Reviewed, UniProtKB/Swiss-Prot P00794 (CHYM_BOVIN)

Names and origin

Protein names

Recommended name:
    Chymosin
    EC=3.4.23.4
Alternative name(s):
    Preprorennin

Gene names

Name:	CYM
Synonyms:	CPC

Organism

Bos taurus (Bovine)

Taxonomic identifier

9913 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Cetartiodactyla › Ruminantia › Pecora › Bovidae › Bovinae › Bos

Protein attributes

Sequence length	381 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Chymosin is synthesized in the mucosa of the abomasum (fourth stomach) of young (unweaned) ruminants. The enzyme hydrolyzes casein to paracasein.
Catalytic activity	Broad specificity similar to that of pepsin A. Clots milk by cleavage of a single 105-Ser-Phe-|-Met-Ala-108 bond in kappa-chain of casein.
Subunit structure	Monomer.
Polymorphism	Forms A and B are probably allelic variants. Form B is the predominant form and differs only in one position.
Sequence similarities	Belongs to the peptidase A1 family.

Ontologies

Keywords
Biological process	Digestion
Domain	Signal
Molecular function	Aspartyl protease Hydrolase Protease
PTM	Disulfide bond Zymogen
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	digestion Inferred from electronic annotation. Source: UniProtKB-KW proteolysis Inferred from electronic annotation. Source: InterPro
Molecular function	aspartic-type endopeptidase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 16

16

Ref.7 Ref.8 Ref.2

Propeptide

17 – 58

42

Activation peptide

PRO_0000025988

Chain

59 – 381

323

Chymosin

PRO_0000025989

Sites

Active site

92

1

Ref.7 Ref.10

Active site

274

1

Ref.7 Ref.10

Amino acid modifications

Disulfide bond

105 ↔ 110

Ref.9

Disulfide bond

265 ↔ 269

Ref.9

Disulfide bond

308 ↔ 341

Ref.9

Natural variations

Natural variant

302

1

G → D in chymosin A. Ref.1 Ref.5

Experimental info

Mutagenesis

308

1

C → D: Propeptide is not cleaved. Ref.14

Mutagenesis

341

1

C → S: Propeptide is not cleaved. Ref.14

Sequence conflict

17

1

A → T in AAA30446. Ref.3

Sequence conflict

109

1

A → G in AAA30446. Ref.3

Sequence conflict

155

1

V → L in AAA30447. Ref.1

Sequence conflict

174

1

Y → T AA sequence Ref.7

Sequence conflict

218

1

N → D AA sequence Ref.7

Sequence conflict

218

1

N → D AA sequence Ref.9

Sequence conflict

230

1

D → N in AAA30448. Ref.2

Sequence conflict

232

1

S → C in AAA30447. Ref.1

Sequence conflict

252

1

T → Y AA sequence Ref.9

Sequence conflict

325

1

M → I Ref.5

Sequence conflict

335

1

S → G Ref.5

Sequence conflict

343

1

S → T Ref.5

Sequence conflict

380

1

A → T Ref.5

Secondary structure

1

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381

Helix Strand Turn

Details...

