ID   CASK_BOVIN              Reviewed;         190 AA.
AC   P02668; O46566; Q597F3; Q6U205; Q9N271; Q9TRQ3; Q9TV96; Q9TV97;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   01-APR-1988, sequence version 1.
DT   08-NOV-2023, entry version 167.
DE   RecName: Full=Kappa-casein;
DE   Contains:
DE     RecName: Full=Casoxin-C;
DE   Contains:
DE     RecName: Full=Casoxin-6;
DE   Contains:
DE     RecName: Full=Casoxin-A;
DE   Contains:
DE     RecName: Full=Casoxin-B;
DE   Contains:
DE     RecName: Full=Casoplatelin;
DE   Flags: Precursor;
GN   Name=CSN3; Synonyms=CSN10, CSNK;
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] (VARIANT A).
RX   PubMed=6328443; DOI=10.1093/nar/12.9.3895;
RA   Stewart A.F., Willis I.M., Mackinlay A.G.;
RT   "Nucleotide sequences of bovine alpha S1- and kappa-casein cDNAs.";
RL   Nucleic Acids Res. 12:3895-3907(1984).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (VARIANT B2).
RX   PubMed=3582972;
RA   Gorodetskii S.I., Kaledin A.S.;
RT   "Nucleotide sequence of the cDNA of kappa casein in cows.";
RL   Genetika 23:596-604(1987).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] (VARIANT A).
RX   PubMed=3208764; DOI=10.1111/j.1432-1033.1988.tb14463.x;
RA   Alexander L.J., Stewart A.F., McKinlay A.G., Kapelinskaya T.V., Tkach T.M.,
RA   Gorodetsky S.I.;
RT   "Isolation and characterization of the bovine kappa-casein gene.";
RL   Eur. J. Biochem. 178:395-401(1988).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] (VARIANTS A AND B).
RC   TISSUE=Blood;
RX   PubMed=15771744; DOI=10.1111/j.1365-2052.2005.01260.x;
RA   Robitaille G., Britten M., Morisset J., Petitclerc D.;
RT   "Polymorphism in the bovine kappa-casein (CSN3) gene and the 5'-flanking
RT   region: sequence analysis of CSN3 A and B alleles.";
RL   Anim. Genet. 36:184-185(2005).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (VARIANT B).
RC   STRAIN=Hereford; TISSUE=Mammary gland;
RG   NIH - Mammalian Gene Collection (MGC) project;
RL   Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   PROTEIN SEQUENCE OF 22-127 (VARIANT B).
RX   PubMed=4577852; DOI=10.1111/j.1432-1033.1973.tb02829.x;
RA   Mercier J.-C., Brignon G., Ribadeau-Dumas B.;
RT   "Primary structure of bovine kappa B casein. Complete sequence.";
RL   Eur. J. Biochem. 35:222-235(1973).
RN   [7]
RP   PROTEIN SEQUENCE OF 22-126 (VARIANT A).
RA   Jolles J., Schoentgen F., Alais C., Jolles P.;
RT   "Studies on the primary structure of cow kappa-casein. The primary sequence
RT   of cow para-kappa-casein.";
RL   Chimia 26:645-646(1972).
RN   [8]
RP   PROTEIN SEQUENCE OF 22-38 AND 97-116, PYROGLUTAMATE FORMATION AT GLN-22,
RP   INTERCHAIN DISULFIDE BONDS, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX   PubMed=1628650; DOI=10.1111/j.1432-1033.1992.tb17040.x;
RA   Rasmussen L.K., Hoejrup P., Petersen T.E.;
RT   "The multimeric structure and disulfide-bonding pattern of bovine kappa-
RT   casein.";
RL   Eur. J. Biochem. 207:215-222(1992).
RN   [9]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 31-45.
RX   PubMed=6897774; DOI=10.1089/dna.1982.1.375;
RA   Willis I.M., Stewart A.F., Caputo A., Thompson A.R., McKinlay A.G.;
RT   "Construction and identification by partial nucleotide sequence analysis of
RT   bovine casein and beta-lactoglobulin cDNA clones.";
RL   DNA 1:375-386(1982).
RN   [10]
RP   NUCLEOTIDE SEQUENCE OF 31-190 (VARIANTS F AND G).
