MUC1_BOVIN
ID MUC1_BOVIN Reviewed; 580 AA.
AC Q8WML4; Q95L89;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 1.
DT 03-AUG-2022, entry version 115.
DE RecName: Full=Mucin-1;
DE Short=MUC-1;
DE AltName: CD_antigen=CD227;
DE Contains:
DE RecName: Full=Mucin-1 subunit alpha;
DE Short=MUC1-NT;
DE Short=MUC1-alpha;
DE Contains:
DE RecName: Full=Mucin-1 subunit beta;
DE Short=MUC1-beta;
DE AltName: Full=MUC1-CT;
DE Flags: Precursor;
GN Name=MUC1;
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], PROTEIN SEQUENCE OF 23-35; 256-264; 276-282;
RP 371-373; 387-397; 402-426 AND 523-528, GLYCOSYLATION, AND STRUCTURE OF
RP CARBOHYDRATE.
RC STRAIN=Holstein; TISSUE=Lactating mammary gland;
RX PubMed=11814015; DOI=10.3168/jds.s0022-0302(01)74713-3;
RA Pallesen L.T., Andersen M.H., Nielsen R.L., Berglund L., Rasmussen L.K.,
RA Petersen T.E., Rasmussen J.T.;
RT "Purification of MUC1 from bovine milk-fat globules and characterization of
RT a corresponding full-length cDNA clone.";
RL J. Dairy Sci. 84:2591-2598(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-554, AND POLYMORPHISM.
RC STRAIN=Friesian; TISSUE=Blood;
RA Rasero R., Sacchi P., Rosati S., Cauvin E., Maione S.;
RT "Molecular analysis of the length polymorphic MUC1 gene in cattle.";
RL J. Anim. Breed. Genet. 119:342-349(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-554.
RX PubMed=16276097; DOI=10.1159/000087520;
RA Perucatti A., Floriot S., Di Meo G.P., Soglia D., Rullo R., Maione S.,
RA Incarnato D., Eggen A., Sacchi P., Rasero R., Iannuzzi L.;
RT "Comparative FISH mapping of mucin 1, transmembrane (MUC1) among cattle,
RT river buffalo, sheep and goat chromosomes: comparison between bovine
RT chromosome 3 and human chromosome 1.";
RL Cytogenet. Genome Res. 112:103-105(2006).
RN [4]
RP GLYCOSYLATION.
RX PubMed=16291619; DOI=10.3168/jds.s0022-0302(05)73114-3;
RA Liu C., Erickson A.K., Henning D.R.;
RT "Distribution and carbohydrate structures of high molecular weight
RT glycoproteins, MUC1 and MUCX, in bovine milk.";
RL J. Dairy Sci. 88:4288-4294(2005).
CC -!- FUNCTION: The alpha subunit has cell adhesive properties. May provide a
CC protective layer on epithelial cells against bacterial and enzyme
CC attack (By similarity). {ECO:0000250}.
CC -!- FUNCTION: The beta subunit contains a C-terminal domain which is
CC involved in cell signaling, through phosphorylations and protein-
CC protein interactions. Modulates signaling in ERK, Src and NF-kappa-B
CC pathways. In activated T-cells, influences directly or indirectly the
CC Ras/MAPK pathway. Promotes tumor progression. Regulates P53-mediated
CC transcription and determines cell fate in the genotoxic stress
CC response. Binds, together with KLF4, the PE21 promoter element of P53
CC and represses P53 activity (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: The alpha subunit forms a tight, non-covalent heterodimeric
CC complex with the proteolytically-released beta subunit. Binds directly
CC the SH2 domain of GRB2, and forms a MUC1/GRB2/SOS1 complex involved in
CC RAS signaling. The cytoplasmic tail (MUC1CT) interacts with several
CC proteins such as, SRC, CTNNB1 and ERBs. Interaction with the SH2 domain
CC of CSK decreases interaction with GSK3B. Interacts with CTNNB1/beta-
CC catenin and JUP/gamma-catenin and promotes cell adhesion. Interaction
CC with JUP/gamma-catenin is induced by heregulin. Binds PRKCD, ERBB2,
CC ERBB3 and ERBB4. Heregulin (HRG) stimulates the interaction with ERBB2
CC and, to a much lesser extent, the interaction with ERBB3 and ERBB4.
CC Interacts with P53 in response to DNA damage. Interacts with KLF4.
