Reviewed, UniProtKB/Swiss-Prot P02666 (CASB_BOVIN)

Names and origin

Protein names

Recommended name:
    Beta-casein
Cleaved into the following 3 chains:
    1- Recommended name:
            Casoparan
    2- Recommended name:
            Antioxidant peptide
    3- Recommended name:
            Casohypotensin

Gene names

Name:

CSN2

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	224 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	Important role in determination of the surface properties of the casein micelles. Ref.12 Ref.21 Ref.24 Ref.25 Casoparan acts as a macrophage activator, increasing the phagocytic activity of macrophages and peroxide release from macrophages. It also acts as a bradykinin-potentiating peptide. Ref.12 Ref.21 Ref.24 Ref.25 Casohypotensin acts as a bradykinin-potentiating peptide. Induces hypotension in rats. Acts as a strong competitive inhibitor of endo-oligopeptidase A. Ref.12 Ref.21 Ref.24 Ref.25 Antioxidant peptide has antioxidant activity. Ref.12 Ref.21 Ref.24 Ref.25
Subcellular location	Secreted.
Tissue specificity	Mammary gland specific. Secreted in milk.
Polymorphism	Leu-152 is present in the variants F and G; Gln-190 and Glu-210 are present in the variant H. The sequence shown is the A2 variant.
Sequence similarities	Belongs to the beta-casein family.
Mass spectrometry	Molecular mass is 872.51 Da from positions 113 - 120. Determined by ESI. Ref.21
Sequence caution	The sequence ABL74247.1 differs from that shown. Reason: Frameshift at positions 65 and 71.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Domain	Signal
Molecular function	Antioxidant Hypotensive agent Metalloenzyme inhibitor Metalloprotease inhibitor Milk protein
PTM	Phosphoprotein
Technical term	Direct protein sequencing
Gene Ontology (GO)
Biological process	regulation of blood pressure Inferred from electronic annotation. Source: UniProtKB-KW transport Inferred from electronic annotation. Source: InterPro
Cellular component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	antioxidant activity Inferred from electronic annotation. Source: UniProtKB-KW metalloendopeptidase inhibitor activity Inferred from electronic annotation. Source: UniProtKB-KW transporter activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 15	15	Ref.8 Ref.9 Ref.10
	Chain	16 – 224	209	Beta-casein		PRO_0000004470
	Peptide	41 – 45	5	Casoparan Ref.12		PRO_0000292031
	Peptide	113 – 120	8	Antioxidant peptide Ref.21		PRO_0000320153
	Peptide	129 – 136	8	Casohypotensin		PRO_0000308464
Amino acid modifications
	Modified residue	30	1	Phosphoserine Ref.8 Ref.28 Ref.29
	Modified residue	32	1	Phosphoserine Ref.8 Ref.28 Ref.29
	Modified residue	33	1	Phosphoserine Ref.8 Ref.28 Ref.29
	Modified residue	34	1	Phosphoserine Ref.8 Ref.28 Ref.29
	Modified residue	50	1	Phosphoserine; in variant A1, variant A2, variant A3, variant B, variant E, variant F, variant G and variant H Ref.28 Ref.29
Natural variations
	Natural variant	33	1	S → K in variant D. Ref.10
	Natural variant	40	1	R → C in variant H.
	Natural variant	51	1	E → K in variant E. Ref.13
	Natural variant	52	1	E → K in variant C.
	Natural variant	82	1	P → H in variants A1, B, C, F and G. Ref.21 Ref.4 Ref.6
	Natural variant	103	1	L → I in variant H.
	Natural variant	108	1	M → L
	Natural variant	121	1	H → Q in variant A3. Ref.5 Ref.22
	Natural variant	132	1	E → Q in variants A1 and G. Ref.24 Ref.11
	Natural variant	137	1	S → R in variant B. Ref.6
	Natural variant	152	1	L → P in variants A1 and H. Ref.1
	Natural variant	153	1	P → L in variants A1, G and H. Ref.1
	Natural variant	167	1	P → L in variant F.
	Natural variant	190	1	Q → E in variants A1 and G.
Experimental info
	Sequence conflict	50	1	S → Z AA sequence Ref.11
	Sequence conflict	69	1	Q → R in ABL74247. Ref.14
	Sequence conflict	112	1	K → R in ABL74247. Ref.14
	Sequence conflict	208	1	Y → V in CAC37028. Ref.16
	Sequence conflict	209 – 210	2	QE → EQ AA sequence Ref.11
	Sequence conflict	210	1	E → Q in AAA30430. Ref.1
	Sequence conflict	210	1	E → Q Ref.8
	Sequence conflict	212	1	V → A in ABR10906. Ref.15