RC   STRAIN=Ayrshire, and Pinzgauer;
RX   PubMed=8930077; DOI=10.1111/j.1365-2052.1996.tb00976.x;
RA   Prinzenberg E.M., Hiendleder S., Ikonen T., Erhardt G.;
RT   "Molecular genetic characterization of new bovine kappa-casein alleles
RT   CSN3F and CSN3G and genotyping by PCR-RFLP.";
RL   Anim. Genet. 27:347-349(1996).
RN   [11]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 31-190 (VARIANT H).
RC   STRAIN=Pinzgauer;
RX   PubMed=10654430; DOI=10.1080/10495399909525921;
RA   Prinzenberg E.M., Krause I., Erhardt G.;
RT   "SSCP analysis at the bovine CSN3 locus discriminates six alleles
RT   corresponding to known protein variants (A, B, C, E, F, G) and three new
RT   DNA polymorphisms (H, I, A1).";
RL   Anim. Biotechnol. 10:49-62(1999).
RN   [12]
RP   PROTEIN SEQUENCE OF 54-59.
RX   PubMed=8161175; DOI=10.1128/aem.60.3.801-806.1994;
RA   Reid J.R., Coolbear T., Pillidge C.J., Pritchard G.G.;
RT   "Specificity of hydrolysis of bovine kappa-casein by cell envelope-
RT   associated proteinases from Lactococcus lactis strains.";
RL   Appl. Environ. Microbiol. 60:801-806(1994).
RN   [13]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 92-190 (VARIANT B2).
RX   PubMed=6689612;
RA   Gorodetskii S.I., Kershulyte D.R., Korobko V.G.;
RT   "Primary structure of cDNA of Bos taurus kappa-casein macropeptide.";
RL   Bioorg. Khim. 9:1693-1695(1983).
RN   [14]
RP   PARTIAL PROTEIN SEQUENCE (VARIANT A).
RX   PubMed=4653404; DOI=10.1002/hlca.19720550820;
RA   Jolles J., Schoentgen F., Alais C., Fiat A.-M., Jolles P.;
RT   "Studies on the primary structure of cow kappa-casein. Structural features
RT   of para-kappa-casein; N-terminal sequence of kappa-caseinoglycopeptide
RT   studied with a sequencer.";
RL   Helv. Chim. Acta 55:2872-2883(1972).
RN   [15]
RP   PROTEIN SEQUENCE OF 127-168 AND 187-190.
RC   TISSUE=Colostrum;
RX   PubMed=4407313; DOI=10.1016/0005-2795(74)90195-0;
RA   Guerin J., Alais C., Jolles J., Jolles P.;
RT   "Kappa-casein from bovine colostrum.";
RL   Biochim. Biophys. Acta 351:325-332(1974).
RN   [16]
RP   PROTEIN SEQUENCE OF 128-190 (VARIANTS A AND B).
RA   Grosclaude F., Mahe M.-F., Mercier J.-C., Ribadeau-Dumas B.;
RT   "Localization of amino-acid substitutions that differenciate bovine kappa-
RT   casein variants A and B.";
RL   Ann. Genet. Sel. Anim. 4:515-521(1972).
RN   [17]
RP   NUCLEOTIDE SEQUENCE OF 133-190 (VARIANT E).
RX   PubMed=1683188; DOI=10.1111/j.1365-2052.1991.tb00687.x;
RA   Schlieben S., Erhardt G., Senft B.;
RT   "Genotyping of bovine kappa-casein (kappa-CNA, kappa-CNB, kappa-CNC, kappa-
RT   CNE) following DNA sequence amplification and direct sequencing of kappa-
RT   CNE PCR product.";
RL   Anim. Genet. 22:333-342(1991).
RN   [18]
RP   NUCLEOTIDE SEQUENCE OF 133-190 (VARIANTS A AND B).
RA   Woollard J.R., Dentine M.R.;
RL   Submitted (FEB-1997) to the EMBL/GenBank/DDBJ databases.
RN   [19]
RP   GLYCOSYLATION AT THR-142; THR-152; THR-154; THR-157; THR-163 AND THR-186.
