ID CHYM_BOVIN Reviewed; 381 AA. AC P00794; A8RRP5; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-2005, sequence version 3. DT 02-SEP-2026, entry version 192. DE RecName: Full=Chymosin; DE EC=3.4.23.4; DE AltName: Full=Preprorennin; DE Flags: Precursor; GN Name=CYM; Synonyms=CPC; 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], AND VARIANT ASP-302. RX PubMed=6183168; DOI=10.1016/0378-1119(82)90197-4; RA Moir D., Mao J., Schumm J.W., Vovis G.F., Alford B.L., Taunton-Rigby A.; RT "Molecular cloning and characterization of double-stranded cDNA coding for RT bovine chymosin."; RL Gene 19:127-138(1982). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=6283469; DOI=10.1093/nar/10.7.2177; RA Harris T.J.R., Lowe P.A., Lyons A., Thomas P.G., Eaton M.A.W., RA Millican T.A., Patel T.P., Bose C.C., Carey N.H., Doel M.T.; RT "Molecular cloning and nucleotide sequence of cDNA coding for calf RT preprochymosin."; RL Nucleic Acids Res. 10:2177-2187(1982). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=3091454; DOI=10.1016/0378-1119(86)90207-6; RA Hidaka M., Sasaki K., Uozumi T., Beppu T.; RT "Cloning and structural analysis of the calf prochymosin gene."; RL Gene 43:197-203(1986). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA]. RA Sun D., Jiang Y.; RT "cDNA encoding bovine calf preprochymosin."; RL Submitted (APR-2007) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] OF 140-381, AND VARIANT ASP-302. RX PubMed=6804449; DOI=10.1093/oxfordjournals.jbchem.a133758; RA Nishimori K., Kawaguchi Y., Hidaka M., Uozumi T., Beppu T.; RT "Nucleotide sequence of calf prorennin cDNA cloned in Escherichia coli."; RL J. Biochem. 91:1085-1088(1982). RN [6] RP PROTEIN SEQUENCE OF 1-30 (PRECURSOR PROTEIN). RX PubMed=2415509; DOI=10.1093/oxfordjournals.jbchem.a135303; RA Ichihara Y., Sogawa K., Takahashi K.; RT "Isolation of human, swine, and rat prepepsinogens and calf preprochymosin, RT and determination of the primary structures of their NH2-terminal signal RT sequences."; RL J. Biochem. 98:483-492(1985). RN [7] RP PROTEIN SEQUENCE OF 17-381. RX PubMed=329280; DOI=10.1073/pnas.74.6.2321; RA Foltmann B., Pedersen V.B., Jacobsen H., Kauffman D., Wybrandt G.; RT "The complete amino acid sequence of prochymosin."; RL Proc. Natl. Acad. Sci. U.S.A. 74:2321-2324(1977). RN [8] RP PROTEIN SEQUENCE OF 17-77. RX PubMed=240697; DOI=10.1111/j.1432-1033.1975.tb02141.x; RA Pedersen V.B., Foltmann B.; RT "Amino-acid sequence of the peptide segment liberated during activation of RT prochymosin (prorennin)."; RL Eur. J. Biochem. 55:95-103(1975). RN [9] RP PROTEIN SEQUENCE OF 59-381, AND DISULFIDE BONDS. RX PubMed=381305; DOI=10.1016/s0021-9258(19)86912-0; RA Foltmann B., Pedersen V.B., Kauffman D., Wybrandt G.; RT "The primary structure of calf chymosin."; RL J. Biol. Chem. 254:8447-8456(1979). RN [10] RP ACTIVE SITE PEPTIDES. RX PubMed=4612029; DOI=10.1093/oxfordjournals.jbchem.a130590; RA Chang W.-J., Takahashi K.; RT "The structure and function of acid proteases. III. Isolation and RT characterization of the active-site peptides from bovine rennin."; RL J. Biochem. 