=111-419. DR PDB; 3KGQ; X-ray; 1.70 A; A=111-419. DR PDB; 4CPA; X-ray; 2.50 A; A/B=111-417. DR PDB; 5CPA; X-ray; 1.54 A; A=111-417. DR PDB; 6CPA; X-ray; 2.00 A; A=111-417. DR PDB; 7CPA; X-ray; 2.00 A; A=111-417. DR PDB; 8CPA; X-ray; 2.00 A; A=111-417. DR AlphaFoldDB; P00730; -. DR MDposit; P00730; -. DR MDRepo; P00730; -. DR SMR; P00730; -. DR DIP; DIP-44716N; -. DR FunCoup; P00730; 195. DR IntAct; P00730; 1. DR STRING; 9913.ENSBTAP00000009745; -. DR BindingDB; P00730; -. DR ChEMBL; CHEMBL3481; -. DR SwissLipids; SLP:000001634; -. DR MEROPS; M14.001; -. DR PaxDb; 9913-ENSBTAP00000009745; -. DR GeneID; 286762; -. DR KEGG; bta:286762; -. DR CTD; 1357; -. DR eggNOG; KOG2650; Eukaryota. DR InParanoid; P00730; -. DR OMA; AAIQFWA; -. DR OrthoDB; 3626597at2759; -. DR BRENDA; 3.4.17.1; 908. DR SABIO-RK; P00730; -. DR EvolutionaryTrace; P00730; -. DR PRO; PR:P00730; -. DR Proteomes; UP000009136; Unplaced. DR GO; GO:0005576; C:extracellular region; ISS:UniProtKB. DR GO; GO:0004181; F:metallocarboxypeptidase activity; ISS:UniProtKB. DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro. DR GO; GO:0006691; P:leukotriene metabolic process; IDA:UniProtKB. DR GO; GO:0006508; P:proteolysis; IBA:GO_Central. DR CDD; cd03870; M14_CPA; 1. DR FunFam; 3.40.630.10:FF:000132; Carboxypeptidase A1; 1. DR FunFam; 3.30.70.340:FF:000001; Carboxypeptidase A5; 1. DR Gene3D; 3.30.70.340; Metallocarboxypeptidase-like; 1. DR Gene3D; 3.40.630.10; Zn peptidases; 1. DR InterPro; IPR057246; CARBOXYPEPT_ZN_1. DR InterPro; IPR057247; CARBOXYPEPT_ZN_2. DR InterPro; IPR034248; CPA_M14_CPD. DR InterPro; IPR036990; M14A-like_propep. DR InterPro; IPR003146; M14A_act_pep. DR InterPro; IPR000834; Peptidase_M14. DR PANTHER; PTHR11705:SF94; CARBOXYPEPTIDASE A1; 1. DR PANTHER; PTHR11705; PROTEASE FAMILY M14 CARBOXYPEPTIDASE A,B; 1. DR Pfam; PF00246; Peptidase_M14; 1. DR Pfam; PF02244; Propep_M14; 1. DR PRINTS; PR00765; CRBOXYPTASEA. DR SMART; SM00631; Zn_pept; 1. DR SUPFAM; SSF54897; Protease propeptides/inhibitors; 1. DR SUPFAM; SSF53187; Zn-dependent exopeptidases; 1. DR PROSITE; PS00132; CARBOXYPEPT_ZN_1; 1. DR PROSITE; PS00133; CARBOXYPEPT_ZN_2; 1. DR PROSITE; PS52035; PEPTIDASE_M14; 1. DR PCDDB; P00730; -. PE 1: Evidence at protein level; KW 3D-structure; Carboxypeptidase; Direct protein sequencing; Disulfide bond; KW Hydrolase; Metal-binding; Metalloprotease; Protease; Reference proteome; KW Secreted; Signal; Zinc; Zymogen. FT SIGNAL 1..16 FT /evidence="ECO:0000269|PubMed:3147705" FT PROPEP 17..110 FT /note="Activation peptide" FT /evidence="ECO:0000269|PubMed:5102489" FT /id="PRO_0000004343" FT CHAIN 111..419 FT /note="Carboxypeptidase A1" FT /id="PRO_0000004344" FT DOMAIN 121..414 FT /note="Peptidase M14" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01379" FT ACT_SITE 380 FT /note="Proton donor/acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01379" FT BINDING 179..182 FT /ligand="substrate" FT /evidence="ECO:0000269|PubMed:12431056, FT ECO:0007744|PDB:1IY7" FT BINDING 179 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01379, FT ECO:0000269|PubMed:12431056, ECO:0007744|PDB:1IY7" FT BINDING 182 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01379, FT ECO:0000269|PubMed:12431056, ECO:0007744|PDB:1IY7" FT BINDING 237 FT /ligand="substrate" FT /evidence="ECO:0000269|PubMed:12431056, FT ECO:0007744|PDB:1IY7" FT BINDING 254..255 FT /ligand="substrate" FT /evidence="ECO:0000269|PubMed:12431056, FT ECO:0007744|PDB:1IY7" FT BINDING 306 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01379, FT ECO:0000269|PubMed:12431056, ECO:0007744|PDB:1IY7" FT BINDING 307..308 FT /ligand="substrate" FT /evidence="ECO:0000269|PubMed:12431056, FT ECO:0007744|PDB:1IY7" FT BINDING 358 FT /ligand="substrate" FT /evidence="ECO:0000269|PubMed:12431056, FT ECO:0007744|PDB:1IY7" FT DISULFID 248..271 FT /evidence="ECO:0000250|UniProtKB:P15085" FT VARIANT 289 FT /note="I -> V (in allelic variant)" FT /evidence="ECO:0000269|PubMed:5817619" FT VARIANT 338 FT /note="E -> A (in allelic variant)" FT /evidence="ECO:0000269|PubMed:5817619" FT VARIANT 415 FT /note="L -> V (in allelic variant)" FT /evidence="ECO:0000269|PubMed:5817619" FT CONFLICT 95 FT /note="S -> L (in Ref. 5; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 199 FT /note="D -> N (in Ref. 3; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 203 FT /note="D -> N (in Ref. 3; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 224 FT /note="D -> N (in Ref. 3; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 232 FT /note="Q -> E (in Ref. 3; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 295 FT /note="D -> N (in Ref. 3; AA sequence)" FT /evidence="ECO:0000305" FT STRAND 24..29 FT /evidence="ECO:0007829|PDB:1PYT" FT HELIX 33..40 FT /evidence="ECO:0007829|PDB:1PYT" FT TURN 41..43 FT /evidence="ECO:0007829|PDB:1PYT" FT HELIX 46..48 FT /evidence="ECO:0007829|PDB:1PYT" FT STRAND 51..54 FT /evidence="ECO:0007829|PDB:1PYT" FT STRAND 63..67 FT /evidence="ECO:0007829|PDB:1PYT" FT HELIX 69..81 FT /evidence="ECO:0007829|PDB:1PYT" FT STRAND 85..91 FT /evidence="ECO:0007829|PDB:1PYT" FT HELIX 93..106 FT /evidence="ECO:0007829|PDB:1PYT" FT TURN 114..116 FT /evidence="ECO:0007829|PDB:1M4L" FT STRAND 119..121 FT /evidence="ECO:0007829|PDB:1BAV" FT HELIX 125..138 FT /evidence="ECO:0007829|PDB:1M4L" FT TURN 140..142 FT /evidence="ECO:0007829|PDB:1M4L" FT STRAND 143..150 FT /evidence="ECO:0007829|PDB:1M4L" FT STRAND 156..162 FT /evidence="ECO:0007829|PDB:1M4L" FT STRAND 164..168 FT /evidence="ECO:0007829|PDB:3FVL" FT STRAND 171..176 FT /evidence="ECO:0007829|PDB:1M4L" FT HELIX 183..199 FT /evidence="ECO:0007829|PDB:1M4L" FT TURN 200..202 FT /evidence="ECO:0007829|PDB:1M4L" FT HELIX 204..212 FT /evidence="ECO:0007829|PDB:1M4L" FT STRAND 214..219 FT /evidence="ECO:0007829|PDB:1M4L" FT HELIX 223..231 FT /evidence="ECO:0007829|PDB:1M4L" FT STRAND 244..247 FT /evidence="ECO:0007829|PDB:1BAV" FT HELIX 253..255 FT /evidence="ECO:0007829|PDB:1M4L" FT STRAND 257..260 FT /evidence="ECO:0007829|PDB:1M4L" FT STRAND 263..267 FT /evidence="ECO:0007829|PDB:1M4L" FT STRAND 273..275 FT /evidence="ECO:0007829|PDB:4CPA" FT HELIX 284..296 FT /evidence="ECO:0007829|PDB:1M4L" FT STRAND 299..309 FT /evidence="ECO:0007829|PDB:1M4L" FT STRAND 311..315 FT /evidence="ECO:0007829|PDB:1M4L" FT HELIX 326..344 FT /evidence="ECO:0007829|PDB:1M4L" FT STRAND 349..352 FT /evidence="ECO:0007829|PDB:1M4L" FT HELIX 353..356 FT /evidence="ECO:0007829|PDB:1M4L" FT HELIX 364..370 FT /evidence="ECO:0007829|PDB:1M4L" FT STRAND 375..382 FT /evidence="ECO:0007829|PDB:1M4L" FT STRAND 384..387 FT /evidence="ECO:0007829|PDB:1M4L" FT HELIX 388..390 FT /evidence="ECO:0007829|PDB:3I1U" FT HELIX 393..395 FT /evidence="ECO:0007829|PDB:1M4L" FT HELIX 396..416 FT /evidence="ECO:0007829|PDB:1M4L" SQ SEQUENCE 419 AA; 47082 MW; 21B86407B3BFC452 CRC64; MQGLLILSVL LGAALGKEDF VGHQVLRITA ADEAEVQTVK ELEDLEHLQL DFWRGPGQPG SPIDVRVPFP SLQAVKVFLE AHGIRYRIMI EDVQSLLDEE QEQMFASQSR ARSTNTFNYA TYHTLDEIYD FMDLLVAEHP QLVSKLQIGR SYEGRPIYVL KFSTGGSNRP AIWIDLGIHS REWITQATGV WFAKKFTEDY GQDPSFTAIL DSMDIFLEIV TNPDGFAFTH SQNRLWRKTR SVTSSSLCVG VDANRNWDAG FGKAGASSSP CSETYHGKYA NSEVEVKSIV DFVKDHGNFK AFLSIHSYSQ LLLYPYGYTT QSIPDKTELN QVAKSAVEAL KSLYGTSYKY GSIITTIYQA SGGSIDWSYN QGIKYSFTFE LRDTGRYGFL LPASQIIPTA QETWLGVLTI MEHTLNNLY //