CASA1_HUMAN
ID CASA1_HUMAN Reviewed; 185 AA.
AC P47710; A1A510; A1A511; E9PB60; Q4PNR5;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 1.
DT 03-AUG-2022, entry version 170.
DE RecName: Full=Alpha-S1-casein;
DE Contains:
DE RecName: Full=Casoxin-D;
DE Flags: Precursor;
GN Name=CSN1S1; Synonyms=CASA, CSN1;
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] (ISOFORMS 1; 2 AND 3).
RC TISSUE=Mammary gland;
RX PubMed=7619062; DOI=10.1042/bj3090237;
RA Johnsen L.B., Rasmussen L.K., Petersen T.E., Berglund L.;
RT "Characterization of three types of human alpha s1-casein mRNA
RT transcripts.";
RL Biochem. J. 309:237-242(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Mammary gland;
RA Yu D.Y., Jeong S., Lee K.K., Lonnerdal B.;
RL Submitted (MAR-1995) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4).
RA Lin L., Nong W., Zhou G., Ke R., Shen C., Zhong G., Zheng Z., Liang M.,
RA Wen S., Li H., Yang S.;
RL Submitted (MAY-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT VAL-117.
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 [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 9-185 (ISOFORMS 1; 2 AND 3).
RA Martin P., Brignon G., Furet J.-P., Leroux C.;
RT "The gene encoding alpha s1-casein is expressed in human mammary epithelial
RT cells during lactation.";
RL Lait 76:525-537(1996).
RN [8]
RP PROTEIN SEQUENCE OF 16-29.
RX PubMed=8192860; DOI=10.1515/bchm3.1994.375.2.149;
RA Cavaletto M., Cantisani A., Giuffrida G., Napolitano L., Conti A.;
RT "Human alpha S1-casein like protein: purification and N-terminal sequence
RT determination.";
RL Biol. Chem. Hoppe-Seyler 375:149-151(1994).
RN [9]
RP PROTEIN SEQUENCE OF 16-29 AND 99-105, AND CHARACTERIZATION.
RX PubMed=7749638; DOI=10.1016/0305-0491(94)00225-j;
RA Rasmussen L.K., Due H.A., Petersen T.E.;
RT "Human alpha s1-casein: purification and characterization.";
RL Comp. Biochem. Physiol. 111B:75-81(1995).
RN [10]
RP PROTEIN SEQUENCE OF 27-42 AND 83-98, PHOSPHORYLATION AT SER-33; SER-41;
RP SER-88 AND SER-90, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=17646876; DOI=10.1039/b701902e;
RA Kjeldsen F., Savitski M.M., Nielsen M.L., Shi L., Zubarev R.A.;
RT "On studying protein phosphorylation patterns using bottom-up LC-MS/MS: the
RT case of human alpha-casein.";
RL Analyst 132:768-776(2007).
RN [11]
RP PROTEIN SEQUENCE OF 28-48, PHOSPHORYLATION AT SER-31; SER-33; SER-41;
RP SER-86; SER-88; SER-89; SER-90 AND SER-91, AND IDENTIFICATION BY MASS
RP 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 [12]
RP PARTIAL PROTEIN SEQUENCE, PHOSPHORYLATION AT SER-33 AND SER-41, LACK OF
RP GLYCOSYLATION, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=12919330; DOI=10.1046/j.1432-1033.2003.03755.x;
RA Sorensen E.S., Moller L., Vinther M., Petersen T.E., Rasmussen L.K.;
RT "The phosphorylation pattern of human alphas1-casein is markedly different
RT from the ruminant species.";
RL Eur. J. Biochem. 270:3651-3655(2003).
RN [13]
RP GENOMIC ORGANIZATION, AND CHROMOSOMAL LOCATION.
RX PubMed=9050925; DOI=10.1007/s004390050374;
RA Fujiwara Y., Miwa M., Nogami M., Okumura K., Nobori T., Suzuki T., Ueda M.;
RT "Genomic organization and chromosomal localization of the human casein gene
RT family.";
RL Hum. Genet. 99:368-373(1997).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-41, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
CC -!- FUNCTION: Important role in the capacity of milk to transport calcium
CC phosphate.