76:467-474(1974). RN [11] RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS). RX PubMed=1942052; DOI=10.1016/0022-2836(91)90934-x; RA Newman M., Safro M., Frazao C., Kahn G., Zdanov A., Tickle I.J., RA Blundell T.L., Andreeva N.; RT "X-ray analyses of aspartic proteinases. IV. Structure and refinement at RT 2.2-A resolution of bovine chymosin."; RL J. Mol. Biol. 221:1295-1309(1991). RN [12] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF MUTANT. RX PubMed=2271625; DOI=10.1021/bi00494a016; RA Strop P., Sedlacek J., Stys J., Kaderabkova Z., Blaha I., Pavlickova L., RA Pohl J., Fabry M., Kostka V., Newman M., Frazao C., Shearer A., RA Tickle I.J., Blundell T.L.; RT "Engineering enzyme subsite specificity: preparation, kinetic RT characterization, and X-ray analysis at 2.0-A resolution of Val111Phe site- RT mutated calf chymosin."; RL Biochemistry 29:9863-9871(1990). RN [13] RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS). RX PubMed=2217166; DOI=10.1002/prot.340080110; RA Gilliland G.L., Winborne E.L., Nachman J., Wlodawer A.; RT "The three-dimensional structure of recombinant bovine chymosin at 2.3-A RT resolution."; RL Proteins 8:82-101(1990). RN [14] RP MUTAGENESIS OF CYS-308 AND CYS-341. RX PubMed=1530626; DOI=10.1016/0006-291x(92)91250-t; RA Huang K., Zhang Z., Liu N., Zhang Y., Zhang G., Yang K.; RT "Functional implication of disulfide bond, Cys250 -Cys283, in bovine RT chymosin."; RL Biochem. Biophys. Res. Commun. 187:692-696(1992). CC -!- FUNCTION: Chymosin is synthesized in the mucosa of the abomasum (fourth CC stomach) of young (unweaned) ruminants. The enzyme hydrolyzes casein to CC paracasein. CC -!- CATALYTIC ACTIVITY: CC Reaction=Broad specificity similar to that of pepsin A. Clots milk by CC cleavage of a single 104-Ser-Phe-|-Met-Ala-107 bond in kappa-chain of CC casein.; EC=3.4.23.4; CC -!- SUBUNIT: Monomer. CC -!- POLYMORPHISM: Forms A and B are probably allelic variants. Form B is CC the predominant form and differs only in one position. CC -!- SIMILARITY: Belongs to the peptidase A1 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; J00002; AAA30447.1; -; mRNA. DR EMBL; J00003; AAA30448.1; -; mRNA. DR EMBL; M14077; AAA30446.1; -; Genomic_DNA. DR EMBL; M14069; AAA30446.1; JOINED; Genomic_DNA. DR EMBL; M14070; AAA30446.1; JOINED; Genomic_DNA. DR EMBL; M14071; AAA30446.1; JOINED; Genomic_DNA. DR EMBL; M14072; AAA30446.1; JOINED; Genomic_DNA. DR EMBL; M14073; AAA30446.1; JOINED; Genomic_DNA. DR EMBL; M14074; AAA30446.1; JOINED; Genomic_DNA. DR EMBL; M14075; AAA30446.1; JOINED; Genomic_DNA. DR EMBL; EF541122; ABU41411.1; -; mRNA. DR PIR; A25631; CMBO. DR RefSeq; NP_851337.1; NM_180994.2. DR PDB; 1CMS; X-ray; 2.30 A; A=59-381. DR PDB; 1CZI; X-ray; 2.30 A; E=59-381. DR PDB; 3CMS; X-ray; 2.00 A; A=59-381. DR PDB; 4AA8; X-ray; 1.80 A; A=59-381. DR PDB; 4AUC; X-ray; 1.60 A; A=59-381. DR PDB; 4CMS; X-ray; 2.20 A; A=59-381. DR AlphaFoldDB; P00794; -. DR SMR; P00794; -. DR FunCoup; P00794; 78. DR STRING; 9913.ENSBTAP00000013970; -. DR Allergome; 3882; Bos d Chymosin. DR MEROPS; A01.006; -. DR PaxDb; 9913-ENSBTAP00000013970; -. DR ABCD; P00794; 11 sequenced antibodies. DR Ensembl; ENSBTAT00000013970.4; ENSBTAP00000013970.3; ENSBTAG00000010565.6. DR GeneID; 529879; -. DR KEGG; bta:529879; -. DR CTD; 229697; -. DR VEuPathDB; HostDB:ENSBTAG00000010565; -. DR eggNOG; KOG1339; Eukaryota. DR GeneTree; ENSGT00940000162710; -. DR