ID   CASB_HUMAN              Reviewed;         226 AA.
AC   P05814; Q4VAZ9; Q9UCM5;
DT   01-NOV-1988, integrated into UniProtKB/Swiss-Prot.
DT   01-AUG-1992, sequence version 4.
DT   24-JAN-2024, entry version 189.
DE   RecName: Full=Beta-casein;
DE   Flags: Precursor;
GN   Name=CSN2; Synonyms=CASB;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=2387396; DOI=10.1016/0014-5793(90)81142-b;
RA   Loennerdal B., Bergstroem S., Andersson Y., Hjalmarsson K., Sundqvist A.K.,
RA   Hernell O.;
RT   "Cloning and sequencing of a cDNA encoding human milk beta-casein.";
RL   FEBS Lett. 269:153-156(1990).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   TISSUE=Placenta;
RX   PubMed=8112603; DOI=10.1016/0378-1119(94)90754-4;
RA   Hansson L., Edlund A., Johansson T., Hernell O., Stroemqvist M.,
RA   Lindquist S., Loennerdal B., Bergstroem S.;
RT   "Structure of the human beta-casein encoding gene.";
RL   Gene 139:193-199(1994).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Mammary gland;
RA   Menon R.S.;
RL   Submitted (OCT-1989) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   TISSUE=Placenta;
RA   Kwiatkowski D.J.;
RT   "A high resolution linkage map of human 9q34.1.";
RL   Submitted (DEC-1997) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [6]
RP   PROTEIN SEQUENCE OF 16-226, AND PHOSPHORYLATION AT THR-18; SER-21; SER-23;
RP   SER-24 AND SER-25.
RX   PubMed=6715339; DOI=10.1016/s0021-9258(17)42966-8;
RA   Greenberg R., Groves M.L., Dower H.J.;
RT   "Human beta-casein. Amino acid sequence and identification of
RT   phosphorylation sites.";
RL   J. Biol. Chem. 259:5132-5138(1984).
RN   [7]
RP   PROTEIN SEQUENCE OF 18-33, PHOSPHORYLATION AT THR-18; SER-21; SER-23;
RP   SER-24 AND SER-25, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX   PubMed=18847231; DOI=10.1021/pr800387s;
RA   Poth A.G., Deeth H.C., Alewood P.F., Holland J.W.;
RT   "Analysis of the human casein phosphoproteome by 2-D electrophoresis and
RT   MALDI-TOF/TOF MS reveals new phosphoforms.";
RL   J. Proteome Res. 7:5017-5027(2008).
RN   [8]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 161-226.
RC   TISSUE=Mammary gland;
RX   PubMed=2717418; DOI=10.1093/nar/17.7.2869;
RA   Menon R.S., Ham R.G.;
RT   "Human beta-casein: partial cDNA sequence and apparent polymorphism.";
RL   Nucleic Acids Res. 17:2869-2869(1989).
RN   [9]
RP   PROTEIN SEQUENCE OF 176-215.
RX   PubMed=1369431; DOI=10.1271/bbb.56.1140;
RA   Azuma N., Yamauchi K.;
RT   "Plasmin cleavage of human beta-casein.";
RL   Biosci. Biotechnol. Biochem. 56:1140-1141(1992).
CC   -!- FUNCTION: Important role in determination of the surface properties of
CC       the casein micelles.
CC   -!- INTERACTION:
CC       P05814; Q14192: FHL2; NbExp=4; IntAct=EBI-1642112, EBI-701903;
CC       P05814; Q9UHD9: UBQLN2; NbExp=6; IntAct=EBI-1642112, EBI-947187;
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- TISSUE SPECIFICITY: Mammary gland specific. Secreted in milk.
CC   -!- PTM: Form 1-P is phosphorylated once; half of the molecules are
CC       phosphorylated on Ser-24, half on Ser-25. {ECO:0000269|PubMed:18847231,
CC       ECO:0000269|PubMed:6715339}.
CC   -!- SIMILARITY: Belongs to the beta-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";
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DR   EMBL; X55739; CAA39270.1; -; mRNA.