CC Interacts with estrogen receptor alpha/ESR1, through its DNA-binding
CC domain, and stimulates its transcription activity. Binds ADAM17 (By
CC similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Apical cell membrane; Single-pass type I membrane
CC protein. Note=Exclusively located in the apical domain of the plasma
CC membrane of highly polarized epithelial cells. After endocytosis,
CC internalized and recycled to the cell membrane (By similarity).
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: [Mucin-1 subunit beta]: Cell membrane. Cytoplasm.
CC Nucleus. Note=On EGF and PDGFRB stimulation, transported to the nucleus
CC through interaction with CTNNB1, a process which is stimulated by
CC phosphorylation. On HRG stimulation, colocalizes with JUP/gamma-catenin
CC at the nucleus (By similarity). {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed on the apical surface of epithelia cells,
CC and on the milk fat globule membrane (MGGM).
CC -!- PTM: Highly glycosylated (N- and O-linked carbohydrates and sialic
CC acid). O-linked glycosylation consists mainly of GalNAc, galactose, and
CC sialic acid. The ratio from pools of milk from different dairy breeds
CC is GalNAc: GlcNAc:galactose:mannose:sialic acid is 14:1:10:1:15.
CC {ECO:0000269|PubMed:11814015, ECO:0000269|PubMed:16291619}.
CC -!- PTM: Proteolytic cleavage in the SEA domain occurs in the endoplasmic
CC reticulum by an autoproteolytic mechanism and requires the full-length
CC SEA domain as well as requiring a Ser, Thr or Cys residue at the P + 1
CC site. Ectodomain shedding is mediated by ADAM17 in uterine epithelial
CC cells (By similarity). {ECO:0000250}.
CC -!- PTM: Dual palmitoylation on cysteine residues in the CQC motif is
CC required for recycling from endosomes back to the plasma membrane.
CC {ECO:0000250}.
CC -!- PTM: Phosphorylated on tyrosines and serine residues in the C-terminal.
CC Phosphorylation on tyrosines in the C-terminal increases the nuclear
CC location of MUC1 and beta-catenin. Phosphorylation by PKC delta induces
CC binding of MUC1 to beta-catenin/CTNNB1 and thus decreases the formation
CC of the beta-catenin/E-cadherin complex. Src-mediated phosphorylation
CC inhibits interaction with GSK3B. Csk- or Src- or EGFR-mediated
CC phosphorylation on Tyr-556 increases binding to beta-catenin/CTNNB1.
CC GSK3B-mediated phosphorylation on Ser-554 decreases this interaction
CC but restores the formation of the beta-cadherin/E-cadherin complex. On
CC T-cell receptor activation, phosphorylated by LCK. PDGFR-mediated
CC phosphorylation increases nuclear colocalization of MUC1CT and CTNNB1
CC (By similarity). {ECO:0000250}.
CC -!- CAUTION: O-glycosylation sites are annotated in first sequence repeat
CC only. Residues at similar position are probably glycosylated in all
CC repeats. {ECO:0000305}.
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DR EMBL; AJ400824; CAC81810.1; -; mRNA.
DR EMBL; AF399757; AAL28023.1; -; Genomic_DNA.
DR RefSeq; NP_776540.1; NM_174115.2.
DR AlphaFoldDB; Q8WML4; -.
DR SMR; Q8WML4; -.
DR STRING; 9913.ENSBTAP00000014051; -.
DR PaxDb; Q8WML4; -.
DR PRIDE; Q8WML4; -.
DR GeneID; 281333; -.
DR KEGG; bta:281333; -.
DR CTD; 4582; -.
DR eggNOG; ENOG502QWCT; Eukaryota.
DR HOGENOM; CLU_029446_1_0_1; -.
DR InParanoid; Q8WML4; -.
DR OrthoDB; 945460at2759; -.
DR TreeFam; TF336301; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0016324; C:apical plasma membrane; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR Gene3D; 6.10.140.600; -; 1.
DR InterPro; IPR000082; SEA_dom.
DR InterPro; IPR036364; SEA_dom_sf.
DR Pfam; PF01390; SEA; 1.
DR SMART; SM00200; SEA; 1.
DR SUPFAM; SSF82671; SSF82671; 1.
DR PROSITE; PS50024; SEA; 1.