HOGENOM; CLU_013253_3_0_1; -. DR InParanoid; P00794; -. DR OMA; TPVFDHM; -. DR OrthoDB; 771136at2759; -. DR BRENDA; 3.4.23.4; 908. DR SABIO-RK; P00794; -. DR EvolutionaryTrace; P00794; -. DR Proteomes; UP000009136; Chromosome 3. DR Bgee; ENSBTAG00000010565; Expressed in urinary bladder and 4 other cell types or tissues. DR ExpressionAtlas; P00794; baseline. DR GO; GO:0004190; F:aspartic-type endopeptidase activity; IBA:GO_Central. DR GO; GO:0006508; P:proteolysis; IBA:GO_Central. DR CDD; cd05478; pepsin_A; 1. DR FunFam; 2.40.70.10:FF:000006; Cathepsin E; 1. DR FunFam; 2.40.70.10:FF:000004; Pepsin A; 1. DR Gene3D; 6.10.140.60; -; 1. DR Gene3D; 2.40.70.10; Acid Proteases; 2. DR InterPro; IPR001461; Aspartic_peptidase_A1. DR InterPro; IPR001969; Aspartic_peptidase_AS. DR InterPro; IPR012848; Aspartic_peptidase_N. DR InterPro; IPR034162; Pepsin_A. DR InterPro; IPR033121; PEPTIDASE_A1. DR InterPro; IPR021109; Peptidase_aspartic_dom_sf. DR PANTHER; PTHR47966; BETA-SITE APP-CLEAVING ENZYME, ISOFORM A-RELATED; 1. DR PANTHER; PTHR47966:SF13; CHYMOSIN; 1. DR Pfam; PF07966; A1_Propeptide; 1. DR Pfam; PF00026; Asp; 1. DR PRINTS; PR00792; PEPSIN. DR SUPFAM; SSF50630; Acid proteases; 1. DR PROSITE; PS00141; ASP_PROTEASE; 2. DR PROSITE; PS51767; PEPTIDASE_A1; 1. DR PDBsum; 1CMS; -. DR PDBsum; 1CZI; -. DR PDBsum; 3CMS; -. DR PDBsum; 4AA8; -. DR PDBsum; 4AUC; -. DR PDBsum; 4CMS; -. PE 1: Evidence at protein level; KW 3D-structure; Aspartyl protease; Digestion; Direct protein sequencing; KW Disulfide bond; Hydrolase; Protease; Reference proteome; Signal; Zymogen. FT SIGNAL 1..16 FT /evidence="ECO:0000269|PubMed:240697, FT ECO:0000269|PubMed:329280, ECO:0000269|PubMed:6283469" FT PROPEP 17..58 FT /note="Activation peptide" FT /evidence="ECO:0000269|PubMed:381305" FT /id="PRO_0000025988" FT CHAIN 59..381 FT /note="Chymosin" FT /id="PRO_0000025989" FT DOMAIN 74..378 FT /note="Peptidase A1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01103" FT ACT_SITE 92 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10094, FT ECO:0000269|PubMed:329280, ECO:0000269|PubMed:4612029" FT ACT_SITE 274 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10094, FT ECO:0000269|PubMed:329280, ECO:0000269|PubMed:4612029" FT DISULFID 105..110 FT /evidence="ECO:0000269|PubMed:381305" FT DISULFID 265..269 FT /evidence="ECO:0000269|PubMed:381305" FT DISULFID 308..341 FT /evidence="ECO:0000269|PubMed:381305" FT VARIANT 302 FT /note="G -> D (in chymosin A)" FT /evidence="ECO:0000269|PubMed:6183168, FT ECO:0000269|PubMed:6804449" FT MUTAGEN 308 FT /note="C->D: Propeptide is not cleaved." FT /evidence="ECO:0000269|PubMed:1530626" FT MUTAGEN 341 FT /note="C->S: Propeptide is not cleaved." FT /evidence="ECO:0000269|PubMed:1530626" FT CONFLICT 17 FT /note="A -> T (in Ref. 3; AAA30446)" FT /evidence="ECO:0000305" FT CONFLICT 109 FT /note="A -> G (in Ref. 3; AAA30446)" FT /evidence="ECO:0000305" FT CONFLICT 155 FT /note="V -> L (in Ref. 1; AAA30447)" FT /evidence="ECO:0000305" FT CONFLICT 174 FT /note="Y -> T (in Ref. 7; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 218 FT /note="N -> D (in Ref. 7; AA sequence and 9; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 230 FT /note="D -> N (in Ref. 2; AAA30448)" FT /evidence="ECO:0000305" FT