DR   EMBL; AF027807; AAC82978.1; -; Genomic_DNA.
DR   EMBL; X17070; CAA34916.1; -; mRNA.
DR   EMBL; BC069554; AAH69554.1; -; mRNA.
DR   EMBL; BC096194; AAH96194.1; -; mRNA.
DR   EMBL; BC096195; AAH96195.1; -; mRNA.
DR   EMBL; BC096196; AAH96196.1; -; mRNA.
DR   EMBL; BC096197; AAH96197.1; -; mRNA.
DR   EMBL; X13766; CAA32017.1; -; mRNA.
DR   CCDS; CCDS3532.1; -.
DR   PIR; I53730; KBHU.
DR   RefSeq; NP_001289699.1; NM_001302770.1.
DR   RefSeq; NP_001882.1; NM_001891.3.
DR   RefSeq; XP_016863249.1; XM_017007760.1.
DR   AlphaFoldDB; P05814; -.
DR   SMR; P05814; -.
DR   BioGRID; 107834; 45.
DR   IntAct; P05814; 15.
DR   MINT; P05814; -.
DR   STRING; 9606.ENSP00000341030; -.
DR   Allergome; 1064; Hom s 8.
DR   iPTMnet; P05814; -.
DR   PhosphoSitePlus; P05814; -.
DR   BioMuta; CSN2; -.
DR   DMDM; 115661; -.
DR   MassIVE; P05814; -.
DR   PaxDb; 9606-ENSP00000341030; -.
DR   PeptideAtlas; P05814; -.
DR   ProteomicsDB; 51861; -.
DR   Antibodypedia; 24273; 252 antibodies from 24 providers.
DR   DNASU; 1447; -.
DR   Ensembl; ENST00000353151.4; ENSP00000341030.3; ENSG00000135222.7.
DR   GeneID; 1447; -.
DR   KEGG; hsa:1447; -.
DR   MANE-Select; ENST00000353151.4; ENSP00000341030.3; NM_001891.4; NP_001882.1.
DR   AGR; HGNC:2447; -.
DR   CTD; 1447; -.
DR   DisGeNET; 1447; -.
DR   GeneCards; CSN2; -.
DR   HGNC; HGNC:2447; CSN2.
DR   HPA; ENSG00000135222; Tissue enriched (breast).
DR   MIM; 115460; gene.
DR   neXtProt; NX_P05814; -.
DR   OpenTargets; ENSG00000135222; -.
DR   PharmGKB; PA26950; -.
DR   VEuPathDB; HostDB:ENSG00000135222; -.
DR   eggNOG; ENOG502RU0R; Eukaryota.
DR   GeneTree; ENSGT00390000001890; -.
DR   HOGENOM; CLU_106775_0_0_1; -.
DR   InParanoid; P05814; -.
DR   OMA; EIMEVPK; -.
DR   OrthoDB; 4933674at2759; -.
DR   PhylomeDB; P05814; -.
DR   TreeFam; TF336929; -.
DR   PathwayCommons; P05814; -.
DR   Reactome; R-HSA-1251985; Nuclear signaling by ERBB4.
DR   SignaLink; P05814; -.
DR   BioGRID-ORCS; 1447; 12 hits in 1126 CRISPR screens.
DR   GeneWiki; CSN2; -.
DR   GenomeRNAi; 1447; -.
DR   Pharos; P05814; Tbio.
DR   PRO; PR:P05814; -.
DR   Proteomes; UP000005640; Chromosome 4.
DR   RNAct; P05814; Protein.
DR   Bgee; ENSG00000135222; Expressed in male germ line stem cell (sensu Vertebrata) in testis and 37 other cell types or tissues.
DR   ExpressionAtlas; P05814; baseline and differential.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR   GO; GO:0005509; F:calcium ion binding; TAS:ProtInc.
DR   GO; GO:0004869; F:cysteine-type endopeptidase inhibitor activity; IDA:CAFA.
DR   GO; GO:0004857; F:enzyme inhibitor activity; TAS:ProtInc.