PE 1: Evidence at protein level;
KW Autocatalytic cleavage; Cell membrane; Cytoplasm;
KW Direct protein sequencing; Glycoprotein; Lipoprotein; Membrane; Nucleus;
KW Palmitate; Phosphoprotein; Reference proteome; Repeat; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..22
FT /evidence="ECO:0000269|PubMed:11814015"
FT CHAIN 23..580
FT /note="Mucin-1"
FT /id="PRO_5000067900"
FT CHAIN 23..426
FT /note="Mucin-1 subunit alpha"
FT /evidence="ECO:0000250"
FT /id="PRO_0000316161"
FT CHAIN 427..580
FT /note="Mucin-1 subunit beta"
FT /evidence="ECO:0000250"
FT /id="PRO_0000316162"
FT TOPO_DOM 23..489
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 490..510
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 511..580
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REPEAT 70..89
FT /note="1"
FT REPEAT 90..109
FT /note="2"
FT REPEAT 110..129
FT /note="3"
FT REPEAT 130..149
FT /note="4"
FT REPEAT 150..169
FT /note="5"
FT REPEAT 170..189
FT /note="6"
FT REPEAT 190..209
FT /note="7"
FT REPEAT 210..229
FT /note="8"
FT REPEAT 230..249
FT /note="9"
FT REPEAT 250..269
FT /note="10"
FT REPEAT 270..289
FT /note="11"
FT DOMAIN 368..475
FT /note="SEA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00188"
FT REGION 28..359
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 70..289
FT /note="11 X 20 AA approximate tandem repeats of P-A-P-S-P-
FT A-A-S-P-G-H-D-G-A-S-T-P-T-S-S"
FT REGION 519..555
FT /note="Interaction with P53"
FT /evidence="ECO:0000250"
FT REGION 544..563
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 550..557
FT /note="Required for interaction with GSK3B"
FT /evidence="ECO:0000250"
FT REGION 560..568
FT /note="Required for interaction with beta- and gamma-
FT catenins"
FT /evidence="ECO:0000250"
FT MOTIF 530..533
FT /note="Interaction with GRB2"
FT /evidence="ECO:0000250"
FT MOTIF 556..559
FT /note="Interaction with SRC and ESR1"
FT /evidence="ECO:0000250"
FT MOTIF 570..572
FT /note="Required for interaction with AP1S2"
FT /evidence="ECO:0000250"
FT COMPBIAS 28..73
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 140..170
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 180..210
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 220..359
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 426..427
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000250"
FT MOD_RES 530
FT /note="Phosphotyrosine; by PDGFR"
FT /evidence="ECO:0000250|UniProtKB:P15941"
FT MOD_RES 539
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P15941"
FT MOD_RES 545
FT /note="Phosphotyrosine; by PDGFR"
FT /evidence="ECO:0000250|UniProtKB:P15941"
FT MOD_RES 551
FT /note="Phosphothreonine; by PKC/PRKCD"
FT /evidence="ECO:0000250|UniProtKB:P15941"
FT MOD_RES 554
FT /note="Phosphoserine; by GSK3-beta"
FT /evidence="ECO:0000250|UniProtKB:P15941"
FT MOD_RES 556
FT /note="Phosphotyrosine; by CSK, EGFR and SRC"
FT /evidence="ECO:0000250|UniProtKB:P15941"
FT MOD_RES 570
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P15941"
FT LIPID 511
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT LIPID 513
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT CARBOHYD 73
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 77
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 84
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 85
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 87
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 88
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 89
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 161
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 201
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 241
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 384
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 460
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 580 AA; 58092 MW; E91C13984AF7D757 CRC64;
MTPDIQAPFL SLLLLFPVLT VANVPTLTTS DSINPRRTTP VSTTQSSPTS SPTKETSWST
TTTLLTASSP APSPAASPGH DGASTPTSSP APSPAASPGH DGASTPTSSP APSPAASPGH
DGASTPTSSP APSPAASPGH DGASTPTSSP APSPAASPGH NGTSSPTGSP APSPAASPGH
DGASTPTSSP APSPAASPGH NGTSSPTGSP APSPAASPGH DGASTPTSSP APSPAASPGH
NGTSSPTGSP APSPTASPGH DSAPSLTSSP APSPTASPGQ HGASSPTSSD TSSMTTRSMS
SSMVTSAHKG TSSRATMTPV SKGTPSSVPS SETAPTAASH ITRTAASSPS IALSTSSNPK
TSQQLSVRVS LYFLSFRITN LQFNSSLENP QTSYYQELQR SIWGLILQIY KQRDFLGLSE
IKFRPGSVVV ELTLAFREGT TAEWVKAQFS QLEAHAASYN LTISGVSVYS APFPSSAQAG
SGVPGWGIAL LVLVCVLVAL AIIYLIALVV CQCGRKKCEQ LDVFPTLDAY HPMSEYSTYH
THGRYVPPGS TKRSPYEEVS AGNGGSNLSY TNLAATSANL