Beta strand

62 – 65

4

Beta strand

67 – 69

3

Turn

70 – 72

3

Beta strand

73 – 80

8

Turn

81 – 84

4

Beta strand

85 – 92

8

Beta strand

98 – 100

3

Helix

108 – 111

4

Helix

118 – 120

3

Beta strand

125 – 135

11

Beta strand

138 – 151

14

Beta strand

154 – 166

13

Helix

170 – 174

5

Beta strand

176 – 182

7

Helix

186 – 188

3

Helix

196 – 202

7

Beta strand

206 – 214

9

Beta strand

223 – 227

5

Helix

231 – 233

3

Beta strand

234 – 242

9

Turn

246 – 248

3

Beta strand

249 – 264

16

Beta strand

269 – 273

5

Beta strand

278 – 283

6

Helix

284 – 294

11

Beta strand

304 – 306

3

Helix

310 – 313

4

Beta strand

317 – 321

5

Beta strand

324 – 328

5

Helix

330 – 333

4

Beta strand

334 – 337

4

Beta strand

340 – 351

12

Beta strand

354 – 356

3

Helix

358 – 361

4

Beta strand

364 – 369

6

Turn

370 – 373

4

Beta strand

374 – 380

7

Sequences

	Sequence		Length	Mass (Da)
	P00794-1 [UniParc]. Last modified February 1, 2005. Version 3. Checksum: A4425013B4E2E56A	FASTA	381	42,180
	10 20 30 40 50 60 MRCLVVLLAV FALSQGAEIT RIPLYKGKSL RKALKEHGLL EDFLQKQQYG ISSKYSGFGE 70 80 90 100 110 120 VASVPLTNYL DSQYFGKIYL GTPPQEFTVL FDTGSSDFWV PSIYCKSNAC KNHQRFDPRK 130 140 150 160 170 180 SSTFQNLGKP LSIHYGTGSM QGILGYDTVT VSNIVDIQQT VGLSTQEPGD VFTYAEFDGI 190 200 210 220 230 240 LGMAYPSLAS EYSIPVFDNM MNRHLVAQDL FSVYMDRNGQ ESMLTLGAID PSYYTGSLHW 250 260 270 280 290 300 VPVTVQQYWQ FTVDSVTISG VVVACEGGCQ AILDTGTSKL VGPSSDILNI QQAIGATQNQ 310 320 330 340 350 360 YGEFDIDCDN LSYMPTVVFE INGKMYPLTP SAYTSQDQGF CTSGFQSENH SQKWILGDVF 370 380 IREYYSVFDR ANNLVGLAKA I

References

[1]	"Molecular cloning and characterization of double-stranded cDNA coding for bovine chymosin." Moir D., Mao J., Schumm J.W., Vovis G.F., Alford B.L., Taunton-Rigby A. Gene 19:127-138(1982) [PubMed: 6183168] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ASP-302.
[2]	"Molecular cloning and nucleotide sequence of cDNA coding for calf preprochymosin." Harris T.J.R., Lowe P.A., Lyons A., Thomas P.G., Eaton M.A.W., Millican T.A., Patel T.P., Bose C.C., Carey N.H., Doel M.T. Nucleic Acids Res. 10:2177-2187(1982) [PubMed: 6283469] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Cloning and structural analysis of the calf prochymosin gene." Hidaka M., Sasaki K., Uozumi T., Beppu T. Gene 43:197-203(1986) [PubMed: 3091454] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"cDNA encoding bovine calf preprochymosin." Sun D., Jiang Y. Submitted (APR-2007) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[5]	"Nucleotide sequence of calf prorennin cDNA cloned in Escherichia coli." Nishimori K., Kawaguchi Y., Hidaka M., Uozumi T., Beppu T. J. Biochem. 91:1085-1088(1982) [PubMed: 6804449] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 140-381, VARIANT ASP-302.
[6]	"Isolation of human, swine, and rat prepepsinogens and calf preprochymosin, and determination of the primary structures of their NH2-terminal signal sequences." Ichihara Y., Sogawa K., Takahashi K. J. Biochem. 98:483-492(1985) [PubMed: 2415509] [Abstract] Cited for: PROTEIN SEQUENCE OF 1-30.
[7]	"The complete amino acid sequence of prochymosin." Foltmann B., Pedersen V.B., Jacobsen H., Kauffman D., Wybrandt G. Proc. Natl. Acad. Sci. U.S.A. 74:2321-2324(1977) [PubMed: 329280] [Abstract] Cited for: PROTEIN SEQUENCE OF 17-381.
[8]	"Amino-acid sequence of the peptide segment liberated during activation of prochymosin (prorennin)." Pedersen V.B., Foltmann B. Eur. J. Biochem. 55:95-103(1975) [PubMed: 240697] [Abstract] Cited for: PROTEIN SEQUENCE OF 17-77.
[9]	"The primary structure of calf chymosin." Foltmann B., Pedersen V.B., Kauffman D., Wybrandt G. J. Biol. Chem. 254:8447-8456(1979) [PubMed: 381305] [Abstract] Cited for: PROTEIN SEQUENCE OF 59-381, DISULFIDE BONDS.
[10]	"The structure and function of acid proteases. III. Isolation and characterization of the active-site peptides from bovine rennin." Chang W.-J., Takahashi K. J. Biochem. 76:467-474(1974) [PubMed: 4612029] [Abstract] Cited for: ACTIVE SITE PEPTIDES.
[11]	"X-ray analyses of aspartic proteinases. IV. Structure and refinement at 2.2-A resolution of bovine chymosin." Newman M., Safro M., Frazao C., Kahn G., Zdanov A., Tickle I.J., Blundell T.L., Andreeva N. J. Mol. Biol. 221:1295-1309(1991) [PubMed: 1942052] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
[12]	"Engineering enzyme subsite specificity: preparation, kinetic characterization, and X-ray analysis at 2.0-A resolution of Val111Phe site-mutated calf chymosin." Strop P., Sedlacek J., Stys J., Kaderabkova Z., Blaha I., Pavlickova L., Pohl J., Fabry M., Kostka V., Newman M., Frazao C., Shearer A., Tickle I.J., Blundell T.L. Biochemistry 29:9863-9871(1990) [PubMed: 2271625] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF MUTANT.
[13]	"The three-dimensional structure of recombinant bovine chymosin at 2.3-A resolution." Gilliland G.L., Winborne E.L., Nachman J., Wlodawer A. Proteins 8:82-101(1990) [PubMed: 2217166] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).
[14]	"Functional implication of disulfide bond, Cys250 -Cys283, in bovine chymosin." Huang K., Zhang Z., Liu N., Zhang Y., Zhang G., Yang K. Biochem. Biophys. Res. Commun. 187:692-696(1992) [PubMed: 1530626] [Abstract] Cited for: MUTAGENESIS OF CYS-308 AND CYS-341.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