DR   GO; GO:0006816; P:calcium ion transport; TAS:ProtInc.
DR   GO; GO:0007595; P:lactation; IDA:UniProtKB.
DR   GO; GO:2000117; P:negative regulation of cysteine-type endopeptidase activity; IDA:CAFA.
DR   InterPro; IPR001588; Casein.
DR   InterPro; IPR016345; Casein_beta.
DR   InterPro; IPR031305; Casein_CS.
DR   PANTHER; PTHR11500; BETA CASEIN; 1.
DR   PANTHER; PTHR11500:SF0; BETA-CASEIN; 1.
DR   Pfam; PF00363; Casein; 1.
DR   PIRSF; PIRSF002372; Beta-casein; 1.
DR   PROSITE; PS00306; CASEIN_ALPHA_BETA; 1.
DR   Genevisible; P05814; HS.
PE   1: Evidence at protein level;
KW   Direct protein sequencing; Milk protein; Phosphoprotein;
KW   Reference proteome; Secreted; Signal.
FT   SIGNAL          1..15
FT                   /evidence="ECO:0000269|PubMed:6715339"
FT   CHAIN           16..226
FT                   /note="Beta-casein"
FT                   /evidence="ECO:0000269|PubMed:6715339"
FT                   /id="PRO_0000004475"
FT   MOD_RES         18
FT                   /note="Phosphothreonine; in form 5-P"
FT                   /evidence="ECO:0000269|PubMed:18847231,
FT                   ECO:0000269|PubMed:6715339"
FT   MOD_RES         21
FT                   /note="Phosphoserine; in form 4-P and form 5-P"
FT                   /evidence="ECO:0000269|PubMed:18847231,
FT                   ECO:0000269|PubMed:6715339"
FT   MOD_RES         23
FT                   /note="Phosphoserine; in form 3-P, form 4-P and form 5-P"
FT                   /evidence="ECO:0000269|PubMed:18847231,
FT                   ECO:0000269|PubMed:6715339"
FT   MOD_RES         24
FT                   /note="Phosphoserine; in form 1-P, form 2-P, form 3-P, form
FT                   4-P and form 5-P"
FT                   /evidence="ECO:0000269|PubMed:18847231,
FT                   ECO:0000269|PubMed:6715339"
FT   MOD_RES         25
FT                   /note="Phosphoserine; in form 1-P, form 2-P, form 3-P, form
FT                   4-P and form 5-P"
FT                   /evidence="ECO:0000269|PubMed:18847231,
FT                   ECO:0000269|PubMed:6715339"
FT   CONFLICT        30
FT                   /note="T -> P (in Ref. 6; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        34
FT                   /note="Missing (in Ref. 1; CAA39270)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        48..50
FT                   /note="EDE -> TDQ (in Ref. 6; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        120
FT                   /note="S -> Q (in Ref. 6; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        133
FT                   /note="L -> V (in Ref. 3; CAA34916)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        140
FT                   /note="H -> Q (in Ref. 3; CAA34916)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        149
FT                   /note="L -> S (in Ref. 6; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        173
FT                   /note="Q -> E (in Ref. 6; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        182..184
FT                   /note="QVV -> EVL (in Ref. 6; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        188
FT                   /note="Q -> V (in Ref. 6; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        207
FT                   /note="T -> P (in Ref. 6; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        214..222
FT                   /note="TQPLAPVHN -> PEPSTTZABH (in Ref. 6; AA sequence)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   226 AA;  25382 MW;  2619C524EA1358E8 CRC64;
     MKVLILACLV ALALARETIE SLSSSEESIT EYKQKVEKVK HEDQQQGEDE HQDKIYPSFQ
     PQPLIYPFVE PIPYGFLPQN ILPLAQPAVV LPVPQPEIME VPKAKDTVYT KGRVMPVLKS
     PTIPFFDPQI PKLTDLENLH LPLPLLQPLM QQVPQPIPQT LALPPQPLWS VPQPKVLPIP
     QQVVPYPQRA VPVQALLLNQ ELLLNPTHQI YPVTQPLAPV HNPISV
//