Sequences

	Sequence		Length	Mass (Da)
	P02666-1 [UniParc]. Last modified July 1, 1989. Version 2. Checksum: F0BBDD8148A238AE	FASTA	224	25,107
	10 20 30 40 50 60 MKVLILACLV ALALARELEE LNVPGEIVES LSSSEESITR INKKIEKFQS EEQQQTEDEL 70 80 90 100 110 120 QDKIHPFAQT QSLVYPFPGP IPNSLPQNIP PLTQTPVVVP PFLQPEVMGV SKVKEAMAPK 130 140 150 160 170 180 HKEMPFPKYP VEPFTESQSL TLTDVENLHL PLPLLQSWMH QPHQPLPPTV MFPPQSVLSL 190 200 210 220 SQSKVLPVPQ KAVPYPQRDM PIQAFLLYQE PVLGPVRGPF PIIV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and sequence analysis of bovine beta-casein cDNA." Jimenez-Flores R., Kang Y.C., Richardson T. Biochem. Biophys. Res. Commun. 142:617-621(1987) [PubMed: 3814153] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS LEU-108; PRO-152 AND LEU-153.
[2]	"Primary structure of bovine beta-casein cDNA." Baev A.A., Smirnov I.K., Gorodetsky S.I. Mol. Biol. (Mosk.) 21:214-222(1987) Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT HIS-82.
[3]	"Complete nucleotide sequences of bovine alpha S2- and beta-casein cDNAs: comparisons with related sequences in other species." Stewart A.F., Bonsing J., Beattie C.W., Shah F., Willis I.M., Mackinlay A.G. Mol. Biol. Evol. 4:231-241(1987) [PubMed: 2833669] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"Complete nucleotide sequence of the bovine beta-casein gene." Bonsing J., Ring J.M., Stewart A.F., Mackinlay A.G. Aust. J. Biol. Sci. 41:527-537(1988) [PubMed: 3271384] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT HIS-82.
[5]	"Overproduction of bovine beta-casein in Escherichia coli and engineering of its main chymosin cleavage site." Simons G., van den Heuvel W., Reynen T., Frijters A., Rutten G., Slangen C.J., Groenen M., de Vos W.M., Siezen R.J. Protein Eng. 6:763-770(1993) [PubMed: 8248100] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT A3 GLN-121. Tissue: Mammary gland.
[6]	NIH - Mammalian Gene Collection (MGC) project Submitted (DEC-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS HIS-82 AND ARG-137. Strain: Crossbred X Angus. Tissue: Liver.
[7]	"Invasive potential of bacterial isolates associated with subclinical bovine mastitis." Anaya-Lopez J.L., Contreras-Guzman O.E., Carabez-Trejo A., Baizabal-Aguirre V.M., Lopez-Meza J.E., Valdez-Alarcon J.J., Ochoa-Zarzosa A. Res. Vet. Sci. 81:358-361(2006) [PubMed: 16624358] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-101. Tissue: Mammary epithelium.
[8]	"Primary structure of bovine beta casein. Complete sequence." Ribadeau-Dumas B., Brignon G., Grosclaude F., Mercier J.-C. Eur. J. Biochem. 25:505-514(1972) [PubMed: 4557764] [Abstract] Cited for: PROTEIN SEQUENCE OF 16-224 (VARIANT A2), VARIANT LEU-108.
[9]	"A new strategy for primary structure determination of proteins: application to bovine beta-casein." Carles C., Huet J.-C., Ribadeau-Dumas B. FEBS Lett. 229:265-272(1988) [PubMed: 3278933] [Abstract] Cited for: PROTEIN SEQUENCE OF 16-224 (VARIANT A2).
[10]	"Biochemical, molecular and physiological characterization of a new beta-casein variant detected in Korean cattle." Han S.K., Shin Y.C., Byun H.D. Anim. Genet. 31:49-51(2000) [PubMed: 10690361] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 18-57, PROTEIN SEQUENCE OF 16-224 (VARIANT H), VARIANT D LYS-33. Strain: Korean. Tissue: Milk.
[11]	"Analysis of bovine beta-casein tryptic digest by continuous-flow fast-atom bombardment mass spectrometry." Jones D.S., Heerma W., van Wassenaar P.D., Haverkamp J. Rapid Commun. Mass Spectrom. 5:192-195(1991) [PubMed: 1804413] [Abstract] Cited for: PROTEIN SEQUENCE OF 41-71; 113-157 AND 180-224, VARIANT GLN-132.
[12]	"Effects of 'casoparan', a peptide isolated from casein hydrolysates with mastoparan-like properties." Lebrun I., Cavallaro V., Juliano L., Juliano M.A., de Sousa e Silva M.C.C. Mediators Inflamm. 13:263-268(2004) [PubMed: 15545057] [Abstract] Cited for: PROTEIN SEQUENCE OF 41-45, FUNCTION.
[13]	"The beta E variant and the phosphorylation code of bovine caseins." Grosclaude F., Mahe M.-F., Voglino G.-F. FEBS Lett. 45:3-5(1974) [PubMed: 4411121] [Abstract] Cited for: PROTEIN SEQUENCE OF 48-63, VARIANT E LYS-51.
[14]	"Polymorphisms in beta and kappa casein genes in bubaline and bovine." Otaviano A.R., Lima A.L.F., Laureano M.M.M., Albuquerque L.G., Tonhati H., Sena J.A.D. Submitted (NOV-2006) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 58-223.
[15]	"Polymorphism in the cattle beta casein gene." Shahla M.N., Cheema F.R., Naeem M.K., Riazuddin S. Submitted (MAY-2007) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 58-223.