RX   PubMed=7734846; DOI=10.1093/glycob/4.6.837;
RA   Pisano A., Packer N.H., Redmond J.W., Williams K.L., Gooley A.A.;
RT   "Characterization of O-linked glycosylation motifs in the glycopeptide
RT   domain of bovine kappa-casein.";
RL   Glycobiology 4:837-844(1994).
RN   [20]
RP   GLYCOSYLATION AT THR-142; THR-152; THR-154; THR-157; THR-163 AND THR-186,
RP   AND PHOSPHORYLATION AT SER-148 AND SER-170.
RX   PubMed=8817876; DOI=10.1016/0021-9673(96)00122-7;
RA   Minkiewicz P., Slangen C.J., Lagerwerf F.M., Haverkamp J., Rollema H.S.,
RA   Visser S.;
RT   "Reversed-phase high-performance liquid chromatographic separation of
RT   bovine kappa-casein macropeptide and characterization of isolated
RT   fractions.";
RL   J. Chromatogr. A 743:123-135(1996).
RN   [21]
RP   ACTIVITY OF CASOXINS.
RX   PubMed=2760302; DOI=10.1017/s0022029900028818;
RA   Chiba H., Tani F., Yoshikawa M.;
RT   "Opioid antagonist peptides derived from kappa-casein.";
RL   J. Dairy Res. 56:363-366(1989).
RN   [22]
RP   ACTIVITY OF CASOPLATELIN.
RX   PubMed=3732274; DOI=10.1111/j.1432-1033.1986.tb09764.x;
RA   Jolles P., Levy-Toledano S., Fiat A.-M., Soria C., Gillessen D.,
RA   Thomaidis A., Dunn F.W., Caen J.P.;
RT   "Analogy between fibrinogen and casein. Effect of an undecapeptide isolated
RT   from kappa-casein on platelet function.";
RL   Eur. J. Biochem. 158:379-382(1986).
RN   [23]
RP   GLYCOSYLATION AT THR-142; THR-152; SER-153; THR-154; THR-157; THR-163;
RP   SER-170 AND THR-186, PHOSPHORYLATION AT THR-166 AND SER-170, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY.
RX   PubMed=25456591; DOI=10.1016/j.chroma.2014.10.046;
RA   Huang L.J., Lin J.H., Tsai J.H., Chu Y.Y., Chen Y.W., Chen S.L., Chen S.H.;
RT   "Identification of protein O-glycosylation site and corresponding glycans
RT   using liquid chromatography-tandem mass spectrometry via mapping accurate
RT   mass and retention time shift.";
RL   J. Chromatogr. A 1371:136-145(2014).
CC   -!- FUNCTION: Kappa-casein stabilizes micelle formation, preventing casein
CC       precipitation in milk.
CC   -!- FUNCTION: Casoxins A, B and C have opioid antagonist activity. Casoxin
CC       C causes biphasic ileal contractions through the binding to the
CC       complement C3a receptors.
CC   -!- FUNCTION: Casoplatelin inhibits platelet aggregation.
CC   -!- SUBUNIT: Monomer or homomultimer; disulfide-linked.
CC   -!- INTERACTION:
CC       P02668; P02668: CSN3; NbExp=2; IntAct=EBI-7234047, EBI-7234047;
CC       P02668; Q9RA63: clpB; Xeno; NbExp=3; IntAct=EBI-7234047, EBI-7698530;
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- TISSUE SPECIFICITY: Mammary gland specific. Secreted in milk.
CC   -!- MISCELLANEOUS: The sequence shown is the A variant.
CC   -!- SIMILARITY: Belongs to the kappa-casein family. {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=Protein Spotlight; Note=Of buttons, digestion and
CC       glue - Issue 16 of November 2001;
CC       URL="https://web.expasy.org/spotlight/back_issues/016";
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; X00565; CAA25231.1; -; mRNA.
DR   EMBL; M36641; AAA30433.1; -; mRNA.
DR   EMBL; X14907; CAA33034.1; -; Genomic_DNA.
DR   EMBL; X14908; CAA33034.1; JOINED; Genomic_DNA.
DR   EMBL; AY380228; AAQ87922.1; -; Genomic_DNA.
DR   EMBL; AY380229; AAQ87923.1; -; Genomic_DNA.
DR   EMBL; BC102120; AAI02121.1; -; mRNA.