J00002 mRNA. Translation: AAA30447.1.
J00003 mRNA. Translation: AAA30448.1.
M14077 , M14069, M14070, M14071, M14072, M14073, M14074, M14075 Genomic DNA. Translation: AAA30446.1.
EF541122 mRNA. Translation: ABU41411.1.

IPI

IPI00714262.

PIR

CMBO. A25631.

RefSeq

NP_851337.1.

UniGene

Bt.394

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1CMS	X-ray	2.30	A	59-381	[»]
1CZI	X-ray	2.30	E	59-381	[»]
3CMS	X-ray	2.00	A	59-381	[»]
4CMS	X-ray	2.20	A	59-381	[»]

ModBase

Search...

Protein-protein interaction databases

STRING

P00794.

Protein family/group databases

MEROPS

A01.006.

Genome annotation databases

Ensembl

ENSBTAT00000013970; ENSBTAP00000013970; ENSBTAG00000010565; Bos taurus. [Genome view]

GeneID

529879.

KEGG

bta:529879.

Organism-specific databases

CTD

529879.

Phylogenomic databases

HOVERGEN

P00794.

Enzyme and pathway databases

BRENDA

3.4.23.4. 251.

Family and domain databases

InterPro

IPR001461. Peptidase_A1.
IPR001969. Peptidase_aspartic_AS.
IPR009007. Peptidase_aspartic_catalytic.
IPR012848. Propep_A1.
[Graphical view]

Gene3D

G3DSA:2.40.70.10. Pept_Aspartc_cat. 1 hit.

PANTHER

PTHR13683. Peptidase_A1. 1 hit.

Pfam

PF07966. A1_Propeptide. 1 hit.
PF00026. Asp. 1 hit.
[Graphical view]

PRINTS

PR00792. PEPSIN.

PROSITE

PS00141. ASP_PROTEASE. 2 hits.
[Graphical view]

ProtoNet

Search...

Entry information

Entry name

CHYM_BOVIN

Accession

Primary (citable) accession number: P00794
Secondary accession number(s): A8RRP5

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	February 1, 2005
Last modified:	September 1, 2009
This is version 97 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)