[16]	"Characterization of milk proteins." Klotz A., Buchberger J., Krause I., Einspanier R. Submitted (JAN-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 63-208. Tissue: Mammary gland.
[17]	"Identification of bacterial clones encoding bovine caseins by direct immunological screening of the cDNA library." Ivanov V.N., Kershulite D.R., Bayev A.A., Akhundova A.A., Sulimova G.E., Judinkova E.S., Gorodetsky S.I. Gene 32:381-388(1984) [PubMed: 6397405] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 68-105.
[18]	"Identification of bacterial clones that encode cow's caseins by direct immunological screening of the cDNA library." Ivanov V.N., Kershulite D.R., Bayev A.A., Akhundova A.A., Silimova G.E. Mol. Biol. (Mosk.) 19:955-963(1985) [PubMed: 3900695] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 68-95.
[19]	"Peptic digestion of beta-casein: Time course and fate of possible bioactive peptides." Schmelzer C.E.H., Schoeps R., Reynell L., Ulbrich-Hofmann R., Neubert R.H.H., Raith K. J. Chromatogr. A 1166:108-115(2007) [PubMed: 17720176] [Abstract] Cited for: PROTEIN SEQUENCE OF 74-108, VARIANT LEU-108, PHOSPHORYLATION, MASS SPECTROMETRY.
[20]	"A new variant in exon VII of bovine beta-casein gene (CSN2) and its contribution among European cattle breeds." Jann O., Ceriotti G., Caroli A., Erhardt G. J. Anim. Breed. Genet. 119:65-68(2002) Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 80-143, VARIANT LEU-108.
[21]	"Studies on antioxidative peptides generated in cheddar cheese." Gupta A., Mann B., Kumar Bajaj R., Sangwan R.B. Submitted (JAN-2008) to UniProtKB Cited for: PROTEIN SEQUENCE OF 113-120, FUNCTION, MASS SPECTROMETRY.
[22]	"Localization in the peptide chain of bovine beta casein of the His-Gln substitution differentiating the A2 and A3 genetic variants." Ribadeau-Dumas B., Grosclaude F., Mercier J.-C. C. R. Hebd. Seances Acad. Sci., D, Sci. Nat. 270:2369-2372(1970) [PubMed: 4997616] [Abstract] Cited for: PROTEIN SEQUENCE OF 118-124, VARIANT A3 GLN-121.
[23]	"Characterization of a non-electrophoretic genetic variant of beta-casein by peptide mapping and mass spectrometric analysis." Dong C., Ng-Kwai-Hang K.F. Int. Dairy J. 8:967-972(1998) [Agricola: IND22004684] Cited for: PROTEIN SEQUENCE OF 125-195 (VARIANTS A1 AND G).
[24]	"Isolation and characterization of a new bradykinin potentiating octapeptide from gamma-casein." Lebrun I., Lebrun F.L.A.S., Henriques O.B., Carmona A.K., Juliano L., Camargo A.C.M. Can. J. Physiol. Pharmacol. 73:85-91(1995) [PubMed: 7600458] [Abstract] Cited for: PROTEIN SQUENCE OF 129-136, FUNCTION, VARIANT GLN-132.
[25]	"Biochemical and pharmacological aspects of two bradykinin-potentiating peptides obtained from tryptic hydrolysis of casein." Perpetuo E.A., Juliano L., Lebrun I. J. Protein Chem. 22:601-606(2003) [PubMed: 14714726] [Abstract] Cited for: PROTEIN SQUENCE OF 129-136, FUNCTION.
[26]	"Identification of a new genetic variant of bovine beta-casein using reversed-phase high-performance liquid chromatography and mass spectrometric analysis." Visser S., Slangen C.J., Lagerwerf F.M., Van Dongen W.D., Haverkamp J. J. Chromatogr. A 711:141-150(1995) [PubMed: 7496485] [Abstract] Cited for: PROTEIN SEQUENCE OF 160-171 (VARIANT F).
[27]	"Construction and identification by partial nucleotide sequence analysis of bovine casein and beta-lactoglobulin cDNA clones." Willis I.M., Stewart A.F., Caputo A., Thompson A.R., McKinlay A.G. DNA 1:375-386(1982) [PubMed: 6897774] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 170-184.
[28]	"Extended Range Proteomic Analysis (ERPA): a new and sensitive LC-MS platform for high sequence coverage of complex proteins with extensive post-translational modifications-comprehensive analysis of beta-casein and epidermal growth factor receptor (EGFR)." Wu S.L., Kim J., Hancock W.S., Karger B. J. Proteome Res. 4:1155-1170(2005) [PubMed: 16083266] [Abstract] Cited for: PHOSPHORYLATION AT SER-30; SER-32; SER-33; SER-34 AND SER-50, MASS SPECTROMETRY.
[29]	"Reference-facilitated phosphoproteomics: fast and reliable phosphopeptide validation by micro LC-ESI-Q-TOF MS/MS." Imanishi S.Y., Kochin V., Ferraris S.E., de Thonel A., Pallari H.M., Corthals G.L., Eriksson J.E. Mol. Cell. Proteomics 6:1380-1391(2007) [PubMed: 17510049] [Abstract] Cited for: PHOSPHORYLATION AT SER-30; SER-32; SER-33; SER-34 AND SER-50, MASS SPECTROMETRY.
[30]	"Characterization of genetic variants of alpha-S1 and beta bovine caseins." Grosclaude F., Mahe M.-F., Mercier J.-C., Ribadeau-Dumas B. Eur. J. Biochem. 26:328-337(1972) [PubMed: 5064450] [Abstract] Cited for: VARIANTS A1; B AND C.

