Mouse anti-Human Muc1 Monoclonal Antibody | anti-Muc1 antibody
Muc1
NCBI and Uniprot Product Information
NCBI Description
This gene encodes a membrane-bound protein that is a member of the mucin family. Mucins are O-glycosylated proteins that play an essential role in forming protective mucous barriers on epithelial surfaces. These proteins also play a role in intracellular signaling. This protein is expressed on the apical surface of epithelial cells that line the mucosal surfaces of many different tissues including lung, breast stomach and pancreas. This protein is proteolytically cleaved into alpha and beta subunits that form a heterodimeric complex. The N-terminal alpha subunit functions in cell-adhesion and the C-terminal beta subunit is involved in cell signaling. Overexpression, aberrant intracellular localization, and changes in glycosylation of this protein have been associated with carcinomas. This gene is known to contain a highly polymorphic variable number tandem repeats (VNTR) domain. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Feb 2011]
Uniprot Description
Function: The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack. Ref.30 Ref.41 Ref.44 Ref.49 Ref.50 Ref.53 Ref.56 Ref.57 Ref.59The beta subunit contains a C-terminal domain which is involved in cell signaling, through phosphorylations and protein-protein interactions. Modulates signaling in ERK, SRC and NF-kappa-B pathways. In activated T-cells, influences directly or indirectly the Ras/MAPK pathway. Promotes tumor progression. Regulates TP53-mediated transcription and determines cell fate in the genotoxic stress response. Binds, together with KLF4, the PE21 promoter element of TP53 and represses TP53 activity. Ref.30 Ref.41 Ref.44 Ref.49 Ref.50 Ref.53 Ref.56 Ref.57 Ref.59
Subunit structure: The alpha subunit forms a tight, non-covalent heterodimeric complex with the proteolytically-released beta-subunit. Interaction, via the tandem repeat region, with domain 1 of ICAM1 is implicated in cell migration and metastases. Isoform 1 binds directly the SH2 domain of GRB2, and forms a MUC1/GRB2/SOS1 complex involved in RAS signaling. The cytoplasmic tail (MUC1CT) interacts with several proteins such as SRC, CTNNB1 and ERBs. Interaction with the SH2 domain of CSK decreases interaction with GSK3B. Interacts with CTNNB1/beta-catenin and JUP/gamma-catenin and promotes cell adhesion. Interaction with JUP/gamma-catenin is induced by heregulin. Binds PRKCD, ERBB2, ERBB3 and ERBB4. Heregulin (HRG) stimulates the interaction with ERBB2 and, to a much lesser extent, the interaction with ERBB3 and ERBB4. Interacts with P53 in response to DNA damage. Interacts with KLF4. Interacts with estrogen receptor alpha/ESR1, through its DNA-binding domain, and stimulates its transcription activity. Binds ADAM17. Ref.28 Ref.30 Ref.34 Ref.36 Ref.38 Ref.40 Ref.41 Ref.43 Ref.44 Ref.45 Ref.46 Ref.47 Ref.48 Ref.49 Ref.50 Ref.53 Ref.54 Ref.55 Ref.56 Ref.57 Ref.59
Subcellular location: Apical cell membrane; Single-pass type I membrane protein. Note: Exclusively located in the apical domain of the plasma membrane of highly polarized epithelial cells. After endocytosis, internalized and recycled to the cell membrane. Located to microvilli and to the tips of long filopodial protusions. Ref.37 Ref.46 Ref.47 Ref.48 Ref.52 Ref.54 Ref.56 Ref.58Isoform 5: Secreted Ref.37 Ref.46 Ref.47 Ref.48 Ref.52 Ref.54 Ref.56 Ref.58. Isoform 7: Secreted Ref.37 Ref.46 Ref.47 Ref.48 Ref.52 Ref.54 Ref.56 Ref.58. Isoform 9: Secreted Ref.37 Ref.46 Ref.47 Ref.48 Ref.52 Ref.54 Ref.56 Ref.58. Mucin-1 subunit beta: Cell membrane. Cytoplasm. Nucleus. Note: On EGF and PDGFRB stimulation, transported to the nucleus through interaction with CTNNB1, a process which is stimulated by phosphorylation. On HRG stimulation, colocalizes with JUP/gamma-catenin at the nucleus. Ref.37 Ref.46 Ref.47 Ref.48 Ref.52 Ref.54 Ref.56 Ref.58
Tissue specificity: Expressed on the apical surface of epithelial cells, especially of airway passages, breast and uterus. Also expressed in activated and unactivated T-cells. Overexpressed in epithelial tumors, such as breast or ovarian cancer and also in non-epithelial tumor cells. Isoform 7 is expressed in tumor cells only. Ref.9 Ref.53
Developmental stage: During fetal development, expressed at low levels in the colonic epithelium from 13 weeks of gestation. Ref.32
Post-translational modification: Highly glycosylated (N- and O-linked carbohydrates and sialic acid). O-glycosylated to a varying degree on serine and threonine residues within each tandem repeat, ranging from mono- to penta-glycosylation. The average density ranges from about 50% in human milk to over 90% in T47D breast cancer cells. Further sialylation occurs during recycling. Membrane-shed glycoproteins from kidney and breast cancer cells have preferentially sialyated core 1 structures, while secreted forms from the same tissues display mainly core 2 structures. The O-glycosylated content is overlapping in both these tissues with terminal fucose and galactose, 2- and 3-linked galactose, 3- and 3,6-linked GalNAc-ol and 4-linked GlcNAc predominating. Differentially O-glycosylated in breast carcinomas with 3,4-linked GlcNAc. N-glycosylation consists