CONFLICT 232 FT /note="S -> C (in Ref. 1; AAA30447)" FT /evidence="ECO:0000305" FT CONFLICT 252 FT /note="T -> Y (in Ref. 9; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 325 FT /note="M -> I (in Ref. 5)" FT /evidence="ECO:0000305" FT CONFLICT 335 FT /note="S -> G (in Ref. 5)" FT /evidence="ECO:0000305" FT CONFLICT 343 FT /note="S -> T (in Ref. 5)" FT /evidence="ECO:0000305" FT CONFLICT 380 FT /note="A -> T (in Ref. 5)" FT /evidence="ECO:0000305" FT STRAND 62..65 FT /evidence="ECO:0007829|PDB:4AUC" FT STRAND 67..69 FT /evidence="ECO:0007829|PDB:4AUC" FT TURN 70..72 FT /evidence="ECO:0007829|PDB:4AUC" FT STRAND 73..80 FT /evidence="ECO:0007829|PDB:4AUC" FT TURN 81..84 FT /evidence="ECO:0007829|PDB:4AUC" FT STRAND 85..92 FT /evidence="ECO:0007829|PDB:4AUC" FT STRAND 98..100 FT /evidence="ECO:0007829|PDB:4AUC" FT HELIX 108..111 FT /evidence="ECO:0007829|PDB:4AUC" FT HELIX 118..120 FT /evidence="ECO:0007829|PDB:4AUC" FT STRAND 125..137 FT /evidence="ECO:0007829|PDB:4AUC" FT STRAND 139..151 FT /evidence="ECO:0007829|PDB:4AUC" FT STRAND 154..166 FT /evidence="ECO:0007829|PDB:4AUC" FT TURN 171..173 FT /evidence="ECO:0007829|PDB:4AUC" FT STRAND 176..182 FT /evidence="ECO:0007829|PDB:4AUC" FT HELIX 186..188 FT /evidence="ECO:0007829|PDB:4AUC" FT HELIX 196..202 FT /evidence="ECO:0007829|PDB:4AUC" FT STRAND 206..214 FT /evidence="ECO:0007829|PDB:4AUC" FT STRAND 217..220 FT /evidence="ECO:0007829|PDB:4AUC" FT STRAND 223..227 FT /evidence="ECO:0007829|PDB:4AUC" FT HELIX 231..233 FT /evidence="ECO:0007829|PDB:4AUC" FT STRAND 234..242 FT /evidence="ECO:0007829|PDB:4AUC" FT STRAND 244..246 FT /evidence="ECO:0007829|PDB:4AUC" FT STRAND 249..253 FT /evidence="ECO:0007829|PDB:4AUC" FT STRAND 255..258 FT /evidence="ECO:0007829|PDB:4AUC" FT STRAND 261..264 FT /evidence="ECO:0007829|PDB:4AUC" FT STRAND 269..273 FT /evidence="ECO:0007829|PDB:4AUC" FT STRAND 279..283 FT /evidence="ECO:0007829|PDB:4AUC" FT HELIX 284..294 FT /evidence="ECO:0007829|PDB:4AUC" FT STRAND 297..299 FT /evidence="ECO:0007829|PDB:3CMS" FT TURN 300..302 FT /evidence="ECO:0007829|PDB:3CMS" FT STRAND 304..306 FT /evidence="ECO:0007829|PDB:4AUC" FT HELIX 308..313 FT /evidence="ECO:0007829|PDB:4AUC" FT HELIX 314..316 FT /evidence="ECO:0007829|PDB:4CMS" FT STRAND 317..321 FT /evidence="ECO:0007829|PDB:4AUC" FT STRAND 324..328 FT /evidence="ECO:0007829|PDB:4AUC" FT HELIX 330..333 FT /evidence="ECO:0007829|PDB:4AUC" FT STRAND 334..337 FT /evidence="ECO:0007829|PDB:4AUC" FT STRAND 340..350 FT /evidence="ECO:0007829|PDB:4AUC" FT STRAND 354..356 FT /evidence="ECO:0007829|PDB:4AUC" FT HELIX 358..361 FT /evidence="ECO:0007829|PDB:4AUC" FT STRAND 364..369 FT /evidence="ECO:0007829|PDB:4AUC" FT TURN 370..373 FT /evidence="ECO:0007829|PDB:4AUC" FT STRAND 374..380 FT /evidence="ECO:0007829|PDB:4AUC" SQ SEQUENCE 381 AA; 42180 MW; A4425013B4E2E56A CRC64; MRCLVVLLAV FALSQGAEIT RIPLYKGKSL RKALKEHGLL EDFLQKQQYG ISSKYSGFGE VASVPLTNYL DSQYFGKIYL GTPPQEFTVL FDTGSSDFWV PSIYCKSNAC KNHQRFDPRK SSTFQNLGKP LSIHYGTGSM QGILGYDTVT VSNIVDIQQT VGLSTQEPGD VFTYAEFDGI LGMAYPSLAS EYSIPVFDNM MNRHLVAQDL FSVYMDRNGQ ESMLTLGAID PSYYTGSLHW VPVTVQQYWQ FTVDSVTISG VVVACEGGCQ AILDTGTSKL VGPSSDILNI QQAIGATQNQ YGEFDIDCDN LSYMPTVVFE INGKMYPLTP SAYTSQDQGF CTSGFQSENH SQKWILGDVF IREYYSVFDR ANNLVGLAKA I //