CC -!- FUNCTION: Casoxin D acts as opioid antagonist and has vasorelaxing
CC activity mediated by bradykinin B1 receptors.
CC -!- SUBUNIT: Heteromultimers of alpha-s1 casein and kappa-casein;
CC disulfide-linked.
CC -!- INTERACTION:
CC P47710; Q9UHD9: UBQLN2; NbExp=3; IntAct=EBI-2433045, EBI-947187;
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=P47710-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P47710-2; Sequence=VSP_000795;
CC Name=3;
CC IsoId=P47710-3; Sequence=VSP_000796;
CC Name=4;
CC IsoId=P47710-4; Sequence=VSP_000795, VSP_046130;
CC -!- TISSUE SPECIFICITY: Mammary gland specific. Secreted in milk.
CC -!- PTM: Not glycosylated.
CC -!- MISCELLANEOUS: In milk, the alpha s1- and beta-caseins precipitate in
CC presence of calcium (so-called calcium-sensitive caseins). Kappa-casein
CC prevents the precipitation of the other caseins by calcium through the
CC formation of large stable colloidal particles termed micelles.
CC -!- SIMILARITY: Belongs to the alpha-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; X78416; CAA55185.1; -; mRNA.
DR EMBL; U23157; AAA69477.1; -; mRNA.
DR EMBL; DQ064604; AAY68392.1; -; mRNA.
DR EMBL; AC108941; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471057; EAX05599.1; -; Genomic_DNA.
DR EMBL; BC128227; AAI28228.1; -; mRNA.
DR EMBL; BC128228; AAI28229.1; -; mRNA.
DR EMBL; X98084; CAA66708.1; -; mRNA.
DR CCDS; CCDS47067.1; -. [P47710-1]
DR CCDS; CCDS54769.1; -. [P47710-4]
DR PIR; S56013; S56013.
DR RefSeq; NP_001020275.1; NM_001025104.1. [P47710-4]
DR RefSeq; NP_001881.1; NM_001890.1. [P47710-1]
DR RefSeq; XP_006714152.1; XM_006714089.2. [P47710-2]
DR RefSeq; XP_006714153.1; XM_006714090.2. [P47710-3]
DR AlphaFoldDB; P47710; -.
DR SMR; P47710; -.
DR BioGRID; 107833; 31.
DR IntAct; P47710; 15.
DR STRING; 9606.ENSP00000246891; -.
DR Allergome; 1064; Hom s 8.
DR GlyConnect; 2932; 81 N-Linked glycans (1 site).
DR GlyGen; P47710; 1 site, 85 N-linked glycans (1 site).
DR iPTMnet; P47710; -.
DR PhosphoSitePlus; P47710; -.
DR SwissPalm; P47710; -.
DR BioMuta; CSN1S1; -.
DR MassIVE; P47710; -.
DR PaxDb; P47710; -.
DR PeptideAtlas; P47710; -.
DR PRIDE; P47710; -.
DR ProteomicsDB; 19152; -.
DR ProteomicsDB; 55785; -. [P47710-1]
DR ProteomicsDB; 55786; -. [P47710-2]
DR ProteomicsDB; 55787; -. [P47710-3]
DR Antibodypedia; 24253; 175 antibodies from 22 providers.
DR DNASU; 1446; -.
DR Ensembl; ENST00000246891.9; ENSP00000246891.4; ENSG00000126545.14. [P47710-1]
DR Ensembl; ENST00000507763.5; ENSP00000422611.1; ENSG00000126545.14. [P47710-4]
DR GeneID; 1446; -.
DR KEGG; hsa:1446; -.
DR MANE-Select; ENST00000246891.9; ENSP00000246891.4; NM_001890.2; NP_001881.1.
DR UCSC; uc003hep.2; human. [P47710-1]
DR CTD; 1446; -.
DR DisGeNET; 1446; -.
DR GeneCards; CSN1S1; -.
DR HGNC; HGNC:2445; CSN1S1.
DR HPA; ENSG00000126545; Tissue enriched (breast).
DR MIM; 115450; gene.
DR neXtProt; NX_P47710; -.
DR OpenTargets; ENSG00000126545; -.