of high-mannose, acidic complex-type and hybrid glycans in the secreted form MUC1/SEC, and neutral complex-type in the transmembrane form, MUC1/TM. Ref.26 Ref.29 Ref.31 Ref.33 Ref.52 Ref.61Proteolytic cleavage in the SEA domain occurs in the endoplasmic reticulum by an autoproteolytic mechanism and requires the full-length SEA domain as well as requiring a Ser, Thr or Cys residue at the P + 1 site. Cleavage at this site also occurs on isoform MUC1/X but not on isoform MUC1/Y. Ectodomain shedding is mediated by ADAM17.Dual palmitoylation on cysteine residues in the CQC motif is required for recycling from endosomes back to the plasma membrane. Ref.54Phosphorylated on tyrosines and serine residues in the C-terminal. Phosphorylation on tyrosines in the C-terminal increases the nuclear location of MUC1 and beta-catenin. Phosphorylation by PKC delta induces binding of MUC1 to beta-catenin/CTNNB1 and thus decreases the formation of the beta-catenin/E-cadherin complex. Src-mediated phosphorylation inhibits interaction with GSK3B. Src- and EGFR-mediated phosphorylation on Tyr-1229 increases binding to beta-catenin/CTNNB1. GSK3B-mediated phosphorylation on Ser-1227 decreases this interaction but restores the formation of the beta-cadherin/E-cadherin complex. On T-cell receptor activation, phosphorylated by LCK. PDGFR-mediated phosphorylation increases nuclear colocalization of MUC1CT and CTNNB1. Ref.27 Ref.28 Ref.34 Ref.38 Ref.40 Ref.41 Ref.42 Ref.43 Ref.50 Ref.53 Ref.58The N-terminal sequence has been shown to begin at position 24 or 28 (Ref.24).
Polymorphism: The number of repeats is highly polymorphic. It varies from 21 to 125 in the northern European population. The most frequent alleles contains 41 and 85 repeats. The tandemly repeated icosapeptide underlies polymorphism at three positions: PAPGSTAP[PAQT]AHGVTSAP[DT/ES]R, DT -> ES and the single replacements P -> A, P -> Q and P-> T. The most frequent replacement DT -> ES occurs in up to 50% of the repeats.
Involvement in disease: MUC1/CA 15-3 is used as a serological clinical marker of breast cancer to monitor response to breast cancer treatment and disease recurrence (Ref.60). Decreased levels over time may be indicative of a positive response to treatment. Conversely, increased levels may indicate disease progression. At an early stage disease, only 21% of patients exhibit high MUC1/CA 15-3 levels, that is why CA 15-3 is not a useful screening test. Most antibodies target the highly immunodominant core peptide domain of 20 amino acid (APDTRPAPGSTAPPAHGVTS) tandem repeats. Some antibodies recognize glycosylated epitopes.
Miscellaneous: The name KL-6 was originally that of a murine monoclonal antibody reacting with pulmonary adenocarcinoma cell lines and pulmonary epithelial cells. This antibody recognizes a sialylated carbohydrate chain on MUC1.
Sequence similarities: Contains 1 SEA domain.
Caution: O-glycosylation sites are annotated in first sequence repeat only. Residues at similar position are probably glycosylated in all repeats. Experimental sites were determined in a synthetic peptide glycosylated in vitro (Ref.29, Ref.33).
Sequence caution: The sequence AAD14369.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.The sequence AAD14376.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.
Research Articles on Muc1
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Product Notes
The Muc1 muc1 (Catalog #AAA395116) is an Antibody produced from Mouse and is intended for research purposes only. The product is available for immediate purchase. The Muc1 reacts with Human and may cross-react with other species as described in the data sheet. AAA Biotech's Muc1 can be used in a range of immunoassay formats including, but not limited to, Immunohistochemistry (IHC) Frozen/Paraffin, ELISA (EIA), Western Blot (WB). Researchers should empirically determine the suitability of the Muc1 muc1 for an application not listed in the data sheet. Researchers commonly develop new applications and it is an integral, important part of the investigative research process. It is sometimes possible for the material contained within the vial of "Muc1, Monoclonal Antibody" to become dispersed throughout the inside of the vial, particularly around the seal of said vial, during shipment and storage. We always suggest centrifuging these vials to consolidate all of the liquid away from the lid and to the bottom of the vial prior to opening. Please be advised that certain products may require dry ice for shipping and that, if this is the case, an additional dry ice fee may also be required.Precautions
All products in the AAA Biotech catalog are strictly for research-use only, and are absolutely not suitable for use in any sort of medical, therapeutic, prophylactic, in-vivo, or diagnostic capacity. By purchasing a product from AAA Biotech, you are explicitly certifying that said products will be properly tested and used in line with industry standard. AAA Biotech and its authorized distribution partners reserve the right to refuse to fulfill any order if we have any indication that a purchaser may be intending to use a product outside of our accepted criteria.Disclaimer
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