DR   EMBL; K01085; AAA30482.1; -; mRNA.
DR   EMBL; AF123250; AAD32139.1; -; Genomic_DNA.
DR   EMBL; AF123251; AAD32140.1; -; Genomic_DNA.
DR   EMBL; AF105260; AAF72097.1; -; Genomic_DNA.
DR   EMBL; M38333; AAA30432.1; -; mRNA.
DR   EMBL; AF041482; AAB97519.1; -; Genomic_DNA.
DR   EMBL; U84250; AAB47260.1; -; Genomic_DNA.
DR   EMBL; U84251; AAB47261.1; -; Genomic_DNA.
DR   PIR; S02076; KKBOB.
DR   RefSeq; NP_776719.1; NM_174294.2.
DR   AlphaFoldDB; P02668; -.
DR   BioGRID; 159044; 3.
DR   IntAct; P02668; 1.
DR   MINT; P02668; -.
DR   STRING; 9913.ENSBTAP00000028685; -.
DR   Allergome; 10200; Bos d 12.0101.
DR   Allergome; 167; Bos d 8.
DR   Allergome; 2737; Bos d 12.
DR   CarbonylDB; P02668; -.
DR   GlyConnect; 309; 19 O-Linked glycans (7 sites).
DR   GlyCosmos; P02668; 8 sites, 20 glycans.
DR   iPTMnet; P02668; -.
DR   PaxDb; 9913-ENSBTAP00000028685; -.
DR   PeptideAtlas; P02668; -.
DR   GeneID; 281728; -.
DR   KEGG; bta:281728; -.
DR   CTD; 1448; -.
DR   eggNOG; ENOG502TM2T; Eukaryota.
DR   HOGENOM; CLU_103388_0_0_1; -.
DR   InParanoid; P02668; -.
DR   OrthoDB; 5265313at2759; -.
DR   TreeFam; TF338369; -.
DR   Proteomes; UP000009136; Unplaced.
DR   GO; GO:0005615; C:extracellular space; IDA:AgBase.
DR   GO; GO:0005794; C:Golgi apparatus; IDA:AgBase.
DR   GO; GO:0005796; C:Golgi lumen; IDA:AgBase.
DR   GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR   GO; GO:0035375; F:zymogen binding; IPI:AgBase.
DR   GO; GO:0007595; P:lactation; IBA:GO_Central.
DR   GO; GO:0050821; P:protein stabilization; IBA:GO_Central.
DR   GO; GO:1903496; P:response to 11-deoxycorticosterone; IDA:AgBase.
DR   GO; GO:1903494; P:response to dehydroepiandrosterone; IDA:AgBase.
DR   GO; GO:0032355; P:response to estradiol; IDA:AgBase.
DR   GO; GO:0032570; P:response to progesterone; IDA:AgBase.
DR   InterPro; IPR000117; Casein_kappa.
DR   PANTHER; PTHR11470; KAPPA CASEIN; 1.
DR   PANTHER; PTHR11470:SF2; KAPPA-CASEIN; 1.
DR   Pfam; PF00997; Casein_kappa; 1.
DR   PIRSF; PIRSF002374; Casein_kappa; 1.
PE   1: Evidence at protein level;
KW   Direct protein sequencing; Disulfide bond; Glycoprotein; Milk protein;
KW   Phosphoprotein; Pyrrolidone carboxylic acid; Reference proteome; Secreted;
KW   Signal.