DR PharmGKB; PA26948; -.
DR VEuPathDB; HostDB:ENSG00000126545; -.
DR eggNOG; ENOG502TEWT; Eukaryota.
DR GeneTree; ENSGT00390000017378; -.
DR InParanoid; P47710; -.
DR OMA; WYYPPQV; -.
DR OrthoDB; 1478191at2759; -.
DR PhylomeDB; P47710; -.
DR TreeFam; TF340763; -.
DR PathwayCommons; P47710; -.
DR Reactome; R-HSA-5223345; Miscellaneous transport and binding events.
DR SignaLink; P47710; -.
DR SIGNOR; P47710; -.
DR BioGRID-ORCS; 1446; 16 hits in 1062 CRISPR screens.
DR GeneWiki; CSN1S1; -.
DR GenomeRNAi; 1446; -.
DR Pharos; P47710; Tbio.
DR PRO; PR:P47710; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; P47710; protein.
DR Bgee; ENSG00000126545; Expressed in parotid gland and 101 other tissues.
DR ExpressionAtlas; P47710; baseline and differential.
DR Genevisible; P47710; HS.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; HDA:UniProtKB.
DR GO; GO:1903496; P:response to 11-deoxycorticosterone; IBA:GO_Central.
DR GO; GO:1903494; P:response to dehydroepiandrosterone; IBA:GO_Central.
DR GO; GO:0032355; P:response to estradiol; IBA:GO_Central.
DR GO; GO:0032570; P:response to progesterone; IBA:GO_Central.
DR DisProt; DP02005; -.
DR InterPro; IPR026999; Alpha-s1_casein.
DR InterPro; IPR031305; Casein_CS.
DR PANTHER; PTHR10240; PTHR10240; 1.
DR PROSITE; PS00306; CASEIN_ALPHA_BETA; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Direct protein sequencing; Disulfide bond;
KW Milk protein; Phosphoprotein; Reference proteome; Secreted; Signal.
FT SIGNAL 1..15
FT /evidence="ECO:0000269|PubMed:7749638,
FT ECO:0000269|PubMed:8192860"
FT CHAIN 16..185
FT /note="Alpha-S1-casein"
FT /id="PRO_0000004450"
FT PEPTIDE 158..164
FT /note="Casoxin-D"
FT /id="PRO_0000004451"
FT MOD_RES 31
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18847231"
FT MOD_RES 33
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:12919330,
FT ECO:0000269|PubMed:17646876, ECO:0000269|PubMed:18847231"
FT MOD_RES 41
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:12919330,
FT ECO:0000269|PubMed:17646876, ECO:0000269|PubMed:18847231,
FT ECO:0007744|PubMed:20068231"
FT MOD_RES 71
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P02662"
FT MOD_RES 85
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O97943"
FT MOD_RES 86
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18847231"
FT MOD_RES 88
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:17646876,
FT ECO:0000269|PubMed:18847231"
FT MOD_RES 89
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18847231"
FT MOD_RES 90
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:17646876,
FT ECO:0000269|PubMed:18847231"
FT MOD_RES 91
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18847231"
FT VAR_SEQ 52
FT /note="Missing (in isoform 2 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:7619062, ECO:0000303|Ref.3,
FT ECO:0000303|Ref.7"
FT /id="VSP_000795"
FT VAR_SEQ 66..73
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:7619062, ECO:0000303|Ref.7"
FT /id="VSP_000796"
FT VAR_SEQ 93..100
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_046130"
FT VARIANT 117
FT /note="A -> V (in dbSNP:rs10030475)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_048614"
FT CONFLICT 80
FT /note="P -> S (in Ref. 3; AAY68392)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 185 AA; 21671 MW; A7717899CDC7D563 CRC64;
MRLLILTCLV AVALARPKLP LRYPERLQNP SESSEPIPLE SREEYMNGMN RQRNILREKQ
TDEIKDTRNE STQNCVVAEP EKMESSISSS SEEMSLSKCA EQFCRLNEYN QLQLQAAHAQ
EQIRRMNENS HVQVPFQQLN QLAAYPYAVW YYPQIMQYVP FPPFSDISNP TAHENYEKNN
VMLQW
