CHYM_BOVIN
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 03-AUG-2022, entry version 178.
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 PDBsum; 1CMS; -.
DR PDBsum; 1CZI; -.
DR PDBsum; 3CMS; -.
DR PDBsum; 4AA8; -.
DR PDBsum; 4AUC; -.
DR PDBsum; 4CMS; -.
DR AlphaFoldDB; P00794; -.
DR SMR; P00794; -.
DR STRING; 9913.ENSBTAP00000013970; -.
DR Allergome; 3882; Bos d Chymosin.
DR MEROPS; A01.006; -.
DR PaxDb; P00794; -.
DR ABCD; P00794; 11 sequenced antibodies.
DR Ensembl; ENSBTAT00000013970; ENSBTAP00000013970; ENSBTAG00000010565.
DR GeneID; 529879; -.
DR KEGG; bta:529879; -.
DR CTD; 229697; -.
DR VEuPathDB; HostDB:ENSBTAG00000010565; -.
DR VGNC; VGNC:108923; CYM.
DR eggNOG; KOG1339; Eukaryota.
DR GeneTree; ENSGT00940000162710; -.
DR HOGENOM; CLU_013253_3_0_1; -.
DR InParanoid; P00794; -.
DR OMA; DEVVACQ; -.
DR OrthoDB; 1619495at2759; -.
DR TreeFam; TF314990; -.
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 tissues.
DR ExpressionAtlas; P00794; baseline.
DR GO; GO:0004190; F:aspartic-type endopeptidase activity; IBA:GO_Central.
DR GO; GO:0007586; P:digestion; IEA:UniProtKB-KW.
DR GO; GO:0006508; P:proteolysis; IBA:GO_Central.
DR CDD; cd05478; pepsin_A; 1.
DR Gene3D; 2.40.70.10; -; 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; PTHR47966; 1.
DR Pfam; PF07966; A1_Propeptide; 1.
DR Pfam; PF00026; Asp; 1.
DR PRINTS; PR00792; PEPSIN.
DR SUPFAM; SSF50630; SSF50630; 1.
DR PROSITE; PS00141; ASP_PROTEASE; 2.
DR PROSITE; PS51767; PEPTIDASE_A1; 1.
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..134
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 TURN 246..249
FT /evidence="ECO:0007829|PDB:4AUC"
FT STRAND 250..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 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