FT   SIGNAL          1..21
FT                   /evidence="ECO:0000269|PubMed:1628650,
FT                   ECO:0000269|PubMed:4577852, ECO:0000269|Ref.7"
FT   CHAIN           22..190
FT                   /note="Kappa-casein"
FT                   /id="PRO_0000004483"
FT   PEPTIDE         46..55
FT                   /note="Casoxin-C"
FT                   /id="PRO_0000004484"
FT   PEPTIDE         54..59
FT                   /note="Casoxin-6"
FT                   /id="PRO_0000004485"
FT   PEPTIDE         56..62
FT                   /note="Casoxin-A"
FT                   /id="PRO_0000004486"
FT   PEPTIDE         79..82
FT                   /note="Casoxin-B"
FT                   /id="PRO_0000004487"
FT   PEPTIDE         127..137
FT                   /note="Casoplatelin"
FT                   /id="PRO_0000004488"
FT   SITE            126..127
FT                   /note="Cleavage; by chymosin/rennin"
FT   MOD_RES         22
FT                   /note="Pyrrolidone carboxylic acid"
FT                   /evidence="ECO:0000269|PubMed:1628650"
FT   MOD_RES         148
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:8817876"
FT   MOD_RES         166
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000269|PubMed:25456591"
FT   MOD_RES         170
FT                   /note="Phosphoserine; alternate"
FT                   /evidence="ECO:0000269|PubMed:25456591,
FT                   ECO:0000269|PubMed:8817876"
FT   MOD_RES         187
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P02670"
FT   CARBOHYD        142
FT                   /note="O-linked (GalNAc...) threonine"
FT                   /evidence="ECO:0000269|PubMed:25456591,
FT                   ECO:0000269|PubMed:7734846, ECO:0000269|PubMed:8817876"
FT   CARBOHYD        152
FT                   /note="O-linked (GalNAc...) threonine"
FT                   /evidence="ECO:0000269|PubMed:25456591,
FT                   ECO:0000269|PubMed:7734846, ECO:0000269|PubMed:8817876"
FT   CARBOHYD        153
FT                   /note="O-linked (GalNAc...) serine"
FT                   /evidence="ECO:0000269|PubMed:25456591"
FT   CARBOHYD        154
FT                   /note="O-linked (GalNAc...) threonine"
FT                   /evidence="ECO:0000269|PubMed:25456591,
FT                   ECO:0000269|PubMed:7734846, ECO:0000269|PubMed:8817876"
FT   CARBOHYD        157
FT                   /note="O-linked (GalNAc...) threonine"
FT                   /evidence="ECO:0000269|PubMed:25456591,
FT                   ECO:0000269|PubMed:7734846, ECO:0000269|PubMed:8817876"
FT   CARBOHYD        163
FT                   /note="O-linked (GalNAc...) threonine"
FT                   /evidence="ECO:0000269|PubMed:25456591,
FT                   ECO:0000269|PubMed:7734846, ECO:0000269|PubMed:8817876"
FT   CARBOHYD        170
FT                   /note="O-linked (GalNAc...) serine; alternate"
FT                   /evidence="ECO:0000269|PubMed:25456591"
FT   CARBOHYD        186
FT                   /note="O-linked (GalNAc...) threonine; partial"
FT                   /evidence="ECO:0000269|PubMed:25456591,
FT                   ECO:0000269|PubMed:7734846, ECO:0000269|PubMed:8817876"
FT   DISULFID        32..109
FT   DISULFID        32
FT                   /note="Interchain (with C-109); in linked form"
FT   DISULFID        109
FT                   /note="Interchain (with C-32); in linked form"
FT   VARIANT         31
FT                   /note="R -> H (in variant F)"
FT   VARIANT         118
FT                   /note="R -> C (in variant G)"
FT   VARIANT         156
FT                   /note="T -> I (in variant G and variant H)"
FT   VARIANT         157
FT                   /note="T -> I (in variant B and variant B2)"
FT   VARIANT         169
FT                   /note="D -> A (in variant B and variant B2)"
FT   VARIANT         174
FT                   /note="I -> T (in variant B2)"
FT   VARIANT         176
FT                   /note="S -> G (in variant E)"
FT   CONFLICT        23
FT                   /note="E -> Q (in Ref. 7; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        26
FT                   /note="Q -> E (in Ref. 7; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        28
FT                   /note="Q -> E (in Ref. 7; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        102
FT                   /note="N -> D (in Ref. 6; AA sequence)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   190 AA;  21269 MW;  F12D8310C3B93EDA CRC64;
     MMKSFFLVVT ILALTLPFLG AQEQNQEQPI RCEKDERFFS DKIAKYIPIQ YVLSRYPSYG
     LNYYQQKPVA LINNQFLPYP YYAKPAAVRS PAQILQWQVL SNTVPAKSCQ AQPTTMARHP
     HPHLSFMAIP PKKNQDKTEI PTINTIASGE PTSTPTTEAV ESTVATLEDS PEVIESPPEI
     NTVQVTSTAV
//