Web resources

Protein Spotlight

Of buttons, digestion and glue - Issue 16 of November 2001

Cross-references

Sequence databases
EMBLGenBankDDBJ	M15132 mRNA. Translation: AAA30430.1. X06359 mRNA. Translation: CAA29658.1. M16645 mRNA. Translation: AAA30480.1. M55158 Genomic DNA. Translation: AAA30431.1. S67277 mRNA. Translation: AAB29137.1. BC111172 mRNA. Translation: AAI11173.1. AY899917 mRNA. Translation: AAW84270.1. Different initiation. AY899918 mRNA. Translation: AAW84271.1. Different initiation. AF104929, AF104928 Genomic DNA. Translation: AAD09813.1. EF123100 Genomic DNA. Translation: ABL74247.1. Frameshift. EF628290 Genomic DNA. Translation: ABR10906.1. AJ296330 Genomic DNA. Translation: CAC37028.1. M64756 mRNA. Translation: AAB59254.1. AY366419 Genomic DNA. Translation: AAR14677.1. K01087 mRNA. Translation: AAA30481.1.
IPI	IPI00697085.
PIR	A59068. KBBOA2. I45873.
RefSeq	NP_851351.1.
UniGene	Bt.53272
3D structure databases
DisProt	DP00329.
ModBase	Search...
Protein-protein interaction databases
STRING	P02666.
Genome annotation databases
Ensembl	ENSBTAT00000003409; ENSBTAP00000003409; ENSBTAG00000002632; Bos taurus. [Genome view]
GeneID	281099.
KEGG	bta:281099.
Organism-specific databases
CTD	281099.
Phylogenomic databases
HOVERGEN	P02666.
Family and domain databases
InterPro	IPR001588. Casein. IPR016345. Casein_beta. [Graphical view]
Pfam	PF00363. Casein. 1 hit. [Graphical view]
PIRSF	PIRSF002372. Beta-casein. 1 hit.
PROSITE	PS00306. CASEIN_ALPHA_BETA. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
PMAP-CutDB	P02666.

Entry information

Entry name

CASB_BOVIN

Accession

Primary (citable) accession number: P02666
Secondary accession number(s): A1YQZ8 , A6N8V0, Q2TA13, Q5EEQ6, Q5EEQ7, Q6UN63, Q9BDG5, Q9TSD5

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	July 1, 1989
Last modified:	September 1, 2009
This is version 96 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)