MUC1_HYLLA
ID MUC1_HYLLA Reviewed; 475 AA.
AC Q29435;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 25-MAY-2022, entry version 91.
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 Hylobates lar (Common gibbon) (White-handed gibbon).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hylobatidae;
OC Hylobates.
OX NCBI_TaxID=9580;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8747930; DOI=10.1007/bf00292441;
RA Spicer A.P., Duhig T., Chilton B.S., Gendler S.J.;
RT "Analysis of mammalian MUC1 genes reveals potential functionally important
RT domains.";
RL Mamm. Genome 6:885-888(1995).
CC -!- FUNCTION: The alpha subunit has cell adhesive properties. Can act both
CC as an adhesion and an anti-adhesion protein. May provide a protective
CC layer on epithelial cells against bacterial and enzyme attack (By
CC 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-kappaB
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. Located to microvilli
CC and to the tips of long filopodial protusions (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 -!- PTM: Probably both N- and O-glycosylated (in repeat region).
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-449 increases binding to beta-catenin/CTNNB1.
CC GSK3B-mediated phosphorylation on Ser-447 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; L41589; AAA69965.1; -; Genomic_DNA.
DR EMBL; L41625; AAA69918.1; -; Genomic_DNA.
DR EMBL; L41624; AAA69918.1; JOINED; Genomic_DNA.
DR AlphaFoldDB; Q29435; -.
DR SMR; Q29435; -.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
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 3: Inferred from homology;
KW Autocatalytic cleavage; Cell membrane; Cytoplasm; Glycoprotein;
KW Lipoprotein; Membrane; Nucleus; Palmitate; Phosphoprotein; Repeat; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..475
FT /note="Mucin-1"
FT /id="PRO_0000019278"
FT CHAIN 24..317
FT /note="Mucin-1 subunit alpha"
FT /evidence="ECO:0000250"
FT /id="PRO_0000317448"
FT CHAIN 318..475
FT /note="Mucin-1 subunit beta"
FT /evidence="ECO:0000250"
FT /id="PRO_0000317449"
FT TOPO_DOM 24..380
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 381..401
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 402..475
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REPEAT 86..105
FT /note="1"
FT REPEAT 106..125
FT /note="2"
FT REPEAT 126..145
FT /note="3"
FT REPEAT 146..165
FT /note="4"
FT REPEAT 166..185
FT /note="5"
FT DOMAIN 259..368
FT /note="SEA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00188"
FT REGION 23..252
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 86..185
FT /note="5 X 20 AA approximate tandem repeats"
FT REGION 412..448
FT /note="Interaction with P53"
FT /evidence="ECO:0000250"
FT REGION 434..460
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 443..450
FT /note="Required for interaction with GSK3B"
FT /evidence="ECO:0000250"
FT REGION 453..461
FT /note="Required for interaction with beta- and gamma-
FT catenins"
FT /evidence="ECO:0000250"
FT MOTIF 423..426
FT /note="Interaction with GRB2"
FT /evidence="ECO:0000250"
FT MOTIF 449..452
FT /note="Interaction with SRC and ESR1"
FT /evidence="ECO:0000250"
FT MOTIF 463..466
FT /note="Required for interaction with AP1S2"
FT /evidence="ECO:0000250"
FT COMPBIAS 23..83
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 89..126
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 163..252
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 437..460
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 317..318
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000250"
FT MOD_RES 423
FT /note="Phosphotyrosine; by PDGFR"
FT /evidence="ECO:0000250|UniProtKB:P15941"
FT MOD_RES 432
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P15941"
FT MOD_RES 438
FT /note="Phosphotyrosine; by PDGFR"
FT /evidence="ECO:0000250|UniProtKB:P15941"
FT MOD_RES 444
FT /note="Phosphothreonine; by PKC/PRKCD"
FT /evidence="ECO:0000250|UniProtKB:P15941"
FT MOD_RES 447
FT /note="Phosphoserine; by GSK3-beta"
FT /evidence="ECO:0000250|UniProtKB:P15941"
FT MOD_RES 449
FT /note="Phosphotyrosine; by CSK, EGFR and SRC"
FT /evidence="ECO:0000250|UniProtKB:P15941"
FT MOD_RES 463
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P15941"
FT LIPID 404
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT LIPID 406
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT CARBOHYD 93
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 99
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 100
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 104
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 177
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 195
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 249
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 275
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 353
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 475 AA; 49372 MW; D7A699D6D68C6622 CRC64;
MTPGTQSLFF LLLLLTVLTV VTGSGHASST PGGEKETSAT QRSSMPSSTE KKVVSMTSSV
LSSHSPGSGS STTQGQDVSL APATEPASGS AATWGQDVTS VPVTRPAPGS TTSPAQDVTS
APDTRPALGS TAPPVHGVTS APDTRPTLGS TAPPVHGVTS APDTRPTLGS TAPPVHNVTS
ASGSASGSAS TLVHNGTSAR ATTTPASKST PFSIPSHHSD TPTTLTSHST KTDASSTHHS
TVSPLTSSNH STSPQLSIGV SFFFLSFHIS NLQFNSSLED PSTNYYQELQ RDISELILQI
YKQGDFLGVS NIKFRPGSVV VQSTLAFREG TTNVHDVEAQ FNQHKTEAAS RYNLTISDVS
VSDVPFPFSA QSGAGVPGWG IALLVLVCVL VALAIVYLIA LAVCQCRRKN YGQLDIFPAR
DAYHPMSEYP TYHTHGRYVP PSSTNRSPYE KVSEGNGGSS LSYTNPAVAA TSANL
